Case Report

Eosinophilic Gastroenteritis Complicated With Perforation andIntussusception in a Neonate

*Tania Siahanidou, *Helen Mandyla, †Dimitris Dimitriadis, ‡Catherine Van-Vliet, and*Dimitris Anagnostakis

*First Department of Pediatrics, Athens University; and the †First Surgical Department and the ‡Pathology Department,“Aghia Sophia” Children’s Hospital, Athens, Greece

Eosinophilic gastroenteritis (EG) is a disease charac-terized by marked eosinophilic infiltration of the gastro-intestinal tract, an absence of vasculitis, and a peripheraleosinophilia in approximately 50% of patients (1). EG isincluded in a standardized diagnostic classificationscheme of gastrointestinal diseases of infants and chil-dren resulting from adverse immunologic reactions tofoods (1). Kaijser originally described this disorder in1937. The prevalence of this disease in the general popu-lation is unknown. Clinical symptoms are related to thegastrointestinal region involved (esophagus, stomach,small intestine, colon) and to the predominant layer af-fected (mucosa, muscularis, serosa). Eosinophilic infil-tration of the mucosal layer causes inflammation; that ofthe muscular layer leads to thickening and rigidity, pro-voking symptoms of obstruction; whereas infiltration ofthe serosa results in ascites (2). The disease is distin-guished into allergic eosinophilic esophagitis, gastritis,or gastroenterocolitis according to the anatomic regionaffected (1). Eosinophilic infiltration of the gastric an-trum is typical in eosinophilic gastritis or gastroentero-colitis and may result in gastric outlet obstruction (1).Intestinal perforation and intussusception are rare com-plications of the disease (3). Even though patients of allages can be affected, a few cases of neonates with EG,without complications, have been reported (4–6). Wedescribe a male neonate who presented typical symptomsof EG on the first day of life and whose condition wascomplicated by perforation of the antral wall and il-eoileal intussusception.

CASE REPORT

A 25-day-old male neonate was referred to our unitfrom a regional hospital because of symptoms compat-ible with obstruction of the upper gastrointestinal tract.He was born at term by vaginal delivery after an uncom-

plicated pregnancy. His birthweight was 3,200 g. TheApgar score was reported to be 8 points at 1 minutes and10 points at 5 minutes. From the first day of life, whilehe was tried on a cow milk formula, he presented epi-sodes of alimentary, nonbilious vomiting, some of whichwere the consistency of coffee grounds. Meconium waspassed normally. Upper gastrointestinal contrast radiog-raphy, after administration of Gastrografin orally, re-vealed large distension of the stomach, and the contrastmaterial could not pass through the pylorus to the duo-denum. On the third day of life, the neonate underwent alaparotomy, during which a markedly dilated stomachwas noticed. The liver and the biliary tract, as well as thesmall intestine and colon, were normal without any ob-vious pathology. The passage of upper gastrointestinallumen was checked by the insertion of a nasogastric tubeand parallel instillation of normal saline via the stomachand pylorus to the jejunum without difficulty. No biop-sies were obtained. The postoperative period was un-eventful and the neonate received total parenteral nutri-tion. On the third day after surgery, an attempt to feed thebaby through a nasogastric tube was unsuccessful be-cause of a high volume of gastric residuals. The feedingdifficulties persisted for the next few days and the babywas referred to our unit.

On the first day after admission to our unit, a bariummeal study was performed that demonstrated a partialgastric outlet obstruction (Fig. 1), marked pylorospasm,and antral dyskinesia. Twenty-four hours later, most ofthe contrast material was still in the stomach, as evi-denced on plain abdominal film. Sonography revealed apyloric muscular wall thickness of 3 mm (normal, <2mm) (7) that remained unchanged on the repeat exami-nation after 2 days. No other abnormalities were de-tected. Results of a barium enema were also normal. Abiopsy from the antrum and the duodenum, obtained viaupper gastrointestinal endoscopy, demonstrated promi-nent eosinophilic infiltration of the antrum (Fig. 2) andduodenal mucosa, whereas the intestinal villi were nor-mal. No cytomegalovirus inclusions were detected. Rec-

Received February 21, 2000; accepted December 1, 2000.Address correspondence and reprint requests to Dr. Tania Siahanidou,

A’ Department of Paediatrics, Athens University, Aghia Sophia Chil-dren’s Hospital, Thivon & Levadias str, 11527, Athens, Greece.

Journal of Pediatric Gastroenterology and Nutrition32:335–337 © March 2001 Lippincott Williams & Wilkins, Inc., Philadelphia

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tal biopsy showed eosinophilic infiltrates in the laminapropria and normal ganglia in the submucosa.

