Healio Rheuminations

Was your psoriasis caused by the Black Death? Learn more than you might have wanted to know about the Black Death and delve into the data on the immunologic/autoimmune ramifications of wiping out nearly half of Europe. ·       Intro 0:11 ·       In this episode 1:09 ·       The Black Death 1:24 ·       The History of IV Immunoglobulin episode 2:07 ·       How the Black Death happened 4:07 ·       How many people died from the Black Death? 6:49 ·       Record keeping 6:53 ·       The modern immune system, the Black Death and HIV 8:43 ·       What is CCR5? 8:55 ·       Current data on autoimmune diseases 10:35 ·       ERAP2 15:55 ·       How yersinia pestis kills you 21:04 ·       The inflammasome 22:03 ·       The Inflammasome for Dunces episode 22:09 ·       Mediterranean fever and mouse model 24:49 ·       Takeaways 30:20 ·       Summary 30:59 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: Wheelis M. Emerg Infect Dis. 2002;doi:10.3201/eid0809.100536. Ratner D, et al. PLoS Pathog. 2016;doi:10.1371/journal.ppat.1006035. Park YH, et al. Nat Immunol. 2020;doi:10.1038/s41590-020-0705-6. Patin E. Nat Immunol. 2020;doi:10.1038/s41590-020-0724-3. Galvani AP, et al. Proc Natl Acad Sci USA. 2003;doi:10.1073/pnas.2435085100.

In this episode we explore ways in which the extracellular matrix can be manipulated, including the story of doxycycline, TGF-beta in Marfan syndrome and whether beta blockers can reduce vascular events in vascular EDS. ·        Intro 0:12 ·        Review of previous episode 0:28 ·        In this episode 2:26 ·        The pressure against the vessels 4:06 ·        The pressure against the wall 8:44 ·        Matrix metalloproteinases 10:16 ·        Tadpole study – collagen breakdown 10:35 ·        Tetracycline antibiotics 14:05 ·        Rat model – periodontal disease and hydroxyproline 14:24 ·        Chemically modified tetracyclines 20:14 ·        Mouse model – tetracycline use 22:00 ·        Tetracyclines and other autoimmune conditions 23:22 ·        Marfan syndrome 24:45 ·        Fibrillin and Marfan syndrome 28:48 ·        TGF-beta 29:36 ·        Mouse model – Marfan syndrome and fibrillin 31:14 ·        ARBs and TGF-beta 33:51 ·        TGF-beta and vascular EDS 37:25 ·        Back to the mouse model 38:38 ·        Protein kinase C 39:56 ·        Summary 40:26 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: Bowen CJ, et al. J Clin Invest. 2020;130:686-698. Brooke BS. Lancet. 2010;doi:10.1016/S0140-6736(10)61155-5 Dietz HC, et al. Am J Med Genet C Semin Med Genet. 2005;doi:10.1002/ajmg.c.30068. Dubacher N, et al. Cardiovasc Res. 2020;116:457-465. Golub LM, et al. SAGE. 1998;doi:10.1177/08959374980120010501. Gross J, et al. PNAS. 1962;doi:10.1073/pnas.48.6.1014 Habashi JP, et al. Science. 2006;312:117-121. Morissette R, et al. Circ Cardiovasc Genet. 2014;7:80-88. Mullen M, et al. Lancet. 2019;394:2263-2270. Neptune ER, et al. Nat Genet. 2003;33:407-411.

