Healio Rheuminations

In this ACR interview, the walking encyclopedia of medical history, Eric L. Matteson, MD, of The Mayo Clinic, sits down with me to discuss what excites him about medical history and then takes a deep dive into the history of vasculitis!  Intro :10 Background on Dr. Matteson :28 The interview 2:00 How did you get into history? Why does it mean so much to you? 2:19 Can you tell us about the archives at Mayo Clinic? 6:49 An appreciation of present time and how we take some medications for granted 7:55 Brief history of vasculitis 9:23 Kussmaul and the first failed ophthalmoscope 14:20 Kussmaul’s second failure: gastroscope 15:43 When did we get to the small vessel vasculitis/glomerulonephritis description? 17:25 The discovery of Wegener 20:44 Wegener was not the first to describe granulomatosis with polyangiitis, and the folly of naming diseases for individuals 23:24 Thank you, Dr. Matteson 24:57 Recap 25:05 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. This information is brought to you by Healio and is not sponsored by, nor a part of, the American College of Rheumatology.

Martin J. Blaser, MD, is director of the Human Microbiome Program at NYU and author of the book, Missing Microbes. He sat down and spoke with us about how the microbiome plays a role in disease pathogenesis, including autoimmunity, and he also answered the question of whether all of our patients should be on probiotics!   Intro :11 Background on Dr. Blaser :35 The interview 1:20 What is the microbiome? 1:25 How unique are individual microbiomes? 1:49 How does an individual’s microbiome change over time? 2:13 Microbial diversity in different populations 3:12 What’s your concern with the loss of microbiome diversity? 4:20 A bit on Blaser’s research on obesity and antibiotic use 5:21 Is the timing of antibiotic administration important, in terms of the side effects it can produce? 6:43 Worldwide antibiotic prescribing rates 7:54 The microbiome and autoimmunity 9:02 The microbiome and type 1 diabetes, IBD 10:45 Research with IL-17 12:23 Microbiota transplants 13:09 For how long is the microbiome perturbed after giving antibiotics? 13:57 Diet and microbiome findings 14:54 Probiotics, prebiotics and symbiotics 15:33 In 10 years, how will people be investigating/manipulating the microbiome? 18:18 Have we shown with research that introducing certain types of bacteria can be sustainable in the gut? 19:47 Thank you, Dr. Blaser 20:26 Summary 20:33 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. 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, explore data from the major study proving uric acid crystals are present in the synovial fluid of patients with gout, as well as the tale of two rheumatologists who injected their own knees (while still working in the hospital) with uric acid to prove it is the trigger for inflammation in gout. The episode finishes with some ripping yarns about the history of the medications we use to treat this condition.   Intro :10 Controversy surrounding uric acid’s role in gout :45 “Game changing” paper published in 1961 2:07 The first description of pseudo gout 5:53 How do you prove uric acid triggered the inflammatory response? 6:37 One of my favorite studies 6:43 Faires and McCarty inject themselves with uric acid 7:49 Details of what they experienced 8:22 4 hours later … 8:52 Both patients receive treatment 9:12 Review of what we’ve discussed so far 10:06 Let’s try and answer the question posited in The History of Gout, Part 1 10:35 Colchicine – previously a medicinal plant 10:41 A look at the history of urate-lowering therapy 12:59 Probenecid was developed to reduce the excretion of penicillin 13:18 The history of allopurinol 14:32 Don’t give allopurinol to patients on azathioprine 17:21 The answer to the question posed in Part 1 17:49 Summary 18:12 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. References: Barnett R. Lancet. 2018;391:2595. Faires JS, Mccarty DJ. Lancet. 1962;280:682-685.   Kippen I, et al. Ann Rheum Dis. 1974;33:391-396. Marson P, Pasero G. Reumatismo. 2011;63:199-206. McCarty DJ, Hollander JL. Ann Intern Med. 1961;54:452-460. Nuki G, Simkin PA. Arthritis Res Ther. 2006;doi: 10.1186/ar1906. Rundles RW. Arch Intern Med. 1985;145:1492-1503. Shyambhavee, Behera BK. J Pharmacol Clin Toxicol. 2017;5:1098. Storey GD. Rheumatology. 2001;40:1189-1190. West JB. Am J Physiol Lung Cell Mol Physiol. 2014;doi:10.1152/ajplung.00223.2014.

