Childhood coeliac disease in Estonia, prevalence in atopic dermatitis and immunological characterisation of coexistence

Abstract

Uuringu eesmärgiks oli hinnata lapseea tsöliaakia haigestumust Eestis, levimust atoopilise dermatiidiga lastel ning iseloomustada nende koosesinemise kliinilisi ja immunoloogilisi eripärasid. Nii tsöliaakia kui ka atoopiline dermatiit on ühed sagedasemad lapseea kroonilised haigused, mille tekkes on oluline roll nii geneetilisel eelsoodumusel, immuunsüsteemi häiretel kui ka keskkonna-faktoritel. Tsöliaakia korral põhjustavad teraviljades esinevate valkude poolt vallandatavad autoimmuunreaktsioonid peensoole limaskesta kahjustuse. Pikka aega peeti tsöliaakiat väga harva esinevaks väikelapseea haiguseks, kuid viimastel aastatel on Euroopas tsöliaakiat leitud kuni 3%-l rahvastikust. Tsöliaakia levimuse hindamiseks Eestis teostati sõeluuringud 1160-l juhuslikult valitud Eesti koolilapsel ning leiti, et tsöliaakiat esineb Eestis oluliselt sagedamini kui varasemalt arvatud (vähemalt 0.34%). Analüüsides kõiki aastatel 1976-2010 diagnoositud tsöliaakiajuhte Eesti lastel selgus, et antud perioodil on haigestumus tõusnud enam kui 30 korda. Kui uuringu algaastail diagnoositi tsöliaakia vaid alla kaheaastastel tüüpiliste kaebustega lastel, siis perioodil 2006-2010 diagnoositi enamus juhte atüüpiliste kaebustega või hoopis kaebusteta üle viie aastastel lastel. Tsöliaakia võib esineda koos ligi 100 erineva haigusega, sagedamini erinevate immuunsüsteemi haigustega, sealhulgas allergiahaigustega. Võrreldes 351 atoopilise dermatiidiga last eelnevalt uuritud koolilastega, esineb tsöliaakiat atoopilise dermatiidiga lastel üle nelja korra sagedamini (1.4%). Seejuures pooltel diagnoositud lastest ei esinenud vaatamata väljendunud soolekahjustusele tsöliaakiale viitavaid kaebusi. Seetõttu tuleks peensoole limaskesta kahjustusest tulenevate tüsistuste vältimiseks kaaluda atoopilise dermatiidi lisamist tsöliaakia riskigruppide hulka. Lisaks leidsime atoopilise dermatiidiga lastel tuumavastaseid autoantikehi veidi kõrgemas tiitris ja nooremas eas kui kontrollgrupis, ei olnud erinevused statistiliselt olulised. Kuna aga autoantikehad ilmuvad sageli aastaid enne autoimmuunhaiguse väljakujunemist, tuleks raskekululise atoopilise dermatiidiga patsiente uurida nende antikehade suhtes ning antikeha-positiivseid isikuid jälgida regulaarselt võimaliku autoimmuunhaiguse väljakujunemise suhtes.

The aim of our study was to find the incidence of childhood coeliac disease in Estonia, the prevalence in atopic dermatitis and to characterise their immunological peculiarities. Coeliac disease and atopic dermatitis are among the most common chronic diseases of childhood. Genetic predisposition, dysregulated immune responses and environmental factors play role in the pathogenesis of both diseases. In coeliac disease the ingestion of wheat gluten and related prolamines leads to inflammation and autoimmune damage of the small intestinal mucosa. For a long time coeliac disease was considered a very rare disease in small children, but in recent decades it has been shown to occur in up to 3% in Western populations. In order to assess the prevalence of childhood coeliac disease, 1160 randomly selected Estonian schoolchildren were studied and the prevalence of 0.34% was found. Analysing data from all coeliac disease cases diagnosed in 1976-2010 in Tallinn Children’s Hospital and Children’s Clinic of Tartu University Hospital, we found more than 30-fold increase in coeliac disease incidence over the years. In 1976-1980 coeliac disease was diagnosed only in under-two-year-old children with classical clinical picture (diarrhoea with failure to thrive and/or weight loss, stomach pain), however, in 2006-2010 it was mostly diagnosed with atypical or silent clinical presentation in over-five-year-old patients. Celiac disease has been described together with nearly 100 different diseases, especially with different diseases of the immune system, including allergic diseases. Comparing prevalence of coeliac disease in 351 children with atopic dermatitis and in 1160 school children, it occurs four times more frequently in atopic dermatitis (1.4%). However, half of the children were asymptomatic for coeliac disease, despite the overt damage at the intestinal mucosa. Therefore, in order to prevent serious long-term complications, children with atopic dermatitis should be considered as a risk-group for coeliac disease, especially in the presence of gastrointestinal symptoms. Although, antinuclear autoantibodies were found in atopic dermatitis patients at an earlier age and higher titer when compared to control group, the difference was not statistically significant. Since, the auto-antibodies are detectable often many years before the development of autoimmune disease, atopic dermatitis patients with early onset and severe dermatitis should be screened for antinuclear antibodies, and antibody positive subjects should be regularly followed-up for the possible development of autoimmune disease.