Absolute Rheumatology Review Petros Efthimiou Editor 123 Absolute Rheumatology Review Petros Efthimiou Editor Absolute Rheumatology Review Editor Petros Efthimiou New York University New York, NY USA ISBN 978-3-030-23021-0 ISBN 978-3-030-23022-7 (eBook) https://doi.org/10.1007/978-3-030-23022-7 © Springer Nature Switzerland AG 2020 This work is subject to copyright All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed The use of general descriptive names, registered names, trademarks, service marks, etc in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland To my wife, Olga, my best friend and gracious critic To my parents, Vasilios and Angeliki, who convinced me to pursue my dreams and that everything is possible To my patients who trust me with their health and teach me something new every single day Foreword Fellowship training is a wonderful start to mastering the art and science of rheumatology Yet, or 3 years of rheumatology fellowship training can be dizzying for the notable volume of work, experiences, knowledge, diagnoses, controversies, and opportunities The educational sustenance is analogous to drinking from the firehose You’ll definitely get wet (experience) but your thirst may go unquenched Time, perspective, and an ongoing effort to learning are necessary to master the art of rheumatology Absolute Rheumatology Review is a new source of perspective and knowledge for the young rheumatologist It was designed to be the resource for those in training and those preparing for board examinations or recertification examinations Textbooks serve the important role of defining the standards of care and where we are in our understanding of rheumatic disorders This is especially important with complex rheumatologic disorders where innovation, pathogenic advances, and new therapeutics change annually When such knowledge is applied, patients win with better opportunities for an early diagnosis and optimal outcome The chapters included in Absolute Rheumatology Review are written by experts who have synthesized historical perspective and recent advances to provide overviews that are accurate, focused, practical, and up-to-date In reviewing and reading Dr Efthimiou’s textbook, I can appreciate the selection of authors and the inclusion of many novel chapters germane to rheumatology, including genetics, immunology, epidemiology, regional musculoskeletal disorders, ultrasound, and autoinflammatory disorders These stand well beside chapters on the most prevalent disorders, such as rheumatoid arthritis, psoriatic arthritis, osteoarthritis, etc Chapter design and readability are both easy and incisive The chapters are led by bulleted key points and finish with test questions to further their educational impact These are novel, well-done, and highly helpful whether you’re a young rheumatologist preparing for board questions or a practicing rheumatologist wishing to stay abreast of the field vii viii Foreword While this compendium will benefit those who are studying rheumatology, it can also exist as a valued source for the rheumatologist engaged in patient care, especially when he or she ponders the last patient, the next drug choice, or the best diagnostic approach John J. Cush, MD Clinical Professor of Internal Medicine, The University of Texas Southwestern Medical School, Dallas, TX, USA Executive Editor, RheumNow.com Preface I am pleased to introduce this concise and comprehensive review of rheumatology to physicians preparing for the rheumatology board certification examination The goal was to provide the most up-to-date information, emphasizing high-yield facts, in an easy-to-read format, accented by tables, figures, and clinical imaging, without burdening the reader with extraneous details Moreover, each chapter was enhanced by a plethora of board-like, multiple-choice questions for the reader to practice and apply the knowledge gained by reviewing the various topics The contributing authors were selected because of their clinical and research expertise as well as their track record on being master educators The readers will recognize among the authors marquee names in academic rheumatology Beyond their involvement in every day clinical care, their research has revivified the specialty while themselves have become role models and nurtured the next generation of rheumatology leaders The intended audience for the book are in-training rheumatology fellows and practicing rheumatologists preparing for the certification and recertification examinations in rheumatology I strongly believe that interested physicians will find useful not only the content of this book but also its format; the use of the time-honored Socratic method of learning through questions and answers has served humanity well since its inception in Ancient Greece Petros Efthimiou New York University New York, NY ix Contents 1 Immunological Basis of Inflammatory Arthritides������������������������������ 1 George D Kalliolias and Dimitris Skokos 2 Clinical Epidemiology in Rheumatology ���������������������������������������������� 37 Bella Mehta 3 Osteoarthritis�������������������������������������������������������������������������������������������� 51 Matlock A Jeffries 4 Regional Musculoskeletal Syndromes and the Use of Musculoskeletal Ultrasound�������������������������������������������������� 77 Karishma Ramsubeik, Laurie Ann Ramrattan, Myint Thway, Jaspreet Kaler, and Gurjit S Kaeley 5 Infectious Arthritis���������������������������������������������������������������������������������� 111 Nicola Berman and Brian D Golden 6 Rheumatoid Arthritis������������������������������������������������������������������������������ 127 Saleha Riaz and Apostolos Kontzias 7 Psoriatic Arthritis������������������������������������������������������������������������������������ 153 Fardina Malik, Rebecca Haberman, and Jose