Healio Rheuminations

This episode dives into the rare Whipple's disease, focusing on the articular manifestations of this infectious masquerader and when a rheumatologist should consider it in the differential.

Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com.

• Intro :20
• In this episode :28
• Background on the organism 5:25
• An important point when making the diagnosis 7:48
• Who gets infected? 8:55
• What is Whipple's disease? 11:48
• This disease is fatal 15:53
• A look at the joints 16:28
• What happens when you give these patients immunosuppression? 26:36
• How to diagnose 28:38
• Summary so far 31:00

Brought to you by GSK. Consider the long-term impact of disease activity, flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com

• Other organ manifestations of Whipple's disease 32:08
• Summary and take-home 44:36

Disclosure: Brown reports no relevant financial disclosures.

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

References:

Bousbia S, et al. Emerg Infect Dis. 2010;16:258-63.

Chan RY, et al. Ophthalmology. 2001;108:2225-2231.

Dobbins 3rd WO, et al. Arthritis Rheum. 1987;30:102-105.

Durand DV, et al. Medicine (Baltimore). 1997;76:170-84.

Fenollar F, et al. BMC Infect Dis. 2011;11:171.

Feurle GE, et al. Eur J Clin Invest. 1979;9:385-389.

Geissdörfer W, et al. J Clin Microbiol. 2012;50:216-22.

Guérin A, et al. Elife. 2018;7:e32340.

Heffner DK. Lancet. 2007;370:738-9; author reply 739.

Keita AK, et al. PLoS Negl Trop Dis. 2011;5:e1403.

Lagier JC, et al. Medicine (Baltimore). 2010;89:337-345.

Lozupone C, et al. Am J Respir Crit Care Med. 2013;187:1110-7.

McAllister Jr. HA, Fenoglio Jr. JJ. Circulation. 1975;52:152-6.

O'Duffy JD, et al. Arthritis Rheum. 1999;42:812-817.

Puéchal X. Joint Bone Spine. 2016;83:631-635.

Puéchal X, et al. Arthritis Rheum. 2002;46:1130-1132.

Puéchal X, et al. Arthritis Rheum. 2007;56:1713-1718.

Raheja AA, et al. Clin Imaging. 2010;34:143-147.

Ramos JM, et al. J Med Case Rep. 2015;9:165.

Raoult D, et al. Emerg Infect Dis. 2010;16:776-82.

Schöniger-Hekele M, et al. Appl Environ Microbiol. 2007;73:2033-2035.

Stein A, et al. Am J Respir Crit Care Med. 2013;188:1036-7.

Additional resource:

Neurosigns.org's video on oculomasticatory myorhythmia can be viewed at: https://www.youtube.com/watch?v=Zwb5bt749Jo

This episode explores the history of cryoglobulinemic vasculitis, from the first person who froze a tube of blood and noticed something strange happened, to the discovery of hepatitis C. We also throw in how the lab test for cryoglobulins is performed and some of the data we have on therapy.

Brought to you by GSK. Consider the long-term impact of disease activity, flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com

• Intro :20
• In this episode :45
• How is this test done? 1:30
• What is the first description of cryoglobulins? 4:15
• The first time "cryoglobulins" is used 10:26
• Hepatitis C is discovered and linked to cryoglobulinemia 16:28
• What do we know about the pathophysiology? 19:38
• Why does HCV do this? 22:12

Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com.

• What's in the blood as a result of immune complex? 24:52
• What do we know about autoimmune diseases and the prevalence of cryoglobulins? 26:03
• What about treatment? 28:25
• Summary of this three-part series 36:16

Disclosure: Brown reports no relevant financial disclosures.

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

References:

Brouet JC, et al. Am J Med. 1974;57:775-788.

Cacoub P, et al. Clin Gastroenterol Hepatol. 2019;17:518-526.

De Vita S, et al. Arthritis Rheum. 2012;64:843-853.

