Healio Rheuminations

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 [email protected]. 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 [email protected]. 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 [email protected]. 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 [email protected]. 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 [email protected]. 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 [email protected]. 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 [email protected]. 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 [email protected]. 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 [email protected]. 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.

How common is asymptomatic bowel involvement in patients with peripheral or axial SpA? Can we use NSAIDs in these patients? What's the difference between sulfasalazine and mesalamine? Listen to hear what a rheumatologist should know about IBD! 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 :20 Let's start with some basics of IBD 4:11 If a patient has axSpA, what are the chances they'll develop IBD? 5:14 What about silent disease? 7:32 When should we send our SpA patients to a GI specialist? 11:22 Two medications: budesonide and mesalamine 13:33 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 This category of drugs – 5-ASA 16:26 NSAIDs 20:02 A look at COX inhibitors 23:06 Selective inhibition with COX-2 seems to be an attractive option for IBD 28:47 Conclusion 29:10 Disclosure: Brown reports no relevant financial disclosures. We'd love to hear from you! Send your comments/questions to Dr. Brown at [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Altomonte L, et al. Clin Rheumatol. 1994;13:565-570. Dougados M, et al. Joint Bone Spine. 2011;78:598-603. de Winter JJ, et al. Arthritis Res Ther. 2016;18:196. El Miedany Y, et al. Am J Gastroenterol. 2006;101:311-317. Long MD, et al. J Clin Gastroenterol. 2016;50:152-160. Mayberry J. J Gastrointestin Liver Dis. 2013;22:375-377. Miao X-P, et al. Curr Ther Res Clin Exp. 2008;69:181-191. Mielants H, et al. J Rheumatol. 1995;22:2273-2278. Morris AJ, et al. Lancet. 1991;doi: https://doi.org/10.1016/0140-6736(91)91300-J. Redfern JS, Feldman M. Gastroenterology. 1989;96:596-605. Sandborn WJ, et al. Clin Gastroenterol Hepatol. 2006;4:203-211. Stolwijk C, et al. Ann Rheum Dis. 2015;74:65-73. Svartz N. Acta Medica Scandinavica. 1942;doi: https://doi.org/10.1111/j.0954-6820.1942.tb06841.x. Takeuchi K, et al. Clin Gastroenterol Hepatol. 2006;4:196-202. Tanaka K, et al. Eur J Pharmacol. 2008;603:120-132. Van Praet L, et al. Ann Rheum Dis. 2013;72:414-417.

The last episode in the series highlighting how the structure of the antibody was discovered, as well as how a chicken butt was critical in understanding B cell biology. 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 :15 Recap: What we know about the antibody so far 1:12 Discovering the structure of the antibody 3:34 What else can we learn about the light chain 7:04 An understanding of what these proteins were 9:49 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 story about a chicken butt 11:40 Backtracking to 1898 – where do antibodies come from? 16:49 An important paper in 1945 argues the lymphocyte is the antibody maker 18:59 Where is the bursa of Fabricius in humans? 20:46 A study from Australia 21:48 The bone marrow is what did it 23:00 Thanks for listening! 24:48 Disclosures: Brown reports no relevant financial disclosures. We'd love to hear from you! Send your comments/questions to Dr. Brown at [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Black CA. Immunol Cell Biol. 1997;doi: 10.1038/icb.1997.10. Coons AH, et al. J Exp Med. 1955;102:49-60. Cooper MD. Nat Rev Immunol. 2015;191-197. Edelman GM. J Am Chem Soc. 1959;81:3155-3156. Ehrich WE, Harris TN. Science. 1945;101:28-31. Fagraeus A. J Immunol. 1948;58:1-13. Glick B, et al. Poultry Sci. 1956;35:224-225. Osmond DG, Nossal GJ. Cell Immunol. 1974;13:132-145. Porter RR. Biochem J. 1959;73:119-126. Ryser JE, Vassalli P. J Immunol. 1974;113:719-728.

Learn about the discovery of immunodeficiencies leading to the use of pooled immunoglobulin as therapy, the struggle to use it intravenously and the eventual use in autoimmune disease. Intro :11 In this episode :15 Splitting Part 3 into two episodes :26 Part A of the history of IV Ig and the antibody :53 A recap on Cohn fractionation 2:40 The history and uses of IV Ig 4:30 What led to the recognition and research of primary immunodeficiencies 7:08 How Charles Janeway Sr. paved the way for IV Ig from intramuscular Ig 9:01 What are protein aggregates? 12:54 Understanding the various mechanisms of Ig reactions 15:49 Managing patients with low IgA and anti-IgA antibodies 18:36 How to go from treating immunodeficiency to treating autoimmunity 21:40 The modern understanding and mystery of IV Ig 25:30 Quick summary 26:05 Thanks for listening! 27:30 Disclosure: Brown reports no relevant financial disclosures. We'd love to hear from you! Send your comments/questions to Dr. Brown at [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Barandun S, et al. Vox Sang. 1962;7:157-174. Eibl MM. Immunol Allergy Clin North Am. 2008;28:737-764, viii. Furusho K, et al. Lancet. 1983;2:1359. Gallagher PE, Buckley RH. J Allergy Clin Immunol. 1982;69:120. Guo Y, et al. Front Immunol. 2018;9:1299. Imbach P, et al. Lancet. 1981;1:1228-31. Intravenous Immunoglobulin: Prevention and Treatment of Disease. NIH Consens Statement Online. 1990;8:1-23. Kustiawan I. PLoS ONE. 2018;13: e0195729. https://doi.org/10.1371/journal.pone.0195729. MRC Working Party on Hypogammaglobulinaemia. Hypogammaglobulinaemia in the United Kingdom. London: Her Majesty's Stationery Office; 1971. Oransky I. Lancet. 2003;362:409. Sandler SG, et al. Transfus Med Rev. 1995;9:1-8.

Part 2 of this series explores how we began to measure antibody levels and how serotherapy evolved and was used to investigate multiple diseases (I'm looking at you, pneumonia). We'll also learn how advances in laboratory techniques like electrophoresis paved the way for a better understanding of the antibody. Intro :11 In this episode :15 Recap of Part 1 :22 In this episode :53 The mechanism of action was theoretical 2:30 The story of convalescent serum 6:22 Pneumonia: "The captain of the men of death" 6:58 How culturing was done then 10:56 A big break: Isolating the antibody 14:26 A 30,000-foot look at pneumonia 17:13 Type 1 pneumonia trials 20:20 1918 influenza pandemic 23:31 Measles 27:59 The story of the antibody 30:30 More fun naming conventions 35:25 Cone fractionation 38:35 Quick summary 42:20 Thanks for listening! 44:27 Disclosure: Brown reports no relevant financial disclosures. We'd love to hear from you! Send your comments/questions to Dr. Brown at [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Black CA. Immunol Cell Biol. 1997;doi: 10.1038/icb.1997.10. Bullowa JGM. JAMA. 1928;90:1354-1358. Cecil RL, Sutliff WD. JAMA. 1928;91:2035-2042. Felton LD. Boston Med Surg J. 1924;190:819-825. Hooper JA. LymphoSign Journal. 2015;2 181-194. Luke TC, et al. Ann Intern Med. 2006;145:599-609. McGuire LW, Redden WR. Am J Public Health. 1918. 741-744. McKhann CF, Chu FT. Am J Dis Child. 1933;45:475-479. Podolsky SH. Am J Public Health. 2005;95:2144-2154. Podolsky SH. J R Soc Med. 2009;102:203-207. Tiselius A, Kabat EA. J Exp Med. 1939;69:119-131.

