Eosinophilic Appendicitis Attributable to Strongyloides Infection in a Pediatric Renal Transplant Patient

Abstract

The patient was born in a town near Bogota, Colombia and was adopted in the United States at 2 years of age. At the time of adoption, there was a suspicion of renal disease with failure to thrive. Within a year of arriving in Alabama, she was diagnosed with hypoplastic-dysplastic syndrome. Her renal disease resulted in dialysis at age 16, and she received a living unrelated renal transplant from her adoptive mother at age 18. She was treated with an immunosuppressive regimen that included tacrolimus, mycophenolate, and prednisone. Her immediate posttransplant course was notable only for complaints of mild diarrhea that worsened when her regimen changed from tacrolimus to sirolimus in the 8th month after transplant for a research protocol. At 9 months posttransplant, she developed severe, constant, right lower quadrant abdominal pain. Her diarrhea worsened and she developed headaches, but she denied having fever, cough, difficulty breathing, vomiting, or bloody stools. A computerized tomography scan showed findings associated with appendicitis, which prompted appendectomy. Pathologic examination of the specimen identified intense transmural eosinophilic infiltration of the appendiceal wall consistent with eosinophilic appendicitis (Figure ​(Figure1).1). Biopsies of the terminal ileum, cecum, and colon at the hepatic flexure also revealed eosinophilic infiltrates. No parasitic forms were found in any of the tissue samples by direct visualization. A peripheral eosinophilia of up to 9.5%was documented, and a stool test was negative for ova and parasites (O&P). Figure 1. Pathology of appendix. Numerous eosinophils fill the lamina propria (left panel) and infiltrate the submucosa (right panel) of the appendix (hematoxylin and eosin stain, ×132). After appendectomy, the patient's abdominal pain resolved and her diarrhea improved. However, her eosinophilia persisted, rising as high as 18.3% 3 months later, even after empiric treatment with 2 doses of mebendazole for “intestinal parasite” 1 month after appendectomy. Subsequent evaluation by the gastrointestinal and allergy/immunology services included negative immunoassays for food and upper respiratory allergens, negative screens for celiac disease, negative serology for Toxocara, and a Strongyloides immunoglobulin G (IgG) antibody by enzyme-linked immunosorbent assay (ELISA) that was positive (4.28, reference range <1.00, sensitivity and specificity of 90%; Focus Diagnostics, Cypress, CA). Based on these results, the eosinophilia and gastrointestinal findings were attributed to infection by Strongyloides. The patient was treated with a 4-day course of ivermectin (200 mcg/kg per day) 2 weeks before initial Infectious Diseases (ID) consultation. In ID clinic, additional history included a positive tuberculin skin test during pretransplant evaluation with a history of Bacillus Calmette-Guerin vaccination, which prompted a 9-month course of isoniazid. The patient reported intermittent “hive-like” rashes in “small red circles” mainly affecting her head, lower extremities, arms, and occasionally buttocks since early childhood, which she attributed to skin allergies. She lived with her parents and with 2 healthy dogs and cats. She reported walking outside barefoot frequently, but she denied any travel outside of the country since arriving in the United States. Investigation of the patient's available records revealed negative human immunodeficiency virus status and negative serologies for Trympanosoma cruzi, but testing was not performed for Strongyloides or other parasites on pretransplant evaluation. Any medical evaluation performed in the international adoption process was not available in our patient's medical record. However, her mother denied any medical issues at the time of adoption other than failure to thrive, a suspicion of renal disease, and bow-leggedness. One finding of particular interest was evidence of long-standing (up to 8 years before transplant) significant eosinophilia (>10%) that subsided with transplant but reappeared with the onset of her abdominal symptoms (Figure ​(Figure22). Figure 2. Eosinophil percentage from peripheral blood samples over a 10-year span. Time of transplant (a: 5/21/09), appendectomy (b: 2/18/10), and completion of first (c: 6/5/10) and second (d: 6/27/10) treatments with ivermectin are marked with arrows. On physical examination the patient was well-appearing and of short stature (143.5 cm, <3% for age), with a soft, nontender abdomen, palpable transplant kidney mass in the lower right quadrant, a well-healed surgical scar over her right abdomen, and no hepatomegaly. No rashes were observed. Although a single stool O&P before initial treatment had been negative, 3 daily stool O&P examinations were repeated and were negative. Serologies for human T-lymphotropic virus (HTLV) and filaria were likewise negative. A complete blood count after the first course of ivermectin revealed that her eosinophilia had improved (white blood cells of 6.27, 3.2% eosinophils). To ensure eradication in an immunocompromised patient, a second course of ivermectin was given (200 mcg/kg per day for 2 days). At a follow-up visit 6 months later the patient continued to do well with no new symptoms and no further reports of rashes. A repeat Strongyloides IgG level was undetectable.