Fuentes A, et al. Curr Rheumatol Rep. 2019;21:doi:10.1007/s11926-019-0859-0.

Lerner AB, Watson CJ. Am J Med Sci. 1947;214:410-415.

Lospalluto J, et al. Am J Med. 1962;32:142-147.

Meltzer M, Franklin EC. Am J Med. 1966;40:828-836.

Pascual M, et al. J Infect Dis. 1990;162:569-570.

Ragab G, Hussein MA. J Adv Res. 2017;8:99-111.

Tzioufas AG, et al. Arthritis Rheum. 1986;29:1098-1104.

Wintrobe MM, Buell, MV. Bull. Johns Hopkins Hosp. 1933;52:156-165.

In Part 2, I sit down with nephrologist Ali Mehdi, MD, and neurologist Ghulam Abbas Kharal, MD, MPH, to discuss their different specialty perspectives on working up patients with suspected cryoglobulinemic vasculitis.

Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com.

• Intro :20
• Introduction of Ali Mehdi, MD :45
• Interview with Dr. Mehdi 2:02

Brought to you by GSK. Consider the long-term impact of disease activity, flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com

• Introduction of Ghulam Abbas Kharal, MD, MPH 25:01
• Interview with Dr. Kharal 26:37
• To hear more of my interview with Abbas, keep listening 44:47
• Thank you, Dr. Kharal 53:07

Ghulam Abbas Kharal, MD, MPH, is a Partners Neurology Resident at Massachusetts General Hospital, Brigham & Women's Hospital, Harvard School of Medicine.

Ghulam Abbas Kharal, MD, MPH, is a staff neurologist at Cleveland Clinic. Kharal did his training in a combined program at Massachusetts General Hospital and Brigham & Women's Hospital, Harvard School of Medicine.

Ali Mehdi, MD, is a Nephrology Fellow at the Cleveland Clinic. Mehdi did his Internal medicine residency and chief year at the Cleveland Clinic.

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

Try your hand at this medical mystery, which is followed by some didactics on a fascinating disease which will hopefully make sense of this inscrutable title.

Brought to you by GSK. Consider the long-term impact of disease activity, flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com

• Intro :22
• What to expect in each episode :30
• The case: A 75-year-old man with Sjogren's and MALT lymphoma presents with recurrent cerebral infarcts of multiple territories 1:10
  • Rheumatology is consulted 6:11
  • Decreased sensation in toes occurs between strokes 7:14
  • What's going on with this patient? 8:36
  • What additional labs can we perform? 9:36
  • We spin the urine 11:10
  • What kind of vasculitis are Sjogren's and lymphoma associated with? 12:22
  • C3 and C4 had already been performed 13:00
  • An overall picture of this patient 13:54
  • What about the strokes? 14:19
  • Should we do more imaging? 15:57
  • At this point we can make a clinical decision 16:33
  • Why make a decision so quickly vs. waiting for biopsy? 18:18
  • Two things you must check before moving forward with a cryoglobulinemic vasculitis 19:46
  • Spoiler alert: The patient is doing really well 20:16

Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com.

• What is cryoglobulinemic vasculitis? 21:00
• What are these immunoglobulins? There are three types of cryoglobulins 22:55
• Usually driven by another identifiable disease 25:18
• What is making these immunoglobulins? 26:49
• We don't know why these immunoglobulins behave this way 27:18
• How do you explain the kidneys? 28:28
• What's occurring at the tissue level? 29:35
• How does type 1 present? 30:50
• Type 2 and type 3 31:12
• What other organ systems are involved? 33:11
• I hope you enjoyed this patient presentation 36:00
• What we'll discuss in episodes 2 and 3 36:05
• Thanks for listening 38:03

**Coming soon from Healio, Unmasking COVID-19, a podcast hosted by Gitanjali Pai, MD, infectious disease physician at Memorial Hospital and Physicians' Clinic in Stilwell, Oklahoma. In this timely new show, Dr. Pai will explore COVID-19's impact on vulnerable patient populations by answering questions from experts in various medical fields, including oncology, endocrinology and rheumatology. To submit your question for Dr. Pai, email [email protected].**

We'd love to hear from you! Send your comments/questions to [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum @LCalabreseDO @CCalabreseDO

Disclosure: Brown reports no relevant financial disclosures.