COVID-19 has brought up the use of the old remedy convalescent serum. What is it? Did it work? This series walks us through the history of the serum, how it was discovered, how it was first used, and how it inspired the field of immunology. Intro :11 In this episode :15 A quick tale :20 Outline of these three episodes 2:51 Quick definitions 3:50 How it all began 7:16 A solo paper on diphtheria 12:57 A trial of children 17:07 Giving fluids from a horse 21:57 What happened with tetanus? 25:12 Switching gears to our understanding of antibodies 27:09 The next target: snakes 29:17 The plague 32:00 Summary of Part 1, what's next 39:05 Disclosure: Brown reports no relevant financial disclosures. We'd love to hear from you! Send your comments/questions to Dr. Brown at [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Butler T. Clin Microbiol Infect. 2014;20:202-209. Crum FS. Am J Public Health. 1917;7:445. Eibl MM. Immunol Allergy Clin North Am. 2008;28:737-764, viii. Graham BS, Abrosino DM. Curr Opin HIV AIDS. 2015;10:129-134. Grundbacher FJ. Immunol Today. 1992;13:188-190. Hawgood BJ. Toxicon. 1999;37:1241-1258. Kantha SS. Keio J Med. 1991;40:35-39. Kaufmann SHE. mBio. 2017;8:e00117-17. Klass, Perri. "An Apocryphal Christmas Miracle." The New York Times, The New York Times, 23 Dec. 2019, www.nytimes.com/2019/12/23/well/family/diphtheria-antitoxin-Christmas-miracle.html. Lindenmann J. Scand J Immunol. 1984;19:281-285. Meyer KF, et al. Ann N Y Acad Sci. 1952;55:1228-1274. Ramon G. Bull Soc Centr Med Vet. 1925;101:227-234. von Behring, Emil. Geschichte der Diphtherie (mit besonderer Berücksichtigung der Immunitätslehre). Leipzig, Germany, Thieme, 1893. von Behring E. Ueber das Zustandekommen der Diphtherie-Immunität und der Tetanus-Immunität bei Thieren. German Medical Weekly; 1890.

With COVID-19 and the question of whether glucocorticoids could be beneficial, this episode digs into the data on the use of glucocorticoids in the setting of infections, from pneumonia and septic arthritis, to meningitis and septic shock. Intro :11 In this episode :25 The first published case series of patients with serious infection 6:45 Otolaryngologic infections 7:43 Pneumonia, malaria and flu 8:26 Cortisone in strep throat 9:22 Major severe infections 11:26 A review article 12:12 Specific organ systems 13:25 Dexamethasone for bacterial meningitis 25:28 Septic shock 26:19 Dearth of data on glucocorticoids for influenza 32:10 Summary and take-home 35:19 Disclosure: Brown reports no relevant financial disclosures. We'd love to hear from you! Send your comments/questions to [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Annane D, et al. JAMA. 2002;288:862-871. Annane D, et al. N Engl J Med. 2018;378:809-818. Bennett IL, et al. JAMA. 1963;183:462-465. Blum CA, et al. Lancet. 2015;385:1511-1518. de Gans J, van de Beek D. N Engl J Med. 2002;347:1549-1556. Dellinger RP, et al. Crit Care Med. 2013;41:580-637. Fogel I, et al. Pediatrics. 2015;136:e776. Hahn EO, et al. J Clin Invest. 1951;30:274-281. Hartman FA, Merle Scott WJ. Proc Soc Exp Biol and Med. 1931;28:478-479. Hinshaw LB, et al. J Surg Res. 1980;28:151-170. Nedel WL, et al. World J Crit Care Med. 2016;5:89-95. Odio CM, et al. Pediatr Infect Dis J. 2003;22:883-888. Perla D, Marmorston J. Endocrinology. 1940;27:368-374. Stern A, et al. Cochrane Database Syst Rev. 2017;12:doi:10.1002/14651858.CD007720.pub3 Venkatesh B, et al. N Engl J Med. 2018;378:797-808. Wenner WF, Cone AJ. Arch Otolaryngol. 1934;20:178-187. Whitehead KW, Smith C. Proc Soc Expert Biol and Med. 1932;29:672-673. Wysenbeek AJ, et al. Ann Rheum Dis. 1998;57:687–690. Zhou Y, et al. Sci Rep. 2020;10:https://doi.org/10.1038/s41598-020-59732-7.

This episode delves into the history of Whipple's disease — from its initial description, to the lengthy process of proving it's an infectious disease. Intro :11 In this episode :12 The initial case report 1:35 How I fit into the history of Whipple's 4:46 Back to the case report 6:56 Bodies in the intestines 10:12 More about George Hoyt Whipple 10:50 Whipple may not have been the first to identify this condition 14:19 First treatment with antibiotics 15:55 Personality change after antibiotics 19:12 Whipple's disease intestines have positive staining 20:20 Using the electron microscope in Whipple's disease 21:18 Summary and take-home 25:19 Disclosure: Brown reports no relevant financial disclosures. We'd love to hear from you! Send your comments/questions to [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Bayless, TM. Adv intern Med. 1970;16:171-189. Black-Schaffer B. Proc Soc Exp Biol Med. 1949;72:225-227. Fenollar F, et al. N Engl J Med. 2007;356:55‐66. Hendrix JP, et al. Arch Intern Med (Chic).1950;85:91-131. Morgan AD. Gut. 1961;2:370-372. Paulley JW. Gastroenterology. 1952;​22:128-133.​ Raoult D, et al. N Engl J Med. 2000;342:620-625. Relman DA, et al. N Engl J Med. 1992;327:293-301. ​ Whipple GH. Bull Johns Hopkins Hosp. 1907;18:382-391.

