Eosinophilic Gastritis in Children

Clinicopathological Correlation, Disease Course, and Response to Therapy

Huaibin M Ko MD; Raffaella A Morotti MD; Oksana Yershov MS; Mirna Chehade MD; MPH

Disclosures

Am J Gastroenterol. 2014;109(8):1277-1285. 

In This Article

Results

As detailed in Figure 1, a total of 523 pathology reports were reviewed. From these, 36 children who met our histological inclusion criteria for HEG were identified. Six of these children had a history of prior solid organ transplantation and were excluded from the study. Thirty children remained for final analysis, fourteen of whom were male (47%) and sixteen were female (53%) indicating a lack of gender predilection in HEG. Median age of the subjects at diagnosis was 7.5 years (range 0.2–15.2 years). Although no specific age peak for HEG was found, almost half of the patients were young children below 6 years of age. The vast majority of patients (29/30) were Caucasians. The only non-Caucasian patient was also the only infant in our cohort (3-month-old), with a history of EG and pyloric stenosis suggestive of both mucosal and muscular eosinophilia.

Main symptoms at presentation were highly variable (Table 2), with abdominal pain being the most common, followed by vomiting. Other main symptoms/signs at presentation included anemia, melena, food aversions, failure to thrive, edema, and ascites.

A large number of children with HEG were atopic, with 45% having history of asthma, 43% having allergic rhinitis, and 22% with atopic dermatitis. History of food allergies as documented by an allergist in the medical record was also common in these patients (43% of the patients). In all, 6 out of 27 (22%) of our children had history of associated PLE, as judged by the treating physician using clinical and laboratory criteria.[4] Interestingly, four out of the six patients with PLE did not have evidence of concurrent duodenal eosinophilia, i.e., eosinophilia was limited to the gastric mucosa. The duodenal mast cells, despite our limited sample size, did not seem to be increased either. The median peak duodenal mast cells for those without PLE and without duodenal eosinophilia (n=6) was 71.5/HPF (range 56–80). Peak duodenal mast cell count in one patient with PLE and without duodenal eosinophilia was 73/HPF. No mast cell degranulation was seen in any of the samples.

In addition, among those whose complete blood count was available for review (16 patients), the median peripheral eosinophil count for all patients was elevated (1,004/mm3, range 100–2,700/mm3). Twelve of sixteen (75%) of the patients with HEG and 50% of patients with gastric eosinophilia limited to the stomach had an elevated peripheral eosinophil count, defined as an absolute eosinophil count of >500/mm3.

Endoscopic features of the gastric mucosa were highly variable and included normal appearance, diffuse erythematous patches, erythematous streaks, erosions, ulcers, white plaques, and nodular lesions with exudates (Table 3, Figure 3).

Figure 3.

Illustrative examples of endoscopic gastric appearance of eosinophilic gastritis. (a) Normal antral mucosa. (b) Antral erythema. (c) Small antral ulcers.

Table 3 depicts findings on concurrent biopsies obtained from various sites of the GI tract. Antral biopsies were obtained in 29 out of 30 patients, with 1 patient having only fundic biopsies. Of the 29 patients who had antral biopsies, 8 also had fundic biopsies; 4 of those had eosinophilia in both antrum and fundus, 3 only in the antrum, and 1 only in the fundus. In all of our patients, eosinophilia was diffuse or multifocal (eosinophilia in >3 HPF). In all of the patients, the eosinophils were the predominant inflammatory cells with minimal/no neutrophilic and plasma cell infiltrates. Eosinophils were predominantly infiltrating the lamina propria in all patients, with few eosinophils seen in the superficial epithelium in the majority of patients and in the glandular epithelium in all patients. No glandular distortion or drop out was seen. The full depth of the lamina propria was infiltrated with eosinophils in every case, with a higher density toward the surface in some patients. When present in the biopsies, the muscularis mucosa was also involved by eosinophils. Eosinophilic abscesses were identified in most patients. Moderate to severe eosinophilic degranulation was also observed in two-thirds of the patients. All the above features were indistinguishable between those patients with HEG alone and those with HEG and concomitant esophageal and/or duodenal eosinophilia. These features were unique and in sharp contrast to our group of excluded patients with either mild gastric eosinophilia or known etiologies for their gastric eosinophilia. For example, gastric eosinophilia was mild and admixed with neutrophils in H. pylori infection and in Crohn's disease. No eosinophilic microabscesses and no eosinophilic infiltration of the superficial and glandular epithelium were found in the excluded cases.