Do you know the etymology of the word “gout,” or how a simple microscope aided in the identification of tophi? Join me as I explore the history of this inflammatory arthritis and highlight the important scientists who shaped the modern era of gout. Intro :10 What to expect in Part 2 :48 A question: Which urate-lowering therapy was made for an expressly different reason than to treat gout? 1:34 The first modern description of gout 1:54 Let’s go back to the Greeks 3:05 Why is it called “gout?” 3:06 An anecdote from medical school 4:13 Hippocrates’ words of wisdom on gout 4:58 First century AD: Gout is linked with excessive eating and drinking 6:01 Things get muddled 6:20 1683: The modern era of gout is described 6:42 “Gout Perspectives” published in The Lancet in 2018 7:06 Self-taught Dutch scientist, Antony van Leeuwenhoek, pioneers the microscope and identifies tophi 8:29 Swedish chemist Carl Wilhelm Scheele discovers uric acid 11:38 William Hyde Wollaston tests tophi and discovers it’s full of uric acid 12:57 Emperor of uric acid, Alfred Baring Garrod, associates elevated serum uric acid with gout 13:48 If anyone knows how the thread test works, please email me 14:58 He theorized that uric acid causes gout 15:37 A look back at what we know 16:09 What we don’t know: What’s in the joints of patients with acute gout? 16:22 Stay tuned for The History of Gout, Part 2 16:34 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. References: Barnett R. Lancet. 2018;391:2595. Faires JS, Mccarty DJ. Lancet. 1962;280:682-685.   Kippen I, et al. Ann Rheum Dis. 1974;33:391-396. Marson P, Pasero G. Reumatismo. 2011;63:199-206. Mccarty DJ, Hollander JL. Ann Intern Med. 1961;54:452-460. Nuki G, Simkin PA. Arthritis Res Ther. 2006;doi: 10.1186/ar1906. Rundles RW. Arch Intern Med. 1985;145:1492-1503. Shyambhavee, Behera BK. J Pharmacol Clin Toxicol. 2017;5:1098. Storey GD. Rheumatology. 2001;40:1189-1190. West JB. Am J Physiol Lung Cell Mol Physiol. 2014;doi:10.1152/ajplung.00223.2014.

This episode discusses the case of an 85-year-old man with a history of hypertension and fairly recently diagnosed bladder cancer who presents with oligoarticular asymmetric inflammatory arthritis. Explore the details of this case and learn how bacillus Calmette-Guérin and reactive arthritis are related in this diagnostic conundrum. Intro :10 An 85-year-old man with a history of hypertension and recently diagnosed bladder cancer presents with oligoarticular asymmetric inflammatory arthritis :18 Details of his cancer history :32 How BCG (bacillus Calmette-Guérin) is used for superficial bladder cancer :53 Patient wakes with acute onset, rapidly progressing joint pain 1:21 Results of synovial aspiration of his right wrist 2:06 Physical exam findings and patient history 2:24 Discharged from outside hospital 2:53 Outpatient rheumatologist orders autoimmune serologies 3:03 Second hospital admission 3:24 Infectious disease evaluation 4:25 Patient presents to Cleveland Clinic 4:54 What do we have? 6:18 The main concern is he’s been instilled with bacteria 6:45 Could this be a reactive arthritis? 7:18 History of BCG 7:45 What do we know about what happens to these patients? 10:28 How do we define disseminated BCG infection vs. a reactive arthritis? 10:58 A single institution cohort of disseminated infection after BCG instillation 11:29 Comparing these definitions in our patient 14:34 A look at reactive arthritis 15:07 What do we use to treat these patients? 16:12 A look back at our patient 16:31 Continued treatment with triple therapy 17:05 A diagnostic conundrum 17:32 The diagnosis, in hindsight 18:11 Summary 18:49 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. References: Bernini L. Autoimmun Rev. 2013;12:1150-1159. Meyer J. Postgrad Med J. 2002;78:449-454. Pérez-Jacoiste Asín MA. Medicine (Baltimore). 2014;93:236-254. To U. Case Rep Med. 2014;doi:10.1155/2014/362845. 