U Scher 8 Axial Spondyloarthritis �������������������������������������������������������������������������� 175 Adam Berlinberg and Kristine A Kuhn 9 Systemic Lupus Erythematosus (SLE)�������������������������������������������������� 195 Teja Kapoor and Pooja Mahadeshwar 10 Sjögren’s Syndrome �������������������������������������������������������������������������������� 225 Anna Rapti, Nikolaos Marketos, and Clio P Mavragani 11 Systemic Sclerosis (Scleroderma) ���������������������������������������������������������� 263 Lazaros I Sakkas xi xii Contents 12 Vasculitis �������������������������������������������������������������������������������������������������� 277 Jason Liebowitz, Brendan Antiochos, and Eric J Gapud 13 Inflammatory Myopathies���������������������������������������������������������������������� 303 Eleni Tiniakou and Michael Wu 14 Osteoporosis���������������������������������������������������������������������������������������������� 321 Aaroop Haridas and Seth Mark Berney 15 Crystal Arthritis �������������������������������������������������������������������������������������� 345 Anastasia Slobodnick, Michael Toprover, and Michael H Pillinger 16 Autoinflammatory Diseases�������������������������������������������������������������������� 375 Min Shen, Di Wu, and Qingping Yao 17 Pediatric Rheumatology for Adult Rheumatologists���������������������������� 401 Natalie Rosenwasser and Karen Onel 18 Musculoskeletal Manifestations of Systemic Diseases�������������������������� 425 Michael Malekan and Apostolos Kontzias 19 Clinical Genetics in Rheumatology�������������������������������������������������������� 447 Ruth Fernandez-Ruiz and Petros Efthimiou Index������������������������������������������������������������������������������������������������������������������ 467 19 Clinical Genetics in Rheumatology 463 nist and mutations affecting the TNF receptor are also causes of monogenic inflammatory syndromes but are not specifically associated with the familial cold autoinflammatory syndrome (options D and E) Which of the following is a true statement about genetic testing? A Genetic testing is strictly regulated and under similar federal regulatory standards as other specialized laboratory tests B Direct-to-consumer testing is an adequate initial approach for patients with a suspected genetic disease C Single-gene testing is most helpful when the clinical presentation is vague and there are multiple candidate genes as potential causes for the disease D Next-generation sequencing has become obsolete since the Sanger sequencing technique became commercially available E Genetic testing is safe; therefore, obtaining an informed consent is not recommended Correct answer: A Genetic testing regulations are similar to other specialized laboratory tests to ensure the analytical and clinical validity, under the Clinical Laboratory Improvement Amendments (CLIA), a Centers for Medicare and Medicaid Services (CMS) program Direct-to-consumer genetic testing is not currently recommended as a diagnostic tool for genetic diseases (option B) In contrast to genetic panels where multiple genes are evaluated, single-gene testing is a much narrower strategy and would only be useful if there is only one or very few candidate genes (option C) Next-generation sequencing (NGS) technologies are widely used in commercial laboratories, while the Sanger technique is mostly used for confirmatory purposes (option D) Even though genetic testing is considered safe, the emotional impact and the possibility of identifying unexpected and unrelated genetic alterations, among other implications of genetic testing, need to be discussed with patients, and an informed consent should be obtained (option E) A 22-year-old woman presents to rheumatology clinic for evaluation of effort- related arthralgias She reports that since childhood she has been more flexible than her peers She can bend her thumbs backward to her wrists but cannot touch the floor with her palms when bending forward with her knees extended She also states that her skin bruises very easily and is thin Her mother died in her 20s while pregnant due to uterine rupture, and her father died in his 30s due to a spontaneous bowel perforation A diagnosis of vascular Ehlers-Danlos syndrome (EDS) is considered What is the most likely affected gene in this type of EDS? A B C D E FBN1 ADAMTS2 COL3A1 PLOD1 TNXB Correct answer: C 464 R Fernandez-Ruiz and P Efthimiou Vascular or type IV EDS is an AD disorder caused by a mutated COL3A1 gene, which codes for a collagen III pro-α1 chain Vascular EDS is a life-threatening disease due to spontaneous rupture of blood vessels and internal organs (intestines or uterus) FBN1 codes for fibrillin 1, the protein affected in Marfan syndrome (option A) ADAMTS2 is a procollagen peptidase associated with EDS VIIC or dermatosparaxis type, an AR characterized by prominent redundant and extremely fragile skin, hernias, and short stature (option B) PLOD1 codes for a lysyl hydroxylase and is associated with EDS type VI or kyphoscoliotic EDS type (option D) TNXB mutations (option E) are associated with classic-like EDS (AR disorder) and in less than 10% of patients with hypermobile EDS (AD inheritance) References Turanlı ET, Everest E, Balamir A, Aydın AK, Kasapỗopur ệ Role of genetics in pediatric rheumatology Turk Pediatri Ars 2017;52(3):113–21 Cornélis F. Genetics and clinical practice in rheumatology Joint Bone Spine 2003;70(6):458–64 Kirmani S. Molecular genetic testing in endocrinology – a practical guide Endocr Pract 2012;18(1):85–9 Domchek SM, Jameson J, Miesfeldt S. The practice of genetics in clinical medicine In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J, editors Harrison’s principles of internal medicine 19th ed New York, NY: McGraw-Hill; 2014 http://accessmedicine.mhmedical.com.ezproxy.med.nyu.edu/content.aspx?bookid=1130§ionid=79728285 