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.

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.

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.

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.

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.

In part 2, we dig into the history of pulmonary hypertension. How did this strange diagnosis first get recognized, what does it have to do with cows with thick necks and urinary catheters in the heart?

• Intro 0:11
• In this episode 0:17
• Recap of part 1 0:26
• How was pulmonary hypertension discovered? 2:38
• 1891 3:51
• 1901 5:07
• 1935 7:02
• Hilar dance 12:58
• Cardiac catheterization: 1929 15:03
• When did cardiac catheterization become relevant? 20:10
• 1965: Aminorex 24:40
• World Health Organization: 1975 26:37
• 1980s: toxic oil syndrome of Spain 28:20
• Preview of part 3 33:15 
• Back to cardiac catheterization 34:08
• Briskets disease 35:45
• 1947 37:56
• Pulmonary physiology and prostaglandin therapies (in the next episode) 38:41
• Schistosomiasis outbreaks in Egypt 1938 40:26
• Chronic thromboembolism 45:03
• Thanks for listening 48:16

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:

Barst RJ. Ann Thorac Med. 2008;doi:10.4103/1817-1737.37832.

Bodo R. J Physiol. 1928;doi:10.1113/jphysiol.1928.sp002447.

Dresdale DT, et al. Am J Med. 1951;doi:10.1016/0002-9343(51)90020-4.

Egypt. Stanford.edu. Published 2015. https://schisto.stanford.edu/pdf/Egypt.pdf.

Hewes JL, et al. Pulm Circ. 2020;doi:10.1177/2045894019892801.

Johnson S, et al. Am J Respir Crit Care Med. 2023;doi:10.1164/rccm.202302-0327SO.

Newman JH. Am J Respir Crit Care Med. 2005;doi:10.1164/rccm.200505-684OE.

Weir EK, et al. Circulation. 1996;doi:10.1161/01.cir.94.9.2216.

Disclosures: Brown reports no relevant financial disclosures.

In this series, we dive into what rheumatologists should know about pulmonary hypertension, starting an interview with Joseph Parambil, MD, where we learn about the disease, when to suspect and how to work up!

• Intro 0:11
• In this episode 0:16
• Preview of the four-part series 4:46
• Interview with Joseph Parambil, MD 6:27
• How did you become interested in pulmonary hypertension? 7:02
• Brown and Parambil discuss the histology of pulmonary hypertension. 10:13
• Brown and Parambil discuss a case of pulmonary hypertension. 12:26
• What is pulmonary hypertension and what does that mean for a rheumatologist? Where is pulmonary hypertension happening? 13:25
• Describe the different groups of pulmonary hypertension. 19:51
• A note about Dr. Chatterjee 20:25
• Brown and Parambil discuss the groups of pulmonary hypertension. 23:35
• What should we know about evaluating patients with pulmonary hypertensions? 26:51
• Brown and Parambil discuss bendopnea and other signs of pulmonary hypertension. 29:58
• What about the heart sound? 33:06
• What should we look for in patients who we suspect to have pulmonary hypertension? 36:52
• What should we look for in the tricuspid jet? 38:18
• Brown and Parambil discuss the use of echocardiograms in pulmonary hypertension. 39:28
• Tell us about the threshold of diagnosis. 40:47
• What is the difference between the mean pressure and the wedge pressure? 41:41
• What about the role of the pulmonary function test? 43:55
• Summary 46:41
• Do you think the pulmonary hypertension in scleroderma and lupus are different entities? 48:37
• Brown and Parambil discuss the connection of autoimmune disease and pulmonary hypertension. 50:49
• Coming up in episode 91 51:50
• Thanks for listening 52:25

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.

We’d love to hear from you! Send your comments/questions to Dr. Brown at [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum.

On this episode, hear the 2024 updates on COVID-19, long COVID and the latest developments in research in rheumatology. Hosted by Dr. Leonard Calabrese.

• Intro 0:12
• In this episode 0:21
• Coming up on Healio Rheuminations 0:56
• COVID-19, long COVID and the rheumatologist with Leonard Calabrese, DO 2:19
• Questions 3:12
• Long COVID 4:46
• Calabrese’s bias 10:15
• The evidence 13:08
• Auto antibodies 14:54
• Why does the body develop auto antibodies? 17:47
• COVID-19 and epidemiologic association 22:25
• New clinical entity 26:40
• Therapeutic implications 31:00
• In conclusion 32:00
• Thanks for listening 33:18

Leonard H. Calabrese, DO, is the chief medical editor, Healio Rheumatology, and professor of medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic.

Disclosures: Calabrese reports professional relationships with AbbVie, AstraZeneca, Bristol Myers Squibb, Galvani, Genentech, GlaxoSmithKline, Janssen, Novartis, Regeneron, Sanofi and UCB.

We’d love to hear from you! Send your comments/questions to Dr. Brown at [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum.

It's that time of year again, everyone rolling up their sleeves to get a flu shot. This throwback episode dives into the history of the struggles pinning down the causative agent of flu and the journey to the vaccine!

• Intro 0:40
• In this episode 1:11
• The history of the flu: 1892 1:41
• What do we know about viruses? 6:29 
• Rabies and dead virus 11:17
• A Sickness in the Serum, Part 2 14:43
• 1918 16:44
• Vaccines and trials 19:13
• Pig influenza 23:12
• Influenza: a filterable agent we can’t see 27:01
• The trials of 1942 33:02
• PS: 1918 influenza 38:57
• Thanks for listening 47:42

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:

Hicks DJ, et al. Clin Exp Immunol. 2012;doi:10.1111/j.1365-2249.2012.04592.x.

Rosenau MJ. Experiments Upon Volunteers to Determine the Cause and Mode of Spread of Influenza, Boston, November and December, 1918. https://quod.lib.umich.edu/f/flu/3750flu.0016.573. Published February 1921. Accessed December 6, 2023.

Rosenau MJ, et al. JAMA. 1925;doi:10.1001/jama.1925.02670070040019.

Taubenberger JK, et al. Antivir Ther. 2007;12(4 Pt B):581-91.

Tobin J. The first flu shot. https://heritage.umich.edu/stories/the-first-flu-shot/. Accessed December 6, 2023.

In the third episode of the NSAIDs saga, we focus on COX-2 inhibition! Did the hopes and dreams of selective COX-2 inhibition pan out? What can the rise and fall of VIOXX teach us about physiology?

• Intro 0:11
• Recap of part 1 & 2 0:28
• In this episode 1:44
• Cyclooxygenase 2 (COX-2) and the rat experiment 3:12
• What do we know about the prostaglandins? And what about COX-2 7:54
• What does prostacyclin do? 10:33
• The first COX-2 inhibitor: VIOXX 10:56
• What is COX-2 doing?: Pfizer and Merck 12:15
• Two more NSAID studies: colon cancer, Alzheimer’s disease and COX-2 inhibitors 18:41
• VIOXX: Why is myocardial infarction risk occurring? 22:34
• Animal models and the Goldilocks theory of thromboxane and prostacyclin 23:49
• PRECISION trial 30:25
• Rheum + Boards 37:14 
• Thanks for listening 37:32

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 GD, et al. J Clin Invest. 1996;doi:10.1172/JCI118717.

Funk CD, et al. J Cardiovasc Pharmacol. 2007;doi:10.1097/FJC.0b013e318157f72d.

Hennan JK, et al. Circulation. 2001;doi:10.1161/hc3301.092790.

Krumholz HM, et al. BMJ. 2007;doi:10.1136/bmj.39024.487720.68.

Nissen SE, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1611593.

Disclosures: Brown reports no relevant financial disclosures.