Rheumatology: Clinical Scenarios

Rheumatology

 

Efim Benenson

Rheumatology Clinical Scenarios

Syndrome or disease?

Author Efim Benenson, MD Professor of Medicine Department of Internal Medicine University of Cologne Cologne Germany The work was first published as a part of a work published in 2009 by Shaker Media in German language with the following title: Rheumatologie: Syndrome und Algorithmen Translation: Beverley Taylor

ISBN 978-0-85729-239-1 DOI 10.1007/978-0-85729-240-7

e-ISBN 978-0-85729-240-7

Springer London Dordrecht Heidelberg New York A catalogue record for this book is available from the British Library Mathematics Subject Classification (2000): insert codes if applicable © Springer-Verlag London Limited 2011 Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the Copyright, Designs and Patents Act 1988, this publication may only be reproduced, stored or transmitted, in any form or by any means, with the prior permission in writing of the publishers, or in the case of reprographic reproduction in accordance with the terms of licenses issued by the Copyright Licensing Agency. Enquiries concerning reproduction outside those terms should be sent to the publishers. The use of registered names, trademarks, etc., in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant laws and regulations and therefore free for general use. Product liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. Cover design: eStudioCalamar, Figueres/Berlin Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)

I dedicate this book to my wife, Irina, for her patience and support, our children, Anna and Vladimir, and to our grandchildren, Patrick, Paulina, and Wlada.

 

Preface

“Clinical Scenarios” is directed toward trainees of rheumatology. Active learning by case studies on the way toward an established diagnosis based on a structured clinical knowledge and thinking – such is the concept of this training. It has arisen from the experience of practical clinical teaching. How can I find a diagnosis for the pictures on the front matter page? Which two commonly confused diseases do the two hands represent? Which syndromes can be seen here: arthritis, osteoarthritis, or both? How can I find the correct diagnosis for diseases I am seeing for the very first time? How to get the ability to apply my knowledge about diseases from the basic books to a real patient? The 73 clinical situations and 156 illustrations provide a realistic simulation of everyday medical practice – not as an illustration of the topic, but as a problem to be solved when seeking a diagnosis. Furthermore the case reports and pictures complete most part of the specific area of rheumatology and present the important basis of what every doctor should be able to identify and interpret correctly. Syndrome or disease? This lately important of questions is the key both to diagnosis and clinical training. During the training with this book you can reach a diagnosis for the first time on your own, using the morphological structured signs or syndromes (terminated as a stable combination of symptoms from the Greek syn. together, dromos passage) which, unlike the symptoms, clearly depict the similarities and distinctions of the individual diseases. The solutions to the images and associated clinical situations are offered not as a process of perception or visual diagnosis, but rather as a flow of thoughts (the Greek term for flow, rheuma, happens to fit perfectly here) and respectively the outcome of integrated morphological and pathophysiological reasoning. The clinical situations and figures enclose the relatively comprehensive collection of rheumatologic leading symptoms and syndromes (Chap. 1). Certain clinical situations – also emergencies – are presented as “typical,” “unusual,” or “memorable.” They are labeled with the combinations of symptoms and syndromes, documented in the images by means of various radiological and morphological methods; also included are the traditional and new therapeutic options (immunosuppressive, biologics, laser therapy, surgeries) partly with therapy outcomes in figures. The syndromes, especially on the images, should be recognized by the reader in the context of the clinical situation and then linked with the correct diagnosis. The exemplary solutions are presented, even in the case when comparing the classical nosological and here favorite syndromes principle (Chap. 1.2).



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The reader is encouraged to enter his/her preliminary diagnosis of all figures and clinical situations in Chap. 3 as self-check and then compare his/her opinion with the diagnosis given in the Appendix. This table also serves as an index for all figures and clinical situations for a quick diagnosis. A critical review of each figure and clinical situation is presented and discussed in terms of specifics of the cases and its boundaries in the overall context with the individual treatment options (Chap. 2). In Clinical Scenarios with the images and clinical cases is also presented the deductive key for their clearing. The standardized diagnostic program (diagnostic skills) achieves a solid structuring of the findings based on morphology and pathophysiology as well as the causal investigation and wide-ranging clinical examination. The Rheumatology Trees 1 and 2 (Tables 1 and 2) offer compact information as basics at a glance and as “shortcut” for the already experienced colleagues who want to fresh up their proficiency. All images were structured as syndrome-specific, non-disease-specific, or disease specific. Rheumatology: Symptoms and Syndromes, E. Benenson, Springer 2011, is a reference work for this book. Thus the clinical routine – from patient to information and back – is in the active learning completely modulated. The idea, how to get a diagnosis, can be applied to other areas of clinical medicine. Training in rheumatology with these clinical cases could vary according to the individual objectives: as self-assessment (quiz) or study program (case-based learning) with the book as a well-structured guide to differential diagnosis (diagnostic Index of all syndromes and diseases in the Appendix), or package of individual therapeutic options with clear outcomes. I wish my readers both enjoyment and success and to myself a broad discussion in the future about clinical training ([email protected]). Cologne, Germany 

Efim Benenson, MD

Acknowledgements

Sincere thanks to my colleagues Professor of Medicine Michael Hallek, Director of Department I of Internal Medicine, University of Cologne for his advice and support, and my former boss, Professor of Medicine Volker Diehl, for welcoming me kindly to this Clinic in 1994, and especially Ursula Voigt-Pfeil for her active support in realizing this project.



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Contents

1  Diagnostic Training and Rheumatology Trees..................................................... 1.1  The Pictures and Clinical Cases That Every Doctor Should Correctly Identify and Interpret......................................................................................... 1.1.1 Pictures of the Major Syndromes in Rheumatology (Fig. 1–132, page onwards) . ...................................................................  1.1.2  Clinical Situations (CS) Marked by Syndromes...................................... 1.2  Solutions to the Clinical Situations.................................................................... 1.2.1  Arthrology................................................................................................ 1.2.2  Connective Tissue Disease (CTD)........................................................... 1.2.3  Vasculitis.................................................................................................. 1.3 Rheumatology Tree 1: Articular and Musculoskeletal Disorders (Table of the Major Syndromes)........................................................................  1.4 Rheumatology Tree 2: Connective Tissue Diseases and Vascilitides (Table of Syndromes of the Major Systemic Diseases)..................................... 

1 1 2 2 27 27 30 32 34 35

2  E  xplanations of Figures and Case Reports with Individual   Therapeutic Options............................................................................................... 39 3  Index of Figures (Fig.) and CS with Syndromes (for Self-assessment)...........................   81 Appendix: Index of the Solutions to the Syndromes and Diagnostics   (for Rapid Diagnosis).................................................................................................................... 89 References ..................................................................................................................... 99 Abbreviations.....................................................................................................................................    101 Pictures With Major Syndromes of Rheumatology................................................... 105 Index������������������������������������������������������������������������������������������������������������������������������ 127



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1.1  The Pictures and Clinical Cases That Every Doctor Should Correctly Identify and Interpret These randomly numbered figures (Fig.) and possibly related, laconically arranged clinical situations (CS) – without anticipated results and superfluous findings – taken from our everyday rheumatology practice may, in our opinion, shape, enhance and train clinical and rheumatological expertise and thinking skills. The Fig. and CS represent, in equal measure, the rheumatological modules of medical training, and illustrative material on the subject and, if you wish, a challenge and appropriate homework for students. No ready answers or solutions are given with the Fig. and CS, for didactic reasons (anticipated findings diminish the educational value!). These Fig. and CS, with diagnoses, are integrated in the Rheumatology: Symptoms and Syndromes E. Benenson, Springer 2011 (RSS) with a description of the relevant syndromes and staged diagnostics. Chap. 2 provides explanations and comments on the pictures and CS in the order one by one. Chap.  3 gives you the opportunity to make your preliminary diagnosis (as a self-­ assessment check). Try to assign the illustrated syndromes, namely whether they are ­specific to a syndrome or condition (A), not specific to a disease (B), or disease-specific (C). Such structuring can be seen in Chaps. 2, 3 and in the Appendix. So the diagnostic reasoning were encouraged by active self-learning based on CS and figures, whereby a well-founded diagnosis will be established independently. Trees of Rheumatology (Chaps. 1.3 and 1.4) clearly show the concept and sequence of the diagnostic search. The Integrated Diagnostic Screening Program (see next page) is the key to structuring the findings and diagnostic reasoning for all clinical cases, for both the Figures (Question 1 and 2) and CS (all 4 issues).

Integrated Diagnostic Screening Program 1. Which structures are diseased? Applying a morphological structure to the available findings is crucial to finding the diagnosis 2. Are inflammatory or degenerative changes, among others, present in these structures? Here the findings are given a pathophysiological structure E. Benenson, Rheumatology, Clinical Scenarios, DOI: 10.1007/978-0-85729-240-7_1, © Springer-Verlag London Limited 2011

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3. Are there concomitant factors causing the changes, i.e., infections, excessive strain, trauma, tumors? Now we are at the stage of causal investigation 4. Are other organs and systems affected? In such a case extensive physical examination is needed, also on the part of other important specialist disciplines The reasoning of experienced physicians of all clinical disciplines is much the same. It is an essential key to the formulation of diagnostic criteria – which are mostly composed of syndromes – and ultimately the diagnosis itself. The Rheumatology: Symptoms and Syndromes (RSS*) specifies and applies such a program to “Articular and Musculoskeletal Disorders” (Chap. 6), “Connective Tissue Diseases and Vasculitis” (Chap. 13). *RSS – Rheumatology: Symptoms and Syndromes (E. Benenson, Springer 2011)

1.1.1  Pictures of the Major Syndromes in Rheumatology (Fig. 1–132, page onwards) 1.1.2  Clinical Situations (CS) Marked by Syndromes The CS, packed into the clear syndromes or figures (Fig.), are presented as a clinical ­problem to be solved, containing the clinical, immunological, morphological, and imaging information under classical or new therapeutic options. Not all Fig. and CS have an unequivocal solution, as is the case in clinical medicine, but all should waken a certain curiosity and encourage consideration, investigation, and discussion.

CS 1: Acute swelling and redness in the ankle joint in immunocompromised female patient, 42 years

• About 3 years’ observation of the patient with therapy-resistant (all admissible bio­

logics, 18 joint operations), definable disease (Figs. 5, 9a, b) UUAcute events (Fig. 6), emergency referral to outpatient clinic • Moderately elevated blood concentrations of CRP 15 mg/l (three times the normal value)* and ESR (36 mm/h). Ultrasound and joint puncture: no effusion. ACE and Il2r are within the normal range • X-ray chest: no adenopathy • Bacteriology: no bacteria in blood cultures • Serology – a fresh Yersinia infection (see RSS, Chap. 11.3.2).

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**Additional question: What diseases or conditions will already be excluded?

UUemergency situations are marked with this symbol (×3, 4 … 15, etc.) indicates a

3, 4 … 15-fold increase of the parameter above the ­normal findings These additional questions will be discussed in Chap. 2.

CS 2: Puffy hands and high titer ANA in 26-year-old female patient

• Pain in the hands (Fig. 7), myalgia (for 3 years) • No organ involvement, only a light reduction of the DLCO (63%) • X-ray hands – no bone erosion (as in Fig. 72) , bone scans reveal no increased uptake #

(as in Fig. 65 on the right versus the left) • Laboratory findings: CRP 20 (×4), ESR 30 mm/h • Immune status: ANA 1:10,000; anti-dsDNA 167 (neg. <29, pos. >75 kU/l), Crithidia test negative. ENA: U1-RNP and anti-Sm positive, other antibodies, RF and anti-CCP negative.  dditional question: Is the diagnosis certain? A -----------------------------------------------------------------------------------------------------

CS 3: Acute claudicatio arteriosa in the form of weakness in the legs and lupus-type immunology in a 40-year-old female patient (56 years old at present)

UUAcute claudicatio arteriosa in the form of extreme weakness in the legs (not a single

step further without having to stop, no strength in the legs), cyanosis extending as far as the thighs UUEmergency angiogram (Fig.  12). Emergency operation for Y-prosthesis (stent) in abdominal aorta (16 years ago) • Adequate anticoagulation (phenprocoumon therapy) ever since, previous diagnosis of SLE • No organ involvement detected during the follow-up period (12 years) • Immunology: ANA, anti-dsDNA-Ab highly positive with negative Crithidia test, ACLA highly positive • Lab: ESR approx. 30 mm/h, CRP negative, lupus anticoagulant 74 s (normal <35) • Skin histology (recently developed livedo reticularis): consistent with APS.

CS 4: Acute peripheral gangrenes of unclear etiology, 48-year-old male patient

UUAcute development of events (Fig. 14)

• Referral by family doctor for the exclusion of systemic vasculitis • Several years of claudicatio intermittens in the legs (the pain-free walking distance is about 300 m), several risk factors: heavy smoker, alcohol abuse, obesity II • A. tibialis posterior and a. dorsalis pedis are not palpable • Vasculitis and CTD serological markers negative, also capillaroscopy • When asked, the patient claimed to have hit two fingers with a hammer.

Additional question: What are the most important indicators for the right diagnosis? # “As shown in Fig.” refers to the same syndrome shown in another patient.

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CS 5: Pain and redness in toes and forefoot, massive CRP increase, male, 63 years

UUTransfer from the dermatology outpatient department (Fig. 15a) with suspected erysipelas and possible sepsis with extremely elevated CRP (120 mg/l, factor × 24)

• MRI of the left forefoot identifies marrow edema, MTP 3–4 • The feet after therapy (Fig. 15b).

Additional question: Do you use the therapy to confirm the diagnosis (ex juvantibus)?

CS 6: Several insults (since the age of 17), normal delivery and currently (after 12 years) suffering dementia, deaf-muteness and spasticity, female patient aged 41 years

UUWhen 17 years old (1993), acute apoplexy in the area of a. cerebri media UUFurthermore progressive amaurosis fugax and transient ischemic attacks

• Generalized, livedo racemosa with accentuation on the trunk (as in Fig. 20a) • 1994 and 1997 morphologically confirmed cutaneous lupus erythematosus, suspected SLE

UU1997 renewed stroke on the right, still in remission

• 1998 trouble-free pregnancy and childbirth, no terminations, no thrombosis

UUStatus post media infarcts on both sides (1999), on the left (2000, 2003), on the right (2002)

• MRI brain (Fig. 17) • At the moment symptomatic epilepsy, the patient is currently deaf and dumb with dementia, spasticity accentuated to the left; no other organ involvement • Immunology: ANA-HEp2-cell test <1:80, no detection of ENA-, anti-dsDNA-, anticardiolipin or b-2 glycoprotein-Ab, no C3-4 consumption, CRP is negative.

Additional question: Which of at least three possible diagnoses for a multi-infarct syndrome would you prioritize?

CS 7: Massive livedo racemosa, reversible under doxycycline, female, 53 years*

• Such skin phenomena (Fig. 20a) occurred over one year • A few months before the patient had three tick bites with local redness specifically in

the upper thighs • Skin biopsy was taken one year ago, but with non-specific findings • Myalgias and arthralgias • ANA-positivity, no other signs of CTD or APS • Serology: ELISA and Western blot for Borrelia-Ab, as in CS 9 positive (see RSS, Chap. 11.3.4) Fig. 20b shows the findings after doxycycline therapy. • * The case is presented with the kind permission of MD Bernhard Heilig

CS 8: Stable mono-/oligoarthritis, HLA-B27 positive, female, 18 years

• More than 1 year with the presented clinical problem in Fig. 21 • The changes described in Fig. 24 emerged 2 months ago

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• Bone scan (10 months ago) showed increased uptake MCP 5 on the right • X-ray – right hand (Fig. 22) • CT imaging of MCP 5 (Fig. 23) • No CRP and ESR increase, HLA-B27 positive, anti-CCP and RF-negative • No comorbidities (also no family history). Additional question: What clinical imaging and laboratory syndromes provide clues to the possible diseases?

CS 9: Acute arthritis of the knee at 50-year-old marathon runner

• Knee problems on the left (Fig. 25) occurred after running about 40 km (after a long training break)

• No clinical and serological evidence of association with an infection. Effusion (about 10 ml) of approximately 1,000 cells/ml, CRP, RF, Borrelia-Ab s. CS 7 undetectable

• MRI of the left knee (Fig. 26).

Additional question: Can a morphological substrate of the illness or condition be seen?

CS 10: PIP bursitis and MCP 2 arthritis, female, 26 years

• These events originated 3 months ago (Fig. 28) • Lab findings: no signs of inflammation; X-ray hands – no changes • Immunology: RF (1:560 kU/l) and anti-CCP-Ab (>300 RE/ml) highly positive • The patient wishes to have children. Additional question: How would you formulate the diagnosis and the therapeutic concept?

CS 11: Livedo racemosa and deep ulcerations involving the lungs and kidneys, ANCA negative, male patient, 42 years*

• Patient (computer scientist) has always been very healthy, slight corpulence (Body

Mass Index 28.9) • One year ago an ulcer appeared (supposedly following a mosquito bite) with livedo racemosa in the right lower leg, which receded after 2 months UUThe same happened in 03/2007, but was extensive (Fig. 30) and increased (Fig. 31), accompanied by leg pain at rest and claudicatio intermittens (hardly able to walk). Three skin biopsies were taken • There were no ground-breaking findings nor any relevant morphological, angiographic, serological, immunological and laboratory findings, but periodic CRP and ESR increases UUConsiderable pulmonary hypertension (to 95 mmHg) has developed (normally 25 mmHg) since 07/2007 with focal infiltration judged to be pneumonia • At the same time renal involvement: proteinuria (1.44 g/l) and decrease in total serum protein (4.7 g/dl)

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• Findings after 1 year (Fig. 32) on a moderate dose of cortisone therapy * From another hospital abroad with the permission of the patient. Additional question: Which vessels are concerned, what syndromes are to be seen, what illnesses are possible? Compare Figs. 30 and 31 to Fig. 2, where the morphological and immunological diagnosis seems to be confirmed.

CS 12: Local erythema, CK elevation and positive ANCA, male, 45 years

• Local skin changes on upper arm (Fig. 33), elbow, knee for many years • Migratory pressure-dolent, subcutaneous induration measuring up to 10 cm in the upper

arms and legs • Arthralgia, myalgia, muscle weakness with CK elevation (factor × 12), UUExtreme testicular pain with swelling, hospital admission, clinically and MRI-confirmed testicular bleeding • No organ involvement, microhematuria, no accompanying illnesses • Electromyography: consistent with less pronounced proximal myositis • Histology: chronic arteritis, necrotic vasculitis, inflammation spreading to the surrounding fatty tissue, perivascular dermatitis with numerous plasma cells • Immunology: ANA and myositis specific antibodies negative, ANCA borderline. Additional question: What morphological correlation do the documented clinical ­syndromes have, and how do you interpret them?

CS 13: Pulmonary foci left, suspected to be tumors, and skeletal tuberculosis (2004), foci with caverns right (2007) in 58-year-old chain-smoker with RA

• Ten years of known disease (Fig. 35), heavy smoker since the age of 15 • Bones (Fig. 36b) /2002/ with the following • Histology: there are granulomatous lesions of TB-type with central necrosis and histio-

cytary giant cells of Langhans type. A reasonable suspicion of existing osseous TB UUFour-combination therapy of bone tuberculosis (over 1.5 years) • X-ray lungs (Fig. 36a) /2004/ UUEmergency operation (segmentectomy) because of a suspected tumor • 2007: Check-ups for bone (Fig. 37) and lungs (Figs. 38, 39) • General condition normal, no adenopathy, CRP (×3), ESR 36 mm/h, anti-CCP-Ab (+) • Tine test (two times) and in vitro Quantiferon test for TB negative • Review of the histological findings in 2002: The small epithelioid cell granulomas are surrounded by a large wall of lymphocytes, typical central necrosis is evident, so a rheumatoid disease with development of rheumatoid-like granulomas can fundamentally be discussed. No indication of TB UUEmergency admission to intensive care unit with acute chest pain and the development of severe respiratory distress (02/2010). Additional questions: What morphological findings can be expected after lung surgery? Are the TB diagnostics certain? How do you interpret the current lung findings, what steps in the diagnosis and therapy are to be prioritized?

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CS 14: Acute swelling of toe 5 on the left, emergency synovectomy with a suspected tumor, female, 52 years

• Eight months ago – massive, acute, painful swelling of toe 5 on the left • At the same time unstable arthritis of PIP joints, cortisone injections • MRI: a serious destruction of MTP 5-head on the left, soft tissue mass arising from the

whole joint space cannot be separated, mostly distinct contrast enhancement, over a total diameter of approximately 2.7 cm. MRI unable to show either an inflammationrelated pseudo-tumor or a true tumor arising from the synovia. This implies unclear osteolysis in the 5th metatarsal UUEmergency MTP 5 synovectomy ensued due to the suspected tumor • After a similar incident on the other side (Fig. 41) and somewhat more stable arthritis in the various finger joints (similar to Fig. 40), the diabetological and rheumatologic investigation of the cause was recommended • Lab findings: no CRP, ESR 36 mm/h, RF-positive, anti-CCP-Ab highly positive. Additional questions: Was the synovectomy adequate? Would it be useful to determine RF and anti-CCP-Ab before the synovectomy?

CS 15: Asymmetric pain and imaging of the sacroiliac joint in HLA-B27 positive patient, male, 42 years

• Back pain in the mornings in the lumbar region, more on the right, about 8 months • X-ray of the sacroiliac joint (Fig. 44) – a balanced attack • MRI (Fig. 45), CT (Fig. 46) shows the different changes on either side. Additional questions: How do you explain the difference between the sides?

CS 16: Acute acral gangrene, high titer of ANA without organ involvement, female, 36 years

UUAcute event (Fig. 47), positive capillaroscopy, as in SSc

• No acrosclerosis, no organ/system involvement, CRP (×2) • Immunology: ANA 1:32,000, indiscriminate antigen, ACLA and RF negative • Angiography: almost complete absence of subsidiary network in the hands • Skin-muscle biopsy from the upper arm on the same side was normal. Additional questions: Can this disease now be defined? What should still be done?

CS 17: Localized pain, small gibbus in the thoracic spine and CRP elevation in HLA-B27-negative female, 50 years

• Sporadic, sometimes severe pain in the last 5 years (up to 100 mm VAS) involving the thoracic spine in the morning, much better after exercise or physiotherapy

• There is a small gibbus in the area of the 6th–9th thoracic vertebrae, with pain on palpation

• MRI thoracic spine (11/2006) at the request of the patient (Fig. 48a) • No comorbidities, Tine-test is negative, normal chest X-ray

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• X-ray sacroiliac joints: no joint space (as in Fig. 127) • Lab findings: HLA-B27 negative, CRP 35 mg/l (×7), ESR 64 mm/h • MRI (03/2007) after 3-month therapy with cortisone and Humira (Fig. 48b) • The CRP over the next 12 months (under Decortin 10–5 mg/day and ®

MTX 15 mg/week SC) were usually normal or slightly increased (up to 7.0 mg/l), ESR 14–24 mm/h • Clinically, the patient was usually free® of symptoms • After suspending MTX and Decortin there was a surge of the disease in 2 weeks which was more pronounced than at the beginning (local back pain up to 30–40 mm of the VAS, CRP 78 mg/l, ESR 62 mm/h) • MRI (28/02/2008) as shown in®Fig. 48a 50 mg the pain decreased significantly, with additional • The following day after Enbrel administration of Decortin® 40 mg – patient was symptom-free for 3 days: 20 mm/h ESR, CRP normal • Therapy® continued with Enbrel® 50 (25) mg/week and Decortin® 5 mg. The omission of Enbrel had no adverse effect. ®

Additional questions: Which underlying disease and condition are involved here? How can the effectiveness of the therapy be evaluated? Does the patient need ongoing maintenance therapy? Which therapy should be continued?

CS 18: Recurrent neurological and visual deficits (since the age of 13), 3-year treatment of multiple sclerosis (MS), high titer ANA, involvement of the central nervous system stabilized with Imurek® therapy, female, 17 years

UUSince the age of 13 (2002), several emergency hospital admissions at intervals of

2 months with significant motor and sensory disturbances (poor or no sight eight times, sometimes she could not walk or write) • Neurologically, optic neuritis and sensitive transverse myelitis were determined • These symptoms were reversible under high-dose cortisone therapy and always returned upon reduction of steroid medication • MS was diagnosed (because of the neurological and MRI findings) and treated with interferon, accordingly • Cranial MRI /2006/ (Fig. 50) • Immunology: 1:32,000 with ANA SS-A and SS-B (known since 10/2004), RF-positive • In childhood, the parotid was swollen without sicca syndrome (until now) • Biopsy of lower lip (2006): submucous salivary gland: lymphocytic infiltrates reaching the duct epithelium and adjacent interstitium.

Additional question: The symptoms during the last 4 years are the same. Which syndromes do not support MS or suggest an inflammatory rheumatic disease right at the start of this medical history?

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CS 19: Acute respiratory distress, pleural effusions and cold hands, male, 58 years

UUAcute onset (12/2005): a feeling of being bound, shortness of breath UUReferral to hospital: bilateral pleural effusions, and later hardening of the skin

• The hands at present (Fig. 52) • Sclerodactyly without contracture (as in Fig. 18) and scleroderma on the forearms and chest wall

• Current CT chest (Fig. 53) • Exertional dyspnea, lung function: DLCO 30% (severe limitation) • Immunology: ANA 1:1,000 with Scl-70 fluorescence pattern, in the last 6 months ANA without differentiation.

Additional question: What is crucial to the diagnosis and prognosis of this disease?

CS 20: Palpable purpura, abdominal pain and renal insufficiency, active hepatitis C, female, 50 years

• Known hepatitis C with massive viral load, unsatisfactory interferon therapy

UUAcute development of lesions (Fig. 56), recurrent, cortisone dose-dependent UURecurrent abdominal pain with emergency hospital referrals (3–4 times per year)

• Stable hematuria (4+), proteinuria (0.5 g/24 h), serum creatinine 1.42 mg/dl • Immunology: RF 189 kU/l, low levels of C3 and C4, ANA (–), ANCA (–) • Virology: Hepatitis C viral load (RNA): 511 977 IU/ml; HBV DNA (PCR) negative • Immune fixation: mixed cryoglobulinemia, type II, monoclonal IgM and IgG Kappa, low polyclonal IgG Lambda.

Additional questions: Is this clinical picture to be considered as the primary or secondary disease? What treatment options are suitable?

CS 21: No pulse on one side (since the age of 20), cardiac arrhythmia and two acute myocardial infarctions, female, 36 years

UUAcute myocardial infarction 3 years ago, single-vessel stenosis was dilated, restenosis the following day with stent insertion. This was followed by angiography (Fig. 61), and rheumatologic assessment following discharge (for the first time) UUTwo months later she suffered a second heart attack under immunosuppression UUAngiological intervention after 3 months (four stents in the stenosed branches of the supraaortal vessels and one in the right a. iliaca superior) Previous history to be considered:

• Since roughly the age of 20 the blood pressure could be measured only in the right arm, because the left pulse could not be palpated, though no clinical relevance was seen • Approx. 5–6 years exertional pain in the left chest and cardiac arrhythmias (interpreted as functional), no cardiac risk factors

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• Pain in the shoulders on exertion (lifting of the arm), diagnosis of tendomyosis with subsequent spinal blockades, no cardiological investigations

• Claudicatio intermittens (pain-free walking distance only about 200–300 m). Additional question: What preceding symptoms are indicative of the current illness, and what type? Does the diagnosis seem certain at present? How can the activity of the disease be controlled?

CS 22: Puffy hands and high CRP of unclear etiology in 17-year-old trainee painter

UUAcute event on the job with movement deficits of the hands (Fig. 66)

• Lab findings: CRP 120 mg/l, no groundbreaking immunological findings • Angiography: normal findings • Response to cortisone: Fig. 67, CRP normal.

Additional questions: Which morphological substrate of the disease is supposed, and what diseases are likely?

CS 23: Acute arthritis and Tietze syndrome with HIV, female, 36 years

• Six months known HIV (ascertained from diagnosis of 1-year-old son)

UUAcute florid arthritis: some PIP (Fig. 68), asymmetrical ankle, knee, hip and sternoclavicular joints (Fig. 69), confirmed by bone scans; significant movement deficits

• No skin changes (not even in the family), no organ involvement • Lab findings: CRP (136 mg/l), CD4 250/ml, HLA-B27, RF and anti-CCP-Ab are negative.

Additional questions: Is there an inflammatory rheumatic disease? If so, which? How would you formulate the therapy concept? If immunosuppressive treatment, should it be administered by a rheumatologist or an infectiologist, or both?

CS 24: Deformities of the hands, myalgia, pacemaker, red feet with ulceration, female 52 years (some episodes during 12-year follow-up period)

• Fifteen years ago marked myalgias with respiratory distress, cardiac arrhythmias

UUSeven years ago dizziness and unconsciousness with bradycardia, pacemaker implan-

tation (emergency surgery) • In the last 6 years, the problem with the hands (Figs. 70, 72) has dominated UUAcute condition (Fig.  71), recurrent, was regarded as erysipelas, no fever, no chills, no response to antibiotics, but to cortisone (Fig. 73) • Immunology: ANA 1: 10,000, ENA pattern: U1-RNP, SS-A, nucleosomes and ­histones; anti-CCP-Ab and RF negative. Additional question: How to define the type of this disease, the acute events and the ­deformities of the hands?

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CS 25: Fever, initially unexplained weight loss and increased inflammatory symptoms, in female of 50 years

UUHospital admission for clarifying the cause of the severe weight loss (15 kg), fever (up to 39°C) and CRP increase (×6) during the last 6 months

• Tumor and chronic infections were excluded by outpatient examinations • All imaging, vasculitis and CTD serology, procalcitonin were negative • PET (Fig. 74) reveals one main finding and a diagnosis. Additional question: Which constellations would advocate the earlier use of PET?

CS 26: Mouth ulcers, heart attack, increased ESR and CRP, female, 73 years

• Recurrent mucosal changes (Fig. 76) for several years, regular therapy with colchicine

UUAcute myocardial infarction without risks and without previous angina pectoris

• At the same time ESR 104 mm/h, CRP (x 8) – is possible) noticeable, but remained stable.

Additional questions: Which approach would best fit this clinical situation? Which additional tests or procedures should be arranged?

CS 27: Skin and mucous membrane bleeding, thrombocytopenia and high positive anti-DNA, no organ involvement, female, 54 years

• Skin and mucous membrane changes in 2007 (Fig. 78), spontaneous, cortisone dose-

dependent • Onset of the disease in 1980 accompanied by petechial lesions on the legs and nasal mucosa bleeding • No organ involvement, no arthritis or other connective tissue symptoms • Lab findings: platelet count was about 6,000/ml • Immunology: high titer of anti-dsDNA (253.3 kU/l), Crithidia test 1:20, SS-A-Ab (+) • Serum: detection of free antibodies against platelet-specific antigens • Good response to cortisone • Since splenectomy in 1981: recurrent course: the platelet count ranging®from 6,000 to 260,000/ml at the time of the Fig. – 12,000/ml when reducing Decortin to 10 mg per day (from 15 mg) and stable doses of CellCept® 1,000 mg during the last year UUIn July 2007 an acute event: fever with chills, CRP 252 mg/l, hospital admission • Urine: bacterial > 100,000/ml, leucocyturia • After intensive antibiotic therapy • Unstable course under therapy with Decortin® 15–20 mg and Myfortic® 360 mg daily × 4 tab. Additional questions: What disease or condition is likely? Is the complication specific to the  therapy? Make an entirely separate evaluation of the specificity of the clinical and immunological data.

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CS 28: Arthritis of the finger joints, rheumatoid factors and appropriate (?) MTX therapy, male, 64 years

• Several years of pain and swelling in the finger joints (Fig. 81) • Six-month regulation of MTX treatment by a colleague • No signs of inflammation, RF 1:40 kU/l. Additional question: Is such a therapy diagnostically justified?

CS 29: Alopecia, acute abdominal pain and massive proteinuria, male, 27 years

• Six years ago: acutely developed arthritis, alopecia areata (Fig. 82), changes in the skin

of the face (as in Fig. 54), massive proteinuria UUSevere abdominal pain: pseudoileus due to adenopathy, surgery UUSevere abdominal pain: thrombosis of v. renalis • Serology: high ANA and anti-dsDNA-Ab titers, low level of C3–C4 • Nephrotic syndrome: proteinuria up to 9.0–10.0 g/24 h, hematuria, leg edema • Strong headaches, responding to diuretics.

CS 30: Pulmonary fibrosis, Raynaud’s syndrome, Scl70 positive, HAP with response, deterioration in general condition and drop in DLCO transfer, abnormal thorax CT, female 66 years

• Nicotine abuses up to 1990, signs of chronic bronchitis • Since 2003-increasing exertional dyspnea, Raynaud’s

syndrome, swallowing difficulties • Lung function: FEV1 75–60%, DLCO 45% (2003), in July 2007 – 55% • Immunology: ANA (1:1,000) with Scl-70 differentiation • Therapy: azathioprine in the form of HAP®(Benenson et al. 2005) (20 cycles, a total of approximately 52,000 mg), then CellCept 2,000 mg/day (3 months) • Since 09/2007 increasing fatigue, shortness of breath, swallowing difficulties, weight loss UUIn the hospital the following were noted: • Lung function: FEV1 54%, DLCO 33%, oxygen saturation at rest 93% • Chest CT (Fig. 85), auscultation of the lungs: bilateral basal sonorous crepitation. Additional questions: What is the disease? What are the risk factors for the second disease? Should the entire medical history be considered a paraneoplastic event, or are there two diseases? Should therapy with azathioprine be seen as a trigger?

CS 31: Multiorgan involvement and MRT of the ENT region under immunosuppression, male patient 62 years (Benenson et al. 2005)

• Heart (myocarditis), CNS (encephalitis) and ENT involvement, ANCA positivity • MRI of the sinuses after four cycles of CYC therapy (Fig. 86) • MRI of the sinuses after six cycles of HAP (Fig. 87)

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• No coronary heart disease and stroke risk profile, stable course on MTX • Five weeks after stopping MTX the patient suffered a stroke with hemiparesis. Additional question: Should involvement of the central nervous system be suspected (RSS, Chap. 10.6) with a stable course under MTX?

CS 32: Arthritis, sicca syndrome and SS-A, CenpB- and anti-CCP antibodies, female, 67 years

• Problems with the hands for years (Fig. 89) with cold sensations • At the same time unstable dryness of the mouth and eyes • Lab findings: CRP (increased fourfold), ESR 36 mm/h • Immunology: 1:32,000 ANA, ENA subtype CenpB (>12,000), SS-A-Ab, Anti-CCP-Ab (> 200), RF (–)

• These constellations were interpreted by colleagues as a primary Sjogren’s syndrome • X-ray hands DIP 3–5 changes, calcinosis, even in the elbows • Slight swallowing difficulties and telangiectasia. Additional question: Which of four possible rheumatic diseases is involved?

CS 33: Multiple focal erythema, high ACE and pulmonary fibrosis, male patient, 42 years

• Skin changes (Fig. 90) in several parts of the body and head (about 2 years) • Morphologically: granulomatous inflammation • Chest X-ray (Fig. 91) • Lung function: DLCO-transfer factor of 62% (slight reduction), hepatosplenomegaly • Lab findings: no CRP, ACE approximately 2,400 U/ml (normal up to 40), Il2r approx. 3,800 U/ml (normal 750).

Additional questions: Could the granulomatous inflammation be non-specific in this case (as in CS 13, Fig. 36b) or present a different clinical picture with the same disease (Fig. 83)? Which of these two forms of granulomatous inflammation do respond better to corticoids?

CS 34: CYC-resistant nephrotic syndrome, unexplained subcutaneous involvement; activity and chronic indices from the perspective of renal biopsy, response to HAP, female, 52 years (Benenson et al. 2005)

• First disease symptoms (12 years ago): arthritis, pneumonia, then GN • Immunology: 1:10,000 ANA, anti-dsDNA-Ab 105.6 (positive > 75 kU/l), nucleosome

(81 RE/ml; normal <20), SS-A-Ab (+) UUAcute arterial hypertension (260/160 mmHg for 1 week), pain and swelling of the right leg, pelvic vein thrombosis (4 years ago) UUAcute events (Fig. 27) – 2 and 3 years ago and also recently with suspected erysipelas (as in Fig. 71), no response to antibiotics • Full recovery from these changes under high-dose cortisone • Five years ago: proteinuria 4.0–5.0 g/24 h, hematuria, serum creatinine up to 2.6 mg/dl

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• Morphologically (at that time) after CYC bolus (N16), Fig.  92 high activity index (9/24), low chronicity index (4/12)

• Renal biopsy after 18 cycles of HAP (Fig. 93): activity index decreased (1/24), chronicity index naturally increased (8/12)

• In the last 5 years under azathioprine 100–50 mg/day, a total of more than 120 g: ­proteinuria up to 200 mg/24 h, hematuria (–), serum creatinine 1.2 mg/dl.