Accessed 28 Jan 2019 Jameson J, Kopp P. Genes, the environment, and disease In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J, editors Harrison’s principles of internal medicine 19th ed New York, NY: McGraw-Hill; 2014 http://accessmedicine.mhmedical.com.ezproxy.med.nyu edu/content.aspx?bookid=1130§ionid=79728075 Accessed 06 Feb 2019 Griffiths AJF, Miller JH, Suzuki DT, et al An introduction to genetic analysis In: Penetrance and expressivity 7th ed New York: W. H Freeman; 2000 Available from: https://www.ncbi nlm.nih.gov/books/NBK22090/ Federici L, Rittore-Domingo C, Koné-Paut I, Jorgensen C, Rodière M, Le Quellec A, Touitou I. A decision tree for genetic diagnosis of hereditary periodic fever in unselected patients Ann Rheum Dis 2006;65(11):1427–32 Caso F, Rigante D, Vitale A, Lucherini OM, Costa L, Atteno M, Compagnone A, Caso P, Frediani B, Galeazzi M, Punzi L, Cantarini L. Monogenic autoinflammatory syndromes: state of the art on genetic, clinical, and therapeutic issues Int J Rheumatol 2013;2013:513782 Colombi M, Dordoni C, Chiarelli N, Ritelli M. Differential diagnosis and diagnostic flow chart of joint hypermobility syndrome/ehlers-danlos syndrome hypermobility type compared to other heritable connective tissue disorders Am J Med Genet C Semin Med Genet 2015;169C(1):6–22 10 Knob AL. Principles of genetic testing and genetic counseling for renal clinicians Semin Nephrol 2010;30(4):431–7 11 Marsick R, Limwongse C, Kodish E. Genetic testing for renal diseases: medical and ethical considerations Am J Kidney Dis 1998;32(6):934–45 12 Institute of Medicine (US) Committee on Assessing Genetic Risks In: Andrews LB, Fullarton JE, Holtzman NA, et al., editors Assessing genetic risks: implications for health and social 19 Clinical Genetics in Rheumatology 465 policy Washington, DC: National Academies Press (US); 1994 2, Genetic testing and assessment Available from: https://www.ncbi.nlm.nih.gov/books/NBK236037/ 13 Finetti M, Omenetti A, Federici S, Caorsi R, Gattorno M. Chronic infantile neurological cutaneous and articular (CINCA) syndrome: a review Orphanet J Rare Dis 2016;11:167 14 Middleton A, Mendes Á, Benjamin CM, Howard HC. Direct-to-consumer genetic testing: where and how does genetic counseling fit? Per Med 2017;14(3):249–57 15 Zhang W, Cui H, Wong LJ. Application of next generation sequencing to molecular diagnosis of inherited diseases Top Curr Chem 2014;336:19–45 16 Nakayama M, Oda H, Nakagawa K, Yasumi T, Kawai T, Izawa K, Nishikomori R, Heike T, Ohara O. Accurate clinical genetic testing for autoinflammatory diseases using the next- generation sequencing platform MiSeq Biochem Biophys Rep 2016;9:146–52 17 Mu W, Lu HM, Chen J, Li S, Elliott AM. Sanger confirmation is required to achieve optimal sensitivity and specificity in next-generation sequencing panel testing J Mol Diagn 2016;18(6):923–32 18 Clinical Laboratory Improvement Amendments (CLIA) Baltimore, MD: Centers for Medicare & Medicaid Accessed 23 Feb 2019 World Wide Web URL: https://www.cms.gov/ Regulations-and-Guidance/Legislation/CLIA/index.html 19 FDA finalizes guidances to accelerate the development of reliable, beneficial next gen eration sequencing-based tests Silver Spring, MD: U.S. Food and Drug Administration Accessed 23 Feb 2019 World Wide Web URL: https://www.fda.gov/NewsEvents/Newsroom/ PressAnnouncements/ucm604462.htm 20 Online Mendelian Inheritance in Man, OMIM® McKusick-Nathans Institute of Genetic Medicine Baltimore, MD: Johns Hopkins University Accessed 23 Feb 2019 World Wide Web URL: https://omim.org/ 21 Adam MP, Ardinger HH, Pagon RA, et al., editors GeneReviews® [Internet] Seattle, WA: University of Washington, Seattle; 1993–2019 Available from: https://www.ncbi.nlm.nih.gov/ books/NBK1116/ 22 Bascom R, Schubart JR, Mills S, Smith T, Zukley LM, Francomano CA, McDonnell N. Heritable disorders of connective tissue: description of a data repository and initial cohort characterization Am J Med Genet A 2019; https://doi.org/10.1002/ajmg.a.61054 [Epub ahead of print] 23 Prockop DJ, Bateman JF. Heritable disorders of connective tissue In: Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J, editors Harrison’s principles of internal medicine 20th ed New York, NY: McGraw-Hill http://accessmedicine.mhmedical.com.ezproxy med.nyu.edu/content.aspx?bookid=2129§ionid=192530885 Accessed 23 Feb 2019 Index A A1 pulley thickening, 102 Abatacept, 139, 144, 165, 181 Abductor pollicis longus, 103, 105 ACE-inhibitor, 217 Acetaminophen, 63, 64, 123 Achilles tendinopathy, 95 Achilles tendon rupture, 96–97, 101 Acrolein, 220 Acromegaly, 425–427 Acromioclavicular (AC) joint, 80 Acro-osteolysis, 264 Acute anterior cruciate ligament (ACL), 91 Acute hemarthrosis, 431 Acute Lyme arthritis, 116 Adalimumab, 138, 186, 366 Adhesive capsulitis, 80, 106 Adult-onset Still’s disease (AOSD), 407 Aerobic exercise, 246 Alendronate, 336, 339 Alkaptonuria, 430 Allopurinol, 361, 362 Alopecia, 205 American Academy of Orthopedic Research (AAOS), 63 American College of Rheumatology (ACR), 63 Amitriptyline, 246 Amyloid arthropathy, 438 Amyloidosis, 437–438 Amyopathic DM, 304 Anakinra, 139, 149 Ankle pain, 95 Ankle pathology, 96 Ankylosing spondylitis, 186, 189, 190 Anterior ankle pain, 95 Anterior drawer test, 92, 96 Anterior hip pain, 86 Anterior knee pain, 90 Antibiotic therapy, septic arthritis, 118 Antibodies to citrullinated protein antigens (ACPAs), 128 Antibodies to citrullinated protein antigens- driven osteoclasogenesis, Anti-CD20, 211 Antigen presentation theory, 15 Anti-nuclear antibodies (ANA), 135, 198, 199, 402, 405 Antiphospholipid syndrome, mortality and morbidity in, 42–43 Anti-TNF, 167 Apprehension test, 93 Apremilast, 164, 181–182 Arrhythmias, 266 Arthralgias, 115 Arthritides, 264 Arthritis, 197, 433 mutilans, 155 primary immunodeficiencies, 434 sarcoidosis, 438 Arthritogenic