Healio Rheuminations

• The Astounding Account of the IL-17 and Spondylarthritis

  In this episode, we focus on the history of researchers discovering the clinical applicability of the IL 23/17 axis, with a particular emphasis on psoriasis, psoriatic arthritis and axial SpA   ·        Intro 0:01 ·        In this episode 0:12 ·        Leonard Calabrese, DO, is listening! 0:54 ·        Recap of last episode 3:09 ·        Putting the pieces together 5:12 ·        Quick overview of this science heavy episode 6:11 ·        What is psoriasis? 7:26 ·        Immunosuppressants for psoriasis/ Throwing meds at people and seeing what happens 10:10 ·        In the modern world of 1986 – olive oil placebo trial 11:36 ·        A quick aside into fungi 12:35 ·        What kind of T-cells are involved here? 16:41 ·        The TH-1 hypothesis 18:20 ·        IL-23 and IL-17 are doing something 19:34 ·        Going back to the drawing board in 2004 20:00 ·        p40 + p19 = IL-23 21:00 ·        IL-23 via minicircle DNA in mice 23:05 ·        Brand new and shiny TH-17 25:23 ·        The family of IL-17 26:36 ·        What do we know about IL-17 and psoriasis? 27:10 ·        IL-17A vs IL-17F in mouse studies 27:35 ·        Finding the difference between IL-17A and IL-17F in humans 28:23 ·        What exactly is IL-17 doing? 29:30 ·        The articular manifestations of psoriatic arthritis 30:57 ·        Spondylarthritis and the IL 23/17 axis 33:56 ·        T-cells we haven’t talked about 35:40 ·        Summary of this episode 39:08 ·        Thanks for listening 41:34   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: Bashyam H. J Exp Med. 2007;doi:10.1084/jem.2042fta Bjerke R J. Acta Derm Venereol. 1982;PMID:6179355 Cargill M, et al. Am J Hum Genet. 2007;doi:10.1086/511051 Chan J R, et al. J Exp Med. 2006;doi:10.1084/jem.20060244 Cuthbert R J, et al. Ann Rheum Dis. 2019;doi:10.1136/annrheumdis-2019-215210 Ellis C N, et al. JAMA. 1986;doi:10.1001/jama.1986​ Ettehadi P, et al. Clin Exp Immunol. 1994;doi:10.1111/j.1365-2249.1994.tb06244.x Furue M, et al. Int J Mol Sci. 2020;doi:10.3390/ijms21041275 Gooderham M J, et al. J Eur Acad Dermatol Venereol. 2018;doi:10.1111/jdv.14868 Lee E, et al. J Exp Med. 2004;doi:10.1084/jem.20030451 Leonardi C L, et al. Lancet. 2008;doi:10.1016/S0140-6736(08)60725-4 Mease P J, et al. Lancet. 2000;doi:10.1016/S0140-6736(00)02530-7 Menon B, et al. Arthritis Rheumatol. 2014;doi:10.1002/art.38376 Moos S, et al. J Invest Dermatol. 2019;doi:10.1016/j.jid.2019.01.006 Muelle W, et al. N Engl J Med. 1979;doi:10.1056/NEJM197909063011016 Papp K A, et al. Lancet. 2008;doi:10.1016/S0140-6736(08)60726-6 Reinhardt A, et al. Arthritis Rheumatol. 2016;doi:10.1002/art.39732 Sherlock J P, et al. Nat Med. 2012;doi:10.1038/nm.2817 Tribe H T. Mycologist. 1998;doi:10.1016/S0269-915X(98)80100-6 Yawalkar N, et al. J Invest Dermatol. 1998;doi:10.1046/j.1523-1747.1998.00446.x Zaba L C, et al. J Allergy Clin Immunol. 2009;doi:10.1016/j.jaci.2009.08.046   Disclosures: Brown reports no relevant financial disclosures.

