A study led by investigators from Johns Hopkins Medicine found that some patients with discoid lupus erythematosus — a form of skin lupus commonly diagnosed in young to middle-aged Black women that causes disc-shaped plaques to form on the body — were less likely to experience complications, such as diabetes, hypertension and coronary artery disease if they were prescribed hydroxychloroquine.
Originally a malaria treatment, hydroxychloroquine is used to treat autoimmune symptoms in patients with systemic lupus erythematosus (SLE). It's not known whether hydroxychloroquine confers the same benefits to patients with a sole diagnosis of discoid lupus erythematosus (chronic cutaneous lupus erythematosus).
Chronic skin lupus has historically been viewed and treated as a skin-limited condition; newer research, however, has linked it to systemic inflammation and elevated heart disease risk similar to SLE, says lead study author Jun Kang, M.D., an assistant professor of dermatology at the Johns Hopkins University School of Medicine.
"Treatments for discoid lupus erythematosus often focus on addressing skin symptoms over known systemic complications, such as cardiovascular issues," says Kang. "Our study found that hydroxychloroquine use was associated with better cardiovascular and cardiometabolic health outcomes, including diabetes, in patients after five years."
The Kang lab's new study results, published in the Journal of the American Academy of Dermatology on April 17, are believed to be among the first to explore how first-line treatments for SLE could also benefit patients with chronic skin lupus.
For the study, the researchers compared the five-year outcomes of two cohorts composed of patients who had been diagnosed only with discoid lupus and no other autoimmune conditions. Each cohort comprised one group that had started taking hydroxychloroquine within five years of being diagnosed and a second group that had never taken hydroxychloroquine. Both cohorts excluded patients who had been treated with oral corticosteroids, immunosuppressive medications or biologic therapies.
The first cohort was composed of 106 adult (mean age 47.8 years) Johns Hopkins Medicine patients of Black (67.0%), white (26.4%) and Asian (6.6%) heritage. Some 46 adults from this group had never taken hydroxychloroquine, and the remainder were actively using it for treatment (60 adults).
The second cohort was composed of 2,260 pairs of adults (mean age 52 years) of white (59.5%), Black (27.1%), Asian (2.3%), other (2.8%) and unknown (7.7%) heritage from TriNetX, a large database of deidentified patient information. TriNetX's size allowed the researchers to identify and match patients of interest based on select traits. For this study, each patient pair consisted of one adult who was prescribed hydroxychloroquine and one adult who had never taken the medication, for a total of 4,520 participants.
Reviewing patient outcomes over five years, the researchers found that Johns Hopkins Medicine patients taking hydroxychloroquine were much less likely than those not taking it to develop hyperlipidemia (elevated cholesterol) (23.3% vs 47.8%), peripheral artery disease (1.7% vs 17.4%), angina (chest pain) (3.3% vs 26.1%) and coronary artery disease (10.0% vs 26.1%). They also found that the risk of hypertension, type 2 diabetes, heart attack and stroke did not differ between the two groups regardless of treatment regimen.
In the TriNetX cohort, the researchers found that hydroxychloroquine use was linked to a lower risk of hypertension (elevated blood pressure) (14.1% among HCQ users vs 17.3% among non-users), hyperlipidemia (8.4% vs 15.1%), type 2 diabetes (4.3% vs 6.3%), stroke (1.0% vs 2.3%) and coronary artery disease (4.2% vs 5.9%).
Overall, the researchers believe that their findings demonstrate how hydroxychloroquine and other systemic therapeutics can provide distinct benefits to topicals often prescribed for discoid lupus erythematosus.
Next, Kang says his team aims to identify which patients with skin lupus may benefit the most from hydroxychloroquine as a first-line drug. They hope to establish new treatment guidelines that clinicians could consider alongside established treatments.
"All patients with skin lupus will benefit if we can shift broader clinical perspectives of the disease and develop clear guidelines that address how it harms health beyond the skin," says Kang.
The study was supported by Jun Kang's Dermatology Foundation Medical Dermatology Career Development Award.
Alongside the principal investigator, Jun Kang, researchers who worked on the study include Anjana Srikumar and Olga Yuvchenko.
Jun Kang reports serving as a site principal investigator for the ongoing LAVENDER trial, which is evaluating anifrolumab, a therapy targeting type I interferon signaling for adults with chronic and/or subacute cutaneous lupus erythematosus.
