We describe a newborn infant with severe eosinophilic enterocolitis requiring immunosuppression. Eosinophilic enterocolitis is an uncommon disease of uncertain immunopathogenesis characterised by infiltration of the intestinal walls with eosinophils, absence of vasculitis, and peripheral blood eosinophilia (1–3). The disease is uncommon in children (4) and rare in newborn infants in the first week of life (5). Eosinophilic enterocolitis in newborn infants is usually a short-lived disorder that responds to the exclusion of cow's-milk protein from the diet (4). Eosinophilic enterocolitis has been reported in infancy, childhood, and adolescence with an immense variety of chronic and debilitating gastrointestinal symptoms (6). Immunosuppression to manage exacerbations has been reported in paediatric and adult populations with eosinophilic enterocolitis (3,7). CASE REPORT The patient was a male infant born following the spontaneous onset of preterm labour at 34 weeks' gestation in a pregnancy that was otherwise normal. The infant was born vaginally with Apgar scores of 9 and 9 at 1 and 5 minutes, respectively, and a birth weight of 2370 g. He was transferred to the Children's Hospital at Westmead, at 1 day of age with a history of watery diarrhoea and haematochezia first noted within 24 hours of birth, during which time he had been given 1 small whey-dominant formula milk feed (S26, Wyeth, Australia). The abdominal examination was normal, an x-ray showed no evidence of necrotising enterocolitis, and an upper gastrointestinal x-ray contrast study excluded malrotation. The coagulation studies and full blood count were normal, except for the presence of eosinophilia (3.1 × 109/L, normal <1.0 × 109/L). An amino acid milk formula (Neocate, Scientific Hospital Supplies, Melbourne, Australia) was introduced at 5 days of age and this was followed by the passage of frequent, large, watery, blood-stained stools with reducing substance, and the development of hyponatremia (serum sodium 113 mEq/L). The infant's diarrhoea decreased when enteral milk feeding was ceased but returned when the amino acid milk formula was reintroduced 5 days later, thereby necessitating the cessation of enteral milk feeding and the commencement of parenteral nutrition, while microscopic blood loss in stools continued. The following investigations were performed to elucidate the aetiology of the infant's presumed enterocolitis. An abdominal ultrasound examination showed centrally located slightly thick-walled and hyperaemic loops of bowel consistent with enteritis. A radionuclide scan with technetium-99m-labelled red cells showed no evidence of intraluminal intestinal bleeding. A similarly labelled radionuclide white cell scan showed evidence of inflammation involving the right side of the colon. Stool microscopy showed numerous leucocytes, and culture was negative for viruses and bacteria. Clostridium difficile toxin was absent in stool. Specific immunoglobulin levels and polymerase chain reaction studies excluded cytomegalovirus and herpes simplex virus infections. T-cell and B-cell subset and neutrophil function values were within normal limits. The serum immunoglobulin E level was elevated (55 kU/L; normal 0–20). Flexible sigmoidoscopy revealed inflammation of the sigmoid colon and rectum. Rectal biopsy was performed to exclude Hirschsprung disease. The histological examination of rectal mucosa showed variably dense infiltrates of eosinophils within the lamina propria, crypt epithelium, and muscularis mucosae (Fig. 1). Immediate hypersensitivity skin prick test was performed at 6 weeks of age. It was negative for milk, egg yolk, egg white, wheat, corn, peanut, soybean, and baker's yeast. On the basis of clinical, endoscopic, and histological evidence, the infant was considered to have idiopathic eosinophilic enterocolitis.FIGURE 1: Rectal mucosa with excessive numbers of eosinophils within the lamina propria and extending into the muscularis mucosae, superficial submucosa, and crypt epithelium.The recurrence of diarrhoea and haematochezia on 2 occasions following the reintroduction of elemental milk feeds prompted treatment with oral prednisolone (2 mg · g−1 · day−1) commencing at 3 weeks of age. The introduction of steroid treatment led to a reduction in diarrhoea, a decrease in the C-reactive protein level and blood eosinophil count, and the successful reintroduction of elemental milk feeds. However, a reduction in the prednisolone dose resulted in a recurrence of the watery diarrhoea and increases in the serum C-reactive protein and blood eosinophil count. Oral cyclosporine (6 mg · g−1 · day−1) was commenced when the infant was 6 weeks of age for its possible steroid-sparing effect. The treatment with cyclosporine and