This episode digs into the pathophysiology of urticaria vasculitis from anti-C1q to the story of bradykinin.

·       Intro 0:11

·       In this episode 0:22

·       Review of episode 83 1:23

·       Listen to previous episode, The Complement System for Dunces 4:09

·       Anti-C1q antibodies 6:26

·       Lupus, anti-C1q and lupus nephritis 9:33

·       What happens when you inject anti-C1q in a mouse? 12:56

·       The allergy component: anti-C1q, urticaria and angioedema 17:36

·       Bradykinin-mediated angioedema and C1q deficiency 24:20

·       What is the kinin kallikrein system? 26:21

·       French researchers in 1909: human urine injected in dogs 27:30

·       How is this relevant to urticarial vasculitis? 31:08

·       SERPING1 gene mutation 31:23

·       Summary 32:06

·       COPD association with urticarial vasculitis 33:51

·       Coming up in episode 85 35:28

·       Thanks for listening 35:45

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:

Busse P, et al. J Allergy Clin Immunol Pract. 2022;doi:10.1016/j.jaip.2021.11.011.

Davis MDP, et al. J Allergy Clin Immunol Pract. 2018;doi:10.1016/j.jaip.2018.05.006.

Dorn JM, et al. Ann Allergy Asthma Immunol. 2023;doi:10.1016/j.anai.2023.06.014.

Marzano AV, et al. J Allergy Clin Immunol. 2022;doi:10.1016/j.jaci.2022.02.007.

Siegert CE, et al. Clin Immunol Immunopathol. 1993;doi:10.1006/clin.1993.1066.

Stojan G, et al. Lupus. 2016;doi:10.1177/0961203316645205.

Venzor J, et al. Clin Rev Allergy Immunol. 2002;doi:10.1385/CRIAI:23:2:201.

Wisnieski JJ, et al. Medicine. 1995;doi:10.1097/00005792-199501000-00003.

Is it an allergy or an autoimmune vasculitis, or a little of both? Find out the story of urticarial vasculitis, how this disease was recognized and eventually sorted out from other types of urticaria.

·       Intro 0:12

·       In this episode 0:21

·       Case study 1:22

·       Chronic spontaneous urticaria, hives and nettles 7:57

·       Dermatographism and witchcraft? 10:15

·       Causes of urticaria 11:17

·       Theory of inflammation and histamines 11:40

·       Urticaria and treatments with histamines 12:09

·       Types of urticaria 13:02

·       Mayo Clinic study 13:39

·       Chronic urticaria as a manifestation of necrotizing venulitis 16:10

·       Connection between types of urticaria and leukocytoclastic vasculitis 20:02

·       More case studies 20:38

·       What do we know about treatments? 22:23

·       In conclusion 24:15

·       Coming up in part two 25:08

·       Thanks for listening 25:47

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:

Czarnetzki BM. Int J Dermatol. 1989;doi:10.1111/j.1365-4362.1989.tb01314.x.

Kolkhir P, et al. J Allergy Clin Immunol. 2019;doi:10.1016/j.jaci.2018.09.007.

McDuffie FC, et al. Mayo Clin Proc. 1973;48(5):340-8.

Natbony SF, et al. J Allergy Clin Immunol. 1983;doi:10.1016/0091-6749(83)90096-9.

Soter NA. N Engl J Med. 1977;doi:10.1056/NEJM197706232962505.

What should rheumatologists know about what we've learned about COVID-19 and long COVID in 2023? Hosted by Dr. Leonard Calabrese.

·       Intro 0:11

·       In this episode 0:21

·       2023: current status and controversies 0:35

·       What is going on with COVID-19? 01:53

·       What do we know about vaccine responses? What should we be telling our patients about vaccines in our immunocompromised population? 2:58

·       Lancet Rheumatology MELODY study summary 3:08

·       What about patients within the rheumatic and autoimmune disease space? 4:15

·       Who is immunocompromised and why does it matter? 5:11

·       What is the immunosuppression we are giving them? 6:39

·       What to tell patients about getting vaccinated 8:56

·       Long COVID 10:09

·       What is long COVID? 10:26

·       JAMA Network Open study on prevalence and characteristics associated with post-COVID conditions 14:19

·       In the clinical arena, what should rheumatologists be thinking about? 16:38

·       What about pathogenesis? What do we know about the controversies in this area? 18:58

·       Autoimmunity: COVID-19 and autoimmune response 20:45

·       What about therapies? 22:22

·       The next generation of rheum agents: Immunomodulation with neonatal Fc receptor targeting? 24:40

·       A question for the rheumatology community: do patients with immune mediated diseases get more long COVID than the control population? 25:40

·       In conclusion 27:37

·       Thanks for listening 28:38

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 episode dives into the history of the struggles pinning down the causative agent of flu and the journey to the vaccine!

