Healio Rheuminations

John Stone, MD, MPH, is the world leader in the field of IgG4-related disease research. In this episode, he breaks down the histology of IgG4-related disease, important aspects of what is known about the pathophysiology of the disease, as well as future directions in treatment. Intro :10 Inside this episode :13 IgG4-related disease background :31 An anecdote 1:15 The interview 4:09 History of IgG4-related disease 4:18 IgG4 pathology and terms 7:48 What makes IgG4 different from other IgG subclasses? 10:23 What do we know about the interplay between B and T cells? 12:31 What is SLAMF7? 16:30 What happens to T cells during B-cell depletion? 18:22 Antigens involved in IgG4 21:06 Future of treatment 23:10 Thank you, Dr. Stone 24:32 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum John Stone, MD, MPH, is director of clinical rheumatology at Massachusetts General Hospital.

In this episode, James Rosenbaum, MD, an expert in inflammatory eye disease, breaks down how systemic autoimmune conditions can affect the eye and highlights pearls that Rheumatologists should know. Intro :10 Inside this episode :15 Introducing Dr. Jim Rosenbaum :51 The interview 1:26 Some basic terms 1:45 TEON pneumonic 5:45 Microbiome work 7:06 Evaluation of inflammatory eye disease 9:01 Workup for inflammatory eye disease 10:23 How do ophthalmologists rule out infection? 18:00 Is there anatomic overlay between the eye and joints? 23:10 A pen light and history 25:30 Treatment algorithm 27:27 What excites you the most about the future of inflammatory eye disease? 33:31 Thank you, Dr. Rosenbaum 37:03 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum James T. Rosenbaum, MD, is professor of ophthalmology, medicine and cell biology; head of the division of arthritis and rheumatic diseases and Edward E. Rosenbaum Professor of Inflammation Research at Oregon Health and Science University.

We journey into the world of metabolic bone in this episode and explore the varied clinical manifestations of hypophosphatasia. We also interview the head of the center for osteoporosis and metabolic bone disease at the Cleveland Clinic, Chad Deal, MD. Intro :10 The four H’s of chondrocalcinosis :18 What we’ll cover in this episode :52 A general overview 2:33 The first description of hypophosphatasia 3:39 History of this condition 13:00 Two cases 16:00 The interview 17:55 Various presentations 18:42 Laboratory findings 21:13 Differentiating the terminology 24:55 The relationship between this and chondrocalcinosis 27:11 Mechanisms of pain 28:15 Treatment options 29:30 Thank you, Dr. Deal 38:00 Episode recap 38:10 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Linglart A, Biosee-Duplan M. Curr Osteoporos Rep. 2016;14:95-105. Rathbun JC. Am J Dis Child. 1948;75:822-831. Robison R. Biochem J. 1923;17:286–293. Turan S, et al. J Clin Res Pediatr Endocrinol. 2011;3:7-11. Whyte MP. Bone. 2017;102:15-25.