References:

Fuentes A, et al. Current Rheumatology Reports. 2019;21:60.

Silva F, et al. J Autoimmun. 2019;105:102313.

In this episode, Leonard H. Calabrese, DO, is joined by his colleague and daughter Cassandra Calabrese, DO, as they discuss specifics of irAEs, including unusual toxicities, rheumatic conditions associated with checkpoint inhibitors and the rheumatologist's role in this new area of medicine.

Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com.

• Intro :22
• Recap of Part 1 :40
• An interview with Cassandra Calabrese, DO 2:02
  • The number of patients with irAEs will grow 2:22
  • How many people actually experience irAEs? 3:40
  • Any examples of unusual toxicities? 5:49
  • What's the timeline? 6:51
  • Have you seen patients with delayed onset? 8:10
  • Most of our patients have had one irAE or another beforehand 9:04
  • Who's the captain of this ship? 10:15
  • What about inflammatory arthritis? 10:55
  • What about polymyalgia rheumatica? 13:48

Brought to you by GSK. Consider the long-term impact of disease activity, flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com

• What about sicca, is it Sjogren's? 16:22
• Can you tell us about myositis in this context? 18:38
• An overview of the guidelines 21:47
• Check out our article in March Current Opinions in Rheumatology 24:12
• What about patients with preexisting autoimmunity? 24:33
• Are you worried about blunting tumor response? 27:10
• Are there any biomarkers to predict this? 28:30
• How have you been working with oncologists to manage/educate? 29:42
• What about meetings? 31:04
• Rheumatologists have a special place in this new area of medicine 31:45

We'd love to hear from you! Send your comments/questions to [email protected]. Follow us on Twitter @HRheuminations @AdamJBrownMD @HealioRheum @LCalabreseDO @CCalabreseDO

Disclosure: Brown and Cassandra Calabrese report no relevant financial disclosures. Leonard Calabrese reports serving as an investigator and a consultant to Horizon Pharmaceuticals.

Cassandra Calabrese, DO, is associate staff member in the department of rheumatic and immunologic disease and department of infectious disease at the Cleveland Clinic. Leonard H. Calabrese, DO, is chief medical editor of Healio Rheumatology and director of the RJ Fasenmyer Center for Clinical Immunology at the Cleveland Clinic.

Checkpoint inhibitors have changed the field of oncology, as well as our understanding of autoimmunity. This episode, hosted by Leonard H. Calabrese, DO, walks us through the history of checkpoint inhibitors — from Dr. William Coley's use of infections in cancer to the development of PD-1 inhibitors.

Brought to you by GSK. Consider the long-term impact of disease activity, flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com

• Intro :20
• In this episode with Dr. Calabrese 3:07
  • Book recommendations 4:28
  • Harnessing the power of the immune system to fight cancer 5:33
  • William Coley and a patient 6:30
  • The search for Fred Stein 11:40
  • Coley designs an experiment 13:09
  • A different strain of streptococcus 16:16
  • The beginning of cancer therapy and immunotherapy 19:18
  • Where do we go from there? 20:49

Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com.

• What about tumor immunology? 21:55
• The breakthrough 24:01
• What do immunology and checkpoints have to do with it? 26:47
• What happens when the danger signal cannot be dispatched? 34:02
• Why do we, as rheumatologists, care about this? 36:04
• CHAI and LATTE 38:49
• Check out some papers on immunopathogenesis of irAEs 40:56
• Checkpoint inhibitors for autoimmune diseases; RA and GCA 41:41
• Come back for part 2 43:00

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

Disclosures: Brown reports no relevant financial disclosures. Calabrese reports serving as an investigator and a consultant to Horizon Pharmaceuticals.

