Malignancy risk in patients with atopic dermatitis: a population-based cohort study.

BACKGROUND: Atopic dermatitis (AD) is associated with immunological dysfunction, which may influence cancer development. Previous studies of AD and cancer demonstrate inconsistent results and few of these studies examined children or AD severity and treatment. OBJECTIVES: To determine malignancy risk among children and adults with AD. METHODS: We conducted a cohort study using electronic health records data from UK general practices in The Health Improvement Network between 1994 and 2015. Children (< 18 years old) and adults (≥ 18 years old) with AD were matched on age, practice and index date to patients without AD. AD was categorized as mild, moderate or severe using treatments and dermatology referrals as proxies. The primary outcome was any incident malignancy, including in situ malignancy, identified using diagnosis codes and categorized into haematological, skin and solid organ malignancies. Secondary outcomes included specific malignancies: leukaemia, lymphoma, melanoma, nonmelanoma skin cancer (NMSC) and common solid-organ cancers. RESULTS: Among 409 431 children with AD (93.2% mild, 5.5% moderate, 1.3% severe) and 1 809 029 children without AD who had median follow-up of 5-7 years, the incidence rates of malignancy were 1.9-3.4 and 2.0 per 10 000 person-years (PY), respectively. The adjusted risk of malignancy overall did not differ with respect to AD [hazard ratio (HR) 1.02 (95% confidence interval 0.92-1.12)]. Severe AD was associated with increased lymphoma risk [HR 3.18 (1.41-7.16), excluding cutaneous T-cell lymphoma (CTCL)], and mild AD was associated with increased NMSC risk [1.55 (1.06-2.27)]. Among 625 083 adults with AD (65.7% mild, 31.4% moderate, 2.9% severe) and 2 678 888 adults without AD who had median follow-up of 5 years, incidence rates of malignancy were 97.4-125.3 per 10 000 PY and 103.7 per 10 000 PY, respectively. The adjusted risk of any malignancy did not differ with respect to AD [HR 1.00 (0.99-1.02)]. However, adults with severe AD had a twofold higher risk of non-CTCL lymphoma. AD was also associated with slightly higher skin cancer risk [HR 1.06 (1.04-1.08)] and slightly lower solid cancer risk [0.97 (0.96-0.98)] but results varied by specific cancers and AD severity. CONCLUSIONS: Epidemiological evidence does not support a strong overall malignancy risk in AD but lymphoma risk may be increased with severe AD.

Severity strata for POEM, PO-SCORAD, and DLQI in US adults with atopic dermatitis.

BACKGROUND: Patient-Oriented Eczema Measure (POEM) is the preferred patient-reported outcome (PRO) for assessing symptoms of atopic dermatitis (AD). Dermatology Life Quality Index (DLQI) is commonly used to assess the burden of skin disease. Previous severity strata were developed for POEM and DLQI in clinical cohorts, which may be biased toward more severe disease. Severity strata were not previously examined in population-based cohorts. Patient-Oriented Scoring AD (PO-SCORAD) is another commonly used PRO for assessing AD symptoms; however, severity strata are not established. OBJECTIVE: We sought to confirm previously developed strata for POEM and DLQI, and to develop strata for the PO-SCORAD in a population-based cohort of adults with AD. METHODS: A cross-sectional, population-based study of 8,217 adults was performed using a structured questionnaire. A diagnosis of AD was determined using modified UK Diagnostic Criteria for AD (n = 602). AD severity was assessed using self-reported global AD severity (anchoring question), POEM, PO-SCORAD, and DLQI. Strata were selected using an anchoring approach based on patient-reported disease severity. RESULTS: We confirmed the existing strata for DLQI (mild = 0-5, moderate = 6-10, severe = 11-30) (kappa = 0.446). However, the preferred strata for POEM was mild = 0-7, moderate = 8-19, and severe = 20-28 (kappa = 0.409) and PO-SCORAD was mild = 1-27, moderate = 28-56, severe = 57-104 (kappa = 0.444). CONCLUSION: Existing strata for DLQI performed well in a population-based cohort of adult AD. The optimal severity strata for the POEM in our AD population varies slightly from those previously published for AD. This may suggest that different strata may be optimal in different study settings and cohorts. Finally, we proposed new strata for PO-SCORAD in adult AD.

Maternal history of angioma is associated with infantile hemangioma and port-wine stain in children: a population-based, cohort study of mother-child pairs from the United Kingdom.