This ripping yarn delves into the history of tumor necrosis factor in relation to rheumatoid arthritis with emphasis on the original studies that set the stage for the use of TNF inhibition in RA.  Intro :11 What we’ll cover here :16 Recap of Part 1 1:25 What I discovered when doing this episode 1:22 What this episode won’t address 2:40 Let the tale begin 3:12 A look at matrix metalloproteinases 3:32 A breakthrough in understanding RA 6:28 Two key players: Dr. Mark Feldman and Dr. Ravinder Maini 6:53 The first cytokine research conducted in RA: IL-1 8:00 The next cytokine: Tumor necrosis factor 11:16 What do we know about cytokine production within the joint? 14:33 IL-6 and TGF-beta 19:16 A bit about IL-10 23:57 *Visit Healio.com/rheum for daily news and updates* How do we choose which cytokines to block to make improvements in RA? 25:16 What about in vivo data? 29:45 The history of infliximab 34:00 Infliximab is approved for RA treatment 45:13 TNF in RA: from bedside, to bench then back to bedside 46:06 It’s important to recognize the researchers who discovered these pathways 46:18 Remember the scientists next time you prescribe a TNF inhibitor 47:05 Read the latest news and commentary on Healio.com/rheumatology and Follow us on Twitter @HealioRheum and @HRheuminations for updates 47:34 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Brennan FM, et al. J Autoimmun. 1989;2 Suppl:177-186. Brennan FM, et al. Lancet. 1989;2:244-247. Butler MD, et al. Eur Cytokine Netw. 1995;6:225-230. Chu CQ, et al. Arthritis Rheum. 1991;34:1125-1132. Dayer JM, et al. J Exp Med. 1985;162:2163-2168. Di Giovine FS, et al. Ann Rheum Dis. 1988;47:768-772. Feldmann, M. Nat Rev Immunol. 2002;2:364-371. Feldmann M, Maini SR. Immunol Rev. 2008;223:7-19. Fontana A, et al. Rheumatol Int. 1982;2:49-53. Haworth C, et al. Eur J Immunol. 1991;21:2575-9. Houssiau FA, et al. Arthritis Rheum. 1988;31:784-8. Keffer J, et al. EMBO J. 1991;10:4025-4031. Kulkarni AB, Karlsson S. Am J Pathol. 1993;143:3-9. Kuruvilla AP, et al. PNAS. 1991;88:2918-2921. Maini RN, et al. Arthritis Rheum. 1998;41:1552-1563. Malaviya AN, Mehra NK. Indian J Med Res. 2018;148:263–278. McInnes IB, Schett G. Nat Rev Immunol. 2007;7:429-442. Mitchison NA, Medawar PB. Proc R Soc Lond [Biol]. 1964;https://doi.org/10.1098/rspb.1964.0093. Pettipher ER, et al. Proc Natl Acad Sci U S A. 1986;83:8749-8753. The Beautiful Cure: The Revolution in Immunology and What It Means for Your Health, University of Chicago Press, Chicago, 2018. Williams RO, et al. Proc Natl Acad Sci U S A. 1992;89:9784-9788. Xu WD, et al. J Clin Invest. 1989;83:876-882.

In Part 1, we look at the original studies that led to the discovery of TNF in two separate labs where researchers were looking for two completely different things. We’ll learn how these discoveries then fueled the use of TNF in the failed trials as an anti-cancer agent, and the eventual development of antibody therapy against TNF in septic shock. Intro :11 The origins of this episode and what we’ll cover here and in Part 2 :18 What Part 1 will cover 2:01 Early cytokine research in general codiscovery of TNF TNF as anticancer agent TNF’s role in cachexia trials of anti-TNF in the setting of septic shock What part 2 will cover 2:59 TNF’s role in rheumatoid arthritis TNF in the late 1800s 3:18 Lipopolysaccharide from gram-negative bacteria is first isolated and discovered 8:16 Fast forward to the 1960s, enter Memorial Sloan Kettering Cancer Center 9:08 Anthony Cerami studies cachexin in his Rockefeller lab 11:10 Focus on cachexia 12:27 Late 1980s: TNF is produced and given to humans using recombinant technology 20:01 Studies of TNF in patients with various types of cancer 20:48 High doses seem to induce shock-like illness 21:38 TNF-secreting tumor is created and tested 25:21 Some take away 26:12 Studying TNF led to the discovery that it’s associated with shock 26:33 Money pours into research on blocking TNF 27:00 A look at studies of TNF in infection 27:22 Study of TNF in sepsis 30:20 Let’s talk about anti-TNF and what it’s doing 34:00 Studies of anti-TNF in humans 36:00 Rat and baboon studies don’t always correlate with humans 40:25 Episode recap 40:45 Stay tuned for Part 2 42:20 Follow us on Twitter @HRheuminations and leave us a review in iTunes 42:50 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum References: Beutler B, et al. Science. 1985;229:869–871. Blick M, et al. Cancer Research. 1987;47:2986-2989. Carswell E, Williamson B. Cancer Imm. 2012;12:4. Feldman M. Nat Rev Immunol. 2002;2:364-371. Fong Y, et al. J Exp Med. 1989;170:1627-1633. Kawakami M. Mol Med. 2014;doi:10.2119/molmed.2014.00177. Lv S, et al. Int J Clin Pract. 2014;68:520-528. Marks JD, et al. Am Rev Respir Dis. 1990;141:94-97. McCarthy EF. Iowa Orthop J. 2006;26:154-158. Michi HR, et al. N Engl J Med. 1988;318:1481-1486. Oliff A. Cell. 1988;54:141-142. Opal SM, et al. J Infect Dis. 1990;161:1148-1152. Qui P, et al. Expert Opin Investig Drugs. 2011;20:1555-1564. Tracey KJ, et al. Nature. 1987;330:662-4. Waage A, et al. Lancet. 1987;1:355-7.

