*Division of Gastroenterology, Children's Hospital, Harvard Medical School, Boston, MA, USA
†Clinical Laboratory of the Black Hills, Rapid City, SD, USA
‡Boys Town National Research Hospital, Boys Town, NE, USA.
Received 30 April, 2009
Accepted 7 September, 2009
Address correspondence and reprint requests to Rosemary Young, APRN, 14040 Boys Town Hospital Road, Boys Town, NE 68010 (e-mail: firstname.lastname@example.org).
The authors report no conflicts of interest.
Collagenous colitis, a cause of chronic diarrhea in adults, occurs infrequently in children and is often associated with autoimmune disease (1,2). It has rarely been reported at <5 years of age, and little data exist on effective treatment in children (3). Table 1 reviews previous pediatric case reports to date. We describe here a 4-year-old child with no coassociated autoimmune disease and her response to oral budesonide.
A 4-year-old girl with a history of chronic diarrhea was referred to the pediatric gastroenterology clinic. The diarrhea had been present for 6 months and was described as watery with food particles present but no visible blood. By history, the patient was the product of a full-term, uncomplicated pregnancy. She received cow's-milk–based formula from birth; however, by 2 months of age she began experiencing frequent, large-volume emesis, which failed to respond to acid suppression. Symptom resolution was noted after 3 weeks of an amino acid formula. The child transitioned to a normal toddler diet at 13 months of age with tolerance for all foods including dairy products. She had no ill visits to the pediatrician until 36 months, at which time she began having frequent loose stools. Stool cultures and viral assays had been obtained on multiple occasions and found to be normal. The pediatrician suspected toddler osmotic diarrhea, and there was slight improvement when juice was restricted from her diet. There was no noted weight loss during this time because her growth was proceeding along the 25th percentile for both weight and height and there were no other noted health issues. Family history was noncontributory, particularly in regards to any history of autoimmune or gastrointestinal disorders.
At the time of presentation to the pediatric gastroenterology clinic, she was noted to have a papular rash on her cheeks and extremities; her abdomen was nonprotuberant and soft with no masses or areas of tenderness identified. Rectal examination was normal with hemoccult-negative stool. Per her mother's report she had no complaints of abdominal discomfort and was having 6 to 9 loose watery stools per day with no noted blood or mucus.
Because of her history of cow's-milk protein intolerance, a strict dairy-free diet was prescribed, but within several days, the patient began having worsening diarrhea, with 10 to 12 watery stools per day. Subsequent workup including an abdominal ultrasound as well as immunoglobulin A tissue transglutaminase, sedimentation rate, C-reactive protein, complete blood count, and comprehensive metabolic profile were obtained and all reported as normal. Stool for culture, giardia antigen, viral assay, white cells, occult blood, fecal elastase, and calprotectin were obtained, with the only abnormality being the calprotectin level, which was elevated at 207 μg/g (normal range ≤50 μg/g).
Upper and lower gastrointestinal endoscopic examinations were performed. Visually the duodenum and colonic intestinal mucosa appeared normal. Biopsies of the esophagus, stomach, duodenal bulb, second portion of the duodenum, and terminal ileum showed no abnormalities. The colonoscopic biopsies obtained from the ascending and descending colon and rectum demonstrated collagenous colitis on all of the specimens obtained, with an average band thickness of 10.7 μm (Fig. 1). The patient was empirically placed on 3 mg of oral budesonide (capsule was opened and granules given with applesauce or yogurt) and within 2 weeks, her diarrhea significantly diminished, with an average of 1 to 2 soft formed bowel movements per day. No dietary changes were made during this time, and the child was able to tolerate all of the major food groups including dairy. After 6 months of therapy, repeat colon biopsies demonstrated significant resolution of the collagen formation in all of the biopsy samples throughout the colon (average band thickness 4.6 μm) and normalization of the fecal calprotectin to 10 μg/mL (Fig. 2). Her weight and height both increased to the 50th percentile and she was transitioned to 3 mg of budesonide every other day for 6 months. An attempt to discontinue the drug at this time resulted in a relapse of loose stools numbering 6 per day within 1 week of drug discontinuation. She continues to receive every-other-day budesonide, with plans to attempt weaning again in a few months with a transition to sulfazalzine or mesalamine therapy. If she continues to be dependent on budesonide, then a bone densitometry study and ophthalmology examination will be performed to monitor for potential steroid adverse effects.
Collagenous colitis was first reported in 1976 by Lindström (4), who described a new condition in which chronic watery diarrhea occurred in association with deposits of the subepithelial collagen obtained endoscopically from normal-appearing colonic mucosa. The first cases of collagenous colitis in children were described in 1989, in 3 separate reports, in children ranging in age from 5 to 12 (5–7). Since that time there have been other pediatric cases described (8,9), but as in adults, many of the previously reported pediatric patients had other coassociated autoimmune disorders and episodes of dehydration, which our case clearly did not. In 2003, Camarero et al (3) published a case report of 2 children with collagenous colitis and highlighted the clinical, histopathological, microbiological, and immunological features of this condition. As in the present report, our patient had evidence of collagen deposition in all of the colonic biopsies taken throughout the colon with no skip areas as reported previously. In contrast to the present report, however, our child had a normal sedimentation rate and no reported Aeromonas hydrophila in multiple stool cultures.
The true incidence of collagenous colitis is unknown in children, but in adults, it has been estimated to range from 1.1 in 100,000 people in Spain to 5 of every 100,000 people in the United States, occurring predominantly in older adult women (9–11). Familial clustering of collagenous colitis has also been reported (12,13). In adults, this condition appears to be lifelong; however, the expected history in children is not known.
The etiology of collagenous colitis is unknown, but 3 possible mechanisms have been suggested. The most common is autoimmune; however, luminal agents and fibroblast dysfunction have also been suggested. The rationale for the autoimmune disease is related to the female predominance, the common occurrence of other autoimmune diseases in those previously reported, and the response to steroid therapy (14). Jarnerot reported that diversion of the fecal stream can normalize or reduce the histopathological changes, suggesting that infectious or chemical irritants may be related (15). Fibroblast dysfunction and drug-induced causes have also been suggested as possible mechanisms (16).
The symptoms of collagenous colitis are generally nonspecific and include chronic watery diarrhea, abdominal discomfort, weight loss, and fecal incontinence (8,17). In adults, it is often misdiagnosed as irritable bowel syndrome and in children as functional diarrhea. Typically, laboratory studies reveal only mild abnormalities and are often nonspecific. The visual appearance of the colonic mucosa is most often normal, and because the collagen deposits in the colonic mucosa have been reported as patchy (8), diagnosis requires colonoscopic biopsy at multiple levels in the colon. It is suggested that collagenous colitis be defined by the appearance of diffuse thickening of subepithelial collagenous band (>10 μm), erosion of surface epithelium, increased numbers of intraepithelial lymphocytes, and mild or moderate mononuclear infiltration of lamina propria (14). Treatment options include oral corticosteroids, bismuth subsalicylate, and probiotics (18). More recently oral budesonide was used successfully in a group of adults (19).
Our case emphasizes that collagenous colitis should be considered in the differential diagnosis of young children with watery diarrhea unresponsive to usual dietary management. Our patient had an excellent response to oral budesonide, suggesting that it should be considered for therapy in children as well as in adults.
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