The two most prevalent childhood vascular abnormalities are infantile hemangioma (IH) and port-wine stain (PWS). They become apparent shortly after birth but have distinct pathophysiology and clinical manifestations. The goal of this study was to determine if mother's history of angioma or PWS is associated with these vascular abnormalities. We evaluated an UK anonymized electronic medical records database with medical records that were linked between children and their mothers. Cox proportional hazards models were used to evaluate the association between maternal factors and the time of onset of either IH or PWS in children. Between 2004 and 2021, 639,085 children were linked to their mom's medical data with a total of 4,270,773 person-years of follow up. Children born to mothers with an angioma as compared to a mother without an angioma were more than 60% more likely to have an IH (HR: 1.64 [1.07, 2.52]). Children born to mothers with a PWS as compared to children born to mothers without a PWS were nearly 20 times more likely to have a PWS (18.95 [4.71,76.26]). Mothers with angiomas were not more likely to have children with PWS and mothers with PWS were not more likely to have children with IH. The effect estimates were minimally changed after adjustment. We demonstrated that children born to mothers with angiomas or PWS were at increased risk of IH or PWS, respectively.

Association between atopic dermatitis, autoimmune illnesses, Epstein-Barr virus, and cytomegalovirus.

Atopic dermatitis (AD) is a Th2-driven inflammatory skin disease that has been associated with other autoimmune illnesses (AI) and has a well-known predisposition to infection with herpes simplex virus infection. Yet, few studies have evaluated the association between atopic dermatitis, autoimmune illness, and other human herpes virus (HHV) infections such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV). We aimed to evaluate the association between AD, specific AIs, CMV, and EBV in a random sample of the Optum Clinformatics Data Mart database, a US administrative claims database. AD was defined based on ICD diagnostic codes. Patients with AD were exact matched to those without AD on sex, age at enrollment, time observed in the dataset and census division. Our outcomes of interest were rheumatoid arthritis (RA), Crohn's disease (CD), ulcerative colitis (UC), multiple sclerosis (MS), CMV, and EBV infection as defined by specific ICD codes. Logistic regression models were used to examine the association between AD and our outcomes of interest [odds ratio (95% confidence intervals)]. Our full cohort included 40,141,017 patients. In total, 601,783 patients with AD were included. As expected, patients with AD had a higher prevalence of asthma and seasonal allergies versus controls. Individuals with AD have an increased risk of EBV, CMV, RA, CD, UC, and MS. While we cannot demonstrate a causal association, the observed associations between AD and AI may be in part mediated by these types of HHV (i.e., CMV and EBV), a finding that merits further study.

Incidence of Cardiovascular Disease and Venous Thromboembolism in Patients With Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) may increase risk for atherothrombotic and cardiovascular (CV) disease. OBJECTIVE: Determine CV disease and venous thromboembolism risk among patients with AD. METHODS: Cohort study using electronic health data from U.K. general practices in 1994 to 2015. Children (<18 y) and adults (≥18 y) with AD were matched to patients without AD on age, same practice, and encounter date. Treatments and specialist referrals served as proxies of AD severity. Outcomes were incident myocardial infarction, cerebrovascular accident (CVA), diabetes, hypertension, dyslipidemia, deep vein thrombosis (DVT), and pulmonary embolism. Cox regression analysis was used to compare outcomes in AD versus non-AD patients. RESULTS: Comparing 409,341 children with AD (93.2% mild, 5.5% moderate, and 1.3% severe) to 1,809,029 unaffected children, AD was associated with higher risk of DVT (hazard ratio [HR] 1.23; 95% confidence interval [95% CI] 1.02-1.48) and severe AD was associated with higher risk of CVA (HR 2.43; 95% CI 1.13-5.22) and diabetes (HR 1.46; 95% CI 1.06-2.01). Comparing 625,083 adults with AD (65.7% mild, 31.4% moderate, and 2.9% severe) to 2,678,888 unaffected adults, AD, especially when severe, was associated with higher risk of DVT (HR 1.14; 95% CI 1.11-1.18; and HR 1.64; 95% CI 1.49-1.82, respectively) and small but increased risks of CVA, diabetes, and dyslipidemia. Adults with severe AD had higher risk of myocardial infarction (HR 1.27; 95% CI 1.15-1.39), CVA (HR 1.21; 95% CI 1.13-1.30), diabetes (HR 1.15; 95% CI 1.09-1.22), dyslipidemia (HR 1.11; 95% CI 1.06-1.17), and pulmonary embolism (HR 1.39; 95% CI 1.21-1.60) compared with adults without AD. CONCLUSIONS: Atopic dermatitis, particularly when severe, is associated with small but increased risks of CV risk factors and events and significantly increased risk of venous thromboembolism.