·       Intro 0:12

·       In this episode 0:17

·       The history of the flu: 1892 3:10

·       Rabies and dead virus 10:52

·       A Sickness in the Serum, Part 2 14:31

·       Vaccines and trials 19:13

·       Pig influenza 23:21

·       Influenza: a filterable agent we can’t see 27:10

·       The trials of 1942 33:18

·       PS: 1918 influenza 39:13

·       Finding the 1918 influenza vaccine 39:54

·       Thanks for listening 47:54

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.

What is silica? How does it impact your risk of developing autoimmunity if you inhale it, inject it or even snort it up your nose? Listen and find out!

·       Intro 0:12

·       In the previous episodes 0:28

·       The Ajax incident of 1979 1:15

·       Silica and its association with autoimmune disease 4:11

·       The history of silica and the health risks 5:21

·       Rheumatoid scleroderma, etc. 8:14

·       Cardiff pneumoconiosis medical panel 9:49

·       Databases 12:51

·       Silica exposure and the development of serologies 15:02

·       What would happen if you injected silica into the veins? 16:51

·       Anca vasculitis 18:33

·       Thanks for listening 23:23

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:

Blanc PD, et al. Am J Med. 2015;doi:10.1016/j.amjmed.2015.05.001.

Boudigaard SH, et al. Int J Epidemiol. 2021;doi:10.1093/ije/dyaa287.

Conrad K, et al. Lupus. 1996;doi:10.1177/096120339600500112.

Hoy RF, et al. Allergy. 2020;doi:10.111/all.14202.

Klockars M, et al. Br Med J (Clin Res Ed). 1987;doi:10.1136/bmj.294.6578.997.

Park CG, et al. Environ Health Perspect. 1999;doi:10.1289/ehp.99107s5793.

Pollard KM. Front Immunol. 2016;doi:10.3389/fimmu.2016.00097.  

In this episode, we dig through the data of lupus in Africa and speak with experts on the Lupus Gradient, the impact of malaria and what we can learn from it all.

·       Intro 0:12

·       In the previous episode 0:30

·       Lupus Gradient 2:01

·       Back to Dr. Brian Greenwood 3:48

·       Polyarthritis 4:04

·       Rates of autoimmune diseases 6:00

·       Malaria and mouse models 7:33

·       Back to lupus 8:48

·       First case of lupus 15:14

·       Prevalence of lupus 17:15

·       Papers on lupus 21:23

·       Dr. Mickael Essouma 23:38

·       Dr. Essouma, how did you conduct this study? 24:01

·       Did you ever believe there was a gradient? 26:09

·       Dr. Sandro Vento 30:56

·       Dr. Vento, do you believe there was a lupus gradient? 31:51

·       What are the connections to infectious disease? 38:51

·       That’s a wrap! 43:04

·       Coming up in part 4 44:55

·       Thanks for listening 45:05

Disclosures: Brown reports no relevant financial disclosures. Healio could not confirm relevant financial disclosures for Essouma and Vento at the time of posting.

Mickael Essouma, MD, is physician from Cameroon specialized in internal medicine at the University of Yaounde I in Cameroon, with a complimentary certificate on rheumatology from the EULAR online course and a certificate on lupus from the European Lupus Society (SLEuro). He is an advocate of lupus and other autoimmune diseases in Africans.

Sandro Vento, MD, is the dean of faculty of medicine at the University of Puthisastra, Phnom Penh, Cambodia and a consultant and collaborating specialist at Mayo Clinic Center for Tuberculosis, WHO Collaborating Center.

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:

Bae SC, et al. Arthritis Rheum. 1998;doi:10.1002/1529-0131(199812)41:123.0.CO;2-D.

Bryc K, et al. Am J Hum Genet. 2015;doi:10.1016/j.ajhg.2014.11.010.

Essouma M, et al. J Autoimmun. 2020;doi:10.1016/j.jaut.2019.102348.

Gilkeson GS, et al. Lupus. 2011;doi:10.1177/0961203311404915.

Micheletti SJ, et al. Am J Hum Genet. 2020;doi:10.1016/j.ajhg.2020.06.012.

Symmons DP. Lupus. 1995;doi:10.1177/096120339500400303.

Vento S, et al. Front Med. 2020;doi:10.3389/fmed.2020.00202.

This episode delves into what we can learn about the impact of the environment on autoimmunity, digging into how rates of autoimmunity can vary drastically in different parts of the world.

·       Intro 0:12

·       In this episode 0:16

·       Dr. Brian Greenwood 0:22

·       The geography of autoimmunity 7:01

·       Type 1 diabetes 10:31

·       Finland and type 1 diabetes 13:57

·       Socioeconomics 17:59

·       Genetics and autoimmune diseases 24:19

·       Migration studies 24:53

·       Denmark and multiple sclerosis 30:06

·       Coming up in part 3 36:02

·       Thanks for listening 38:16

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:

Bach JF. N Engl J Med. 2002;doi:10.1056/NEJMra020100.