Additional questions: How can the changes in Fig. 27 be classified? Is renal biopsy suitable for monitoring therapy? Should azathioprine continue, despite the large doses (looking at CS 30, where 52 g of azathioprine is suspected to be a trigger for the development of a neoplasm)?

CS 35: Severe hip pain in RA patient with minimal activity, male, 53 years

• Known earlier seropositive RA with polyarthritis, obesity II-III • Good response to Rituximab (as part of a study) • Increase in pain (pain on initial exertion) in the right hip • The state of the hips (Fig. 97). ®

Additional questions: Is this one or two diseases? What is the reasoning?

CS 36: Refractory heel pain and MRI confirmed response to laser therapy, female, 63 years (Benenson et al. 2006)

• Three years of severe, persistent pain (VAS 80–92 mm) in the heel area with motion

deficits which occurred after an intestinal infection; a fresh Yersinia infection was ascertained (RSS, Chap. 11.3.2) • Heel pain was resistant to local therapy (24 cortisone injections, repeated ultrasound and acupuncture, four cycles of shock therapy, local radiotherapy with improvement during the next 6 months) • Fig. 98, MRI of the foot (after standard therapy, or before laser therapy) • Fig. 99, MRI of the foot (after laser therapy) • Symptom-free during the subsequent 2 years. Additional questions: What are the suspected causes of the heel pain? Do you see a ­morphological correlate?

CS 37: Recurrent arthritis, tendinitis and enthesitis associated with Yersinia infection; responsive to laser therapy, female 36 years (Benenson et al. 2006)

UUAcute severe heel pain right (should not occur, walking only with support)

• MRI calcanea at the given time (Fig. 102) • MRI calcanea (Fig. 103) after therapy (785 mm soft laser N 10) • During 8 years recurrent, unstable arthritis in the small joints (as in Figs. 21, 24, 41), dactylitis (as in Fig. 65), tenosynovitis (as in Fig. 63)

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• No erosions (hand X-ray), no increased uptake in the joints (bone scans) • Anti-CCP-Ab, RF and CRP are not detectable • Serology: fresh Yersinia infection (RSS, Chap. 11.3.2), stable pattern of antibodies over the following 3 years.

Additional questions: Are the recurrent soft tissue disorders consistent with the associated Yersinia infection? What are the differences and similarities to seronegative RA?

CS 38: ANA positive mastitis, resistant nephrotic syndrome, nephrocalcinosis, questionable APS, phenprocoumon therapy, iatrogenic renal failure, female 27 years

• Since infancy, episodes of fever, floppiness • 1998: mastitis, developed under sun exposure, ANA positive • 2004: proteinuria (8.0–9.0 g/24 h), 2–3+ hematuria, exudative pleurisy • 2004: initiation of strict phenprocoumon therapy (due to the existence of APS resis-

tance and IgG antiphospholipid Ab, as well as hormonal contraception) • 2005: after renal biopsy (membranous and proliferative GN, class V) 8 cycles of CYC bolus, but without response • 09/2006 to 03/2007, therapy was switched to cyclosporine UUMassive abdominal bleeding as a result of follicle rupture, necessitating transfusion and emergency surgery • Since then renal insufficiency (serum creatinine up to 1.8 mg/dl, Hb 8.4 g/dl) UUAcute renal failure (creatinine 3.9 mg/dl, creatinine clearance of 14 ml/min) • Ultrasound and CT (Fig. 105) of the abdomen produced this image (fine granular), anti-dsDNA-Ab borderline, positive Coombs test • Immunology: ANA 1:160 ® 04th 2007: Decortin 20–10 mg and CellCept® 2,000–3,000 mg/day, Erypopoetin 8,000 • U/weekly • At present: good condition, normal creatinine and creatinine clearance, Hb 12 g/dl, IgG 2.68 g/l, non-selective glomerular proteinuria /approx. 0.5 g/24 h/, alpha-1-microglobulin (+), hematuria (–). Additional questions: Try to classify the syndromes of the basic disease and those which are associated with the side effects of therapy! Does the ANA-positive mastitis represent a rare manifestation of the underlying disease? Is the phenprocoumon therapy adequate from a diagnostic and therapeutic point of view? Can the kidney damage be caused by ciclosporin therapy? Is it wise to treat Coombs-positive anemia with erythropoetin medications? Should immunosuppression or other therapeutic options be reinforced?

CS 39: Refractory shoulder pain, MRI-assured response to laser therapy, female, 61 years (Benenson et al. 2006)

• Six months of constant pain in the left shoulder, under certain movements • MRI of the left shoulder before laser therapy (Fig. 106) • MRI after laser treatment (Fig. 107) • Symptom-free (observation time 14 months).

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CS 40: Attacks of fever with high CRP and erythema nodosum, female, 26 years Since the age of 16, recurrent episodes with similar symptoms:

• Skin changes (Fig. 109) • Fever as high as 39.5° with chills, CRP increased (×5–6) • The patient (nurse) takes Decortin 30 mg for 2–3 days with success • Pathogen serology: fresh Yersinia infection (RSS, Chap. 11.3.2), no other antibodies. ®

Additional questions: Does the diagnosis seem certain? Would an earlier diagnosis and introduction of antibiotics have been possible?

CS 41: Drug-induced generalized polymorphism in the efflorescences following TNF blockers, female doctor 49 years

• For 10 years, known psoriatic SpA, HLA-B27 positive, BASDAI 5.8 • Psoriasis with typical plaques on elbows and scalp • Three years of MTX therapy, efficacy not convincing • Conversion to Arava 20 mg/day, and Humira 40 mg once every 2–3 weeks • Therapy was effective (but better in 2-weekly intervals), also with regard to the lesions ®

®

(only a few plaques on the scalp), and well tolerated ® was stopped because of tingling in the ® hands. Monotherapy with Humira was continued UUTwo days after the regular injections the following changes suddenly occurred in the • Hands (Fig. 110) and • Soles (Figs. 111a, b) and at the same time the entire trunk and extremities • After stopping Humira®, the patient was given local therapy and switched to MTX • After 4 weeks the lesions were mostly reversible (only desquamation, without redness and pustules), but a short time later massive pustules appeared on the soles of the feet and hands accompanied by fever (relapse with secondary infection).

• In the last 2 months the therapy with Arava

Additional questions: Are these lesions specific to TNF-blockers? What should be ­prescribed for the increase in SpA activity, possibly a switch to other TNF-blockers or immunosuppressive therapy?

CS 42: Depression and treatment-associated gangrene, male, 50 years History: cerebellar infarction (6 months ago), obstructive pulmonary emphysema (COLD since the age of 25), marked depression, therapy necessary

UU(2003) sudden pain and cyanosis in the tips of toes 2–3 on the right, which regressed relatively rapidly under cortisone therapy

UUA few months later a more pronounced pattern appeared with distal gangrene on the same toes (Fig. 113), necessitating emergency surgery

• Because of the suspicion of systemic vasculitis, cortisone therapy was introduced

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• Rheumatologic assessment followed and clarification of the type of vasculitis and basic therapy (in question: muscle biopsy)

• The general condition is not reduced, no organ or tissue involvement, no Raynaud’s phenomenon

• Lab findings: no signs of inflammation, no pathological coagulation • Immunology: ANA, ANCA, complement consumption, immune complexes – no findings • Angiography: normal presentation of the abdominal aorta, pelvis, upper and lower leg vessels. The peripheral vessels are easily palpable.

Additional questions: Is the diagnosis of vasculitis certain? Do you see the specifics of the drug-induced vasculitis? Should further diagnostic methods be carried out (possibly muscle biopsy)? Are cortisone and basic therapy indicated?

CS 43: Acute puffy right hand after tophus ablation of first toe, male, 56 years

• Planned tophus operation (Fig. 114) in patient with known gout arthritis

UUThree days after surgery, acute problems in the right hand (Fig.  115) accompanied by severe pain and limited movement in the wrist, fever with chills and CRP increased (×6).

Additional questions: How is the acute puffy hand to be evaluated causally? The optimal therapy option?

CS 44: Polyarthritis, cortisone therapy, acute motion deficits in the hip, female, 25 years

• Florid asymmetric arthritis of the knees (with a massive effusion) and ankle, CRP

increased (×4) RA treated for about 4 months with cortisone and MTX arthritis was regressive • Severe pain in the left hip followed, active movements were hardly possible • Bone scans: focal increase in bone metabolism in the left acetabular roof. Clear ­etiological classification was difficult • MRI of the left hip (Fig. 121) • CRP, RF, and anti-CCP-Ab not detectable, fresh evidence of Yersinia infection.

• Suspected

Additional questions: Do you see a correlation in the findings of the MRI and the severe hip pain? How can the primary disease best be described? What treatment options should be introduced?

CS 45: Massive tumor on lower arm with bone destruction and ulnar compression syndrome in female patient with RA aged 55 years

• For 10 years, known seropositive RA without subcutaneous nodules, stage 3, moderate activity

• Hospitalization during childhood for TB

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• Two years ago, rituximab therapy (two infusions), no response • For 1 year, an elastic swelling (pain on palpation) in the forearm (reported by the patient to be approximately 10 × 4 cm and 2 cm above the skin) which had grown in about 2 weeks

• At the same time, numbness in digit 2–5. A neurologist had supposedly claimed: The

patient should not pay so much attention to her body. Consequently there were no doctor’s visits in the next 6 months and, incidentally, no increase in the tumor mass. Advanced ulnar nerve compression was diagnosed • MRI (Figs. 122a, b): Extensive soft tissue density mass with linear diameter 17 × 2.5 × 3 cm, inhomogeneous enhancement of the signal intensity, forming a wall around the distal ulna, partly destroying bone as well as local tendons. Recommendation: schedule surgery UUOperation (University of Cologne, van Loon, MD): a tumor with slimy yellow-brown, rough fluid surrounding, and infiltrating the extensor digitorum tendons, was removed • Histology: fibrinoid necrosis surrounded by histiocytes and granulocyte cells, necrotic destruction of the synovia • Postoperative: full remission of pain and neurological symptoms. Additional question: Was the clinical diagnosis of a suspected soft tissue tumor justified?

CS 46: Years of cortisone therapy in RA, vertebral fracture and acute paraplegia, male, 73 years

• For 12 years, known RA with minimal activity under mild immunosuppression (MTX

15 mg/week and Decortin® 10–5 mg daily), biphosphonate, vitamin D, calcium UUTwelve years ago – fracture of thoracic vertebra, emergency surgery (Fig. 125) UUOn 13/01/2008, the patient fell on his back. He then noticed that he was not able to lift his legs and had to be carried to bed. Involuntary urination ensued. The legs can no longer be lifted. The imaging shows: • MRI (Figs. 126 and 127a before surgery, Neurosurgery University of Cologne, Germany, 17/01/2008) • MRI (Fig. 127b postoperative, 19/01/2008). Additional question: In principle, could such a complication be predicted?

CS 47: Unclear arthritis and contractures of the fingers, diagnosis of RA, radiographic signs of OA and gout, male, 70 years

• Referred diagnosis of GP: suspected RA • Ten years ago, intermittent (some days), florid, sudden occurrence of arthritis (asym-

metric MTP 1, ankles, knees, PIP), right fist closure deficits • Hands (Fig. 130a) and X-ray feet (Fig. 130b) • Irregular use of diclofenac (150 mg) suppository • Lab findings: Uric acid 87 mg/dl, CRP negative, creatinine 1.34 mg/dl, RF and antiCCP-Ab (–). Additional questions: What are the diseases, and in what succession are they to be considered?

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CS 48: Acute severe pain in the legs, dramatic weight loss, abdominal pain, intestinal infarction, and positive cANCA, male, 30 years

• 25/06/2005: acute myalgias, weakness and paresthesia in the legs

UU03/07/2005: hospital admission for 3 weeks, neurology ward, cANCA (1:640), cortisone and CYC infusions

• 22/07/2005: 15 kg weight loss during the last few months with normal appetite

UUBrief hospital admission because of constipation, discharged after 3 days UU27/07/2005 subacute abdominal pain approximately 1 week, increased pain the next

day, abdominal tension disappeared; CRP (×10), cANCA positive, no abdominal CT findings. Antibiotics, cortisone UUAcute abdomen: general health deteriorated, severe abdominal pain and tension UUSurgical consultation and operation: intestinal perforation, 40 cm jejunumectomy. Additional questions: Which clinical syndromes are morphologically associated with the involvement of the small and medium-sized vessels? Are these syndromes disease-specific?

CS 49: Exudative pleuritis, adenopathy and morphological diagnosis of lupus in the skin biopsy, female, 40 years

• Exudativa pleuritis of unknown etiology (at discharge) • Subclavicular lymphadenopathy, biopsy: no indication of lymphoma • No arthritis or other connective tissue symptoms, no sicca syndrome • Biopsy of the unmodified skin: diagnosis cutane LE • Immunology: 1:10,000 ANA, ENA with fluorescence pattern SS-A, SS-B; RF (360 kU/l) • In the last 3 years the patient has been symptom-free, only immunology is remarkable. Additional questions: Is the diagnosis now certain? Neither of the biopsies showed any groundbreaking findings. Is biopsy essential in this disease? What findings - ­immunological or morphological, which appear to conflict - are to be given priority in the diagnosis? Can this condition be treated?

CS 50: MCP 2–3 and other forms of arthritis, MTX therapy, ferritin increase, male, 56 years

• Referred by a colleague for further therapy with a diagnosis of RA • Pattern (as shown in Fig. 58 bilateral MCP 2, as well as both ankles and right knee) can be confirmed by the bone scans

• X-ray hands (as in Fig. 59), erosions in the MCP 2–3 bilaterally, joint space narrowing in ankles and osteosclerosis

• Several years of MTX and cortisone injections with short-term effect • Normal CRP, ESR 1–3 mm/h, Hb 16 g/dl, ferritin 800 mg/dl (these tests were carried out for the first time).

Additional questions: What are the two main indications for a certain diagnosis? Which treatment options should be used?

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CS 51: Acute hemolytic anemia and pneumonia, at first associated with Chlamydia infection, female, 25 years

• Several years of anemia, further undifferentiated

UUPneumonia with positive Chlamydia pneumoniae serology and hemolytic anemia first interpreted as a Chlamydia-related condition, CTD immunology was not performed

• Later (outpatient): ANA 1:3,200, anti-dsDNA-Ab ELISA 216 kU/l, Crithidia luciliae test 1:160 (normally negative), nucleosomes and anti-Scl-70-Ab positive

• Over the course: unchanged ANA; dsDNA and nucleosome Ab negative; ACLA/G and M/, lupus anticoagulant and Coombs test positive

UUHospital admission with numbness in the left arm (as if gone to sleep), rotary vertigo with nausea

• MRI: non-specific former demyelization on the left and right • In the cerebrospinal fluid a protein increase to 89.2 mg/dl (normal up to 50 mg/dl) • Urine: mild proteinuria up to 400 mg/24 h, hematuria. Additional questions: Is this one or two diseases? Where does the opinion of a Chlamydiaassociated condition originate? What syndromes do you recognize? Therapeutic option?

CS 52: Minimal activity of RA and excessively high CRP and ESR, male, 68 years

• Polyarthritis of large and small joints (several years), rheumatoid nodules, high titers of

RF, anti-CCP-Ab, CRP (×4), ESR 40 mm/h • Regular®intake of 15–20 mg MTX/week, Decortin® 10 mg/day, during the last 6 months Humira 40 mg with stable improvement and clinical remission Over the course there was serious fatigue, indisposition, pain in the shoulders and neck, • arthritis of various PIP joints • Elevated CRP (increase up to 15-fold) and ESR (up to 65 mm/h) • Bone scans – no arthritis in the large joints • Exclusion of a hidden infection or neoplasia. Additional questions: Which disease(s) is/are likely? How do you explain the increase in CRP levels with minimal arthritic activity and a clear response to cortisone?

CS 53: Pain and swelling of the finger joints and high titers of RF, ANA and ENA, long-standing diagnosis of RA has been revised, female, 45 years

• Eight years ago developed the onset of pain and swelling in the hands and periarticular involvement of the finger joints. No organ involvement • Without Voltaren® the patient could not do her work (nurse) • Good response to therapy (MTX 10 mg/week, Decortin® 5 mg/day) • X-ray hands and bone scans reveal no deviations • Main lab findings: no signs of inflammation

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• Immune status: RF 1,046 kU/l/ml, ANA: 1:3,200 titer, fine speckled staining pattern, antigen specificity for SS-A and SS-B; dsDNA-ELISA and anti-CCP-Ab negative, C3 complement level normal.

Additional questions: What disease is suspected, which symptoms should actively be queried? Where are the boundaries between the RA and the newly defined disorder?

CS 54: Raynaud Sy, massive increase in CK and TSH in Scl-70-positive patient, female, 30 years (several episodes in a 5-year observation period)

• Hands (Fig. 130c) later developed digital pitting scars (as in Fig. 47) • Capillaroscopy of hands: rarefied capillary bed with avascular areas

(30–60%), i­solated ectasias (0–30%) and ramifications (30–60%) • Scleroderma of the skin proximal to the MCP (sclerodactyly), and chest wall which regressed under CYC • Immunology: ANA to 1:3,200 with the SCL-70-staining pattern UU07/2007: severe fatigue, muscle weakness, patient can barely walk or squat, CK (4,400 U/E) normalized by increasing the immunosuppressant UU09/2007: slow speech, concentration difficulties at work (civil servant) and with selfsufficiency, pronounced fatigue and muscle weakness, unable to work CK normal, TSH (300 mU/l, normal 0.27–4.20), free T3 0.6 ng /l (normal 2.0–4.4) and free T4 1.7 ng/l (normal 9–17), TPO 1,069 kU/l (normal <200) • After l-thyroxine (100 mg/day) significantly better with TSH (about 40 mU/l), normal T3, T4 values • Under l-thyroxine (150 mg/day) increase, the clinical symptoms improved. Additional question: Is the almost identical muscle problem with CK elevation during two separate episodes associated with the underlying disease or with hypothyroidism?

CS 55: Acute recurrent attacks of pain in toe 1 in 10-year-old girl, polyarthritis with deformities and elevated creatinine (20 years later) (Kurmanalieva et al. 1986)

UUAcute severe pain in the first right toe at night with increasing swelling and redness,

which in 1 week was completely reversible without treatment • These attacks alternated in both MTP 1 every year until the age of 27, since then ­polyarthritis (PIP as seen on Fig. 13, MCP, MTP, ankles) • The patient has always mainly followed a purine free diet, the attacks are associated more with stressful situations and colds, appear more frequently, the arthritis was almost stable with deformities, movement deficits • The first diagnosis was seronegative RA • Over the next 4 years nodes as large as beans developed, para-articular and auricular, X-ray feet, as in Fig. 130b • In the last 4 years, serum creatinine increased (to 2.3 mg/dl). Additional questions: What adult disease is similar to the clinical picture in the 10-year-old girl? What distinctions to seronegative RA do you see over the course?

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CS 56: Sicca Sy, enlargement of glandular parotid, acute increase in serum calcium and epistaxis (three emergency situations during regular 12-year period of observation, female, 65 years)

• 1995 increasing sicca syndrome and parotid swelling, RF highly positive

UU1997 left parotid enlargement, biopsy sample: MALT lymphoma, followed by total parotidectomy and radiotherapy, after which the sicca syndrome increased

• 2003 skin disorders as in Figs. 56a, b, no evidence of relapse

UU2004 during monitoring: serum calcium 3.40 mmol/l, b2-microglobulin (×2.5). Hospital

admission just 3 hours after blood withdrawal, no increase in parathyroid hormone (a distinction from real hyperparathyroidism), follow-up revealed non-malignant NHL, six cycles of chemotherapy; no vasculitis since, full remission; only massive sicca syndrome, parathormone replacement therapy UU2007 follow-up: Hb 7.6 g/dl, nose bleeds almost every day for 2 months. Emergency hospital admission: relapse of non-malignant NHL, six cycles of chemotherapy, ­currently full remission, substitution therapy for massive sicca syndrome. Additional questions: Which syndromes belong to the underlying disease, and which are of a paraneoplastic nature?

CS 57: Known PsA with minimal activity, polyarthralgias, long-term incapacity, discharge from cure therapy because of acute relapse (?), engineer, 46 years

• Skin efflorescences (Fig. 84b) • Polyarthralgias, minimal swelling in individual finger joints, fatigue • No CRP/ESR increases • Inability to work for a few months (certified by GP) • Initiation of MTX and cure therapy

UUDue to severe arthralgies, usually in the fingers, the patient was discharged within a week upon suspected relapse with the recommendation to seek rheumatological treatment for his PsA • General state is not compromised, no florid arthritis, even on bone scan, no erosions • No signs of inflammation in the blood, highly positive tender points.

Additional questions: Would you see two different diseases in this case? How do you assess the diagnosis, the long incapacity and the discharge from cure therapy?

CS 58: Arthritis, dramatic weight loss, severe swallowing difficulties, ANA with anti-Cenp differentiation, female 68 years

• Non-erosive arthritis of MCP 2–3 (more pronounced than in Figs. 58 and 89) • Raynaud’s syndrome, not so pronounced as in Fig. 52, telangiectasia • Difficulty swallowing, so that solid foods get stuck • Since 6 months increased weight loss (15 kg) without loss of appetite • CRP (×3–4), ESR (up to 40 mm/h), anemia (Hb 8.3 g/dl), normal ferritin values

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• Immunology: 1:10,000 ANA, ENA: CenpB (centromere)-Ab • Examination: no tumors found, TSH 300 mU/l, T3 0.6 ng/l, T4 1.7 ng/l. Additional questions: What disease is to be defined, and what syndrome is predominant?

CS 59: 31-year-old female patient with systemic symptoms, fever and discrete lymphadenopathy (NHL histology). After 14 years of general symptoms, “pain all over”, fatigue, depression, incapacitated

• Since the age of 31 subacute developments of the above symptoms • In the blood: ESR 30 mm/h, no CRP, ANA and anti-dsDNA-Ab borderline • Two-month hospital stay, diagnosis of suspected myocarditis, M. Still,

SLE (my diagnosis) UUBiopsy specimen of minimally enlarged, iliacal lymph node with diagnosis: highly malignant B-NHL. Polychemotherapy, able to work • After 14 years, again general symptoms, especially fatigue, subfebrile temperatures (not documented), diffuse pain. Incapable of work • Normal CRP, ESR 30 mm/h, ANA and anti-dsDNA-Ab borderline • Restaging showed no relapse of NHL or infection • Current therapy: strong painkillers and psychotropic drugs. Additional questions: Where are the distinguishing syndromes between the two disease patterns during the 14-year observation period? Do these diseases have not only common clinical, but also similar pathogenetic symptoms?

CS 60: Fever of unknown etiology, polyarthritis, positive Yersinia serology, lack of RF and anti-CCP-Ab, male, 40 years

UUAcute deterioration with fever (about 6 months), sweating, CRP (×30)

• Asymmetric arthritis of large joints (knee, hand, hip), back pain • Inpatient admission, discharge without a diagnosis, with almost identical symptoms • On presentation: some florid arthritis (knee with Baker’s cyst, ankle, hand, PIP joints

3–4 left and 2, 5 right, left shoulder, right elbow), confirmed by bone scans • CRP ×10 (currently ×2), RF and anti-CCP-Ab undetectable, fresh Yersinia infection (RSS, Chap. 11.3.2). Additional questions: Which diseases of such a pattern are likely? Where are the boundary syndromes between these disorders?

CS 61: Minimal activity of RA, diffuse pain, stable Fentanil requirement over the last 5 years, female, 80 years

• Hands, as in Fig. 129c • Has taken Decortin 5 mg and 20 mg Arava ®

®

daily for 5 years, CRP and ESR normal

24

1  Diagnostic Training and Rheumatology Trees

• Due to severe diffuse pain, the patient receives regular Fentanil 50 mg • Consultation because of severe pain, no improvement after increasing Decortin

to 20 mg/day UUThe patient attended without an appointment for treatment because of pain (needing a prescription for Fentanil). ®

Additional questions: Which diseases or conditions dominate which therapy the patient should be given and by which specialist, together with a rheumatologist? Would you agree that a stable and long-standing need for Fentanil excludes isolated RA?

CS 62: Fever, polyserosis, elevated CRP, GGT, LDH, and anti-DNA antibodies, male, 70 years

UUReferral to hospital with fever and shortness of breath, identifying:

• Fever 39° (approx. 2 months), exudative pericarditis and pleuritis • CRP (×20), GGT (×10) and LDH (×2) increases • Immunology: anti-dsDNA-Ab only about 50 kU/l (normal <25), ANCA negative • At check-up: no tumors or infections • No response to antibiotics • Corticoid prescription for suspected SLE with clinical response • Hospital discharge with unclear clinical picture and Decortin 70 mg daily • Presentation for rheumatologic examination, which confirmed: • No organ involvement, no CRP or LDH increase, only GGT (×2), no anti-DNA-Ab. ®

Additional questions: Which syndromes fit in with SLE, and which do not? Do you try, if necessary, to find a different approach by using the various syndromes (fever, polyserositis, GGT increase) which are shown in RSS, Chaps. 8.1 and 10.4?

CS 63: Cervical syndrome and isolated C1-C2 arthritis initially of unknown etiology, female, 53 years

UUSudden onset of persistent neck pain without neurological symptoms

• Cervical spine MRI findings: arthritis in atlantodental joint with bone marrow edema in

the arch of the atlas, the dens axis and an effusion in the atlantoaxial joints (in the area of Fig. 60) • Lab findings: HLA-B27 negative, CRP (×9), ESR 76 mm/h • X-ray sacroiliac joints (undertaken by other colleagues despite the lack of lumbosacral symptoms): sacroiliitis grade III, delicate syndesmophytes (as in Fig. 60) in the thoracic vertebral bodies 9/10 • Since CT-controlled transoral, peridental glucocorticoid injection (Dr P. BartzBazzanella) the patient is symptom-free. Additional questions: Should isolated bone edema with arthritis in the area of the neck or thoracic spine always be indicative of SpA and thus lead to investigation of the sacroilial joints? Would you prefer local or systemic therapy?

1.1  The Pictures and Clinical Cases That Every Doctor Should Correctly Identify and Interpret

25

CS 64: Acute myelitis with paraplegia, mouth ulcers, hemolytic anemia with thrombocytopenia, and positive ANCA, female, 47 years At present (09/2007):

UUPatient was admitted to central ER due to atypical pneumonia and reduced general health. Also remarkable:

• Hemolytic anemia and thrombocytopenia, initial fragmentocytes of around 20 per thousand

• ANA (1:1,000) +; anti-dsDNA, RF, anti-CCP-Ab, C3-4 normal, creatinine • Clearance 58 ml/min, proteinurie 0.18 g/l, ANCA positive (titer 1:160) without any ­specific pattern

• Syndrome-orientated treatment was initially given: • Fever removed by antibiotic therapy • Under treatment with cortisone, vincristine as well as four doses of rituximab: platelets

stabilized at a level of 130,000–140,000/ml, fragmentocytes decreased to 3 per thousand, other hemolytic parameters improved over the course (RSS, Chap. 10.10.1) UUHistory (2006) Status post brainstem encephalitis (pons and medulla oblongata) with paraplegia (6-month hospitalization and rehabilitation, completely reversed so far) • Arthritis of the wrists, Hb 10.4 g/dl • Malar rash, oronasal ulcers, anemia, and thrombocytopenia • Skin biopsy (05/2006): fibrosis, sclerosis, discrete lymphocytic infiltrates. Not a typical pattern for SLE • Proteinuria with renal insufficiency (creatinine clearance reduced to 32 ml/min). Additional questions: Which structures are affected in this case, connective tissue, small vessels, or both? Should the Moschkowitz syndrome, as well as the oronasal ulcers and ANCA antibodies, be regarded as disease-specific findings in terms of primary vasculitis? Would you interpret these constellations under the context of connective tissue disease, and if so, what type?

CS 65: Pain and swelling in the ankles of a physically active woman, 62 years, with known psoriasis vulgaris

• Known psoriasis vulgaris (as in Fig. 84b), intermittent gonarthritis right • During the last 6 months, severe pain with swelling and limited movement in the left

ankle joint • Lab findings: CRP (×3), ESR 36 mm/h; RF, anti-CCP-Ab, Yersinia serology negative • MRI of the left ankle: fluid-filled tendon sheath of the M. tibialis posterior, edematous changes of the distal signal in insertion area, bone marrow edema of Malleolus medialis. Additional questions: How would you formulate the imaging diagnosis? Would you regard these problems to be of a local mechanical nature or related to psoriasis?

26

1  Diagnostic Training and Rheumatology Trees

CS 66: Fever of unknown etiology, lymphadenopathy, and coughing in a patient aged 15 at the time (six episodes during the past 12 years)

UU1990: fever up to 39°, chills, cough, lymphadenopathy, rash macular edema, CRP (×10), GPT (×3), GOT (×2), GGT (×1.5), LDH (×2); RF, ANA, ANCA negative

• Exclusion of other diseases (sepsis, mononucleosis, endocarditis, CTD, vasculitis, and lymphoma)

• Biopsy of supraclavicular and hilar lymph nodes (by thoracotomy): no findings • Diagnosis at the age of 15 (which one, in your opinion?) • Over the next 12 years, six episodes with the same clinical and laboratory patterns, but always with a DD with a broad view of the above mentioned diseases visit on 7/03/2008: 3 weeks of cough, no fever, no deterioration in general condition.

• Last

Additional questions: Would these constellations correspond with those of CS 62 in a 70-year old male? In fact, is a full check-up necessary every time in such situations, and should the lymph nodes be removed?

CS 67: Emergency hospital admission with increased serum Ca, RA patient, female, 42 years The patient presented for the first time at our outpatient clinic in a relatively good general state of health, with:

• Polyarthritis (as Fig. 49a), positive RF and anti-CCP-Ab • The diagnosis of RA was clear. The standard laboratory

tests were ordered, as always • A few hours later, the duty doctor was informed by the laboratory that the calcium in the blood was 3.37 mmol/l (normal up to 2.5) UUThe patient was brought to hospital as an emergency and treated with infusions. The Ca values did not change, hence surgery was performed • Over the next 5 years a more stable course of RA and normal calcium levels. Additional questions: What happened? Which operation was carried out and what ­complication can be expected in this case under conservative therapy?

CS 68: RA patient with known, long-term MTX therapy and leucopoenia, response to CellCept®, female, 62 years

• Known RA (as in Fig. 40), RF, high anti-CCP-positive Ab, polyarthritis, high activity (CRP ×5)

• Nine years ago, corticoid MTX therapy prescribed (approximately 1 year) • Then: white blood cell count 1,000–800/ml, neutrophils (abs.), 650 cells/ml • Antineutrophil Ab (+) • Hepatolienal syndrome

1.2  Solutions to the Clinical Situations

27

• Bone marrow: no myelodysplasia, no toxic damage, rather regenerative changes. Additional questions: Would it be correct to interpret this condition as correlated to MTX? Which immunological studies could explain the cause of the neutropenia? Is immunosuppressive therapy indicated, or should it be seen as a contraindication?

1.2  Solutions to the Clinical Situations 1.2.1  Arthrology CS 69: Back and joint pain which cannot be clearly assigned – one of the most common problems of everyday rheumatology, male engineer, 63 years History: • Low spine pain (since 1992) and slipped disc • Increased intake of analgesics to be investigated • Abdominal pain and soft stools for some weeks (11/1999) • Gastroscopy: gastritis with Helicobacter infection resulting in recognized • Three-way combination therapy (for 2 weeks) • At the same time, severe, deep-seated lower back pain with stiffness and restricted mobility, cortisone injections in lumbar region (subsequently no symptoms) • Massive, painful swelling in right mid-foot as well as in right knee • Severe fatigue and drop in performance • This resulted in three hospital stays, one in orthopedics and two in internal medicine, for • New onset of massive elevation in CRP (to 61 mg/l), ESR (88 mm/h), GGT (220 U/l) with diagnosis of stage II borreliosis, treatment accordingly with • Proof of Borrelia-Ab, Rocephin® 2 g/day for 3 weeks, but no effect • Patient remains unable to work for roughly 5 months. On presentation (1999): • Pronounced painful swelling of (right) midfoot (as in Fig.  65 left) and (right) knee (as in Fig. 25), tenderness in forefoot and MTP 2–4 (right) • General health reduced due to drop in performance and movement deficits of right foot • Lab: same changes (see above), HLA-B27 positive, Ab (to Yersinia, IgG and IgA and to Antistreptolysin-O). The relatively complicated clinical pattern is characterized by the degenerative and newly occurring inflammatory joint and spinal problems on the one hand and by the general ­deterioration in health with massive signs of inflammation, elevated liver enzymes and infection-related antibody detection on the other. At this point, attempt to

28

1  Diagnostic Training and Rheumatology Trees

formulate a preliminary diagnosis. The diagnostic result has been presented using a syndrome principle (RSS, Chaps. 1–3) and staged diagnostics (RSS, Chap. 6), as follows. 1. Which structures are diseased? A. Clinical • Swollen right knee (DD inflammatory OA, arthritis of the knee) • Swelling of midfoot right (suspected tendinitis) • Tenderness of MTP 2–4 (suspected arthritis) • Lower back pain (degenerative low back pain syndrome, suspected sacroiliitis). B. Radiological (findings): • OA of right knee (initial stage and retropatellar OA) • Upper ankle joint (initial degenerative changes) • Status post compression fracture vertebrae 2 and 4 • Suspected sacroiliitis (as in Fig. 44) Response: right knee, MTP, tendon sheaths, possibly sacroiliac joints. 2. Are inflammatory or non-inflammatory processes taking place? C. Bone joint scintigraphy: • Increased activity in the early phase in • Right foot (as in Fig. 65b) • Right knee • Caudal portions of iliosacral joints • Both hips (late phase) D. MRI: • Right knee with synovialitis and effusion (arthritis) • Right foot: • Tendinitis in the region of midfoot • Arthritis at the level of the Lisfranc joints and MTP 2–3 Signal enhancement of bone marrow in MTP 2–3 region (osteitis, as in Fig. 102) • These findings should be verified in connection with clinical and laboratory (CRP 64 mg/l; ESR 86 mm/h) data. Response: the data suggest:

• Arthritis of the knee right • Arthritis of MTP 2–3 • Sacroiliitis, symmetrical • Tendinitis of right midfoot • Bone edema, reactive. 3. Are there infections, tumors or other diseases? Leading to the following considerations: • History: Indications of diarrhea prior to joint and back pain which incidentally was associated with certain, and treated, Helicobacter infection • Immunology and serology: • HLA-B27 positive

29

1.2  Solutions to the Clinical Situations

• Borrelia (IgG and IgM) Ab positive. Subsequently, Rocephin

therapy which brought no dynamics to the findings (neither clinically nor serologically) → RSS, Chap. 11.3.4 Yersinia Ab (IgG and IgA in ELISA and Western Blot) positive (→RSS, Chap. 11.3.2) Antistreptolysin-O-Ab slightly elevated→ RSS, Chap. 11.3.1 Chlamydia Ab negative Hepatitis serology negative CMV-Ab negative. ®

• • • • •

Response: fresh Yersinia infection and HLA-B27 positivity. 4. Are other systems or organs affected? Yes, namely the liver: • Selective increases in GGT and alkaline phosphotase • Clinical: fatigue, drop in performance, inability to work (6 months) • Chest X-ray, abdominal sono, gastroscopy, coloscopy, abdominal CT, ERCP, liver biopsy: findings unremarkable. Response:

• Neoplasia is thus mostly ruled out • Drug-induced liver damage (possibly Voltaren , Rocephin ) • Degenerative joint (knee, ankle) and spine (lumbar vertebral compressions) diseases ®

®

(known history).

Diagnosis:

• Reactive arthritis (ReA), Yersinia-induced, HLA-B27 positive (*) • Spondyloarthropathy with symmetrical sacroiliitis • Oligoarthritis: gonarthritis and MTP 2-4 right • Tendinitis of toe flexors 3–5 right • Reactive bone marrow edema (osteitis) of metatarsal bones 2–3 • Hepatopathy, most likely drug-toxic • Degenerative joint (knee, ankle joints) and spinal diseases • Status post compression fractures of lumbar vertebrae 2 and 4. (*) – Diagnosis is justified, also to formulate it as such (ReA could be assigned to SpA):

• Spondyloarthropathy, HLA-B27 positive • ReA etc. Therapy (28.3–26.5.00):

• Decortin 20 mg → 0 per day • Sulfasalazine 1,000 mg-0-1,000 mg per day • MTX 10 mg per week, SC N5 • Diclofenac 75 mg/day • Cortisone (soluble prednisone) – infiltration of right midfoot • Laser therapy: infrared (785 mm) ten sessions (one session 25 min) (Benenson et al. 2006) ®

Subsequently (follow-up period 14 months) the inflammatory and rheumatic symptoms and liver problems went into regression.

30

1  Diagnostic Training and Rheumatology Trees

CS 70: Resistant course of RA, full employment during five-year therapy with biologics, or procedures for therapy-resistant RA, electrician, 50 years

• Fig. 129c: seropositive RA (first diagnosis 7/95), polyarthritis, increased activity, constantly progressive course with episodes, stage III – a “classic” form (approx. 85% of all cases)

• Such a course is also reflected radiologically in progressive erosive changes (as in Fig. 9a) and with the less pronounced late sequelae as in Figs. 9b, 42, and 43.

