Alan M. Leichtner

Allergic esophagitis in children: a clinicopathological entity.

Infiltration of esophageal epithelium by eosinophils is seen in reflux esophagitis and allergic gastroenteritis. This study was performed to identify differences between patients with acid reflux esophagitis and those with non-acid reflux, possibly allergic, esophagitis. Intraepithelial eosinophils were demonstrated in posttherapy esophageal biopsy specimens in 28 children treated for gastroesophageal reflux disease (GERD). These patients were divided into three groups based on their response to treatment and the results of esophageal pH probe monitoring. Eleven patients (Group A) had incomplete clinical response and normal pH probe monitoring results. Ten patients (Group B) had incomplete response but did not have pH probe monitoring. These two groups formed the index population. Seven patients (Group C) had clinical improvement with GERD therapy and abnormal pH probe monitoring characteristic of GERD; they constituted the control population. Clinical, laboratory, and pathologic features were evaluated to detect differences between index and control populations. Dysphagia, food impaction, failure to thrive, peripheral eosinophilia, and abnormal allergen skin test results were detected only in Group A and B patients. Biopsy specimens of the distal 9 cm of the esophagus, after GERD therapy, contained larger numbers of eosinophils in Groups A and B than in Group C as shown on high-power fields (HPF) (A: 31/HPF +/- 19.5; B: 28/HPF +/-23.7; versus C: 5/HPF +/-6.7; p = 0.009). Eosinophil aggregates were identified only in Groups A and B (p = 0.07). Eosinophils located preferentially in the superficial layers of the squamous epithelium were noted only in Groups A and B (p = 0.02). Group A and B patients demonstrated clinical improvement when given antiallergic therapy. The authors identified a group of pediatric patients characterized by an allergic history, lack of adequate response to GERD therapy, normal esophageal pH probe monitoring results, and large numbers of eosinophils in esophageal biopsy specimens obtained after GERD treatment. On the basis of these features, the authors propose that these patients represent examples of allergic esophagitis.

Serologic Testing with ANCA, ASCA, and Anti-OmpC in Children and Young Adults with Crohn's Disease and Ulcerative Colitis: Diagnostic Value and Correlation with Disease Phenotype

OBJECTIVES:Serologic testing is increasingly being utilized to evaluate children with suspected inflammatory bowel disease (IBD). The aim of this paper was to evaluate the sensitivity and specificity of a currently available panel involving four antibodies: deoxyribonuclease (DNase)-sensitive perinuclear antineutrophil cytoplasmic antibody (DNase-sensitive pANCA), IgA and IgG antibodies to Saccharomyces cerevisiae (IgA and IgG ASCA), and antibody to Escherichia coli outer membrane porin (anti-OmpC). We also wished to determine whether antibody levels correlated with disease activity, and whether a specific antibody pattern correlated with location and outcome of disease in children.METHODS:We studied sera from 81 children with Crohns disease (CD), 54 with ulcerative colitis (UC), and 63 controls. Clinical data, disease activity, and disease diagnosis were gathered at the time of serum sampling, and charts were re-reviewed at time of the study to determine long-term outcome. Enzyme-linked immunosorbent assay was utilized to determine titers of antibodies to ASCA, DNase-sensitive pANCA, and anti-OmpC; the presence of perinuclear staining for ANCA was confirmed by immunofluorescence.RESULTS:We identified ASCA antibodies in 44% of CD patients, 0% of UC patients, and 1 control patient. DNase-sensitive pANCA antibodies were found in 70% of patients with UC, 18% of CD patients (predominantly Crohns colitis), and 3% of controls. Anti-OmpC as an isolated assay had low sensitivity for both CD (24%) and UC (11%), and displayed a 5% false-positive rate. However, anti-OmpC did identify a small number of IBD patients not detected by the other assays. If any one or more of the four antibodies was positive, the overall sensitivity of the four antibody panel was 65% for CD and 76% for UC, with a specificity of 94%. Patients who were ASCA-positive were more likely to have disease of the ileum or ileum and right colon than patients who were ASCA-negative (58% vs 18%, p < 0.001). Patients with ASCA-positive were also more likely to require ileocecal resection (36% vs 13%, p < 0.05).CONCLUSIONS:A currently available commercial antibody panel has good sensitivity and excellent specificity for CD and UC. The ASCA antibodies, while highly specific for CD, identify predominantly the subset of children with disease of the ileum and ascending colon who may be at increased risk of surgery.