This episode dives into the rare Whipple's disease, focusing on the articular manifestations of this infectious masquerader and when a rheumatologist should consider it in the differential. 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 :20 In this episode :28 Background on the organism 5:25 An important point when making the diagnosis 7:48 Who gets infected? 8:55 What is Whipple's disease? 11:48 This disease is fatal 15:53 A look at the joints 16:28 What happens when you give these patients immunosuppression? 26:36 How to diagnose 28:38 Summary so far 31:00 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 Other organ manifestations of Whipple's disease 32:08 Summary and take-home 44:36 Disclosure: Brown reports no relevant financial disclosures. We'd love to hear from you! Send your comments/questions to [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Bousbia S, et al. Emerg Infect Dis. 2010;16:258-63. Chan RY, et al. Ophthalmology. 2001;108:2225-2231. Dobbins 3rd WO, et al. Arthritis Rheum. 1987;30:102-105. Durand DV, et al. Medicine (Baltimore). 1997;76:170-84. Fenollar F, et al. BMC Infect Dis. 2011;11:171. Feurle GE, et al. Eur J Clin Invest. 1979;9:385-389. Geissdörfer W, et al. J Clin Microbiol. 2012;50:216-22. Guérin A, et al. Elife. 2018;7:e32340. Heffner DK. Lancet. 2007;370:738-9; author reply 739. Keita AK, et al. PLoS Negl Trop Dis. 2011;5:e1403. Lagier JC, et al. Medicine (Baltimore). 2010;89:337-345. Lozupone C, et al. Am J Respir Crit Care Med. 2013;187:1110-7. McAllister Jr. HA, Fenoglio Jr. JJ. Circulation. 1975;52:152-6. O'Duffy JD, et al. Arthritis Rheum. 1999;42:812-817. Puéchal X. Joint Bone Spine. 2016;83:631-635. Puéchal X, et al. Arthritis Rheum. 2002;46:1130-1132. Puéchal X, et al. Arthritis Rheum. 2007;56:1713-1718. Raheja AA, et al. Clin Imaging. 2010;34:143-147. Ramos JM, et al. J Med Case Rep. 2015;9:165. Raoult D, et al. Emerg Infect Dis. 2010;16:776-82. Schöniger-Hekele M, et al. Appl Environ Microbiol. 2007;73:2033-2035. Stein A, et al. Am J Respir Crit Care Med. 2013;188:1036-7. Additional resource: Neurosigns.org's video on oculomasticatory myorhythmia can be viewed at: https://www.youtube.com/watch?v=Zwb5bt749Jo

This episode explores the history of cryoglobulinemic vasculitis, from the first person who froze a tube of blood and noticed something strange happened, to the discovery of hepatitis C. We also throw in how the lab test for cryoglobulins is performed and some of the data we have on therapy. 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 :20 In this episode :45 How is this test done? 1:30 What is the first description of cryoglobulins? 4:15 The first time "cryoglobulins" is used 10:26 Hepatitis C is discovered and linked to cryoglobulinemia 16:28 What do we know about the pathophysiology? 19:38 Why does HCV do this? 22:12 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. What's in the blood as a result of immune complex? 24:52 What do we know about autoimmune diseases and the prevalence of cryoglobulins? 26:03 What about treatment? 28:25 Summary of this three-part series 36:16 Disclosure: Brown reports no relevant financial disclosures. We'd love to hear from you! Send your comments/questions to [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Brouet JC, et al. Am J Med. 1974;57:775-788. Cacoub P, et al. Clin Gastroenterol Hepatol. 2019;17:518-526. De Vita S, et al. Arthritis Rheum. 2012;64:843-853. Fuentes A, et al. Curr Rheumatol Rep. 2019;21:doi:10.1007/s11926-019-0859-0. Lerner AB, Watson CJ. Am J Med Sci. 1947;214:410-415. Lospalluto J, et al. Am J Med. 1962;32:142-147. Meltzer M, Franklin EC. Am J Med. 1966;40:828-836. Pascual M, et al. J Infect Dis. 1990;162:569-570. Ragab G, Hussein MA. J Adv Res. 2017;8:99-111. Tzioufas AG, et al. Arthritis Rheum. 1986;29:1098-1104. Wintrobe MM, Buell, MV. Bull. Johns Hopkins Hosp. 1933;52:156-165.

In Part 2, I sit down with nephrologist Ali Mehdi, MD, and neurologist Ghulam Abbas Kharal, MD, MPH, to discuss their different specialty perspectives on working up patients with suspected cryoglobulinemic vasculitis. 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 :20 Introduction of Ali Mehdi, MD :45 Interview with Dr. Mehdi 2:02 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 Introduction of Ghulam Abbas Kharal, MD, MPH 25:01 Interview with Dr. Kharal 26:37 To hear more of my interview with Abbas, keep listening 44:47 Thank you, Dr. Kharal 53:07 Ghulam Abbas Kharal, MD, MPH, is a Partners Neurology Resident at Massachusetts General Hospital, Brigham & Women's Hospital, Harvard School of Medicine. Ghulam Abbas Kharal, MD, MPH, is a staff neurologist at Cleveland Clinic. Kharal did his training in a combined program at Massachusetts General Hospital and Brigham & Women's Hospital, Harvard School of Medicine. Ali Mehdi, MD, is a Nephrology Fellow at the Cleveland Clinic. Mehdi did his Internal medicine residency and chief year at the Cleveland Clinic. We'd love to hear from you! Send your comments/questions to [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum

Try your hand at this medical mystery, which is followed by some didactics on a fascinating disease which will hopefully make sense of this inscrutable title. 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 :22 What to expect in each episode :30 The case: A 75-year-old man with Sjogren's and MALT lymphoma presents with recurrent cerebral infarcts of multiple territories 1:10 Rheumatology is consulted 6:11 Decreased sensation in toes occurs between strokes 7:14 What's going on with this patient? 8:36 What additional labs can we perform? 9:36 We spin the urine 11:10 What kind of vasculitis are Sjogren's and lymphoma associated with? 12:22 C3 and C4 had already been performed 13:00 An overall picture of this patient 13:54 What about the strokes? 14:19 Should we do more imaging? 15:57 At this point we can make a clinical decision 16:33 Why make a decision so quickly vs. waiting for biopsy? 18:18 Two things you must check before moving forward with a cryoglobulinemic vasculitis 19:46 Spoiler alert: The patient is doing really well 20:16 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. What is cryoglobulinemic vasculitis? 21:00 What are these immunoglobulins? There are three types of cryoglobulins 22:55 Usually driven by another identifiable disease 25:18 What is making these immunoglobulins? 26:49 We don't know why these immunoglobulins behave this way 27:18 How do you explain the kidneys? 28:28 What's occurring at the tissue level? 29:35 How does type 1 present? 30:50 Type 2 and type 3 31:12 What other organ systems are involved? 33:11 I hope you enjoyed this patient presentation 36:00 What we'll discuss in episodes 2 and 3 36:05 Thanks for listening 38:03 **Coming soon from Healio, Unmasking COVID-19, a podcast hosted by Gitanjali Pai, MD, infectious disease physician at Memorial Hospital and Physicians' Clinic in Stilwell, Oklahoma. In this timely new show, Dr. Pai will explore COVID-19's impact on vulnerable patient populations by answering questions from experts in various medical fields, including oncology, endocrinology and rheumatology. To submit your question for Dr. Pai, email [email protected].** We'd love to hear from you! Send your comments/questions to [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum @LCalabreseDO @CCalabreseDO Disclosure: Brown reports no relevant financial disclosures. References: Fuentes A, et al. Current Rheumatology Reports. 2019;21:60. Silva F, et al. J Autoimmun. 2019;105:102313.