Features and treatments for RA:

• Cortisone-induced

diabetes mellitus (first diagnosed 6/2001), currently treated with glibenclamide, Decortin® 10 mg daily (20 mg on deterioration of joint status) since 1995 • Inefficacy of all basic preparations and their combinations: • MTX 20 mg per week, SC (with ®short breaks, since 1995) Arava also in combinations with MTX • Sulfasalazine, ciclosporin, • Biologics: Kineret®, Remicade®, Enbrel® • Ibuprofen 800 mg 2–3 times daily • Rituximab 1,000 mg – two infusions per cycle (up to nine cycles at present) • Initial infusion since 10/2003 as part of a multicenter, randomized, placebo-­ controlled study. From the clinical course (clear improvement in pain and joint swelling) it can be presumed that the patient is in the verum arm • Thereafter, open retreatment cycles with Rituximab were undertaken on account of recurrent deteriorations, at intervals of between 6 and 10 months. The patient has been able to pursue his trade effectively during the entire follow-up period.

1.2.2  Connective Tissue Disease (CTD) CS 71: Rheumatic fever (Chorea minor, anamnestic) and new onset of arthralgias with swelling and massive proteinuria, 16-year-old male On presentation (03/2006): • Three weeks ago developed arthralgia in almost all joints (moderate and severe), minimal tenderness, swelling in six joints, particularly PIP 3 (Fig.  128c) and right knee, fatigue, no clinically detectable organ/system involvement. Two weeks ago showed a normal pulmonary function and cardiac findings. CRP-1.5 mg/dl (normal <0.5), Hb 13.7 g/dl History (08/2003): • Sudden onset of Chorea minor with left-sided hyperkineses at the same time • Minimal aortic valve insufficiency with aortic valve and mitral valve sclerosis • Antistreptolysin-O 220 IU/ml, anti-streptococcal DNase B 314 IU/ml (normal up to 200) • ESR – 45 mm/h, (03/2003) angina tonsillaris (recurrent)

1.2  Solutions to the Clinical Situations

31

Labs from initial examination (03/2006): • CRP 7.8 mg/l (normal <5), ESR 26 mm/h, fibrinogen 594 mg/dl (normal <350), Hb 13.3 g/dl, PTT 49.2 s (normal 26–36.0), urine: proteinuria 2.5+, hematuria 1+ • One week later (with no therapy): clinically no dynamics, lab findings: CRP 26 mg/l, ESR 30 mm/h, proteinuria 4+, Hb 13.0 g/dl, other values as above • Immunology: anti-dsDNA-Ab 1:3,200, homogeneous (IFL), 385 kU/l , normal <100 (ELISA), Crithidia test positive; ENA (six subtypes) negative, ACLA negative; Lupus anticoagulant positive; b2-glycoprotein negative, C3–C4 consumption in normal range. Other values (antistreptolysin, anti-DNase B, Yersinia, Chlamydia, anti-CCP- Ab, RF) negative. CS interpretation: 1. Which clinical and laboratory syndromes exist? History (2003): • Angina tonsillaris (recurrent) /03/2003/ • Acute CNS involvement (Chorea minor, anamnestic 2003 with sudden onset /08/2003) • Minimal aortic valve insufficiency with aortic valve and mitral valve sclerosis • ESR 45 mm/h • Anti-streptococcal Dnase-Ab slightly positive, antistreptolysin-O-Ab negative. At present (2006): • Articular involvement (polyarthralgias, periarticular swelling, Fig. 128c) • Renal involvement (massive proteinuria, hematuria) • APS (positive lupus anticoagulant, with associated PTT prolongation) • SLE serology (anti-dsDNA-Ab, homogeneous pattern in IFL, ELISA and Crithidia test). 2. Do you regard these syndromes as diagnostic criteria (→ Rheumatology Tree 1 and 2, Chaps. 1.3 and 1.4) and the stages of diagnosis → RSS, Chap. 13). Certainly yes. 3. To which diseases would such syndromes apply? Look at the diagnostic criteria of SLE and rheumatic fever. The present syndromes fulfill the diagnostic criteria of SLE:

• Clinical (lupus nephritis →

RSS, Chap. 10.1, periarthritides → RSS, Chap. 1.3.2; Fig. 128c) • Immunological (lupus serology → RSS, Chap. 11.1) • Chemical (lupus anticoagulant, PTT prolongation →APS→ RSS, Chap. 11.4). Where rheumatic fever is concerned, the acknowledged Jones criteria are in fact present, but in terms of time are not consistent with streptococcal infection:

• The syndromes occur at the same time as each other (cardiac and CNS involvement, elevated ESR, but with questionable streptococcal serology → RSS, Chap. 11.3.1)

• But what would not fit with rheumatic fever is the angina, which occurred 6 months prior to the organ manifestations (not 2–3 weeks, as the criteria state) and should therefore hardly be correlated with this, and certainly not with acute CNS involvement

32

1  Diagnostic Training and Rheumatology Trees

• The elevated ESR at the time (2003) of the cardiac valve sclerosis and Chorea minor

(negative MRI finding with respect to CNS vasculitis) could more likely be explained using the SLE concept • In detail: The minimal aortic valve insufficiency established at that time with aortic valve and mitral valve sclerosis could, as is well known, be induced by APS (and not necessarily endocarditis) • The question whether the patient had rheumatic fever at that time at all, I would answer as no. The event 3 years ago was, in my opinion, also SLE but with a different clinical pattern. The urine, PTT and lupus serology was not investigated in 2003. 4. On the activity of the disease. At present, there is active SLE with LN. 5. Therapy: Immediately after establishing the diagnosis, a combination of Decortin® 30 mg with CellCept® 2,000 mg and aspirin 100 mg was instigated with gradual, full reduction (over 9 months) of both preparations. The patient was free of symptoms during the next 6 months, taking only aspirin, and there were no deviations in standard and immunological parameters. Such a condition could be defined as a remission, but should continue to be monitored (especially the urine every 3 months). 6. Course: After a break from therapy of 3 months (just aspirin) and intensive sun exposure, an episode of SLE developed with virtually identical symptoms: LN, Coombs anemia (up to 7.8 g/dl) and positive lupus serology. Therapy with cortisone, CellCept® and erythropoetin resulted in clinical remission after 3 months (no proteinuria, no hematuria, Hb 13 g/dl).

1.2.3  Vasculitis CS 72: Polyneuropathy, bronchial asthma, attacks of dizziness and eosinophilia, 41-year-old male

UUAcute process (on 26/02/2006): sharp pain in left metatarsal bone, followed the next

morning by numbness in the arch of the foot, hypesthesia in digit I and paresis of the left foot jack (hospitalization) • On the evening of 04/03/2006, sudden severe arthralgia in several joints UUOn the evening of 06/03/2006, sudden petechiae in the region of both feet, backs of the hands, elbows and at the same time left-sided medial pain in the upper and lower legs • History: multiple tick bites, also with erythema migrans, influenza and shortly before admission gastroenteritis with diarrhea • MRI of the spinal column: myelon normal • Clinical: no headaches, no meningism, normal liquor • EMG (and also clinical): sensomotoric, axonal-demyelinating polyneuropathy. Patient on crutches • Muscle and nerve biopsy: Pronounced vasculitis of the medium and small blood vessels with moderately severe, axonal neuropathy with muscular atrophy UUBronchial asthma (12/2005), acute, recurrent and serious (hospital stay)

1.2  Solutions to the Clinical Situations

33

UUOn 03/2007: (sub) acute attacks of dizziness and unconsciousness

• MRI brain scan (as in Fig. 50), MRI scan of CS: suspected initial myelopathy • Pansinusitis with almost full congestion of the main left nasal cavity (as in Fig. 86) • Blood: Eosinophilia 33%, CRP (×5), ESR 44 mm/h, CK-1033 U/l (over the course

35 U/l), CK-MB 58.2%, fibrinogen 773 mg/dl (normal value up to 350), IgE-578.0 kU/l (reference <160) • Immune status: ANA negative, positive: cANCA 1:160, pANCA 1:20, myeloperoxidase 42.2 RE/ml (+); circulating immune complexes (+), RF IgA increased to 106.7 kU/l ­(reference <25). The hospital diagnostics were based on the nosological principle, i.e., reaching the disease by starting with the symptom or syndrome (doctor’s letter):  he patient was initially admitted for acute-onset, progressive neurological sympT toms and petechial bleeding in both feet and the left hand, despite a lack of cephalgias and no meningism, suspected to have a meningococcal infection. Despite normal lumbar puncture, antibiotic therapy with Baypen® and Rocephin® was initiated. During differential diagnosis, consideration was also given to an atypical form of Guillain-Barre syndrome on account of the progressive distal pareses and sensory disorders. As a result of the known history of recurrent infections and exacerbation of bronchial asthma, consideration was given to a potential infection-induced autoimmune disease. In keeping with this, immunological diagnostics revealed eosinophilia and elevated values for pANCA and particularly cANCA, but normal findings for ANA. In accordance with the clinical symptoms and lab findings, consideration is to be given to acute primary systemic vasculitis. The correct entity was mentioned thereby that you have probably suspected and diagnosed. Using the syndrome principle, which explains the morphological and pathophysiological criteria of a disease, and an integrated diagnostic program (→Chap. 1.1, RSS, Chap. 13), the correct diagnosis can be achieved (clearly identifiable from Rheumatology Tree → Chap. 1.4): 1. The lead symptoms are clearly diverse (see above), and all clinical and Lab findings must be ascertained 2. This disease is evidently systemic in its nature 3. Diagnostic deliberations should always treat the issue of infection as a priority. In this case there is no evidence, as given in the report, of meningitis but only neurological symptoms and petechiae, which elsewhere are to be regarded in the context of other syndromes. Accordingly, it was time to consider an immunological disease 4. Which syndromes are involved? Try to compile them from the clinical pattern: –– It is primarily vascular involvement (cutaneous vasculitis in the form of petechiae, asymmetrical polyneuropathy, CNS involvement in the form of diffuse demyelination, myelopathy), detected microscopically. In addition there are the other –– Connective tissue symptoms, namely the severe arthralgias, pansinusitis and myositis (myalgia, CK elevation), then –– Inflammatory syndrome (increased CRP, ESR, fibrinogen)

34

1  Diagnostic Training and Rheumatology Trees

–– Allergy syndrome (bronchial asthma, elevations in eosinophils and IgE) and the –– Immunological activities (RF and immunocomplexes, cANCA and pANCA-Ab). Such syndromes depict the morphological substrate and pathophysiology of the disease 5. In terms of pathophysiology, all these syndromes are inflammatory in nature; this is also indicated by the efficacy of the subsequent immunosuppression (CYC, cortisone). Moreover, they are associated with allergy (bronchial asthma, eosinophilia, elevated IgE) and specific immunological activities (ANCA) 6. Other diseases (tumors, infections) were not detectable during the follow-up period. 7. These constellations are unique and, at the same time, represent the diagnostic criteria of primary vasculitis (mentioned in the hospital discharge report) 8. Subsequently, this suspected diagnosis should be compiled with appropriate criteria (make an attempt at this) and, if they fit, a diagnosis definitively made. The ultimate question: can the correct diagnosis be made without having ever seen such a disease? In such a case, the correct diagnosis can be achieved, nevertheless, by other means and identified syndromes, e.g., bronchial asthma (with pansinusitis) or by the severe arthralgias and myositis with polyneuropathy or by the investigation of the CNS vasculitis or by positive ANCA. It is important thereby to ascertain the morphology and pathophysiology of the process and rule out other diseases.

1.3  Rheumatology Tree 1: Articular and Musculoskeletal Disorders (Table of the Major Syndromes) Such a categorization concerns the diseases and pathological conditions of the musculoskeletal system and is applied in a hierarchical manner. Right at the top is the list of major diseases which have been outlined fairly extensively in textbooks. Right at the bottom, the leading arthrological symptoms are listed. Between the lead symptoms and diseases come the syndromes, as a bridge between the symptoms and diseases. In order to structure the clinical data, the syndromes are firstly linked to the morphologically diseased structures and secondly to the pathophysiological relationships. Hence the appropriate theoretical and practical knowledge is already tested during the initial diagnostic steps (recording history, clinical examinations, syndrome structure), i.e., each symptom or finding is to be considered with a view to morphology and pathophysiology. Here, you have an overview of the said diversity of arthrological problems at the same time as the scope or units of teaching as modules of this discipline. These modules – which take the form of syndromes based on morphology (Chaps. 1–3) and algorithms and a diagnostic screening program (Chaps. 6 and 7) – are presented in Rheumatology: Symptoms and Syndromes /RSS/ (E. Benenson, Springer 2011).

1.4  Rheumatology Tree 2: Connective Tissue Diseases and Vascilitides (Table of Syndromes of the Major Systemic Diseases) 35

The Rheumatology Trees cover the difficulties in differentiation at every stage of clinical investigation. Thus, in just a short time the entity and individual features of a disease or condition can be established. The most common emergency situations and new, effective therapeutic options, which remain to be discussed, have been listed herein (RSS, Chaps. 7, 12 and this book, Chap. 2).

1.4  Rheumatology Tree 2: Connective Tissue Diseases and Vascilitides (Table of Syndromes of the Major Systemic Diseases) Tree 2 presents all the diagnostic problems on this topic, namely – as in Tree 1 – the goals and stages of investigations, the scope of teaching, the teaching points, the structured diagnostic pathways and reasoning, and most common emergency situations. To begin with, the most important lead symptoms have been presented which have no disease-­ specificity and reflect the broad scope of the clinical symptoms. Such symptoms are fundamentally the same as in other systemic diseases such as tumors, infections, etc. Hence, consideration should first be given to exclusion of these diseases in order to then form the concept, as early as possible, of a systemic rheumatic disease. The next step should be to link the symptoms to diseased structures, thereby forming syndromes according to priority (RSS, Chaps. 8–12). These can be grouped, in turn, into four megasyndromes, namely connective tissue, system-/organ involvement, (auto) immune phenomena and other, possibly concomitant diseases and conditions. In order to be able to decide on the direction in which the systemic rheumatic disease is developing, a subsequent mental and diagnostic step should be taken (RSS, Chaps. 13 and  14), to define an exceptional morphological substrate or morphological correlate of the disease. Moreover, the question has to be answered whether the systemic disease is present in the form of CTD (predominantly involving connective tissue structures and small vessels) or vasculitis (mainly vascular involvement). At the same time, consideration should be given to the pathophysiology of the given disease. The specific, indicative observations on all Figs. and CS with individual therapeutic options are presented in Chap. 2.

Microcrystals

Inflammatory

Spondyloarthritis

Mono-/oligoarthritis

Mechanic

Osteoarthritis/ spondyloarthrosis

Osteoarthritis: * Heberden’s * Bouchard’s * Thumb base * Knee * Hip

* Secondary Osteoarthritis * Artrhitis, * Traumata • Malpositions * Bone necrosis (Perthes disease, etc.) • Paget’s disease

Degenerative

Arthropathy

* Diabetesmellitus * Osteochondrosis * Neuropathic arthritis • DISH * Cheiropathy

Hyper/ hypothyroidsm Acromegaly Hemophilia Neoplasia (leukemia, hypertrophic osteoarthropathy) Plantar Fasciitis

Tendinitis Tendinosis

Bone

Bursa Nerve

Myositis Myopathies Bursitis Poly-/mononeuritis Osteoporosis Osteitis

Local

Soft tissue rheumatism

Muscle

Tendomyopathy Diffuse (Fibromyalgia) Local (Muscle strain)

Enthesis Enthesitis

Fascia

Tendon

Subcutis Panniculitis Erythema nodosa

Systemic

Extra-articular features

Organ-/systeminvolvement, B-symptoms, CRP and BSG increase

• Arthritis and spondylois arthropathy with extra-joints features: * M. Still, * Juvenile arthritis * Connective tissue diseases * Vasculitis * Polymyalgia rheumatica * Accompanying diseases and conditions * Therapy-induced state * Osteoporosis

Paraneoplasia

* High florid arthritis because of gout and other arthritis/arthropathy * Joint blockade * Acute lumbago (sciatica) and other nerve root compression * Polyserositis (pericarditis), and other severe organ involvement

Emergencies:

Leading symptoms: Pain in the locomotor or ‘‘everywhere,’’ stiffness, movement restrictions, not clear origin of the CRP, ESR, rheumatoid factor increase, antibody to Streptococci, Borrelia burgdorferi

Arthritis

Polyarthritis

Idiopathic

Sponyloarthropathies (HLA-B27)

(Para) infection

Secondary

Rheumatic fever

ß-hemolyticStreptococci

Still’s disease, JIA

Rheumatoid arthritis

Neck and low back pain * Spondylosis * Spondylolisthesis • Disc herniation * Spinal stenosis

Rheumatology Tree 1 Articular and musculoskeletal disorders

Ankylosing spondylitis * Psoriatic arthritis * Reactive arthritis Arthritis associated with enteropathy, * Oligoarthritis, HLAB27 positive

Sarcoidosis, OA with synovitis

Sepsis, virus infection tuberculosis, gonorrhea

Lyme borreliosis

Gout, pseudogout chondrocalcinosis

New therapeutic options in RA, AS, PsA, JIA: * Remicade ® * Enbrel ® * Humira ® * Kineret ® (for RA) * MabThera ® (RA) * Orencia ® (RA) * Actemra ® (RA) * Cimzia ® (RA) * Simponi ® (RA, PsA AS)

Table 1  Rheumatology tree of the articular and musculoskeletal disorders

Diseases

Syndrome

Disorders pattern

36 1  Diagnostic Training and Rheumatology Trees

Exquisite morphologic substrate at

Pathophysiology of inflammation in

Diseases

Dystrophy

Final phase of the disease

T-B-dysregulation B-activation

Exocrine gland, Serosal

Mono-/polyneuropathy

Heart Kidney

Joints and parajoints

Subcutis, fascia, ligaments

Skin, mucus

Accompanying syndromes 2. As early as possible to think about the system- or connective tissue disorders

(Auto) immunological phenomena

General symptoms: Weight loss, fever, CRP, ESR – Increase

Accompanying diseases and conditions (tumors, pregnancy)

Metabolic syndrome

Therapy-induced states: Cushing’s syndrome Diabetes mellitus Ulcer of the gastrointestinal tract Osteoporosis

* Sepsis

* Asthma status by Churg – Strauss syndrome

* ‘‘Fulminant’’ APS

* Hypertensive crisis in SSc

* Amaurosis and deafness in giant cell arteritis

* High activity (CNS, renal, cardiac involvement) in SLE, PM/DM, SSc, PAN, Polymyalgia rheumatica

Emergencies:

proteinuria) and immune status (ANA, rheumatoid factor, Borrelia burgdorferi antibody)

Raynaud’s phenomenon, aphthae, weight loss, fever, shortness of breath, and variations in the laboratory (CRP, ESR increase, anemia,

Leading symptoms: Individual symptoms of connective tissue, organ involvement, and B symptoms (see above) mostly arthralgia, myalgia, purpura,

1. Cancer screening, exclusion of infection and endocrinological disorders

System-/organ

Connective tissue diseases Immunology

Lungs

Muscle, tendon

Lymphadenopathy, splenomegaly, MAS syndrome

Vasculitis Immunology

Esophagus, stomach, intestine Central nervous system, CNS

Bone, cartilage, bone marrow

Antiphospholipid syndrome (APS)

Immunomorphology

Cytopenia Eye, ear, nose, and throat

Vessel

Connective tissue diseases: 1. System-/organ involvement, muscles by PM/DM, parotids for Sjögren syndrome, 2. Small vessels (arteries, arterioles, capillaries, venules, veins)

Disease-specific immunology: ANA, ENA, ACLA, dsDNS, Sm, RNP, Scl-70, Cenp-, Jo-1antibody

A. Exudative B. Proliferative, sclerosing features

Connective tissue diseases with secondary vasculitides

A. Systemic lupus erythematosus (SLE) Poly-/dermatomyositis (PM/DM) Mixed connective tissue disease (MCTD), Primary Sjögren’s syndrome, relapsing polychondritis B. Systemic sclerosis (SSc)

CK, LDH – Increase

Vasculitis: (a) Large-artery (b) Medium-vessel (c) Small-vessel

(a) Proliferative (b) Necrotizing (c) Granulomatous, exudative Disease-specific immunology: ANCA, cryoglobulin, rheumatoid factor

Primary vasculitis

(a) Giant cell arteritis and PMR, Takayasu arteritis, Cogan syndrome (b) Panarteritis nodosa, CNS-V, Buerger (c) Wegener granulomatosis, Churg-Strauss syndrome, Behçet disease Microscopic polyangiitis, HenochSchönlein purpura, Hypersensitivity V Cryoglobulin-associated vasculitis

Mega syndromes: Connective tissue symptoms

Syndrome

Rheumatology Tree 2 Connective tissue diseases and vasculitides

Table 2  Rheumatology tree of the connective tissue diseases and vasculitides

1.4  Rheumatology Tree 2: Connective Tissue Diseases and Vascilitides (Table of Syndromes of the Major Systemic Diseases) 37

Explanations of Figures and Case Reports with Individual Therapeutic Options

2

All figures clearly present the clinical, radiological and morphological findings detected during everyday rheumatology practice. In accordance with their approximation to the morphological substrate of a condition or disease, they have been categorized into three divergent and loosely delimited groups: A. Condition-specific syndromes, when the depicted stable combination of the assembled symptoms represents a morphological substrate or morphological diagnosis of a condition; subsequently causal investigation should ensue. B. Non-disease-specific syndromes, when the figures can be assigned to more individual conditions and diseases. C. Disease-specific syndromes, when pathognomonic (Greek “indicative of a disease”) symptoms or the relevant diagnostic criteria of a certain disease can be identified. The diagnostic value of all syndromes, particularly of the most representative subgroup B of non-disease-specific syndromes, can be decisively (but not absolutely) enhanced if they are considered together with the pertinent CS (Chap. 1.1.2). The explanations of these pictures, with references to the relevant (sub) chapters of the text where the diagnosis is actually to be found (in RSS ), and the implemented concepts of i­ndividual therapy, have been provided as teaching support in Chap. 2. 1. This picture best represents our discipline. This classic pattern of targets in rheumatology should be visualized with the other structures not presented, namely connective tissues of the internal organs, nerves, vessels, immune and endocrine systems. 2. (B) A clinical syndrome (RSS, Chap. 9.1.2; see also Figs. 10, 11, 30, 31). Linked with the clinical data (weight loss and exhaustion, no organ involvement, ANCA negative, histologically involvement of the small arterial vessels in the subcutis with perivascular eosinophilia and granulomatous changes, capillary microscopy – highly pathological pattern consistent with vasculitis), this syndrome is to be assessed as certain vasculitis, though not disease-specific, most likely PAN cutanea benigna. Therapy: immunosuppression (Urbason® 30 mg and Imurek® 100 mg daily), nevertheless the course was resistant. 3. (C) Two diseases present here (RSS, Chaps. 1.3.1, 1.4.1, 3.1.1). Therapy: systemic (for primary disease) and as necessary local (cortisone injections). 4. (C) A disease (RSS, Chaps. 1.4 and 4.6; Fig. 8). Therapy: none since this patient had any arthralgia, evidently because she had been on several years of moderate immunosuppression (Urbason® 4 mg and Imurek® 100 mg) for the underlying disease (PM/DM).

E. Benenson, Rheumatology, Clinical Scenarios, DOI: 10.1007/978-0-85729-240-7_2, © Springer-Verlag London Limited 2011

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2  Explanations of Figures and Case Reports with Individual Therapeutic Options

5. (C) A disease (RSS, Chap. 1.3, CS 1) with specific radiomorphological pattern (Fig. 9a). Therapy: during the last 8 years, strong immunosuppression (at present Decortin® 10 mg and MTX 15 mg/week SC, earlier Enbrel® and Remicade®, recently Rituximab and Humira®), 18 orthopedic operations (some of which can be seen in Fig. 9b). Prognosis (RSS, Chap. 7.4) and the course of the disease (only the 8-year-old medical history) in this case is extremely unfavorable in spite of modern therapy. 6. (B) A clinical syndrome (RSS, Chaps. 3.2.1, 9.4.1; see also Figs. 27, 71) can be explained by serological investigation (CS 1). Therapy: doxycycline 100 mg for 3 weeks, increase in cortisone doses. These changes were reversible after 3 weeks.

CS 1: Acute swelling and reddening in the ankle joint in immunosuppressed female patient, 42 years In this patient with advanced disease (Figs. 5, 9a, b), an acute process with reddening, pain, and fever should probably be assessed first as sepsis, or erysipelas (this was the suspected diagnosis also in CS 5, 24, 34; Fig. 27). Septic arthritis of the ankle cannot be confirmed in this case, on the following grounds: non-synovialitic involvement (no dramatic functional deficits, no effusion in the joint), more likely the periarticular structures are affected, no septic fever, only moderate increase in CRP. Fresh Yersinia infection appears to be a good explanation for this process. 7. (B) A clinical syndrome (RSS, Chap. 4.6.2; see also Figs. 66, 115). Only in association with the clinical data (CS 2) can it be correctly interpreted in causal terms. Therapy: Decortin® 80 mg (!) more than 1 year (hardly appropriate in light of the activity and organ involvement, hence marked Cushing’s syndrome developed) and azathioprine 150 mg/day. With additional administration of MTX 15 mg/week, the symptoms and findings regressed and at present no cortisone, normal CRP.

CS 2: Puffy hands and high-titer ANA in 26-year-old female patient In this case a difference between synovitis and non-synovialitic, periarticular swelling of the joints (puffy hands) is first detectable (see also Fig. 128c). The term synovitis (like arthritis) implies that the swelling originates from the synovial membrane. That is not the case here. Diagnosis is found in the disease-specific immunology (RSS, Chap. 11.1), namely the high ANA titers with U1-RNP and Sm pattern with no anti-CCP-Ab and RF. Radiomorphological data (no enhancement on bone scan and no bone destruction on X-ray) also indicate an extra-articular cause for the swollen fingers. A definable, systemic disease is thereby involved. Increased immunosuppression produced clinical remission.   8. (C) A radiological syndrome (X-ray hands → RSS, Chap. 1.4.4; Fig. 4 belongs to the same patient). The destructive involvement of the PIP joints is the same, as in Fig. 9a. But here, we have the other disease. The polar differences between the two diseases,

2  Explanations of Figures and Case Reports with Individual Therapeutic Options

41

which are the two most ­commonly confused, can be seen, as in Fig. 9b, particularly well in the MCP and wrist joints. Therapy: local, as necessary.  9a. (C) A radiological syndrome (X-ray hands → RSS, Chap. 1.3.4 prior to surgery), belonging to the female patient in Fig. 5. Therapy: systemic medicinal (see CS 1) and orthopedic (see Fig. 9b) treatment. 9b. (C) A radiological syndrome (X-ray hands, following surgery, see Fig.  9a). Here, a typical, individual pattern of involvement (mainly MCP involvement) should be implied, i.e., the PIP joints are typical of the condition for both diseases (OA and RA); though whether the MCP (in RA) or DIP (in OA) are affected at the same time is important. 10. (C) A disease (RSS, Chaps. 9.1.2, 9.2.2; see also Figs. 2, 30–32). Acute course of a disease developed 30 years ago, i.e., before the era of immunosuppression. The dramatic traits of such a disease would today, as at that time, be prognostically unfavorable. Changes are suggestive, clearly, of inflammatory thrombotic involvement with necroses of the medium vessels. There we have the entity already (see the nomenclature of systemic vasculitis, Jennette et al. 1994). 11. (C) A disease (RSS, Chap. 13.4), see comments on Fig. 10. Which other diseases are possible? 12. (A) A radiological syndrome: Leriche’s syndrome (aortic angiography /RSS, Chaps. 9.2.5, 9.2.7, 9.2.9/ ascertained shortly before surgery and in fact Y-prosthesis). Causal interpretation in conjunction with clinical (CS 3) and above all lab findings (RSS, Chaps. 11.1, 11.4) only (the dramatic stenoses could also emerge from other diseases; see also CS 21, Fig. 132). Therapy: emergency OP (Y-prosthesis).

CS 3: Acute Claudicatio arteriosa manifested as weakness in the legs and lupus-type immunology in 40-year-old female patient (56 years at present) Of clinical interest here is the acute development of Claudicatio arteriosa, which, on exertion, was not characterized by pain in the legs – as is the case with peripheral circulatory disorders – but by extreme weakness in the legs (“no strength in the legs, not a single step further without having to stop”). The acuteness of this condition and its morphological correlate can be seen in Fig. 12, i.e., the extreme narrowing of the abdominal aorta and A. iliaca. The causes for this are certainly associated with the abnormal immunology, i.e., the high ANA titers, anti-dsDNA-Ab (but with negative Crithidia test) and ACLA with lupus anticoagulant. Such a anti-constellation is at once to be regarded as a condition or, in my opinion, a disease (RSS, Chap. 11.4). Clinically, the deciding factors are the lack of organ/system involvement and the recent development of livedo reticularis in the legs (see histological findings in RSS, Chap. 11.6). The lifelong therapy with phenprocoumon (16 years already) certainly appears to be optimal. Earlier prescriptions of cortisone and Imurek® were ultimately discontinued. 13. (C) A disease (RSS, Chap. 1.3.1) on account of the pattern of involvement: sudden developments (monoarthritis with redness, widespread swelling, intense pain with movement deficits) are already the diagnosis of a disease, regardless of whether the

42

2  Explanations of Figures and Case Reports with Individual Therapeutic Options

patient has stable hyperuricemia (as in this case) and which joint is affected (cf. Fig. 68 where there is also florid arthritis of the same joint, but with a completely different model). Pseudogout usually protects the schmall joints (RSS, Chap. 1.5.3). Therapy: Mainly anti-inflammatory (Arcoxia® 90 mg daily, prednisone 30 mg, later possibly colchicine). The patient cannot tolerate the allopurinol and benzbromarone, so could be eligible for febuxostat /Adenuric® 80–120 mg daily/, a novel non-purine selective inhibitor of xanthine oxidase or pegloticase, new uricosuric agent. The options with IL-1 blockers (RSS, Chap. 7.3.2) are also open. 14. (B) A clinical syndrome (RSS, Chaps. 9.1.2, 9.2.3, 9.2.5; see also Figs. 47, 52, 113) explicable only on account of the detailed history (CS 4); suspicion of systemic vasculitis could not be verified.

CS 4: Acute peripheral gangrene of unknown etiology in 48-year old male patient Diagnostics for vasculitis were initially instigated (Jennette et al. 1994). In this regard, no criteria were established, i.e., (a) no organ involvement, except for the lungs (COLD due to nicotine abuse) and liver (transaminase increase due to alcohol abuse), (b) negative CTD and vasculitis serology, (c) negative capillaroscopy for CTD and vasculitis, (d) no signs of inflammation. Accordingly, vasculitis was questioned as the appropriate diagnosis. When asked, the patient claimed to have typical Claudicatio intermittens (cf. Claudicatio arteriosa in CS 3), and the affected fingers had already been painful and blue during the last 2 years approximately. The patient reported to have accidentally hit these fingers with a hammer. Thus, the patient was not rheumatic. Therapy and prophylaxis to be managed at a practice for internal medicine or angiology. 15a. (C) A disease (CS 5; see also Figs. 84a, b). A condition prior to therapy: conventional immunosuppression (Decortin® 30–10 mg for 4 months and MTX 15 mg/weekly SC) was effective, but the baseline condition was still clearly visible. Subsequently, experimental therapy (double-blind, randomized, controlled study with Apremilast®) as part of a study also ensued. 15b. (B) The disease in this picture is not identifiable (cf. Fig. 15a; CS 5). The condition resulted following experimental therapy (double blind randomized controlled study with Apremilast®).

CS 5: Pain and reddening in the toes and forefoot, massive CRP increase, 63-year-old male patient The symmetrical dactylitis skin (reddening) and nail changes, leaves no doubt as to the diagnosis of the underlying disease. The suspected diagnosis of erysipelas seems rather unlikely on account of the symmetrical involvement. The degree of MRI changes would, in my opinion, be commensurate with the high CRP values. The response (ultimately complete regression of these changes due to intensified immunosuppression with MTX and Apremilast®) is an indirect confirmation of the immunological cause behind the process.

2  Explanations of Figures and Case Reports with Individual Therapeutic Options

43

16. (A) A clinical syndrome (RSS, Chaps. 3.2.1 and 9.4.1) emerged in a female patient (Fig. 3) after subcutaneous Kineret® injections; this was completely reversible upon discontinuation of the medication. 17. (B) A radiological syndrome (MRI of the brain, native: large cortical defects and atrophic changes: the demyelination areas periventricular and subcortical, predominantly in the region of the posterior horns of lateral ventricle, leukoencephalopathic changes in the frontal region, clear dilatation of lateral ventricles, particularly of 3rd ventricle, microangiopathy). Such changes can be interpreted correctly only in conjunction with the medical history (CS 6) and immunology (RSS, Chaps. 10.6 and 11.4). Therapy: initially, on suspicion of an inflammatory/vasculitic etiology to the multi-infarct situation, anticoagulation (ASA and Clopedogrel®) and cortisone therapy were initiated. During such therapy media infarctions repeatedly developed, necessitating the use of phenprocoumon (no new clinically distinguishable processes have since occurred). In my opinion there was no indication for extension of the immunosuppression (without signs of further organ manifestations and no ACLA). Furthermore, life-long anticoagulation (phenprocoumon therapy) is being administered, if necessary minimal doses of cortisone, social and medicinal rehabilitation.

CS 6: Several insults (since age of 17), normal delivery and at present (after 12 years) dementia, ­ deaf-muteness and spasticity, 41-year-old female The patient had residual symptoms following multiple infarctions, such as anacusis, aphasia, impaired vision, intellectual deficit and spasticity, emphasized on the left and symptomatic epilepsy. These media infarcts could fundamentally be correlated to vasculitis, thromboses or both. Primary CNS vasculitis was at no time detected by MRI. The lack of lupus-specific organ involvement and dsDNA-Ab almost certainly rules out the existence of SLE, despite the histological examination of the skin (suspected LE). Immunology also revealed no ACLA in the blood. These contradictory clinical and immunological data are, in my opinion, most likely to be interpreted within the context of primary APS (Sneddon’s syndrome). This concept, and the phenprocoumon therapy given as a consequence, achieved a certain degree of stability in the disease.   18. (C) A disease with several syndromes and symptoms (RSS, Chaps. 1.3.3, 3.1.4, 4.6.1, 9.1.4, 9.3.3, and 9.4.3). On DD, CREST syndrome could also be a possibility. Therapy was determined from the activity (some signs of activity /look at the right wrist/; the consequences of such inflammation /contractures/ are visible) and organ involvement. For the hands: heat, movement therapy, Dolobene Gel®.   19. (A) A clinical syndrome (RSS, Chaps. 1.3.3 and 9.3.3; see also Figs. 18, 43, 62, 80, 130a), here in a patient with tetraplegia. Condition not active. Therapy: only movement and physiotherapy, no surgery. 20a. (A) A clinical syndrome (RSS, Chaps. 9.1.1, 9.2.1, and 13.6) is explicable only in ­conjunction with clinical findings (CS 7). 20b. (B) A clinical syndrome following therapy (cf. Fig. 20a). Lasting regression of such symptoms from two cycles of doxycycline therapy infers causal involvement.

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2  Explanations of Figures and Case Reports with Individual Therapeutic Options

CS 7: Massive Livedo racemosa, reversible with doxycyclines, female, 53 years Causality is a major problem in this case. Neither the biopsy nor CTD immunology was indicative. The positive borreliosis serology (RSS, Chap. 11.3.4) and curative effect of doxycyclines (Fig.  20b) are most likely to be seen as criteria for Lymphadenitis cutis  benigna in borreliosis (Fig.  20a) (this is how the case was interpreted by Dr B. Heilig). 21. (B) A clinical syndrome (RSS, Chap. 1.3.1). Only is explicable causally in the context of Figs. 22–24 and CS 8. Monoarthritis is visible (where?). Therapy: biphosphonates and local cortisone injections; at the spread of arthritis, MTX option is to be considered. 22. (B) A radiological syndrome (X-ray hands): cystic changes in the same joint. 23. (B) A radiological syndrome (CT hands): marked erosive changes in this joint (two projections pictured). They can be interpreted only in conjunction with certain diseases (RSS, Chap. 1.3.4). 24. (B) A clinical syndrome: MTP monoarthritis and oligoarthritis represent, in an HLAB27-positive female patient, the typical pattern of involvement for the relevant ­diseases (RSS, Chap. 2.2.1). Namely, not the individual clinical or radiological investigations, but together with CS 8, such findings may be disease-specific.

