Healio Rheuminations

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 [email protected]. 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 [email protected]. 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 [email protected]. 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 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 [email protected].

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 [email protected].

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 [email protected].

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 [email protected].

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 [email protected].

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 [email protected].

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 [email protected].

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.