Take a listen to this medical mystery and learn about a not-so-rare condition — depending on where you live. Hear some interesting historical stories about the physicians who helped establish the diagnosis, as well as an interview with a renowned expert. Intro :11 A 57-year-old woman presents with multiple-week history of joint pain. She also complains of lesions on her forearms. :32 Initial lab results 1:30 She arrives at my office 1:50 Review of her vitals 1:57 Physical exam findings and patient history 2:05 What about the nodules on her skin? 3:20 Tests leading to diagnosis 4:40 What’s the diagnosis? 4:55 A personal anecdote 5:20 Symmetrical polyarticular inflammatory arthritis in the setting of erythema nodosum 6:18 What do we know about Löfgren Syndrome? 7:45 History of this diagnosis 8:35 What we know 100 years later 11:13 Focus on the inflammatory arthritis of Löfgren Syndrome 14:25 Are these different diseases? 18:07 Summary of what we’ve discussed so far 19:13 Unsung heroes who showed sarcoidosis is associated with inflammatory arthritis 20:40 Introduction of Dr. Daniel Culver 28:26 An update on sarcoidosis with Dr. Culver 29:17 Why should we care about staging on X-ray? 29:22 Are there any clues that it may be sarcoid based on histology and morphology of the granuloma itself? 30:56 How does bronchoalveolar lavage help? 32:58 How often do you see remissions in non-Löfgren’s sarcoidosis? 34:41 What are your thoughts on the serum biomarkers? 36:34 Can you comment with your thoughts on the link between the environment and the disease? 38:25 What about infectious triggers? 40:06 Do you think genetic studies will eventually be used for diagnosis or prognosis? 41:18 Where do you think we’ll be with the diagnosis and treatment of sarcoidosis in 10 years? 42:38 Thank you, Dr. Dan Culver 44:28 Episode recap 44:40 Follow us on Twitter @HRheuminations and leave us a review in iTunes 45:18 Daniel Culver, DO, is director of the Interstitial Lung Disease Program at Cleveland Clinic and director of The Sarcoidosis Center of Excellence at Cleveland Clinic. We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @AdamJBrownMD @HealioRheum @HRheuminations References: Grunewald J, Eklund A. Am J Respir Crit Care Med. 2009;179:307-312. Le Bras E, et al. Arthritis Care Res (Hoboken). 2014;66:318-322. Lofgren S, Lundback H. Acta medica Scandinavica. 1952;142. Maña J, et al. Am J Med. 1999;107:240-245. Palmer DG, Schumacher HR. Ann Rheum Dis. 1984;43:778–782. Segura BT, et al. Medicina Clinica (Barc). 2014;143:166-9.

In this guest episode, Leonard Calabrese, DO, provides the history of systemic lupus erythematosus, with special emphasis on the discovery of the LE cell and the two clinics involved in its detection.   Introduction of Leonard Calabrese, DO :11 In this episode … 1:44 A brief history of systemic lupus erythematosus and the major players 2:15 Laurent-Theodore Biett 2:55 Casanave 3:05 von Hebra 3:24 Moritz Kaposi 4:05 Sir William Osler 5:25 Fast-forward to observations made during WWII era 7:00 The story of two clinics 8:55 The Mayo Clinic 9:00 The Cleveland Clinic 16:24 A race against time 18:29 Lupus is no longer a diagnostic problem 20:02 In a nutshell 20:15 Housekeeping items 20:51 Leonard Calabrese, DO, is head of Cleveland Clinic’s Section of Clinical Immunology, co-director of Center for Vasculitis Care and Research, and chief medical editor of Healio Rheumatology. We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Follow us on Twitter @AdamJBrownMD @HealioRheum @HRheuminations @LCalabreseDO