In this episode, Leonard H. Calabrese, DO, is joined by his colleague and daughter Cassandra Calabrese, DO, as they discuss specifics of irAEs, including unusual toxicities, rheumatic conditions associated with checkpoint inhibitors and the rheumatologist's role in this new area of medicine. 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 :22 Recap of Part 1 :40 An interview with Cassandra Calabrese, DO 2:02 The number of patients with irAEs will grow 2:22 How many people actually experience irAEs? 3:40 Any examples of unusual toxicities? 5:49 What's the timeline? 6:51 Have you seen patients with delayed onset? 8:10 Most of our patients have had one irAE or another beforehand 9:04 Who's the captain of this ship? 10:15 What about inflammatory arthritis? 10:55 What about polymyalgia rheumatica? 13:48 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 about sicca, is it Sjogren's? 16:22 Can you tell us about myositis in this context? 18:38 An overview of the guidelines 21:47 Check out our article in March Current Opinions in Rheumatology 24:12 What about patients with preexisting autoimmunity? 24:33 Are you worried about blunting tumor response? 27:10 Are there any biomarkers to predict this? 28:30 How have you been working with oncologists to manage/educate? 29:42 What about meetings? 31:04 Rheumatologists have a special place in this new area of medicine 31:45 We'd love to hear from you! Send your comments/questions to [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum @LCalabreseDO @CCalabreseDO Disclosure: Brown and Cassandra Calabrese report no relevant financial disclosures. Leonard Calabrese reports serving as an investigator and a consultant to Horizon Pharmaceuticals. Cassandra Calabrese, DO, is associate staff member in the department of rheumatic and immunologic disease and department of infectious disease at the Cleveland Clinic. Leonard H. Calabrese, DO, is chief medical editor of Healio Rheumatology and director of the RJ Fasenmyer Center for Clinical Immunology at the Cleveland Clinic.

Checkpoint inhibitors have changed the field of oncology, as well as our understanding of autoimmunity. This episode, hosted by Leonard H. Calabrese, DO, walks us through the history of checkpoint inhibitors — from Dr. William Coley's use of infections in cancer to the development of PD-1 inhibitors. 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 :20 In this episode with Dr. Calabrese 3:07 Book recommendations 4:28 Harnessing the power of the immune system to fight cancer 5:33 William Coley and a patient 6:30 The search for Fred Stein 11:40 Coley designs an experiment 13:09 A different strain of streptococcus 16:16 The beginning of cancer therapy and immunotherapy 19:18 Where do we go from there? 20:49 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. What about tumor immunology? 21:55 The breakthrough 24:01 What do immunology and checkpoints have to do with it? 26:47 What happens when the danger signal cannot be dispatched? 34:02 Why do we, as rheumatologists, care about this? 36:04 CHAI and LATTE 38:49 Check out some papers on immunopathogenesis of irAEs 40:56 Checkpoint inhibitors for autoimmune diseases; RA and GCA 41:41 Come back for part 2 43:00 We'd love to hear from you! Send your comments/questions to [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum @LCalabreseDO Disclosures: Brown reports no relevant financial disclosures. Calabrese reports serving as an investigator and a consultant to Horizon Pharmaceuticals. Leonard H. Calabrese, DO, is chief medical editor of Healio Rheumatology and director of the RJ Fasenmyer Center for Clinical Immunology at the Cleveland Clinic.

Join Peter Grayson, MD, MSc, and I as we discuss a range of topics, including imaging in large-vessel vasculitis, doctors going into research, Twitter, rock 'n' roll and Disney World. Intro :10 A bit about Peter Grayson :55 Come see me in Phoenix in February 3:35 The interview 4:07 How did you make it to the NIH? 4:27 Why do you think MDs aren't going into research these days 6:45 Social media and major meetings 9:43 Tell us about the NIH rock 'n' roll band 11:10 What imaging modalities are most used for large-vessel vasculitis? 13:32 What is PET scan? 14:23 Do you think PET scanning is the best imaging modality? 15:29 What are the limitations to PET? 17:48 Does vessel size affect PET scanning? 20:01 Are these machines available in most hospitals? 21:12 Grayson's secret sauce 22:27 How do glucocorticoids affect imaging? 23:19 Are you ever using PET as follow-up? 25:07 Do you have hope for any specific targets for Takayasu's arteritis? 27:12 What drives the surgical intervention process for these patients? 28:23 Collateral artery formation 30:30 Where do you think Takayasu's will be in 10 years? 31:35 Thank you, Dr. Grayson 33:36 We'd love to hear from you! Send your comments/questions to [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum Disclosures: Brown and Grayson report no relevant financial disclosures. Peter Grayson, MD, MSc, is head of the Vasculitis Translational Research Program at National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and associate director of the NIAMS Fellowship Program, Systemic Autoimmunity Branch.

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 [email protected]. 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 [email protected]. 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 [email protected]. 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 [email protected]. 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 [email protected]. 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 [email protected]. 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 [email protected]. 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 [email protected]. 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 [email protected]. 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 [email protected]. 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.

In Part 1, we look at the original studies that led to the discovery of TNF in two separate labs where researchers were looking for two completely different things. We'll learn how these discoveries then fueled the use of TNF in the failed trials as an anti-cancer agent, and the eventual development of antibody therapy against TNF in septic shock. Intro :11 The origins of this episode and what we'll cover here and in Part 2 :18 What Part 1 will cover 2:01 Early cytokine research in general codiscovery of TNF TNF as anticancer agent TNF's role in cachexia trials of anti-TNF in the setting of septic shock What part 2 will cover 2:59 TNF's role in rheumatoid arthritis TNF in the late 1800s 3:18 Lipopolysaccharide from gram-negative bacteria is first isolated and discovered 8:16 Fast forward to the 1960s, enter Memorial Sloan Kettering Cancer Center 9:08 Anthony Cerami studies cachexin in his Rockefeller lab 11:10 Focus on cachexia 12:27 Late 1980s: TNF is produced and given to humans using recombinant technology 20:01 Studies of TNF in patients with various types of cancer 20:48 High doses seem to induce shock-like illness 21:38 TNF-secreting tumor is created and tested 25:21 Some take away 26:12 Studying TNF led to the discovery that it's associated with shock 26:33 Money pours into research on blocking TNF 27:00 A look at studies of TNF in infection 27:22 Study of TNF in sepsis 30:20 Let's talk about anti-TNF and what it's doing 34:00 Studies of anti-TNF in humans 36:00 Rat and baboon studies don't always correlate with humans 40:25 Episode recap 40:45 Stay tuned for Part 2 42:20 Follow us on Twitter @HRheuminations and leave us a review in iTunes 42:50 We'd love to hear from you! Send your comments/questions to [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Beutler B, et al. Science. 1985;229:869–871. Blick M, et al. Cancer Research. 1987;47:2986-2989. Carswell E, Williamson B. Cancer Imm. 2012;12:4. Feldman M. Nat Rev Immunol. 2002;2:364-371. Fong Y, et al. J Exp Med. 1989;170:1627-1633. Kawakami M. Mol Med. 2014;doi:10.2119/molmed.2014.00177. Lv S, et al. Int J Clin Pract. 2014;68:520-528. Marks JD, et al. Am Rev Respir Dis. 1990;141:94-97. McCarthy EF. Iowa Orthop J. 2006;26:154-158. Michi HR, et al. N Engl J Med. 1988;318:1481-1486. Oliff A. Cell. 1988;54:141-142. Opal SM, et al. J Infect Dis. 1990;161:1148-1152. Qui P, et al. Expert Opin Investig Drugs. 2011;20:1555-1564. Tracey KJ, et al. Nature. 1987;330:662-4. Waage A, et al. Lancet. 1987;1:355-7.