Allergic proctocolitis in infants: a prospective clinicopathologic biopsy study.

Allergic proctocolitis is a major cause of rectal bleeding in infants, but its clinical features and laboratory results are often nonspecific. Our previous retrospective study demonstrated that large numbers of eosinophils in colonic mucosal biopsy specimens were highly associated with cases of allergic proctocolitis. Therefore, we prospectively examined 60 colonic mucosal biopsy specimens from the same sites (4, 8, and 12 cm from the anal verge) in 20 infants with clinically confirmed allergic proctocolitis to validate this morphologic feature, to characterize its distribution, and to correlate these data with the clinical information. The patients (age range, 4 to 304 days) were fed breast milk or a variety of formulas and all presented with rectal bleeding. Sigmoidoscopic examination was abnormal in 19 cases, typically characterized by focal areas of mucosal erythema. The major histologic finding was a strikingly focal increase in the number of eosinophils in all mucosal compartments, with a predilection to aggregate in close association with lymphoid nodules. Eosinophilic infiltration varied not only between biopsies at different sites, but also within individual biopsy specimens. Only 12 of 20 patients (60%) had all three of their biopsy specimens categorized as abnormal; in the remainder, only one (four patients) or two (four patients) of the three biopsy specimens were abnormal. The average number of eosinophils per high-power field of lamina propria for all cases was 15.6. No significant correlation was identified between the number of eosinophils in the mucosa and the patients age, length of illness, endoscopic appearance, or type of inciting formula. In summary, eosinophils appear to be an excellent marker for infantile allergic proctocolitis. Given the focal distribution of the eosinophils, multiple mucosal biopsy specimens should be obtained and several levels of each examined to confirm the diagnosis.

Complementary Medicine Use in Children and Young Adults With Inflammatory Bowel Disease

OBJECTIVES:We examined the use of complementary alternative medicine (CAM) in children and young adults with inflammatory bowel disease.METHODS:After validation of a questionnaire and completion of a pilot survey, children and young adults with inflammatory bowel disease were enrolled in three centers of pediatric gastroenterology (Boston, Detroit, and London).RESULTS:Two hundred eight questionnaires were completed in total (Boston, 120; Detroit, 37; London, 51). Ages ranged from 3.8 to 23.0 yr, 58% were male, 57% had Crohns disease, and 35% had ulcerative colitis. The frequency of CAM use was 41%. The most common CAMs were megavitamin therapy (19%), dietary supplements (17%), and herbal medicine (14%). Parental CAM use and the number of adverse effects from conventional medicines were predictors of CAM use (odds ratio = 1.9, 95% CI = 1.2–3.1, p = 0.02; odds ratio = 1.3, 95% CI = 1.2–1.5, p < 0.001, respectively). The most important reasons respondents gave for using CAM were side effects from prescribed medicines, prescribed medicines not working as well as they had hoped, and hoping for a cure. Fifty-nine percent of respondents not taking CAM were interested in learning more about it.CONCLUSIONS:In our survey over 40% of children with chronic inflammatory bowel disease used complementary medicine in addition to conventional therapies. Parental CAM use and number of adverse effects from conventional therapies were the only independent predictors of CAM use. Some complementary therapies have potential for adverse effects and for drug interactions with conventional treatments. Physicians should take a thorough history of CAM use in children with chronic inflammatory bowel disease.

Pediatric patients with untreated ulcerative colitis may present initially with unusual morphologic findings.

