Antinuclear antibodies in atopic dermatitis: a cross-sectional study on 346 children.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease that can be classified into an extrinsic or intrinsic type. A high percentage of patients, especially adults with the extrinsic type of AD, have been reported to show antibodies to antinuclear proteins (ANA). We aimed to study the prevalence of ANA in children with AD and to evaluate clinical differences between patients with ANA-positive and ANA-negative AD. METHODS: A total 346 serum samples from children with active AD (mean age 5.8 years) and 117 hospital controls without known skin, inflammatory, or immune-mediated disease (mean age 7.9 years) were tested for IgG ANA with indirect immunofluorescence on HEp-2 cells, total serum IgE levels, and IgE type antibodies to food allergen panels. RESULTS: In total, 47 patients with AD (13.6%) and 15 subjects in the control group (12.8%) were ANA positive at screening dilution 1:10 (P > 0.05). In patients with AD, ANA was found already at the age of 2 years, significantly more often in females (P < 0.005) and at slightly higher titers (up to 1:160). No differences were found in ANA positivity regarding the severity of AD or sensitization to food allergens. CONCLUSION: No significant differences were observed between AD and the control group, or between different subtypes of AD in ANA prevalence. In both groups, ANA frequency increased with age, but in patients with AD, ANA had a tendency to appear earlier. Therefore, active AD during the early years of life could dispose selected patients towards earlier development of systemic autoreactivity and stress the need for regular follow-up of patients with ANA-positive AD.

Low prevalence of IgA anti-transglutaminase 1, 2, and 3 autoantibodies in children with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a multifactorial chronic inflammatory skin disease presenting with a relapsing clinical pattern similar to chronic autoimmune disease. Several human transglutaminases have been defined and keratinocyte transglutaminase (TG1) and epidermal transglutaminase (TG3) expressed in the epidermis are associated with epidermal barrier dysfunction. Since impairments to the epidermal barrier represent an important factor in AD, we hypothesized that IgA autoantibodies specific for TG1 (IgA-anti-TG1) and TG3 (IgA-anti-TG3) may affect AD development during childhood. METHODS: Active AD patients (n = 304), 28 patients with biopsy-confirmed coeliac disease (CD), 5 patients with active AD and CD, and 55 control patients without CD and skin diseases were enrolled into the study. IgA-anti-TG1 and IgA-anti-TG3 reactivity was determined using an enzyme-linked immunosorbent assay. IgA-anti-TG2 were defined using a fluoroenzyme immunoassay. RESULTS: IgA-anti-TG1 antibodies were found in 2% and IgA-anti-TG3 antibodies in 3% of patients with active AD. Two out of the 5 patients with AD and concomitant CD had IgA-anti-TG1 and IgA-anti-TG2 antibodies. In CD patients, 36% of individuals presented with elevated IgA-anti-TG1 antibodies and 18% presented with elevated IgA-anti-TG3 antibodies and all CD patients presented with IgA-anti-TG2 antibodies (significantly different from AD patients and controls, p < 0.05). In CD patients, IgA-anti-TG1 and/or IgA-anti-TG3 seropositivity tended to appear concurrently, whereas only one patient with AD had both types of autoantibodies. CONCLUSIONS: IgA-anti-TG1 and IgA-anti-TG3 seropositivity was rare in active AD but frequent in CD patients. The level of circulating antibodies related to skin lesions could be studied by determining the levels of IgA-anti-TG1 and IgA-anti-TG3 in skin biopsies of AD patients.

Celiac disease in children with atopic dermatitis.

Celiac disease (CD) is an autoimmune disorder of the small intestine with highly variable clinical presentation and frequently associated with various immune-mediated diseases. Among these immune-mediated diseases, atopy has been found frequently in individuals with CD. We aimed to study the prevalence of CD in Estonian children with atopic dermatitis (AD), a common multifactorial chronic inflammatory skin disease. We recruited 351 consecutive children with active AD (mean age 5.8 yrs, 57.6% boys) at Tallinn Children's Hospital, Estonia. Sera of all patients were tested for total serum immunoglobulin (Ig) A, for IgA- and IgG-type autoantibodies to tissue transglutaminase (IgA-anti-TG2, IgG-anti-TG2) and to deamidated gliadin peptides (IgA-anti-DGP, IgG-anti-DGP). The diagnosis of CD was confirmed histologically by small intestine biopsy according to the European Society of Paediatric Gastroenterology, Hepatology and Nutrition diagnostic criteria. IgA deficiency was detected in nine patients with AD (2.6%), none of whom had IgG-anti-TG2 or IgG-anti-DGP seropositivity. IgA-anti-TG2 positivity was found in 4 (1.1%), IgG-anti-TG2 positivity in 2 (0.6%), IgA-anti-DGP positivity in 11 (3.1%), and IgG-anti-DGP in 10 (2.8%) patients. Celiac disease was confirmed in five (1.4%) patients with AD (95% confidence interval 0.46, 3.32) and all were histologically characterized as Marsh IIIa-IIIc stages and two presented with silent CD. In AD patients, CD prevalence was more than four times as high as in previously studied randomly selected schoolchildren in Estonia. Two patients with AD diagnosed with CD had no symptoms indicative of CD, in spite of extensive histologic changes in the small intestine mucosa. Therefore our study emphasizes the need for evaluating the cost-effectiveness of screening individuals with AD for CD in time to prevent long-term complications.