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• The Tumultuous Tale of Th17-and the IL23/IL17 immune axis

  In this episode, we dive into a two-part story of intrigue starting from a paradigm shift in understanding of T cell biology because of a mouse model of post-measles encephalopathy, to the eventual recognition of the IL-23/17 immune axis. •    Intro 0:01 •    In this episode 0:12  •    Interleukin-17 (IL-17) is a relatively recent discovery 1:34 •    The beginning of TH-17 2:20 •    Looking at autoimmune encephalopathy: A story of measles 03:30 •    1790’s woman with post measles inflammatory process in the brain 10:26 •    What is causing post-infection encephalitis? 12:00 •    Acute disseminated encephalomyelitis 12:30 •    How did we find out the immune system was behind this - The rabies vaccine 13:09 •    Similarity between the rabies vaccine and infections like measles 16:04 •    T-cell lymphocytes 17:12 •    The forgotten thymus 18:00 •    What’s the function of T-cells? 19:35 •    How do you tell T-cells apart? 21:14 •    The Human Leukocyte Differentiation Antigens Party 24:05 •    The godfather of T-cells 24:45 •    The TH-1 and TH-2 axis 27:30 •    Experimental Autoimmune Encephalomyelitis model screwed everything up 29:16 •    Interferon gamma 32:32 •    What’s missing? IL-23 surprise 33:40 •    IL-17 in the 1990’s 36:44 •    The world is introduced to TH-17 39:12 •    Let’s recap what we learned 40:30 •    That is the end! 42:30 •    Thanks for listening 42:39 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: Bashyam H. J Exp Med. 2007;doi:10.1084/jem.2042fta Bennetto L, et al. J Neurol Neurosurg Psychiatry. 2004;doi:10.1136/jnnp.2003.034256 Berche P. Presse Med. 2022;doi:10.1016/j.lpm.2022.104149 El-behi M, et al. J Neuroimmune Pharmacol. 2010;doi:10.1007/s11481-009-9188-9 Gooderham MJ, et al. J Eur Acad Dermatol Venereol. 2018;doi:10.1111/jdv.14868 Hawkes JE, et al. J Immunol. 2018;doi:10.4049/jimmunol.1800013 Rogozynski N, et al. Immunol Lett. 2024;doi:10.1016/j.imlet.2024.106870 Sospedra M, et al. Annu Rev Immunol. 2005;doi:10.1146/annurev.immunol.23.021704.115707 Steinman L. Nat Med. 2007;doi:10.1038/nm1551 Disclosures: Brown reports no relevant financial disclosures.

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• History of polymyalgia rheumatica: The origin of the pain & link to giant cell arteritis

  In this episode, we dive into the history of polymyalgia rheumatica, how it was discovered and its link to giant cell arteritis. Intro 0:01 In this episode 0:10 What is polymyalgia rheumatica (PMR)? 0:24 The history of PMR 02:12 PMR in the 1950s: A formally recognized disease 04:52 What was probably PMR in the 1880s 06:27 Naming PMR: Senile rheumatic gout 07:26 1957: The witch’s shot and finally landing on polymyalgia rheumatica 08:30 Where is PMR coming from? 14:42 Injecting joins with saline 16:39 A biopsy study in 1964 19:54 Technetium bone scintigraphy in 1971 and bone scan history 23:01 First look at a PMR ultrasound in 1993 27:00 1997: First use of MRI on PMR patients in Italy 27:49 Going back to 1962: PMRs association with giant cell arteritis 30:40 A paper on muscular involvement in giant cell arteritis: 80-year-old ‘robust’ partially blind seaman 32:15 First systematic approach: The link between PMR and giant cell arteritis 35:14 80 cases of PMR 38:13 Swedish autopsy studies 41:07 Introduction of advanced imaging in the 1990s 42:40 Summing up PMR through the decades 43:28 That is the end! 45:25 Thanks for listening 45:50 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: Bruk MI. Ann Rheum Dis. 1967;doi:10.1136/ard.26.2.103. Cantini F, et al. J Rheumatol. 2001;28(5):1049-55. De Miguel E, et al. Rheumatology (Oxford). 2024;doi:10.1093/rheumatology/kead189. Dixon AS, et al. Ann Rheum Dis. 1966;doi:10.1136/ard.25.3.203. Hamrin B, et al. Ann Rheum Dis. 1968;doi:10.1136/ard.27.5.397. Salvarani C, et al. Ann Intern Med. 1997;doi:10.7326/0003-4819-127-1-199707010-00005. Shah S, et al. Rheumatology (Oxford). 2025;doi:10.1093/rheumatology/keae569. Disclosures: Brown reports no relevant financial disclosures.