CS 8: Stable mono-/oligoarthritis, HLA-B27-positive female patient, 18 years Firstly, the clinical and radiomorphological syndrome diagnostics are to be interpreted. Clinical findings showed stable monoarthritis (more than 1 year); hand X-ray revealed suspected erosive arthritis (massive cystic changes). CT produced the most important ­feature of MCP 5 arthritis, which with such clinical findings and radiology is only to be suspected. In terms of cause, attention is to be paid mostly to stable monoarthritic involvement, and later onset of oligoarthritic involvement. At such an age, three diseases are ­possible. One can be differentiated immunologically (see above, negative RF and ­anti-CCP-Ab). The other two are to be suspected, rather, from the changes revealed by CT (RSS, Chaps. 1.3.4 and 2.2.1). Therapy should, in my opinion, first be local and later ­systemic (see comments on Fig. 21). 25. (B) A clinical syndrome (RSS, Chaps. 1.3.1, 1.4.7, and 4.10.1) only to be correctly interpreted within the context of the clinical findings (CS 9) and MRI (Fig. 26). 26. (C) A radiological syndrome (MRI of left knee → RSS, Chap. 1.4.6): clear chondromalacia in medial femorotibial joint compartment, mild bone marrow edema of medial femoral condyle, medially emphasized capsulitis, manifest suprapatellar joint effusion. This finding itself is a diagnosis and provides an exact explanation for CS 9. Therapy (local): Triam® 40 N 4, with MTX 20 mg N 2 twice, hyaluronic acid Synvisc® N 5. No pain during or after running a marathon (recently under 4 h).

2  Explanations of Figures and Case Reports with Individual Therapeutic Options

45

CS 9: Acute arthritis of the knee at 50-year-old marathon runner In such a case, MRI is highly appropriate for primary morphological diagnosis. A next step was joint puncture with subsequent punctate testing (leukocytes <1,000/ml, mostly ­lymphocytes, negative CRP and RF). To be thorough, certain serological tests (RSS, Chap. 11.3) could be conducted. The aforementioned therapy was functionally effective. 27. (B) A clinical syndrome (RSS, Chaps. 3.2.1 and 9.4.1; see also Figs. 6, 71, and 73 / following therapy/) should in this case /CS 34/ be causally ascribed to the underlying disease as with CS 24 (on exclusion of a septic process). Therapy: high-dose cortisone (Decortin® 40 mg/daily) and MTX, good response. 28. (C) A disease (RSS, Chaps. 1.3.1 and 3.8, CS 10) in initial stage. Therapy: provided the  patient agreed (desire for children!), induction therapy was first undertaken for 4 months, namely with cortisone (Decortin® 30 mg to 0/daily with MTX 15 mg/week), then maintenance therapy (hydroxychloroquine Quensyl® 200 mg). No routine ­therapy in the last 8 months (patient takes cortisone for any minor episodes).

CS 10: PIP bursitis and MCP 2 arthritis, 26-year-old female Stable (bursitis indicative thereof) PIP 2-3 arthritis in a young woman, highly suspicious of a diagnosis which can be confirmed by immunological investigations. Consequently, on consulting the patient (due to the desire for children) pathogenetic therapy was undertaken, resulting in immediate remission (see above). Patient is presently in the 24th week of pregnancy. Normal first-born. 29. (C) A clinical syndrome (RSS, Chaps. 3.11.6 and 9.8) with cartilaginous inflammation in typical areas that should be considered a rare condition. In this case, it first advances to a systemic inflammatory disease due to the symmetric infestation of the ears (5 months ago) and RA-like arthritis of the finger joints (2 months later), CRP increase (factor × 9). Other disorders (CTD, systemic vasculitis or myelodysplastic syndrome) or typical organ involvement (nose, trachea, airways, eyes, heart) are not apparent. Here, or even generally, a cartilage biopsy is not required to make the diagnosis (a traumatic event with morphological data, which is also seen clinically). Therapy: the patient, a 66-year-old male with persistent disease, has diabetes mellitus and did not respond to current therapy (prednisolone 25 mg daily), therefore he was prescribed MTX 15 mg/wk SC. Intensification of the immunosuppressive therapy as far as ­allogenic bone marrow transplantation cannot be ruled out. 30–31. (A) A clinical syndrome (RSS, Chaps. 9.1.2, 9.2.1, and 9.2.2; see also Fig. 2 with histologically defined disease) with disease not clearly definable (CS 11). Therapy (from my perspective): strong immunosuppression (cortisone and CYC pulse therapies), certainly accompanied by symptom-oriented therapy for pulmonary hypertension, ongoing at this time together with low doses of cortisone.

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2  Explanations of Figures and Case Reports with Individual Therapeutic Options

32. (A) A clinical syndrome (RSS, Chap. 9.1.2) after one year (complete scarring of the deep ulcerations presented in Figs.  30–31). Therapy: low-dose cortisone without immunosuppression.

CS 11: Livedo racemosa and deep ulcerations with pulmonary and renal involvement, ANCA negative, 42-year-old male patient It is a serious clinical problem. Diagnosis: The diagnosis was formulated thus at a hospital abroad: primary pulmonary hypertension, leg ulcer. Dyspnoea. Livedoid vasculopathy. Nephrotic range proteinuria, mild nephrosclerosis for biopsy, pulmonary hypertension, right ventricle dysfunction, monoclonalgammopathy, ANA positive 1/160. Thereby, all syndromes are compiled without consideration of the development of the disease (initially there were the changes in the legs) and without formulating a common nosological concept which could unite such syndromes pathogenetically and would permit therapy to be devised in more than a syndrome-oriented way. Hence, with the exception of prednisone, only symptomatic therapy with a view to pulmonary hypertension (24 h) is being undertaken at present. My interpretation: Livedo racemosa and deep ulcerations, which were the first manifestations of the disease, signify the involvement of the small and medium vessels (establishment of this fact is virtually a diagnosis (RSS, Chaps. 9.1.1, 9.2.1, 9.2.2, and 9.2.9), although the biopsies performed in triplicate evidently were unable to furnish any clues regarding morphological diagnosis. The above mentioned pulmonary and renal symptoms are to be assessed within the context of such graphic pathomorphology. In such patients, four diseases or states are most likely (Jennette et al. 1994). Two diseases (APS and Cry-V) can be identified from blood tests. The non-specific morphological and immunological findings do not, as is well known, rule out vasculitis, i.e., PAN. If this concept, which I favor, does not fit, such a situation can also be described as non-­ differentiated vasculitis, without pathognomonic symptoms – which in the case of CTD (see CS 16) or vasculitis is often the case. Such an assumption can justify the strong immunosuppression in similar, not very distinct cases – which in this event appears to be necessary. Even one state came into question, although livedoid vasculopathy. It has been recognized mainly as skin involvement and a nonvasculitic disorder of coagulation, but authentic vasculitis in the underlying subcutis can occur in cases of CTD and PAN with organ involvement typical of these diseases, as seen in this case. The association of the non-inflammatory livedoid vasculopathy with progressive pulmonary hypertension has not yet been addressed. Therapy: (from my perspective in terms of the inflammatory nature of this event) strong immunosuppression (cortisone and CYC pulse therapies), accompanied certainly by symptom-oriented therapy. In addition, place the full regression of these ulcerations (Fig. 32) and a certain stabilization of the disease (patient has been able to work for about 6 months). Over the course there was progressive right heart failure, despite maximal therapy for pulmonary hypertension, and the patient died 3 years after the outbreak of the disease (December 2009, you can see the dates of the images). 33. (B) A clinical syndrome (RSS, Chaps. 9.1.1, 9.2.1) appears, in conjunction with CS 12, to certainly be disease-specific. Systemic therapy to be conducted, also with the ­present

2  Explanations of Figures and Case Reports with Individual Therapeutic Options

47

lack of organ involvement, primarily on account of the massive spread in skin changes; several medications were applied (CYC, MTX, Arava®) without success; moderate cortisone therapy (Decortin® 40 mg daily for 2 weeks) conducted, at present MMF therapy (up to about 4 months ago) so far achieving a certain stabilization of the ­disease and regression of myositis.

CS 12: Localized erythema, elevated CK and positive ANCA, 45-year-old male All the clinical data suggest, in line with the criteria, a rare form of prognostically unfavorable vasculitis (most likely MPA) with cutaneous, subcutaneous, testicular and muscular involvement, but to date with no organ involvement, apart from selective hematuria with no renal insufficiency. Nevertheless, on account of the massive cutaneous/subcutaneous changes and the highly unpredictable course, intensified immunosuppression should be initiated (see comments on Fig. 33).   34. (B) A radiological syndrome (CT wrist bone left). A clear radiomorphological diagnosis (RSS, Chaps. 1.3.4, 3.10.1, and 4.5): sharply demarcated cystic lesions around the bone of the wrist, particularly the Os lunatum, mainly on the left (small singular cysts on the right). Morphologically: the bony tissue appears vital and free of inflammation; the soft tissue has localized necrotizing, florid inflammation with a predominance of neutrophilic granulocytes. In conjunction with pain in the areas of both hands and unstable swelling of the wrists, for about 1 year, the causes for such multiple osteolyses in a 72-year-old woman are difficult to identify. The extensive sclerosis of the cyst walls and central localization of the cysts does not suggest bony lesions as part of gout (cf. Fig. 130b). A lack of immunological activity (anti-CCP-Ab, RF) and clinical evidence (no other joints involved, no previous illnesses, including psoriasis, no organ involvement) also does not seem to provide any indications. A colleague also believed this case to be RA. It is difficult, with a lack of RA criteria, to accept such a concept. With a localized problem, e.g., intraosseous ganglion, TB, sarcoidosis, possibly multiple myeloma, lymphoma, there was no indicative finding. Consideration should more likely be given, in my opinion, to an osteolytic syndrome (etiologically unexplained bone absorption /vanishing bone disease/ with “non-­reactive” bone defects, as in Fig. 34).   35. (C) A disease (RSS, Chaps. 1.3.2, 1.3.3, and 3.1.1) based on the pattern of involvement, also with respect to symmetrical involvement. Other radiomorphological syndromes in this patient (see below) can be interpreted only in the context of this picture and CS 13. 36a. (B) A radiological syndrome (X-ray chest → RSS, Chaps. 1.6, 3.1.1, 10.2.2, and 13.3): such nodules should first be investigated from an oncology viewpoint. Open lung biopsy ensued, with diagnosis of “rheumatoid nodules” which were also visible in Fig. 35. 36b. (B) A radiological syndrome (MRI tibia → RSS, Chaps. 3.1.1, 13.3, and 3.11.8); these local bone changes are clinically consistent with cysts, enchondroma, possibly chondroblastoma or other tumors (e.g., villonodular synovitis). A morphological finding

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from the bioptate was described as granulomatous inflammation with necrosis and interpreted as bone TB. Consequently, tuberculostatic therapy was undertaken for 1½ years. At present (2008) this morphological pattern is interpreted differently, namely in association with the rheumatoid nodules (see histological reference finding in CS 13, Chap. 1.1.2). 37. (B) A radiological syndrome (X-ray tibia → RSS, Chap. 13.3). Ostitis cystoides multiplex. Such a picture confirms the ultimate interpretation of the bone involvement (see above). 38. (B) A radiological syndrome (X-ray thorax → RSS, Chaps. 1.6, 3.1.1, 10.2.2, and 13.3): Detection of disseminated and poorly demarcated, rounded swelling projecting onto the whole right and left lung. They are mostly consistent in terms of number and size with the previous examinations ... rounded transparency with horizontal reflection projecting onto the right mid lobes. Here, no radiomorphological differentiation can be made between disintegrated rheumatoid nodules and, for example, a tuberculous cavern or abscess cavity. This picture poses the same questions as Fig. 36a (2004, see comments). A chest CT was arranged (see Fig. 39). 39. (B) A radiological syndrome (CT thorax → RSS, Chaps. 1.6, 3.1.1, 10.2.2, and 13.3) enables confirmation of Fig. 38: “Detection of partly pleural nodules of a maximum of 3 cm in diameter. Ventrally, in the mid lobe, and touching the pleura, there is a cavern of 2 cm in diameter. These pulmonary lesions are highly consistent with necrobiotic rheumatoid nodes. Radiomorphologically, there is a concurrent malignant growth which cannot be ruled out with absolute certainty”(all the more so in a chain-smoker). In comparison with Fig. 85, where a small-cell carcinoma was morphologically confirmed at almost the same localization as the nodules (dorsal, paravertebral), hardly any difference is to be found. One cavern (right front) is suggestive of TB (a diagnosis which was formulated in 2004). The third (my) version – involving several extraarticular rheumatoid nodules – can be justified over the course, since the general health was by no means impaired during the last 3 years. The patient refused a repeat lung biopsy.

CS 13: Pulmonary foci left, suspected to be tumors, and tuberculosis of the bone (2004), foci with caverns right (2007) in 58-year-old chain-smoker with RA The diagnostic problems could and cannot be missed. Initially there were nodules in the left lung (Fig. 36a) in 2004 which were highly suspicious of a tumor or metastatic mass. The morphology – “pulmonary abscesses consistent with rheumatoid nodules with vasculitis in the marginal zone” – was in fact surprising (the first morphological finding was non-specific), but easily explained in the context of seropositive RA and peripheral rheumatoid nodules (Fig. 35). The diagnosis of bone TB can be established from the remarkable changes in the tibia (Fig. 36b), in addition there were the bone biopsy findings at this point (granulomatous inflammation with necrosis), leading to the conclusion of TB. This second disease could quite clearly even rule out the use of the possible TNF blockers. Another surprise was the negative outcome of in vivo and in vitro (QuantiFERON® TB) TB specimens, which actually questioned the history of the TB. Incidentally, on

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­ orphological examination of this finding, this granulomatous tissue was interpreted as m being different from TB – in fact, it was associated with the rheumatoid nodules (see reference finding CS 13, Chap. 2). The third surprise emerged from the latest radiomorphology of the lungs in 2007 (Figs. 38, 39). The three major causes for several foci, including one cavern, are to be considered – namely the rheumatoid nodules (a priority for me in light of the good health of the patient), TB, and ultimately the tumors (chain-smoker!). When further invasive diagnostics were refused by the patient, combination therapy (Arava® 20 mg/ day with Enbrel® 50 mg/week) was initiated and produced a good response in the joints after a further 3 months. Over the course, pulmonary infestation in the form of acute ­pneumothorax developed as a complication and necessitated mechanical ventilation. 40. (C) A disease (RSS, Chap. 1.3.1; see also Fig. 49a) based on the pattern of involvement. Therapy: immunosuppression (cortisone with MTX and possible biologics, in this case Enbrel®, currently approved for early forms of this disease) as early as ­possible in order to achieve remission, as applicable. 41. (B) A clinical syndrome (RSS, Chaps. 1.3.1 and 4.6.3) in conjunction with CS 14, ­disease-specific. Therapy: immunosuppression (MTX with or without cortisone) as early as possible; it was possible to use a biologic as part of a study.

CS 14: Acute swelling of toe 5 on the left and emergency synovectomy with a suspected tumor, female, 52 years This case should demonstrate the not untypical difficulties of early diagnosis of a classic disease. Instead of instigating immunological examinations synovectomy of MTP 5 left was carried out upon suspicion of neoplasia (this is how severe arthritis /see Figs. 41, 65/ looks). Once the arthritis had spread, especially symmetrically (Fig. 41), rheumatological examination ensued. About synovectomy: In the case of definable, earlier RA with (a) symmetrical involvement of a knee (but not the small joints), such surgery could even be curative. 42. (C) A disease (RSS, Chaps. 1.3.3 and 4.6.1) in light of the pattern of involvement; the late sequelae or damage from a medical history spanning more than 20 years, without basic therapy, are visible (cf. early forms of the same disease, Figs. 28, 40). Telescopic finger (shortened, slack and without function). Therapy: all therapies (currently taking only Decortin® 5 mg/day) were refused by this patient due to potential side effects (compliance difficulties). Optimization of systemic (at the sign of activity, possibly MTX with biologics; Enbrel® is approved without MTX) and local (cortisone injections, surgery due to risk of tendon rupture, orthesis, possibly TEP of PIP, MCP, MTP, see Fig. 9b) therapies should be considered, however. 43. (C) A disease (RSS, Chaps. 1.3.3 and 4.6.1) on account of the pattern of involvement (same patient as in Fig. 42); here, the late sequelae (fixed malpositioning of the toe joints) in the feet are visible (cf. early forms of the same disease, Figs. 41, 65). Therapy: only orthopedic care, as necessary. 44. (A) A radiological syndrome (conventional X-ray of sacroiliac joints → RSS, Chap. 6.8) produced a certain morphological diagnosis of sacroiliac joints involvement

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b­ ilaterally (RSS, Chap. 2.2.3). The nosological entity is to be considered in context with CS 15 and the radiological procedures (Figs.  45 and 46). On account of this ­picture, further diagnostics and antiinflammatory therapy (local essential, possibly systemic) are indicated.

CS 15: Asymmetrical pain and imaging of sacroiliac joints in HLA-B27-positive male patient, 42 years The criterium for radiology was the inflammatory back pain (RSS, Chap. 2.1.5) on initial diagnosis of AS (RSS, Chap. 2.2). Thereby, the methods must be expected to provide both possibilities and limitations. Several methods can reveal the various clinical aspects of back pain, namely the presence of involvement (X-ray and bone scintigram, Fig. 44, show inflammatory or degenerative backgrounds), activity (Fig. 45) and damage (Fig. 46), which can be laterally different. Depending on the issue at hand, the relevant methods should be employed in a particular sequence. Such methods are to be regarded as the starting points for optimal therapy: initially local, CT-controlled cortisone injection into the right sacroiliac joints joint where the pain and activity are located, then left, where the erosions or damage are more to be found. Such therapy was initially successful, so that the need for biologics is not given at present (according to guidelines). 45. (A) A radiological syndrome (CT of sacroiliac joints → RSS, Chap. 6, Step 8) in the same patient with left-sided changes: bilateral sacroiliitis with erosions and subchondral sclerosis, emphasized on the left, “colorful picture”, but with acute inflammatory, extensive corticalis destruction on the right. 46. (A) A radiological syndrome (MRI of sacroiliac joints → RSS, Chap. 6, Step 8) in the same patient revealed more right-sided changes (bone edema in the right and increased sclerosis of the left sacroiliac joint), confirming the diagnosis of sacroiliitis (RSS, Chap. 2.2.3) with therapeutic consequences (see above). 47. (B) A clinical syndrome (RSS, Chaps. 9.1.2, 9.2.3) even in conjunction with CS 16, difficult to assign causally during the short period of observation (3 months). Most such cases involve non-differentiated vasculitis associated with CTD, most likely SSc or Buerger’s disease. Therapy: immunosuppression (high doses of cortisone with e.g., MTX SC) and vasodilation (Prostavasin®, Iloprost, Bosentan).

CS 16: Acute acral gangrene, high-titer ANA with no organ involvement, 36-year-old female In this case the main difficulty was finding the cause of the acute acral gangrene. Initially this process is to be assessed as a true Raynaud’s phenomenon, where the other – but not all (e.g., digits 4–5 not affected) – vessels of the hands (some with minor gangrene, others with cyanosis) are affected. Skin-muscle biopsy from the same side of the upper arm ­produced unremarkable findings. Thereby, there was no clinical involvement of the feet. Another pattern of circulatory disorders in the fingers can be seen from Fig. 14. No organ (endocarditis should be ruled out due to the risk of embolism) or connective tissue involvement could be ascertained. Some evidence of such is to be seen in the capillaroscopic

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p­ attern (similar to SSc) and the high ANA titers, but with no differentiation, ruling out primary Raynaud’s phenomenon. The slight CRP increase is attributable to the existing gangrene. In men, consideration is to be given more to Buerger’s disease, which in this case is also relevant. Another, rare cause for such digital gangrene (APS, cryoglobulinemia or other forms of vasculitis, cholesterol embolism) was ruled out clinically, immunologically, morphologically and angiographically. The course could be stabilized by 2 weeks of therapy with Decortin® and MTX as well as Prostavasin® infusions. The underlying diagnosis was unclear during the follow-up period (6 months). Most likely, this case is in my opinion the initial manifestation of SSc. 48a. (A) A radiological syndrome (MRI of thoracic spine before therapy (RSS, Chap. 2.2.2): Irregular contouring of the base and top plates with an indication of erosive character, clear edematous zone in the vertebral body and barrier disruption of the vertebral disc or reduction in the intervertebral space and edematous signal changes in the medullary cavity. At the same time, the base and top plates are poorly outlined. Such changes can be clarified causally only in the context of CS 17. The same changes developed after a 2-week break during years of maintenance therapy (CS 17, Chap. 1.1.2). 48b. (A) A radiological syndrome, MRI-confirmed syndrome (after 3 months of therapy, see CS 17): the patient had no symptoms, clinical findings correlated with positive dynamics of the MRI changes in T6/7 and T8/9.

CS 17: Localized pain, small gibbus in thoracic spine and CRP elevation in HLA-B27-negative female, 50 years A deciding factor in the local diagnosis of the five years of medical history is the MRI finding (Fig. 48a). The most common cause for this are infections (TB, among others) and tumors. They can be ruled out anamnestically, for certain. Indicative to the causal diagnosis of such relatively rare, but prognostically relevant, local thorax spine changes was the sacroiliac jonts’s finding (as with CS 63 with isolierte arthritis of C1-C2, initially of unknown origin), in a similar way to Fig. 124. The second feature of such a case is its dependency on the strength of immunosuppression: only very intensive and sustained immunosuppression with cortisone was effective. During a therapeutic interval of 2 weeks, the same MRI changes developed as in Fig. 48a, and at the same time there was a dramatic rise in CRP (from normal to × 15) and moderate back pain (40 mm VAS). Therapy with Enbrel® 50 mg and Decortin® 40 mg left the patient free of symptoms in 3 days, with normal CRP. Maintenance therapy (Decortin® 5 mg and Enbrel® 25 mg in 3 weeks) was initiated. The further reduction of such therapy is noticeable clinically (from the mild back pain and rise in ESR and fibrinogen), hence treatment is continued. 49a. (C) A disease (RSS, Chap. 1.3.1, see also Fig. 40) on account of the pattern of involvement, pictured on a bone scan (Fig. 49b). The highly active, anti-CCP-positive female patient with a 2-year medical history did not respond to several basic medications (MTX, Arava® also in combination), biologics (Enbrel®, Rituximab, RoActembra®)

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and RSO; high-dose cortisone is needed. At present, Remicade® is used with unconvincing efficacy. 49b. (B) A radiological syndrome (bone scan → RSS, Chap. 6, Step 8) is in the same patient as Fig. 49a. Without clinical findings it is hardly possible to draw any diagnostic conclusions (could also be PsA), initially showing accumulation in the early phase as an expression of exudative inflammation (RSS, Chap. 1.3.1); secondly, a pattern of involvement indicative to the distinctions between the various joint diseases and of the introduction of systemic and/or local therapy.   50. (A) A radiological syndrome (MRI of the skull): extensive demyelination zones bilaterally, parietooccipital, with space-occupying nature and smaller, peripheral areas in the left frontal region. In relation to the medical history (CS 18), such CNS involvement is consistent with an immunological disease, and also serves as a follow-up control (demyelination of cortical structures). Therapy: relatively mild immunosuppression (17-year-old female!) with Imurek® (100 mg daily) stabilized the disease quite rapidly but did not prevent the occasional, mild epidose.

CS 18: Recurrent neurological and visual deficits (since the age of 13), 3-year treatment of multiple sclerosis (MS), high-titer ANA, CNS involvement stabilized with Imurek® therapy, female patient, 17 years This case of a 13-year-old girl is exquisite and is characterized by the episodic occurrence of CNS involvement with optic neuritis and transverse myelitis (all of which improved well with glucocorticoids). The case represents the syndromal similarity of a disease which is easily definable using immunological examinations (RSS, Chap. 11.1) on the one hand and MS on the basis of criteria on the other. MRI was performed upon diagnosis of known MS: extensive demyelination zones bilaterally, parietooccipital, with space-occupying nature and smaller, peripheral areas in the left frontal region. For 3 years, these diseases could not be differentiated either neurologically or radiologically, and were ultimately controllable only with high-dose cortisone (interferon was ineffective). This response to cortisone as well as the immunological (known since 2004) and histological (2006) aspects are to be regarded in discriminatory terms with a view to MS. Consequently, present therapy with Imurek® 150 mg and Decortin® 2.5 mg/day appears to effect clinical remission with rare episodes. 51. (C) A radiological syndrome (conventional X-ray; → RSS, Chaps. 1.3.3, 1.3.4, and 6, Step 8) revealed partially bony fusion of the carpalia, massive cysts and usures (stage IV), also in a visually normal wrist (Fig. 62). Bone destruction and erosion are a component of many types of articular diseases (see Figs. 8, 9a, 23, 59, 130b), and can be differentiated only in conjunction with the medical history and first and foremost the pattern of involvement. 52. (B) A clinical syndrome (RSS, Chaps. 9.1.4, and 9.2.3) easy to define in conjunction with CS 19 and Fig. 53. Therapy (during the last 2 years) daily: CYC 150 mg Decortin® 10 mg, Trental® 400 mg × 2, ASA 100 mg, ACE inhibitors. No episodes, full regression of sclerodactyly and sclerodermia on the thoracic wall. 53. (B) A radiological syndrome (CT lungs → RSS, Chap. 10.2.3): finely streaked/reticular pattern in the sense of inflammatory fibrosing alveolitis (the finding on the left can be

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described as pneumonitis or pulmonary fibrosis). CT is the method of choice for interstitial diseases. This syndrome can be clarified in conjunction with the medical history (CS 19, Fig. 52; see also Figs. 79, 85, 91), and is highly significant to therapy (see above) and prognosis.

CS 19: Acute respiratory distress, pleural effusions and cold hands, male, 58 years This disease, which is easy to define clinically and immunologically, should on the one hand show the association between the acute onset with multiorgan involvement and on the other hand the unfavorable course. Nevertheless, therapy (systematic immunosuppression with CYC and cortisone for 2 years) positively influenced the regression of sclerodactyly and sclerodermia on the trunk and the pulmonary fibrosis, without the occurrence of any clinically relevant adverse effects.   54. (A) A radiological syndrome (MRI of right ankle → RSS, Chap. 4.9): showing an extensive osteolytic process approx. 3 cm distal to tip of fibula, right, resulting in a pathological fracture. The 75-year-old female patient had suffered 5 months of painful swelling in the lower leg (as formulated in the referral diagnosis). Extensive diagnostics (blood count, immunology, infectious serology, conventional X-ray) produced no findings. MRI performed by a practitioner (I was asked by radiologists to assess the usefulness of such a procedure) produced the suspicious malignant finding (bone tumor, osteolytic metastasis with pathological fracture). Check-up revealed no signs of primary tumor, metastasis or osteomyelitis (also possible radiomorphologically). The diagnosis of a stress fracture emerged during the surgery.   55. (A) A clinical syndrome (RSS, Chaps. 9.1.2 and 9.2.2, see also Figs. 71, 101a), as if punched out, Ulcera cruris in a patient with RA (could also be the case with CTD or vasculitis). Thereby, massive extra-articular disease activity (RSS, Chap. 2.6) is to be expected. Therapy: systemic immunosuppression (see CS 11, 24). 56ab. (B) A clinical syndrome (RSS, Chaps. 9.1.1 and 9.2.1) only assignable precisely in context with CS 20, has the key role in the assessment of the activity of the immunological disease including renal involvement. Therapy: with existing HCV infection and renal involvement, there was a lack of efficacy with MTX and azathioprine and the patient could not tolerate CYC; initially responded well to MMF (CellCept® 1,500-2,000 mg/day with Decortin® 7.5–10 mg/day). In the last 2 years, the course has been recurrent (skin changes, abdominal pain, “black stools”, anemia), necessitating several emergency hospital admissions with high-dose cortisone treatment.

CS 20: Palpable purpura, abdominal pain and renal insufficiency, active hepatitis C, female, 50 years This case should demonstrate that the rheumatological aspects (Figs. 56a, b) of the underlying disease (in this case hepatitis C) could be predominant. Such skin changes (palpable purpura of necrotizing venulitis) are associated clinically with the current renal ­involvement

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(stable hematuria, mild albuminuria and elevated creatinine) and recurrent ­abdominal pain. The cryoglobulinemia (mixed type 2) induced by the active hepatitis C caused the systemic affectation of small vessels; dermatohistologically: leukocytoclastic vasculitis. At this time there is no evidence of a progression to lymphoproliferative disease (in type 2 roughly 15% of patients). It is best to instigate therapy for the underlying disease (specific therapy with interferon and Ribavarin® was not effective and poorly tolerated). At the same time, immunosuppression was administered (daily Decortin® 10 mg and Cellcept® 2,000 mg), which proved to be ineffective (as above). In this refractory case, therapy with 500 mg rituximab weekly (four times) was undertaken. After the second infusion, there was a recurrence of the skin changes. The immediate effect was revealed after the fourth infusion (all were tolerated well), i.e., a symptom-free condition under reduction of Decortin® to 5 mg and CellCept® to 1,000 mg daily. Clinical remission was sustained for the following 18 months with such therapy. 57. (B) A clinical syndrome of ocular involvement (RSS, Chap. 10.8.1); such cases should be clarified and managed together with an ophthalmologist. In conjunction with the clinical findings (patient has similar changes to those in Fig. 44 and HLAB27 antigen), the causes mostly were easily identifiable. Therapy: ciclosporin 150 mg/day, Ultralan® 10 mg/day, Humira® 40 mg at intervals of 2 weeks, careful monitoring of concomitant diseases (obesity class III, arterial hypertension, poorly controlled diabetes mellitus II, drug-toxic liver damage). Ophthalmological examination detected relatively rapid (within 6 weeks), positive dynamics of ocular involvement and vision. At the same time there was an increase in serum creatinine (1.40 mg/dl). After a break, CellCept® was administered with renal values normal thereafter. 58. (B) A clinical syndrome (RSS, Chaps. 1.3.2 and 1.5.3), namely MCP 2 involvement, could be interpreted only in the context of the clinical findings (polyarthritis, anti-CCP positivity) and radiomorphology (Fig. 59; see CS 50 with identical involvement and different diagnosis). Therapy: MTX and a biologic (Cimzia®/certolizumab as part of a study) resulted in remission in line with the criteria, with the exception of the affected joint (Fig. 59). Consequently, several cortisone injections and ultimately RSO were administered, with short-term regression of the local clinical activity. 59. (B) A radiological syndrome (conventional X-ray → RSS, Chap. 1.3.4) revealing selective destruction of the right MCP 2 and a cyst in MCP 4 of this female patient (see Fig. 58). Refer to the comments on CS 50. 60. (C) A radiological syndrome (conventional X-rays of C1-C2) with absolute disease specificity (RSS, Chap. 2.2.2), fresh syndesmophyte left); in this case the early disease was documented. Therapy: according to disease activity. 61. (C) A radiological syndrome (aortoangiogram → RSS, Chaps. 9.2.2, 9.2.6, 9.2.7, and 13.4). The pictured morphological diagnosis can be confirmed by the clinical data (CS 21). Therapy: angiological treatment (3 stents inserted into A. brachiocephalica, A. carotis and A. iliaca) and immunosuppression (azathioprine, then MTX with Decortin®, then Arava®). The course was stable, with no clinically relevant circulatory disorders.

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CS 21: No pulse on one side (since the age of 20), cardiac arrhythmias and two acute myocardial infarctions, female, 36 years Many years of disease with varied angiological/cardiological symptoms, not initially regarded as relevant in this young woman. Only after two myocardial infarctions in quick succession was a rheumatic disease first postulated. Angiological (4 stent implants into the coronary (1), supraaortic (2) vessels and A. iliaca (1)) and immunosuppressive (MTX, azathioprine, cortisone) therapies enabled stabilization of the course, apart from (a) the extremely painful, red and swollen scar (post thoracotomy; synchondrosis /perichondritis/ manubriosternalis /RSS, Chaps. 3.11.7 and 4.2.4/ suspected) and (b) the left thoracic pain during the last 4 years, which increased with exercise. These two syndromes are completely reversible with Arava® therapy. 62. (C) A clinical syndrome (RSS, Chap. 1.3.3; see also Figs. 35, 42, 80, 129c, where partly similar, but less pronounced changes are to be seen) which is virtually disease specific: button-hole deformity digits 2–5 left and 5 right, flexion contractures in the distal interphalangeal joints 2–4 right, so-called claw hand which here is arthrogenically fixed, in Fig.  18 dermatogenic, in Fig.  19 neurogenic, in Fig.  130a osteoarthritisinduced. The hands in Fig.  62 are a diagnosis, particularly in conjunction with radiomorphology (Fig. 51) and clinical findings (more than 20 years of symmetrical polyarthritis with restrictions to passive movement (why?) of the fingers and wrists; patient recently arrived from abroad). At the same time the patient currently has stable CRP elevations (×4–6) and therefore needs a more than moderate level of immunosuppression (cortisone, MTX + Arava®; if there is no response, biologics should be used), despite stage IV disease. 63. (A) A clinical syndrome (RSS, Chap. 3.3.1) with a clear morphological correlate (see Fig. 95), associated with arthritis of PIP 3 (as in Fig. 68), whereby two articular diseases are possible (serological diagnostics indicative, namely anti-CCP positivity). Therapy: basic therapy (Decortin® 5 mg/day and MTX 15 mg/week) were first intensified (Decortin® 30 mg/day + Remicade® N3) but unsuccessful, suggesting that orthopedic measures would be required. 64. (B) A radiological syndrome (bone scan → RSS, Chaps. 1.3.1 and 6, Step 8) revealing the activity of the disease (differing intensity in early-phase enhancement) and pattern of involvement (“hot-spot” affectation both DIP and PIP joints to be seen in left dig. 3), hence both RA and PsA would be possible. Clinically, these two diseases are mostly easily distinguishable. Therapy: according to nature and activity of disease. 65a. (B) A clinical syndrome causally identifiable only in the context of the clinical findings (RSS, Chap. 4.6.3) and imaging (RSS, Chap. 6, Step 8) (see Figs. 15a, 41). This case involves a young man with recurrent Acne vulgaris and Tietze syndrome (as in Fig. 69). The dactylitis visible in Figs. 65a, b would fit with acne-induced arthropathy (roughly the same as SAPHO syndrome → RSS, Chap. 4.2.1, but no psoriasis). Therapy: systemic (cortisone and MTX), response was registered. 65b. (B) A radiological syndrome (bone scan in the early phase → RSS, Chaps. 1.3.1 and 6, Step 8) confirms the dactylitis (→RSS, Chap. 4.6.3).

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66. (B) A clinical syndrome (RSS, Chap. 4.6.2 see also Figs. 7 and 115) cannot, in fact, be clarified by the clinical findings (CS 22): no morphological correlate was found. The good response maintained with cortisone (Fig.  67) suggests that there is an (auto) immunological cause or cortisone-dependent disease (RSS, Chap. 13.3), most likely associated with vasculitis. Therapy: cortisone pulse therapy + MTX 15 mg/week, with hospitalized treatment for the flares. 67. (B) A clinical syndrome (see Fig. 66) following cortisone pulse therapy.

CS 22: Puffy hands and high CRP of unclear etiology in 17-year-old trainee painter This case (Fig. 66) demonstrated the difficulties of morphological diagnosis in rheumatology (what should be biopsied here?). It is certainly an inflammatory/rheumatic disease, namely acute swelling in both hands (see also Fig. 7), massive CRP increase, good response to cortisone from the first episode (Fig. 67) with sustained remission also during the second episode and identical therapy. No organ involvement, non-specific immunology. Acute Sudeck’s syndrome seems unlikely on account of the symmetrical involvement. Remitting seronegative symmetrical Synovitis with Pitting Edema (RS3PE syndrome) also seems unlikely because of the missing pattern of arthritides, young age of the patient and extremely high CRP. Vasculitis of the small vessels cannot be confirmed morphologically or angiologically. An allergic process during painting work is not really consistent with elevated CRP. The fact remains that the dramatic disease or condition was healed without having secured a diagnosis. 68. (B) A clinical syndrome (RSS, Chap. 1.3.1; see also Figs. 3 and 64, a radiomorphological correlate of such changes). It cannot be clearly explained in conjunction with the clinical findings (CS 23). This case is more likely the joint disease associated with HIV (RSS, Chap. 12.4.3; see Fig. 88). Therapy: cortisone and MTX under CD4-level control produced a clear improvement. 69. (B) A clinical syndrome (RSS, Chap. 4.2.1). Only in conjunction with CS 23 and Fig. 68 can HIV-associated joint disease be postulated based on the almost specific pattern of joint involvement (RSS, Chap. 12.4.3). Therapy: (see comment to Fig. 68).