immune cells, 16–17 Arthritogenic memory, Articular cartilage, 11, 54–56 Assessment of Spondyloarthritis International Society (ASAS) classification criteria, 177 Asymmetric oligoarthritis, 155 Autoantibodies in rheumatoid arthritis, 2–3 Sjögren’s syndrome, 231–233 in SLE, 200 Autoimmune epithelitis, 228 © Springer Nature Switzerland AG 2020 P Efthimiou (ed.), Absolute Rheumatology Review, https://doi.org/10.1007/978-3-030-23022-7 467 468 Autoimmunity in rheumatoid arthritis, 3–4 serologic evidence of, 129 Autoinflammatory diseases (AIDs), 376 Blau syndrome, 386–387 classification of, 377 colchicine, 395 familial Mediterranean fever, 376–380 mevalonate kinase deficiency, 384–386 monogenic diseases, 391–394 NLRP12-associated autoinflammatory disease (NLRP12-AID), 382–383 NLRP3-associated autoinflammatory disease, 380–382 periodic fever and oral ulcers, 396 phenotypes and genotypes, 389 rashes in, 390 TNF receptor-associated periodic fever syndrome, 383–384 Yao syndrome, 387–389 Autoinflammatory syndromes, 450–454 Autosomal dominant (AD), 447–448 Autosomal recessive (AR), 447–448 Avascular necrosis, 426 Axial spondyloarthritis, 155 Azathioprine, 211, 216, 220 B Baker’s cyst, 93–94 Baricitinib, 139, 140 Barium esophagography, 267 Basic calcium phosphate (BCP), 353 clinical presentation, 353–354 diagnosis, 354 pathophysiology, 353 risk factors, 353 treatment, 354 Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), 182, 183 B-cell activating factor (BAFF), 243 Behỗets disease, 284285 Belimumab, 211 Bias, 45 Biceps tendon pathology, 78 Bicipital tendinopathy, 101 Binary variables, 39 Biologic DMARDs, 181 Biologics, 140 Bisphosphonates, 330–331 Blau syndrome (BS), 386–387, 397, 454 Bone biopsy, 441 Brodalumab, 23 Index Bronze diabetes, 430 Brown tumor, 429 Brucella, 117, 121 Bursectomy, 366 C Calcaneal ultrasound, 326 Calcinosis, 264 Calcinosis cutis, 305 Calcitonin, 332, 336 Calcium oxalate crystals, 354–355 Calcium phosphate arthritis, 367 Calcium pyrophosphate crystal deposition (CPPD), 350 clinical presentation, 351–352 diagnosis, 352 pathophysiology, 350–351 risk factors, 350 treatment, 352 Calcium pyrophosphate deposition disease, 368 Calf pain, 93 Camptocormia, 306 Carpal tunnel syndrome (CTS), 84, 102 Case control studies, 43 Case report/case series, 43 Categorical variables, 38 Celecoxib, 66, 371, 442 Cellular crescents, 215 Central tendency, measures, 40 Certolizumab, 138 Cervical spine involvement, 133 Charcot’s arthropathy, 428 Chikungunya viral infection, 147 Chikungunya virus, 116 Chilblain lupus, 205, 221 Cholesterol crystals, 355 Cholestyramine, 145 Chronic cutaneous lupus erythematosus (CCLE), 204–212 Chronic kidney disease (CKD), gout and, 356 Cigarette smoking, 5–6 Citrulline, 128, 129 Classification Criteria for Psoriatic Arthritis (CASPAR), 158, 170 Clinical Disease Activity Index (CDAI), 137 Clostridium difficile infection, 185 Clotting factor, 440 Cogan’s syndrome, 284, 298 Cohort studies, 43 COL3A1 gene, 464 Colchicine, 360 Index Collateral ligament injuries, 91 Congenital contractural arachnodactyly, 459 Continuous variables, 38, 39 Conventional synthetic DMARDs, 180 Corneal deposits, 145 Corticosteroid myopathy, 425 Corticosteroids, 211 Costimulatory modulator, 139 COX2-selective NSAID, 66, 70 Coxa saltans, see Snapping hip syndrome Cross section studies, 43 Cryopyrin, 462 Cryopyrin-associated periodic syndromes (CAPS), 451 Crystal arthritis, 434 basic calcium phosphate, 353–354 calcium oxalate crystals, 354–355 calcium pyrophosphate deposition disease, 350–352 gout, 345–350 rhomboid-shaped crystals, 371 Crystalline arthropathies, 61 Cubital tunnel syndrome, 82–83 Cushing syndrome, 425 Cutaneous punctuate ulcers, 305 Cutis laxa, 459 Cyclic citrullinated peptide (CCP) antibody, 143 Cyclooxygenase (COX), 176 Cyclooxygenase (COX2), 24 Cyclophosphamide, 45–46, 211, 220 Cytokine network and hierarchy, Cytokine perturbations, 130 Cytokine-driven osteoclastogenesis, 6–7 Cytopenias, 206–207 D Dactylitis, 155 Danger-associated molecular patterns (DAMPs), 55 De Quervain’s tenosynovitis, 83–85, 102 Deficiency of the interleukin-1 receptor antagonist (DIRA), 454 Denosumab, 22, 331 Dermatomyositis, 304, 435 Diabetes, and septic arthritis, 122 Diabetes Mellitus type (DM2), 426–427 Dialysis, 364 Dichotomous variables, 39 Diffuse cutaneous SSc (dcSSc), 264 Diffuse idiopathic skeletal hyperostosis, 187 Diffuse large B cell lymphoma (DLBCL), 240 469 Digital ulcers (DUs), 264, 270 Discoid lesions, 204 Discoid rash, 197 Discoid rash of ear, 201 Discoid rash of lip, 201 Disease modifying anti-rheumatic drugs (DMARDs), 136–140, 164, 238 biologic, 181 conventional synthetic, 180 target-specific, 181–182 Dispersion, measures of, 40–41 Disseminated gonococcal infection (DGI), 119 Distal interphalangeal (DIP) pain, 69 Distal muscle weakness, 305 Dorsiflexion-eversion test, 99 Double-stranded DNA (dsDNA), 199 Doxycycline, 122 Drug-induced SLE, 199–200, 212 Drug-induced vasculitis, 281 Dry eye disease, 237 Dual-energy X-ray absorptiometry (DEXA), 189, 327, 334 Dupuytren’s contracture, 86 E Early-onset sarcoidosis (EOS), 454 Ehlers Danlos syndrome (EDS), 459, 463 Elastography, 236 Elbow pain, 81, 82 Electrophoresis, 444 Empty can test, 78 Endocrine disorders, 425–429 Endoplasmic reticulum aminopeptidase (ERAP1), 15 Endothelin-1(ET-1), 266 Enthesitis, 20, 155, 176, 178 Enthesitis related arthritis (ERA), 402, 404 Eosinophilic fasciitis (EF), 269 Eosinophilic granulomatosis with polyangiitis (EGPA), 288–289 Epigenetics, 56 Epithelial barrier disruption, 16 Epstein–Barr virus (EBV), 128, 196 Erosive disease, 148 Erosive osteoarthritis, 59, 61, 368 Erythrodermic psoriasis, 155 Esophageal dysmotility, 307 Etanercept, 23, 138, 144, 149, 165, 181, 184 EULAR Sjogren’s Syndrome Patient Report Index (ESSPRI), 238 EULAR Sjogren's syndrome Disease Activity Index (ESSDAI), 238 470 European League Against