Joyce D. Gryboski

Crohn's disease in children 10 years old and younger : comparison with ulcerative colitis

SummaryIn order to examine the presentation and course of Crohns disease (CD) versus those of ulcerative colitis (UC) in children ±10 years of age, a retrospective review of children ±10 years old with inflammatory bowel disease singled out 40 patients and compared their findings with those of 38 children with UC. The mean age at onset was 7.5 years for CD, as compared with 5.9 years for UC. A family history of inflammatory bowel disease was present in 13 patients (32%). Abdominal pain (97%), diarrhea (78%), and weight loss (88%) were the major initial complaints, with growth retardation present in 12 (30%) children. At onset, four children had diffuse small-bowel disease, nine had terminal ileal disease, 15 had ileocolitis, and 12 had colitis; at the end of the study two had diffuse small-bowel disease, four had terminal ileal disease, 25 had ileocolitis, and seven had colitis. Extraintestinal manifestations increased with duration of disease. Although the number of recurrences did not differ greatly between groups, those with ileocolitis and colitis needed longer steroid therapy and more days in hospital than did those with only small-bowel disease. Operation was required in 42.5% of children with CD, as compared with 5% of those with UC, with six CD children (35%) requiring later reoperation for recurrent disease or fistula and abscess. Two children died from causes unrelated to their disease (gastric volvulus, carcinoma of the breast). The number of operations, duration of steroid therapy in the course of a year, and days in hospital for children with CD exceeded those for a similar group of children with UC. The quality of life noted at the end of the study period was considered only fair in the majority (70%) of CD patients, in contrast to those with UC, 75% of whom considered life good after 2 years of illness.

Relationship of common laboratory parameters to the activity of Crohn's disease in children

The Pediatric Crohns Disease Activity Index (PCDAI) has been proposed as a simple instrument to aid in the classification of patients by disease severity. The PCDAI includes subjective patient reporting of symptoms, physical examination, nutritional parameters, and several common laboratory tests (hematocrit, erythrocyte sedimentation rate, albumin). In this report we examine the relationship of each of the laboratory parameters to the PCDAI, as well as to a modified Harvey-Bradshaw Index score and physician global assessment of disease activity. Data were gathered from the clinical and laboratory observations from 133 children and adolescents at 12 pediatric gastroenterology centers in North America. A statistically significant relationship (p < 0.05) was noted between each of the laboratory tests and the PCDAI for patients with either disease limited to the small bowel or in those with colonic in volvement. For patients with disease limited to the small bowel, a statistically significant (p < 0.05) relationship was also noted between the three laboratory parameters and the modified Harvey-Bradshaw Index and global assessment. For patients with large-bowel involvement, the erythrocyte sedimentation rate was statistically related to the modified Harvey-Bradshaw Index and global assessment (p < 0.01), as was hematocrit to global assessment (p < 0.01). Although the laboratory parameters used in the PCDAI appear to generally reflect disease activity in most patients, no single laboratory test is adequate to reflect disease activity in all patients. Future work will need to identify additional laboratory measures to reflect the inflammatory process and serve as important adjuncts in the assessment of disease activity.

Olsalazine Versus Sulfasalazine in Mild to Moderate Childhood Ulcerative Colitis: Results of the Pediatric Gastroenterology Collaborative Research Group Clinical Trial

The safety and efficacy of olsalazine sodium was compared to sulfasalazine over 3 months in a multicenter, randomized, double-blind study of 56 children with mild to moderate ulcerative colitis. Twenty-eight children received 30 mg/kg/day of olsalazine (maximum, 2 g/day) and 28 received 60 mg/kg/day of sulfasalazine (maximum, 4 g/day). Side effects were frequent in both groups. Eleven of 28 patients (39%) on olsalazine reported headache, nausea, vomiting, rash, pruritus, increased diarrhea, and/or fever. Thirteen of 28 on sulfasalazine (46%) reported similar side effects and/or neutropenia, and four patients had the drug stopped because of an adverse reaction. After 3 months, 11 of 28 (39%) on olsalazine were asymptomatic or clinically improved, compared to 22 of 28 (79%) on sulfasalazine (p = 0.006). In addition, 10 of 28 patients on olsalazine versus one on sulfasalazine required prednisone because of lack of response or worsening of colitis (p = 0.005). The dose of olsalazine used in this clinical trial was thought to be equivalent to a standard dose of sulfasalazine, but fewer patients on olsalazine improved and a greater number had progression of symptoms when compared to sulfasalazine. Although side effects were slightly less frequent for olsalazine, the number of patients was too small to detect a clinically significant difference.

Cerebral Thromboembolic Disease in Pediatric and Adult Inflammatory Bowel Disease: Case Report and Review of the Literature

Cerebral and retinal vascular disease are rare complications of inflammatory bowel disease. Most reports are of adult patients, with only seven instances described in children. The eighth case, a 14-year-old boy with ulcerative colitis and cerebral venous thrombosis is reported in whom the diagnosis was confirmed by magnetic resonance imaging. The adult and pediatric literature is also reviewed.