CS 23: Acute arthritis and Tietze syndrome with HIV, female, 36 years The rheumatological question was whether this illness (whereby HIV is not implied) can be attributed to an inflammatory rheumatic disease. Most certainly is on account of the stable, florid arthritis with extremely high CRP. Which inflammatory and rheumatic disease with such a pattern of involvement in HIV (the disease in Fig. 84b) is involved? Other rheumatic diseases can almost certainly be ruled out on the basis of the immunological tests performed. The necessary, and effective, immunosuppression was administered in collaboration with infectiologists while carefully monitoring CD4. 70. (B) A clinical syndrome (RSS, Chap. 3.9, 4.6.1, and 9.3.4) described as Jaccoud’s arthropathy. Only by taking an X-ray of the hands (Fig. 72) and considering CS 24

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can such changes be correctly interpreted. Therapy: systemic, namely several years of Decortin® 5 mg/day + MTX 10–15 mg/week. 71. (B) A clinical syndrome (RSS, Chaps. 3.2.1, 9.1.2, 9.2.1, and 9.4.1) in the same female patient could only be interpreted on the basis of morphology and in the context of CS 24. An attempt was first made to consider this condition as an independent disease – erysipelas. Therapy: antibiotics for 3 weeks but with no success; intensified immunosuppression (Decortin® 30–20 mg/day + MTX 15 mg/week) produced a regression in the changes in 2 weeks and they were later (Fig. 73) totally reversible. 72. (B) A radiological syndrome (conventional X-ray → RSS, Chaps. 1.3.4, 6, Step 8, and 13.9), indicating the characteristics of deformed hands (Fig. 70), should be considered in conjunction with the medical history (CS 24). 73. (B) A clinical syndrome (RSS, Chaps. 3.2.1 and 9.4.1) showing the regressiveness of the changes (cf. Fig. 71) after cortisone therapy. This conveys an important generic term in rheumatology, namely cortisone dependency (RSS, Chap. 13, Step 3), which is to be regarded as an important criterium, but of no nosological specificity, for the presence of an inflammatory rheumatic disease.

CS 24: Deformities of the hands, myalgia, pacemaker, red feet with ulceration, female, 52 years (some episodes during 12-year follow-up period) Over the course of this disease (which?), definable on the basis of clinical findings and immunological tests, various clinical patterns emerge which at times can be interpreted as independent diseases, e.g., are the problems with the hands related to RA (Fig. 70, ulnar deviation, contractures, tendinitis → RSS, Chaps. 1.3.2, 3.3, and 3.9)? This should be strictly contradicted on the basis of a lack of erosions (Fig. 72), but also RF and anti-CCP-Ab. The other manifestation of the changes depicted in Fig. 71 (RSS, Chaps. 3.2.1, 9.2.2, and 9.4.1) was initially interpreted as erysipelas. But there was no fever with chills, no migratory erythema, and no response to antibiotics - which thus contradict this. Such changes are certainly among the extra-articular symptoms of the disease. The response to intensified immunosuppression (Fig. 73) is indicative of the immunological basis of such changes. 74. (C) A radiological syndrome (PET, 2 positions → RSS, Chaps. 8.1, 9.2.2, and 9.2.7; cf. Fig. 77b) assigned to fever of unknown origin and suspected inflammatory changes in the vessels (in vasculitis of the large vessels) and perivascular (in Ormond’s disease) structures, if other methods (RSS, Chap. 13, Step 9) furnished no evidence. Causes can only be interpreted in conjunction with CS 25. Therapy: relatively strong immunosuppression (moderate doses of cortisone and e.g., azathioprine or MMF) in this case brought satisfactory results.

CS 25: Fever, weight loss and increased inflammatory symptoms of initially unexplained origin in a 50-year-old female This case presents the diagnostic problems and possibilities of causal investigation into months of unexplained B symptoms with fever, elevated CRP and ESR, weight loss,

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e­ specially in young women. This PET method should come last in the sequence of staged diagnostics (possibly after ultrasound, CT or MRI) for suspected vasculitis of the large vessels or Ormond’s disease. Therapy: immunosuppression with Decortin® (40 mg/day) and azathioprine (150 mg/day). After a few days the remarkable symptoms were regressive, and remained so long-term. 75. (B) A radiological syndrome (chest X-ray → RSS, Chap. 10.2; cf. Fig.  79): multiple nodular pulmonary infiltrations with caverns and bronchoectasis, fibrosis - causally explicable only in the context of the medical history (patient suffered for approx. 10 years from cANCA-positive WG with involvement of the lungs). Therapy: lung transplantation was refused here on account of the advanced pulmonary and cardiac insufficiency (picture taken shortly before the fatal outcome). In other cases with pulmonary involvement, more or less strong immunosuppression should be instigated depending on the entity, activity, organ involvement and concurrent diseases and conditions. 76. (B) A clinical syndrome (RSS, Chap. 9.1.5) only to be interpreted in association with other syndromes and constellations (CS 26). Therapy: immunosuppression, colchicine, sustained response generally to cortisone pulse therapy (Decortin® 250 mg IV N3).

CS 26: Mouth ulcers, heart attack, severely increased ESR and CRP, female, 73 years These common problems (acute myocardial infarction in a 73-year-old woman, otherwise no risk factors) have remarkable clinical aspects, namely known MB with recurrent mouth ulcers, extremely elevated ESR and CRP during and shortly before the event. Such constellations are suggestive of vasculitis of the large and medium (coronary) vessels possible in association with MB. Therapy: cortisone pulse therapy produced a stable response (no vascular symptoms, no increase in CRP or ESR). No further diagnostics were undertaken, therefore. It must be noted that continued elevation of CRP, which is regarded as a significant trigger for atherosclerosis (RSS, Chap. 12.4.2), markedly increases the rate of myocardial infarction. 77a. (C) A radiological syndrome (MRI angiogram → RSS, Chaps. 9.2.2, and 13, Step 6): Irregularities of the external aortic wall and A. iliaca bilaterally. Lumen fluctuations of A. iliaca communis bilaterally, but somewhat greater on the right than the left, but with no higher stages of stenosis. Clinically there was severe back pain, initially treated intensively (reportedly 60 injections in one month), as well as episodic fever and abdominal pain. A. temporalis biopsy (before therapy) was normal. Such symptoms are dependent upon the strength of immunosuppression. No other large vessels affected. Therapy: relatively strong and systematic (for 5 years) immunosuppression (MTX 10 mg/week, Arava® 20 mg/day, Decortin® 15 mg/day). The thickness of the aortic wall (on MRI and ultrasound) could be reduced over the course. Nevertheless, intermittent abdominal pain and episodes of fever remain. 77b. (C) A radiological syndrome (PET → RSS, Chaps. 8.1, 9.2.2, and 9.2.7; cf. Fig. 74) in the same patient (see Fig. 77a): band-shaped enhancement in abdominal aorta – (level approx. L 2/3), as with minimally active aortitis, which is relatively rare (approx. 10–15% cases in such a rare disease), particularly in men (cf. Fig. 61, CS 21).

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78. (A) A clinical syndrome → RSS, Chaps. 9.1.1 and 10.10.2; cf. Fig. 33, where are the differences? To be causally explained only in context (no organ involvement, specific Ab spectrum, cortisone dependency! cf. CS 27). Therapy: immunosuppression (more with induction therapy, less with maintenance therapy). Daily over the previous months: Decortin® 15–30 mg and CellCept® 2,000-3,000 mg, which are resulting in a serious urinary tract infection. Cellcept® was stopped for 1 month and then reissued. The above mentioned therapy, at high doses, was ineffective (platelet count was below 30,000–50,000/ml, whereupon rituximab (1,000 mg in two infusions) was prescribed.

CS 27: Skin and mucous membrane bleeding, thrombocytopenia and high positive anti-dsDNA with no organ involvement, female, 54 years The problem here is the causal classification of the selective thrombocytopenia with antithrombocytic Ab. Indicative of such are the high ANA and dsDNA-Ab titers with positive Crithidia test. In the event of disease with such specific serology → RSS, Chap. 11.1), intensified immunosuppression (cortisone and CYC pulse therapy, azathioprine) should first be attempted in accordance with current guidelines. Over the course, following splenectomy, the clinical findings under cortisone (Decortin® 10 mg and azathioprine 150 mg daily) during the 8 years of follow-up did not remain entirely stable: fluctuating thrombocytopenia, dependent on the cortisone doses, concurrent basic therapy and infections, especially after CellCept®, as is well known. As a result, close monitoring of organ involvement and platelet count, as well as the potential complications of immunosuppression (one of which was described above), is essential. In recent months, by increasing the doses of Decortin® (20 mg/day) and Myfortic® 360 mg (4 tabs/day) to way beyond those which are safe, clinically relevant thrombocytopenia (below the critical count) resulted, thereby necessitating introduction of label of use therapy with rituximab 1,000 mg (two infusions at 2-weekly intervals) which has recently been positively evaluated in the literature. Following such therapy, which was tolerated well, an improvement appeared to ensue and there was a rise in the platelet count up to 76,000/ml despite the reduction in maintenance therapy (Decortin® to 7.5 mg and Myfortic® to 720 mg daily). Clinical remission was seen from such therapy during the following 18 months. 79. (B) A radiological syndrome (CT thorax, → RSS, Chaps. 10.2.2 and 10.2.3). Honeycomb lung: massive, multiple, cystic changes, confluent focal shadowing mainly in the upper lobe, interstitial shadow pattern left, pleural effusion, massive bihilar lymphadenopathy. The case involves a 70-year-old male patient known to have had respiratory ­distress for about 15 years and exophthalmos (until recently evidently of unknown etiology → RSS, Chap. 10.8.5, though it belongs to the underlying disease). Histologically (lung, 12 years ago), chronic granulomatous inflammation was established (RSS, Chaps. 10.2.2, 10.2.3, and 11.6), and with ongoing cortisone therapy the patient was able to work until recently. Rapid deterioration in general health and pulmonary function were ascertained on discontinuation of cortisone (chest X-ray taken shortly before death). The cortisone (Decortin® 1,000 mg – 5 days) and CYC (1,000 mg – 3 days) pulse therapy was ineffective.

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80. (C) A disease (RSS, Chap. 1.3; see Figs. 3, 5, 35, 42, 62, 104, 129c). Can the differences to Figs. 4, 13, 81, 89, where the other diseases was illustrated, be seen? Therapy: mostly immunosuppression. 81. (A) A clinical syndrome (RSS, Chap. 1.4.2), definable in conjunction with CS 28 (see Fig.  80, where are the differences? or Fig.  4, where similar changes can be seen). Therapy: prescription of MTX should not be deemed appropriate; local therapy is to be applied (cortisone injections, RSO or Dolobene Gel®).

CS 28: Arthritis of the finger joints, rheumatoid factors and appropriate (?) MTX therapy, 64-year-old male The patient was referred for continuation of basic therapy in existing RA. The distinction from inflammatory osteoarthritis (OA) was the main problem here as well as generally in arthrology. In terms of the pattern of involvement (MCP joints not affected, see Figs. 8, 80, 128a, b), the arthritis of the individual PIP joints (Bouchard’s OA) is to be interpreted, in conjunction with Heberden’s OA, clearly as OA of the fingers. The patient does not need MTX. 82. (B) A clinical syndrome (RSS, Chap. 9.1.6) definable as a sign of vasculitis of the small vessels only in conjunction with the clinical findings (CS 29). Therapy: after the effective immunosuppression (see below), these changes disappeared completely.

CS 29: Alopecia, acute abdominal pain and massive proteinuria, 27-year-old male This case initially showed, over the course, peculiar clinical masks of a disease. Acute onset of systemic organ involvement characterized mostly by an unfavorable course. In such a case, the non-typical symptoms predominated: severe abdominal pain (due to pseudoileus on account of lymphadenopathy, another time due to renal vein thromboses), severe headaches (due to cerebral edema), and edema of the legs (due to marked nephrotic syndrome). Therapy: Cellcept® 2,000 mg and ciclosporin 50 mg ´ 2, CYC, azathioprine, 4  ´ rituximab 1,000 mg. The nephrotic syndrome proved resistant to all basic therapy, hence autologous cell transplantation has been carried out successfully. 83. (B) A clinical syndrome (RSS, Chaps. 9.1.4 and 9.4.1) in a male patient with tattoos can be considered only morphologically (in this case granulomatous inflammation, large nodular-type Lupus pernio compared with small nodular, disseminated type, Fig. 90) and radiologically (here, bihilar lymphadenopathy was found, but only on CT). Such a constellation is typical for sarcoidosis but also for lymphoma, hence these diseases are hardly distinguishable. The lack of B symptoms and only hilar involvement are more indicative of sarcoidosis, despite the negative finding of ACE. Such changes should be differentiated from pigment granuloma (the deciding factor, thereby, is the pulmonary involvement). Therapy: due to the massive proliferation of skin changes, cortisone therapy was instigated. The skin changes and hilar lymphoma were reversible (except for the slight growth at the location of the Fig.).

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84ab. (C) A clinical syndrome (RSS, Chap. 9.1.1) which is of great diversity (a – Psoriasis hyperkeratotica and b – Psoriasis vulgaris), with great specificity and clinical significance on investigation of the joint and back pain. Should also be checked as a potential occurrence in relatives (has the same indicative, clinical value). Induration of the skin is similar to leukemic infiltration. Therapy: in collaboration with dermatologists, particularly for similar (as in Fig. 84a) cases.    85. (B) A radiological syndrome (CT thorax, compare against Fig.  53, CS 19). Radiomorphological diagnosis of new onset (when comparing with previous imaging from 06/2007), clearly pronounced mediastinal and hilar lymphoma as well as solid nodule of 2.5 cm subpleurally in S6 left. The finely streaked, reticular pattern of the lung parenchyma presented here, was known. The finding should be investigated immediately (see below) and compared against Fig. 79.

CS 30: Pulmonary fibrosis, Raynaud’s syndrome, Scl-70 positive, HAP with response, deterioration in general condition and drop in DLCO transfer, abnormal thorax CT, 66-year-old female The present, primary finding is seen in Fig. 85 (see above). The moderate interstitial fibrosis (increased reticular streaking, emphasized hilus region bilaterally) reflects the underlying disease. Consideration must be given thereby to: multiorgan involvement without sclerodactyly and with positive Scl-70 tends to contradict SSc. The extent of the pulmonary fibrosis is not proportionate to the highly impaired pulmonary function and general health deteriorating in the previous 3–4 months. The decisive explanation for this was furnished by the perthoracal punch biopsy of the mass on the left, namely the proof of small-cell, anaplastic carcinoma. Metastases were found in the liver. Chemotherapy was instigated. The decisive question: should the entire medical case history be viewed as a paraneoplastic process or are two diseases involved (→ RSS, Chap. 5, CS 73 with virtually the same issues as in the patient with WG and colon carcinoma)? Thereby, the other ­possible triggers are to be considered, i.e., the systematic azathioprine therapy during the last 4 years. 86. (A) A radiological syndrome (MRI of the skull for ENT → RSS, Chap. 10.9.2 following CYC therapy): an almost circular, soft-tissue structure in the left maxillary sinus (T2-T1-weighted, hypointense). This is a radiomorphological diagnosis to be interpreted causally only in conjunction with the medical history (CS 31); the maxillary sinuses were affected (sinusitis) after four cycles of CYC pulse therapy. Induction therapy: 6 cycles of HAP (Benenson et al. 2005). 87. (A) A radiological syndrome (MRI of the skull → RSS, Chap. 10.9.2 after HAP therapy): significant structures of soft-tissue density no longer detectable in sinus region. The method would be suitable for follow-up control. Maintenance therapy: immunosuppression (Decortin® 10–5 mg/day and MTX 10 mg/week). With 2-year clinical remission under the aforementioned therapy, an attempt to stop MTX was made. Shortly thereafter there was a cerebral insult, which cannot be ruled out as the sign of a flare.

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CS 31: Multiorgan involvement and MRI of the ENT region under immunosuppression, 62-year-old male This case, with multiorgan involvement and pANCA positivity, poses few diagnostic difficulties. Perhaps there is just one aspect with a view to the activity of the disease during many years of maintenance therapy (with MTX), and justification for such therapy is to be highlighted. This question can be answered only by attempting to stop MTX, as a detector for the initial activity. Stroke after the 5-week break in MTX appears to be causally related to dormant, minimal activity. For this reason, I would in future continue with the immunosuppressive maintenance therapy in the remission of such (and perhaps other) diseases. Another aspect is a new therapeutic option in WG with refractory ENT involvement. HAP achieved full regression of the specific mass (Benenson et al. 2005). 88. (B) A clinical syndrome (RSS, Chap. 4.6.4) explicable causally only in association with clinical findings. The case involves a 29-year-old HIV-positive patient with no cardiac or lung disease, no skin changes; he was evaluated as one case (CS 23, Figs. 68, 69). 89. (B) A clinical syndrome (RSS, Chaps. 1.4, 4.6.1, 9.3.2), behind which are two other systemic diseases which can only be diagnosed by disease-specific immunology (CS 32). Therapy: mild immunosuppression (daily Decortin® 20 mg – at present 5 mg + Arava® 20 mg); consequently stabilized.

CS 32: Arthritis, sicca syndrome and SS-A, CenpB- and anti-CCP antibodies, female, 67 years This case in fact involves all 4 rheumatic diseases. One is to be seen in the DIP nodules (Fig. 89 and radiologically, as in Fig. 8). The second is noticeable from the MCP swellings (MCP 2-3) and high-titer anti-CCP antibodies. The third can be established from the clinical findings (Calcinosis cutis, Raynaud’s syndrome, Teleangiectases, swallowing difficulties) and first and foremost from the CenpB-Ab (RSS, Chap. 11.1). The fourth can be postulated from the sicca syndrome and possibly SS-A-Ab, but viewed as secondary. All inflammatory rheumatic diseases have relatively minimal activity at present, with no organ involvement and thus are easy to control with mild immunosuppression (Arava® 20 mg + Decortin® 5 mg/ day). The further reduction in such therapy was always associated with deterioration in general health, arthritis and elevated CRP, which can be described as drug-induced remission. 90. (B) A clinical syndrome (RSS, Chap. 9.1.1) can be clarified nosologically only by the morphology (granulomatous changes, small-nodule, disseminated type compared with large-nodule type Lupus pernio Fig. 83), though in association with the clinical findings, chest findings (Fig. 91) and lab findings (CS 33). Therapy: strong immunosuppression (due to broad spread of efflorescences and pulmonary involvement). High-dose cortisone therapy (70 mg/day for 3 months) was administered by family doctor, but without any effect and long-term adverse effects (diabetes mellitus, requiring treatment). No response (during 2 years) to CYC, MTX, azathioprine PO and pulse therapy, MMF, Arava® also in combination with Humira® (3 months). Ultimately, a clear response was achieved with Remicade® (three infusions) with full regression of ACE and IL2r, lasting no longer than 8 weeks.

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CS 33: Multiple focal erythema, high ACE and pulmonary fibrosis, 42-year-old male The nature of the skin changes can be identified by biopsy. However, such morphological data should be viewed in a clinical context, namely with highly specific chest X-ray findings (Fig. 91) in the form of the hilar lymphoma. The potential, prognostically unfavorable involvements of the CNS, heart and liver, could not be verified. Due to pulmonary involvement (stage II) and primarily because of the massive skin changes, systemic therapy was initiated, but had no effect (see comments on Fig. 90). The 2-month response was registered only with Remicade® (three infusions). Measurement of ACE and IL2r, which was normal only under such therapy, is suitable as a follow-up control. Incidentally, the same morphological finding could look completely different in this disease (Fig. 83) and respond completely differently to cortisone (in the latter case very well, and not at all in CS 33). 91. (B) A radiological syndrome (CT thorax → RSS, Chap. 10.2.3) – bihilar lymphadenopathy, increased small-nodule interstitial streaking (see also Figs. 53, 85) – can be explained causally only in conduction with clinical findings (CS 33) and morphologically confirmed skin changes (Fig.  90). Therapy was in this case based mainly on these changes and less so on the lung involvement. 92. (A) A morphological syndrome of lupus nephritis /LN/ (RSS, Chap. 10.1) on renal biopsy after 16 cycles of CYC pulse therapy (CS 34). Top: 2 damaged and 1 intact glomeruli with tubular atrophy (A); Bottom: fibrinoid necrosis (big arrow), extracapillary proliferation (small arrow) (activity index 9/24; chronicity index 4/12). This implies signs of specific lupus activity and moderate chronicity. Induction therapy is in refractory LN in the form of HAP (18 cycles) (Benenson et al. 2005). 93. (B) A morphological syndrome of LN (RSS, Chap. 10.1, CS 34) renal biopsy after intensified HAP with healing of a defect as focal segmental glomerulosclerosis. Top left: biopsy with extracapillary proliferation (arrow). Top right: normal glomerulus. Bottom: segmental sclerotic glomerulus (activity index 1/24; chronicity index 8/12) (Benenson et al. 2005). Thereby, no lupus-specific changes, significant regression of activity or increased chronicity of LN are to be seen. In the subsequent 6 years, sustained remission is to be evaluated under maintenance therapy (azathioprine 100 mg or 50 mg and Decortin® 10 mg/daily). At present there are no indications for secondary neoplasia.

CS 34: CYC-resistant nephrotic syndrome, unexplained subcutaneous involvement; activity and chronicity of LN from the perspective of renal biopsy, response to HAP, female, 52 years The multiorgan involvement and specific immunology enable confirmation of the diagnosis. The emergency aspects developed initially from acute onset of arterial hypertension (260/160 mm Hg for one week); at the emergency department, hypotensives were prescribed, with pain and swelling of the entire right leg appearing later. The pelvic/leg vein thrombosis was confirmed by ultrasound and CT, since which time the patient has been on phenprocoumon. A second acute process (firstly in the elbow region, then lower leg/foot, Fig. 27) occurred twice during 4 years. This was initially considered to be an infection in

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an immunosuppressed patient, treated with antibiotics but to no effect. A response to intensified immunosuppression indicates specific panniculitis within the context of the underlying disease. The therapeutic aspects of this case are found firstly in the CYC-resistant course of LN (Fig. 92). The new option, namely intensified HAP, triggers clinical remission of the disease and GN, sustained over the last 6 years by 100 or 50 mg azathioprine PO. The successive renal biopsies taken during this period enable the favorable (minimal renal insufficiency, no lupus-specific changes) yet progressive (increasing chronicity index) course of LN to be easily controlled (Benenson et al. 2005). 94. (B) A clinical syndrome (RSS, Chap. 9.1.1) which can only be interpreted in conjunction with the anamnestic evidence of acute myasthenia syndrome and myalgia (RSS, Chap. 9.6). At present, there is minimal activity in the disease (myalgia, CK elevation). Therapy: Decortin® 10 mg and azathioprine 100 mg (daily) with response in the skin. 95. (A) A clinical syndrome (RSS, Chaps. 3.3.1, 3.7.1 and 9.5) with consistent morphological correlate (see also Fig. 63). Therapy: during the early stage of inflammatory activity of the process and underlying disease, respectively, antiinflammatory therapy (cortisone PO or locally – but no crystal suspension! – preferably Lipotalon® or if possible laser therapy); for late-onset forms and fibrosing changes surgery may be indicated. 96. (A) A radiological syndrome (CT of the skull → RSS, Chap. 10.8.5) should be diagnosed not only radiomorphologically, but histologically (granulomatous inflammation is detectable, no lymphoma) and immunologically (cANCA, ACE are in this case not detectable). Such orbital granuloma is to be regarded as a progression of the inflammation in the sinuses, as in Fig.  86 (same disease). Therapy: immunosuppression (incidentally not tolerated in a 72-year-old woman with certain RA). 97. (A) A radiological syndrome (conventional X-ray → RSS, Chaps. 1.4.4, 4.11.2, and 6, Step 8) only explicable in the context of the medical history (CS 35). The intensified pain symptoms in the right hip, on response to rituximab, necessitate orthopedic consultation. Therapy: total hip replacement was highly successful.

CS 35: Severe hip pain in RA patient with minimal activity, 53 years The inflammatory and noninflammatory joint diseases may present a unique mixture of the symptoms, depending on the clinical and radiological pattern of involvement. This patient, with standard RA and minimal activity, developed severe hip pain during drug-induced remission which was mostly load-dependent and accompanied on initial steps (run-in pain) by asymmetrical narrowing of the joint space and osteophytes (Fig. 97). When interpreting this case, a unique disease in the right hip with RA is most likely. 98. (A) A radiological syndrome (MRI of the feet → RSS, Chaps. 3.7.2 and 4.7) represented the certain morphological diagnosis in the Fascia plantaris region, explicable in the context possibly of the Yersinia infection (CS 36). Mostly this has a mechanical cause (Fig.  108 shows a different radiomorphological correlate for this process). Therapy: local (several cortisone injections in the heel region were only effective

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short-term, physiotherapy) or systemic (cortisone, biologics would be possible only within the framework of AS). 99. (B) Radiological syndrome (MRI of the feet → RSS, Chaps. 3.7.2 and 4.7; CS 36), with full regression of the changes presented in Fig.  98, which should be regarded as a parameter for follow-up control (after laser therapy). Subsequently the patient is free of symptoms (2 years).

CS 36: Refractory heel pain and MRI confirmed response to laser therapy, 63-year-old female (Benenson et al. 2006) This is initially a diagnostic problem which can be solved by MRI. Then it becomes a causal problem, namely with the associations of such changes to the intestine and Yersinia infection, possible linked to mechanical causes. Resistant heel pain was treated with the new option, namely curatively with soft laser therapy (confirmed clinically and by MRI).   100. (A) A clinical syndrome (RSS, Chaps. 2.6 and 9.1.1): palmar erythema associated with pain in the finger tips, in this case in a 36-year-old female patient with RA. Therapy: these changes were regressive upon intensification of the immunosuppression. 101a. (B) A clinical syndrome (leg ulcers → RSS, Chaps. 2.6 and 9.1.2, see also Figs. 2, 30, 31, 55) which can be explained only in conjunction with the medical history (severe RA, long-term cortisone therapy, venous insufficiency, resistance to TNF blockers and basic medication). Therapy: strong immunosuppression (CYC, rituximab). 101b. (B) A clinical syndrome (RSS, Chap. 9.1.2) in the same patient (after rituximab therapy, Dr A. Rubbert). The scarring should be considered when making a diagnosis just as much as the ulcerations (see also Fig. 32).   102. (A) A radiological syndrome (MRI of the calcaneus → RSS, Chaps. 3.3.2, 4.7.1, and 9.5), prior to laser therapy: marked plantar fasciitis: edema of calcaneus (osteitis), perifascial, surrounding of soft tissue and m. flexor digitorum brevis (Benenson et al. 2006). This is a morphological diagnosis with resistant heel and Achilles tendon pain. Causes can only be interpreted in conjunction with CS 37. Therapy: anti­ inflammatory, systemic and/or local therapy (irrespective of cause, extent and bone marrow involvement) indicated.   103. (B) A radiological syndrome (MRI of the heel after therapy in CS 37, complete regression (restitution) of the changes which were to be seen in Fig. 102) used as a radiomorphological parameter for follow-up control (Benenson et al. 2006).

CS 37: Recurrent arthritis, tendinitis, enthesitis, associated with Yersinia infection. Response to laser therapy, 32-year-old female The clinical aspects of this case, documented over 8 years, consist of recurrent arthritis of the small joints (MCP, MTP, and PIP), dactylitis (Digito 2), tenosynovitis, enthesitis and plantar fasciitis. Only the association with the 3 years of serologically fresh Yersinia ­infection can be verified thereby. Fig. 102 shows the tendinitis with bone marrow edema

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around the heel. Therapy: systemic cortisone boosts and MTX for flares, recently Arava®. Laser therapy was used for localized problems (Benenson et al. 2006). 104. (C) A disease (RSS, Chaps. 1.3.2, 3.1.1, and 3.3, see also Figs. 3, 35, 80, 112, 122a, b, 129c). Therapy: systemic (RSS, Chaps. 7.3 and 12.3). 105. (A) A radiological syndrome (CT of the abdomen → RSS, Chaps. 10.1, and 13, Step 9), a morphological diagnosis /nephrocalcinosis/ with unclear clinical significance in a patient with SLE (CS 38) and status post acute renal failure. In other cases, namely in primary hyperparathyroidism and Sjögren’s syndrome, this syndrome is associated with an unfavorable prognosis for the kidneys. Clinically the renal problems present as a nephrotic syndrome (RSS, Chaps. 10.1.2 and 10.1.5). Therapy: systemic, i.e., daily Decortin® (15 mg, 5 mg at present) and MMF (CellCept® 3,000 mg, 1,000 mg at ­present); patient currently has no symptoms, proteinuria up to 500 mg/24 h.

CS 38: ANA-positive mastitis, resistant nephrotic syndrome, nephrocalcinosis, questionable APS, phenprocoumon therapy, iatrogenic renal failure, 27-year-old female This case is of clinical interest first and foremost because of the untypical onset of the disease at the age of 16 with ANA-positive mastitis following exposure to the sun. Six years later, exudative pleuritis developed, pronounced nephrotic syndrome (proteinuria up to 9.0 g per 24 h), thirdly iatrogenic renal damage resulting in acute renal failure after abdominal hemorrhage which occurred during the unnecessary phenprocoumon therapy. Too systematic a therapy with ciclosporin is, incidentally, known to increase the creatinine levels. Furthermore, it is highly likely that diagnosis of APS (due to proof of ACLA) was not standardized and hence the phenprocoumon therapy was stringent. I also find the stringent therapy with erythropoietin for Coombs-positive anemia (this substance was too highly quantified in the serum) superfluous (in the absence of renal insufficiency). The positive dynamics of proteinuria were seen during CellCept® therapy. Thereby, mixed proteinuria is to be evaluated as glomerular on the one hand and tubular on the other (RSS, Chap. 10.1.2). The latter could be connected to nephrocalcinosis (Fig. 105). If so, limitations to immunosuppressive therapy are possible (in the event of a flare). The switch to rituximab does not at this time seem appropriate due to the clearly reduced proteinuria (to 0.5 g/24 h). 106. (A) A radiological syndrome (MRI of the shoulder → RSS, Chaps. 3.3, 3.6, and 4.1): subdeltoid and subcoracoid bursitis in combination with tendinitis and peritendinitis of the supraspinatus tendon, small amount of joint effusion (Benenson et al. 2006). This is a radiomorphological diagnosis in resistant shoulder pain (CS 39). Therapy: local (physiotherapy, cortisone injections) was ineffective; laser therapy was undertaken. 107. (B) A radiological syndrome (MRI of the shoulder, CS 39) following laser therapy (Benenson et al. 2006): the inflammatory changes in the clinical and MRI findings regressed completely over the long term. MRI should be employed in such a condition for follow-up.

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CS 39: Refractory shoulder pain, MRI-assured response to laser therapy, 61-year-old female This is a presentation, initially, of an appropriate radiomorphological procedure for unexplained shoulder pain. Secondly, we have a relatively new therapeutic option for a common process, i.e., mechanically induced, persistent pain in the shoulder. The complex inflammation was treated effectively with laser therapy confirmed clinically and by MRI (Benenson et al. 2006). 108. (A) A radiological syndrome (X-ray of the heel→ RSS, Chaps. 3.6.2 and 4.7.1), a radiomorphological diagnosis for fresh, not yet calcified osteophytes. In this case the patient could hardly walk; in other cases the radiological changes are not consistent necessarily with the symptoms of pain. Therapy: local (physiotherapy, cortisone injections, radiotherapy, laser therapy). 109. ( B) A clinical syndrome (RSS, Chaps. 3.2.1 and 9.4.1) and clinical diagnosis, respectively, explicable causally only in relation to the medical history (CS 40). Therapy: cortisone (Decortin® 20–10 mg/day, approx. 2 weeks). Discontinuation upon regression of the symptoms.

CS 40: Attacks of fever with high CRP and Erythema nodosum, 26-year-old female The problem was the causal investigation of the last 16 years of feverish episodes and skin changes (Fig. 109). One of the most common causes thereof is sarcoidosis and streptococcal infection, followed by Yersinia infection, which in this case was detected (RSS, Chap. 11.3.2). The diagnosis certainly could have been ascertained sooner. Therapy: most effective is cortisone therapy with e.g., Decortin® 30 mg/day. Antibiotic therapy (tetracyclines/ quinolones) is recommended only if the infection is fresh (e.g., positive stool culture). 110. (A) and 111ab. (A) A clinical syndrome (RSS, Chaps. 9.1.1 and 9.1.3; see also Figs.  15a, 84a, b) developed suddenly, with generalization, 2 days after Humira® injection (CS 41): in the extremities and the whole body, except the face, and particularly dense on the hands and soles of the feet, in the following sequence: first pustules (Fig. 111a), after 2–3 days massive vasculitic and hemorrhagic (massive on the heels), epidermal patches of necrolysis with Urticaria vasculitis, somewhat later psoriasis (Figs. 110 and 111b). Therapy: prescription by dermatologists of mostly local therapy, with good effect.

CS 41: Drug-induced generalized polymorphic efflorescences following TNF blockers, female doctor, 49 years Such changes (Figs. 110, 111a, b) are to be viewed as drug-induced (RSS, Chap. 9.1.3); they developed simultaneously, without prior signs, following injection of Humira® in a patient with psoriatic SpA who was HLA-B27 positive. There is a history of regular intake of this medication for 1.5 years, with good response, also in the plaques, without any

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adverse effects. Also remarkable was the extent and the step-wise progression of these changes: initially pustulous efflorescences, then the vasculitic component and ultimately in those areas the massive superficial plaques. Also remarkable was the efficacy of the local therapy prescribed by dermatologists. Despite the known associations of such changes with TNF blockers the question must be asked whether the other members of this TNF family should be prescribed upon increased activity of the underlying disease. In one almost identical case a patient with AS was effectively treated with Remicade® for 3 years. Thereafter, the changes on the hands and soles of the feet developed after the 4th injection when switching to Humira® /Fig. 129b/. Such pustulous keratoderma blenorrhagica (RSS, Chaps. 9.1.1 and 9.1.3) could be regarded as another variant of pustulous psoriasis in SpA, particularly in ReA or SAPHO syndrome. A switch to Remicade® (together with local therapy) produced a marked improvement in the skin symptoms. The known psoriasisinducing effect of TNF blockers, however, in the form of Psoriasis vulgaris, appears from the last summary (Wollina et al. 2008) to be family-specific. Recently we have seen such changes using Cimzia®. 112. (B) A radiological syndrome (CT thorax → RSS, Chap. 10.2.2) in ANCA-positive female patient, 63 years, demonstrated a progression in size of bipulmonary and intrapulmonary infiltrates and caverns: in the mid lobe clearly connected to the bronchial system (caverns almost 6 × 5 cm), in the right dorsocaudal lower lobe (cavern approx. 4.3 × 6.2 cm). The two granulomas in the left lungula were confluent and now measure 4.3 cm in diameter. At the time of examination (after 3rd cycle of CYC bolus therapy) the general condition was seriously deteriorated, CRP increased (to factor ´ 30), and procalcitonin normal. Having ruled out superinfection and neoplasia, rituximab therapy (two infusions of 1,000 mg each) and CellCept® 2,000 mg per day were initiated (Dr A. Rubbert). Complete regression of the aforementioned pulmonary changes ensued in 6 weeks. 113. (B) A clinical syndrome (RSS, Chaps. 9.1.2 and 9.2.2, see also Fig. 14) can be assessed causally only in the context of the medical history (CS 42). Therapy: at present the disease appears to be self-limiting and not in need of therapy.

CS 42: Depression and treatment-associated gangrene, 50-year-old male The diagnosis of vasculitis (2 years ago) had very certain criteria (status post amputation of toes 2 and 3 on the right shown in Fig. 113). On the cause. Previous history: treatment with psychopharmaceuticals (for depression) ensued at the same time as the above mentioned acute condition. From the first event onwards, Trevilol® was prescribed but the ­correlation to the product was not evident, or such a correlation was not questioned. Prior to the second event other antidepressants were taken (Remergil® and Edronax®), and the changes were not reversible. On the nature of the vasculitis. To obtain a true picture, cortisone was first stopped. Subsequently, no criteria for systemic vasculitis were found: neither Raynaud’s syndrome, nor organ or connective tissue involvement, nor laboratory parameters (CRP, ANA, ANCA, coagulation problems were not indicative). The pulmonary hypertension (40 mmHg) which developed shortly after stopping cortisone was seen

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as related to COLD, with diminished one-second capacity (48%) and no diffusion disorders. We could find no criteria as to whether the vasculitic symptoms existed whatsoever 2  years following surgery. Such constellations could almost exclusively involve druginduced vasculitis. This form of hypersensivity angiitis often has, as in this case, a terminated, self-limiting course (upon discontinuation of medication) as well as untypical symptoms, e.g., no organ involvement (cerebellar infarction is to be seen as an independent problem) or Raynaud’s phenomenon. Therefore it is not wise, in my opinion, to undertake further diagnostics, e.g., muscle biopsy or MRI of the thighs. The diagnosis could ultimately be established from the extensive history, namely by determining the close timerelated connections of the two episodes of bleeding disorders with the intake of psychopharmaceuticals. The basic therapy appears, on account of the lack of activity, not to be indicated. 114. (A) A clinical syndrome (RSS, Chaps. 3.1.2 and 4.7), post-operative status of 1st toe (CS 43).

