A population-based study showed a slightly elevated risk of developing skin disorders in patients, including alopecia areata (AA), alopecia totalis (AT), vitiligo, and bullous pemphigoid (BP), more than 6 months after COVID-19 infection. Additionally, the authors reported that COVID-19 vaccination appears to reduce these risks.

The study was published In JAMA Dermatology on November 6.

“Convincing evidence”

“This well-executed study by Heo et al. provides compelling evidence to support an association between COVID-19 infection and the development of subsequent autoimmune and autoinflammatory skin diseases,” wrote the authors led by Lisa M. Arkin, MDfrom the Department of Dermatology, University of Wisconsin School of Medicine and Public Health in Madison, Wisconsin, in an accompanying document editorial.

Using databases from the Korean National Health Insurance Service and the Korea Disease Control and Prevention Agency, investigators led by Yeon-Woo Heo, MDresident in dermatology at Yonsei University Wonju School of Medicine, Wonju, Republic of Korea, compared 3.1 million people with COVID-19 with 3.8 million controls, all with follow-up of at least 180 days until December 31, 2022.

With a mean follow-up of 287 days in both cohorts, the authors found significantly elevated risks of AA and vitiligo (adjusted relative risk (AHR), 1.11 for both), AT (AHR, 1.11 for both), 24), Behçet’s disease (AHR, 1.45), and TA (AHR, 1.62) in the post-COVID-19 cohort. Infection also increased the risk of other conditions such as systemic lupus erythematosus (AHR, 1.14) and Crohn’s disease (AHR, 1.35).

In subgroup analyses, demographic factors were associated with various outcomes: COVID-19 infection was associated with a significantly higher risk of developing AA (for both men and women), vitiligo (both men), Behçet’s disease (men and women), Crohn’s disease (men and women). ), ulcerative colitis (men), rheumatoid arthritis (men and women), systemic lupus erythematosus (men), ankylosing spondylitis (men), AT (women) and AP (women) than controls.

People aged younger than 40 years were more likely to develop AA, primary scarring alopecia, Behçet’s disease, and ulcerative colitis, while those aged 40 years or older were more likely to develop AA, AT, vitiligo, Behçet’s disease, Crohn’s disease, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, ankylosing spondylitis and blood pressure.

Additionally, severe COVID-19 requiring intensive care unit admission was associated with a significantly increased risk of autoimmune diseases, including AA, psoriasis, BP, and sarcoidosis. By period, the risks of AA, AT and psoriasis were significantly higher in the initial Delta-dominant period.

Effect of vaccination

Additionally, vaccinated individuals were less likely to develop AA, AT, psoriasis, Behçet’s disease, and various nondermatologic conditions than those who were not vaccinated. This finding, Heo and colleagues wrote, “may provide evidence supporting the hypothesis that COVID-19 vaccines can help prevent autoimmune diseases.”

“This is the element we all need to bring into our offices tomorrow,” said Brett King, MD, PhDdermatologist in private practice based in Fairfield, Connecticut. He was not involved in the study but was asked to comment.

Overall, King said, the study conveys two main messages. “The first is that COVID-19 infection increases the likelihood of developing an autoimmune or autoinflammatory disease in a large population. » The second, very important message, he added, is that being vaccinated against COVID-19 offers protection against the development of an autoimmune or auto-inflammatory disease.

“What concerns me is that the popular media is emphasizing the first part,” King said, “and everyone who develops alopecia areata, vitiligo or sarcoidosis is blaming COVID-19. That’s not what this work says.

The foregoing distinction is particularly important in the fall and winter, he added, when people who have been vaccinated against flu are routinely offered COVID-19 shots. “Many patients have said, ‘I got the COVID vaccine and developed alopecia areata 6 months later.’ Almost everyone who has developed a new or worsening health problem in the past five years has had the perfect fall: the COVID vaccine or infection.

While virtually all patients ask whether they should receive an updated COVID-19 vaccine or booster, he added, many report hearing that these vaccines cause AA, vitiligo or other diseases. “Anchoring these conversations in real data and not just anecdotes from a blog or Facebook is very helpful,” King said, “and we now have very good data that the COVID vaccine protects against these disorders.” »

George Han, MD, PhDassociate professor of dermatology at the Donald and Barbara Zucker Hofstra/Northwell School of Medicine in Hempstead, New York, applauds the investigators’ use of a large and robust database, but suggests interpreting the results with caution. He was not involved in the study but was asked to comment.

“You could do a thorough, well-conducted study,” Han said, “but it might not necessarily be generalizable. These autoimmune diseases they study have obvious ethnic and racial biases. Heo and his colleagues recognized the shortcomings, including the monomorphic nature of their study population.

Other issues that limit the study’s impact, Han said, include the difficulty of conceptualizing a 10 to 20 percent increase in conditions that initially are rare. And many of the results reflect natural trends, he said. For example, blood pressure affects older people more often, despite COVID-19.

Han said that for him, the main value of the study going forward is to help explain the worsening of an inflammatory skin disease that many dermatologists saw early in the pandemic. “We regularly saw well-controlled patients, for example suffering from psoriasis or eczema. But after a COVID-19 infection or a vaccine (usually of the mRNA type), in some cases they would manifest themselves seriously. This happened at least a dozen times in the first year of appointments after the shutdown, he said.

“We’ve seen patients who have had flare-ups multiple times – they get the booster shot and then again,” Han added. Similar patterns have occurred with pyoderma gangrenosum and other inflammatory skin diseases, he said.

Given the modest effect sizes of the associations reported in the Korean study, Arkin and colleagues wrote in their JAMA Dermatology editorial that surveillance for autoimmune diseases is probably not warranted without new test results or new symptoms. “Of course,” King said, “we shouldn’t go looking for things that clearly aren’t there.”

On the contrary, Arkin and colleagues write, the higher rates of autoimmunity observed in unvaccinated people, as well as during the Delta phase (when patients were sicker and hospitalizations more likely) and in patients requiring intensive care, suggest that “interventions that reduce disease severity could also potentially reduce the long-term risk of subsequent autoimmune sequelae.”

Future research investigating whether people with pre-existing autoimmune diseases are at greater risk of flare-ups or developing new autoimmune diseases after COVID-19 infection “would help define an evidence-based approach for patients with autoimmune diseases who develop COVID-19 infection, including the role for antiviral treatments,” they added.

The study was supported by grants from the Korea Medical Institute Research Program, the Korea Health Industry Development Institute, and the National Research Foundation of Korea. Han and King reported no relevant financial relationships. Arkin disclosed receiving research grants for his institution from Amgen and Eli Lilly and Company, personal fees from Sanofi/Regeneron for consultations, and personal consulting fees from Merck outside the submitted work. Another author reported personal consulting fees from Dexcel Pharma and Honeydew outside the submitted work. No further disclosures have been reported.

John Jesitus is a freelance medical writer and editor based in Denver.