This interview with Chester V. Oddis, MD, will have you standing from a seated position without the need to use your arms as we discuss the inflammatory myopathies. We cover the classification, pathophysiology and treatment approaches to these diseases, as well as all the antibodies you must learn about for boards! Intro :20 The interview 1:05 How did you become involved in inflammatory myopathies? 1:12 What’s your approach to a patient with suspected inflammatory myopathy? 1:50 What’s your opinion on the pathogenesis of these antibodies? 6:20 Any pearls for muscle biopsy? 9:30 Brought to you by GSK. Consider the long-term impact of disease activity, flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com Any pearls for reading EMGs? 12:20 What should we look for once we have a biopsy? 14:16 What do we know from a cytokine perspective? 17:52 Where do you think we’ll be with inflammatory myopathies in 10 years? 21:50 Thank you, Dr. Oddis 24:12 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com. Disclosures: Brown reports no relevant financial disclosures. Oddis reports receiving clinical trial support from Corbus Pharmaceuticals and Genentech. Chester V. Oddis, MD, is professor of medicine and director of the Myositis Center in the division of rheumatology and clinical immunology at University of Pittsburgh Department of Medicine.

Things get a little nerdy in this episode, which focuses on the basic science of what makes the inflammasome tick in CAPS, as well as data on the use of interleukin 1 inhibition. Hint: Listen to “The Inflammasome for Dunces” episode first, and this one will make more sense. Intro :20 Recap of Part 1 :33 Overview of this episode 1:56 Familial cold autoinflammatory syndrome 3:04 Muckle-Wells syndrome 6:34 The two checkpoint problem 8:36 What do we know about the inhibition of the inflammasome? 11:13 Back to the trebuchet analogy 11:48 Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com A paper on CARD8 in the setting of CAPS 13:50 Let’s talk about prostaglandins 15:27 There are over 100 mutations in CAPS 18:15 Let’s talk about treatment 18:42 One caveat 25:41 That’s CAPS 26:45 Reach out to me via email and on Twitter 27:03 Episode recap 27:41 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum Brought to you by GSK. Consider the long-term impact of disease activity, flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com. Disclosure: Brown reports no relevant financial disclosures. References: Agostini L, et al. Immunity. 2004;20:319-325. Brogan PA, et al. Arthritis Rheum. 2019;71:1955-1963. Marsaud C, et al. J Rheumatol. 2014;41:1721-1722. Hawkins PN, et al. NEJM. 2003;348:2583-2584. Hoffman HM, et al. Lancet. 2004;364:1779-1785. Hoffman HM, et al. Clin Ther. 2012;34:2091-2103. Ito S, et al. Arthritis Res Ther. 2014;16:doi:10.1186/ar4483. Kuemmerle-Deschner JB, et al. Ann Rheum Dis. 2011;70:2095-2102. Lachmann HJ, et al. NEJM. 2009;360:2416-2425. Mamoudjy N, et al. Orphanet J Rare Dis. 2017;12:doi:10.1186/s13023-017-0589-1. Rosengren S, et al. J Allergy Clin Immunol. 2007;119:991-996. Ross JB, et al. J Cutan Med Surg. 2008;12:8-16. Tassi S, et al. Proc Natl Acad Sci USA. 2010;107:9789-9794. Thornton BD, et al. Am J Kidney Dis. 2007;49:477-481.

