Healio Rheuminations

In this episode, I interview the NIH team who brought you VEXAS! Hear different points of view of this disease, how it was discovered, clinical presentations, as well as where this research could lead. Then, we wrap up with Dr. Kastner’s historical take on autoinflammatory disorders! Intro :11 In this episode :12 Big thanks to Peter Grayson, MD, MSc 2:07 About our guests 2:30 The interview 5:10 How did VEXAS come about? 5:37 You had an idea of where to start looking? 6:58 What should rheumatologists know about ‘somatic mutation’? 12:31 Do you think this could be a clue to other conditions? 13:37 Can you tell us about some of the unique aspects that we see in these patients with MDS that make them atypical? 17:14 How’s the clinician going to see or note the vacuoles? 18:53 Do we have kind of a pathway for how the vacuoles are forming based on what we know about ubiquitization or is that unclear? 20:51 What’s going to raise the antenna that this isn’t “run of the mill x disease”? 23:33 How, in your experience, have patients responded to diagnoses being changed? 37:15 Where does everyone see the therapy going for this condition in the future? 41:15 Do we think that with this approach that this is going to “reshuffle the deck” of what we call certain diseases from multiple different specialties over the next decade? 44:02 Would you mind walking us through a little bit about FMF and how the different variants you saw led to further discoveries? 49:46 What was known about IL1 at the time? How did that knowledge of IL1 come along? 52:53 It’s such a true honor to have you all on 57:42 David Beck, MD, PhD, is a genetics fellow at the NIH. He can be reached at david.beck@nih.gov. Marcella A. Ferrada, MD, is Lawrence Shulman scholar at NIAMS. She can be reached at ferradama@mail.nih.gov. Peter Grayson, MD, MSc, is head of the Vasculitis Translational Research Program at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and associate director of the NIAMS fellowship program. He can be reached at peter.grayson@nih.gov. Dan Kastner, MD, PhD, is an NIH distinguished investigator in the Metabolic, Cardiovascular and Inflammatory Disease Genomics Branch; director in the Division of Intramural Research; and head of the Inflammatory Skin Disease Section at the National Human Genome Research Institute. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum Disclosures: Beck, Brown, Ferrada, Grayson and Kastner report no relevant financial disclosures.

In this episode, we delve into Parvovirus B19: What does it do? How does it affect the joints? How was it discovered? Does it only infect young female schoolteachers? Find out! Brought to you by Actemra Intro :12 Shout out to Cleveland Clinic Biologic Therapies Summit 1:22 In this episode 2:11 An overview of the virus 3:46 What causes the aplastic crisis? 6:16 What does the virus do in humans? 11:46 A two-phase trial on young adults 14:29 A summary of studies 18:55 So, what happens to these patients? 22:59 How about a long-term study? 24:39 Summing up Parvovirus 19 26:42 The big takeaway from this episode 27:33 The next episode 28:06 Disclosures: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Anderson MJ, et al. J Infect Dis. 1985;152:257-265. Chorba T, et al. J Infect Dis. 1986;154:383-393. Moore TL. Curr Opin Rheumatol. 2000;12:289-294. Mortimer PP. Nature. 1983;302:426-429. Ogawa E, et al. J Infect Chemother. 2008;14:377-382. Potter CG. J Clin Invest. 1987;79:1486-1492. Reid DM, et al. Lancet. 1985;1:422-425. Speyer I, et al. Clin Exp Rheumatol. 1998;16:576-578. Takahashi Y, et al. Proc Natl Acad Sci USA. 1998;95:8227-8232. White DG, et al. Lancet. 1985;1:419-421. Young N, et al. J Clin Invest. 1984;74:2024-2032. Young NS, Brown KE. N Engl J Med. 2004;350:586-597.

This episode details how psoriatic arthritis and the spondyloarthropathies came to be recognized as a distinct clinical entity after decades of nerdy arguing. Brought to you by Actemra. Intro :10 Shout out to Cleveland Clinic Biologic Therapies Summit :30 In this episode 1:29 A 30,000-foot view 2:34 When did PsA separate from rheumatoid arthritis? 3:34 Mary Stults Sherman 7:11 Verna Wright and Dr. John Moll put PsA on the map 9:09 Recognizing PsA as a disease 15:20 An anecdote about Wright 16:18 Putting the SpA puzzle pieces together 18:19 The severity of disease 19:08 Episode wrap-up 20:46 Disclosures: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Ankylosing Spondylitis, Churchill Livingstone, Edinburgh, London, Melbourne, New York, 1980. Espinoza LR, Helliwell P. Clinical Rheumatology. 2014;33:1335-1336. Gladman DD, et al. Q J Med. 1987;62:127-141. Kane D, et al. Rheumatology. 2003;42:1460-1468. Moll JMH. Reumatismo. 2007;59 Suppl 1:13-18. Moll JM, Wright V. Semin Arthritis Rheum. 1973;3:55-78. Seronegative polyarthritis, North-Holland Pub. Co., New York, Amsterdam, 1976. Sound effects obtained from https://www.zapsplat.com Wright V. Am J Med. 1959;27:454-462. Wright V. Ann Rheum Dis. 1956;15:348-356. Wright V. BMJ. 1994;309:1739-1740.