Rheumatism (EULAR), 238 European scleroderma trials and research (EUSTAR) group, 268 Eversion (Talar Tilt) stress test, 96 Exercise, 62 Experimental studies, 42 Extensor pollicis brevis tendons, 103, 105 External rotation test, 96 Extra-articular manifestations, 134, 431 Extracellular matrix (ECM), 54, 55, 265 F Facioscapulohumeral dystrophy (FSHD), 306, 316 Familial Mediterranean fever (FMF), 397, 451 clinical presentation, 377–378 diagnosis, 378–379 pathophysiology, 376–377 safety monitoring, 379 secondary amyloidosis, 378 treatment, 379–380 Febuxostat, 358 Felty syndrome, 134, 141 Femoroacetabular hip impingement (FAI), 88 Fibrinoid necrosis, 279 Fibroblast-like synoviocytes, 8–9, 22 Fibromyalgia, diagnoses of, 43–45 Flexion, abduction, external rotation (FABER) test, 87, 88 Flexion, adduction, and internal rotation (FAIR) test, 87, 89 Flexor digitorum superficialis (FDS), 86 Flexor pollicis longus tendon (FPL), 85–86 Fms-like tyrosine kinase ligand (Flt-3l), 243 Foot pathology, 99 Forefoot pain, 98–99 Foucher sign, 93 Fracture risk assessment (FRAX), 322, 328–329 Fragility fractures, 322 Frozen shoulder, see Adhesive capsulitis Fungal infections, 115 G Gastrocnemius injury, 93 Gastrointestinal disease, 307 Gastrointestinal tract (GIT), 267, 271 Genetic testing, 447–448 autoinflammatory syndromes, 450–454 clinically available methodologic approaches, 449–450 federal regulatory standards, 463 Index heritable disorders of connective tissue, 454–460 in rheumatology, 449 Genetics, 56 Genome sequencing, 450 Genome-wide association studies (GWAS), 5, 56, 128 Giant cell arteritis (GCA), 282–283 Glenohumeral (GH) joint, 80 Glucocorticoid induced osteoporosis (GIOP), 332, 333 Glucose-6-phosphatase-dehydrogenase (G6PD) deficiency, 359 Gluteal tendinopathy, 89 Golfer’s elbow, 82 Golimumab, 138 Gonococcal infection, 114 Gottron’s papules, 304 Gottron’s sign, 304 Gout, 368 ACR classification, 348 American College of Rheumatology guidelines, 349 chronic kidney disease and, 356 clinical presentation, 347 diagnosis, 347–348 HLA-B∗5801 testing, 357 low-dose aspirin, 356 pathophysiology, 346–347 patient management, 357 risk factors, 345–346 tobacco, 357 tophaceous, 358 treatment, 349 Graft-versus-host Disease (GVHD), 437 Gram negative enteric organisms, 114 Granulomatosis with Polyangiitis (GPA), 287–288, 299 Graves’ disease, 427 Growing pains, 421–422 Guselkumab, 21 Gut-joint axis, 16–17 H Hair-on-end appearance, 432, 433 Hamstring syndrome, see Proximal hamstring tendinopathy Hand deformities, 132 Hawkins-Kennedy test, 78 Heerfordt syndrome, 438 Heliotrope rash, 304 Hemarthrosis, 440 Hematologic disorder, 198, 431–434 Index Hemochromatosis (HHC), 430–431, 442 Hemodialysis, 440 Hemoglobinopathies, 432 Hemophilia, 431 Hemophilic arthropathy, 431, 432 Henoch-Schonlein Purpura (HSP), 289–290 Heritable disorders of connective tissue (HDCT), 454–460 Hip OA, 52, 56, 59, 64 Hip pathology, 87 HIV infection, 184 HIV testing, 184 Holster sign, 304 Human leukocyte antigen (HLA) HLA-B27, 176, 187, 192, 405 rheumatoid arthritis and, 4–5 Hydroxychloroquine, 138, 150, 210, 214, 215, 220, 343 Hyperoxaluria, 355 Hyperparathyroidism, 429–430 Hyperthyroidism, 427–428 Hypomyopathic DM, 304 Hypoparathyroidism, 428 Hypothyroidism, 427–428 I Ibuprofen, 63, 184, 363 Idiopathic inflammatory myopathies (IIM) antibodies, 310 asymmetric weakness, 306 autoantibodies, 309 clinical presentation, 304–305 differential diagnosis, 312–313 EMG/NCS, 311 epidemiology, 303–304 falls, 306 gastrointestinal disease, 307 heart, 307 imaging studies, 309 immunosuppression, 306 interstitial lung disease, 307 laboratory findings, 308–309 malignancy, 307–308 muscle biopsy, 311, 315 muscle findings, 305–306 oculobulbar symptoms, 306 overlap myositis, 308 patient’s management, 320 physical examination, 316, 320 PM/IMNM, 306 skin biopsy, 312 standardized incident ratio, 308 treatment, 313 471 types, 303 IFN gamma release assay, 141 IgA deposition, 298 IgA vasculitis, 419–420 IL-17 IL-17A inhibition, 165, 188 organ-specific role for, 17–18 pathway, 23 IL-23, 24 inhibitors, 23 organ-specific role for, 17–18 production, 16–17 IL-6 receptor antagonist, 139 Immune cell targeted therapy, 211 Immune related adverse effects (irAEs), 443 Immunofixation, 444 Immunofluorescent staining, 279 Immunoglobulin levels, 444 Immunologic disorder, 198 Impingement syndrome, 78–80 Imprinted aggressors, Incidence, 44 Indomethacin, 123 Infectious arthritis, see Septic arthritis Inflammaging, 57 Inflammasomes, 129 Inflammation-driven inhibition, of osteoblasts, 7–8 Inflammatory arthritis, 308 Infliximab, 138, 146, 295 Influenza vaccination, 149 Intention-to-treat (ITT), 48–49 Interleukin-6, 55 Internal rotation lag sign, 78 Interquartile range, 41 Interstitial lung disease (ILD), 169, 265, 270, 307 Intraarticular (IA) injections, 67 Intraarticular corticosteroid crystals, 355 Intracranial pressure (ICP), 381 Intravenous immunoglobulin therapy, 415 Inversion (talar tilt) stress test, 96 Iron overload, 434 IVIG, 295 Ixekizumab, 165 J Janus kinase (JAK) inhibitors, 140, 182 Juvenile dermatomyositis (jDM) calcinosis, 412 clinical features, 411 diagnosis, 410 pathology and pathogenesis, 411 treatment, 411–412 472 Juvenile idiopathic arthritis (JIA), 401 clinical features, 402–403 diagnosis of, 401–402 etiology, 403–404 leg length discrepancy, 406 treatment, 404 K Kawasaki disease (KD), 286 clinical features, 413–414 diagnosis, 413 pathology and pathogenesis, 414 treatment, 414 Keratoconjunctivitis sicca (KCS) symptoms, 225, 236 Kleiger’s test, 96 Knee ligamentous, provocation tests for, 92–93 Knee-only OA, 63 L Lachman test, 92, 105 Lactose intolerance, 218 Land-based exercise, 66 Lateral ankle pain, 97–98 Lateral epicondylitis, 82 Lateral femoral cutaneous nerve entrapment, 100 Lateral hip pain, 89 Lead-time bias, 46 Leflunomide, 138, 149 Lesinurad, 359 Leukopenia, 206 