Richard Furie, MD, is chief, division of rheumatology, at Northwell Health, and professor of medicine at Hofstra/Northwell School of Medicine. Join us in this ACR interview, as we discuss the story of interferon, lupus therapeutics — including B cell depletion — and the future of lupus research and treatments. Intro :10 Background on Dr. Furie :16 The interview :56 What advancements in the pathophysiology of lupus are you most excited about? 1:10 The interferon story 1:23 The interferon story is not finished yet 7:18 Dendritic cells in lupus patients 7:41 What is “interferon signature?” 8:07 Do we see different clinical phenotype in patients with high interferon signature? 9:38 What’s your opinion on the role of B cells? 10:07 Any other pathophysiology mechanisms being used to target B cells? 13:15 Are we stretched thin in terms of number of lupus patients in trials? 15:21 How would designating lupus as an orphan disease change the way it’s investigated? 16:40 What is your main concern regarding study design? 17:37 Looking 10 years ahead, do you think what we call “lupus” will still be referred to as such, or will it be decompartmentalized into different diseases? 21:26 What’s the expense of cytokine profiling? 22:40 What excites you the most about the future of lupus research? 23:21 Thank you, Dr. Furie 24:41 Recap 24:43 Shout out to the 7th Annual Basic and Clinical Immunology for the Busy Clinician: What is New and Hot in Immunology bootcamp in Scottsdale, AZ, Feb. 15-16, 2019 25:31 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. And be sure to follow us on Twitter @AdamJBrownMD and @HealioRheum. This information is brought to you by Healio and is not sponsored by, nor a part of, the American College of Rheumatology.

In this episode, John Stone, MD, MPH, director of clinical rheumatology at Massachusetts General Hospital, sits down to discuss his approach to giant cell arteritis and the results of the GiACTA trial. Learn why Stone believes the most important diagnostic test in GCA is the patient’s history. Intro :10 Background on Dr. Stone :59 The interview 2:10 Differentiating subtle GCA from the “classic case” 2:20 Data from Stone’s recent paper in Rheumatology 5:17 Using bilateral biopsies 9:00 Recommendations for temporal artery biopsy – who, when, where 11:13 Thoughts on imaging for GCA diagnosis 13:14 IL-6 and treatment of GCA 15:16 GiACTA trial – what surprised you most about the efficacy of prednisone alone? 19:05 Findings with tocilizumab 21:29 Inflammatory markers in GCA 24:47 Should we use tocilizumab right off the bat? 26:50 What excites you the most about the future of this field? 29:59 Thank you, Dr. Stone 31:33 Recap 31:38 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. And be sure to follow us on Twitter @AdamJBrownMD and @HealioRheum.

John J. O’Shea, MD, is scientific director of the NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases, and chief of their Molecular Immunology and Inflammation Branch. In this ACR interview, he joins me to talk about the JAK/STAT pathway, what we’ve learned from mouse models, current FDA-approved JAK inhibitors and the future of this exciting field. Intro :10 Background on Dr. O’Shea :45 The interview 2:37 How did you start looking into the JAK/STAT pathway? 3:16 What should a clinician understand about this pathway? 5:22 What do these cytokines have in common? 6:37 What have we learned from mouse models? 8:48 GWAS studies in JAK/STAT 11:49 Can we quantify how much a certain cytokine may be using this pathway? 12:39 Can you explain suppressor of cytokine signaling, aka SOCS? 14:15 What do we know about how these different cytokines can have individual signaling controls? 16:40 An explanation of phenocopy 18:01 What evidence do we have that JAK may circumvent STAT, and vice versa? 18:41 An overview of FDA-approved JAK inhibitors and the pipeline 20:52 What excites you the most about the future of this field? 23:26 In a state of wonder over success of biologics 25:50 Thank you, Dr. O’Shea 27:20 Recap 27:30 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. And be sure to follow us on Twitter @AdamJBrownMD and @HealioRheum. This information is brought to you by Healio and is not sponsored by, nor a part of, the American College of Rheumatology.