The final episode summarizes the human data on complement in ANCA vasculitis, with a quick discussion of the trials of C5a receptor antagonism. Brought to you by Actemra. Intro :10 Welcome :21 Recap of previous episodes :22 In this episode 2:12 Let’s start with neutrophil data 5:24 Studies in humans 11:54 A summary of the data so far 21:20 What does all this amount to? 25:41 Trials of avacopan 28:25 Side effect profile 36:25 Thanks for listening 37:06 Disclosures: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Augusto JF, et al. PLoS One. 2016;https://doi.org/10.1371/journal.pone.0158871. Bekker P, et al. PLoS One. 2016;https://doi.org/10.1371/journal.pone.0164646. Chen SF, et al. Arthritis Res Ther. 2015;https://doi.org/10.1186/s13075-015-0656-8. Falk RJ, et al. Proc Natl Acad Sci USA. 1990;87:4115-4119. Gou SJ, et al. Clin J Am Soc Nephrol. 2013;8:1884-1891. Gou SJ, et al. Kidney Int. 2013;83:129-137. Jayne DRW, et al. J Am Soc Nephrol. 2017;28:2756-2767. Jayne DRW, et al. N Engl J Med. 2021;384:599-609. Merkel PA, et al. ACR Open Rheumatol. 2020;2:662-671. Schreiber A, et al. J Am Soc Nephrol. 2009;20:289-298. Xiao H, et al. Am J Pathol. 2007;170:52-64.

This episode walks us through the initial research that paved the way for a game changing therapeutic in ANCA vasculitis, as well as the story of how host Adam J. Brown, MD, finally learned how to spell complement. 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. Intro :10 Welcome :21 Today’s episode :24 So how did we get there? 4:18 How do we start teasing apart the effect of the complement in ANCA vasculitis? 8:13 Discussing and simplifying the mouse model 9:00 Quickly reviewing the complement cascade 12:06 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. Taking the puzzle pieces away in the mouse model 17:04 What about the next steps? 22:05 What happens when you block C5a? 25:12 CCX168: Summing up the mouse tale 28:44 In the next episode 30:20 Thanks for listening 30:46 Disclosures: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Brilland B, et al. Autoimmun Rev. 2020;19:102424. Freeley SJ, et al. J Pathol 2016;240:61-71. Haas M, Eustace JA. Kidney Int 2004;65:2145-2152. Huugen D, et al. Kidney Int 2007;71:646-654. Marder SR, et al. Arg. J Immunol. 1985;134:3325-3331. Schreiber A, et al. J Am Soc Nephrol. 2009;20:289-298. Xiao H, et al. Am J Pathol. 2007;170:52-64. Xiao H, et al. J Clin Invest 2002;110:955–963. Xiao H, et al. J Am Soc Nephrol, 2014;25:225–231.

Here I break down the confusing system that is the ire of medical learners who aim to memorize it, only to forget it later. Join me on a medieval journey that will help you visualize this complex system in a way that will stay with you. 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. Intro :10 Welcome :24 How do you explain the complement system? :44 What is the complement system? 1:39 How does it complement the adaptive immunity? 3:43 Two major aspects of the complement system 4:50 Formation of the membrane attack complex 5:21 Why is this pathway so confusing? 5:55 Why do I have to memorize all of this? 8:33 Let’s talk about the cascades themselves 11:15 Breaking down the three pathways 12:55 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. The alternative pathway – walking to the beat of its own drum 16:15 A medieval tale of the classic and lectin pathway 22:36 The tale of the alternative pathway 28:00 Summary 31:55 In the next episode 32:40 Disclosures: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Music: The Medieval Banquet by Shane Ivers - https://www.silvermansound.com

We end the year with Leonard Calabrese, DO, giving us a summary of what we’ve learned about COVID-19 from the perspective of a rheumatologist. 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. Intro :10 Calabrese introduction :24 In this episode :43 Nobody has complete control of the literature on COVID-19 1:39 What was ugly about COVID-19? 2:16 What was bad about COVID-19? 4:05 What good came from the COVID-19 pandemic? 7:07 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. The good things continued 10:20 JAK inhibitors 11:30 The best outcomes: Vaccines 14:15 Pertinent questions for the rheumatology community 16:45 Recap 20:12 Conclusion 21:41 Disclosures: Calabrese reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum

The completion of the Endocarditis for the Rheumatologist trilogy! This episode focuses on the glomerulonephritis of endocarditis as well as the immunologic abnormalities you can see on labs. 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. Intro :11 In this episode :22 Recap of previous episodes :39 About episode three 1:00 How labs can give a clue to endocarditis being a culprit 1:23 The immune complex nature of infective endocarditis 6:30 How do you measure immune complex? 9:10 What are the effects of immune complex formation on the organ systems? 12:37 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. Cryoglobulins and rheumatoid factor in infective endocarditis 15:12 The kidneys and infective endocarditis 16:45 Glomerulonephritis and infective endocarditis 24:15 ANCA-positive vasculitis and infective endocarditis 29:09 A summary of infective endocarditis 32:21 Takeaways 33:28 A preview of next episode 33:48 Conclusion 34:12 Disclosure: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Bayer AS, et al. N Engl J Med. 1976;295:1500-1505. Boils CL, et al. Kidney Int. 2015;87:1241-1249. Forte WC, et al. Arq Bras Cardiol. 2001;76:43-52. Hurwitz D, et al. Clin Exp Immunol. 1975;19:131-141. Langlois V, et al. Medicine (Baltimore). 2016;95:e2564. Levy RL, Hong R. Am J Med. 1973;54:645-652. Ma T-T, et al. PLoS One. 2014;9: https://doi.org/10.1371/journal.pone.0097843. Messias-Reason IL, et al. Clin Exp Immunol. 2002;127:310-315. Petersdorf RG. N Engl J Med. 1976;295:1534-1535. Spain DM, King DW. Ann Intern Med. 1952;36:1086-1089. Williams Jr RC, Kunkel HG. J Clin Invest. 1962;41:666-675. Tire squealing sound effect by Mike Koenig.

This episode focuses on the clinical aspects of endocarditis you can catch in the exam room, emphasizing the joint and skin manifestations, along with some interesting historical insights on Osler nodes and Janeway lesions. 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. Intro :11 In this episode :22 About episode two 2:28 Rheumatologic manifestations of infectious endocarditis 4:28 Musculoskeletal manifestations of infectious endocarditis in the back 5:55 The lack of patterns for infectious endocarditis causing joint pain 9:48 Myalgias and the connection with endocarditis 12:48 The skin and its connection with endocarditis 15:37 What are Janeway lesions 17:13 What are Osler nodes? 19:28 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. What causes these lesions? 21:24 Differentiating Osler’s nodes and Janeway lesions 25:20 What are splinter hemorrhages? 28:08 Petechiae and its association to infective endocarditis 31:43 What about leukocytic vasculitis? 33:17 Other puzzle pieces to look for 37:18 A preview of next episode 40:30 Conclusion 42:12 Disclosure: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Chahoud J, et al. Cardiol Rev. 2016;24:230-7. Farrior JB, Silverman ME. Chest. 1976;70:239-43. Godeau P, et al. Rev Med Interne. 1981;2:29-32. Gunson TH, Oliver GF. Australas J Dermatol. 2007;48:251-5. Heffner JE. West J Med. 1979;131:85-91. Loricera J, et al. Clin Exp Rheumatol. 2015;33:36-43. Koslow M, et al. Am J Med. 2014;S0002-9343(14)00188-0.    Murillo O, et al. Infection. 2018;46. Meyers OL, Commerford PJ. Ann of the Rheum Dis. 1977;36:517-519. Parikh SK, et al. J Am Acad Dermatol. 1996;35:767-8. Young J. et al. J R Coll Physicians Lond. 1988;22:240-3.

Infectious endocarditis can present with rheumatic features in 15% to 25% of cases. This series focuses on what a rheumatologist should know about the clinical puzzle of endocarditis. 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 Intro :11 In this episode :22 About episode one 2:33 How did people diagnose infectious endocarditis back in the day? 5:15 What is a Gulstonian Lecture? 6:25 So, who was Dr. Emanuel Libman? 13:33 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. How Gustav Mahler’s endocarditis diagnosis was made 19:15 The evolution of diagnosing endocarditis 20:45 The story of Alfred S. Reinhart and his self-diagnosis of endocarditis 21:45 Clinical signs and symptoms of endocarditis and how they hold up today 28:00 Recap and a preview of next episode 33:20 Conclusion 35:15 Disclosure: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Flegel KM. CMAJ. 2002;167:1379-1383. Harrison's Principles of Internal Medicine, Nineteenth edition, McGraw-Hill Education, New York, 2015. Levy D. Br Med J (Clin Res Ed). 1986;293:1628-1631. Libman E, Celler HL. Am J Med Sci. 1910;140. Osler W. Br Med J. 1885;1:467-470. Parsons WB Jr, et al. J Am Med Assoc. 1953;153:14-16. Pelletier LL Jr, Petersdorf RG. Medicine (Baltimore). 1977;56:287-313. Ramin S. Hektoen International. 2013;5.