Gluten challenge in children with coeliac disease. With special reference to dose dependence and impact on growth markers and growth hormone secretion

Abstract: Coeliac disease is a prevalent food intolerance in both children and adults, in which ingestion of gluten causes inflammation of the small intestine. This inflammation resolves upon gluten withdrawal, and gluten challenge induces relapse of enteropathy in susceptible individuals. To identify the impact of gluten dose upon the manifestations of coeliac disease, the outcomes of two defined gluten doses were compared using gluten challenges of fixed duration. The aims were to evaluate the effects of the two gluten doses on the small intestinal mucosa and on serological markers. Further aims were to explore the effects of these doses on symptoms, signs and liver function tests and to investigate whether the development of symptoms has an impact on gluten consumption. A symptom score (SS) and an enteropathy score (ES) were developed as instruments for evaluating dose differences. The impact of gluten challenge on growth markers and growth factors was explored and the relationship to other clinical parameters was evaluated, including spontaneous growth hormone (GH) secretion. The results showed the degree of enteropathy to be dose dependent, but anti-gliadin antibody (AGA) or endomysium antibody (EmA) levels were not. Ninety-four percent of the children relapsed within 4 weeks. The symptom score increased with increased gluten dose. Symptoms were common and correlated with the degree of enteropathy. There was a sex difference with more conspicuous change of weight and serum albumin in girls. The patients adapted their gluten consumption with respect to the prescribed dose and symptoms. A reduction of alkaline phosphatase (ALP) activity and serum levels of insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) was observed. Part of the reduction of IGF-I was correlated with the development of enteropathy. Gluten challenge was however not associated with a reduction of spontaneous GH secretion.These studies demonstrate that lower gluten doses and a shorter duration than in previous studiesof gluten challenge may be used to confirm coeliac disease. Gluten doses of 0.2 g/kg/d may be used for gluten challenge in patients with "classic" presentation of coeliac disease.