Healio Rheuminations

The second episode in the series delves into the experiments and observations of Dr. Clemens (Baron) von Pirquet who first proposed that antibodies and antigens join forces to wreak havoc.  Brought to you by GSK. Intro :10 Today’s episode :26 A recap of the previous episode :43 About Baron von Pirquet 4:40 What’s going on in the study of infectious disease and immunology in the early 1900s? 6:41 Writing the paper, “Serum Sickness” 13:13 What are the antibodies doing at that time? 19:10 What happened to Dr. Pirquet? 20:44 Pirquet’s medical student, Bela Schick 25:35 Episode wrap-up 27:27 The next episode 27:56 Thanks again for listening! 29:17 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: Shulman ST. J Pediatric Infect Dis Soc. 2017;6:376-379. Silverstein AM. Nat Immunol. 2000;1:453-455.

This episode delves into the clinical presentation of serum sickness along with a dash of Arthus reaction, to boot! Brought to you by GSK. Intro :10 Today’s episode :26 Let’s get into some cases 4:11 The Arthus reaction 6:06 What is another example of the same thing happening but on a systemic level? 7:25 Breaking down the clinical features of serum sickness 14:20 How confident are we that the compliment levels always drop? 16:26 How common is serum sickness? 19:45 The mechanistics of rituximab 21:36 A preview of parts two and three 27:37 Episode wrap-up 28:38   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: Bayer G, et al. Eur J Intern Med. 2019;67:59-64. Karmacharya P, et al. Semin Arthritis Rheum. 2015;35-334-340. Lawley TJ, et al. J Invest Dermatol. 1985;85:129s-132s.

Why is hemochromatosis so common? What is iron actually doing to the joint? Does phlebotomy help? What’s going on with iron and Popeye? These are the questions we tackle in the second episode of hemochromatosis: Iron and Bone! Brought to you by GSK. Intro :19 Today’s episode :29 Why is hemochromatosis so common? 1:06 The history of Popeye the Sailor Man 3:37 Treatment with phlebotomy 8:35 Why doesn’t join pain improve? 12:03 What is Kashin-Beck disease? 14:18 Mouse studies from the 1970s 19:45 What about histology? 25:36 Episode wrap-up 28:34 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: Adams PC, et al. Hepatology. 1997;25:162-166. Adams PC, et al. N Engl J Med. 2005;352:1769-1778. Brighton CT, et al. Arthritis Rheum. 1970;13:849-857. Heiland GR, et al. Ann Rheum Dis. 2010;69:1214-1219. Hiyeda, K. Jap Med Sci. 1939;4:91-106. Powell LW, et al. Lancet. 2016;388:706-716. Rametta R, et al. Int J Mol Sci. 2020;21:3505. Sella EJ, Goodman AH. J Bone Joint Surg Am. 1973;55:1077-1081. Sutton M. Internet Journal of Criminology. 2010;1-34.

In this episode, we dig into hemochromatosis to better understand what it is, how it affects the joints, available screening methods, as well as clues to presentation and physical exam findings. Brought to you by GSK. Intro :10 Today’s episode :26 What is hemochromatosis? 1:42 What does the iron do? 3:03 How much iron is in the body? 5:30 When do you suspect it? 7:46 What do we want to know about the joints? 9:33 About Ralph Schumacher Jr., MD, and his work 12:15 How have Schumacher’s observations held up? 14:42 What about radiographs … can they help? 16:09 What about hand OA and the gene mutation? 16:44 So, what about people with undiagnosed hemochromatosis? What do their hands look like? 18:09 What about chondrocalcinosis? 19:13 Tune in next time for part two 21:59 Episode wrap-up 22:25 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: Bulaj ZJ, et al. N Engl J Med. 2000;343:1529-1535. Carroll GJ, et al. Arthritis Care Res. 2012;64:9-14. Hamilton EB, et al. Q J Med 1981;199:321–329. Jordan JM. Curr Opin Rheumatol. 2004;16:62-66. Rametta R, et al. Int J Mol Sci. 2020;21:3505. Ross JM, et al. J Rheumatol. 2003;30:121-5. Schumacher HR. Arthritis Rheum. 1964;7:41–50. Timms AE, et al. Ann Rheum Dis. 2002;61:745–747. Ulvik RJ. Tidsskr Nor Laegeforen. 2016;136:2017-2021.

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