Background: Anecdotal observations by the authors of this study, together with the results of a few previous smaller studies, suggest that children with new-onset (previously untreated) ulcerative colitis (UC) may occasionally present with discontinuous disease, relative or absolute rectal sparing, and may lack histologic features of chronicity. Therefore, the objectives of this study were to determine the clinical and pathologic features of new-onset UC in children and to compare the initial presentation of UC in this group with a control group of adults. Design: Routinely processed rectal and colonic mucosal biopsies from 73 pediatric (male/female ratio 33/40, mean age 11.5 years, range 2.5–18 years) and 38 adult patients (male/female ratio 15/23, mean age 41.5 years, range 27–64 years) who presented with new-onset UC were evaluated for a variety of clinical and pathologic features, including duration of symptoms prior to presentation, crypt architectural (e.g., atrophy, branching) and nonarchitectural (e.g., basal plasmacytosis, Paneth cell metaplasia) features of chronicity, degree of active inflammation, and distribution and extent of disease. Results: A significant proportion of children with new-onset UC had patchiness of microscopic features of chronicity (21% of patients), relative (23%), or absolute (3%), rectal sparing, and had little or no crypt architectural distortion in their rectal biopsies (8%). These features were not observed in adult patients with UC. In addition, a higher proportion of children with UC initially presented with subtotal or with pancolitis compared with the adults (42% vs. 11%; P < 0.002). Conclusions: A significant proportion of children with new-onset UC may show unusual patterns of disease. Pathologists should be aware of these findings since they have significant implications for the differential diagnosis of pediatric inflammatory bowel disease.

Depressive symptoms and inflammatory bowel disease in children and adolescents: A cross-sectional study

Objectives: This study assessed the rates of depressive symptoms in older children and adolescents with inflammatory bowel disease (IBD) and the associations between depressive symptoms and IBD disease characteristics. Methods: One hundred and two youths (aged 11–17 years) with IBD seen consecutively in a gastroenterology clinic were screened for depressive symptoms using the Children’s Depression Inventory (CDI). Subjects with CDI scores ≥12 were evaluated for current psychiatric diagnoses using the Schedule for Affective Disorders and Schizophrenia for School-Age Children—Present and Lifetime Version (K-SADS-PL). Disease characteristics examined included IBD type, duration, current severity, course, age at diagnosis and steroid treatment. Results: Of the total sample, 25 (24.5%) had a CDI score ≥12, consistent with clinically significant depressive symptoms. Nineteen of 25 qualified subjects participated in the K-SADS-PL semi-structured interview and 16 of 19 met criteria for major or minor depressive disorder. Mean CDI scores positively correlated with age at IBD diagnosis but not with IBD type, duration or course. Youths with moderate/severe current IBD-related symptoms had significantly higher mean CDI scores than those with inactive disease activity. Anhedonia, fatigue and decreased appetite were selectively correlated with IBD disease severity. Subjects on steroids were more likely to have CDI scores ≥12, and those with such scores were on higher doses of steroids than subjects without clinically significant depressive symptoms (both P values < 0.05). Conclusions: These findings support the recommendation that adolescents with IBD in outpatient medical care settings, particularly older adolescents and those on steroids, should be screened for depression.

Clinical and Laboratory Correlates of Esophagitis in Young Children

To develop clinical and laboratory criteria to identify young children with gastroesophageal reflux (GER) who are at particular risk for esophagitis and then to monitor their clinical course we have prospectively studied 40 subjects (ages 2-22 months, mean 8 months) with persistent symptoms of GER with 18 h intraesophageal pH monitoring, endoscopy, and grasp and suction esophageal biopsies. Esophagitis was found in 16 of 20 patients under 7 months, 12 of 14 between 7 and 12 months, and five of six between 12 and 24 months. Esophagitis was equally frequent in those patients with or without poor weight gain, wheezing, or irritability. Only 15% of patients with esophagitis had occult blood in their stool. No parameter of intraesophageal pH monitoring was both sensitive and specific in identifying patients who were ultimately found to have either mild or severe esophagitis. Follow-up data (37 patients) revealed that fundoplication was eventually required in four of eight patients with severe esophagitis, three of 22 with mild esophagitis, and none of seven without esophagitis. Currently used clinical and laboratory assessments of GER have limited value in identifying those children with either normal esophageal mucosa or at risk for varying degrees of esophagitis. Preliminary observations suggest that the presence of severe histologic esophagitis at the time of initial evaluation may have prognostic value in identifying those patients most likely to fail medical therapy and require fundoplication.

