Dr Calabrese reviews his address from the review course at ACR Convergence 2023 about caring for patients with rheumatic diseases who contract viral infections and emphasizes the need for interdisciplinary management.

Leonard Calabrese, DO, is professor of medicine, vice chair of the Department of Rheumatic and Immunologic Diseases and director of the RJ Fasenmyer Center for Clinical Immunology at Cleveland Clinic in Cleveland, Ohio.

TRANSCRIPT:

This is Dr. Len Calabrese. I'm a professor of medicine at the Cleveland Clinic and the head of the R.J. Fasenmyer Center for Clinical Immunology, where we focus on the intersection of infections and immune mediated diseases. I am just returning from the ACR Convergence 23, where I was given the privilege to speak at the review course on the topic of clinical challenge of viral infections and rheumatic diseases. I'm going to give you a few-minutes summary of that talk and refer you to just some references that can summarize this for you if you want to take a deeper dive.

I broke this down into three parts. I first talked about viral arthritis. I then talked about chronic persistent viral infections, and then I talked about some aspects of prevention and management. So viruses are a common cause of joint pain, as we all know, but this is usually self-limited and unassociated with signs of articular inflammation. However, certain viruses kind of stand out in the field, if you will, and they can result in a syndrome that lasts more than a few days during the course of the acute viral infection, mostly respiratory infections, and sometimes bring themselves to the rheumatologist as a problematic diagnostic issue.

The virus I concentrated mostly on this talk at the review course was Parvovirus B19, a ubiquitous pathogen transmitted readily in crowded situations. About 50% of people have already had this infection, and it causes a number of syndromes. In children, it causes the Fifth disease slapped-face appearance, rarely develop arthritis. But in adults, it can result in a syndrome that is difficult to diagnose; they lack the characteristic rash, and it can develop, along with it, a migratory and often additive polyarthritis that may last for a number of weeks. So in patients seen with early onset migratory, polyarticular, often additive arthritis, this has to be added to our differential diagnosis.

Complicating is the fact that many patients with Parvovirus B19 can generate autoantibodies, including rheumatoid factor, ANA, anti-DNA, ENA, and antiphospholipid antibodies. So it can confound this situation. The diagnostic test of choice is IgM, antiparvovirus B19. IgG is present in 50% of normal people, and particularly young people, particularly women who have exposure to young children are the most culpable.

In the returning traveler from exotic areas, Southeast Asia, Africa, South America, Caribbean, we still have to think of alpha virus infections. These are arbovirus in classification, they're transmitted by mosquitoes, a number of viruses, including Zika and dengue can develop some musculoskeletal manifestations, but the one that we still think about is chikungunya. Ninety-seven percent of those patients are symptomatic, it's self-limiting in 50 to 60%, but some can go on to develop a syndrome that lasts for up to 3 months that can be quite severe and bring them to the attention of a rheumatologist. Serologies can help us make this diagnosis, getting the travel history is often very helpful. And managing it is still not evidence-based, but people who take care of this occasionally use NSAIDs, low-dose glucocorticoids, antimetabolites, and there are anecdotes of using biologics to treat this. The takeaway points are that you have to take a good travel history and understand the region that it's been in, and the good news is that in 2023, chikungunya is a deaccelerating pathogen.

The second group of viral infections that represent a challenge to the rheumatologist are the chronic persistent infections. These are viruses that are replicating all the time. This is billions of particles are produced of hepatitis C or hepatitis B or HIV. So these represent challenges in comorbidity, you know, you have a patient with hepatitis B and RA, I'm going to make the point, we need to screen for it and we need to suppress it. All of these have the potential to produce rheumatic syndromes by themselves. Hepatitis C, you know, well-known to be associated with hepatitis C-associated cryoglobulinemia, fortunately is a deaccelerating pathogen. It is going away because we now have cures for hepatitis C, 6 weeks of direct antiviral therapy. I think it's more of a challenge to treat chronic hepatitis C and an existing rheumatic disease. My pearl for this is that I screen for hep B, hep C, and HIV in virtually all patients going on immunosuppressives. When I see hep C, I usually try to stall the therapy if possible, I send them to the hepatologist and get them cured in 6 weeks and then take care of it the way I could take care of it in most patients. That's the bottom line for hepatitis C.

Hepatitis B, we used to talk about this a generation ago, causing acute polyarthritis that looked like acute onset RA and being the etiology for many cases of polyarteritis nodosa. I want you to do me a favor. Anyone out there that has seen a case of acute hepatitis B polyarteritis nodosa in the past 12 months, please send me an email or a direct tweet

to me and tell me about it because this is a deaccelerating infection. I can't tell you the last patient that I've seen in our vasculitis center. But screening for it's important because the adage for hepatitis B is “potentially fatal yet preventable.” We need to order hepatitis B surface antigen, anticore and anti-HBsAb, because that will tell us who may need to be immunized and patients who are surface antigen positive or even those who are anticore going on drugs like rituximab that have black box warnings need ongoing suppressive therapy to treat their rheumatic disease.

And finally, HIV, which is slowly deaccelerating, still is associated with some new onset rheumatic diseases, mostly reactive arthritis, which can be very severe, can look like acute or fulminant psoriatic arthritis, keratodermic features. And these patients can be treated with biologics, but collaboratively with the HIV doc, because they all need to be on combination ART. Other rare manifestations of HIV, we have almost disappeared in the antiretroviral era. And I've given some references to guide you if you have further interests.

Finally, let me just make a few points about viral infections as complications. You know, we're not out of the woods in this. Patients who are immunosuppressed, particularly those on rituximab therapy, are more vulnerable to SARS-CoV-2 infection. And that's a separate topic for a different day. But there are now growing reports of even patients on rituximab getting severe arboviral neuroinvasive diseases like West Nile. We have to remember that patients with lupus are particularly vulnerable to progressive multifocal leukoencephalopathy. And that all of our patients on immunosuppressants, particularly those on high-dose glucocorticoids and JAK inhibitors and antifrolumab are highly susceptible to herpes zoster. And that may be associated with more complications such as postherpetic neuralgia and stroke, myocardial infarction, and central nervous system zoster and ocular complications. So finally, the EULAR in 2022 made recommendations for screening and prophylaxis. I refer you to this article.

And then lastly, I emphasize the point that caring for viral infections and rheumatic disease patients is not just our job. And it's not the primary care job. And it's not just the ID job. It is an interprofessional job. We have to be talking to each other. Is that primary care physician going to feel comfortable recommending to the 30-year-old to get recombinant zoster vaccine? As we are, as we know that this patient has lupus and will be at high risk on glucocorticoids, et cetera, moving ahead. We need to have a good

friend as an ID doc for when patients get serious and opportunistic infections. And we need to work collaboratively with ID docs for all those patients with chronic persistent viral infections, Hep C, Hep B, HIV, to manage this accurately.

Finally, arthritis in the returning traveler, arthritis in the early stages of inflammatory arthritis. Think about viruses. Read our reviews. Please follow me on Twitter. Len Calabrese. Easy to find. I like to talk about this stuff. Send me an email or a tweet if you've seen acute hepatitis B in the last year. Thank you for tuning in.