Take a listen to this medical mystery and learn about a not-so-rare condition — depending on where you live. Hear some interesting historical stories about the physicians who helped establish the diagnosis, as well as an interview with a renowned expert. Intro :11 A 57-year-old woman presents with multiple-week history of joint pain. She also complains of lesions on her forearms. :32 Initial lab results 1:30 She arrives at my office 1:50 Review of her vitals 1:57 Physical exam findings and patient history 2:05 What about the nodules on her skin? 3:20 Tests leading to diagnosis 4:40 What's the diagnosis? 4:55 A personal anecdote 5:20 Symmetrical polyarticular inflammatory arthritis in the setting of erythema nodosum 6:18 What do we know about Löfgren Syndrome? 7:45 History of this diagnosis 8:35 What we know 100 years later 11:13 Focus on the inflammatory arthritis of Löfgren Syndrome 14:25 Are these different diseases? 18:07 Summary of what we've discussed so far 19:13 Unsung heroes who showed sarcoidosis is associated with inflammatory arthritis 20:40 Introduction of Dr. Daniel Culver 28:26 An update on sarcoidosis with Dr. Culver 29:17 Why should we care about staging on X-ray? 29:22 Are there any clues that it may be sarcoid based on histology and morphology of the granuloma itself? 30:56 How does bronchoalveolar lavage help? 32:58 How often do you see remissions in non-Löfgren's sarcoidosis? 34:41 What are your thoughts on the serum biomarkers? 36:34 Can you comment with your thoughts on the link between the environment and the disease? 38:25 What about infectious triggers? 40:06 Do you think genetic studies will eventually be used for diagnosis or prognosis? 41:18 Where do you think we'll be with the diagnosis and treatment of sarcoidosis in 10 years? 42:38 Thank you, Dr. Dan Culver 44:28 Episode recap 44:40 Follow us on Twitter @HRheuminations and leave us a review in iTunes 45:18 Daniel Culver, DO, is director of the Interstitial Lung Disease Program at Cleveland Clinic and director of The Sarcoidosis Center of Excellence at Cleveland Clinic. We'd love to hear from you! Send your comments/questions to [email protected]. Follow us on Twitter @AdamJBrownMD @HealioRheum @HRheuminations References: Grunewald J, Eklund A. Am J Respir Crit Care Med. 2009;179:307-312. Le Bras E, et al. Arthritis Care Res (Hoboken). 2014;66:318-322. Lofgren S, Lundback H. Acta medica Scandinavica. 1952;142. Maña J, et al. Am J Med. 1999;107:240-245. Palmer DG, Schumacher HR. Ann Rheum Dis. 1984;43:778–782. Segura BT, et al. Medicina Clinica (Barc). 2014;143:166-9.

In this guest episode, Leonard Calabrese, DO, provides the history of systemic lupus erythematosus, with special emphasis on the discovery of the LE cell and the two clinics involved in its detection. Introduction of Leonard Calabrese, DO :11 In this episode … 1:44 A brief history of systemic lupus erythematosus and the major players 2:15 Laurent-Theodore Biett 2:55 Casanave 3:05 von Hebra 3:24 Moritz Kaposi 4:05 Sir William Osler 5:25 Fast-forward to observations made during WWII era 7:00 The story of two clinics 8:55 The Mayo Clinic 9:00 The Cleveland Clinic 16:24 A race against time 18:29 Lupus is no longer a diagnostic problem 20:02 In a nutshell 20:15 Housekeeping items 20:51 Leonard Calabrese, DO, is head of Cleveland Clinic's Section of Clinical Immunology, co-director of Center for Vasculitis Care and Research, and chief medical editor of Healio Rheumatology. We'd love to hear from you! Send your comments/questions to [email protected]. Follow us on Twitter @AdamJBrownMD @HealioRheum @HRheuminations @LCalabreseDO

Richard Furie, MD, is chief, division of rheumatology, at Northwell Health, and professor of medicine at Hofstra/Northwell School of Medicine. Join us in this ACR interview, as we discuss the story of interferon, lupus therapeutics — including B cell depletion — and the future of lupus research and treatments. Intro :10 Background on Dr. Furie :16 The interview :56 What advancements in the pathophysiology of lupus are you most excited about? 1:10 The interferon story 1:23 The interferon story is not finished yet 7:18 Dendritic cells in lupus patients 7:41 What is "interferon signature?" 8:07 Do we see different clinical phenotype in patients with high interferon signature? 9:38 What's your opinion on the role of B cells? 10:07 Any other pathophysiology mechanisms being used to target B cells? 13:15 Are we stretched thin in terms of number of lupus patients in trials? 15:21 How would designating lupus as an orphan disease change the way it's investigated? 16:40 What is your main concern regarding study design? 17:37 Looking 10 years ahead, do you think what we call "lupus" will still be referred to as such, or will it be decompartmentalized into different diseases? 21:26 What's the expense of cytokine profiling? 22:40 What excites you the most about the future of lupus research? 23:21 Thank you, Dr. Furie 24:41 Recap 24:43 Shout out to the 7th Annual Basic and Clinical Immunology for the Busy Clinician: What is New and Hot in Immunology bootcamp in Scottsdale, AZ, Feb. 15-16, 2019 25:31 We'd love to hear from you! Send your comments/questions to [email protected]. And be sure to follow us on Twitter @AdamJBrownMD and @HealioRheum. This information is brought to you by Healio and is not sponsored by, nor a part of, the American College of Rheumatology.

In this episode, John Stone, MD, MPH, director of clinical rheumatology at Massachusetts General Hospital, sits down to discuss his approach to giant cell arteritis and the results of the GiACTA trial. Learn why Stone believes the most important diagnostic test in GCA is the patient's history. Intro :10 Background on Dr. Stone :59 The interview 2:10 Differentiating subtle GCA from the "classic case" 2:20 Data from Stone's recent paper in Rheumatology 5:17 Using bilateral biopsies 9:00 Recommendations for temporal artery biopsy – who, when, where 11:13 Thoughts on imaging for GCA diagnosis 13:14 IL-6 and treatment of GCA 15:16 GiACTA trial – what surprised you most about the efficacy of prednisone alone? 19:05 Findings with tocilizumab 21:29 Inflammatory markers in GCA 24:47 Should we use tocilizumab right off the bat? 26:50 What excites you the most about the future of this field? 29:59 Thank you, Dr. Stone 31:33 Recap 31:38 We'd love to hear from you! Send your comments/questions to [email protected]. And be sure to follow us on Twitter @AdamJBrownMD and @HealioRheum.