Ligamentous injuries, 91–93 Limb-girdle muscular dystrophy (LGMD), 306 Limited cutaneous SSc (lcSSc), 264 Lipid liquid crystals, 355 Lipid panel, 188, 189 Loeys-Dietz syndrome (LDS), 459 Long head of the biceps (LHB) tendon, 78 Losartan, 362 Low bone mineral density, 329–330 Low-dose aspirin, 362 Ludloff test, 87 Lupus nephritis, 207–209 advanced sclerosing, 208 diffuse proliferative, 208 focal proliferative, 208 ISN/RPS 2003 classification of, 207 membranous, 208 Index mesangial proliferative, 207–208 minimal mesangial, 207 treatment of, –, 45, 46 Lupus pernio, 221 Lupus profundus, 205, 221 Lupus tumidus, 204, 221 Lyme arthritis, 116, 122 Lyme disease, 441 Lymphomagenesis, 240–244 Lymphoproliferation, 240–244, 248 M Macrophage activation syndrome (MAS), 407 Macrophage-like synoviocytes (MLS), Magnetic resonance imaging (MRI), 61, 161–162 Majeed syndrome (MS), 454 Malar rash, 197, 201, 203, 304 Marfan syndrome (MFS), 459, 461 McMurray test, 92, 93 Mean, 40 Mechanic’s hands, 305 Mechanical stress hypothesis, 19 Medial collateral ligament (MCL), 82, 105 Medial epicondylitis, 82, 105, 106 Medial foot pain, 97 Median, 40 MEFV gene, 376–377 Meloxicam, 368 Meningococcal arthritis, 117 Meniscal injuries, 91–93 Meralgia paresthetica, 100 Mesenchymal stem cells (MSC), 19 Mesna, 220 Metabolic disorders, 430–431 Metatarsalgia, 98 Methicillin Resistant Staph Aureus (MRSA), 120 Methotrexate, 138, 141, 142, 144, 147, 211, 294 Mevalonate kinase deficiency (MKD), 384–386, 451 Microscopic polyangiitis (MPA), 288 Midfoot pain, 98 Minocycline, 216 Minor salivary gland biopsy (MSGB), 230–235, 249 Mitochondrial disorders, 448 Mixed connective tissue disease (MCTD), 308 Mode, 40 Modifiable risk factors, 61 Index Monogenic autoinflammatory diseases, 452–453 Mortality rate, 46 Morton’s neuroma, 98, 101 Mosaicism, 448 MTX, 168 Muckle-Wells syndrome (MWS), 381 Mucosa associated lymphoid tissue (MALT) lymphomas, 240, 251 Mulder sign, 99 Multicentric reticulohistiocytosis, 435, 436 Multijoint OA, 63 Muscle atrophy, 403 Musculoskeletal manifestations, 206 Musculoskeletal ultrasound (MSKUS), 77, 161 Mycobacterium, 115 Mycophenolate mofetil (MMF), 45–46, 211, 220 Mycoplasma, 117 Myopathy, 427, 436 N Nailfold capillary changes, 304 Naproxen, 63, 66 Neer test, 78 Negative predictive value, 44 Neisseria gonorrhoeae, 122 Neonatal lupus rash, 201 Nephrogenic systemic fibrosis (NSF), 269 Neurologic disorder, 198 Neuropsychiatric SLE (NPSLE), 209, 219 Next-generation sequencing (NGS) technologies, 450, 463 Nivolimumab, 443 NLRP12-associated autoinflammatory disease (NLRP12-AID), 382–383 NLRP3-associated autoinflammatory disease (NLRP3-AID) clinical features, 380–381 diagnosis, 381–382 NOMID/CINCA, 381 pathophysiology, 380 treatment, 382 N-methyl-D-aspartate receptor (NMDAR) antibody, 209 Nodal marginal zone lymphoma (NMZL), 240 NOD-like receptor (NLR), 380 Nominal variables, 39 Non-inferiority trial, 48–49 Non-radiographic SpA (nrSpA), 13 Non-randomized controlled trials, 42 473 Non-steroidal anti-inflammatory drugs (NSAIDs), 19, 63, 66 spondyloarthritis, 180 systemic lupus erythematosus, 210 Normal distribution, 41 Number needed to harm (NNH), 46 Number needed to treat (NNT), 46 O Ober tests, 87, 88 Obesity, 57 Observational study, 43 Ochronosis, 430 Ocular tests, 236–238 Odds ratio (OR), 47 Oligoarticular JIA, 405 Omega-3 fatty acid, 148 Omeprazole, 66 Oral pain, 305 Oral ulcer, 197, 201, 205 Ordinal variables, 39 Osteitis condensans ilii, 187 Osteoarthritis (OA) ACR classification criteria, 60 case study, 64–71 clinical presentation, 58–59 development and progression, 52 diagnosis, 59–61 environmental risk factor, 57 genetic association studies, 52 hand, 59 pathogenesis, 69 pathophysiology, 52–56 pharmacologic treatment, 62 physical examination, 64, 67 physical therapy, 62 radiographic findings, 70 risk factors, 56–57 surgical treatment, 64 treatment, 52, 61–64 Osteoarthritis Initiative (OAI) study, 58 Osteoarthritis Research Society International (OARSI), 62–63, 68 Osteoarthropathy, 430 Osteoblasts (OB), 7–8 Osteoclastogenesis, Osteoclasts (OC), Osteogenesis imperfecta (OI), 459 Osteomalacia, 322 Osteomyelitis, 433 Osteonecrosis, 434 Osteopenia, 321, 329–330, 403 474 Osteophytes, 55, 80 Osteoporosis, 321, 329–330, 336, 432 aging, 341 bisphosphonates, 330–331 bone physiology, 323 calcaneal ultrasound, 326 calcitonin, 332 clinical indications, 328 clinical manifestations, 325 denosumab, 331 dual energy X-ray absorptiometry (DEXA), 327, 337, 340 economic burden, 323 etiology of, 323–324, 332 evaluation, 325 FDA approved agents for, 332 fracture risk assessment, 328–329 fragility fracture, 333 history, 321 incidence and prevalence, 322 intermittent pulses, 333–334 least significant change, 328 lumbar radiograph, 341 in men, 325 morbidity and mortality, 322–323 natural course of, 322 non-pharmacologic interventions, 329–330 patient education, 334–336 pharmacologic interventions, 330–336 pharmacological therapy, 334 prior fracture, 338 quantitative CT scan, 326 radiographs, 326 reassessment of risk, 334 risk factors for, 324–325 single photon absorptiometry, 326 teriparatide, 331 World Health Organization criteria, 327–328 Ovariectomy, 227 Ovoid palatal patch, 305 Oxalosis, 354 P Pain, 58 Palmar fibromatosis, 86 Pancytopenia, 206 Pannus, 130 Papules, 305 Parvovirus, 115–116, 121 Passive aggressors, Patellar tendinopathy, 89–90 Patellofemoral pain syndrome (PFPS), 90–91, 100 Index Pathogen associated pattern recognition receptors (PARPs), 129 Patrick’s test, 87 Pediatric systemic lupus erythematosus (SLE) clinical features, 409 diagnosis, 408 pathology and pathogenesis, 409 treatment, 409 Pegloticase, 359 Pencil in cup deformity, 170 Peptidyl-arginine deiminase (PADI), Periodic Fever with Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA), 416–417 Peripheral SpA (perSpA), 12–13 Periungual erythema, 304 Peroneal tendinopathy