From the laboratory findings, a peripheral eosinophiliaof 13% to 27% was noticed repeatedly from the first daysof life, with the total eosinophil count ranging from1,300 eosinophils/mm3 to 4,000 eosinophils/mm3 (nor-mal, 40–440 eosinophils/mm3). Serum immunoglobulinE (IgE) concentration was elevated (22, IU/mL; normal,1–12 IU/mL) and a radioallergosorbent test to cow’smilk protein was class 2 positive. Serum electrolytes;albumin; tests of liver and kidney function; IgG, IgA,and IgM; complement (C3 and C4) levels; interleukin(IL)-4; IL-5; �-interferon; blood T cell; T subset; andB-cell numbers were all within normal limits. Fecal A1antitrypsin was normal. Guaiac tests on the stools weremildly positive. There was no evidence of cytomegalo-virus infection in the neonate or his mother.

Cow’s milk formula was discontinued, and small,gradually increased amounts of amino acid-free-basedformula (Nutri-Junior) were administered and seemed tobe well tolerated. Twelve days after admission to our unit(3 days after initiating the elemental diet), the infant’scondition deteriorated markedly. He exhibited bilious

vomiting and abdominal distension. Plain abdominalfilm taken with the child in an upright position demon-strated the presence of gas levels in dilated proximalloops of the small intestine, suggestive of small bowelobstruction. The infant underwent a second laparotomywith the following findings: an overdistended stomachwith a sealed perforation at the front antral wall and a7-cm ileoileal intussusception. The intussusception wasreduced manually and the gastric perforation was closedsurgically. The invaginated part of the intestine washealthy. Examination of biopsy specimens, obtainedfrom the perforated gastric wall area, revealed eosino-philic infiltration of the mucosa, submucosa, and mus-cularis.

Postoperatively, the patient’s recovery was unevent-ful. The elemental diet was reintroduced and his vomit-ing gradually subsided. He was discharged after 2months, in good health with a body weight of 4,100 g. Heattended follow-up clinics regularly. At 13 months ofage, a challenge with cow’s milk formula was well tol-erated. Now, at 18 months, the infant is free of symptomsand is gaining weight. Total eosinophil blood count isnormal, serum IgE levels are less than 2 IU/mL and theresults of the radioallergosorbent test to cow’s milk pro-tein and multiple food antigens (fruits, fish, egg, cereal)were negative.

DISCUSSIONThe gastrointestinal diseases of infants and children

resulting from adverse immunologic reactions to foodswere classified, during a workshop held in November1998 in Washington, DC, USA, according to the immu-nologic mechanisms involved, symptom complex, andanatomic regions affected as follows (1): 1) IgE-mediated disorders (immediate gastrointestinal hyper-sensitivity, oral allergy syndrome), 2) non-IgE-mediateddisorders (dietary protein enterocolitis, dietary protein

FIG. 1. Barium meal study demonstrating a partial gastric outletobstruction.

FIG. 2. Gastric biopsy specimen showing eosinophilic infiltrationof the lamina propria. Hematoxylin–eosin stain, original magnifi-cation ×400.

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proctitis, dietary protein enteropathy, celiac disease), and3) mixed IgE- and non-IgE-mediated disorders (allergiceosinophilic esophagitis, allergic eosinophilic gastritis,allergic eosinophilic gastroenterocolitis).

In our patient, the diagnosis of EG was based on gas-trointestinal symptomatology, radiographic and sono-graphic signs of gastric outlet obstruction, peripheral eo-sinophilia, elevated serum IgE, specific IgE to cow’smilk protein, and histology. The term allergic eosino-philic gastroenterocolitis can be applied to this patientbecause the antrum, duodenum, and colon were infil-trated markedly. Our patient presented gastric outlet ob-struction, which is characteristic for the disease, and tworare complications: perforation of the stomach and il-eoileal intussusception. As far as we know, no other casewith such an early onset of symptoms and serious com-plications has been reported to date.

The gastric antrum is thought to be the target organ inEG (8). Its eosinophilic infiltration and edema from ac-companying inflammation often cause obstructive symp-toms. Although the gastric antrum is usually affected,perforation of stomach, as far as we know, has not beenreported so far. Eleven cases of intestinal perforation inpatients with EG have been reported, seven in adults andfour in children (3,9,10). Eight of these, were localized inthe small intestine, one in the duodenum, and two in thecolon. The perforation of the stomach in our patient canbe attributed to the eosinophilic infiltration of its mucosa,which possibly resulted in the development of a pepticulcer and/or may be the consequence of increased intra-luminal pressure resulting from pyloric wall thickness(10,11).

