Patients with atopic dermatitis (AD) had a 28% increased risk of herpes zoster (HZ) in a matched cohort study of more than 13 million people in the United Kingdom — and the association persisted after adjustment for comorbidities, obesity, and treatments, rising sharply with AD severity.

The study, published August 5 in JDDG: Journal der Deutschen Dermatologischen Gesellschaft, drew on primary care data from a UK research database comprising 14,081,774 observations from 13,426,267 people: 11,636,684 observations from participants without AD and 2,445,090 from participants with AD. The investigators used treatments as a proxy for disease severity.

The severity gradient was the study's central finding. Compared with individuals without AD, adjusted hazard ratios (aHRs) for HZ were 1.22 for mild AD, 1.28 for moderate AD, and 2.33 for severe AD. When the researchers adjusted for topical corticosteroid use, HZ risk remained elevated in the AD population (aHR, 1.17).

"We have known for some time that patients with AD can have increased susceptibility to certain infections, and we also know that some of our systemic treatments can increase the risk of HZ. What is particularly notable here is the suggestion that AD itself may confer some additional risk, independent of those treatments," Peter Lio, MD, told Medscape Medical News. "Importantly, adjusting for oral corticosteroids and traditional systemic immunosuppressants only modestly changed that association."

Lio, founder of the Chicago Integrative Eczema Center and clinical assistant professor of dermatology at Northwestern University in Chicago, commented on the results and was not involved in the study.

Theodora K. Karagounis, MD, assistant professor of dermatology at NYU Grossman School of Medicine in New York City, also commented as an independent expert. She flagged a key interpretive limit: the study cannot disentangle disease severity from its treatment. "It is unclear from their study if it is the disease severity itself or the treatment that is leading to increased HZ risk with increasing AD disease severity," she said. "Still, when excluding treatments, they find AD is associated with HZ."

Age shaped the association in an unexpected pattern. Hazard ratios were highest among individuals aged 30-40 years (HR, 1.51), followed by those aged 40-50 years (HR, 1.42), then declined across older groups: 1.29 for ages 50-60 and a low of 1.23 for ages 70-80.

The experts said this gradient likely reflects baseline incidence rather than a true age-specific biological effect. Absolute HZ incidence in the database ran from 1.58 events per 1000 person-years among individuals younger than 30 to 8.85 events per 1000 person-years among those aged 80 or older. "The interaction the authors observe with age is interesting, with the effect of AD on HZ risk being most pronounced in the younger age groups," Karagounis said. "Notably, this may just reflect that young people overall have a low risk for HZ and so just a few more added cases due to the added risk with AD gives a higher hazard ratio as compared to older people."

The findings open several research avenues. One is dupilumab, a common AD treatment that prior work has shown to reduce HZ risk. Karagounis also posed a set of unresolved clinical questions: "Does HZ in AD patients take longer to resolve? Do we need to be treating with valacyclovir for longer? This study just looked at first episodes of HZ. How frequently do patients with AD get HZ?... We should [also] investigate the risk of HZ in AD patients who have received zoster vaccination and see if that modifies the risk/number of outbreaks."

For Lio, the practical implication is preventive. "The practical takeaway is not that we should alarm our patients with AD about shingles," he said, "but that we should recognize another potentially preventable complication and keep vaccination and infectious-risk assessment in mind as part of thoughtful, comprehensive AD care."

None of the study authors had disclosures, and no funding source was listed. Karagounis had no relevant disclosures. Lio disclosed speaking, advising, consulting, and educational activities with AbbVie, Apogee Therapeutics, Arcutis Biotherapeutics, Eli Lilly, Galderma, Incyte, Kenvue, L'Oréal Groupe, Nektar Therapeutics, Pfizer, Regeneron/Sanofi, Skinfix, Sun Pharma, and Verrica Pharmaceuticals, along with ownership or investment interests in 11 companies including Alphyn Biologics, LearnHealth, and Modernizing Medicine.

Whether dupilumab and zoster vaccination blunt the excess risk observed in this cohort — and whether recurrent HZ follows the same severity gradient as first episodes — now sits squarely on the research agenda for comprehensive AD management.