John J. O'Shea, MD, is scientific director of the NIH's National Institute of Arthritis and Musculoskeletal and Skin Diseases, and chief of their Molecular Immunology and Inflammation Branch. In this ACR interview, he joins me to talk about the JAK/STAT pathway, what we've learned from mouse models, current FDA-approved JAK inhibitors and the future of this exciting field. Intro :10 Background on Dr. O'Shea :45 The interview 2:37 How did you start looking into the JAK/STAT pathway? 3:16 What should a clinician understand about this pathway? 5:22 What do these cytokines have in common? 6:37 What have we learned from mouse models? 8:48 GWAS studies in JAK/STAT 11:49 Can we quantify how much a certain cytokine may be using this pathway? 12:39 Can you explain suppressor of cytokine signaling, aka SOCS? 14:15 What do we know about how these different cytokines can have individual signaling controls? 16:40 An explanation of phenocopy 18:01 What evidence do we have that JAK may circumvent STAT, and vice versa? 18:41 An overview of FDA-approved JAK inhibitors and the pipeline 20:52 What excites you the most about the future of this field? 23:26 In a state of wonder over success of biologics 25:50 Thank you, Dr. O'Shea 27:20 Recap 27:30 We'd love to hear from you! Send your comments/questions to [email protected]. And be sure to follow us on Twitter @AdamJBrownMD and @HealioRheum. This information is brought to you by Healio and is not sponsored by, nor a part of, the American College of Rheumatology.

In this ACR interview, the walking encyclopedia of medical history, Eric L. Matteson, MD, of The Mayo Clinic, sits down with me to discuss what excites him about medical history and then takes a deep dive into the history of vasculitis! Intro :10 Background on Dr. Matteson :28 The interview 2:00 How did you get into history? Why does it mean so much to you? 2:19 Can you tell us about the archives at Mayo Clinic? 6:49 An appreciation of present time and how we take some medications for granted 7:55 Brief history of vasculitis 9:23 Kussmaul and the first failed ophthalmoscope 14:20 Kussmaul's second failure: gastroscope 15:43 When did we get to the small vessel vasculitis/glomerulonephritis description? 17:25 The discovery of Wegener 20:44 Wegener was not the first to describe granulomatosis with polyangiitis, and the folly of naming diseases for individuals 23:24 Thank you, Dr. Matteson 24:57 Recap 25:05 We'd love to hear from you! Send your comments/questions to [email protected]. This information is brought to you by Healio and is not sponsored by, nor a part of, the American College of Rheumatology.

Martin J. Blaser, MD, is director of the Human Microbiome Program at NYU and author of the book, Missing Microbes. He sat down and spoke with us about how the microbiome plays a role in disease pathogenesis, including autoimmunity, and he also answered the question of whether all of our patients should be on probiotics! Intro :11 Background on Dr. Blaser :35 The interview 1:20 What is the microbiome? 1:25 How unique are individual microbiomes? 1:49 How does an individual's microbiome change over time? 2:13 Microbial diversity in different populations 3:12 What's your concern with the loss of microbiome diversity? 4:20 A bit on Blaser's research on obesity and antibiotic use 5:21 Is the timing of antibiotic administration important, in terms of the side effects it can produce? 6:43 Worldwide antibiotic prescribing rates 7:54 The microbiome and autoimmunity 9:02 The microbiome and type 1 diabetes, IBD 10:45 Research with IL-17 12:23 Microbiota transplants 13:09 For how long is the microbiome perturbed after giving antibiotics? 13:57 Diet and microbiome findings 14:54 Probiotics, prebiotics and symbiotics 15:33 In 10 years, how will people be investigating/manipulating the microbiome? 18:18 Have we shown with research that introducing certain types of bacteria can be sustainable in the gut? 19:47 Thank you, Dr. Blaser 20:26 Summary 20:33 We'd love to hear from you! Send your comments/questions to [email protected]. This information is brought to you by Healio and is not sponsored by, nor a part of, the American College of Rheumatology.

In this episode, explore data from the major study proving uric acid crystals are present in the synovial fluid of patients with gout, as well as the tale of two rheumatologists who injected their own knees (while still working in the hospital) with uric acid to prove it is the trigger for inflammation in gout. The episode finishes with some ripping yarns about the history of the medications we use to treat this condition. Intro :10 Controversy surrounding uric acid's role in gout :45 "Game changing" paper published in 1961 2:07 The first description of pseudo gout 5:53 How do you prove uric acid triggered the inflammatory response? 6:37 One of my favorite studies 6:43 Faires and McCarty inject themselves with uric acid 7:49 Details of what they experienced 8:22 4 hours later … 8:52 Both patients receive treatment 9:12 Review of what we've discussed so far 10:06 Let's try and answer the question posited in The History of Gout, Part 1 10:35 Colchicine – previously a medicinal plant 10:41 A look at the history of urate-lowering therapy 12:59 Probenecid was developed to reduce the excretion of penicillin 13:18 The history of allopurinol 14:32 Don't give allopurinol to patients on azathioprine 17:21 The answer to the question posed in Part 1 17:49 Summary 18:12 We'd love to hear from you! Send your comments/questions to [email protected]. References: Barnett R. Lancet. 2018;391:2595. Faires JS, Mccarty DJ. Lancet. 1962;280:682-685. Kippen I, et al. Ann Rheum Dis. 1974;33:391-396. Marson P, Pasero G. Reumatismo. 2011;63:199-206. McCarty DJ, Hollander JL. Ann Intern Med. 1961;54:452-460. Nuki G, Simkin PA. Arthritis Res Ther. 2006;doi: 10.1186/ar1906. Rundles RW. Arch Intern Med. 1985;145:1492-1503. Shyambhavee, Behera BK. J Pharmacol Clin Toxicol. 2017;5:1098. Storey GD. Rheumatology. 2001;40:1189-1190. West JB. Am J Physiol Lung Cell Mol Physiol. 2014;doi:10.1152/ajplung.00223.2014.

Do you know the etymology of the word "gout," or how a simple microscope aided in the identification of tophi? Join me as I explore the history of this inflammatory arthritis and highlight the important scientists who shaped the modern era of gout. Intro :10 What to expect in Part 2 :48 A question: Which urate-lowering therapy was made for an expressly different reason than to treat gout? 1:34 The first modern description of gout 1:54 Let's go back to the Greeks 3:05 Why is it called "gout?" 3:06 An anecdote from medical school 4:13 Hippocrates' words of wisdom on gout 4:58 First century AD: Gout is linked with excessive eating and drinking 6:01 Things get muddled 6:20 1683: The modern era of gout is described 6:42 "Gout Perspectives" published in The Lancet in 2018 7:06 Self-taught Dutch scientist, Antony van Leeuwenhoek, pioneers the microscope and identifies tophi 8:29 Swedish chemist Carl Wilhelm Scheele discovers uric acid 11:38 William Hyde Wollaston tests tophi and discovers it's full of uric acid 12:57 Emperor of uric acid, Alfred Baring Garrod, associates elevated serum uric acid with gout 13:48 If anyone knows how the thread test works, please email me 14:58 He theorized that uric acid causes gout 15:37 A look back at what we know 16:09 What we don't know: What's in the joints of patients with acute gout? 16:22 Stay tuned for The History of Gout, Part 2 16:34 We'd love to hear from you! Send your comments/questions to [email protected]. References: Barnett R. Lancet. 2018;391:2595. Faires JS, Mccarty DJ. Lancet. 1962;280:682-685. Kippen I, et al. Ann Rheum Dis. 1974;33:391-396. Marson P, Pasero G. Reumatismo. 2011;63:199-206. Mccarty DJ, Hollander JL. Ann Intern Med. 1961;54:452-460. Nuki G, Simkin PA. Arthritis Res Ther. 2006;doi: 10.1186/ar1906. Rundles RW. Arch Intern Med. 1985;145:1492-1503. Shyambhavee, Behera BK. J Pharmacol Clin Toxicol. 2017;5:1098. Storey GD. Rheumatology. 2001;40:1189-1190. West JB. Am J Physiol Lung Cell Mol Physiol. 2014;doi:10.1152/ajplung.00223.2014.