This episode covers a rare but life-threatening complication of lupus nephritis called complement-mediated thrombotic microangiopathy. Rheumatologist Lisa Zickuhr, MD, helps us better understand this often-overwhelming topic with a clinical case example, treatment options and practice pearls. Intro :10 Introduction of Lisa Zickuhr, MD, rheumatologist :44 Complement-mediated thrombotic microangiopathy in lupus is an overwhelming topic 1:50 Definition of TMA 2:15 What is MAHA? 3:10 Four classic symptoms associated with TMA syndromes 3:35 What causes TMA? 3:50 Complement-mediated TMA 5:35 How this is seen in clinical practice 9:10 Case example of complement-mediated TMA 10:10 Summary of case presentation 13:05 What’s next? 13:50 Takeaways from this clinical presentation 15:48 Primary and secondary complement-mediated TMA 18:23 An argument for a primary etiology of complement-mediated TMA in lupus 18:51 CliffsNotes version for rheumatologists, HCPs caring for lupus patients 21:12 Therapy for complement-mediated TMA is two-pronged 22:35 Patient profile 24:05 Summary 25:10 Thank you to Dr. Lisa Zickuhr 26:13 Lisa Zickuhr, MD, is a rheumatologist at Washington University in St. Louis. We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. References: Dragon-Durey MA, et al. J Am Soc Nephrol. 2005:555-563. Dragon-Durey MA, et al. Semin Thromb Hemost. 2010:633-640. George JN, et al. N Engl J Med. 2014 Aug 14;371:654-666. Jönsen A, et al. Arthritis Res Ther. 2011;13:R206. Laszlo MH, et al. Ann Intern Med. 1955;42:1308-1320. Nesher G, et al. Semin Arthritis Rheum. 1994;24:165-72. Zickuhr L, et al. Arthritis Care Res (Hoboken). 2018;doi: 10.1002/acr.23561.

A young woman presents with migraine-like headaches, black spots in her vision and emotional lability. Think you know the diagnosis? You may be surprised – this medical mystery is not what it seems. In this episode, learn more about this rare diagnosis, and gain clinical insight from neurologist Devon Conway, MD, and ophthalmologist Arthi Venkat, MD. Intro :11 A 24-year-old woman presents with gradual worsening of a migraine-like headache accompanied by nausea :22 Description of symptoms :37 ER visit 1:23 Onset of new symptoms 1:44 Second ER visit 2:11 Outpatient MRI findings 2:28 Lumbar puncture findings 2:50 Patient is admitted to hospital 3:52 Second MRI findings 4:16 Ophthalmology consult and results of fluorescein angiography 4:46 Audiogram is ordered 5:17 Case summary 5:40 What is the most likely diagnosis? 6:05 Triad of Susac syndrome 6:27 Remember: This is not a vasculitis 7:11 History of Susac syndrome 7:40 CNS manifestations of the Susac triad 8:27 Consult with Devon Conway, MD 10:13 Flare signals for non-radiologists/neurologists 11:05 Anything specific that says “demyelinating” on MRI? 13:35 Distinguishing the lesions in this case from those of MS 15:36 Neurology work-up approach to this type of case 16:28 The utility of lumbar puncture in this situation 18:05 About ADEM (acute disseminated encephalomyelitis) 21:06 Ocular manifestations of Susac syndrome 22:26 Consult with Arthi Venkat, MD 23:17 Ophthalmology differential in a patient with intermittent vision loss in various fields of vision 23:55 Overview of branch retinal artery occlusions 25:22 Difference between branch retinal artery occlusions and other ophthalmologic presentations common to rheumatologists 27:51 How the ophthalmologic exam helps differentiate MS from Susac syndrome 30:07 Overview of sensorineural hearing loss in Susac syndrome 34:09 Do we know for sure this is an autoimmune disease? 34:59 Aggressive immunosuppression seems to halt the progression of disease 35:34 What are treatment options? 35:42 What do we know about long-term outcomes? 36:31 Who takes care of these patients? 37:29 Treatment, outcome of this patient 38:07 Episode/case summary 38:20 Devon Conway, MD, is a staff neurologist at Cleveland Clinic’s Mellen Center for Multiple Sclerosis. Arthi Venkat, MD, is a retinal and uveitis specialist at Cole Eye Institute at Cleveland Clinic. We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. References: Aubart-Cohen F, et al. Medicine (Baltimore). 2007;86:93-102. Greco A, et al. Autoimmun Rev. 2014;13:814-821. Rennebohm RM, et al. Int J Stroke. 2018;doi:10.1177/1747493017751737.