Dive into vascular Ehlers-Danlos syndrome. What is it? How does it present? Get clues to its diagnosis and learn more about collagen than you ever wanted to know. Intro 0:12 In this episode 0:17 Why vascular Ehlers-Danlos syndrome? 0:28 Case study: Dr. Mories 2:20 What can we learn about vascular Ehlers-Danlos syndrome? 05:02 Collagen and elastin 05:57 Collagen: horses and glue 07:07 More about collagen 10:35 Why is it a problem to miss a little bit of collagen? 14:14 The problem in vascular Ehlers-Danlos syndrome 15:06 The history of vascular EDS 15:41 How is vascular Ehlers-Danlos syndrome diagnosed? 16:36 A vascular Ehlers-Danlos syndrome diagnosis 22:33 Mouse models 23:29 Clinical and genetic features of vascular Ehlers-Danlos syndrome 24:39 Question of vasculitis 25:55 The skin: the most common symptom of vascular EDS 28:00 Family history, de novo mutations and pregnancy 29:43 Surgery or vascular intervention 31:39 How do patients do in the long-term? 32:54 Summary 34:00 Preview of part 2 35:42 Thanks 36:25 Disclosures: Brown reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum. References: Barabas AP. J Cardiovasc Surg (Torino). 1972;13(2):160-7. Chow MJ, et al. Biophys J. 2014;doi:10.1016/j.bpj.2014.05.014. Liu X, et al. Proc Natl Acad Sci USA. 1997;doi:10.1073/pnas.94.5.1852. Mories A. Scott Med J. 1960;5:269-72. Pepin M, et al. N Engl J Med. 2000;doi:10.1056/NEJM200003093421001. Pepin MG, et al. Genet Med. 2014;doi:10.1038/gim.2014.72. Piez KA. Matrix Biol. 1997;doi:10.1016/s0945-053x(97)90037-8. Pope FM, et al. Proc Natl Acad Sci USA. 1975;doi:10.1073/pnas.72.4.1314. Wagenseil JE, et al. J Cardiovasc Transl Res. 2012;doi:10.1007/s12265-012-9349-8. Zilocchi M, et al. AJR Am J Roentgenol. 2007;doi:10.2214/AJR.07.2370.

In this episode, Dr. Benjamin Claytor walks us through his approach to suspected sensory ganglionopathies. I also cover other neurologic complications of Sjogren’s syndrome and some interesting history on vitamin B6. Intro 0:12 In this episode 0:46 Neurologic complications of Sjogren’s Syndrome 1:55 Intro of Dr. Benjamin Claytor 6:00 The interview 6:49 Case study: process of diagnosis 7:17 Dorsal root ganglion in Sjogren’s 10:46 Facial numbness in sensory ganglionopathies 11:42 Dorsal root ganglion biopsies 13:36 Prognosis of sensory ganglionopathies vs other distal neuropathies 14:03 Sensory loss and weakness 15:51 Sensory ataxia 16:24 Attacks on the dorsal root ganglion 18:25 Loss of fibers in the dorsal root ganglion and regrowth 19:21 Treating cancer and sensory ganglionopathies 20:03 Idiopathic patients and treatments 20:45 Interview wrap-up 21:43 Pearls of wisdom from the interview 22:11 History of sensory ganglionopathies 23:35 Thanks 29:09 Disclosures: Brown and Claytor report no relevant financial disclosures. Benjamin Claytor, MD, is assistant professor of neurology at the Neuromuscular Center at Cleveland Clinic. 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: Antopol W, et al. J Neuropathol Exp. 1942;doi:10.1097/00005072-194207000-00006. Pavlakis PP, et al. J Autoimmun. 2012;doi:10.1016/j.jaut.2012.01.003. Schaumburg H, et al. N Engl J Med. 1983;doi:10.1056/NEJM198308253090801.