This episode discusses the case of an 85-year-old man with a history of hypertension and fairly recently diagnosed bladder cancer who presents with oligoarticular asymmetric inflammatory arthritis. Explore the details of this case and learn how bacillus Calmette-Guérin and reactive arthritis are related in this diagnostic conundrum. Intro :10 An 85-year-old man with a history of hypertension and recently diagnosed bladder cancer presents with oligoarticular asymmetric inflammatory arthritis :18 Details of his cancer history :32 How BCG (bacillus Calmette-Guérin) is used for superficial bladder cancer :53 Patient wakes with acute onset, rapidly progressing joint pain 1:21 Results of synovial aspiration of his right wrist 2:06 Physical exam findings and patient history 2:24 Discharged from outside hospital 2:53 Outpatient rheumatologist orders autoimmune serologies 3:03 Second hospital admission 3:24 Infectious disease evaluation 4:25 Patient presents to Cleveland Clinic 4:54 What do we have? 6:18 The main concern is he's been instilled with bacteria 6:45 Could this be a reactive arthritis? 7:18 History of BCG 7:45 What do we know about what happens to these patients? 10:28 How do we define disseminated BCG infection vs. a reactive arthritis? 10:58 A single institution cohort of disseminated infection after BCG instillation 11:29 Comparing these definitions in our patient 14:34 A look at reactive arthritis 15:07 What do we use to treat these patients? 16:12 A look back at our patient 16:31 Continued treatment with triple therapy 17:05 A diagnostic conundrum 17:32 The diagnosis, in hindsight 18:11 Summary 18:49 We'd love to hear from you! Send your comments/questions to [email protected]. References: Bernini L. Autoimmun Rev. 2013;12:1150-1159. Meyer J. Postgrad Med J. 2002;78:449-454. Pérez-Jacoiste Asín MA. Medicine (Baltimore). 2014;93:236-254. To U. Case Rep Med. 2014;doi:10.1155/2014/362845.

This episode covers a rare but life-threatening complication of lupus nephritis called complement-mediated thrombotic microangiopathy. Rheumatologist Lisa Zickuhr, MD, helps us better understand this often-overwhelming topic with a clinical case example, treatment options and practice pearls. Intro :10 Introduction of Lisa Zickuhr, MD, rheumatologist :44 Complement-mediated thrombotic microangiopathy in lupus is an overwhelming topic 1:50 Definition of TMA 2:15 What is MAHA? 3:10 Four classic symptoms associated with TMA syndromes 3:35 What causes TMA? 3:50 Complement-mediated TMA 5:35 How this is seen in clinical practice 9:10 Case example of complement-mediated TMA 10:10 Summary of case presentation 13:05 What's next? 13:50 Takeaways from this clinical presentation 15:48 Primary and secondary complement-mediated TMA 18:23 An argument for a primary etiology of complement-mediated TMA in lupus 18:51 CliffsNotes version for rheumatologists, HCPs caring for lupus patients 21:12 Therapy for complement-mediated TMA is two-pronged 22:35 Patient profile 24:05 Summary 25:10 Thank you to Dr. Lisa Zickuhr 26:13 Lisa Zickuhr, MD, is a rheumatologist at Washington University in St. Louis. We'd love to hear from you! Send your comments/questions to [email protected]. References: Dragon-Durey MA, et al. J Am Soc Nephrol. 2005:555-563. Dragon-Durey MA, et al. Semin Thromb Hemost. 2010:633-640. George JN, et al. N Engl J Med. 2014 Aug 14;371:654-666. Jönsen A, et al. Arthritis Res Ther. 2011;13:R206. Laszlo MH, et al. Ann Intern Med. 1955;42:1308-1320. Nesher G, et al. Semin Arthritis Rheum. 1994;24:165-72. Zickuhr L, et al. Arthritis Care Res (Hoboken). 2018;doi: 10.1002/acr.23561.

A young woman presents with migraine-like headaches, black spots in her vision and emotional lability. Think you know the diagnosis? You may be surprised – this medical mystery is not what it seems. In this episode, learn more about this rare diagnosis, and gain clinical insight from neurologist Devon Conway, MD, and ophthalmologist Arthi Venkat, MD. Intro :11 A 24-year-old woman presents with gradual worsening of a migraine-like headache accompanied by nausea :22 Description of symptoms :37 ER visit 1:23 Onset of new symptoms 1:44 Second ER visit 2:11 Outpatient MRI findings 2:28 Lumbar puncture findings 2:50 Patient is admitted to hospital 3:52 Second MRI findings 4:16 Ophthalmology consult and results of fluorescein angiography 4:46 Audiogram is ordered 5:17 Case summary 5:40 What is the most likely diagnosis? 6:05 Triad of Susac syndrome 6:27 Remember: This is not a vasculitis 7:11 History of Susac syndrome 7:40 CNS manifestations of the Susac triad 8:27 Consult with Devon Conway, MD 10:13 Flare signals for non-radiologists/neurologists 11:05 Anything specific that says "demyelinating" on MRI? 13:35 Distinguishing the lesions in this case from those of MS 15:36 Neurology work-up approach to this type of case 16:28 The utility of lumbar puncture in this situation 18:05 About ADEM (acute disseminated encephalomyelitis) 21:06 Ocular manifestations of Susac syndrome 22:26 Consult with Arthi Venkat, MD 23:17 Ophthalmology differential in a patient with intermittent vision loss in various fields of vision 23:55 Overview of branch retinal artery occlusions 25:22 Difference between branch retinal artery occlusions and other ophthalmologic presentations common to rheumatologists 27:51 How the ophthalmologic exam helps differentiate MS from Susac syndrome 30:07 Overview of sensorineural hearing loss in Susac syndrome 34:09 Do we know for sure this is an autoimmune disease? 34:59 Aggressive immunosuppression seems to halt the progression of disease 35:34 What are treatment options? 35:42 What do we know about long-term outcomes? 36:31 Who takes care of these patients? 37:29 Treatment, outcome of this patient 38:07 Episode/case summary 38:20 Devon Conway, MD, is a staff neurologist at Cleveland Clinic's Mellen Center for Multiple Sclerosis. Arthi Venkat, MD, is a retinal and uveitis specialist at Cole Eye Institute at Cleveland Clinic. We'd love to hear from you! Send your comments/questions to [email protected]. References: Aubart-Cohen F, et al. Medicine (Baltimore). 2007;86:93-102. Greco A, et al. Autoimmun Rev. 2014;13:814-821. Rennebohm RM, et al. Int J Stroke. 2018;doi:10.1177/1747493017751737.