low-dose prednisolone was successful, and full enteral amino acid milk feeding was established before discharge from hospital at 10 weeks of age. Oral prednisone treatment was ceased when the infant was 3 months of age. On last review at 5 months of age, the infant was thriving on elemental milk feeds and oral cyclosporine (1.5 mg · g−1 · day−1) with no reported episodes of enterocolitis. The trough level of cyclosporine was below the level of detection (<10 ng/mL). In addition, the cyclosporine had been well tolerated clinically and there had been no laboratory evidence of haematological, renal, or hepatic dysfunction. DISCUSSION Idiopathic eosinophilic enterocolitis was diagnosed in the newborn infant reported herein because the colon was inflamed on visual inspection and radionuclide scanning, and on histopathological examination, the rectal mucosa lamina propria was infiltrated with eosinophils (8,9). Eosinophilic enterocolitis is an uncommon condition in newborn infants (4). The disorder is usually thought to be an allergic response to cow's-milk protein and accordingly most infants recover with a short period of bowel rest, parenteral nutrition, and subsequent feeding with a cow's-milk protein–free milk formula or breast milk from a mother who has excluded all dairy products from her diet (4,10,11). The present infant was unusual in that he did not respond to the aforementioned treatment measures, and symptom control required the use of prednisone and cyclosporine. This is the first report to describe a newborn infant with eosinophilic enterocolitis treated with immunosuppressant drug therapy, although prednisolone and cyclosporine have been used to treat neonatal eosinophilic pneumonia (12). The natural history of the disorder in the present infant is not readily explained on the basis of cow's-milk protein allergy, and the aetiology of eosinophilic enterocolitis in this infant is uncertain. Nevertheless, eosinophils are unstable cells that can readily release cytotoxic chemical mediators even in the absence of antigenic stimulation (10). A subgroup of infants with allergic gastroenteritis with protein-losing enteropathy who have peripheral oedema have been reported, with the youngest in the case series presenting at 2 months of age (13). However, none of the patients in this case series needed immunosuppressant therapy. In another series of 17 infants and children with eosinophilic gastroenteropathy (7), 5 were treated with prednisolone, but no newborns were reported to receive immunosuppression. In adult-onset eosinophilic gastrointestinal disease, glucocorticoid steroids have been used to induce remission with symptomatic and histologic improvement (14), presumably because steroids disrupt the cytokine network and indirectly diminish eosinophil generation, survival, and function (15). Low-dose prednisolone did not control the present infant's colitic symptoms and cyclosporine had to be added to the treatment regimine before a sustained remission was achieved. Cyclosporine is a calcineurin inhibitor that inhibits activation of eosinophil-induced cytokine, migration of eosinophils from circulation, and T-cell stimulation of antigen-presenting cells (12). The present case report and others in the literature recording serious complications in neonates with eosinophilic gastroenteritis, including ileal perforation, bile duct obstruction and death (16), and perforation of the stomach and ileoileal intussusception (17), indicate that eosinophilic enterocolitis can be a serious illness in newborn infants. Immunosuppression may be required when dealing with eosinophilic enterocolitis that does not respond to food withdrawal and after exclusion of other aetiologies of intractable diarrhoeas that can present in the neonatal period.
Abstract Hirschsprung's disease is characterized by the absence of ganglia in the distal colon, resulting in a functional obstruction. It is managed by excision of the aganglionic segment and anastomosis of the ganglionated bowel just above the dentate line. The level of aganglionosis is determined by performing multiple seromuscular biopsies and/or full thickness biopsy on the antimesenteric border of the bowel to determine the level of pullthrough. The transition zone is described as being irregular, and hence a doughnut biopsy is recommended so that the complete circumference can be assessed. Herein, we described a child in whom there was a selective absence of ganglion cells in 30% of the circumference of the bowel along the mesenteric border for most of the transverse colon. This case defies the known concept of neural migration in an intramural and transmesenteric fashion and emphasizes the importance of a doughnut biopsy of the pulled-down segment.
