Atopic Dermatitis and Risk of Autoimmunity Conditions: Population-based Cohort Study

To determine the risk of autoimmune conditions in people with newly diagnosed atopic dermatitis (AD), to describe the co-occurrence of common autoimmune conditions with AD, and to evaluate whether the risk of autoimmune disease is related to the severity of AD.

All patients of all ages contributing to a large primary care database in the United Kingdom between 2009 and 2018.

Patients newly diagnosed with AD in that time frame were identified using a validated algorithm. Demographic information and comorbidities were characterized and AD severity classified by predefined criteria. Roughly 4-fold more matched control patients without AD were identified. Fifteen common autoimmune diseases (population prevalence ≥0.3%) were included in the analysis. Overall and condition-specific prevalence of autoimmune diseases was estimated at cohort entry (date of AD diagnosis). Subjects and controls with pre-existing autoimmunity were excluded. Hazard ratios (HR) were used to associate AD with each outcome and adjusted for multiple variables (adusted HR [aHR]).

There were 173 709 newly diagnosed AD cases (52.7% children, and 47.1% adults) and 694 836 controls with similar baseline demographics studied. AD patients were more likely to have pre-existing autoimmunity than controls (5.84%, confidence interval [CI] 5.73–5.95 vs 4.31%, CI 4.26–4.36). Over a mean follow-up of 4.1 years, cumulative incidence of any new onset autoimmune disease was higher in cases than controls (10-year incidence 3.9%, CI 3.6–4.2 vs 2.7%, CI 2.6–2.9). Adjusted analysis identified an association between AD and new onset of any autoimmune disease (aHR 1.28, CI 1.23–1.34, P < .001). In particular, there was an association between AD and new-onset Crohn Disease, ulcerative colitis, pernicious anemia, autoimmune hypothyroidism, rheumatoid arthritis, psoriatic arthritis, Sjogren Syndrome, vitiligo, and alopecia areata (aHR range 1.17–2.06). Severity of AD progressed in 20 744 patients. In the whole group, increasing severity of AD was associated with a greater risk of autoimmune disease as compared with controls with P < .001 for all severities (severe AD: aHR 1.99, CI 1.77–2.23; moderate AD: aHR 1.33 CI 1.19–1.49; mild AD aHR 1.22, CI 1.16–1.28). In children, a greater risk of any autoimmune disease was seen for severe (aHR 2.41, CI 1.88–3.07) but not moderate (aHR 1.23, CI 0.88–3.07) or mild (aHR 1.03, CI 0.93–1.15) AD. In children, individual autoimmune disease associations were only observed for vitiligo and alopecia areata.

People with AD have a higher prevalence and incidence of autoimmune conditions as compared with matched non-AD controls. In subjects with severe AD, the risk of new-onset autoimmune disease was double that of controls.

Interleukin 17, produced by T _H17 lymphocytes, is a pro- inflammatory cytokine known to be associated with autoimmune disease. Over recent years, the increasing role of T_H1, T _H17, and T_H22 cells in the patho-immunology of chronic AD is becoming increasingly evident. This study indicates that the two conditions may be related and share a degree of risk and commonality. With great frequency, the onset of AD is before 5 years old. Some patients improve and redevelop AD later in life. It is not clear from this analysis how many adults with “new onset” AD had childhood onset AD that improved, then recurred. Might that be a risk factor for autoimmune disease in adult onset AD? Clinicians should be aware of the risk for autoimmune conditions in patients with severe or worsening AD.