Do you know which U.S. president had Addison's disease? Or how rumors from WWII led to funding for research on cortisol? In this episode, take a trip down memory lane as we detail the history of steroids and the scientists whose work lead to the discovery of prednisone. Intro :14 A query: What other disease is attributed to Thomas Addison? :40 Overview of the layers of the adrenal gland 1:18 History of the adrenal gland 2:10 Thomas Addison enters the scene 3:39 Kennedy and terminology 6:15 Charles Brown-Sequard helps describe function of adrenal glands 7:13 George Oliver and Edward Sharpey-Schafer help understand adrenal gland 8:44 Adrenaline is discovered 10:03 Steroid chemistry begins in earnest 10:14 Steroids discovered, but questions remain 10:25 WWII rumors spur research on cortin 11:15 Edward Calvin Kendall, Tadeus Reichstein and Philip Showalter Hench receive Nobel prize for their discoveries relating to the hormones of the adrenal cortex 12:23 Committee of 14 chemists assembled 14:24 1948: The case of Mrs. G 15:21 Pharmaceutical companies race to produce cortisone 17:08 How we arrived at prednisone 17:43 The answer to the question: "What other disease was described by Thomas Addison?" 18:34 We'd love to hear from you! Send your comments/questions to [email protected]. References: Benedek TG. Clin Exp Rheumatol. 2011;29:S-5-12. Burns CM. Rheum Dis Clin North Am. 2016;doi: 10.1016/j.rdc.2015.08.001. Lawrence L. Controversial 'father' of endocrinology: Brown-Séquard. Endocrine Today. February 2008. https://www.healio.com/endocrinology/news/print/endocrine-today/%7B0b1791e0-0e1c-42ac-bec3-d5b67bb054f6%7D/controversial-father-of-endocrinology-brown-squard. Accessed April 10, 2018. Pearce JMS. J R Soc Med. 2004;97:297-300.

Biosimilars are a fascinating new category of medication and are quickly becoming part of the rheumatologist's treatment armamentarium, but they can be confusing to understand. This episode will enhance your knowledge of this new class of medications by providing a better understanding of how biologics differ from most other medications, and why biosimilars aren't just generics of biologics. This episode also takes a brief look into the history of drug regulation with a focus on biosimilars and how they're FDA approved. Intro :12 What is a biologic? 1:21 What makes a generic? 5:05 History of drug regulation in the U.S. 5:10 What makes a biologic? 11:43 Monoclonal antibodies 11:51 Where do biosimilars come from? 14:16 Definition 15:03 Manufacturing process 15:17 FDA approval process 16:00 Trials of biosimilars 19:44 We'd love to hear from you! Send your comments/questions to [email protected]. Resources: Bridges SL Jr., et al. Arthritis Rheumatol. 2018;doi:10.1002/art.40388. Hornecker JR. Generic Drugs: History, Approval Process, and Current Challenges. U.S. Pharmacist. 2009;34(6)(Generic Drug Review suppl):26-30. Janssen WF. The Story of the Laws Behind the Labels. https://www.fda.gov/downloads/AboutFDA/WhatWeDo/History/FOrgsHistory/EvolvingPowers/UCM593437.pdf. Published June 1981. Accessed April 14, 2018. Liu JKH. Ann Med Surg (London). 2014;doi:10.1016/j.amsu.2014.09.001. Morrow T, Felcone LH. Biotechnol Healthc. 2014;1:24-26,28-29.

Leonard Calabrese, DO, details the clinical manifestations of giant cell arteritis, the complex scenarios rheumatologists face when working with GCA, and the pathogenesis of this disease. Calabrese also shares clinical pearls and tips for success. Introduction of Leonard Calabrese, DO :12 Goals of this episode :31 The disease that rheumatologists love 1:02 History of giant cell arteritis 1:51 Gene Hunder, MD, defines large vessel involvement in late '80s, '90s 4:18 Epidemiology of giant cell arteritis 4:32 Manifestations in detail 5:13 Cranial arteritis 5:20 Jaw claudication 6:04 Ocular involvement 6:44 Signs and symptoms 7:03 The most important thing about ocular ischemia in GCA 9:01 Stroke: A major complication of cranial ischemic GCA 9:25 PMR and/or systemic inflammatory presentations 11:33 A more recent presentation: inflammatory disease of unknown origin 12:19 Large vessel presentations 13:12 Diagnosis of GCA is based on clinical suspicion 14:00 Ophthalmologists must have hypervigilance 14:22 It's a team sport to attack this disease 14:58 Overview of clinical manifestations 15:08 Histopathology 16:10 How the biopsy should be done 16:38 What about healed arteritis? 17:18 What about arteritis of the vasa vasorum? 17:41 Episode recap 17:54 The most important thing to know 18:17 Leonard Calabrese, DO, is head of Cleveland Clinic's Section of Clinical Immunology, co-director of Center for Vasculitis Care and Research, and chief medical editor of Healio Rheumatology. We'd love to hear from you! Send your comments/questions to [email protected].

What do a fever, stiff neck and leukocytosis have in common with a large swollen knee? Listen to this medical mystery to see if you can figure out the diagnosis, then stick around to hear interesting information you may not know about the disease, including historical perspectives. Intro :10 A 71-year-old man presents with unilateral knee swelling, fever and neck stiffness :37 Medication overview 2:12 Physical exam findings 2:24 Laboratory findings 3:03 Imaging results 3:33 Rheumatology consult 4:30 Now what? 5:08 CT scan is ordered 6:04 The meningitis mimicker 6:24 History of pseudo-gout 6:54 What do we know about chondrocalcinosis? 7:53 History of Crowned Dens syndrome 9:37 Cervical spine anatomy review 11:05 Data from a single center 12:40 Can this be dangerous? 13:40 Are we sure this is pseudo-gout? 14:20 The role of the CT in the diagnosis of this case 14:50 Treatment options 15:44 "Why not treat the patient with steroids from the start?" 16:12 Email me with questions, or if you know any cases of hydroxyapatite-induced Crowned Dens 16:39 We'd love to hear from you! Send your comments/questions to [email protected]. References: Ali S, et al. J Radiol Case Rep. 2011;doi:10.3941/jrcr.v5i8.802. Bouvet JP, et al. Arthritis Rheumatism. 1985;28:1417-20. Ciricillo SF, Weinstein PR. J Neurosurg. 1989;71:141-143. Goto S, et al. J Bone Joint Surg Am. 2007;89:2732-2736. Marson P, Pasero G. Reumatismo. 2012; 63: 199-206. Salaffi F, et al. Clin Exp Rheumatol. 2008;26:1040-1046.