CS 43: Acute puffy hand right after tophus ablation of first toe, 56-year-old male patient This patient’s problems emerged 3 days after outpatient surgery, manifested as acute puffy hand-like changes (Fig.  115; cf. Figs.  7, 66), but accompanied by asymmetrical joint involvement (!), fever and extreme pain in the wrist as well as elevated CRP. Such an association between surgery and distant arthritis should always raise the suspicion of ­septic arthritis. Positive pathogen diagnostics ensued (from blood and joint punctate). Conservative therapy (see comments on Fig.  115) is most commonly employed, lasted 4 weeks and was effective. 115. ( B) A clinical syndrome (RSS, Chaps. 1.3.1, 4.4, and 4.6.2) can be clarified causally only in the context of the medical history (CS 43). Therapy: wrist puncture (repeated, preferably with irrigation /lavage/ of the joint), long-term antibiotic therapy; if such therapy is inadequate, synovectomy is indicated. 116. (C) A radiological syndrome (X-ray spine → RSS, Chaps. 2.3 and 6, Step 8, see also Figs.  118, 123), radiomorphological diagnosis, not necessarily consistent with the pain and other spinal syndromes. Therapy (orthopedic): depending on concomitant syndromes (RSS, Chaps. 3.4 and 3.12.1), could be surgical in the case of spinal canal stenosis, for example. 117. (C) A radiological syndrome (X-ray spine → RSS, Chaps. 2.2.1 and 6, Step 8, see also Figs. 60, 124) is absolutely specific (diagnostic criterium) in the causal investigation of back pain. Therapy (rheumatological): according to disease activity. 118. (C) A radiological syndrome (CT spine → RSS, Chaps. 1.5.2, 2.3, and 6, Step 8), marked spondylophytes, described as DISH (diffuse idiopathic skeletal hyperostosis) syndrome, with high diagnostic value in the causal investigation of back pain; is not necessarily consistent with its intensity, common in patients with Diabetes mellitus, often confused with syndesmophytes (cf. Figs.  116, 117). Therapy (orthopedic): depends on concurrent symptoms (RSS, Chaps. 3.4 and 3.12.1).

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119. (B) A radiological syndrome (conventional X-ray hip → RSS, Chaps. 1.3.3, 2.4.1, 4.10.1, and 6, Step 8), radiomorphological diagnosis (concentric narrowing of joint space) which can be causally explained only in conjunction with the medical history. It is important to find symmetrical involvement (see also Fig. 97). At the same time, there is increased subchondral sclerosis in the symphysis region which, at the time, appeared together with pain in this area. To be regarded as symphysitis (see Fig.  120). Therapy: surgical (Fig.  120). Figs.  119, 120, 124 belong to the same patient. 120. (B) A radiological syndrome (conventional X-ray hip → RSS, Chaps. 1.3.3, 2.4, 4.11, and 6, Step 8). Postoperative status in patient in Fig. 119 (total hip replacement bilaterally and stabilization of lower sacroiliac joints). Can another radiomorphological syndrome be identified? Yes. 121. (A) A radiological syndrome (MRI of the hip → RSS, Chaps. 2.4.3, 3.10.1, and 4.11), highly specific morphological finding: marked signal changes in left acetabulum, ­following application of contrast agent the changes in the acetabular roof show strong enhancement, entire left acetabulum clearly surrounded by bone marrow edema. The finding can be clarified causally in relation to the medical history (CS 44). Is spontaneous osteonecrosis in the acetabulum or coxitis most likely? Therapy: ­primary disease not active at present, hence cortisone should be discontinued. In terms of the acute process, MTX should be applied. A good response could be achieved immediately: the patient remains mobile, and almost free of pain. Prognosis of the process is unclear.

CS 44: Polyarthritis, cortisone therapy, acute motion deficits in the hip, female, 25 years Once the morphological correlate to severe hip pain has been clarified by MRI (Fig. 121), the question of causes for this condition and the underlying disease arises. Asymmetrical arthritis of the large joints and proven fresh Yersinia infection are the criteria for diagnosis of ReA → RSS, Chap. 11.3.2. This was possibly treated too systematically with cortisone, resulting in the new onset of left-sided hip pain influencing the clinical picture. This is a common occurrence sometimes unavoidable with long-term cortisone therapy (RSS, Chaps. 3.10.1 and 12.1) and should be dealt with separately - in our case with MTX and good functional results. 122ab. (B) A radiological syndrome (MRI of the right forearm, 2 projections): extensive linear mass of soft-tissue density with a diameter of 17 × 2.5 × 3 cm, inhomogeneous contrast enhancement, producing a wall around the distal ulna which partly causes destruction of bone as well as the immediate tendons). Recommendation: schedule surgery. Such tumor-type, painless changes were first assessed as a malignant tumor e.g., sarcoma (CS 45) and biopsied three times (!). Thereafter, surgery ensued with fusion of the right wrist joint (Fig. 122c).   122c. (C) A radiological syndrome (conventional X-ray of forearm, → RSS, Chaps. 1.3.4, 3.1.1, and 4.4); post arthrodesis of the wrist (stabilized with a plate) for instability of the joint (see comments on Figs. 122a, b). The underlying disease can be seen from the histological finding of the above mentioned tumorous changes (massive

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mass of rheumatoid nodules) and the considerable destruction of the wrist bones (also as in Fig. 9a; a different form of destruction and a different disease can be seen in Fig. 34). Surgery ensued to prevent luxation in this joint with deficits in hand mobility. The hand function was thus clearly improved.

CS 45: Massive tumor on lower arm with bone destruction and ulnar compression syndrome in female patient with RA aged 55 years This patient appears to be “exquisite”, initially by diagnosis and then therapeutic outcome. The seropositive RA without rheumatoid nodules and anamnestic evidence of bone TB revealed a massive linear mass in the lower arm, suspected to be tumorous, infiltrating the surrounding structures (nerves, tendons, muscles, synovial membrane) and destroying the bones. Hence there is a variety of rheumatological and neurological symptoms. Painless soft-tissue swelling should generally lead to the suspicion of sarcoma. During surgery, an enormous, histologically confirmed rheumatoid nodule was found as a liquid mass and was curatively removed; the wrist and wrist bone were fused for the purposes of stabilization. The peculiarities of this case are: (1) the extent of the only linear rheumatoid nodule with necrosis which developed following the ineffective rituximab therapy, or this therapy was not able to prevent growth of the nodule, (2) the specific malignancy of the local symptoms (N. ulnar compression syndrome, bone destruction, tendon damage), (3) local symptoms treated curatively by orthopedic colleagues. As basic therapy, other biologics – namely Enbrel® (with a view to the history of TB) – are used successfully but not persistent. The disease activity was minimized in the last 4 months with Simponi® (50 mg monthly SC). 123. (C) A radiological syndrome (conventional X-ray of the lumbar spine and sacroiliac joints), a radiomorphological diagnosis (RSS, Chaps. 2.3 and 6, Step 8, see also Fig. 116) in the form of massive osteophytes, sacroiliac joints have in this case a key role in the assessment of the lumbar problems (cf. Fig. 124). Therapy: orthopedic. 124. (C) A radiological syndrome (conventional X-ray of sacroiliac joints; → RSS, Chap. 2.2.2), radiomorphological diagnosis in the form of massive syndesmophytes in lumbar region, no sacroiliac joints space (total ankylosis). Therapy: predominantly rheumatological and as necessary orthopedic. 125. (B) A radiological syndrome (conventional X-ray of thoracic spine at level of thoracic vertebrae 6–8, → RSS, Chap. 3.11.1). Post osteosynthesis of a fracture to the thoracic spine (1995) with incorporated osteosynthetic material (cage and pedicle screws). 126. (A) A radiological syndrome (CT of thoracic spine of 17.01.08 → RSS, Chaps. 2.1.2, 3.11.1, and 3.12.1): narrowing of the spinal canal at level T3 with collapsed posterior edge of vertebra from fracture at the same level, of unexplained etiopathology. 127a. (B) A radiological syndrome (CT of thoracic spine of 17.01.08 → RSS, Chap. 3.11.1): osteoporotic sintering fracture of vertebra T3. 127b. (B) A radiological syndrome (CT of thoracic spine of 19.08.08): status post emergency surgery, spondylodesis T2 (thoracic vertebra)/T4, open repositioning of spine by osteosynthesis, computer-navigated (Drs W. P. Groß and G. Schiffer, Neurosurgery, Cologne University).

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CS 46: Years of cortisone therapy in RA, vertebral fracture and acute paraplegia, 73-year-old male Patient taking maintenance therapy for RA for 15 years (MTX and Decortin® 5–10 mg/ day), also since surgery in 1995 (acute event at that time considered as related to osteoporosis). The patient has since been relatively well mobilized, with regular outpatient followup, lastly on 08/01/2008. The acute paraplegia is causally related to a fall and osteoporosis-induced compression fracture of the spine, clearly visible in Figs. 127a, b. The case illustrates the almost unavoidable consequences of long-term cortisone therapy in an elderly patient with RA and restricted mobility. The patient died 2 months after the event (probably as a result of pulmonary embolism). 128 (abc) Visual diagnosis hands 129 (abc) Visual diagnosis hands/feet 130 (abc) Visual diagnosis hands/feet 131 Visual diagnosis of the systemic rheumatic disease 132 Visual diagnosis of the systemic rheumatic disease

CS 47: Unclear arthritis and contractures of the fingers, referral diagnosis of RA, radiological signs of OA and gout, 70-year-old male patient The patient was referred several times in about 5 years for rheumatological consultation. In terms of the pattern of involvement, there is a mixture of clinical and radiological data most likely attributable to OA (flexor contractures, Fig. 130a) and chronic gout arthritis (intermittent florid, asymmetrical arthritis in toe 1, wrist, knee and ankle joints), tophi in toe 1 /Fig. 130b/, auricles (as in a 10-year-old girl, CS 55). Seronegative RA appears rather unlikely.

CS 48: Acute, severe pain in the legs, dramatic weight loss, abdominal pain, intestinal infarctions and positive cANCA, 30-year-old male patient This case of a life-threatening condition initially posed enormous difficulties with diagnosis in a 30-year-old man. Acute sensory and motor deficits developed in the legs and feet (polyneuropathy), then rapid weight loss (retrospectively it is clear that this was linked to malabsorption or with the involvement of the small intestine) and, following abdominal pain with mild tension (of unclear etiology at that time) there were several intestinal perforations. A further problem: how is such intestinal involvement to be evaluated in an ANCA-positive patient: on the one hand as ANCA-associated vasculitis with involvement of the medium and small vessels or as an entity, namely PAN. Subsequent therapy (40 cm of small intestine removed), basic therapy with CYC ­(discontinued due to liver damage) and rituximab, then maintenance therapy with MMF, resulted in complete restitution of the symptoms (normal weight, no vasculitic symptoms, ability to work). In a further 3 years, showed the increasing renal insufficiency.

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CS 49: Exudative pleuritis, lymphadenopathy and morphological diagnosis of lupus in skin biopsy, female, 40 years This case demonstrated the significant value of immunological data as compared to morphological data when considering the diagnosis of CTD. In this case, the disease-specific immunology (ANA, SS-A, SS-B, high RF) is pivotal to the diagnosis (RSS, Chap. 11.1) and morphological diagnosis must be considered for skin biopsy (of LE). This morphological finding depicts the common changes typical to CTD and should not be described as an entity (RSS, Chap. 11.6). This also applies to the biopsy of the lymph nodes in this disease, which is not entirely indicated (was almost always carried out, as in CS 66), particularly with such a constellation. In such a symptom-free state, the patient certainly does not require treatment.

CS 50: MCP 2-3 and other forms of arthritis, status post MTX therapy, ferritin increase, male, 56 years Stable polyarthritis is commensurate with RA, which in this case had been treated by colleagues systematically, for several years. Whether this term – arthritis – is correct in this case depends on the cause of the condition. A disease-specific laboratory value can explain the causal diagnosis. Other keys to this case lead from the pattern of involvement, namely asymmetrical oligoarthritis of the large joints, as with inflammatory OA, primarily MCP 2-3 (Figs. 58, 59) bilaterally, with no inflammatory signs. Isolated MCP 2-3 arthritis should always be indicative of a fairly common genetic disease in which, incidentally, primary arthrotic and secondary arthritic changes predominate. Thus, first identify the underlying disease and then the pattern of joint involvement! Or vice versa. In terms of therapy, pathogenetic (what is meant by this?) comes first (RSS, Chap. 1.5.4) and then symptom-oriented (joint punctures with cortisone injection, RSO, orthopedic measures) therapy.

CS 51: Acute hemolytic anemia and pneumonia associated with Chlamydia and dsDNA antibodies, female, 25 years This case first demonstrated the diagnostic problems in explaining the new onset of hemolytic anemia. In a young woman with hemolytic anemia and pneumonia, the systemic disease should primarily be ruled out immunologically. In this case, these syndromes were associated with Chlamydia infection. This could well be the case, or more specifically that hemolytic anemia presents as a mono symptom in chronic SLE. Over the course the patient experienced involvement of other organs and systems, namely the CNS, kidneys, lungs, APS. As a consequence, the diagnosis of SLE appears to be certain. The basic therapy required should be adjusted to the patient’s explicit wish to have children. To treat the CNS involvement, pulse therapy with cortisone, then maintenance therapy (Decortin® 10 mg/ day and for a short period over 5 weeks MTX 15 mg/week SC) was initiated. Stabilization was achieved (Decortin® 5 mg and azathioprine 100 mg daily).

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CS 52: Minimal RA activity, excessively high CRP and ESR, male, 68 years This case demonstrated how, with RA already established, diagnostic problems may arise if the deterioration in general health (fatigue, massive myalgias and elevated CRP and ESR → RSS, Chaps. 8.4 and 8.5) is not proportionate to the (minimal) activity of RA. At such an age, tumor and infection screening should basically be initiated. The next step was to clarify whether this condition was dependent on cortisone or not. Therapy: no response to intensified immunosuppression (MTX 25 mg/week SC combined with Arava® 20 mg/ day, Decortin® 20 mg/day, Humira® 40 mg/2 weeks). The cortisone pulse therapy administered twice (Fortecortin® 8–2 mg over 3 weeks PO) was clearly effective, clinically as well as in terms of CRP and ESR. On reducing the cortisone dosage, the neck/shoulder pain returned along with minimal arthritis in individual PIP joints, higher CRP and ESR values. At present, therapy is ongoing with Decortin® 7.5 mg and Azathioprin 100 mg daily and MTX 10 mg per week, with no arthritis or signs of inflammation. In summary, a response to cortisone must be specifically evaluated. This leads to the suspicion – particularly at the given age – of another inflammatory/rheumatic concomitant disease. One of which involves shoulder and neck pain – of that I am certain.

CS 53: Pain and swelling of the finger joints and high-titer RF, ANA and ENA, long-standing diagnosis of RA revised, female, 45 years This case showed that periarticular arthralgias, non-synovialitic swelling of the fingers and high-titer RF may have other causes than RA. The lack of erosions and signs of arthritic activity on bone scan were the criteria for further causal investigation. The unremarkable sicca symptoms (RSS, Chap. 10.7) and remarkable, specific CTD serology (RSS, Chap. 11.1) produced other diagnostic aspects which could explain all the syndromes ascertained in one concept, better than RA.

CS 54: Raynaud’s syndrome, massive increase in CK and TSH in Scl-70-positive female patient, 30 years (some episodes during 5-year follow-up) The 5-year period of follow-up in this patient showed that systematic immunosuppression (CYC and Decortin®) for SSc can be effective: the swelling (Fig. 130c), induration, livid discoloration and substance defects in the fingers, as well as extensive sclerosis of the skin on the arms and shoulders receded. Over the course, two different masks of this disease were seen, with virtually identical symptoms: fatigue and myasthenia, accompanied ­initially by a massive increase in CK (with normal TSH). Somewhat later, there was a noticeable, massive increase in TSH with low readings of free T3 and T4, but at that time no CK elevation. These common syndromes of SSc were largely stabilized by increasing the immunosuppression for the myositis syndrome on the one hand and l-thyroxine ­therapy for the massive hypothyroidism (RSS, Chap. 12.4.4).

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CS 55: Acute recurrent attacks of pain in toe 1 in 10-year-old girl, polyarthritis with deformities and elevated creatinine (20 years later) This case has been described under the heading “juvenile gout in women” (Kurmanalieva et al. 1986). It revealed the classic variant of “male” gout at that age and over the course, characterized by the serious consequences of hyperuricemia, as far as concerns the joints (destruction, deformity, motion deficits) and renal involvement (interstitial nephritis with renal insufficiency). The initial diagnosis of seronegative RA certainly did not have a positive influence on such damage. The potential pathogenetic background is evidently found in the endogenic, hereditary enzyme deficiency (excess purine load excluded). The therapeutic options are the same as those for adults with gout.

CS 56: Sicca syndrome, enlarged parotid, acute increase in serum calcium epistaxis (three emergency situations over a 12-year follow-up period, female, 65 years) This case showed that lymphoma possibly developed from Sjögren’s syndrome. The question is how to identify as early as possible the degeneration or relapse in the ­lymphoma. This concept, or postulation of such, should be reached based on (1) the clinical (deteriorated general health, increase in parotid mass and lymphadenopathy, development of systemic vasculitis /small vessel disease/, could at the same time be part of Sjögren’s syndrome), (2) the biochemical (hypercalcemia with no increase in parathormone; increased anemia, polyclonal B-activation, b-2-microglobulins) and (3) the morphological (cell transformation in the parotid and bone marrow) data. The case also demonstrates that complete remission is highly likely if lymphoma is diagnosed early.

CS 57: Known PsA with minimal activity, polyarthralgias, long-term incapacity to work, discharge from cure therapy because of acute relapse, engineer, 46 years The inflammatory joint disease appears certain, but with minimal activity (no florid arthritis, even on bone scan, no increase in CRP or ESR). The many months of incapacity to work and sudden discharge from cure therapy have, in my opinion, other causes – namely the diffuse pain symptoms or undiscovered fibromyalgia, which represented the justification for such organizational measures. Therapy: MTX 15 mg/ week SC appears to have an effect on the skin changes, but less on the arthralgia. The  trial use of Remicade® (three times) was ineffective in terms of the joint and back pain. The prognosis of PsA (RSS, Chap. 7.4) in this case seems to me to be better than that of fibromyalgia, which is often associated with depression and disability (see CS 59).

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CS 58: Arthritis, dramatic weight loss, swallowing difficulties, ANA with anti-Cenp differentiation, female patient, 68 years Such a case should be viewed from two angles. Firstly, a systemic rheumatic disease ­(stable, non-erosive arthritis, swallowing difficulties, calcinosis, telenagiectases and, above all, anti-Cenp-Ab) is identifiable. The paraneoplastic aspects are possible on account of the loss of up to 15 kg in weight without changes in appetite (over a period of 6 months); they could not be confirmed by tumor screening. In such circumstances, massive esophageal motility disorders are involved, in my opinion, developing as part of the CREST syndrome and possibly affecting the small intestine by means of malabsorption. The excessive increases in TSH and low values for T3 and T4, which are often association with such an illness, are not insignificant when considering the general condition. Such a condition is always to be found with CREST syndrome and always requires treatment.

CS 59: 31-year-old female patient with general symptoms, fever and discrete lymphadenopathy (histology NHL). After 14 years of general symptoms, “pain all over”, fatigue, depression, incapacitated In this patient, the two entirely distinct diseases, with partly identical symptoms, should not be overlooked. 14 years ago the clinical pattern was entirely non-specific until a colleague (Dr E. Erdmann, Cardiology, Cologne University) reached the unobvious conclusion to have a minimally enlarged, iliac lymph node biopsied. Consequently, the diagnosis of B-cell NHL was ascertained and treated effectively. Another clinical pattern developed 14 years later, also with general symptoms, fever, abdominal symptoms and mainly with diffuse pain, leaving the patient reliant on strong analgesics. Once a relapse of the underlying disease, infections and CTD had been ruled out, the condition was interpreted as fibromyalgia with diffuse pain syndrome. This was certainly a secondary somatogenic fibromyalgia as a result of the previous serious disease, with medicinal and social sequelae. The referral diagnosis, namely PMR (from age alone), appears to be ruled out.

CS 60: Fever of unknown etiology, polyarthritis, positive Yersinia serology, lack of RF and anti-CCP-Ab in 40-year-old male patient The diagnostic problems were considerable with an unexplained clinical pattern over 6 months, with septic pathology (fever, nocturnal sweating, asymmetrical arthritis of the large joints, extremely high CRP). Polyarthritic involvement ensued with symmetrical arthritis of both wrist joints and individual PIP joints. The initial clinical pattern can be explained in association with the later detection of Yersinia infection as its rare variant (RSS, Chap. 11.3.2). The subsequent development of polyarthritis would be characteristic on account of the pattern of involvement of the second joint disease, which did not reveal any immunological markers, however. Therapy: initially resistance and in the last 2 years response to basic medication (Decortin® 20 to 5 mg/day, MTX 15 mg/wks SC, Arava® 20 mg/day, Remicade® N2, Rituximab N2, several RSO). Hence, the distinctions between

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seronegative RA and ReA are sometimes difficult, particularly if two diseases exist, as I would suggest in this case.

CS 61: Minimal activity of RA, diffuse pain, stable requirement for Durogesic® over the last 5 years, female patient, 80 years This case represents a disease or condition causing the need for Durogesic®. Whatever the case it is not RA, which is certainly very well controlled. It is a diffuse pain syndrome which can possibly be described as secondary to RA. Pain therapy with opiates should, in my opinion, be administered at a pain management clinic.

CS 62: Fever, polyserosis, elevated CRP, GGT, LDH and anti-dsDNA antibodies in 70-year-old male patient Two important criteria for further diagnosis and therapy were identified at the hospital, namely the exclusion of other diseases and the cortisone dependency. The individual syndromes of the disease are entirely non-specific and suggestive of many diseases, but the combination of these syndromes is highly specific for an inflammatory/rheumatic disease which can be distinguished from SLE. The minimal increase in anti-dsDNA-Ab in such constellations should not carry any lupus specificity, since the other components of SLE, namely connective tissue symptoms, renal involvement and even vascular problems, are absent (RSS, Chaps. 8.1 and 8.4). What is the concept for Still’s in adults? To be certain, the quantity of cortisone should first be reduced, if possible, at least as far as the clinical threshold. Rheumatological check-up should then be repeated. Therapy: Arava® 40 mg/ day once per week, then 20 mg/day and Decortin® for 2 months, reducing from 70 to 10 mg/day, without any reactivation of the clinical symptoms.

CS 63: Severe cervical syndrome and isolated C1-C2 arthritis, initially of unknown etiology, female, 53 years The initially, apparently isolated C1-C2 involvement (cervical syndrome, no other joint or back pain) was interpreted, by myself, as secondary inflammatory osteoarthritis with osteitis (thus explaining the high CRP and ESR) on the basis of the MRI finding, and scheduled for local therapy (cortisone installation). A colleague devised and confirmed a different concept by verifying sacroiliitis, but with HLA-B27-negativity. I would still adhere to this procedure, have the entire spine examined despite the local symptoms and commence with local therapy.

CS 64: Acute myelitis with paraplegia, mouth ulcers, hemolytic anemia with thrombocytopenia and positive cANCA, female, 47 years The systemic nature of the disease, with extraordinarily varied clinical, laboratory and immunological symptoms, is evident. The inflammatory nature of the disease is also clear. What was unclear, in particular, upon admission, was the question whether vasculitis or

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CTD was involved. The atypical pneumonia and pronounced Moschkowitz syndrome with ANCA positivity are more suggestive of primary (which?) or secondary vasculitis. Ultimately, this prognostically very unfavorable Moschkowitz syndrome was treated (cortisone, vincristine and rituximab, but also antibiotics) successfully. Nevertheless, the entity remains unexplained. To this aim, analysis of previous history should help. The first question to be answered is which vessels are affected. Acute brain stem encephalitis, butterfly erythema, GN with renal insufficiency, oronasal ulcerations, cytopenias, all suggest involvement of the small vessels, most likely as part of SLE. But this concept is contradicted by the immunological (no anti-dsDNA-Ab but ANCA) and morphological (not a typical pattern for SLE in main bioptate, rather fibrosis and sclerosis, as is typical for SSc) data. In the context of clinical findings, such results should be assessed retrospectively as non-specific (ANCA) or common with SLE (ulcerations). They certainly do not rule out SLE. Over the course, therapy with Decortin® 10–5 mg and CellCept® 1,000 mg daily enabled stabilization and release from the symptoms, which can be described as a clinical and immunological (no ANCA detectable) remission of SLE.

CS 65: Pain and swelling in the ankles of a physically active woman, 62 years, with known psoriasis When investigating the resistant pain in the feet and heels, radiomorphological diagnosis should initially be the aim (with MRI), thereby revealing polydimensional, inflammatory involvement of, namely, the tendon sheath (tendinitis), attachments (enthesitis) and bones (osteitis). The causal explanation is reliant on the distinction between mechanical and inflammatory pain. Based on the pattern (at rest, better than on exercise), history (psoriasis vulgaris, arthritis of the knee) and clearly elevated CRP and ESR, such constellations are more likely to be interpreted as inflammatory in nature due to the known psoriasis, if serological and immunological markers of other diseases are absent. After therapy (5 weeks: Decortin® 20–0 mg/day and MTX 15 mg/week SC, then soft laser therapy 785 mm N10 (Benenson et al. 2006)), the patient was free of symptoms (8-month follow-up).

CS 66: Fever of unknown etiology, lymphadenopathy and cough in a male patient aged 15 at the time (six episodes during the last 12 years) When the disease first appeared, there were considerable diagnostic problems when investigating the multitude of clinical and laboratory symptoms. The exclusion of the most common diseases in such constellations is to be seen as the first necessary step, in which case the similar (infections such as sepsis or infectious mononucleosis) and the distinct (possible malignancies) DD spectrum should be introduced in the case of younger (this case) and older (CS 62) patients. When ruling out such diseases, “consideration is necessary”: namely of a relatively rare disease with no specific, morphological, radiological or immunological markers but luckily virtually stable clinical and biochemical constellations, whereby fever of unknown etiology with elevated CRP and liver enzyme-LDH, but also macular exanthem and arthralgias should be prioritized. Such a disease is always an ­exclusion diagnosis. The virtually stable clinical and biochemical constellations, and

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79

c­ ortisone (dose) dependency, are helpful in this case. Therapy: initially high-dose cortisone (pulse and then maintenance therapy for 3–4 months), then combined with MTX (good response); with no response and adverse effects (nausea) to such therapy, Arava® (initially 100 mg – 3 days, then 20 mg/day) without cortisone was used 2004–2005, with prompt response and full clinical remission (2 years); patient was convinced that Arava® achieved more than high-dose cortisone.

CS 67: Emergency hospitalization of 42-year-old RA patient, female, after outpatient attendance with increased serum calcium levels This patient, whose general health was not diminished, was clinically diagnosed at the first visit (28.02.04) as having seropositive RA (polyarthritis, positive RF and anti-CCP-Ab). A couple of hours later, increased levels of calcium in the blood (3.37 mmol/l; upper limit 2.6 mmol/l) were ascertained. Such an emergency situation developed during the asymptomatic phase of the newly discovered condition. To avoid hypercalcemic crisis, which without precursors could have been exacerbated (cardiac arrhythmias with sudden death, polyuria, and somnolence), such patients should be sent to a hospital immediately. At a serum calcium level > 3 mmol/l, surgery is indicated in an asymptomatic state. Consideration should be given to the cause of the condition prior to surgery. Paraneoplastic hypercalcemia takes a different course (see CS 56). In such a case (CS 67) the patient was suffering from a primary disease (the myeloma was excluded) and was cured long-term by surgery.

CS 68: Female patient with known RA, long-term MTX therapy and leukopenia. Response to CellCept®, 62 years To obtain the correct diagnosis, it is important to establish the following constellations: firstly, confirmed RA, then absolute, pronounced neutropenia, postulated as a result of one-year administration of MTX. Subsequently, isolated middler doses cortisone therapy (Decortin® 20–10 mg/day) was applied with no basic preparations. This concept of druginduced myeloplasia cannot be confirmed by bone-marrow biopsy (more a regenerative condition). Hepatolienal syndrome suggests activation of the reticuloendothelial system, which is to be regarded as the target for immunosuppression. Determination of antineutrophil antibodies is pivotal to the diagnosis. Therapy: to begin with, immunosuppressive therapy for neutropenia (by hematologists) was refused and, on account of the high RA activity, only high-dose cortisone (no basic therapy) was prescribed. Addition of CellCept® 2,000 mg per day for 2 months produced a successive rise in leukocytes (to 3,500/ml) and neutrophils (abs. 1,400/ml). The antineutrophil antibodies were no longer detectable. After reduction of therapy (to Decortin® 5 mg and CellCept® 1,000 mg daily), neutropenia again developed and the antineutrophil antibodies could again be detected. Intensified immunosuppression for 2 years already had a positive influence (incidentally without side effects) on the clinic state and relevant laboratory parameters (currently under treatment CellCept® 1,000 mg and Decortin® 5–7.5 mg daily). If such therapy were ineffective, rituximab would be a possibility.

3

Index of Figures (Fig.) and CS with Syndromes (for Self-assessment)

All figures have been classified according to the proximity of their morphological substrate to a condition or disease into three groups which are either all-encompassing or non-­ delimitable (see Chap. 2) A. Syndromes specific to a condition B. Non disease-specific syndromes C. Disease-specific syndromes Try to formulate the suspected diagnosis belonging to the figures and clinical situations. Fig.

CS

Syndromes or complexity of problems of the CS

1

Answer: diagnosis or condition Figurative image of rheumatology

2 (B) 3 (C) 4 (C) 8 (C) 5 (C) 9ab (C) 6 (B)

1

Acute swelling and redness in the ankle joint in immunocompromized female patient, 42 years

7 (A) 8 (C) 4 (C)

2

Puffy hands and high titer ANA in 26-year-old female patient

9a (C) 9b (C)

1

10 (C) 11(C) 12 (B)

3

Acute claudicatio arteriosa in the form of weakness in the legs and lupus-type immunology in a 40-yearold female patient (56 years old at present) (continued)

E. Benenson, Rheumatology, Clinical Scenarios, DOI: 10.1007/978-0-85729-240-7_3, © Springer-Verlag London Limited 2011

81

82 (continued) Fig.

3  Index of Figures (Fig.) and CS with Syndromes (for Self-assessment)

CS

13 (C)

Syndromes or complexity of problems of the CS

Monoarthritis with redness, broad swelling of the MCP 2 right and hand

14 (B)

4

Acute peripheral gangrenes of unclear etiology, 48 year-old male patient

15a (C) 15b (B)

5

Pain and redness in toes and forefoot, massive CRP increase, male, 63 years

6

Several insults (since the age of 17), normal delivery and currently (after 12 years) suffering dementia, deaf-muteness and spasticity, female patient aged 41 years

20a (A) 20b (B)

7

Massive livedo racemosa, reversible under doxycycline, female, 53 years

21 (B) 22 (B) 23 (B) 24 (B)

8

Stable mono/oligoarthritis, HLA-B27-positive, female, 18 years

25 (B) 26 (C)

9

Acute arthritis of the knee in 50-year-old marathon runner

27 (A)

34

28 (C)

10

PIP bursitis and MCP 2 arthritis, female, 26 years

30 (A) 31 (A) 32 (A)

11

Livedo racemosa and deep ulcerations involving the lungs and kidneys, ANCA negative, male patient, 42 years

33 (B)

12

Local erythema, CK elevation and positive ANCA, male, 45 years

13

Pulmonary foci left, suspected tumors, and skeletal tuberculosis (2004), foci with caverns right (2007) in 58-year-old chain-smoker with RA

16 (A) 17 (B)

18 (C) 19 (A)

29 (C)

34 (B) 35 (C) 36a (B) 36b (B) 37 (B) 38 (B) 39 (B) 40 (C)

Answer: diagnosis or condition

83

Index of Figures (Fig.) and CS with Syndromes (for Self-assessment) (continued) Fig.

CS

Syndromes or complexity of problems of the CS

14

Acute swelling of toe 5 on the left, emergency synovectomy with a suspected tumor, female, 52 years

44 (A) 45 (A) 46 (A)

15

Asymmetric pain and imaging of the sacroiliac joint in HLA-B27-positive patient, male, 42 years

47 (B)

16

Acute acral gangrene, high titer ANA without organ involvement, female, 36 years

48a (A) 48b (A)

17

Localized pain, small gibbus in the thoracic spine and CRP elevation in HLA-B27-negative female, 50 years

18

Recurrent neurological and visual deficits (since the age of 13), 3-year treatment of multiple sclerosis (MS), high titer ANA, involvement of the central nervous system stabilized with Imurek® therapy, female, 17 years

19

Acute respiratory distress, pleural effusions and cold hands, male, 58 years

20

Palpable purpura, abdominal pain and renal insufficiency, active hepatitis C, female, 50 years

21

No pulse on one side (since the age of 20), cardiac arrhythmia and 2 acute myocardial infarctions, female, 36 years

41 (B)

Answer: diagnosis or condition

42 (C) 43 (C)

49a (C) 49b (B) 50 (A)

51 (C) 52 (B) 53 (B) 54 (A) 55 (A) 56a (B) 56b (B) 57 (B) 58 (B) 59 (B) 60 (C) 61 (C)

62(C) 51 (C) 63 (A) (continued)

84 (continued) Fig.

3  Index of Figures (Fig.) and CS with Syndromes (for Self-assessment)

CS

Syndromes or complexity of problems of the CS

66 (B) 67 (B)

22

Puffy hands and high CRP of unclear etiology in 17-year-old trainee painter

68 (B) 69 (B)

23

Acute arthritis and Tietze’s syndrome with HIV, female, 36 years

70 (B) 71 (B) 72 (B) 73 (B)

24

Deformities of the hands, myalgia, pacemaker, red feet with ulceration, female 52 years (a number of episodes during 12-year follow-up period)

74 (C)

25

Fever, weight loss and increased inflammatory symptoms of initially unexplained origin in a 50-year-old female

26

Mouth ulcers, heart attack, increased ESR and CRP, female, 73 years

27

Skin and mucous membrane bleeding, thrombocytopenia and high positive anti-dsDNA, no organ involvement, female, 54 years

81(A)

28

Arthritis of the finger joints, rheumatoid factor and appropriate (?) MTX therapy, male, 64 years

82 (B)

29

Alopecia, acute abdominal pain and massive proteinuria, male, 27 years

85 (B)

30

Pulmonary fibrosis, Raynaud’s phenomenon, Scl-70 positive, HAP with response, deterioration in general condition and drop in DLCO transfer, abnormal thorax CT, female, 66 years

86 (B) 87 (B)

31

Multiorgan involvement and MRT of the ENT region under immunosuppression, male patient 62 years (Benenson et al. 2005)

64 (B) 65a (B) 65b (B)

75 (B) 76 (B) 77a (C) 77b (C) 78 (A)

79 (A) 80 (C)

83 (A) 84a (C) 84b (C)

88 (B)

Answer: diagnosis or condition

85

Index of Figures (Fig.) and CS with Syndromes (for Self-assessment) (continued) Fig.

CS

Syndromes or complexity of problems of the CS

89 (B)

32

Arthritis, sicca syndrome and SS-A, CenpB and anti-CCP-antibody, female, 67 years

90 (B) 91 (B)

33

Multiple focal erythema, high ACE and pulmonary fibrosis, male patient, 42 years

92 (A) 93 (B) 27 (A)

34

CYC-resistant nephrotic syndrome, unexplained subcutaneous involvement; activity and chronic indices from the perspective of renal biopsy, response to HAP, female, 52 years (Benenson et al. 2005)

97 (A)

35

Severe hip pain in RA patient with minimal activity, male, 53 years

98 (A) 99 (B)

36

Refractory heel pain and MRI confirmed response to laser therapy, female, 63 years (Benenson et al. 2006)

37

Recurrent arthritis, tendinitis and enthesitis associated with Yersinia infection; responsive to laser therapy, female, 36 years (Benenson et al. 2006)

105 (A)

38

ANA positive mastitis, resistant nephrotic syndrome, nephrocalcinosis, questionable APS, phenprocoumon therapy, iatrogenic renal failure, female 27 years

106 (A) 107 (B)

39

Refractory shoulder pain, MRI-assured response to laser therapy, female, 61 years (Benenson et al. 2006)

109 (B)

40

Attacks of fever with high CRP and erythema nodosum, female, 26 years

110 (A) 111ab (A)

41

Drug-induced generalized polymorphism in the efflorescences following TNF blockers, female doctor 49 years

Answer: diagnosis or condition

94 (B) 95 (A) 96 (A)

100 (A) 101a (B) 101b (B) 102 (A) 103 (B) 104 (C)

108 (A)

112 (B) (continued)

86 (continued) Fig.

