Pathologic Quiz Case: Right Lower Quadrant Pain in a 2-Year-Old Boy

A 2-year-old Latin American boy from Honduras visiting the United States with his mother presented with a 2-day history of abdominal pain, nausea, and vomiting. He was febrile, with a temperature of 38.6°C. He was appropriately developed for his age (weight 12.9 kg), and physical examination was unremarkable except for a diffusely tender abdomen. Hematology data collected included a white blood count of 12.3 × 103 cells/μL with 5% bands and 5% eosinophils, hematocrit of 35%, and normal serum electrolytes. Stool examination for ova and parasites was negative. Chest radiographs revealed no abnormalities, and abdominal radiographs revealed a prominent bowel gas pattern consistent with adynamic ileus.The patient underwent appendectomy for suspected acute appendicitis. Intraoperative findings were those of gangrenous acute appendicitis. Postoperative course was uneventful.On gross examination, the appendiceal serosa was dusky with purple-gray discoloration and fibrinopurulent exudate. The lumen was patent and contained liquid hemorrhagic feces. No parasites were grossly seen. On microscopic examination, there were numerous intramural and periappendiceal eosinophilic abscesses and parasitic organisms in mesenteric vessels (Figure 1). Higher power examination revealed eosinophilic abscesses surrounding ovoid structures consistent with parasite eggs (Figure 2), which were embedded in the mucosa and in the wall. A foreign body giant cell reaction was focally present (Figure 3). Within the appendiceal lumen and most strikingly within periappendiceal mesenteric artery branches, several parasitic organisms were seen (Figure 4).What is your diagnosis?Angiostrongylus costaricensis is a filiform intestinal nematode endemic to Central and South America; up to 600 human cases per year are diagnosed in Costa Rica.1 Another member of this species capable of causing human disease is Angiostrongylus cantonensis, which occurs in Southeast Asia and the South Pacific region and causes eosinophilic meningitis.Rare cases of infection with A costaricensis have been reported in the United States, and most of these infections appeared to have been acquired abroad.23 The usual definite host is the rat, and the obligatory intermediate host is the snail or slug.4 In the rat, the adult worms live in mesenteric arteries near the cecum. Eggs are laid in the intestinal wall, where they embryonate. First-stage larvae migrate to the intestinal lumen, where they are passed with feces. Slugs are infected by contact with feces. The larvae mature to the second and third stages in the digestive tract of the slug. When rats eat the slugs, the larvae penetrate the intestinal mucosa and mature in the lymphatics, and the young adult worms burrow into the arteries of the ileocecal region where they mate and the cycle is completed. Humans are infected accidentally by contact with mucous secretions of slugs on unwashed vegetables or by eating slugs. The location of the adult worm in humans is similar to that in the rat, but unlike in the rat, eggs or early stage larvae degenerate and never reach the intestinal lumen, presumably because of the intense inflammatory reaction they elicit. Therefore, no larvae or eggs are passed with the stools, and to our knowledge there have been no reports of human-to-human transmission.In humans, the time interval between infection and symptoms ranges from 14 days to 38 months. Children between 6 and 13 years of age are most commonly affected, with a male-female ratio of 2:1. Clinical presentation is similar to acute appendicitis, with right iliac fossa pain, acute abdominal pain, a tumorlike palpable mass, or a painful rectum.5 Low-grade fever and leukocytosis with eosinophilia are common. The inflammatory process is typically located in the ileocecal region (cecum, ascending colon, appendix, or small bowel), with less common involvement of mesenteric lymph nodes, omentum, liver, and testicles. Necrosis of the bowel wall with or without perforation is related to parasitic vascular occlusion, arteriolitis, or thrombosis.The differential diagnosis of gastrointestinal eosinophilia includes other parasitic infections, particularly those by nematodes such as Strongyloides stercoralis, Schistosoma mansoni, Enterobius vermicularis, Toxacara canis (visceral larva migrans), Anisakis sp, and Trichuris trichiura. However, there is no other nematode of this size that produces a lesion that is focused on mesenteric vessels. Also, Angiostrongylus is the only nematode infection in humans with transmural presence of both eggs and larvae in the bowel. Adult female Strongyloides live in the mucosal epithelium and intestinal crypts and are only 30 to 40 μm. Their eggs are limited to the crypts. The eggs of the Schistosoma species that commonly infect humans (S mansoni and S haematobium) are considerably larger (>100 μm) than those of A costaricensis, and adult Schistosoma worms are found in the venous, not the arterial system. Enterobius vermicularis is commonly found in the gut lumen and rarely invades the intestinal wall. The lateral alae in the cuticle, which are characteristic of Enterobius, are not seen in Angiostrongylus. Visceral larva migrans is caused by Toxocara larva, which are much smaller than those of Angiostrongylus. The adult form of Toxocara is not found in humans. Anisakiasis can present as intestinal lesions grossly similar to angiostrongyliasis. These lesions, however, contain only larvae with no eggs. Anisakis larvae can be recognized by their thick multilayered cuticle and large Y-shaped lateral chords. Trichuris trichiura resides within the cecum and colon, with the slender anterior portion of the worm attached to the mucosa.Nonparasitic causes of gastrointestinal eosinophilia include food and drug allergies, inflammatory bowel disease, and some systemic illnesses such as polyarteritis nodosa. Of these, Crohn disease deserves special mention because clinical and histologic features may overlap with those of angiostrongyliasis, such as involvement of the ileocecal region, thickening of the cecal wall, and granulomatous inflammation.The definite diagnosis of angiostrongyliasis is made when parasites are identified in the surgically resected specimen. However, in practice, surgical specimens are rarely obtained and diagnosis relies on a constellation of findings, including clinical signs, peripheral eosinophilia, and a positive serologic test. A serologic enzyme-linked immunosorbent assay is offered through the Centers for Disease Control (Atlanta, Ga). This test is highly sensitive but not very specific because it cross-reacts with other nematodes.6 It is most useful in conjunction with appropriate clinical findings. Examination of feces for ova and parasites is not helpful because they are not excreted in human feces.The most effective treatment is surgical removal of the affected area. Anthelmintic drug therapy is often used, but its efficacy has been questioned.