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.

The aims of the study were to analyze the trends and characteristics of the incidence and clinical presentation of childhood celiac disease (CD) from 1976 to 2010 in Estonia. The study included all children up to 19 years of age diagnosed with small bowel biopsy proven CD. During a 35-year period, CD was diagnosed in 152 children in Estonia (68 boys, median age 2.3 years). From 1976 to 1980, the age-standardized incidence rate of CD was 0.10 per 100,000 person-years. After the introduction of gliadin and endomysium antibody screening (in conjunction with activities directed to increase the physicians awareness), the incidence rate increased from 0.48 in 1986-1990 to 1.55 per 100,000 person-years in 1991-1995. After initiating screening with anti-tissue transglutaminase antibodies in 2003 and routine screening for CD among all children with newly diagnosed type 1 diabetes in 2005, the incidence rate increased from 1.59 in 2001-2005 to 3.14 per 100,000 person-years in 2006-2010 (median age 6.8 years). Our nationwide study demonstrates a more than 30-fold increase in the incidence of childhood CD over a 35-year period in Estonia, along with changing patterns in the presentation of pediatric CD. In addition to the impact of use of novel CD screening methods, active search and rising of the awareness among doctors may have strongest effect. Both environmental and social factors could be also involved in the increase in CD incidence.

BackgroundAtopic 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.MethodsActive 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.ResultsIgA-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.ConclusionsIgA-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.

In the present study we aimed to evaluate the impact of langerin (CD207)+ dendritic cells (DCs) and FOXP3+ Treg cells in the intestinal mucosa of children with celiac disease (CD) and atopic dermatitis (AD) in comparison to children with functional gastrointestinal disorders (FGD). Seventy-five children (37 male, mean age 8.4 ± 4.8 years), who randomly underwent small bowel biopsy, were studied. The CD was diagnosed in 14 children, including five persons with concomitant AD (all positive for anti-tissue transglutaminase IgA antibodies and with small bowel atrophy). Normal small bowel mucosa was found in eight patients with AD and in 53 patients with FGD. The sera of all patients were tested for total and specific IgE antibodies to food allergen panels. Staining for CD11c+, langerin (CD207+) DCs, CD4+, and FOXP3+ Treg cells was performed on paraffin-embedded sections of bioptates using immunohistochemistry. The density of CD11c+ DCs, CD4+, and FOXP3+ Treg cells was higher in the CD patients compared to the AD and FGD patients (p = 0.02; p = 0.001). In AD, significantly higher density of CD11c+ DCs was detected in patients positive for specific IgE to food allergen panels (p = 0.02). The FGD patients with elevated total IgE had increased density of langerin (CD207)+ DCs compared to the patients with normal total IgE levels (p = 0.01). The increased density of FOXP3+ Treg cells, CD4+, cells and CD11c+ DCs was associated with CD but not with AD. The elevated level of total IgE or specific IgE to food allergens was associated with more pronounced expression of DCs, indicating a possible link between the presence of these cells in small bowel mucosa with elevated level of serum IgE.

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.