Leonard H. Calabrese, DO, is chief medical editor of Healio Rheumatology and director of the RJ Fasenmyer Center for Clinical Immunology at the Cleveland Clinic.

Join Peter Grayson, MD, MSc, and I as we discuss a range of topics, including imaging in large-vessel vasculitis, doctors going into research, Twitter, rock 'n' roll and Disney World.

• Intro :10
• A bit about Peter Grayson :55
• Come see me in Phoenix in February 3:35
• The interview 4:07
  • How did you make it to the NIH? 4:27
  • Why do you think MDs aren't going into research these days 6:45
  • Social media and major meetings 9:43
  • Tell us about the NIH rock 'n' roll band 11:10
  • What imaging modalities are most used for large-vessel vasculitis? 13:32
  • What is PET scan? 14:23
    • Do you think PET scanning is the best imaging modality? 15:29
    • What are the limitations to PET? 17:48
    • Does vessel size affect PET scanning? 20:01
    • Are these machines available in most hospitals? 21:12
    • Grayson's secret sauce 22:27
    • How do glucocorticoids affect imaging? 23:19
    • Are you ever using PET as follow-up? 25:07
  • Do you have hope for any specific targets for Takayasu's arteritis? 27:12
    • What drives the surgical intervention process for these patients? 28:23
    • Collateral artery formation 30:30
  • Where do you think Takayasu's will be in 10 years? 31:35
• Thank you, Dr. Grayson 33:36

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

Disclosures: Brown and Grayson report no relevant financial disclosures.

Peter Grayson, MD, MSc, is head of the Vasculitis Translational Research Program at National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and associate director of the NIAMS Fellowship Program, Systemic Autoimmunity Branch.

This interview with Chester V. Oddis, MD, will have you standing from a seated position without the need to use your arms as we discuss the inflammatory myopathies. We cover the classification, pathophysiology and treatment approaches to these diseases, as well as all the antibodies you must learn about for boards!

• Intro :20
• The interview 1:05
  • How did you become involved in inflammatory myopathies? 1:12
  • What's your approach to a patient with suspected inflammatory myopathy? 1:50
  • What's your opinion on the pathogenesis of these antibodies? 6:20
  • Any pearls for muscle biopsy? 9:30

Brought to you by GSK. Consider the long-term impact of disease activity, flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com

• Any pearls for reading EMGs? 12:20
• What should we look for once we have a biopsy? 14:16
• What do we know from a cytokine perspective? 17:52
• Where do you think we'll be with inflammatory myopathies in 10 years? 21:50

• Thank you, Dr. Oddis 24:12

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

Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com.

Disclosures: Brown reports no relevant financial disclosures. Oddis reports receiving clinical trial support from Corbus Pharmaceuticals and Genentech.

Chester V. Oddis, MD, is professor of medicine and director of the Myositis Center in the division of rheumatology and clinical immunology at University of Pittsburgh Department of Medicine.

Things get a little nerdy in this episode, which focuses on the basic science of what makes the inflammasome tick in CAPS, as well as data on the use of interleukin 1 inhibition. Hint: Listen to "The Inflammasome for Dunces" episode first, and this one will make more sense.

• Intro :20
• Recap of Part 1 :33
• Overview of this episode 1:56
• Familial cold autoinflammatory syndrome 3:04
• Muckle-Wells syndrome 6:34
• The two checkpoint problem 8:36
• What do we know about the inhibition of the inflammasome? 11:13
• Back to the trebuchet analogy 11:48

Brought to you by GSK. Considering a treatment change for patients with active SLE? Learn about a treatment option for your patients at treatfortodayandtomorrow.com

• A paper on CARD8 in the setting of CAPS 13:50
• Let's talk about prostaglandins 15:27
• There are over 100 mutations in CAPS 18:15
• Let's talk about treatment 18:42
• One caveat 25:41
• That's CAPS 26:45
• Reach out to me via email and on Twitter 27:03
• Episode recap 27:41

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

Brought to you by GSK. Consider the long-term impact of disease activity, flares and corticosteroid use on patients with active SLE. Learn more now at treatfortodayandtomorrow.com.