Intussusception is also a very rare complication of EG.Two cases of intussusception have been reported in pa-tients with EG so far, and only one occurred in a child(3). The intussusception in our patient is unlikely to berelated to the laparotomy performed on the third day oflife (34 days before the intussusception), because it isknown that the majority of cases of postoperative intus-susception occur within a week after surgery (12). Theabsence of typical symptoms of intussusception in ourneonate is probably the result of his age and the locationof the intussuscepted intestinal segment (13). Eventhough no biopsies were obtained (because the intussus-ception was reduced manually), the intussusception inour opinion was the result of eosinophilic infiltration ofthe small intestine. This suggestion is supported by thefinding of eosinophilic infiltration of the duodenum andcolon, which is indicative of a universal infiltration of thegastrointestinal tract (1).

Sensitivity to cow’s milk protein was exhibited by ourpatient. Although an IgE-mediated dietary protein sensi-tivity often occurs in patients with EG, the immuno-pathogenic mechanism of the disease is not clear. Insome patients, the symptoms resolve after removal of theoffending antigen from the diet (2,9,14) whereas, in oth-ers, dietary restriction does not influence the progression

of the disease (15) presumably because of a non-IgEreaction resulting from several other food antigens. Pa-tients younger than 2 years of age usually respond well tohydrolyzed protein formula or to L-amino acid formula(1). A causal relation between milk allergy and EG in ourpatient is probable, because symptoms subsided after theremoval of the offending antigen, and serum IgE levels,peripheral eosinophil count, and radioallergosorbent testto cow’s milk protein normalized. The appearance ofsymptoms on the first day of life can be attributed totransplacental sensitization. The young age of our pa-tient, the response to dietary elimination of the docu-mented allergen, and the absence of sensitization to otherfood antigens are facts consistent with a favorable prog-nosis. This case points out the need for peripheral eo-sinophilia and food allergy testing, even in neonates withvomiting and sonographic signs of pyloric hypertrophy,to initiate the appropriate treatment with antigen elimi-nation and to avoid unnecessary surgery and complication.

REFERENCES

1. Sampson HA, Anderson JA. Summary and recommendations:classification of gastrointestinal manifestations due to immuno-logic reactions to foods in infants and young children. J PediatrGastroenterol Nutr 2000;30:S87–94.

2. Whitington PF, Whitington GL. Eosinophilic gastroenteritis inchildhood. J Pediatr Gastroenterol Nutr 1988;7:379–85.

3. Hoefer RA, Ziegler MM, Koop CE, Schnaufer L. Surgical mani-festations of eosinophilic gastroenteritis in the pediatric patient. JPediatr Surg 1977;12:955–62.

4. Vanderplas Y, Quenon M, Renders F, Dab I, Loeb H. Milk-sensitive eosinophilic gastroenteritis in a 10-day-old boy. Eur JPediatr 1990;149:244–5.

5. Hummer–Ehret BH, Rohrshneider WK, Oleszczuk–Raschke K,Darge K, Nutzenadel W, Troger J. Eosinophilic gastroenteritismimicking idiopathic hypertrophic pyloric stenosis. Pediatr Radiol1998;28:711–3.

6. Blankenberg FG, Parker BR, Sibley E, Kerner JA. Evolving asym-metric hypertrophic pyloric stenosis associated with histologic evi-dence of eosinophilic gastroenteritis. Pediatr Radiol 1995;25:310–1.

7. O’Keeffe FN, Stansberry SD, Swischuk LE, Hayden CK. Antro-pyloric muscle thickness at US in infants: What is normal? Radi-ology 1991;178:827–30.

8. Blackshaw AJ, Levison DA. Eosinophilic infiltrates of the gastro-intestinal tract. J Clin Pathol 1986;39:1–7.

9. Agertoft A, Husby S, Host A. Intestinal perforation in a two-year-old child with eosinophilic gastroenteritis. Acta Paediatr Scand1991;80:389–91.

10. Deslandres C, Russo P, Gould P, Hardy P. Perforated duodenalulcer in a pediatric patient with eosinophilic gastroenteritis. Can JGastroenterol 1997;11:208–12.

11. Holgersen LO. The etiology of spontaneous gastric perforation ofthe newborn: a reevaluation. J Pediatr Surg 1981;16:608–13.

12. Ein SH, Ferguson JM. Intussusception—the forgotten postopera-tive obstruction. Arch Dis Child 1982;57:788–90.

13. Stringer MD, Pablot SM, Brereton RJ. Paediatric intussusception.Br J Surg 1992;79:867–76.

14. Justinich C, Katz A, Gurbindo C, et al. Elemental diet improvessteroid-dependent eosinophilic gastroenteritis and reverses growthfailure. J Pediatr Gastroenterol Nutr 1996;23:81–5.

15. Katz AJ, Twarog GJ, Zeiger RS, Falchuk ZM. Milk-sensitive andeosinophilic gastroenteropathy: similar clinical features with con-trasting mechanisms and clinical course. J Allergy Clin Immunol1984;74:72–8.

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