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• Pulmonary hypertension, part 4: The therapeutics, with Dr. Joseph Parambil

  In the final part of this series, Joseph Parambil, MD, walks us through the approach of managing pulmonary hypertension, reviews the pathophysiology and digs into the mechanisms and the differences in the medications. Intro 0:12 In this episode 0:17 Interview with Joseph Parambil, MD 2:53 Reviewing and clarifying pathophysiology prior to initiating therapeutics 4:13 Evaluating patients in terms of their functional status and how does that play a role in initiating therapies 4:25 Vasoreactivity testing 10:21 The categories of medications 14:40 Endothelin receptor antagonists 37:07 TGF pathway 42:13 Scleroderma patient and treatment 50:19 Do patients get a repeat right-heart catheterization? 55:51 What about the TGF-beta? 56:55 Thank you, Dr. Parambil 58:34 Thanks for listening 59:17 We’d love to hear from you! Send your comments/questions to Dr. Brown at [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum. Disclosures: Brown and Parambil report no relevant financial disclosures. Joseph Parambil, MD, is a staff member in the Respiratory Institute and the director of the HHT Center of Excellence and the Vascular Anomalies Center at the Cleveland Clinic. He is associate professor of medicine at Cleveland Clinic’s Lerner College of Medicine. He is certified by the American Board of Internal Medicine with additional specialty certification in pulmonary medicine and critical care medicine.

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• Pulmonary hypertension, part 3: Early therapies and vascular physiology

  In this episode, we dive into the early therapies and how our understanding of vascular physiology drastically changed the management of pulmonary hypertension. Intro 0:12 In this episode 0:18 Recap of part 1 & 2 0:31 What part 3 is about 2:31 WHO conference in 1975: Treating pulmonary hypertension 3:48 The Discovery of Non-Steroidal Anti-inflammatory Drugs (NSAIDs), Part 1 5:20 Epoprostenol 6:18 Prostacyclin 10:37 Endothelin antagonists 11:41 Phosphodiesterase type 5 (PDE5) inhibitors 14:08 Interaction of nerves and blood vessels 15:06 The Soups VS the Sparks 17:36 A dreamed experiment 19:06 Acetylcholine 23:23  Enter “the calabar bean” 24:45 Acetylcholine and vasodilation: 1976 26:01 Rabbit aorta 27:45 Nitric oxide 29:38 Why are we using nitric oxide to treat pulmonary hypertension? 31:31 Tachyphylaxis 33:48 TNT factories 35:09 Nitrous oxide and tachyphylaxis 36:52 Pfizer in the 1980s 38:06 Understanding the trigger of pulmonary hypertension 40:53 PDE5 and nitric oxide and pulmonary hypertension 43:07 The end of the ripping yarns 44:20 Coming up in part 4 46:17 Thanks for listening 47:29 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: Bernard C. C R Soc Biol. 1851;3:163-164. Furchgott RF, et al. Nature. 1980;doi:10.1038/288373a0. Galiè N, et al. N Engl J Med. 2005;doi:10.1056/NEJMoa050010. Ghofrani HA, et al. Nat Rev Drug Discov. 2006;doi:10.1038/nrd2030. Giordano D, et al. Biochim Biophys Acta. 2001;doi:10.1016/s0167-4889(01)00086-6. Guthrie F. Q J Chem Soc. 1859;doi:10.1039/QJ8591100245. Higenbottam T, et al. Lancet. 1984;doi:10.1016/s0140-6736(84)91452-1. Marsh N, et al. Clin Exp Pharmacol Physiol. 2000;doi:10.1046/j.1440-1681.2000.03240.x. Montastruc JL, et al. Clin Auton Res. 1996;doi:10.1007/BF02281906. Nejad SH, et al. Future Cardiol. 2024;doi:10.1080/14796678.2024.2367390. Tansey EM. C R Biol. 2006;doi:10.10116/j.crvi.2006.03.012. Warren JV. Trans Am Clin Climatol Assoc. 1988;99:10-6. Disclosures: Brown reports no relevant financial disclosures.

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