Disclosure: Brown reports no relevant financial disclosures.

References:

Agostini L, et al. Immunity. 2004;20:319-325.

Brogan PA, et al. Arthritis Rheum. 2019;71:1955-1963.

Marsaud C, et al. J Rheumatol. 2014;41:1721-1722.

Hawkins PN, et al. NEJM. 2003;348:2583-2584.

Hoffman HM, et al. Lancet. 2004;364:1779-1785.

Hoffman HM, et al. Clin Ther. 2012;34:2091-2103.

Ito S, et al. Arthritis Res Ther. 2014;16:doi:10.1186/ar4483.

Kuemmerle-Deschner JB, et al. Ann Rheum Dis. 2011;70:2095-2102.

Lachmann HJ, et al. NEJM. 2009;360:2416-2425.

Mamoudjy N, et al. Orphanet J Rare Dis. 2017;12:doi:10.1186/s13023-017-0589-1.

Rosengren S, et al. J Allergy Clin Immunol. 2007;119:991-996.

Ross JB, et al. J Cutan Med Surg. 2008;12:8-16.

Tassi S, et al. Proc Natl Acad Sci USA. 2010;107:9789-9794.

Thornton BD, et al. Am J Kidney Dis. 2007;49:477-481.

This first episode delves into the clinical aspects of the Cryopyrin-Associated Periodic Syndromes and includes some helpful tips for sorting out some of the autoinflammatory diseases in the spectrum.

• Intro :10
• Cryopyrin-Associated Periodic Syndromes (CAPS) :25
• Outline of Part 1 2:25
• What is CAPS? 3:12
• Case #1 – a 25-year-old female with urticaria after cold exposure 4:25
• Case #2 – a 55-year-old female with progressive deafness 5:45
• The index case of familial cold autoinflammatory syndrome 9:00
• The final disease in the spectrum 11:00
• A lot of names for the same disease 13:50
• Genetics prove these three diseases are in the same spectrum 14:22
• Over 100 mutations have been found to-date 16:31
• Let's talk about mosaicism 17:03
• Disease characteristics of CAPS 18:15
  • Neutrophilic infiltrate in chronic urticaria vs. CAPS 20:00
  • Schnitzler syndrome 20:45
  • Sensorineural hearing loss 21:58
  • Joint pain 24:10
• Complication: Amyloidosis 25:29
• These diseases were very debilitating 28:38
• Episode recap 29:46
• Part 2 sneak peek 30:38
• Come say hi at ACR! 30:51

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

References:

Ahmadi N, et al. Otolaryngol Head Neck Surg. 2011;145:295-302.​

Aksentijevich I, et al. Arthritis Rheum. 2002;46:3340-3348.

Alecu M, et al. Romanian Journal of Morphology and Embryology = Revue Roumaine de Morphologie et Embryologie. 2015;56:7-14.

Hassink SG, Goldsmith DP. Arthritis Rheum. 1983;26:668–673.

Hoffman HM, et al. Nat Genet. 2001;29:301-305.​

Hoffman HM, et al. J Allergy Clin Immunol. 2001;108:615-620.

Kile RM, Rusk HA. JAMA. 1940;114:1067-1068.

Levy R, et al. Ann Rheum Dis. 2015;74:2043-2049.

Marzano AV, et al. Clin Exp Rheumatol. 2018;36 Suppl 110:32-38.

Muckle TJ, Wells M. Q J Med. 1962;31:235-248.

Prieur AM, Griscelli C. Rev Rhum Mal Osteoartic. 1980;47:645–649.

Tran TA. Open Access Rheumatol. 2017;9:123-129.