Celiac disease predominantly afflicts the proximal small bowel whereas Crohn’s pathology is most often seen in distal small bowel and proximal colon. The present case is interesting as Celiac disease manifested much before Crohn’s disease (CD).

Case report

A 17 year old male presented in 2003 with painless large volume diarrhea since 5 years without any associated blood, mucus, tenesmus or steatorrhea. On examination he had short stature, pallor and secondary sexual characters were absent. Systemic examination was normal. Laboratory studies showed hemoglobin: 7.6 gm/dl, WBC count: 5600 cells/mm3, neutrophils: 61%, lymphocytes: 33%, platelet count: 417,000/mm3, ESR: 10 mm and MCV:72 fL. RBC morphology on peripheral blood examination showed predominantly microcytic, hypochromic red blood cells with anisocytosis, poikilocytosis and target cells. Stool examination was positive for occult blood and showed no ova, cyst or fat globules. Renal function tests, serum bilirubin and liver enzymes were normal. Total protein was 4.2 gm/dl, and serum albumin was 2.7gm/dl. HIV serology was negative.Upper GI endoscopy showed decreased duodenal folds with few nodules. Biopsy from second part of duodenum showed villous atrophy, crypt hyperplasia with increased intraepithelial lymphocytes. IgA TTG was 36.74 U (normal < 10 U). IgA antigliadin antibodies level was 7.8 U (normal < 2.8 U).Patient was diagnosed with celiac disease and started on gluten free diet with iron and vitamin supplements. The patient gained 4 kg weight over next two years and was symptomatically better with improved hemoglobin. Between 2006 and 2007 he had episodes of intermittent abdominal pain with diarrhea, weight loss and easy fatigability despite a gluten free diet. He consulted a local practitioner, and was found to have severe anemia with a hemoglobin level of 5.5 gm/dl. The patient also received multiple blood transfusions. In 2008, he was admitted at our centre for persistent symptoms. He had significant weight loss with increased frequency and severity of abdominal pain. On examination he had severe malnutrition with a BMI of 13.8 kg/m2 and peripheral edema. Investigations revealed hemoglobin: 5.0 gm/dl, MCV: 60.0 fL, total protein: 3.0 gm/dl, albumin: 1.7 gm/dl. Stool examination was positive for occult blood, with no fat globules, ova or cyst.Upper GI endoscopy showed normal duodenal folds. Duodenal biopsy showed well preserved villi with normal crypt architecture with no increase in intraepithelial lymphocytes. IgA TTG was at 2.0 U/ml (normal < 7 U/ml). Colonoscopy was normal up till the terminal ileum. BaMFT showed mild mucosal thickening of jejunum, with free flow of barium in jejunal and ileal loops. Push enteroscopy was performed and showed normal jejunal folds and biopsy from the region showed features of non specific jejunitis.Capsule endoscopy was performed to investigate small bowel mucosal morphology which showed normal proximal jejunal mucosal folds and there were no ulceration but the capsule got retained in distal jejunum. The patient was asymptomatic, despite the capsule inside the intestine for 14 days which did not pass out. CT scan abdomen showed the capsule in distal jejunum without proximal dilation of bowel loops (Figure 1). The patient was subjected to exploratory laparotomy. During the surgery the patient was discovered to have multiple strictures in distal jejunum and ileum and the capsule was trapped above one of these strictures. Biopsy of the resected segment showed ulcerated mucosa with tall villi and intraepithelial lymphocytes. Lamina propria showed dense inflammatory cells, submucosal edema with lymphoid follicles, dilated lymphatics and proliferating nerve bundles. The serosa showed creeping of fat, suggesting the diagnosis of Crohn’s disease.The patient was started on azathioprine, was continued on gluten free diet and he gained weight with improvement in symptoms.

Discussion

Literature showing celiac disease preceding Crohn’s disease is sparse. In a reported series patients had predominant colonic CD in association with celiac disease.[1] Our patient presented with celiac disease much before CD manifested. Five years after the diagnosis of celiac disease when the disease specific parameters were negative, the patient experienced episodes of abdominal pain with weight loss and was investigated to be diagnosed with jejunal and ileal structuring CD. Immunopathogenesis of celiac and Crohn’s disease are similar.[2] Both diseases are mediated by the T-helper type 1(TH1) pathway[2,3] and are characterized by decreased cellular apoptosis[4,5,6] which provokes a chronic inflammation predominantly in the lamina propria accompanied with IL-15 over expression, increased TNFa, interferon ?, and IL-8.[3,7,8,9,10] Celiac disease is characterized by increased gut permeability due to zonulin reduction[11] and in CD it is related to the action of TNFa.[12,13,14] It is believed that increased gut permeability in CD may expose the mucosal immune system to several bacteria and their antigens mimicking gliadin sequences, resulting in activation of cytokine networks to initiate a TH1 immunologic reaction with development of celiac disease lesions. However, why all CD patients do not develop manifestations of celiac disease, remains unexplained. Celiac disease has been noted to have a definitive association with HLA-DQ2 and HLA-DQ8[15] whereas the relation between CD and HLA genes seems to be lacking. So, probably only patients with CD having above haplotypes may develop celiac disease like lesions.

References