Clinical Quiz

Abstract

A 17-month-old boy with cystic fibrosis presented with a 2-month history of bloody diarrhea and poor weight gain. He had no previous history of meconium ileus, constipation, distal intestinal obstruction syndrome or abdominal surgery. The patient's mother reported giving the child six capsules of pancreatic enzymes (Ultrase, 4500 units lipase/capsule) with each breastfeeding session. Stool culture was negative for any pathogens; stool Clostridium difficile toxin was negative. Colonoscopy was performed showing edema, erythema and friability; a stricture was noted in the distal ascending colon in proximity of the hepatic flexure. Pinch biopsies of the colonic mucosa showed an increase in capillaries and extravasation of erythrocytes into the lamina propria but no evidence of colitis. A barium enema was done (Fig. 1).FIG. 1: Barium enema showing a featureless colon with retraction and narrowing of the proximal colon (arrow). There is flow of contrast material into the terminal ileum and appendix (*).What is the diagnosis? Crohn disease. Distal intestinal obstruction syndrome. Fibrosing colonopathy. Stricture from necrotizing enterocolitis. Adenocarcinoma. ANSWER/DISCUSSION The diagnosis is C, fibrosing colonopathy. Medical management was instituted with elemental formula, decreasing pancreatic enzymes, and eventually nil per os and total parenteral nutrition. Symptoms did not abate and the patient was taken to surgery, where 9 cm of fibrotic ascending colon was resected (Fig. 2). Histologic findings were consistent with fibrosing colonopathy, including submucosal and serosal fibrosis with a few inflammatory cells present; there was no evidence of cryptitis or granuloma formation (Fig. 3).FIG. 2: Surgical specimen showing the thickened mucosa and narrowed lumen of the proximal colon.FIG. 3: Histology shows an expanded submucosal layer with severe fibrosis. A, hematoxylin and eosin stain, original magnification ×40. The fibrosis is highlighted with a trichrome stain that stains collagen blue. B, Masson trichrome stain, original magnification ×40.Submucosal inflammation and fibrosis leading to colonic stricture and subsequent bowel obstruction characterize fibrosing colonopathy (1,2). The initial description of this disorder was temporally related to the introduction of high-strength pancreatic enzyme supplement (up to 20,000 U of lipase/capsule) in children with cystic fibrosis. Case-controlled studies confirmed a higher risk of developing fibrosing colonopathy with the use of large amounts of high-strength pancreatic enzyme supplements (3,4). Subsequently, a consensus statement was issued recommending limiting enzyme supplementation to <2500 units lipase/kg/meal and <10,000 units lipase/kg/day (3,4). The patient described here was receiving the recommended enzyme supplementation per meal; however, he was breastfeeding 10 to 12 times per day. The mother diligently gave replacement enzymes with each feed to optimize growth, resulting in a total daily dose of 27,000 to 32,000 units lipase/kg/day. The exact pathogenic mechanism for the development of fibrosing colonopathy is unclear, but proposed contributors to the development of fibrosing colonopathy include abnormal intestinal permeability, genetic predisposition and resins in the enteric coating of the pancreatic enzyme capsules (1,2). Radiological modalities that are useful in the investigation of colonic inflammation in patients with cystic fibrosis include barium enema and abdominal ultrasound. Characteristic barium enema findings in fibrosing colonopathy include stricture, abnormal haustra, and longitudinal shortening of the colon, beginning in the right colon and sometimes involving the distal colon without skip areas (5). Abdominal ultrasound has also been used to evaluate intestinal wall thickness as a sign of inflammation of preinflammatory processes in the setting of cystic fibrosis (6). Diagnosis of fibrosing colonopathy is based on histologic findings. A full-thickness biopsy is required because endoscopic pinch biopsies are too superficial to show the extensive submucosal fibrosis. The natural history of fibrosing colonopathy is difficult to ascertain. Although less severe subclinical cases may exist, most reported cases have involved advanced disease with stricture formation. It is unlikely that the degree of fibrosis present in symptomatic cases will respond to medical therapy. The patient we describe had a stricture that was treated conservatively with medication, bowel rest and nutritional support for 6 months without any improvement in symptoms. Surgical resection of the stenotic area is the best option for advanced disease. Fibrosing colonopathy does not recur after surgery and decreasing the pancreatic enzyme supplementation (7).