Do you know which U.S. president had Addison’s disease? Or how rumors from WWII led to funding for research on cortisol? In this episode, take a trip down memory lane as we detail the history of steroids and the scientists whose work lead to the discovery of prednisone. Intro :14 A query: What other disease is attributed to Thomas Addison? :40 Overview of the layers of the adrenal gland 1:18 History of the adrenal gland 2:10 Thomas Addison enters the scene 3:39 Kennedy and terminology 6:15 Charles Brown-Sequard helps describe function of adrenal glands 7:13 George Oliver and Edward Sharpey-Schafer help understand adrenal gland 8:44 Adrenaline is discovered 10:03 Steroid chemistry begins in earnest 10:14 Steroids discovered, but questions remain 10:25 WWII rumors spur research on cortin 11:15 Edward Calvin Kendall, Tadeus Reichstein and Philip Showalter Hench receive Nobel prize for their discoveries relating to the hormones of the adrenal cortex 12:23 Committee of 14 chemists assembled 14:24 1948: The case of Mrs. G 15:21 Pharmaceutical companies race to produce cortisone 17:08 How we arrived at prednisone 17:43 The answer to the question: “What other disease was described by Thomas Addison?” 18:34 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. References: Benedek TG. Clin Exp Rheumatol. 2011;29:S-5-12. Burns CM. Rheum Dis Clin North Am. 2016;doi: 10.1016/j.rdc.2015.08.001. Lawrence L. Controversial ‘father’ of endocrinology: Brown-Séquard. Endocrine Today. February 2008. https://www.healio.com/endocrinology/news/print/endocrine-today/%7B0b1791e0-0e1c-42ac-bec3-d5b67bb054f6%7D/controversial-father-of-endocrinology-brown-squard. Accessed April 10, 2018. Pearce JMS. J R Soc Med. 2004;97:297-300.

Biosimilars are a fascinating new category of medication and are quickly becoming part of the rheumatologist’s treatment armamentarium, but they can be confusing to understand. This episode will enhance your knowledge of this new class of medications by providing a better understanding of how biologics differ from most other medications, and why biosimilars aren’t just generics of biologics. This episode also takes a brief look into the history of drug regulation with a focus on biosimilars and how they’re FDA approved. Intro :12 What is a biologic? 1:21 What makes a generic? 5:05 History of drug regulation in the U.S. 5:10 What makes a biologic? 11:43 Monoclonal antibodies 11:51 Where do biosimilars come from? 14:16 Definition 15:03 Manufacturing process 15:17 FDA approval process 16:00 Trials of biosimilars 19:44 We’d love to hear from you! Send your comments/questions to rheuminationspodcast@healio.com. Resources: Bridges SL Jr., et al. Arthritis Rheumatol. 2018;doi:10.1002/art.40388. Hornecker JR. Generic Drugs: History, Approval Process, and Current Challenges. U.S. Pharmacist. 2009;34(6)(Generic Drug Review suppl):26-30.   Janssen WF. The Story of the Laws Behind the Labels. https://www.fda.gov/downloads/AboutFDA/WhatWeDo/History/FOrgsHistory/EvolvingPowers/UCM593437.pdf. Published June 1981. Accessed April 14, 2018. Liu JKH. Ann Med Surg (London). 2014;doi:10.1016/j.amsu.2014.09.001. Morrow T, Felcone LH. Biotechnol Healthc. 2014;1:24-26,28-29.

Leonard Calabrese, DO, details the clinical manifestations of giant cell arteritis, the complex scenarios rheumatologists face when working with GCA, and the pathogenesis of this disease. Calabrese also shares clinical pearls and tips for success.    Introduction of Leonard Calabrese, DO :12 Goals of this episode :31 The disease that rheumatologists love 1:02 History of giant cell arteritis 1:51 Gene Hunder, MD, defines large vessel involvement in late ‘80s, ‘90s 4:18 Epidemiology of giant cell arteritis 4:32 Manifestations in detail 5:13 Cranial arteritis 5:20 Jaw claudication 6:04 Ocular involvement 6:44 Signs and symptoms 7:03 The most important thing about ocular ischemia in GCA 9:01 Stroke: A major complication of cranial ischemic GCA 9:25 PMR and/or systemic inflammatory presentations 11:33 A more recent presentation: inflammatory disease of unknown origin 12:19 Large vessel presentations 13:12 Diagnosis of GCA is based on clinical suspicion 14:00 Ophthalmologists must have hypervigilance 14:22 It’s a team sport to attack this disease 14:58 Overview of clinical manifestations 15:08 Histopathology 16:10 How the biopsy should be done 16:38 What about healed arteritis? 17:18 What about arteritis of the vasa vasorum? 17:41 Episode recap 17:54 The most important thing to know 18:17 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.