3  Index of Figures (Fig.) and CS with Syndromes (for Self-assessment)

CS

Syndromes or complexity of problems of the CS

113 (B)

42

Depression and treatment-associated gangrene, male, 50 years

114 (A) 115 (B)

43

Acute puffy right hand after tophus ablation of first toe, male, 56 years

121 (A)

44

Polyarthritis, cortisone therapy, acute motion deficits in the hip, female, 25 years

122a (B) 122b (B) 122c (B)

45

Massive tumor on lower arm with bone destruction and ulnar compression syndrome in female patient with RA, aged 55 years

46

Years of cortisone therapy for RA, vertebral fracture and acute paraplegia, male, 64 years

116 (C) 117 (C) 118 (C) 119 (B) 120 (B)

123 (C) 124 (C) 125 (B) 126 (A) 127a (B) 127b (B)

Visual diagnosis Figs. 128–132

128a 128b 128c 129a 129b 129c 130a 130b

47

Unclear arthritis and contractures of the fingers, diagnosis of RA, radiographic signs of OA and gout, male, 70 years

130c

54

“Madonna fingers” (early stage): taut skin, white-reddish discoloration, incipient flexion contractures

131

Fever, not persistent maculopapular rash and arthritis, increased CRP and ANA, response to steroids

132

Multiple deep ulcerations, acute gangrene in the upper third of both thighs with symmetric horizontal demarcation

Answer: diagnosis or condition

87

Index of Figures (Fig.) and CS with Syndromes (for Self-assessment) (continued) Fig.

CS

Syndromes or complexity of problems of the CS

48

Acute severe pain in the legs, dramatic weight loss, abdominal pain, intestinal infarction, and positive cANCA, male, 30 years

49

Exudative pleuritis, adenopathy and morphological diagnosis of lupus in the skin biopsy, female, 40 years

50

MCP 2-3 and other form of arthritis, MTX therapy, ferritin increase, male, 56 years

51

Acute hemolytic anemia and pneumonia, at first associated with Chlamydia infection, female, 25 years

52

Minimal activity of RA and excessively high CRP and ESR, male, 68 years

53

Pain and swelling of the finger joints and high titer RF, ANA and ENA, long-standing diagnosis of RA has been revised, female, 45 years

54

Raynaud phenomenon, massive increase of CK and TSH in Scl-70-positive patient, female, 30 years (several episodes in a 5-year observation period)

55

Acute recurrent attacks of pain in first toe in 10-year-old girl, polyarthritis with deformities and elevated creatinine (20 years later) (Kurmanalieva et al. 1986)

56

Sicca syndrome, parotid enlargement, acute increase in serum calcium and epistaxis (3 emergency situations during 12 years of observation, female, 65 years)

57

Known as PsA with minimal activity, polyarthralgias, long-term incapacity, discharge from cure therapy because of acute relapse (?), engineer, 46 years

58

Arthritis, dramatic weight loss, severe swallowing difficulties, ANA with anti-Cenp-antibody differentiation, female, 68 years

59

31-year-old female patient with systemic symptoms, fever and discrete lymphadenopathy (NHL histology). After 14 years of general symptoms, “pain all over”, fatigue, depression, incapacitated

60

Fever of unknown etiology, polyarthritis, positive Yersinia serology, lack of RF and anti-CCP-antibody, male, 40 years

Answer: diagnosis or condition

(continued)

88 (continued) Fig.

3  Index of Figures (Fig.) and CS with Syndromes (for Self-assessment)

CS

Syndromes or complexity of problems of the CS

61

Minimal activity of RA, diffuse pain, stable Fentanil requirement over the last 5 years, female, 80 years

62

Fever, polyserosis, elevated CRP, GGT, LDH, and anti-dsDNA antibodies, male, 70 years

63

Cervical spine syndrome and isolated C1-C2 arthritis initially of unknown etiology, female, 53 years

64

Acute myelitis with paraplegia, mouth ulcers, hemolytic anemia with thrombocytopenia, and positive ANCA, female, 47 years

65

Pain and swelling in the ankles of a physically active woman, 62 years, with known psoriasis vulgaris

66

Fever of unknown etiology, lymphadenopathy, and coughing in a patient aged 15 at the time (6 episodes during the past 12 years)

67

Emergency hospital admission with increased serum calcium, RA patient, female, 42 years

68

RA patient with known, long-term MTX therapy and leukopenia, response to CellCept®, female, 62 years The diagnoses of these diseases are presented as examples in this book, Chap. 1.2 (CS 69–72); CS 73 in RSS, Chap. 5

69

Back and joint pain which cannot be clearly assigned - one of the most common problems of everyday rheumatology, male engineer, 63 years

129c

70

Resistant course of RA, full employment during five-year therapy with biologics, or procedures for therapy-resistant RA, electrician, 50 years

128c (A)

71

Rheumatic fever (Chorea minor, anamnestic) and new onset of arthralgias with swelling and massive proteinuria, 16-year-old male

72

Polyneuropathy, bronchial asthma, attacks of dizziness and eosinophilia, 41-year-old male

73

Wegener’s granulomatosis, cANCA positive. Sinusitis, nasal bleeding, arthritis. Colon carcinoma (7 months later)

Answer: diagnosis or condition

Appendix

Index of the Solutions to the Syndromes and Diagnostics (for Rapid Diagnosis) Fig.

Syndromes

1

Figurative image of rheumatology

2 (B)

Ulcers and Livedo reticularis

PAN cutanea benigna

3 (C)

Exudative arthritis, rheumatoid nodules, and Heberden’s nodes

Rheumatoid arthritis (RA) and osteoarthritis (OA)

4 (C)

Heberden’s and Bouchard’s nodes

OA

5 (C)

1

6 (B)

Fibrotic-proliferative arthritis with deformities, contractures, status post-arthrodesis of the right wrist Panniculitis

7 (B)

Puffy hands

2

8 (C)

Erosive changes in the PIP and DIP joints (without involvement of MCP joints)

9a (C)

Erosive changes in the PIP, MCP, wrist joints (pre-op)

9b (C)

Post-op: PIP 3,4, and carpal joints were stabilized or stiffened, MCP 1–4 were supplied with artificial joints

10 (C)

Generalized deep ulcers and cachexia

9ab (C)

CS

Diagnosis or differentiated diagnosis

RA, advanced stage (III-IV) Reactive arthritis MCTD OA, erosive

1

RA, stage III-IV

PAN

11 (C) 12 (B)

Aortoiliac disease/Leriche syndrome (stenosis of Aorta abdominalis)

13 (C)

Monoartritis with redness, broad swelling of the MCP 2 right

3

Primary APS (Sneddon’s syndrome) Acute gout arthritis (continued)

E. Benenson, Rheumatology, Clinical Scenarios, DOI: 10.1007/978-0-85729-240-7, © Springer-Verlag London Limited 2011

89

90

Appendix

(continued)

Fig.

Syndromes

CS

Diagnosis or differentiated diagnosis

14 (B)

Digital necrosis

4

Arteriosclerosis obliterans Post-trauma

15a (C)

Dactylitis (before therapy)

5

PsA

15b (A)

Normal finding (after treatment)

16 (A)

Panniculitis

17 (B)

CNS multi-infarct syndrome

18 (C)

Contractures, calcinosis

SSc

19 (A)

Flexion contracture (claw hand)

Neuropathic arthropathy

20a (A)

Livedo racemosa (before therapy)

20b (B)

Normal finding (after treatment)

21 (B)

MCP 5 right arthritis

22 (B)

Cysts in the right MCP 5

23 (B)

MTP 2 right arthritis

24 (B)

Erosive changes in the right MCP 5

25 (B)

Arthritis of the knee left

26 (C)

Chondromalacia

27 (A)

Condition after Kineret® injection SC 6

Primary APS (Sneddon’s syndrome)

7

Suspected Lyme disease in the form of lymphadenitis cutis benigna

8

HLA-B27 positive oligoarthritis DD. PsA sine psoriasis vulgaris

9

OA with synovitis and chondromalacia

Lupus profundus

34

SLE

28 (C)

PIP 3 bursitis and MCP 2-3 arthritis

10

RA

29 (C)

Erythematous swelling on the auricular part of the ears with sparing of the earlobe (symmetrical in this case, associated with polyarthritis)

30 (A)

Livedo racemosa

31 (A)

Deep ulcerations

32 (A)

Scars as evidence of vasculitis

33 (B)

Local erythema with nodes in subcutis

34 (B)

Osteolysis with multiple round non-sclerotic bone defects (“without reaction”)

35 (C)

RA with rheumatoid nodules

36a (B)

Several round foci in lungs

36b (B)

Rheumatoid nodules in bone

37 (B)

Osteitis cystoides multiplex 3 years later

Auricular chondritis most likely in a setting of the relapsing polychondritis 11

PAN, DD non-differentiated vasculitis, ANCA-negative, Livedoid vasculopathy

12

MPA, ANCA-positive Osteolysis of unknown etiology (“vanishing bone disease”)

13

RA, seropositive, rheumatoid nodules with localization in subcutis, lungs, and bone

91

Index of the Solutions to the Syndromes and Diagnostics (for Rapid Diagnosis) (continued)

Fig.

Syndromes

CS

Diagnosis or differentiated diagnosis

38 (B)

Disseminated circular foci, one cavity

39 (B)

Disseminated circular foci, one cavity

40 (C)

Polyarthritis (MCP, PIP), symmetric

41 (B)

Dactylitis MTP 5 right

42 (C)

Arthritis, bursitis, “telescoping finger”

RA (advanced stage, IV)

43 (C)

Claw toe, contracture, mutilation

RA (advanced stage, IV)

44 (A)

Sacroiliac joints involvement (subchondral sclerosis)

45 (A)

Sacroiliitis left with erosions

46 (A)

Sacroiliitis (bone edema more on the right)

47 (B)

RA (early form) 14

RA, seropositive (early form) DD tumor (suspected diagnosis before surgery)

15

AS

Acute acral gangrene

16

SSc, initial manifestation, DD Buerger’s disease

48a (A)

Spondylodiscitis (before therapy)

17

AS

48b (A)

Spondylodiscitis (after treatment)

49a (C)

Polyarthritis (MCP, PIP joints)

RA

49b (B)

Increased uptake in the early stages as an expression of arthritis with exudates

In the same patient

50 (A)

CNS involvement (multiple infiltrates)

51 (C)

Massive cysts and carpal usures

18

Juvenile Sjögren syndrome RA, stage IV

62 (C) 52 (B)

Raynaud’s phenomenon

53 (B)

Reticular pattern of lung involvement right, ground glass opacities on the left

54 (A)

Osteolysis with pathological fracture

Stress fracture, Suspicion of the Bone tumor (primary)

55 (A)

Ulcera cruris with rheumatoid noduli decay, maculopapular rash

RA with secondary vasculitis

56a (B)

Palpable purpura with necrotizing venulitis

56b (B)

19

20

SSc with fibrotic alveolitis

Cryoglobulinemia with vas­culitis in chronic hepatitis C

57 (B)

(Epi)Scleritis

AS

58 (B)

MCP 2 arthritis

RA, stage III;

59 (B)

Destructive, erosive MCP 2, 4 arthritis

DD hemochromatosis (continued)

92

Appendix

(continued)

Fig.

Syndromes

60 (C)

Fresh syndesmophyte left (C1, C2 involvement)

61 (C)

Stenosis of right brachiocephalic artery and left carotid artery

62 (C)

Claw hand (buttonhole deformity of fingers 2–5 left and contractures of finger 5 right)

RA, stage IV

63 (A)

Tendinitis of 3rd finger

RA

64 (B)

Concentrated in the early phase of bone scan, “hot spots” 3rd finger right

RA, DD PsA

65a (B)

Dactylitis 3–5 left

Acne-induced arthropathy

65b (B)

Correlate with bone scan (the same patient)

66 (B)

Puffy hands (before therapy)

67 (B)

Normal finding (after cortisone therapy)

68 (B)

Inflammatory arthritis PIP 2-3

69 (B)

Tietze’s syndrome left

70 (B)

Jaccoud arthropathy

71 (B)

Panniculitis profunda, vasculitis

72 (B)

Deformity of the hands, non-erosive

73 (B)

Normal finding (after cortisone therapy)

74 (C)

Thoracic aorta involvement in PET

75 (B)

Multiple nodular pulmonary infiltrations with caverns, bronchiectasis, and fibrosis

76 (B)

Aphthous ulcer (lower lip)

77a (C)

MRI: Irregularities of the outer wall of Aorta and A. iliaca bilaterally PET: Ribbon–like accumulation Abdominal aorta

51 (C)

77b (C)

CS

Diagnosis or differentiated diagnosis AS

21

TA

DD SAPHO syndrome 22

Unclear diagnosis

23

PsA in HIV patient (sine Psoriasis)

24

MCTD with arthropathy and secondary vasculitis

25

TA thoracic aorta WG, cANCA positive

26

MB TA of the abdominal aorta

78 (A)

Hemorrhagic purpura and petechiae

27

SLE with thrombocytopenia

79 (A)

Honeycomb lung: massive, multiple cystic changes, upper lobe with confluent round infiltrates, interstitial shadowing, left pleural effusion, massive hilar lymphadenopathy, bilateral

Histiocytosis X

80 (C)

Proliferate arthritis with contractures, symmetric

RA, advanced stage (III)

93

Index of the Solutions to the Syndromes and Diagnostics (for Rapid Diagnosis) (continued)

Fig.

Syndromes

CS

Diagnosis or differentiated diagnosis

81 (A)

Arthritis of each PIP and DIP joint (no involvement of MCP joints)

28

Heberden’s and Bouchard’s OA with synovitis (PIP 4 left, PIP 3 right)

82 (B)

Alopecia areata

29

SLE

83 (A)

A granulomatous inflammation with large nodes, Lupus pernio

Sarcoidosis, DD dye granuloma

84a (C)

Psoriasis hyperkeratotica

PsA

84b (C)

Psoriasis vulgaris

Psoriasis vulgaris

85 (B)

A solid solitary nodule in S6 left, a mediastinal and hilar lymphoma, finely streaked reticular pattern of lung parenchyma

30

Small cell lung carcinoma MCTD with pulmonary fibrosis, DD paraneoplasia

86 (B)

Circular soft tissue structure in the left maxillary sinus (after CYC therapy)

31

WG with ENT involvement, cANCA-positive

87 (B)

Normal finding (after HAP therapy)

88 (B)

Drumstick fingers and hour glass nails

89 (B)

MCP 2-3 arthritis, DIP nodes

32

Anti-CCP-positive RA, CREST syndrome, anti-Cenpantibody positive, and Heberden’s OA

90 (B)

Red maculopapular and nodular skin lesions/erythema multiforme, granulomatous changes, bihilar lymphadenopathy Interstitial fine nodular pulmonary fibrosis

33

Sarcoidosis

92 (A)

Morphological signs of lupus-specific activity, moderate changes in chronic course (after CYC therapy)

34

93 (B)

No lupus-specific changes, significant regression of activity and increase in chronic changes of LN (after HAP therapy)

SLE with LN, refractory to CYC therapy, clinical and morphological remission after HAP treatment. Maintenance therapy with azathioprine (5-year follow-up) see Fig. 27 (the same patient)

94 (B)

Periorbital edema, “lilac ring”

PM/DM

95 (A)

Dupuytren contracture

Idiopathic contracture

96 (A)

Pseudotumor in the left orbit, granulomatous inflammation

WG (Patient with long-standing RA)

97 (A)

Joint space narrowing, femoral and acetabular osteophytes, asymmetric

91 (B)

PsA sine Psoriasis in HIV patient

35

RA, minimal activity, with OA of the hip right (continued)

94

Appendix

(continued)

Fig.

Syndromes

CS

Diagnosis or differentiated diagnosis

98 (A)

Thickening in the field of fascia plantaris (prior to therapy)

36

99 (B)

Normal findings (after laser therapy)

Plantar fasciitis with fresh Yersinia infection and mechanical overload

100 (A)

Palmar erythema

RA with vasculitis

101a (B)

Leg ulcers (before therapy)

101b (B)

Scarring as a result of vasculitis (after rituximab therapy)

RA with secondary vasculitis (medium vessels)

102 (A)

Plantar fasciitis, tendinitis m. flexor digitorum brevis, osteitis in the heel area (before treatment)

103 (B)

Normal findings (after soft laser therapy)

Status post laser therapy

104 (C)

Proliferative and fibrotic polyarthritis with multiple nodules and contractures, mutilations, arthrodesis of both wrists

RA, stage IV

105 (A)

Nephrocalcinosis

38

SLE with LN and nephrocalcinosis

106 (A)

Bursitis subdeltoidea and subcoracoidea, tendinitis and peritendinitis of the supraspinatus tendon, exudates in the joint (before therapy)

39

Shoulder pain syndrome, mechanically induced

107 (B)

Normal findings (after soft laser therapy)

Status post laser therapy

108 (A)

Osteophytes, fresh, not yet calcified in the heel area

Fibrositis or bone spur, radiographic diagnosis of enthesiopathy

109 (B)

Erythema nodosum

110 (A)

Polymorphic lesions: pustules, hemorrhagic (extensively on the heels), 111ab (A) epidermal necrolysis, pustules, psoriasis

37

ReA, induced by Yersinia

40

Yersinia infection

41

Drug (TNF-blockers)-induced pustular psoriasis DD pustular Keratoderma blennorrhagicum (Fig. 129b)

112 (B)

Intrapulmonary infiltrates and caverns

WG, intrapulmonary granulomas with destructions

113 (B)

Peripheral gangrene (Dig. 2–4)

42

Drug (psychotropic) – induced hypersensitivity vasculitis

114 (A)

Postoperative condition (Tophi-ablation in the field of first right toe)

43

Chronic gout arthritis, tophi in region of first toe, post-op condition

115 (B)

Puffy hands, exudative arthritis of the right wrist

Acute septic arthritis

116 (C)

Osteophytosis marginal (spondylosis), subchondral sclerosis (osteochondrosis), and disc space narrowing (chondrosis)

Degenerative spondylosis or osteoarthritis of the spine (Spondylitis deformans)

95

Index of the Solutions to the Syndromes and Diagnostics (for Rapid Diagnosis) (continued)

Fig.

Syndromes

CS

117 (C)

Syndesmophyte

AS

118 (C)

Hyperostosis (florid marginal bony proliferation) of the spine (osteophytosis)

Diffuse Idiopathic Skeletal Hyperostosis/DISH/

119 (B)

Total destruction of the hip joints, symmetrical (concentric space narrowing, deformation of the femoral head) subchondral sclerosis in the area of symphysis (before surgery)

AS with destructive arthritis of both hips, symphysitis

120 (B)

Condition after endoprosthetic replacement. Sclerosis in symphysis region

Condition after total replacement of both hips. Symphysitis

121 (A)

A strong enhancement in the acetabular roof (after contrast application), clearly defined bone marrow edema in the entire left acetabulum

44

Osteonecrosis in the left acetabulum (cortisoneinduced) and hip arthritis in ReA patient

122a (B) 122b (B)

Extensive soft tissue linear mass, Inhomogeneous contrast enhancement around the distal ulna

45

Massive rheumatoid nodules mass in RA patient

122c (B)

Status post surgical arthrodesis, instability of the wrist at the joint and significant destruction of the carpal bones

DD sarcomas (suspected diagnosis before surgery)

123 (C)

Marginal osteophyte, subchondral sclerosis, minimal in sacroiliac joints, scoliosis, and disc space narrowing

Degenerative spine disease (spondylosis, osteochondrosis, OA in sacroiliac joints), scoliosis

124 (C)

Syndesmophytes in the lumbar spine area, ankylosis of both sacroiliac joints

AS, sacroiliitis, stage 4

125 (B)

Status post osteosynthesis of a thoracic vertebra fracture with introduced osteosynthetic material (cage and pedicle screw)

126 (A)

T3 spinal stenosis in the collapsed vertebral body and fractures at the same level

2007: Vertebral compression fracture with acute paraplegia following emergency surgery

127a (B)

Sintering fractures of osteoporotic vertebral body T3 (before surgery)

Spondylodesis T3/T4, open repositioning of the spine with osteosynthesis

127b (B)

Post-operative spondylodesis T2/T4 with osteosynthesis

128a (C)

PIP 3 arthritis (no MCP involvement)

46

Diagnosis or differentiated diagnosis

1995: Cortisone-induced osteoporosis: Fracture of thoracic vertebra following osteosynthesis

Bouchard’s (PIP 3) OA with synovitis (continued)

96

Appendix

(continued)

Fig.

Syndromes

128b (C)

Joint space narrowing of the PIP, DIP joints (same patient)

128c (B)

PIP 3 swelling

129a (C)

Arthritis of MCP 2-3 (both sides), left wrist

RA, early

129b (B)

Pustular Keratoderma blennorrhagicum

129c (C)

Proliferative and fibrotic arthritis, with rheumatoid nodules, symmetrical

70

Psoriasis, ReA, SAPHO, acne-associated syndrome “classic” RA

130a (A)

Flexion contractures in the hands

47

OA

130b (C)

Bone tophi: multiple irregular, circular hole defects (MTP 1, 5; DIP 1) with subluxation, no sclerotic margin

130c (C)

“Madonna fingers” (early stage): taut skin, white-reddish discoloration, incipient flexion contractures

54

SSc, sclerodactyly, Raynaud’s syndrome

Acute severe pain in the legs, dramatic weight loss, abdominal pain, intestinal infarction, and positive cANCA, male, 30 years

48

PAN, cANCA positive

Exudative pleuritis, adenopathy and morphological diagnosis of lupus in the skin biopsy, female, 40 years

49

Primary Sjogren’s syndrome

MCP 2-3 and other arthritis, MTX therapy, ferritin increase, male, 56 years

50

Hemochromatosis

130c

CS

Diagnosis or differentiated diagnosis Heberden’s and Bouchard’s OA

71

Periarticular (not synovialitic) swelling in SLE patient

Chronic gout arthritis

Acute hemolytic anemia and pneumonia, at 51 first associated with Chlamydia infection, female, 25 years

SLE

Minimal activity of RA and excessively high CRP and ESR, male, 68 years

52

PMR (emerging) and RA (known)

Pain and swelling of the finger joints and high titer RF, ANA and ENA, long-standing diagnosis of RA has been revised, female, 45 years

53

Primary Sjogren’s syndrome

Raynaud phenomenon, massive increase of CK and TSH in Scl70-positive patient, female, 30 years (several episodes in a 5-year observation period)

54

SSc, sclerodactyly, Raynaud’s syndrome, lung fibrosis, myositis, hypothyroidism

97

Index of the Solutions to the Syndromes and Diagnostics (for Rapid Diagnosis) (continued)

Fig.

Syndromes

CS

Diagnosis or differentiated diagnosis

Acute recurrent attacks of pain in first toe in 10-year-old girl, polyarthritis with deformities and elevated creatinine (20 years later)

55

Chronic gout

56 Sicca syndrome, parotid enlargement, acute increase in serum calcium and epistaxis (3 emergency situations during 12 years of observation, female, 65 years)

Primary Sjogren’s syndrome, MALT lymphoma, paraneoplasia: vasculitis, hypercalcemic crisis

Known as PsA with minimal activity, polyarthralgias, long-term incapacity, discharge from cure therapy because of acute relapse (?), engineer, 46 years

57

Fibromyalgia (secondary), PsA, minimal activity

Arthritis, dramatic weight loss, severe swallowing difficulties, ANA with anti-Cenp-antibody differentiation, female, 68 years

58

CREST syndrome

31-year-old female patient with systemic symptoms, fever and discrete lymphadenopathy (NHL histology). After 14 years of general symptoms, “pain all over”, fatigue, depression, incapacitated

59

B-NHL (14 years ago), currently fibromyalgia

Fever of unknown etiology, polyarthritis, positive Yersinia serology, lack of RF and anti-CCP-antibody, male, 40 years

60

ReA, Yersinia-induced, RA, seronegative

Minimal activity of RA, diffuse pain, stable Fentanil requirement over the last 5 years, female, 80 years

61

Somatogenic pain syndrome (secondary fibromyalgia) RA in remission

62 Fever, polyserosis, elevated CRP, GGT, LDH, and anti-dsDNA antibodies, male, 70 years

Adult onset Still’s disease

Cervical spine syndrome and isolated C1-C2 arthritis initially of unknown etiology, female, 53 years

63

AS, sacroiliitis, C1-C2 arthritis with osteitis

Acute myelitis with paraplegia, mouth ulcers, hemolytic anemia with thrombocytopenia, and positive ANCA, female, 47 years

64

SLE, CNS involvement, acute myelitis, Moschkowitz syndrome

Pain and swelling in the ankles of a physically active woman, 62 years, with known psoriasis vulgaris

65

PsA, oligoarthritis, tendinitis

(continued)

98

Appendix

(continued)

Fig.

Syndromes

CS

Diagnosis or differentiated diagnosis

Fever of unknown etiology, lymphadenopathy, and coughing in a patient aged 15 at the time

66

Juvenile idiopathic arthritis (Still’s disease)

Emergency hospital admission with increased serum calcium, RA patient, female, 42 years

67

RA, hypercalcemic crisis (primary hyperparathyroidism)

RA patient with known, long-term MTX therapy and leukopenia, response to CellCept®, female, 62 years

68

Felty’s syndrome

69

SpA or ReA, HLA-B27­positive, Yersinia-induced

The diagnoses of these diseases are presented as examples in this book, Chap. 1.2 (CS 69–72); CS 73 in RSS, Chap. 5 Back and joint pain which cannot be clearly assigned - one of the most common problems of everyday rheumatology, male engineer, 63 years 131 (B)

Fever, not persistent maculopapular rash and arthritis, increased CRP and ANA, response to steroids

Adult onset Still’s disease See RSS, Chap. 8.1

132 (B)

Multiple deep ulcerations, acute gangrene in the upper third of both thighs with symmetric horizontal demarcation

Aortoiliac disease, Systemic vasculitis, monoclonal gamma-pathy, not pronounced cryoglobulinemia (Dzau, Creaber, 1991) See RSS, Chap. 9.2.5

129c

Resistant course of RA, full employment during five-year therapy with biologics, or procedures for therapy-resistant RA, electrician, 50 years

70

RA, therapy-resistant course

128c

Rheumatic fever (Chorea minor, anamnestic) and new onset of arthralgias with swelling and massive proteinuria, 16-year-old male

71

Rheumatic fever (history), currently SLE, lupus nephritis, anemia

Polyneuropathy, bronchial asthma, attacks of dizziness and eosinophilia, 41-year-old male

72

Churg-Strauss syndrome

Wegener’s granulomatosis, cANCA positive. Sinusitis, nasal bleeding, arthritis. Colon carcinoma (7 months later)

73

WG as a paraneoplasia of colon carcinoma

Index of the Solutions to the Syndromes and Diagnostics (for Rapid Diagnosis)

99

References Benenson E, Fries JW, Heilig B et al. High-dose azathioprine pulse therapy as a new treatment option in patients with active Wegener’s granulomatosis and lupus nephritis refractory or intolerant to cyclophosphamide. Clin Rheumatol. 2005;24:251–257. Benenson E, Blank H, Pelzer R et al. Magnetic resonance imaging (MRI)-confirmed soft tissue disorders as “model” for anti-inflammatory effect of LLLT (785 mm). Proceedings of the 6th International Congress of the World Association of Laser Therapy. Limassol (Cyprus), October 25–28, 2006. Medimond, 63–67. Dzau VJ, Creaber MA. Diseases of the aorta. In: Harrison’s Principles of Internal Medicine. 12th Edition, McGraw-Hill, 1991, 1018. Jennette JC, Falk RJ, Andrassy K et  al. Nomenclature of systemic vasculitis. Arthritis Rheum. 1994;37:187–192. Kurmanalieva AK, Benenson E, Mambetalieva LB. Juvenile gout in a woman. Revmatologiia (Mosk). 1986;3:67–68 [Russian]. Wollina U, Hansel G, Koch A et  al. Tumor necrosis factor-alpha inhibitor-induced psoriasis or psoriasiform exanthemata: first 120 cases from the literature including a series of six new patients. Am J Clin Dermatol. 2008;9:1–14.

Abbreviations

Ab antibodies ACE angiotensin-converting enzyme ACLA anticardiolipin (antiphospholipid) antibody ANA antinuclear antibody APS antiphospholipid syndrome ASA acetylene salicil acid AS ankylosing spondylitis BASDAI Bath Ankylosing Spondylitis Indices of Disease Activity cANCA cytoplasmic anti-neutrophil cytoplasmic antibody Chap. chapter C3, C4 components of the complement system CCP cyclic citrullinated peptide CenpB centromere proteins (designation of specific ENA antigens) CK creatine kinase CK-MB isoenzyme of CK CMV cytomegalovirus CNS central nervous system COLD chronic obstructive lung disease CREST calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, teleangiectasia CRP C-reactive protein Cry-V cryoglobuline-associated vasculitis CT computed tomography CTD connective tissue disease CS clinical situation CYC cyclophosphamide DD differential diagnosis DIP distal interphalangeal DLCO diffusing capacity for carbon monoxide dsDNA double-stranded DNA EMG electromyography ELISA enzyme-linked immunosorbent assay ENA extractable nuclear antigen ENT ear, nose and throat E. Benenson, Rheumatology, Clinical Scenarios, DOI: 10.1007/978-0-85729-240-7, © Springer-Verlag London Limited 2011

101

102

ER ERCP ESR FEV1 Fig. GGT GN GOT GP GPT HAP HBV HCV HIV HLA-B27 IFL Ig IV IL LE LDH LN MB MCP MMF MPA MRI MS MTP MTX NHL OA PAN p-ANCA PCR PET PIP PM/DM PMR PO PsA PTT RA ReA RF

Abbreviations

emergency room endoscopic retrograde cholangiopancreatography erythrocyte sedimentation rate forced vital capacity in 1 sec figure gamma glutamyl transferase glomerulonephritis glutamic oxaloacetic transaminase (in serum) general practitioner glutamic pyruvic transaminase (in serum) high-dose azathioprine pulse hepatitis B virus hepatitis C virus human immunodeficiency virus human leukocyte antigen of the major histocompatibility complex immunofluorescence immunoglobulin (AMGE) intra-venous interleukin lupus erythematosus lactate dehydrogenase lupus nephritis Morbus Behçet metacarpophalangeal mycophenolate mofetil microscopic polyangiitis magnetic resonance imaging multiple sclerosis metatarsophalangeal methotrexate non-Hodgkin’s lymphoma osteoarthritis polyarteritis nodosa perinuclear anti-neutrophil cytoplasmic antibody polymerase chain reaction positron emission tomography proximal interphalangial polymyositis/dermatomyositis polymyalgia rheumatica per os psoriatic arthritis partial thromboplastin time rheumatoid arthritis reactive arthritis rheumatoid factor

103

Abbreviations

RNP-U1 RSO RSS SAPHO SC Scl-70 SLE Sm SpA SSc SS-A (Ro) SS-B (La) TB T3 T4 TNF TPO TSH VAS WG

ribonucleoprotein (designation of specific ENA antigens) radiosynoviorthesis Rheumatology: Symptoms and Syndromes, E. Benenson, Springer 2011 synovitis, acne, pustulosis, hyperostosis and osteitis subcutaneos designation of specific ENA antigens (Topoisomerase-I) systemic lupus erythematosus Smith antigen (designation of specific ENA antigens) spondyloarthropathy systemic sclerosis designation of specific ENA antigens designation of specific ENA antigens tuberculosis triiodothyronine level free thyroxine level tumor necrosis factor thyroid peroxidase antibody thyroid-stimulating hormone visual analog scale Wegener’s granulomatosis

Pictures With Major Syndromes of Rheumatology

This collection of figures (Figs.) is designed:

• As a self-test for flash diagnosis (syndrome or disease?) • As a clear index of rheumatologic syndromes • As a study program involving the most important teaching points. The (Figs.) are interpreted in the individual chapters under diagnostic and therapeutic aspects: In RSS the syndromes are described and ascribed diagnoses. The integrated diagnostic program and the basic questions 1 and 2 (this book, Chap. 1.1.1) should help when considering the (Figs.) Chapter 1.1.2 presents the clinical situations (CS) belonging to the (Figs.) Chapter 2 provides explanations and comments on the (Figs.) Chapter 3 gives you the opportunity to make your preliminary diagnosis (as a selfcheck). The Appendix lists the diagnoses belong to all the (Figs.) and CS.

E. Benenson, Rheumatology, Clinical Scenarios, DOI: 10.1007/978-0-85729-240-7, © Springer-Verlag London Limited 2011

105

106

Pictures With Major Syndromes of Rheumatology

1

3

2

4

107

Pictures With Major Syndromes of Rheumatology

5 CS 1

7 CS 2

10

11

6 CS 1

8

9a CS 1

12 CS 3

13

9b CS 1

108

Pictures With Major Syndromes of Rheumatology

14 CS 4

15a CS 5

18

16

15b CS 5 (after therapy)

17 CS 6

20a CS 7

19

20b CS 7 (after therapy)

109

Pictures With Major Syndromes of Rheumatology

21 CS 8

22 CS 8

24 CS 8

23 CS 8

110

Pictures With Major Syndromes of Rheumatology

25 CS 9

27 CS 34

30 CS 11

33 CS 12

26 CS 9

28 CS 10

29

31 CS 11

32 CS 11

34

111

Pictures With Major Syndromes of Rheumatology

36a CS 13 (2004)

35 CS 13

36b CS 13

(2004) 37 CS 13

38 CS 13

39 CS 13

(2007)

(2007)

(2007)

40

42

41 CS 14

43

112

Pictures With Major Syndromes of Rheumatology

44 CS 15

46 CS 15

45 CS 15

47 CS 16

48a CS 17

49a

48b CS 17 (after therapy)

49b

50 CS 18

51

113

Pictures With Major Syndromes of Rheumatology

52 CS 19

54

53 CS 19

56a CS 20

57

55

56b CS 20

60

58

59

114

Pictures With Major Syndromes of Rheumatology

61 CS 21

62

65a 63

65b

64

66 CS 22

67 CS 22 (after therapy)

68 CS 23

69 CS 23

115

Pictures With Major Syndromes of Rheumatology

70 CS 24

71 CS 24

72 CS 24

73 CS 24 (after therapy)

74 CS 25

75

76 CS 26

77a

77b

116

Pictures With Major Syndromes of Rheumatology

78 CS 27

79

80

82 CS 29

83

81 CS 28

84a

84b

85 CS 30

117

Pictures With Major Syndromes of Rheumatology

88 86 CS 31

87 CS 31 (after therapy)

89 CS 32

118

90 CS 33

92 CS 34

Pictures With Major Syndromes of Rheumatology

91 CS 33

93 CS 34 (after therapy)

119

Pictures With Major Syndromes of Rheumatology

94

96

95 97 CS 35

120

Pictures With Major Syndromes of Rheumatology

98 CS 36

99 CS 36 (after therapy)

100

101a

101b (after therapy)

121

Pictures With Major Syndromes of Rheumatology

102 CS 37

103 CS 37 (after therapy)

105 CS 38

104

106 CS 39

108

107 CS 39 (after therapy)

109-2 CS 40

109-1 CS 40

122

Pictures With Major Syndromes of Rheumatology

110 CS 41

112

111a CS 41

113 CS 42

111b CS 41

114 CS 43

116

115 CS 43

117

118

123

Pictures With Major Syndromes of Rheumatology

119

121 CS 44

120 (after op) 122a CS 45

123

124

125 CS 46

122b CS 45

126 CS 46 (before op)

127a CS 46 (before op)

127b CS 46

122c CS 45

124

128a

129a

130a

131a

Pictures With Major Syndromes of Rheumatology

128b

128c

129b

129c

130b

131b

130c

131c

Figs. 131abc  Fever with chills, skin lesions, arthritis, increased CRP and ANA, response to steroids, female, 25 years 2 weeks previously acute diarrhea (up to 15 times per day) -2 days Fever with chills up to 39.5° C Skin changes (see Fig.) Oligoarthritis, florid (PIP 2-3, left knee) CRP (20.5 mg/dl, factor x 21), LDH 488 U/L (normal <250) ANA 1:1.600 fine granular, immunology negative (rheumatoid factor, anti-CCP-Ab, HLA- B27) Negative serology (Parvovirus, B. burgdorferi, Yersinia, and Chlamydia-Ab) Response to glucocorticoid (prednisolone from 80 mg/d, in 6 weeks 10 mg/d) and leflunomide 20 mg/d.