and tenosynovitis, 97–98 Photosensitive rash, 201, 203 Photosensitivity, 197 Pigmented cirrhosis, 430 Pigmented villonodular synovitis (PVN), 372 Pilocarpine, 247 Plasmacytoid dendritic cells (PDCs), 228 Pneumococcal polysaccharide, 146 Polyarteritis nodosa (PAN), 285–286 Poncet’s disease, 123 Popliteal aneurysm, 93 Popliteal cyst, 103 Popliteal synovial cysts, see Baker’s cyst Porphyromonas gingivalis, 129 Positive predictive value, 44 Positive stool alpha-1-antitrypsin, 218 Posterior ankle pain, 95–97 Posterior cruciate ligament (PCL), 91 Posterior drawer test, 92 Posterior hip pain, 88–89 Posterior knee pain, 93–94 Posterior tibial nerve, 107 Posterior tibial tendon dysfunction, 97 Posterior transverse, 102 Prednisone, 297 Prednisone taper, 443 Predominant DIP involvement disease, 155 Prepatellar bursa, 91 Prevalence, 45 Primary immunodeficiencies (PIDs), 434–435 Probenecid, 358, 361, 362 Procedure bias, 46 Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION) trial, 63 Prostaglandin E2 (PGE2), 24 Prosthetic joint infections, 117–118 Proximal hamstring tendinopathy, 89 Index Pruritus, 305 Psoriatic arthritis (PsA), 154, 168 clinical features, 154–158 comorbidities, 162 differential diagnosis, 162, 163 epidemiology and disease burden, 154 laboratory tests, 159 magnetic resonance imaging, 161–162 MRI of the SI joints with contrast, 169 musculoskeletal ultrasound, 161 outcomes, 166 pathogenesis, 162–164 plain X ray, 159–161 prevalence, 154 treatment, 164–166 Psoriatic arthritis (psJIA), 402 Pulmonary arterial hypertension (PAH), 270 Pulmonary artery aneurysms, 298 Pulmonary function testing (PFT), 265, 307 Pulmonary hypertension (PH), 265–266 Pyogenic arthritis pyoderma gangrenosum and cystic acne syndrome (PAPAs), 454 Q Quantitative CT Scan (QCT), 326 R Radiography, 61 Randomized controlled design, 42, 45–46 Range, 40 RANK Ligand (RANKL), 6–7, 323 Raynaud’s phenomenon (RP), 264, 270 Recall bias, 45 Rectus femoris tendinopathy, 88 Regional musculoskeletal pain, 77 acromioclavicular joint, 80 adhesive capsulitis/frozen shoulder, 80 ankle, 95 anterior hip pain, 86 anterior knee pain, 90 biceps tendon pathology, 78 elbow pain, 82 full thickness supraspinatus tendon tear, 79 glenohumeral joint, 80 impingement syndrome, 78–80 knee, 94 lateral hip pain, 89 lower limb, 86–99 posterior hip pain, 88–89 prepatellar bursa, 91 rectus femoris tendinopathy, 88 rotator cuff tears, 78–80 shoulder pain, 77–78 475 snapping hip syndrome, 86–88 subacromial-subdeltoid bursa, 81 upper limb, 77–86 Renal biopsy, 209 Renal colic, 247 Renal disorder, 198 Renal osteodystrophy, 428–429 Renal stones, 364 Retrocalcaneal bursa, 97 Rheumatic diseases, and malignancy, 435–437 Rheumatic gout, Rheumatoid arthritis (RA), 368 ACPA-driven osteoclasogenesis, autoantibodies, 2–3 autoimmunity, 3–4 bone loss, 22 cigarette smoking, 5–6 clinical presentation, 132–135 co-morbidities and prognosis, 141 cytokine network and hierarchy, cytokine perturbations, 130 cytokine-driven osteoclastogenesis, 6–7 diagnosis, 131–132 differential diagnosis, 132 early, environmental triggers, 128–129 epidemiology, 127 established, extra-articular manifestations, 134 fibroblast-like synoviocytes, 8–9, 22 genetic inheritance, 127–128 genome-wide association studies, 5, 128 historical perspective, HLA-association, 4–5 inflammation-driven inhibition of osteoblasts, 7–8 influenza vaccination, 149 laboratory findings, 135 lung and, 21 median and interquartile range, 40 pathogenesis, 10 pathogenetic concepts, pathophysiology, 127 phases, preclinical phase, preoperative assessment, 143 2010 RA classification criteria, 131 radiographic hallmarks, 135–136 serologic evidence of autoimmunity, 129 seronegative, 1, seropositive, 1, synovial histopathology, 130 synovial joints, 9–11 therapeutic agents, 138–139 treatment, 136–137 476 Rheumatoid factor (RF), 129, 402 Rheumatoid nodules, 133, 146 Rheumatology, clinical epidemiology in, 37–49 Rhomboid-shaped crystals, 371 Risankizumab, 23 Rituxan, 144 Rituximab, 139, 140, 211 Rotator cuff (RC), 81 Rotator cuff impingement syndrome, 106 Rotator cuff tears, 78–80 Routine Assessment Patient Index Data (RAPID) scores, 137 S Salivary gland biopsy, 230–234 Sarcoidosis, 47–48, 435, 438–439 Scapular winging, 306 Scarring discoid alopecia, 201 Schirmer test, 236 Schober’s test, 178 Scintigraphy, 252 Scleredema, 269, 273, 308 Scleroderma renal crisis (SRC), 267–268, 271, 272 Sclerodermatous chronic graft-versus-host disease (scGVHD), 269 Scleromyxedema, 269, 274 Second hit hypothesis, 9–11 Secukinumab, 21, 23, 165, 188, 190 Segmental arterial mediolysis, 296 Selection/sampling bias, 45 Senescence-associated secretory phenotype (SASP), 55 Sensitivity, 44 Septic arthritis acute Lyme arthritis, 116 antibiotic therapy, 118 chikungunya virus, 116 clinical manifestations, 112–113 diabetes and, 122 diagnosis, 112–113 drainage, 118 fungal infections, 115 gonococcal infection, 114 gram negative enteric organisms, 114 microbiology, 113–117 mycobacterium, 115 parvovirus, 115–116 pathogenesis, 112, 113 prognosis and complications, 118 Staphylococcus, 113 Streptococcus, 114 Index treatment, 118 Seronegative spondyloarthritis, 153 Serositis, 197, 206 Serum ferritin, 370 Serum tissue transglutaminase, 218 Shared epitope, 4, 128 Shawl sign, 304 Short tau inversion recovery (STIR), 309 Shoulder pain, 77–78 Shrinking lung syndrome, 213 Sialography, 235, 252 Sickle cell disease (SCD), 433–434, 440 Single nucleotide polymorphism (SNP), 13, 56 Sjögren’s syndrome (SS), 209, 225 autoantibodies, 231–233 classification, 229, 249 clinical manifestations, 238–240 diagnostic tests, 251 differential diagnosis, 228, 230, 244 disease activity indexes, 238 disease management, 238–240 epidemiology, 226 etiopathogenesis, 226–228 etiopathogenetic events, 252 extraglandular features, 239 extra-glandular manifestations, 241 glandular manifestations, 240 