Ulcerative Colitis in Children 10 Years Old or Younger

The onset and course of ulcerative colitis diagnosed in 38 children at or before 10 years of age were reviewed. The mean age at onset was 5.9 years. A family history of inflammatory bowel disease was present in 24% of patients, and 13% had a history of cow milk allergy in infancy. Initially, by radiologic or colonoscopic studies, 71% had total colonic disease, 13% had left-sided colitis, and 6% had proctitis; extensive examination was not performed in 4 patients. Four patients (11%) presented with severe colitis, 14 (37%) with moderate colitis, and 20 (53%) with mild colitis. The most frequent symptoms were abdominal pain (94%), diarrhea (84%), and rectal bleeding (84%). Between 2 and 10 years after diagnosis, 89% of children had total colonic disease and 11% had left-sided disease. All four patients with severe disease at onset responded to medical therapy with one having a colectomy 15 years later with pathology consistent with Crohns disease. Of those with moderate disease, half had infrequent moderate recurrences and half had intermittent mild disease. One patient had colectomy at 21 years for intractable disease. Of the 20 with mild disease, 16 continued to have intermittent mild recurrences, 1 had chronic mild disease, 2 had moderate recurrent disease, and 1 has remained asymptomatic for 5 years. Psychiatric disturbances requiring therapy were identified in 5 (13%) children. Results are encouraging: after the first 2 years of illness, two thirds of the children have had subsequent mild colitis with infrequent relapses and three quarters consider their life to be of good quality.

Clostridium difficile in inflammatory bowel disease relapse

Stools of 65 patients with exacerbation of symptoms of inflammatory bowel disease were examined for the presence of enteric pathogens and Clostridium difficile. Ten (16%) had C. difficile toxin. Symptoms in all patients cleared after therapy, with improvement correlating with elimination of toxin from the stool.

Esophageal dysfunction in Down's syndrome.

Abnormalities in esophageal function were identified in seven children with Downs syndrome. Three had recurrent episodes of pneumonia from gastroesophageal reflux; two of these and one other patient had esophageal strictures. Two patients with Downs syndrome revealed no evidence of gastroesophageal reflux but did show significant abnormalities in esophageal peristalsis. These data would suggest that ambulatory children with Downs syndrome may be at risk of developing serious sequellae of gastroesophageal reflux. The spectrum of data of these seven patients is discussed, and pertinent prior reports from the literature are reviewed.

Effect of Bethanechol and Metoclopramide on Upper Gastrointestinal Motility in the Kitten

Summary Gastroesophageal reflux (GER) during infancy is a disorder of unknown etiology which may be associated with abnormalities of upper gastrointestinal motor function. Bethanechol, a muscarinic agonist, and metoclopramide, a dopamine antagonist, have been utilized as pharmacologic agents in an attempt to improve upper gastrointestinal motility in this disorder. We have studied the effect of these agents on upper gastrointestinal motility in an infant model, the kitten. Bethanechol is found to greatly increase lower esophageal sphincter (LES) pressure and have no effect on esophageal peristaltic amplitude or gastric emptying of a liquid meal. Metoclopramide causes a small and nonsignificant increase in LES pressure, has no effect on esophageal peristalsis, and increases the rate of gastric emptying of a liquid meal. These results suggest that these two agents may have specific actions on the infants upper gastrointestinal tract.

High incidence of hypogammaglobulinemia in infants with diarrhea.

Summary: Examination of 136 children who were referred to the Pediatric Gastroenterology Clinic at Yale‐New Haven Hospital for chronic or severe diarrhea between 1977 and 1981 revealed that 31 patients (22.8%) had serum immunoglobulin levels below the 5th percentile for age. Twenty‐four of these 31 patients (77.4%) had normal or near normal serum immunoglobulin levels by their third birthday and most could therefore be classified under the heading “transient hypogammaglobulinemia of infancy,” an unexpected finding, as this condition has previously been thought to be rare; only 27 patients with this disorder were reported prior to 1978. While the basic cause of the defect is unknown, it has been linked to a slower than normal maturation of the neonates ability to secrete immunoglobulins. Comparison of our patients with hypogammaglobulinemia and those with chronic diarrhea but normal immunoglobulins revealed that the former group are younger at presentation (mean, 8.2 months) and at the onset of their diarrhea (3.1 months); the figures for patients without hypogammaglobulinemia were 18.2 and 8.2 months, respectively. Males and females were equally affected, and the diarrhea, which was responsive to a hypoallergenic diet, resolved by 3 years of age as did the hypogammaglobulinemia in nearly all cases. While the etiology of the diarrhea remains obscure, significant problems outside the gastrointestinal tract did not occur. Circumstantial evidence suggests that the most likely cause for the failure of production of IgG, and to a lesser extent IgA antibody, in infants seen with diarrhea may result from a failure of maturation of T cell helper systems rather than any intrinsic defect in the B cell system itself.

Juvenile polyps and ulcerative colitis

Four children with ulcerative colitis, three of whom were in clinical remission of their disease, experienced rectal bleeding due to solitary juvenile polyps. Only one of the four polyps was detected radiologically. Two children passed their polyps spontaneously, one was identified at colonoscopy, and the fourth caused colocolic intussusception and was removed during surgery.