• • • • • • • •

125

Pictures With Major Syndromes of Rheumatology

132a

132b

133c

133c

133c

Figs. 132  (a) Multiple deep ulcerations, monoclonal gammopathy, cryoglobulins not pronounced (2 years of disease), female, 38 years. (b) Sudden development (3 days after the last examination). (c) Angiography abdomen, pelvis and legs arteries (present). Amputation of both legs at the border of the demarcation line Histological: Endothelial proliferations and thrombosis in the vessels Question: How to explain the strict symmetry of the vessel infestation? Reply : Dsau VJ,Creaber MA. Diseases of the aorta. In Harrison‘s principles of internal medicine, 1991, p. 1018. Benenson E. Rheumatology: Symptoms and Syndromes. Springer-London, 2011, Chap. 9.2.5

Index

A Acral gangrene arteriosclerosis obliterans, CS 4, Fig. 14 drug-induced hypersensivity vasculitis, CS 42; Fig. 113 SSc (DD Buerger’s disease), CS 16; Fig. 47 Acute gangrene in the upper third of thighs, deep ulcers, Figs. 132a, 132b Acute respiratory distress and cold hands, SSc, Figs. 52, 53 and myalgias, cardiac arrhythmias, MCTD, CS 24 ANA and anti-Cenp-Ab, CS 32, 58 and anti-RNP-Ab, CS 2, 24 and anti-Scl–70-Ab, CS 19, 54 and dsDNA-Ab, not confirmed by Crithidia test, CS 16, 38 and dsDNA-Ab, confirmed by Crithidia test, CS 27, 51, 71 and mastitis, as initial signs of SLE, CS 38 and no differentiation, CS 3 and SS-A, SS-B and RF, CS 18, 49, 53, 56 Anemia Coombs positive, SLE, CS 38, 51 haemolytic, CS 51 and thrombocytopenia, SLE, CS 64 Ankle swelling oligoarthritis, tendinitis, PsA, CS 65 Antiphospholipid syndrome primary (Sneddon’s), Figs. 12, 17 secondary, SLE, CS 51, 71 questionable, SLE, CS 38 Aorta enhancement on PET, Figs. 74, 77b irregularities of the wall and A. iliaca on MRI angiography Fig. 77a Aortic arch syndrome stenosis of the supraaortal vessels, TA, Fig. 61

Aortoiliac disease thrombosis in the bifurcation of the aorta/ Leriche syndrome/, Fig. 12 thrombosis in a preexisting narrowed segment of the aorta, Fig. 132 Aphthous ulcer mouth ulcers in Morbus Behçet, Fig. 76 SLE, CS 64 Arthritis acute gout, Fig. 13 atlanto-dental, AS, Fig. 60, CS 63 erosive, Figs. 9a, 51, 59, 119 exudative, Figs. 3, 13, 25, 40, 41, 49a, 68, 115, 128a, 129a fibrosing and ankylosing, Figs. 42, 43, 51, 62, 104 proliferative, Figs. 5, 35, 58, 80, 104, 129c non-erosive, Figs. 7, 72, CS 2, 53 Arthrology back and joint pain which cannot be clearly assigned, CS 69 basic questions for their clearing, 28–29 which structures are diseased? are there infections, tumors or other diseases? is inflammatory or non-inflammatory process taking place? are other systems or organs affected? Arthropathy acne-induced (DD SAPHO syndrome), Fig. 65ab enteropathic Yersinia infection CS 69, Fig. 102, CS 60 metabolic, gout, Figs. 13, 130b diabetic, DISH, Fig. 118 hemochromatosis, CS 50 neuropathic, Fig. 19 paraneoplastic hypertrophic osteoarthropathy, Fig. 88

E. Benenson, Rheumatology, clinical Scenarios, DOI: 10.1007/978-0-85729-240-7, © Springer-Verlag London Limited 2011

127

128 Ankylosing spondylitis (AS) cervical spine syndrome, CS 63 (epi) scleritis, Fig. 57 hips arthritis, destructive, Fig. 119 sacroiliitis, Figs. 44–46, 124 spondylodiscitis, Figs. 48ab syndesmophyte, fresh, Fig. 60 already formed, Figs. 117,124 Auricular chondritis, Fig. 29 B Bone ankyloses, AS, Figs. 117, 119 aseptic necrosis cortisone-induced, Fig. 121 destruction erosion CT, Figs. 23, 45 hips, total, AS, Fig. 119 MRT, Figs. 122ab MTP 5, early RA, CS 14 symphysis, AS, Fig. 120 X-ray, Figs. 8, 9a, 51, 59, 97 osteolysis due to rheumatoid nodules, Figs. 36b, 37 spondylolyses, AS, Fig. 48a stress fracture (DD bone tumor), Fig. 54 “vanishing bone disease”, Fig. 34 hypertrophic osteoarthropathy, Fig. 88 increased uptake in bone scans pattern of arthritis, Figs. 49b, 64 dactilitis, Fig. 65b no increased uptake in bone scans no arthritis in puffy hands MCTD, Fig. 7 Primary Sjogren’s syndrome, CS 53 nodes Bouchard’s nodes, Figs. 4, 8, 81, 128a Heberden’s nodes, Figs. 3, 4, 8, 81, 128b rheumatoid nodules, Fig. 36b osteoprose cortisone-induced, Figs. 125–127 tophy chronic gout arthritis, Fig. 130b Bouchard’s OA (PIP), Figs. 4, 8, 81, 128a Bronchiectasis and pulmonary infiltrations with caverns, and fibrosis, WG, Fig. 75 Bursitis RA, early, Fig. 28 advanced stage, Fig. 42 subdeltoidea and subcoracoidea shoulder pain syndrome, Figs. 106, 107

Index C Cachexia or dramatic weight loss CREST syndrome, CS 58 PAN, Figs. 10; CS 48 TA, CS 25 Calcaneopathy fibroostitis, Fig. 108 plantar fasciitis, Figs. 98, 102 tendinitis, osteitis, Fig. 102 Calcinosis CREST syndrome, CS 32 SSc, Fig. 18 Calcium elevation in serum hyperparathyroidism, CS 67 paraneoplastic, CS 56 Callosities on the skin /Lupus pernio/, Fig. 83 cANCA WG, Fig. 75; CS 48 WG and colon carcinom, RSS, 67, CS 73 and pANCA, CSS, 72 Cardiac arrhythmia and myocardial infarctions TA, CS 21, Fig. 61 MCTD, CS 24 Cervical syndrome arthritis in atlantodental joint, AS, CS 63; Fig. 60 Chlamydia infection as initial diagnosis for SLE, CS 51 Chondromalacia sport injury, Fig. 26 CK elevation CSS, 72 MPA, ANCA-positive, CS 12, Fig. 33 and TSH increase, SSc, CS 54, Fig. 130c Claudicatio arteriosa Leriche syndrome, CS; Figs. 13, 132b Claudication intermittens arteriosclerosis obliterans, CS 4 PAN (DD livedoid vasculopathy), CS 11 TA, CS 21 Clinical syndromes (several) in Figs. acute arthritis, Figs. 13, 25, 41, 115 acute panniculitis, Figs. 6, 16, 27, 71 aortitis, Figs. 74, 77ab deep ulcers of unknown etiology, Figs. 30, 31 ENT region under immunosuppression, Figs. 86, 87 honeycomb lung, Fig. 79 indefinable steroid-dependent disease, Figs. 66, 67 leg ulcers under immunosuppression, Figs. 101ab lupus nephritis under immunosuppression, Figs. 92, 93

129

Index lymphadenitis cutis benigna, guess-work, Fig. 20a maculopapular rash, Fig. 131abc massive tumor on lower arm, Figs. 122abc MTP 5 arthritis (DD tumor), early RA, Fig. 41 multiple focal erythema, Fig. 90 osteolysis of unknown etiology, Fig. 34 palpable purpura and hepatitis C, Fig. 56ab plantar fasciitis, osteitis under laser therapy, Figs. 102, 103 refractory shoulder pain, Fig. 106 rheumatoid and Heberden’s nodules, Fig. 3 rheumatoid nodules in bone, Fig. 36b rheumatoid nodules in lungs, Figs. 36a, 38, 39 septic arthritis, Fig. 115 spinal canal stenosis, Fig. 126 solutions to the Clinical Situations (CS) arthrology, 27–30 connective tissue disease (CTD), 30–32 vasculitis, 32–34 CNS involvement (See Myelitis) attacks of dizziness and unconsciousness, SLE, CS 51; CCS, CS 72 Chorea minor, SLE, CS 71 dementia, deaf-muteness and spasticity, primary APS, Fig. 17 protein increase in cerebrospinal fluid, SLE, CS 51 recurrent neurological and visual deficits (DD with MS), Sjögren’s, Fig. 50 stroke after the 5-week break in MTX, WG, Fig. 86 Contractures, fingers AO, “Fat fingers”, Fig. 130a all fingers, Figs. 5, 19, 43, 130a individual fingers, Fig. 63 Dupuytren, Fig. 95 MCTD, Figs. 70, 72 neuropathic arthropathy, Fig. 19 RA, Figs. 5, 19, 63, 80, 104, 129c “Claw hand”, Fig. 62 SSc, calcinates and sclerodactyly, Fig. 18 CREST syndrome calcinosis, CS 32 dramatic weight loss, dysphagia, CS 58 CRP, hight level (factors x 6–50) fever for 6 months, procalcitonin normal, adult M. Still, RSS, p. 110 fever with chills, SLE under CellCept®, urinary tract infection, CS 27 minimal activity of RA, PMR, CS 52 mounth ulcers, heart attacks, MB, suspicion of vasculitis, CS 26

polyneuropathy, bronchial asthma, eosinophilia, CCS, CS 72 puffy hands, unknown disease for myself, Figs. 66, 67; CS 22 return of CRP in definite WG, Colon carcinoma, CS 73, RSS, p. 67 spine pain, gibbus, spondylodiscitis, Figs. 48ab unexplained weight loss, TA, CS 25 Cyst light cystic changes, Fig. 22 lungs, histiocytosis; Fig. 79 massive with carpal users, RA, Fig. 51 Cytopenia with neutropenia, Felty’s syndrome, CS 68 D Dactylitis acne-induced arthropathy, Fig. 65ab PsA, Fig. 15a RA, Fig. 41 Deaf and dumb, and amaurosis fugax, in female, 17 years, primary APS, Fig. 17, CS 6 acute, headache, CRP elevation, Giant-cell arteriitis, RSS, p. 157 Deformity MCTD with non-erosive arthritis, Figs. 70, 72 OA, Figs. 4, 81, 130a PA, Figs. 5, 35, 40, 42, 43, 62, 80, 104, 129c and erosions Figs. 9ab, 51, 59 PsA, Figs. 15a, 68, 88 Deep ulcerations cryoglobulinemia and monoclonale gammapathy, Fig. 132a MCTD, Fig. 71 PAN, Figs. 2, 10–11 DD livedoid vasculopathy, Figs. 30–31 RA, Figs. 55, 101a Diffuse idiopathic skeletal hyperostosis (DISH), Fig. 118 Drug - induced damages cortisone aseptic necrosis in female, 25 years, Fig. 121 cerebral edema with fatal outcome, RSS, p. 148 diabetes mellitus, Figs. 90, 129c vertebral fracture with acute paraplegia, Figs. 125–127 Kineret® panniculitis, Fig. 16

130 psychotropic hypersensitive vasculitis with gangrene, Fig. 113 TNF- Blockers pustular psoriasis, Figs. 110, 111ab Dupuytren contracture, Fig. 95 Dysphagia CREST syndrome, CS 58 E Emergency acute abdomen intestinal perforation, PAN, CS 48 abdominal bleeding under phenprocoumon therapy by questionable APS, CS 38 distal gangrene drug- induced vasculitis, Fig. 113, CS 42 pacemaker implantation, unconsciousness with bradycardia, MCTD, CS 24 pseudoileus due to the lymphadenopathy, SLE, CS 29 stents insertion (5), female, 36 years, TA, Fig. 61, CS 21 suspicion of sarcoma, rheumatoid nodules, RA, Figs. 122abc lungs carcinoma, rheumatoid nodules, RA Fig. 36a MTP 5 tumor, early RA, Fig. 41 total parotidectomy, MALT lymphoma, Sjögren’s syndrome, CS 56 vertebral fracture, acute paraplegia, Figs. 126, 127ab, cortisone- induced osteoporosis Enthesiopathy/Enthesitis inflammatory fibroostisis (calcaneal spur), Fig. 108 plantar fasciitis, ReA, Fig. 98 with tendinitis, osteitis, Figs. 102, 103 mechanical, shoulder, Figs. 106, 107 symphysitis pubis, AS, Figs. 119, 120 synchondrosis (Tietze syndrome) PsA sine psoriasis, HIV, Fig. 69 (Epi) Scleritis, Fig. 57 Erosive arthritis HLA-B27 positive oligoarthritis, Fig. 24 OA, Fig. 8 RA, Figs. 9a, 51, 59 Erysipelas as initially interpretation to Lupus profundus, SLE, Fig. 27 Panniculitis profunda, MCTD, Fig. 71

Index PsA with osteitis, Fig. 15a Erythema diffuse, red patches in CTD, Figs. 27, 71 maculopapular rash, Still’s disease Figs. 131abc nodosum, Yersinia infection, Fig. 109 multiple, lymphadenopathy, sarcoidosis, Figs. 90, 91 periorbital, PM/DM, Fig. 94 and subcutaneous nodes, MPA, Fig. 33 Extra-articular systemic changes fever (about 6 months), ReA, CS 60 eyes, (epi) scleritis, AS, Fig. 57 kidneys renal insufficiency, chronic gout, CS 55 lungs fibrosis as in Fig. 53a exudative pleuritis, RSS, p. 17 rheumatoid nodules, Figs. 36a, 38, 39 musculature amyothrophy, Figs. 5, 35, 42, 80, 104 low-lying rheumatoid nodules, Figs. 122ab nerven compression syndrome, CS 45, Figs. 122ab skin and subcutaneous tissue (RA) deep ulcerations, Figs. 55, 101a palmar erythema, Fig. 100 rheumatoid nodules (See Rheumatoid nodules) enthesiopathy/enthesitis (See Enthesiopathy/ Enthesitis) Exudative pleuritis and exudative pericarditis, fever Adult onset Still’s disease, CS 62 as SLE, CS 38 initial signs in SSc, CS 19 Sjögren syndrome, CS 49 F Ferritin increase in arthritis hemochromatosis, CS 50 Fever of unknown origin arthritis, maculopapular rash, Still’s disease, Fig. 131, CS 62, 66 positive Yersinia serology, septic form of ReA, CS 60 weight loss and high CRP, TA, Fig. 74 Fibromyalgia (secondary) 14 years after B-NHL, CS 59 PsA, CS 57 RA, stable Fentanil requirement, CS 61

131

Index Fibrotic-proliferative arthritis (See Arthritis) Fingers (See Arthritis, PsA, RA) absence of subsidiary network in the hands, SSc (DD Buerger’s disease), Fig. 47, CS 16 drumstick and hour glass nails, PsA sine psoriasis, Fig. 88 joints arthritis Bouchard’s and Heberden’s nodes, OA, Figs. 3, 4, 81, 89, 128a MCTD, Jaccoud’s arthropathy, Figs. 70, 71 RA, early form Figs. 28, 40, 41, 49a, 129a and bursitis, Fig. 28 and OA, Figs. 3, 89 “telescoping”, Fig. 42 “Madonna finger”, Fig. 130c periarthritis, SLE, Fig. 128c reddened tips with palmar erythema, RA, Fig. 100 G Gout acute arthritis, Fig. 13 typical form in 10-year-old girl, CS 55 chronic arthritis with bone tophi, Fig. 130b renal failure, CS 55 H Heberden’s OA (DIP), Figs. 3, 4, 8, 81, 89 Hemolytic anemia acute and pneumonia, SLE, CS 51 thrombocytopenia, Moschkowitz syndrome, SLE, CS 64 Hemorrhagic purpura selective thrombocytopenia, SLE, Fig. 78 HLA-B27 positive oligoarthritis Figs. 21–23 erosive, Fig. 23 Honeycomb lung histiocytosis X, Fig. 79 Hypereosinophilia polyneuropathy, bronchial asthma, dizziness, CCS, CS 72 Hypersentivity vasculitis cryoglobulinemia in chronic hepatitis C, Figs. 56ab drug- induced, Fig. 113 I Integrated Diagnostic Screening Program, 1–2

J Jaccoud’s arthropathy MCTD, Figs. 70, 71 K Keratoderma blennorrhagicum pustular PsA, Fig. 129b drug- induced pustular psoriasis, Figs. 110, 111ab L Leriche’s syndrome (See Aortoiliac disease) Leucopoenia/neutropenia RA, antineutrophil Ab, Felty’s syndrome, CS 68 Livedo racemosa as initial sings of primary APS, Fig. 17, CS 6 PAN, Figs. 30–31 (DD livedoid vasculopathy) suspected Lyme disease, Fig. 20a Livedo reticularis PAN, cutanea benigna, Fig. 2 Sneddon’s syndrome, Figs. 12, CS 3 Livedoid vasculopathy (DD PAN, non-differentiated vasculitis), Figs. 30–31 Liver enzymes /high level/ and LDH Still’s disease chills, cough, lymphadenopathy, Juvenile, CS 66 fever, polyserositis, CRP elevation, Adult, CS 62 Lungs basal sclerosis/reticular fibrosis, as in Fig. 85 hilar lymphadenopathy, sarcoidosis, Fig. 91 solid nodule, mediastinal lymphoma, MCTD and lung carcinoma, Fig. 85 without hilar lymphadenopathy and diffuse milky changes, SSc, Fig. 53 caverns, infiltrates, cysts and bihilar lymphadenopathy, Fig. 79 Honeycomb lung multiple infiltrates, caverns RA (rheumatoid nodules), Figs. 36a, 38,39 WG, Fig. 112 fibrosis and bronchoectasis, WG, Fig. 75 pulmonary hypertension, PAN, CS 11 Lupus nephritis nephrotic syndrome alopecia areata, Fig. 82 periarthritis, Fig. 128c, CS 34

132 renal failure, Figs. 92, 93 (chronic), (acute), CS 38 activity and chronicity index on renal biopsy, Figs. 92, 93 without nephrotic syndrome and renal failure, Figs. 105, 128c; CS 51 Lupus pernio, Sarcoidosis (DD dye granuloma), Fig. 83 Lupus/panniculitis/ profundus MCTD, Fig. 71 SLE, Fig. 27 Lyme Borreliose, suspected lymphadenitis cutis benigna, Fig. 20a Lymphadenopathy bihilar cystic changes, infiltrates, fibrosis, histiocytosis X, Fig. 79 erythema, pulmonaly fibrosis, sarcoidosis, Figs. 90, 91 mediastinal, solitary nodule, lung carcinoma, Fig 85 hilar supraclavicular, fever, chills, and cough, Still’s disease, CS 66 supraclavicular, exudative pleuritis, Sjögren syndrome, CS 49 iliac fatigue, subfebrile temperatures, B-NHL, CS 59 as a cause for pseudoilius, SLE, CS 29 M “Madonna finger”, Fig. 130c MPA local erythema, nodes in subcutis, histology: necrotic vasculitis, Fig. 33 myalgia, myasthenia, CK elevation, testicular bleeding, CS 12 MCTD Jaccoud arthropathy, Fig. 70 non-erosive deformity of the hands, Fig. 72 panniculitis profunda, Fig. 71 pacemaker implantation, CS 24 puffy hands, Fig. 7 pulmonary fibrosis, Fig. 85 small cell lung carcinoma, Fig. 85 (DD paraneoplasia) Monoarthritis/Oligoarthritis acute gout, Fig. 13 oligoarthritis HLA-B27 positive, Figs. 21–23 RA with bursitis, early form, Fig. 28 MCP 2–3, Figs. 58, 59 ferritin increase, hemochromatosis, CS 50

Index MTP 5 as initial signs, Fig. 41 (DD tumor) OA with Bouchard’s nodes, with contractures of the fingers, Fig. 130a without other finger joints involvement, Fig. 128a PsA sine psoriasis, HIV infection, Fig. 68 SLE, periarthritis, Fig. 128c Mono-/polyneuropathy myalgia, weight loss, PAN, CS 48 bone pain, petechiae, CCS, CS 72 optic neuritis, motor and sensory disturbances (DD MS), Sjögren’s, CS 18 Mouth ulcers acute myelitis with paraplegia, Moschkowitz syndrome, SLE, CS 64 myocardial infarction without risks factors, MB, Fig. 76 Multiple focal erythema nodes in subcutis, histology: necrotic vasculitis, MPA, Fig. 33 sarcoidosis, Figs. 90, 91 Myalgia CCS, as initial signs, CS 72 fibromyalgia, CS 59 MPA, Fig. 33 PAN, as initial signs, CS 48 SSc, Fig. 130c Myelitis, acute with paraplegia Sjögren’s syndrome juvenile, CS 18 SLE, CS 64 Myositis/Myopathy amyothrophy, intercostals, Figs. 5, 35, 42, 80, 104 CCS, CS 72 MPA, CS 12 myasthenia with CK and TSH elevation, SSc, Fig. 130c, CS 54 drug-induced, long-term use of statins, RSS, p. 131 fibromyalgia, RSS, p. 130 Myocardial infarction(s) acute female, 36 years, 2 events, TA, Fig. 61, CS 21 female, 73 years with mouth ulcers, MB, Fig. 76, CS 26 Myocarditis or its sequelae pacemaker implantation, MCTD, Fig. 70–73, CS 24 N Nephritis (See Lupus nephritis) and renal insufficiency, Cry-V, HCV infection, Figs. 52ab

Index and proteinuria (PAN,livedoid ­vasculopathy), Figs. 30–31 Nephrocalcinosis, SLE, Fig. 105 O Osteitis in the arch of the atlas and dens axis, AS, CS 63 Osteitis cystoides, RA, Fig. 37 PsA, Fig. 15a rheumatoid inflammation in bone, Fig. 36b and tendinitis ReA, Fig. 102 Osteoarthritis (OA) Bouchar’d nodes (See bone node) erosive, Fig. 8 Heberden’s nodes (See bone node) hip, in RA, Fig. 97 inflammatory with synovitis Bouchar’d , Figs. 4, 81, 128a knee, Fig. 25 knee with chondromatosis, Figs. 25, 26 noninflammatory Heberden’s, Figs. 3, 81, 89 hip, Fig. 97 and RA, Figs. 3, 89, 97 spine (See, Spondyloarthrosis) thumb base, Fig. 9ab, 59 Osteolysis (See bone) Osteonecrosis cortisone-induced, ReA, Fig. 121 Osteophytosis acetabular in hip OA, Fig. 97 the heel area, Fig. 108 vertebral, Spondylitis deformans, Fig. 116 hyperostosis, DISH, Fig. 118 OA in sacroiliac jonts, Fig. 123 P Palmar erythema vasculitis, RA, Fig. 100 Palpable purpura necrotizing venulitis, Cry-V, Figs. 56ab PAN cutanea benigna, Fig. 2 deep ulcers, Figs. 2, 30–31 (DD livedoid vasculopathy) cachexia, Figs. 10–11 weight loss, and intestinal infarction, CS 48 Panniculitis drug- induced (Kineret®), Fig. 16 lupus profundus, Fig. 27

133 lupus pernio, Fig. 83 nodes in subcutis granulomatous changes, sarcoidosis, Figs. 83, 90 vasculitic changes, MPA, Fig. 33 paraneoplastic, chronic leukemia, as in Fig. 27, RSS, p. 35 profunda, MCTD, Fig. 71 reactive arthritis, Figs. 6, 109 Paraneoplasia Sjögren syndrome MALT lymphoma, vasculitis, and hypercalcemic crisis, CS 56 WG and colon carcinoma, RSS, p.67, CS 73 Parotid enlargement Sjögren syndrome, MALT lymphoma, CS 56 juvenile , CS 18, Fig. 50 Periarthropathy humeroscapularis, Figs. 106, 107 Periorbital destruction, WG, Fig. 96 edema with erythema, PM/DM, Fig. 94 Petechiae hemorrhagic purpura, SLE, Fig. 78 severe arthralgies and bone pain, CCS, CS 72 Phenprocoumon therapy (See Response to) Plantar fasciitis inflammatory origin, Figs. 98, 102 mechanical, Fig. 108 Polyarthralgias long-term incapacity, minimal activity of PsA, CS 57 myalgia, fatigue, and B-NHL (14 years ago), CS 59 Polyarthritis (See Arthritis) Polymyositis/Dermatomyositis (See Myositis) periorbital edema, Fig. 94 Polyserositis fever, and elevated CRP, CS 62 Post-operative spondylodesis sintering fracture in osteoporotic vertebral body, Fig. 127b Primary APS (See Sneddon’s syndrome) Proliferative and fibrotic arthritis (See Arthritis) Psoriasis hyperkeratotica, Fig. 84a pustular, drug (TNF- blockers)- induced, Figs. 110, 111ab sine psoriasis, HIV patients, Figs. 68, 69, 88 vulgaris, Fig. 84b Psoriasis arthritis dactylitis, erysipelas as initial diagnosis, Fig. 15a oligoarthritis, tendinitis, CS 65

134 predilection for finger joints, Fig. 64 sine psoriasis, Fig. 68 drumstick fingers, and hour glass nails, Fig. 88 oligoarthritis, HLA-B27 positive, Figs. 21–24 Tietze syndrome, Fig. 69 Puffy hands and high CRP unclear diagnosis, Fig. 66 septic arthritis, Fig. 115 and high titer ANA MCTD, Fig. 7 SSc, Fig. 130c asymmetrical Fig. 115 fibromyalgia, CS 57 symmetrical Figs. 7, 66, 130c Pulse and blood pressure differences arteriosclerosis obliterans, Fig. 14, CS. 4 TA, Figs. 61 Pustular Keratoderma blennorrhagicum drug- induced pustular psoriasis, Figs. 110, 111ab PsA, Fig. 129b R Raynaud’s phenomenon MCTD, associated with lung carcinoma, Fig. 85, CS 30 SSc, Figs. 47 (DD Buerger’s disease), 52, 130c acute respiratory distress and pleuritis, Fig. 53, CS 19 no Raynaud’s phenomenon drug-induced vasculitis, Fig. 113 Reactive arthritis attacks of fever and erythema nodosum, Fig. 109, CS 40 fever many months and polyarthritis, CS 60 panniculitis, Fig. 6 plantar fasciitis, Figs. 98, 102 and tendinitis, osteitis, Fig. 102 osteonecrosis, cortisone-induced, Fig. 121 sacroiliitis, HLA-B27 positive, CS 69 Refractory heel pain, Figs. 98, 102, 108 Refractory shoulder pain, Figs. 106, 107 Relapsing polychondritis, Fig. 29 Response to Antibiotica doxicicline in cases of suspected Lyme disease, Figs. 20ab Non response in suspicion of erysipelas in lupus profundus, Fig. 27 panniculitis profunda, MCTD, Fig. 71 PsA, Fig 15a

Index Azathioprin, maintenance therapy juvenile Sjögren syndrome, CNS involvement, Fig. 50 SLE, Figs. 92, 93 Biologics Apremilast® (with MTX) in PsA, Figs. 15ab Enbrel® (with cortisone) in spondylodiscitis, Figs. 48ab Remicade® in sarcoidosis, Fig. 90 Rituximab (mostly with MMF) cryoglobulinemia with vasculitis in chronic hepatitis C, Figs. 56ab, p. 54 SLE with thrombocytopenia, Fig. 78, p. 59 Ulcus cruris in RA, Figs. 101ab, p. 65 WG, infi ltrates, caverns, Fig. 112, p. 68 Non response (with CYC) in SLE, CS 29, 34 to four biologics, RA, Fig. 49a, p. 51 cortisone acute deafness, giant-cell arteritis, RSS, p. 157 adult onset Still’s disease (with Arava®), RSS, (without leflunamid) p. 110, CS. 62; Fig. 131abc disease unknown origin, Figs. 66, 67 Lupus pernio, Fig. 83 panniculitides, Figs. 27, 71, 73 TA, Figs. 61, 74 CYC PAN(with rituximab), CS 48 SSc, Figs. 52, 53 CYC-resistant course of SLE, Figs. 82, 92, 105 WG, Fig. 86 High Azathioprine Pulse (HAP) MCTD, Fig. 85 SLE, clinical and morphological efficacy, Figs. 92, 93 WG, sinus maxilaris involvement, Figs. 86, 87 non response in sarcoidosis, Fig. 90 Leflunamid Still’s disease, Fig. 131; CS 62; CS 66 Synchondrosis/perichondritis/ manubrio-sternalis, CS 21 non response in sarcoidosis, Fig. 90 Phenprocoumon therapy pelvic/leg vein thrombosis in SLE, Fig. 27, CS 34 Sneddon’s syndrome, Figs. 12, 17 Rheumatoid nodules bone, therapy of bone tuberculosis (over 1.5 years), Fig. 36b

Index lungs, surgery in suspected tumor, Figs. 36a, 38, 39 subcutaneous Figs. 35, 80, 104, 129c and Bouchard’ nodes, OA, Fig. 3 tumor-like structure, Figs. 122ab and compression syndrome, CS 45 ulceration Fig. 55 Rheumatoide arthritis and bursitis, Fig. 28 and cytopenia or neutropenia, CS 68 early form, Figs. 28, 40, 41 (DD tumor), 49ab, 129a and osteoarthritis Figs. 3, 89 minimal activity and high CRP, PMR, CS 52 stage III-IV, Figs. 5, 9a, 42, 43, 51, 62, 80, 104, 129c post-operative arthrodese, Figs. 5, 9b, 122c artificial joints, Fig. 9b Rheumatoid factors and anti-CCP-Ab, CS 1, 10, 14, 68 and ANA, SS-A, SS-B, CS 18, 49, 53, 56 without anti-CCP-Ab, CS 20, 53, 56, 70 Rheumatic fever as initial diagnosis of SLE, Fig. 128c, CS 71 Root compression syndrome medullar and vascular compression, osteoporose, Figs. 126, CS 46 Loge de Guyon syndrome (distal ulnar nerve), Figs. 122ab, CS 45 radicular spine/sciatica, CS 63 S Sacroiliitis AS, Figs. 44–46, 124 asymmetric, SpA, Fig. 46 no joint space in Spondylodiscitis, Figs. 48ab symmetric, AS, Figs. 117, 119, 124 and cervical spine syndrome, CS 63 Sarcoidosis erythema multiforme, Fig. 90 Lupus pernio, Fig. 83 pulmonary fibrosis, and bihilar lymphadenopathy, Fig. 91 Scars as evidence of vasculitis PAN, Fig. 32 (DD livedoid vasculopathy) RA, Fig. 101b SSc, pitting scars, Fig. 47 (DD Buerger’s disease) Scleritis, Fig. 57 Sicca syndrome (See Sjögren syndrome) and SS-A, CenpB- and anti-CCP antibodies, Fig. 89

135 Sinus masses, a granulomatous inflammation, WG, Figs. 86, 87 Sjögren Syndrome (See Sicca syndrome) ANA, SS-A, SS-B, high RF, pleuritis, CS 49 no Sicca syndrome, LE in skin biopsy, CS 49 juvenile, CNS involvement (DD with MS), Fig. 50 long-standing diagnosis of RA, CS 53 MALT lymphoma, vasculitis, hypercalcemic crisis, CS 56 Skeletal tuberculosis as initial diagnosis for bone involvement in RA, Figs. 36b, 37 Skin (See Erythema) palpable purpura, hemorrhagic type, Cry-V, Fig. 56a necrotizing ulcerating type, Cry-V, Fig. 56b petechiae and hemorrhagic purpura, SLE, Fig. 78 purpura with hemorrhage, plaques, epidermal necrosis, Psoriasis, Figs. 110, 111 SLE acute hemolytic anemia and pneumonia, as initial signs, CS 51 Lupus profundus, Fig. 27 Lupus nephritis, nephrotic syndrome acute myelitis with paraplegia, and Moschkowitz syndrome, CS 64 Alopecia areata, Fig. 82 chorea minor (anamnestic), periarthritis, Fig. 128c, CS 71 morphological sings of lupus- specific activity, Fig. 92 no lupus-specific changes after therapy, Fig. 93 nephrocalcinosis Fig. 105 trombocytopenic purpura, Fig. 78 Sneddon’s syndrome, Figs. 12, 17 (See primary APS) Somatogenic pain syndrome (See Fibromyalgia) Spinal stenosis and vertebral compression fracture, Fig. 126 Spondyloarthrosis chondritis, Figs. 123, 127a osteochondrosis, Fig. 116 DISH, Fig. 118 spondylosis, Figs. 116, 123, 127b Spondylodiscitis small gibbus in the thoracic spine, and CRP elevation, Figs. 48ab, CS 17 Soft laser therapy (785 µm)

136 bursitis, tendinitis, and peritendinitis, Figs. 106, 107 plantar fasciitis, Figs. 98, 99 tendititis, enthesitis, and osteitis, Figs. 102, 103 SSc acute acral gangrene, Fig. 47 (DD Buerger’s disease) acute respiratory distress, pleural effusions, as initial signs, Fig. 53, CS 19 calcinosis, Fig. 18 contractures, Fig. 18 fibrotic alveolitis, Fig. 53 “Madonna fingers”, Fig. 130c increase in CK and TSH, CS 54 Raynaud’s phenomenon, Figs. 52, 130c sclerodactyly and scleroderma, as initial signs, Fig. 52 with contractures, Fig. 18 Stenosis arterielle aorta, Figs. 12, 132c (See Aortoiliac disease) A. subclavia and carotid, TA, Fig. 61 Still’s disease adult onset, Figs. 131abc; CS 62 juvenile, CS 66 Surgery arthrodese Figs. 5, 9b, 122c osteosynthesis in osteoporose vertebral fracture, Figs. 127ab pseudoileus due to lymphadenopathy, SLE, Fig. 82, CS. 29 removal of rheumatoid nodules mass, Figs. 122abc TEP in hip destruction, AS, Figs. 119, 120 Symphysitis, Fig. 120 Synchondrosis /perichondritis/ manubriosternalis, CS 21 Syndesmophyte (See Ankylosing spondylitis) T Tendinitis and Dupuytren contracture, Fig. 95 and enthesitis, and osteitis, PsA, CS 65 MCTD, Jaccoud’s arthropathy, Fig. 70 mechanical, shoulder syndrome, Fig. 106 RA, Fig. 63 De Quervain’s tenosynovitis, Fig. 5 Yersinia-induced and enthesitis, Fig. 102 reactive arthritis, HLA-B27 positive, CS 69 Thrombocytopenia and hemolytic anemia, SLE, CS 64 and purpura, SLE, Fig. 78 Thrombosis See Sneddon’s syndrome

Index See Aortoiliac disease PAN, intestinal infarction, CS 48 SLE of pelvic/leg vein, CS 34 of v. renalis, CS 29 WG, stroke with hemiparesis, Fig. 86, CS 31 Tietze syndrome PsA sine psoriasis, Fig 69 Toe pain acne- induced arthropathy (DD SAPHO syndrome), dactilitis, Figs. 65ab gout acute, in toe 1 in 10-year-old girl, CS 55 after tophus ablation, Fig. 114 PsA, dactilitis with ulcers, Fig. 15a oligoarthritis, HLA-B27 positive, Figs. 23, 24 RA claw toe, Fig. 43 MTP 5 as initial signs, Fig. 41 Trees of rheumatology articular and musculoskeletal disorders, 34–36 connective tissue diseases and vasculitides, 35, 37 U Ulcus cruris PAN, Fig. 2 RA, Figs. 55, 101a Ulcers deep PAN, Figs. 10–11 DD livedoid vasculopathy, Figs. 30–31 MCTD, Fig. 71 cryoglobulinemia and monoclonale gammapathy, Figs. 132ab Ulnar nerve compression by rheumatoid nodules, Fig. 122abc V Vasculitis primary Churg- Strauss syndrome, CS 72 Giant-cell arteriitis, acute deafness, headache, CRP (up to factor x 64), RSS, p. 157 mm/h, Fig. 76, CS 26 Morbus Behçet mouth ulcers, heart attack, ESR 104 microscopic polyangiitis (See MPA) polyarteritis nodosa (See PAN) Wegener’s granulomatosis (See WG) secondary medium-sized vessels involvement (See Aortiis) cardiac, myocardial infarction

137

Index TA, CS 21 MB, CS 26 cerebral, multi-infarct syndrome Sneddon’s syndrome, Fig. 17 intestinal, several intestinal perforations ANCA-associated vasculitis, CS 48 skin, extremities (with thrombosis) monoclonal gammapathy, cryoglobulinemia, Figs. 132ab PAN, Figs. 10, 11 SSc (DD Buerger’s diseases), Fig. 47 small vessel involvement, also vasa vasorum (See also Aphthous ulcers, Erythema, Skin) cryoglobulinemia in chronic hepatitis C, Figs. 56ab cryoglobulinemia and monoclonale gammapathy acute gangrene in the upper third of thighs, Fig. 132b Lupus profundus, Fig. 27 palmar erythema, RA, Fig. 100 panniculitis profunda in MCTD, Fig. 71 paraneoplastic CS 56, as in Figs. 56

ulcera cruris, RA, Figs. 55, 101a drug induced, Fig. 113 Vertebral fracture and acute paraplegia osteoporose, cortisone-induced, Figs. 125–127 W WG (Wegener’s granulomatosis) as a paraneoplasia of colon carcinoma, RSS, p. 67, CS 73 ENT involvement, Fig. 86 intrapulmonary infiltrates and caverns, Fig. 112 and bronchiectasis, and fibrosis, Fig. 75 pseudotumor in the left orbit, Fig. 96 Y Yersinia infection erythema nodosum, Fig. 109 fever of initially of unknown etiology, CS 60 plantar fasciitis, Fig. 98 reactive arthritis, HLA-B27 positive, CS 69 tendinitis, enthesitis and osteitis, Figs. 102, 103