Desquamative enteropathy and pyloric atresia without skin disease caused by a novel intracellular beta4 integrin mutation.

BACKGROUND: Mutations in alpha6 or beta4 integrins (ITGA6, ITGB4) are known to cause junctional epidermolysis bullosa with pyloric atresia (JEB-PA), often lethal in infancy through skin desquamation. There is 1 report of pyloric atresia associated with a desquamatory enteropathy but without skin disease, of unknown molecular basis. PATIENTS AND METHODS: We report 2 Kuwaiti siblings with pyloric atresia and life-threatening intestinal desquamation without significant skin abnormality. The older sibling died of intractable diarrhoea, and the younger sibling suffered episodes of massive protein-losing enteropathy, triggered by viral infections, in addition to obstructive uropathy. Mutation analysis was performed for ITGA6 and ITGB4 and expression of ITGA6 and ITGB4 protein was examined in skin and intestinal biopsies. Her serum also was incubated with normal intestine. RESULTS: We identified a novel mutation in ITGB4, with homozygous deletion of a single residue (isoleucine 1314) within the intracellular plectin-binding domain. Expression of ITGA6 and ITGB4 within skin, duodenal, and colonic epithelium was normal or minimally reduced, in contrast to previous reports. Biopsies taken during relapse showed accumulation of immunoglobulin G and C1q within intestinal basement membrane, whereas immunoglobulin G from her serum bound to basement membrane of normal small intestine. Immunomodulatory therapy induced significant improvement following relapses. CONCLUSIONS: ITGB4 mutation may induce a desquamative enteropathy in infancy without significant skin disease. A history of pyloric atresia is important in infants with severe chronic diarrhoeal disease and should prompt investigation for JEB-PA associated mutations. Acquired immune responses may exacerbate primary genetic disorders of epithelial adhesion and immunomodulatory therapy may be beneficial.

Use of serologic markers as a screening tool in inflammatory bowel disease compared with elevated erythrocyte sedimentation rate and anemia.

OBJECTIVES: The purpose of this work was to evaluate the use of serologic testing as a screening test for inflammatory bowel disease compared with erythrocyte sedimentation rate and hemoglobin in a referred patient population with suspected inflammatory bowel disease. PATIENTS AND METHODS: A retrospective study was performed, reviewing medical charts of patients who had inflammatory bowel disease serology performed at Prometheus Laboratories from September 2002 to September 2004. Patients were divided into 4 categories: ulcerative colitis, Crohn disease, indeterminate colitis, and noninflammatory bowel disease groups. Patients were categorized based on clinical evaluation by board-certified pediatric gastroenterologists. RESULTS: A total of 227 patients seen at the Lucile Packard Children's Hospital Gastroenterology Clinic had inflammatory bowel disease serology performed at or before the time of diagnosis. Seventeen charts were excluded secondary to inadequate information. Forty children were found to have inflammatory bowel disease, a prevalence of 19%. Overall, serologic testing for inflammatory bowel disease had 60% sensitivity and 92% specificity. A positive laboratory test for anemia or an elevated erythrocyte sedimentation rate had 83% sensitivity, whereas the combination of anemia and elevated erythrocyte sedimentation rate had 96% specificity. The positive predictive value of serologic testing was 60% compared with 79% in patients with anemia and elevated erythrocyte sedimentation rate. The positive predictive value of serologic testing in the subgroup of subjects without rectal bleeding (139 subjects) was only 35% compared with 60% using routine tests. Almost one third of all positive serologic tests were in patients with no demonstrable inflammatory bowel disease. CONCLUSIONS: As a pediatric inflammatory bowel disease screening strategy for the general pediatrician or gastroenterologist, the measurement of the combination of erythrocyte sedimentation rate and hemoglobin has a higher positive predictive value and is more sensitive, more specific, and less costly than commercial serologic testing.