A sensational (or lack thereof) series on the signs and symptoms of the spellbinding sensory ganglionopathies. Intro :12 Today’s episode :16 Anatomy review 1:32 Large fiber vs. small fiber nerves 4:47 Case presentation 6:11 Neurologic examination of patient 8:31 What is pseudoathetoid posturing? 10:11 What does it mean to be length independent? 14:30 What is sensory ganglionopathy? 16:19 How did the differential evolve throughout history? 18:50 How do things get out of the synovium? 23:19 Why does rheumatology get involved? 26:12 Case series of patients with Sjogren’s syndrome and sensory ganglionopathy 28:20 How do we treat it? 32:48 Summary 34:09 Thank you 36:59 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: Amato AA, et al. N Engl J Med. 2020;doi:10.1056/NEJMra2023935. Denny-Brown D. J Neurol Neurosurg Psychiatry. 1948;doi:10.1136/jnnp.11.2.73. Griffin JW, et al. Ann Neurol. 1990;doi:10.1002/ana.410270313. Malinow K, et al. Ann Neurol. 1986;doi:10.1002/ana.410200416.

In part two, Leonard Calabrese, DO, discusses the symptoms of long COVID and the role that rheumatologists play in diagnosing and treating patients with long COVID. Brought to you by Tremfya. Intro 1:06 Calabrese introduction 1:11 In this episode 1:36 Defining long COVID 1:49 Reviewing symptoms of long COVID 2:51 Long COVID fatigue 3:44 Studies and research on fatiguability 4:38 Phenomena of post-exertional malaise 6:18 Chronic fatigue syndrome 7:25 Neurocognitive dysfunction 7:52 Co-factors of intercurrent mood disorders and neurocognitive dysfunction 9:30 Pandemic-related sequelae 10:30 What about pain? 10:53 Long COVID pain and criteria for fibromyalgia 11:40 Pandemic-related long COVID 13:16 Diagnoses of long COVID 14:46 Immunopathogenesis 15:27 What about infections and autoimmunity? 17:50 What about treatments for long COVID? 19:28 Validation of long COVID 20:52 What do rheumatologists have to do with long COVID? 21:56 Wrap up 21:13 Thanks 24:02 Disclosures: Calabrese reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum

In this episode, Leonard Calabrese, DO, reviews the history and controversies of post-infection sequelae, as well as the facts and epidemiology of long COVID. Intro :12 Calabrese introduction :15 COVID-19 and the history of modern medicine :48 In this episode 1:39 The course of COVID-19 2:05 COVID-19 vaccines and immunity 2:50 Controversy, facts, fascination, long COVID 3:16 The history of post-acute sequelae 3:59 Post-infectious sequelae 10:15 What is long COVID and how do we define it? 11:02 How common is long COVID? 13:50 The epidemiology of long COVID 15:32 What are protective factors? 16:53 Preview of Part 2 17:36 Shoutout to rheumatologists 18:46 Conclusion 19:08 Wrap up of Part 2 preview 20:11 Thanks 21:02 Disclosures: Calabrese reports no relevant financial disclosures. We’d love to hear from you! Send your comments/questions to Dr. Brown at rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum

How is the synovial fluid produced? Who figured it out? It’s a ripping yarn involving corpses, cats, anti-hypertensives, steroids and streptococcus. Brought to you by Tremfya. Intro :11 Today’s episode :15 Synovium 101 :22 Overview of the synovium and synovial fluid 2:06 How they figured it out? Dr. Marian Ropes 5:37 Investigating synovial fluid 7:46 Cows experiment and where synovial fluid comes from 11:25 Clinical review of synovial fluid 14:57 What’s inside the fluid? 18:54 What makes up the fluid? 20:51 How do things get out of the synovium? 23:19 How are things absorbed into the synovium? 27:21 How well do steroids get picked up systemically? 29:39 Summary 32:30 Thank you 34:59 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: Edwards JC. J Anat. 1994;184:493-501. Rhinelander FW, et al. J Clin Invest. 1939;doi:10.1172/JCI101011. Shaffer MF, et al. J Exp Med. 1939;doi:10.1084/jem.70.3.293. Stout A, et al. PM R. 2019;doi:10.1002/pmrj.12042.

