The Role of Corticosteroids in Celiac Disease

Abstract

Since Dickie first described the benefits of a gluten-freediet in the 1940s and 1950s, this diet is the standard of carefor all patients with celiac disease [1, 2]. For patients with anew diagnosis, dietary compliance can be difficult toachieve, possibly resulting in a clinical course marked bydelayed recovery and persistent symptoms. This is of par-ticular concern for patients in the developing world, wheregluten-free food items may be difficult to obtain or toidentify. While dietary modifications are likely to remainthe treatment of choice in celiac disease, the use of adju-vant corticosteroids in newly diagnosed patients is a topicthat has been addressed previously. In this issue ofDigestive Diseases and Sciences, Shalimar et al. [3] revisitthe concept of corticosteroids in the management of celiacdisease, focusing on their effects on cellular death andregeneration. Their objective was to identify whetheradjuvant treatment with corticosteroids can help expediteclinical and histological recovery in patients with newlydiagnosed celiac disease.The use of systemic corticosteroids for severe celiacdisease is not new. Dr. Jerry Trier [4, 5] described their usein severe disease in 1978 and in subsequent reviews.Currently, the most common indication for the use ofcorticosteroids in celiac disease is the treatment of refrac-tory symptoms. Refractory celiac disease is defined aspersistent malabsorption symptoms and villous atrophydespite strict adherence to a gluten-free diet for6–12 months [5, 6]. There are two subtypes of refractoryceliac disease: type 1 disease is characterized by normalintra-epithelial lymphocytes, whereas type 2 disease ischaracterized by aberrant intra-epithelial lymphocytes ofclonal origin. Type 2 disease has an extremely poorprognosis as it is considered a cryptic T cell lymphomawith a high rate of progression to enteropathy-associated Tcell lymphoma (EATL) [6]. Although both subtypesrespond to corticosteroids, type 1 patients may need addi-tional immunosuppression, but usually do well, whereasthose with type 2 disease may respond initially but oftenlater deteriorate [6]. Corticosteroids, however, remain themainstay of treatment for refractory celiac disease.A second and less common indication for the use cor-ticosteroids in celiac disease is for the treatment of life-threatening celiac crisis. Although rare, celiac crisis isassociated with high morbidity and mortality rates andnecessitates immediate intervention and supportive care[7]. The goal of treatment is to promptly reverse mucosaldamage and metabolic derangements. Although cortico-steroids have not yet been studied prospectively, they havehistorically been given to individuals who are notresponding rapidly enough to gluten restriction. Theauthors of a recent retrospective study of patients withceliac crisis reported that patients who received cortico-steroids experienced rapid clinical improvement within2 weeks of treatment initiation and were eventually able tobe maintained on a gluten-free diet alone [7]. The datafrom this study set a precedent for the short-term use ofcorticosteroids when prompt reversal of symptoms isneeded.Due to the systemic side effects of systemic cortico-steroids, interest in locally active corticosteroids hasincreased. Evidence confirming their effectiveness in celiacdisease first came from in vitro studies involving samplesof intestinal mucosa in tissue culture. In 1981, Brambleet al. [8] examined intestinal enzyme activity in patients