Healio Rheuminations

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 rheuminationspodcast@healio.com. 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 rheuminationspodcast@healio.com. 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 rheuminationspodcast@healio.com. 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 rheuminationspodcast@healio.com. 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 rheuminationspodcast@healio.com. 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 rheuminationspodcast@healio.com. 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 rheuminationspodcast@healio.com. 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 rheuminationspodcast@healio.com. 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 rheuminationspodcast@healio.com. 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 rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum