Atopic dermatitis in adults : epidemiological studies of comorbidity and studies of patients on systemic treatment

Abstract

Background: Atopic dermatitis (AD) is one of the most common chronic skin disorders globally. It is an itchy inflammatory skin disease that can have a detrimental impact on health-related quality of life. In recent years, AD has been associated with non-atopic conditions, though this requires further exploration. Novel understanding of AD pathogenesis has recently led to development of the first biological treatment. The overall aims of the thesis were to assess cardiovascular disease (CVD), autoimmune disease and depression among adults with AD, and to investigate the response to, and some adverse events from, systemic treatment that includes the first biological for AD.

Methods: Register-based, case-control studies were conducted to assess CVD and autoimmune comorbidity among patients with AD. The source population comprised the entire Swedish population aged ≥ 15 years. Cases, including all those with an inpatient diagnosis of AD (from 1968) and/or a specialist outpatient diagnosis of AD (from 2001) through 2016, were matched by sex and age to healthy controls (104,832 cases of AD, 1,022,435 controls). Patients were classified as having severe AD if they had received systemic pharmacotherapy for AD or had been treated in a dermatological ward with AD as the main diagnosis. Otherwise, AD was classified as non-severe. The clinical cohort studies and the case-series used data from a register containing prospectively collected data from adult patients with AD on systemic treatment at the Karolinska University Hospital from 2017. The register was launched for national use in 2019.

Result: Studies I–II: After multivariable adjustments for comorbidities and socioeconomic status, AD was associated with angina pectoris (adjusted odds ratio (aOR) 1.13, 95% confidence interval (CI) 1.08–1.19). Non-severe AD was associated with myocardial infarction (aOR 1.15, 95% CI 1.07–1.23) among men. Severe AD was associated with ischaemic stroke, with similar estimates in men and women (aOR 1.19, 95% CI 1.07–1.33). Diabetes mellitus, hyperlipidaemia, and hypertension were more prevalent in patients with severe AD than in controls, and hyperlipidaemia and hypertension were also more prevalent in patients with non-severe AD than in controls. Having AD was significantly associated with having one or more autoimmune diseases as compared with controls: (aOR 1.97, 95% CI 1.93–2.01), and this association was significantly stronger for having multiple autoimmune diseases than for having only one. The association was strongest for autoimmune disorders involving the skin, the gastrointestinal tract or the connective tissue. Studies III–V: In a caseseries of 10 patients with severe, long-lasting AD and most often also previous eye disease, 9/10 developed eye complications during dupilumab treatment, most commonly conjunctivitis (7/10). In a cohort study of patients treated with dupilumab (n = 12), weight gain (mean 6.1 kg, range 0.1–18.0 kg, p = 0.002) was seen after 1 year on treatment. In spite of these adverse events, dupilumab was very effective and safe. More than half of patients with moderate-to-severe AD eligible for systemic treatment (n = 60) had depressive symptoms, 25% of whom presented with moderate-to-severe depression and 5% of whom had pronounced suicidal ideation. Systemic treatment for AD significantly reduced depressive symptoms, in addition to relieving symptoms of AD.

Conclusion: AD was associated with CVD and several autoimmune disorders. More than half of the patients with moderate-to-severe AD in routine dermatological care had depressive symptoms. Dupilumab was very effective and safe overall, but was associated with ocular adverse events and weight gain in these small studies. Systemic treatment for AD significantly reduced depressive symptoms in parallel with reducing AD symptoms.