This first episode delves into the clinical aspects of the Cryopyrin-Associated Periodic Syndromes and includes some helpful tips for sorting out some of the autoinflammatory diseases in the spectrum. Intro :10 Cryopyrin-Associated Periodic Syndromes (CAPS) :25 Outline of Part 1 2:25 What is CAPS? 3:12 Case #1 – a 25-year-old female with urticaria after cold exposure 4:25 Case #2 – a 55-year-old female with progressive deafness 5:45 The index case of familial cold autoinflammatory syndrome 9:00 The final disease in the spectrum 11:00 A lot of names for the same disease 13:50 Genetics prove these three diseases are in the same spectrum 14:22 Over 100 mutations have been found to-date 16:31 Let’s talk about mosaicism 17:03 Disease characteristics of CAPS 18:15 Neutrophilic infiltrate in chronic urticaria vs. CAPS 20:00 Schnitzler syndrome 20:45 Sensorineural hearing loss 21:58 Joint pain 24:10 Complication: Amyloidosis 25:29 These diseases were very debilitating 28:38 Episode recap 29:46 Part 2 sneak peek 30:38 Come say hi at ACR! 30:51 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Ahmadi N, et al. Otolaryngol Head Neck Surg. 2011;145:295-302.​ Aksentijevich I, et al. Arthritis Rheum. 2002;46:3340-3348. Alecu M, et al. Romanian Journal of Morphology and Embryology = Revue Roumaine de Morphologie et Embryologie. 2015;56:7-14. Hassink SG, Goldsmith DP. Arthritis Rheum. 1983;26:668–673. Hoffman HM, et al. Nat Genet. 2001;29:301-305.​ Hoffman HM, et al. J Allergy Clin Immunol. 2001;108:615-620. Kile RM, Rusk HA. JAMA. 1940;114:1067-1068. Levy R, et al. Ann Rheum Dis. 2015;74:2043-2049. Marzano AV, et al. Clin Exp Rheumatol. 2018;36 Suppl 110:32-38. Muckle TJ, Wells M. Q J Med. 1962;31:235-248. Prieur AM, Griscelli C. Rev Rhum Mal Osteoartic. 1980;47:645–649. Tran TA. Open Access Rheumatol. 2017;9:123-129.

A quick take on one of the little-appreciated engines of the innate immune system.  Intro :10 A little about this episode :25 The inflammasome is a component of the innate immune system 3:12 Remember NLRP3 4:12 The toll-like receptors 5:05 Triggering the inflammasome 7:05 The proteins 8:04 A medieval battle and a trebuchet 9:56 A disclosure 17:00 I hope you enjoyed this episode 18:06 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Booshehri LM, Hoffman HM. J Clin Immunol. 2019;39:277-286. Hasudungan A. Immunology – NOD like receptors and the inflammasome [Video]. YouTube. https://www.youtube.com/watch?v=biunM2iD8qM&t=4s. Published March 29, 2015. Accessed September 4, 2019.

“Acute rheumatic fever is proceeded by an infection with Group A strep” is a mantra that all health care workers know. This episode digs through the history of how we came to understand this fact, as well as how our understanding of the pathophysiology and treatment of rheumatic fever developed. Intro :10 Why I made this episode :30 Outline of this episode 1:55 Rheumatic fever was really bad 3:10 The early 1700s 4:10 A big leap 6:15 The Jones criteria 11:07 History of the bacteriology 14:23 The heroic ASO titre 20:51 Rheuminations is powered by Healio 21:40 Another breakthrough: penicillin 21:51 Not all group A strep is the same 25:06 The decline of rheumatic fever 25:56 What about the host? 29:30 The joints 38:56 Summary 40:28 Never appreciated how bad rheumatic fever was 42:18 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: A History of Medical Bacteriology and Immunology, First Edition, Butterworth-Heinemann, Oxford, 1970. Aspinall GO, et al. Infect Immun. 1994;62:2122-2125. Carapetis JR, et al. Nat Rev Dis Primer. 2016;doi:10.1038/nrdp.2015.84. Cox CJ, et al. J Immunol. 2013;doi:10.4049/jimmunol.1102592. Engel ME, et al. PLoS One. 2011;6:e25326. FW Denny, et al. JAMA. 1950;143:151-153. Gray LA, et al. J Infect Dis. 2017;216:1460-1470. Kaplan MH, et al. Lancet. 1962;1:706-710. Karthikeyan G, Guilherme L. Lancet. 2018;392:161-174. Khandke KM, et al. J Exp Med. 1987;doi:10.1084/jem.166.1.151. Paul O, et al. Clin Cardiol. 1990;13:367-369. Quinn A, et al. Infect Immun. 2001;69:4072-4078. Robertson KA, et al. BMC Cardiovasc Disord. 2005;5:11. Rojas Manuel, et al. J Autoimmun; 2018;95:100-123. Tandon R, et al. Nat Rev Cardiol. 2013;10:171-177.

