Coeliac disease and Crohn's disease: an association not to be forgotten

A10-month-old girl presented with a 2-month history of diarrhoea, 5–6 times a day. She was otherwise healthy, had a good appetite, and was thriving on a normal infant diet. She was born at full term by normal delivery, birth weight being 3.29 kg (25th centile). Immunizations were up to date and the development was normal. There was no other relevant past history. Her father had Crohn's disease, her maternal grandmother had coeliac disease and her maternal grandfather had ulcerative colitis. She did not improve after changing to a soya-based milk formula. Given the family history, her mother was anxious that she might have coeliac disease and began a gluten-free diet before any formal investigations. This diet led to resolution of her symptoms and she thrived. After medical review, a gluten-free diet was continued and it was decided that a dietary gluten challenge to confirm the diagnosis would be performed at a later date. A gluten challenge was performed at 18 months of age. Duodenal biopsy by Crosbie capsule after 4 weeks showed some normal villi, but was poorly oriented. Gluten intake was not formally assessed. Her diarrhoea recurred and her parents recommenced gluten exclusion, which again led to resolution of her symptoms. A second gluten challenge was arranged when she was 4 years old. This time she tolerated gluten. She did not have a repeat biopsy or serological testing and was discharged from medical follow up on a normal diet. The presumption was that her enteropathy had resolved. Soon after this, however, her parents restarted the gluten-free diet because her symptoms had returned. They did not re-present to her physician and her subsequent compliance with the diet was poor. Thus she remained undiagnosed but on a mostly gluten-free diet. She was referred for reassessment at the age of 12 years with 4 months history of recurrent abdominal pain and profuse diarrhoea. She had lost weight and had developed a secondary amenorrhoea, having started her periods at the age of 11 years. Her recent symptoms had responded, at least in part, to avoiding milk and gluten. Neither the gluten nor the milk exclusion was complete. Her height and weight were between the 25th and 50th centile. Physical examination was unremarkable. Her mother had been diagnosed with coeliac disease 3 years earlier. Investigations showed a normal full blood count, erythrocyte sedimentation rate, C-reactive protein and serum immunoglobulins. Her immunoglobulin A (IgA) anti-endomysial antibody was moderately positive. IgG and IgA anti-gliadin antibodies were negative. IgE RASTs (radioallergosorbent test) to wheat and milk were negative. Barium studies of the small bowel were normal. Three separate stool specimens were negative for bacterial and viral pathogens. She was kept on a strict gluten-free diet for 6 months and improved symptomatically, gaining weight and restarting her periods. Repeat IgA anti-endomysial antibody testing was negative. She had a third gluten challenge in order to formalize the diagnosis of coeliac disease. This was supervised and gluten intake was good. Her symptoms worsened while on the gluten-containing diet. Duodenal biopsy, done after 3 months, showed partial villous atrophy consistent with coeliac disease (Figure 1a). Although she went back to a strict gluten-free diet, there was only moderate improvement in her clinical state. She deteriorated, developing symptoms typical of colitis. Sigmoidoscopy with biopsy showed granulomatous changes in her sigmoid colon consistent with Crohn's disease. She started to improve without additional treatment and her parents were therefore keen to defer further investigation until a relapse. Repeat upper gastrointestinal endoscopy and colonoscopy done after 2 months, while excluding milk and gluten, showed healing of the duodenum (Figure 1b) but a severe colitis consistent histologically with Crohn's disease (Figures 2a and b). Some biopsies showed transmural inflammatory changes and there was a marked inflammatory infiltrate, with granulomata. Her colitis responded well initially to corticosteroids. Milk was successfully reintroduced. She is treated with azathioprine, commenced after a symptomatic relapse, and has remained well for over 12 months. Coeliac antibody titres are normal. She is HLA-DQ2 positive.