laboratory tests, 228–230 lymphomagenesis, 240–244 lymphoproliferation, 240–244, 248 non-MHC class genes with, 227 ocular dryness, 245 ocular tests, 236–238 oral dryness, 246 oral involvement assessment tests, 235–236 pathogenesis, 226, 245 predictive score tool, 250 prevalence, 227, 231–233 primary and secondary, 226 salivary gland biopsy, 230–234 symptoms, 248 therapeutic strategies, 247 vascular inflammation, 280 Skin and musculoskeletal disease, 270 Skin psoriasis, 167, 169 Skin thickening, 264 Small intestinal bacterial overgrowth (SIBO), 267 Small-vessel digital vasculitis, 201 Snapping hip syndrome, 86–88 Specificity, 44 Spondyloarthritis (SpA), 181 abnormal bone formation, 18–21 Index arthritogenic antigens, 14–15 axial, 175, 178 biologic DMARDs, 181 clinical trials, 11 clinicopathologic hallmarks, 12 comorbidities, 182–183 conventional synthetic DMARDs, 180 diagnosis, 177–178 differential diagnosis, 180 disease monitoring, 182 emergent neurosurgery evaluation, 186 endotypes, 11, 12 epidemiology, 177 epithelial barrier disruption, 16 etiology, 176 fine mapping, 13 genetic landscape, 13–14 gut-joint axis, 16–17 HLA-B27, 14–16, 187 homodimerization hypothesis, 15 imaging, 179 inflammation, 18–21 inflammatory phase, 19 lab testing, 179 mechanical stress, 18–21 misfolding hypothesis, 15 MRI, 179, 184 NSAID, 180, 186 pathogenetic themes, 14 pathophysiology, 176 patient history, 178 peripheral, 178 peripheral joint, 175 physical exam, 178 physical therapy, 182 prognosis, 183 spectrum of, 12–13 target-specific DMARDs, 181–182 TNF, 18 treatment, 180–182 type inflammation, 11, 13, 17–18 Spondyloarthropathy, 177, 179, 438 Squamous cell carcinoma, 217 Standard deviation (SD), 41 Staphylococcus, 113 Stinchfield test, 87 Straight leg raise, 87 Streptococcus, 114 Subacromial-subdeltoid (SA-SD) bursa, 81, 104 Subacute cutaneous lupus erythematosus (SCLE), 201, 204 Subchondral bone, 55 Subluxation, 103 Subtalar joint, 99 477 Sulfasalazine, 138 Symmetric polyarthritis, 155 Synovial fluid, 122, 135 Synovial histopathology, 130 Synovial joints, 9–11 Synovitis, 184, 431 Synovium, 55 Systemic juvenile idiopathic arthritis (sJIA) autoantibody, 408 clinical features, 407 diagnosis, 406, 408 pathology and pathogenesis, 407 symptoms, 408 treatment, 407 Systemic lupus erythematosus (SLE), 200, 209 autoantibodies, 200 classification criteria, 196–199 demographics and epidemiology, 195–196 drug-induced, 199–200 environmental factors, 196 fertility, 213 genetics role in, 196 hydroxychloroquine, 210 idiopathic inflammatory myopathies, 308 malar rash, 203 medication, 210–212 medications, 210–211 mortality, 212 mucocutaneous manifestations of, 201 NSAIDs, 210 oral or nasal ulcers, 205 photosensitive rash, 203 pregnancy and reproductive effects, 209–210 primary immunodeficiencies, 434 SELENA trial, 209 vasculopathy in, 280 Systemic sclerosis (SSc), 263, 281 cardiac manifestations, 266–267 classification, 268 cutaneous and musculoskeletal manifestations, 264–265 diagnosis, 268 differential diagnosis, 274 etiology, 263–264 gastrointestinal tract manifestations, 267 interstitial lung disease, 272 pathogenesis, 263–264, 273 prognosis, 269–270 pulmonary manifestations, 265–266 scleroderma renal crisis, 267–268 sings, 273 skin thickening, 265 treatment, 270–272 vasculopathic manifestations, 272 478 T Takayasu’s arteritis, 283–284 Talocalcaneal joint, see Subtalar joint Talocalcaneonavicular joint, see Subtalar joint Target-specific DMARDs, 181–182 Tarsal tunnel syndrome, 98–99, 107 Telangiectasias, 264 Tendon friction rubs, 264 Tennis elbow, 82 Tennis leg, 93 Teriparatide, 331, 336 Thalassemia, 432 Thomas test, 87 Thompson test, 96 Thrombocytopenia, 206 Tibial tuberosity (TT), 90 Tocilizumab, 139, 140, 150 Tofacitinib, 139, 140, 144, 148–150, 165 Toll-like receptors (TLRs), 55 Transferrin saturation, 370 Transporters of antigen processing (TAP), 15 Transverse myelitis (TM), 219 Trauma, 57 Trendelenburg test, 87 Trigger finger, 85–86 Trochanteric bursitis, 89, 100 Tropheryma whippelii, 117, 192 Tumor necrosis factor (TNF) antagonist, 138 inhibition, 140 spondyloarthritis, 18 Tumor necrosis factor-alpha (TNF alpha), 55 Tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS), 383–384, 397, 451 Tylenol, 167 Index V Valgus displacement injures, 91 Valgus stress test, 92, 93 Vasculitis, 277 chest CT angiography, 293 diagnosis of, 278–279 diagnostic consideration, 277–278 giant cell arteritis, 283 histology, 278–279 IL-6, 292 imaging, 279–280 large vessel vasculitis, 282–285 manifestations, 280 medium vessel vasculitis, 285–286 minocycline acne therapy, 293 paraneoplastic, 281 primary, 282 primary immunodeficiencies, 435 secondary causes of, 280–281 single organ vasculitis, 290 small vessel vasculitis, 287–290 Vasculitis mimics, 278 Viral arthritis, 115 V-sign, 304 W Water-based exercise, 66 Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), 38, 39 Whipple’s disease, 117, 192 Whole genome sequencing (WGS), 450 Wilson’s disease (WD), 430 Wrist-to-forearm ratio (WFR), 83, 102 X Xerostomia, 225 U Ulnar nerve entrapment, 82–83 Ultrasound guided parotid biopsy, 297 Urate-lowering therapy, 358 Ureaplasma, 117 Urine drug screen, 296 Ustekinumab, 23, 165, 167 Uveitis, 403 Y Yao syndrome (YAOS), 387–389, 397 Z Zika virus, 292 .. .Absolute Rheumatology Review Petros Efthimiou Editor Absolute Rheumatology Review Editor Petros Efthimiou New York University New York, NY USA ISBN 97 8-3 -0 3 0-2 302 1-0 ISBN 97 8-3 -0 3 0-2 302 2-7 (eBook)... IL-23 and IL-17 in SpA: (a) Inflammation in axial skeleton is IL-17-dependent but IL-23-independent (b) Inflammation in peripheral skeleton and skin (psoriasis) is IL-1 7- and IL-23-dependent (c)... are SpA-predisposing variants (e.g., HLA-B27: 05, HLA-B27:02, HLA- B27:04, HLA-B27:07, HLA-B27:03, and HLA-B27:10) and variants with neutral or even protective impact (e.g., HLA-B27:06, HLA-B27:09)