Purpose: Ectopic nephrogenic rests (ENR) are rare. The significance of ENR and their role in tumourgenesis is largely unknown, although they have been associated with Extrarenal Wilms’ Tumours (ERWT). We review our experience with the surgical management of ENR and discuss the clinico‐surgical implications of their incidental discovery. Methodology: We reviewed the hospital records of patients with histopathologically confirmed ERWT and ENR treated at our hospital over a ten year period. Results: Ninety‐five children with WT were identified but only one case of ENR and ERWT. This patient was a fourteen month old boy who was incidentally found to have a mass in the left inguinal canal during orchiopexy. Following histology, a provisional diagnosis of ENR was made. Six months later the child went onto develop an ERWT at the same site. Periodic post surgical follow‐up has been uneventful. Conclusion: The discovery of a site of ENR raises two distinct possibilities: either it is an isolated developmental abnormality or, of more clinical significance, the early stages of a neoplastic process. Our experience lends support for the theory that ENR are precursor lesions to the development of WT in ectopic sites. Histopathologically, ENR can be difficult to differentiate from ERWT and this adds to the uncertainty in identifying a natural clinical progression for these lesions and in labelling them as putative pre‐ cursor lesions to ERWT. Children with confirmed ENR should be considered as high risk for the development of ERWT and require long term post – operative follow up.
Previous studies in diabetic animal models have demonstrated altered pancreatic islet-cell populations. To further characterize the diabetic syndrome in our athymic nude mouse colony, we studied the population of endocrine cells in pancreatic islets of 4-week-old normoglycemic and 8-week-old hyperglycemic athymic nude (nu/nu) mice using immunohistochemistry, morphometry, and electron microscopy. In normoglycemic 4-week athymic nu/nu mice, the proportions of B (insulin-secreting) cells and A (glucagon-secreting) cells were similar to those in control Balb/c mice; however, the D (somatostatin-secreting) cells were significantly decreased in nu/nu mice. The populations of B and A cells appeared to be normal in hyperglycemic 8-week-old nu/nu mice while there was a significant increase in the proportion of D cells when compared with the proportion in Balb/c mice. Electron microscopic studies indicated that the appearance of B and A cells was similar in the 8-week-old hypergiycemic nu/nu and in controls; however, the D cells appeared to be enlarged and were finely packed with electron-dense secretory granules. Radioimmunoassays of the pancreatic content (μg/g fresh pancreas) of insulin, glucagon, and somatostatin in pancreata in 8-week-old normal Balb/ c and hyperglycemic athymic nude mice were similar; however, the somato-statin content was significantly increased in the 8-week-old hyperglycemic nu/nu mice compared with age and sex-matched controls. These results demonstrate an altered D cell population and an increase in somatostatin levels in the pancreatic islets of the hyperglycemic athyrnic nude mouse animal model. Whether these changes in the D cell population may in part explain the development of the diabetic state is yet unknown and warrants further investigation.
'/%3e%3c/defs%3e%3cpath fill='%23012169' d='M0 0h10080v5040H0z'/%3e%3cpath stroke='%23fff' stroke-width='.6' d='m0 0 6 3m0-3L0 3' clip-path='url(%23b)' transform='scale(840)'/%3e%3cpath stroke='%23e4002b' stroke-width='.4' d='m0 0 6 3m0-3L0 3' clip-path='url(%23c)' transform='scale(840)'/%3e%3cpath stroke='%23fff' stroke-width='840' d='M2520 0v2520M0 1260h5040'/%3e%3cpath stroke='%23e4002b' stroke-width='504' d='M2520 0v2520M0 1260h5040'/%3e%3cg fill='%23fff'%3e%3cuse xlink:href='%23d' x='2520' y='3780'/%3e%3cuse xlink:href='%23a' x='7560' y='4200'/%3e%3cuse xlink:href='%23a' x='6300' y='2205'/%3e%3cuse xlink:href='%23a' x='7560' y='840'/%3e%3cuse xlink:href='%23a' x='8680' y='1869'/%3e%3cuse xlink:href='%23e' x='8064' y='2730'/%3e%3c/g%3e%3c/svg%3e)
