Coexistence of celiac disease and eosinophilic gastroenteropathy.

Abstract

The average incidence of celiac disease in Europe is 1 case in every 1,000 live births, ranging from 1 in 250 observed in Sweden to 1 in 4,000 observed in Denmark (1). The prevalence of celiac disease in the United States is probably comparable with that of Europe (1). The idiopathic form of eosinophilic gastroenteropathy (EG) is a relatively uncommon disorder, usually affecting the upper gastrointestinal tract, that may present at any age and that often requires steroid therapy (2). Review of the literature did not reveal any association between these diseases. We describe a teenager with near-fatal asthmatic crisis at presentation. CASE REPORT A 14-year-old boy with a history of severe asthma was referred to the Pediatric Gastrointestinal Clinic because of loose stool, poor weight gain (weight and height in the third percentile), and ascites. Physical examination revealed diffuse expiratory wheezing and mildly distended abdomen with minimal shifting dullness. Laboratory studies showed eosinophilia of 0.10 to 0.15 of total white blood cell count and normal blood chemistry results, including serum protein and albumin. The results of repeated sweat tests were normal. Antiendomysial antibodies were positive. Duodenal biopsy showed flat villi and deep crypts with mitoses in the epithelium and chronic inflammatory infiltrate in the stroma spreading also into the epithelium. These findings were compatible with severe celiac disease. Abdominal paracentesis revealed ascitic fluid with 1,500 white blood cells/mm3, mostly eosinophils. Chest radiography revealed peribronchial thickening. Computed tomography of the abdomen demonstrated nodular mesenterium. The boy was otherwise healthy. The boy was advised to adopt a gluten-free diet. However, despite avoiding gluten-containing food, his weight gain was less than expected. The results of repeated duodenal biopsies were never considered normal. Asthmatic attacks necessitated frequent admissions to the hospital, where intravenous corticosteroids were administered. Diminution of ascitic fluid was noted when the patient was given high doses of corticosteroids. Persistent eosinophilia, ascites containing large number of eosinophils, and reduction of ascitic fluid after intravenous corticosteroid administration, persistent damaged duodenal mucosa, and uncontrollable asthmatic attacks raised the suspicion of coexistent EG with celiac disease. Assessment of major basic protein by immunofluorescence staining of duodenal biopsy from the patient substantiated the diagnosis of EG (Fig. 1) (3).FIG. 1.: Localization of eosinophil granule major basic protein (MBP) in gastrointestinal biopsy tissue specimen (original magnification, ×400). A: Section stained with affinity-purified rabbit antihuman MBP. B: Same section as in A, counterstained with hematoxylin and eosin. Note the marked extracellular MBP deposition and the relative paucity of intact eosinophils.Figure 1: ContinuedDISCUSSION Eosinophilic gastroenteropathy was described first by Kaijser in 1937 (4). The most common gastrointestinal symptoms of EG are vomiting (50%), abdominal pain (40%), and growth failure (35–100%) (5). Diarrhea may be associated with rectal bleeding (23%), especially in infants (5). Systemic symptoms include fatigue, headache, dizziness, and joint pain in two thirds of the patients (6). Hypoalbuminemia and peripheral edema result from protein-losing enteropathy. As in the current patient, ascitic fluid is rich in eosinophils. In some cases, specific foods may precipitate symptoms. This condition may be difficult to distinguish from allergic gastroenteropathy. Duodenal biopsy in children with allergic gastroenteropathy is characterized by mucosal injury that includes partial or subtotal villous atrophy rather than tissue eosinophilia, which is usually encountered in EG (7,8). However, duodenal biopsy in patients with celiac disease shows absent or stunted villi, long crypts, and an increased number of plasma cells in the lamina propria. Evidence exists that assessment of eosinophil involvement in disease should use a more functional approach to trace eosinophil granules or their products, for example, major basic protein rather than their number in tissue or circulation (3). Although demonstration of cellular major basic protein indicates presence of eosinophils, the demonstration of extracellular major basic protein signifies eosinophilic degranulation, clearly a more significant indicator for eosinophilic involvement. Major basic protein immunofluorescence staining of gastrointestinal tissue from this teenager substantiated the diagnosis of EG. Finally, a combination of respiratory and gastrointestinal disease logically is first suspected to be a presenting symptom of cystic fibrosis. However, clinicians should bear in mind the possibility of the coexistence of two diseases rather than one.