Bodansky HJ, et al. BMJ. 1992;doi:10.1136/bmj.304.6833.1020.

Dean G, et al. J Neurol Neurosurg Psychiatry. 1997;doi:10.1136/jnnp.63.5.565.

Hammond SR, et al. Brain. 2000;doi:10.1093/brain/123.5.968.

Hawkes CH, et al. Mult Scler Relat Disord. 2019;doi:10.1016/j.msard.2019.08.001.

Karvonen M, et al. Diabetes Care. 1999;doi:10.2337/diacare.22.7.1066.

Kondrashova A, et al. Diabetes Care. 2007;doi:10.2337/dc06-0711.

Marciulionyte D, et al. Diabetologia. 2001;doi:10.1007/s001250051574.

Nielsen NM, et al. Brain. 2019;doi:10.1093/brain/awz088.

Patterson CC, et al. Diabetologia. 2012;doi:10.1007/s00125-012-2571-8.

Sandy JL, et al. Pediatr Diabetes. 2021;doi:10.1111/pedi.13191.

This episode delves into the history of the hygiene hypothesis. What do we know about different exposures changing risk for asthma and allergies, and do these exposures have the same protection for autoimmunity?

·       Intro 0:12

·       In this episode 0:18

·       Hygiene hypothesis 0:33

·       Allergic rhinitis (or Hay fever) 2:32

·       Pollen and the allergy skin test 8:58

·       Exposure and cleanliness 10:22

·       Allergic rhinitis and Cree Native Americans 11:51

·       Appendicitis 13:10

·       Family size and asthma 14:36

·       Rural versus urban populations 17:41

·       Dust 18:31

·       Children, day care and infections 22:43

·       The “old friends” theory 28:29

·       Farming and allergies 30:07

·       The Amish and the Hutterites 33:02

·       Mice, dust and asthma 34:47

·       Thanks for listening 37:40

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:

Emanuel MB. Clin Exp Allergy. 1988;doi:10.1111/j.1365-2222.1988.tb02872.x.

Flohr C, et al. Clin Exp Allergy. 2010;doi:10.1111/j.1365-2222.2009.03346.x.

Genuneit J. Pediatr Allergy Immunol. 2012;doi:10.1111/j.1399-3038.2012.01312.x.

Karvonen AM, et al. J Allergy Clin Immunol. 2019;doi:10.1016/j.jaci.2019.07.035.

Perkin MR, et al. Front Allergy. 2022;doi:10.3389/falgy.2022.1051368.

Rantala AK, et al. Epidemiol. 2020;doi:10.1097/EDE.000000000001163.

Sangrador CO, et al. Allergol Immunopathol (Madr). 2018;doi:10.1016/j.aller.2018.03.006.

Stein MM, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1508749.

Strachan DP. BMJ. 1989;doi:10.1136/bmj.299.6710.1259.

Weber J, et al. Am J Respir Crit Care Med. 2015;doi:10.1164/rccm.201410-1899OC.

On this special episode of Rheuminations, I interview comedian and ophthalmologist William Flanary, MD, and Kristin Flanary, also known as the Glaucomfleckens, on hypermobility and physician burnout.

Kristen Flanary highlights what it's like to live with hypermobility, and Dr. William Flanary discusses his thoughts on physician burnout and using their podcast, Knock Knock, Hi, as comedy relief.

·       Intro 0:11

·       In this episode 0:45

·       Interview with Dr. William and Kristin Flanary, also known as Doctor and Lady Glaucomflecken 2:49

·       Rheumatology and ophthalmology overlap 3:11

·       Can you tell me a few things about yourselves? 7:48

·       Kristin Flanary, MA: when did you notice your hypermobility and when did you start having complications from it? 12:19

·       Do you ever fully dislocate or do you kind of feel like you’re about to? 19:53

·       Chest compressions and William Flanary 25:23

·       Have you done any bracing? 26:24

·       Dr. Linda Bluestein, @hypermobilityMD, on the Glaucomfleckens podcast 30:24

·       William Flanary, MD: can you talk about your experience with physician burnout? And are you optimistic about AI solving the physician burnout problem? 31:16

·       Artificial Intelligence with Cardiologist Dr. Eric Topol | Knock Knock, Hi with the Glaucomfleckens, @EricTopol 37:01

·       Can you tell us more about your podcast, Knock Knock, Hi? 41:06

·       Thank you 44:59

Disclosures: Brown and the Flanarys report no relevant financial disclosures.

William E. Flanary, MD, is an ophthalmologist and part-time comedian, also known as Dr. Glaucomflecken. You can follow him on Twitter @DGlaucomflecken.

Kristin Flanary, MA, is a marketing and communications specialist, also known as Lady Glaucomflecken. You can follow her on Twitter @LGlaucomflecken.

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

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 [email protected]. 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 [email protected]. 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.