Risk of Herpesvirus, Serious and Opportunistic Infections in Atopic Dermatitis

A Population-based Cohort Study

J. Wan; D.B. Shin; M.N. Syed; K. Abuabara; A.R. Lemeshow; J.M. Gelfand


The British Journal of Dermatology. 2022;186(4):664-672. 

In This Article

Abstract and Introduction


Background: Staphylococcal and herpes simplex virus (HSV) infections are commonly recognized in atopic dermatitis (AD), but less is known about other types of infections.

Objectives: To determine the risk of herpesvirus infections, serious infections and opportunistic infections in patients with AD.

Methods: We conducted a population-based cohort study using UK-based electronic medical records data. Patients with AD were each matched to up to five unaffected patients on age, practice and index date. AD severity was defined using treatments as a proxy. Outcomes were incident herpesvirus infections [cytomegalovirus (CMV), Epstein–Barr virus (EBV), HSV or varicella zoster virus (VZV)], serious infections and opportunistic infections.

Results: Among 409 431 children and 625 083 adults with AD matched to 1 809 029 children and 2 678 888 adults without AD, respectively, adjusted Cox regression models showed children and adults with AD had a 50–52% greater risk of HSV and 18–33% greater risk of VZV, with risk increasing in parallel with AD severity. CMV risk was elevated among children with AD [hazard ratio (HR) 2·50, 95% confidence interval (95% CI) 1·38–4·54] and adults with severe AD (HR 4·45, 95% CI 1·76–11·25). Patients with AD had a 26–40% increase in risk of serious infections, with severe AD carrying the greatest risk. Although rare, opportunistic infections were associated with all severities of AD in adults (overall HR 1·31, 95% CI 1·20–1·42), but were not associated with AD in children. All estimates remained consistent after excluding patients receiving immunosuppressive treatments for AD.

Conclusions: AD is significantly associated with herpesvirus infections, serious infections and opportunistic infections in a 'dose-dependent' manner with increasing severity. AD may increase susceptibility to infections exclusive of immunosuppressive medications.


Atopic dermatitis (AD) is associated with epidermal barrier defects, decreased antimicrobial peptide expression and altered innate and adaptive immunity in the setting of T-helper (Th)2-skewed inflammation, which can increase susceptibility to infections.[1,2] Staphylococcal and herpes simplex virus (HSV) infections are commonly recognized infections in AD.[3] Eczema herpeticum (EH), a disseminated cutaneous HSV infection linked to defective interferon response and cathelicidin deficiency, is uncommon but may be more prevalent in moderate-to-severe AD.[4–6] Patients with AD may also be at greater risk for extracutaneous infections, such as respiratory, gastrointestinal and urinary tract infections, owing to systemic immune dysregulation due to AD and/or its treatment.[7–10] However, previous studies of infections in AD are primarily cross-sectional and have not examined the influence of AD severity on infection risk.[7,8] Additionally, the risk of serious (i.e. hospitalized) and opportunistic infections has not been fully characterized. Although cutaneous HSV infections are widely recognized in patients with AD, few epidemiological investigations of HSV in AD exist.[11] Some studies have suggested greater rates of varicella zoster virus (VZV), cytomegalovirus (CMV), and Epstein–Barr virus (EBV) infections among patients with AD,[7,8,12–15] but the incidence of these other herpesvirus infections in AD remains unknown. Thus, we sought to determine the risk of herpesvirus infections, serious infections and opportunistic infections among patients with AD.