Twenty-eight of the thirty patients with HEG had concurrent esophageal biopsies, twelve of whom (43%) had concurrent EoE (≥15 eosinophils per HPF). Of the 28 patients with duodenal biopsies, 6 (21%) showed significant eosinophilia (≥50/HPF), fulfilling diagnostic criteria for EGE. Two of those patients (7%) had both esophageal and duodenal eosinophilia, compatible with the diagnosis of EGE with esophageal involvement. Fourteen patients had eosinophilia limited to the stomach, fulfilling diagnostic criteria for EG.

Seven children had concurrent colonoscopies based on clinical indications by their treating physician, none showed markedly increased eosinophils (≥70/HPF).

Follow-up was available for 22 children, all of whom received treatment for their HEG before their follow-up evaluation. Therapy consisted of dietary restriction in 17 patients (3 of whom had concomitant proton pump inhibitor therapy), proton pump inhibitor therapy exclusively in 2 patients, cromolyn sodium in 2 patients, and pyloromyotomy in 1 patient (for the infant with pyloric stenosis). Dietary restriction therapy consisted of either use of an elemental diet (amino acid-based formula) while allowing concomitant ingestion of 1–12 foods in six patients, a seven-food empiric dietary elimination therapy consisting of removal of foods known to be common triggers for EoE (milk, wheat, soy, egg, nuts, seafood, and red meats) in six patients, and empiric avoidance of 1–3 foods (milk, egg, soy, and/or wheat) in five patients.

Of the 17 children who received dietary restriction therapy, 14 (82%) had clinical response, defined by resolution of symptoms. Fourteen had post-dietary therapy biopsies, 11 of whom (78%) had histological response, defined as resolution of gastric eosinophilia (<10 eosinophils per HPF). Table 4 summarizes response to the individual types of dietary restriction therapies. Among the histological non-responders to dietary restriction therapy, one had clinical response. However, all histological responders to the dietary restriction also had clinical response to this therapy.

Next, we checked for differences in clinical features and response to therapy between patients with HEG restricted to the stomach (EG), and those with HEG and concurrent eosinophilia at various other sites (Table 2). Symptoms were similar in those with EG and those with HEG with eosinophilia elsewhere in the GI tract. Although the prevalence of food allergy, food sensitizations, and atopy seemed higher in those with HEG+EoE, all subgroups of HEG including those with eosinophilia limited to the stomach had very good response to dietary therapy. This was reflected in the overwhelmingly high rate of clinical and histological response to the various dietary restrictions in the overall cohort and in the subset of patients with HEG alone (Table 4).

The majority of patients (86%) showed evidence of sensitization to several foods, defined by positive skin prick tests and/or serum food-specific IgE levels, as depicted in Table 5. Total serum IgE was elevated in some patients as well. However, response to dietary therapy did not correlate with the patients' total serum IgE levels or food sensitization profile. Clinical and histological response to other therapies when available is summarized in Table 4. As for the peripheral eosinophil count following therapy, it remained elevated in all those with initially elevated counts regardless of histological response to therapy. Median (range) of eosinophil count/mm3 pre- and post-therapy in six patients on whom data were available for both time points was 1,597 (1,000–2,700) and 750 (400–1,500), respectively.

Sixteen patients had esophageal biopsies post-therapy. Six of those patients had persistent esophageal eosinophilia despite histological resolution of their gastric eosinophilia. Two patients who previously had negative esophageal biopsies developed de novo EoE following therapy; these patients had persistent gastric eosinophilia. All but one of these patients had received dietary restriction therapies, the one patient having received proton pump inhibitor therapy.

We separately analyzed the six patients with significant gastric eosinophilia and prior history of organ transplantation (four liver and two heart) who we excluded from our analysis, and found several interesting findings previously not reported in the transplant population. A disproportionately higher number of non-Caucasians was seen (one Caucasian, one Black, two Hispanics, and two Asians), in sharp contrast to our non-transplant patients. In addition, although our non-transplant patients had no colonic eosinophilia, two out of four post-transplant patients who had colonoscopies showed markedly increased colonic eosinophils (≥70/HPF). As for the histological features of the gastric eosinophilia in the post-transplant patients, the eosinophilic infiltrates were indistinguishable from the non-transplant patients with respect to severity, location, and lack of admixed acute inflammatory infiltrate. Remarkably, clinical and histological response to dietary therapy was also seen in 2/2 patients that received dietary elimination therapy (one received a seven-food empiric dietary elimination therapy and another an elemental diet), with resolution of gastric eosinophilia.

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