What does the PAPA spectrum disorder teach us about SAPHO? Is SAPHO an autoinflammatory condition or part of the SpA spectrum? Why have antibiotics been used to treat this condition? Find out in this episode! Brought to you by Tremfya. Intro :01 Welcome to another exciting episode of Rheuminations :11 About today’s episode :17 A summary of SAPHO Part 1 :24 What to expect in this episode 1:28 Earlier long-term data 2:27 A more recent paper from Italy 6:47 Therapeutics in detail 12:17 Summary so far 21:39 IL-1 inhibition in SAPHO 22:32 Monogenic pediatric conditions 33:58 Why can’t we check the genes in SAPHO? 40:00 Episode summary 41:55 We went through a lot in this paper 45:29 Thanks for listening 43:53 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 and be sure to check out Rheum + Boards – your destination for rheumatology education and quizzes! References: Agak GW, et al. J Invest Dermatol. 2014;134:366-373. Aksentijevich I, et al. N Engl J Med. 2009;360:2426-2437. Assmann G, Simon P. Best Pract Res Clin Rheumatol. 2011;25:423-434. Boursier G, et al. J Invest Dermatol. 2021;141:1141-1147. Cai R, et al. Front Cell Dev Biol. 2021;doi:10.3389/fcell.2021.643644. Colina M, et al. Arthritis Rheum. 2009;61:813-821. Daoussis D, et al. Semin Arthritis Rheum. 2019;48:618-625. Eun IS, et al. J Clin Neurosci. 2021;92:153-158. Ferguson PJ, El-Shanti H. Biomolecules. 2021;11:367. Grosse J, et al. Blood. 2006;107:3350-3358. Guignard S, et al. Joint Bone Spine. 2002;69:392-396. Hayem G, et al. Semin Arthritis Rheum. 1999;29:159-171. Holzinger D, Roth J. Curr Opin Rheumatol. 2016;28:550-559. Hurtado-Nedelec M, et al. J Rheumatol. 2010;37:401-409. Liao HJ, et al. Rheumatology (Oxford). 2015;54:1317-1326. Lindor NM, et al. Mayo Clin Proc. 1997;72:611-615. Nguyen MT, et al. Semin Arthritis Rheum. 2012;42:254-265. Trimble BS, et al. Agents Actions. 1987;21:281-283. Yeon HB, et al. Am J Hum Genet. 2000;66:1443-1448. You H, et al. J Clin Immunol. 2021;41:565-575.

What is SAPHO? What does the ‘H’ stand for, again? This episode explores some basics about the condition and delves into the history of how this disease came to be. Intro :01 Welcome to another exciting episode of Rheuminations :11 About today’s episode :17 What does the acronym ‘SAPHO’ stand for? :37 How do you define this condition? 2:35 So, what is SAPHO syndrome? 4:59 Are any of the letters specific for SAPHO syndrome? 15:20 How the puzzle pieces were put together 15:48 Over the next ensuing decades, when did we start realizing that patients could have dermatologic manifestations? 23:00 So, what about hyperostosis? 30:46 Why isn’t the Sonozaki group getting the credit? 39:22 So, how did we get SAPHO? 40:26 How did they get 85 patients? 42:50 We went through a lot in this paper 45:29 Next episode preview 46:29 Thanks for listening 47:03 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 and be sure to check out Rheum + Boards – your destination for rheumatology education and quizzes! References: Chamot AM, et al. Rev Rheum Mal Osteoartic. 1987;54:187-196. Giedion A, et al. Ann Radiol (Paris) 1972;15:329-342. Köhler H, et al. Ann Intern Med. 1977;87:192-194. Nguyen MT, et al. Semin Arthritis Rheum. 2012;42:254-265. Raposo I, Torres T. Am J Clin Dermatol. 2016;17:349-358.  Romani M, et al. Clin Podiatr Med Surg. 2021;38:541-552.  Sonozaki H, et al. Ann Rheum Dis. 1981;40:547-553. Windom RE, et al. Arthritis Rheum. 1961;4:632-635.