Join me as I explore a case of fever and migratory inflammatory arthritis, then discuss the case with the double-boarded rheumatologist/infectious disease expert, Cassandra Calabrese, DO. Intro :10 My new book :24 Inside this episode 1:20 Case presentation 1:38 Introducing Dr. Cassandra Calabrese 9:22 The interview 10:40 Was the patient’s presentation typical for rheumatic fever? 10:58 Do most rheumatic fever cases have migratory arthritis? 13:23 How different is this from reactive arthritis? 15:42 What’s the deal with aspirin in this condition? 17:26 What are the skin manifestations? 18:19 Tell us about Sydenham chorea 20:23 What’s the difference between valvulitis and carditis? 22:07 Tell us about heart disease and recurrence 23:13 Can you talk about rheumatic fever recurrence? 24:32 Continuous prophylaxis 25:41 Can you walk us through the ASO (antistreptolysin O) titer? 26:20 How long is this on the differential? 28:38 Summary of our discussion 29:43 Thank you, Dr. Calabrese 32:18 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum Cassandra Calabrese, DO, is a rheumatologist in the department of rheumatic and immunologic disease and the department of infectious disease at Cleveland Clinic.

John Stone, MD, MPH, is the world leader in the field of IgG4-related disease research. In this episode, he breaks down the histology of IgG4-related disease, important aspects of what is known about the pathophysiology of the disease, as well as future directions in treatment. Intro :10 Inside this episode :13 IgG4-related disease background :31 An anecdote 1:15 The interview 4:09 History of IgG4-related disease 4:18 IgG4 pathology and terms 7:48 What makes IgG4 different from other IgG subclasses? 10:23 What do we know about the interplay between B and T cells? 12:31 What is SLAMF7? 16:30 What happens to T cells during B-cell depletion? 18:22 Antigens involved in IgG4 21:06 Future of treatment 23:10 Thank you, Dr. Stone 24:32 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum John Stone, MD, MPH, is director of clinical rheumatology at Massachusetts General Hospital.

In this episode, James Rosenbaum, MD, an expert in inflammatory eye disease, breaks down how systemic autoimmune conditions can affect the eye and highlights pearls that Rheumatologists should know. Intro :10 Inside this episode :15 Introducing Dr. Jim Rosenbaum :51 The interview 1:26 Some basic terms 1:45 TEON pneumonic 5:45 Microbiome work 7:06 Evaluation of inflammatory eye disease 9:01 Workup for inflammatory eye disease 10:23 How do ophthalmologists rule out infection? 18:00 Is there anatomic overlay between the eye and joints? 23:10 A pen light and history 25:30 Treatment algorithm 27:27 What excites you the most about the future of inflammatory eye disease? 33:31 Thank you, Dr. Rosenbaum 37:03 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum James T. Rosenbaum, MD, is professor of ophthalmology, medicine and cell biology; head of the division of arthritis and rheumatic diseases and Edward E. Rosenbaum Professor of Inflammation Research at Oregon Health and Science University.

We journey into the world of metabolic bone in this episode and explore the varied clinical manifestations of hypophosphatasia. We also interview the head of the center for osteoporosis and metabolic bone disease at the Cleveland Clinic, Chad Deal, MD. Intro :10 The four H’s of chondrocalcinosis :18 What we’ll cover in this episode :52 A general overview 2:33 The first description of hypophosphatasia 3:39 History of this condition 13:00 Two cases 16:00 The interview 17:55 Various presentations 18:42 Laboratory findings 21:13 Differentiating the terminology 24:55 The relationship between this and chondrocalcinosis 27:11 Mechanisms of pain 28:15 Treatment options 29:30 Thank you, Dr. Deal 38:00 Episode recap 38:10 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Linglart A, Biosee-Duplan M. Curr Osteoporos Rep. 2016;14:95-105. Rathbun JC. Am J Dis Child. 1948;75:822-831. Robison R. Biochem J. 1923;17:286–293. Turan S, et al. J Clin Res Pediatr Endocrinol. 2011;3:7-11. Whyte MP. Bone. 2017;102:15-25.

This ripping yarn delves into the history of tumor necrosis factor in relation to rheumatoid arthritis with emphasis on the original studies that set the stage for the use of TNF inhibition in RA.  Intro :11 What we’ll cover here :16 Recap of Part 1 1:25 What I discovered when doing this episode 1:22 What this episode won’t address 2:40 Let the tale begin 3:12 A look at matrix metalloproteinases 3:32 A breakthrough in understanding RA 6:28 Two key players: Dr. Mark Feldman and Dr. Ravinder Maini 6:53 The first cytokine research conducted in RA: IL-1 8:00 The next cytokine: Tumor necrosis factor 11:16 What do we know about cytokine production within the joint? 14:33 IL-6 and TGF-beta 19:16 A bit about IL-10 23:57 *Visit Healio.com/rheum for daily news and updates* How do we choose which cytokines to block to make improvements in RA? 25:16 What about in vivo data? 29:45 The history of infliximab 34:00 Infliximab is approved for RA treatment 45:13 TNF in RA: from bedside, to bench then back to bedside 46:06 It’s important to recognize the researchers who discovered these pathways 46:18 Remember the scientists next time you prescribe a TNF inhibitor 47:05 Read the latest news and commentary on Healio.com/rheumatology and Follow us on Twitter @HealioRheum and @HRheuminations for updates 47:34 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Brennan FM, et al. J Autoimmun. 1989;2 Suppl:177-186. Brennan FM, et al. Lancet. 1989;2:244-247. Butler MD, et al. Eur Cytokine Netw. 1995;6:225-230. Chu CQ, et al. Arthritis Rheum. 1991;34:1125-1132. Dayer JM, et al. J Exp Med. 1985;162:2163-2168. Di Giovine FS, et al. Ann Rheum Dis. 1988;47:768-772. Feldmann, M. Nat Rev Immunol. 2002;2:364-371. Feldmann M, Maini SR. Immunol Rev. 2008;223:7-19. Fontana A, et al. Rheumatol Int. 1982;2:49-53. Haworth C, et al. Eur J Immunol. 1991;21:2575-9. Houssiau FA, et al. Arthritis Rheum. 1988;31:784-8. Keffer J, et al. EMBO J. 1991;10:4025-4031. Kulkarni AB, Karlsson S. Am J Pathol. 1993;143:3-9. Kuruvilla AP, et al. PNAS. 1991;88:2918-2921. Maini RN, et al. Arthritis Rheum. 1998;41:1552-1563. Malaviya AN, Mehra NK. Indian J Med Res. 2018;148:263–278. McInnes IB, Schett G. Nat Rev Immunol. 2007;7:429-442. Mitchison NA, Medawar PB. Proc R Soc Lond [Biol]. 1964;https://doi.org/10.1098/rspb.1964.0093. Pettipher ER, et al. Proc Natl Acad Sci U S A. 1986;83:8749-8753. The Beautiful Cure: The Revolution in Immunology and What It Means for Your Health, University of Chicago Press, Chicago, 2018. Williams RO, et al. Proc Natl Acad Sci U S A. 1992;89:9784-9788. Xu WD, et al. J Clin Invest. 1989;83:876-882.