Vitamins A and E serum levels in children and young adults with inflammatory bowel disease : Effect of disease activity

BACKGROUND Hypovitaminosis and fat-soluble vitamin deficiency have been reported in adults with inflammatory bowel disease (IBD). A prospective study was undertaken to determine the prevalence of low serum levels of vitamins A and E in children and young adults with IBD. METHODS Clinical information and serum for vitamin levels was gathered prospectively from 61 patients with Crohns disease, 36 patients with ulcerative colitis, and 23 control subjects. Disease activity and disease location were determined for IBD patients. Serum retinol and alpha-tocopherol levels were determined by high-performance liquid chromatography. RESULTS The prevalence of hypovitaminosis A (defined as serum vitamin A < 20 micrograms/dl) or hypovitaminosis E (defined as serum vitamin E < 5 mg/l) was 16% in the pediatric IBD population studied. Low vitamin A levels were more common than low vitamin E levels. Serum retinol levels correlated significantly with alpha-tocopherol levels. Hypovitaminosis was significantly more prevalent in the Crohns disease patients who had active disease, an erythrocyte sedimentation rate of more than 25 mm/hour, or a serum albumin level less than 3 mg/dl. CONCLUSIONS Children and young adults with active IBD frequently have low serum levels of vitamin A or vitamin E. The severity of disease activity is a better predictor of risk for hypovitaminosis than is nutritional status. Further work is necessary to determine whether the hypovitaminosis seen in children with IBD reflects true deficiency.

Complications following percutaneous endoscopic gastrostomy and subsequent catheter replacement in children and young adults

BACKGROUND Percutaneous endoscopic gastrostomy has gained wide acceptance for patients who require prolonged tube feeding support. We sought to identify complications and associated risk factors of endoscopic gastrostomy and subsequent catheter replacement in pediatric patients. METHODS Medical records were reviewed for 137 patients. Odds ratios were calculated for complications related to patient age, weight, weight-for-age Z score, and principal diagnosis. RESULTS Seventeen patients (12.4%) developed significant complications after gastrostomy: cellulitis occurred in 10 patients (7.3%); other complications included gastrocolic fistula (2), duodenal hematoma (1), complicated pneumoperitoneum (1), necrotizing fasciitis (1), gastric perforation (1), and catheter migration (1). Patients with cancer had significantly greater odds for developing a wound infection, and patients with AIDS had significantly greater odds for total complications. A trend toward increased wound infection was observed in patients with cardiac disease. Age, weight, and weight-for-age Z score were not associated with adverse outcome. Two complications occurred in 85 patients (2.4%) after gastrostomy catheter replacement. CONCLUSIONS Pediatric patients with cancer and AIDS are at increased risk for complications after endoscopic gastrostomy regardless of age, weight, or nutritional status. Infrequent yet life-threatening complications may occur after replacement of initial gastrostomy catheter.

Elevated serum vascular endothelial growth factor in children and young adults with Crohn's disease.

Vascular endothelial growth factor (VEGF) is acytokine released by fibroblasts, epithelial cells, andleukocytes that potentiates vascular permeability andgrowth of new capillaries. Because of these multiple effects, VEGF has been postulated to play arole in the pathogenesis of autoimmune disease, as wellas in wound healing. We hypothesized that VEGF waspotentially important in mediating the vascularpermeability and angiogenesis seen in Crohns disease, andtherefore that VEGF would be increased in the serum ofchildren with Crohns disease. Serum was obtained from73 children and young adults with Crohns disease, 47 with ulcerative colitis, and 29 controls.VEGF levels were measured by enzyme-linked immunosorbentassay. Mean VEGF levels were significantly higher inpatients with Crohns disease (436.4 ± 37.2pg/ml) than in ulcerative colitis (306 ± 41.1pg/ml) or control (167.8 ± 29.6 pg/ml) patients.Serum VEGF also correlated significantly with diseaseactivity, being elevated in patients withmoderate/severe Crohns disease and ulcerative colitis. Weconclude that serum VEGF is released by inflamed tissuesin children with Crohns disease. This multifunctionalcytokine could promote inflammation by increasing vascular permeability or promote wound healingby mediating capillary growth.