A case of invasive gastrointestinal Basidiobolus ranarum infection involving the cecum, appendix, right colon, liver and abdominal lymph nodes is reported in a 12-year-old child. This is the second case of culture-proved gastrointestinal B. ranarum infection reported to date in a pediatric patient.
Zygomycetes are filamentous fungi that cause subcutaneous and soft tissue zygomycoses. There are two orders belonging to this group, Mucorales and Entomopthorales. Members of both orders produce granulomatous inflammatory lesions. These infections are encountered mostly in immunocompetent healthy individuals living in tropical and subtropical regions. Rarely the genus Basidiobolus of the order Entomopthorales produces deeply invasive fungal infection. 1 Only a few cases of gastrointestinal infection caused by Basidiobolus ranarum have been reported, mostly in adults. 2–4 To date only one pediatric case of invasive gastrointestinal B. ranarum infection is on record. 5 We report the second case of culture-proved intraabdominal B. ranarum infection in a 12-year-old nonimmunocompromised child.
A 12-year-old boy from the Southern Province of Jizan, Saudi Arabia presented to the local hospital with a 2-month history of abdominal pain, occasional vomiting, occasional fever, poor appetite, weight loss and constipation. There was no history of diarrhea, contact with animals or a tuberculous patient. Before this history the child had been healthy and his immunization was on schedule.
His complexion was pale, his weight was 23.3 kg (2.5 sd below the mean), and he had no evidence of generalized lymphadenopathy. Abdominal examination revealed marked tenderness in the right iliac fossa with a 5- by 5-cm palpable mass. Routine laboratory tests revealed hemoglobin 10.6 g/dl, white blood cell count 17.9 × 109/l, neutrophils 65%, lymphocytes 15%, eosinophils 20% and erythrocyte sedimentation rate 94 mm at the end of l h. A sickle cell test was negative. Serum electrolytes, urea and creatinine values and liver function tests were normal. Total protein were 67 g/l and globulin 41 g/l (high).
With a presumptive diagnosis of acute appendicitis, minilaparotomy was performed. The appendix was not visualized. Instead omentum, cecum, terminal ileum and ascending colon were entangled as an adhesive mass. Biopsy was taken from this mass. The biopsy result was inconclusive revealing only nonspecifically inflamed omental tissue. One week later the child developed colicky pain at the right iliac fossa and one episode of loose bloody stool. He was then referred to our tertiary care hospital for further management. Computerized tomography (CT) scan of the abdomen revealed a large irregular mass in the right lower quadrant surrounding the thickened cecum with multiple enlarged lymph nodes around it. A well-defined low attenuation area was present in the medial segment of left lobe of liver and an extrinsic low attenuation lesion was seen compressing the lateral edge of the right lobe of the liver. Ultrasound guided fine needle aspiration of the mass in the right iliac fossa revealed a necroinflammatory lesion with profuse eosinophilic and acute and chronic inflammatory cell infiltrate. No granulomas were defined. Zeihl-Neilson stain for acid-fast bacillus was negative. Because the diagnosis was uncertain, it was decided to perform a laparotomy. At operation multiple soft masses were identified in the cecal and retrohepatic area. Extensive involvement of root of the mesentry with enlarged lymph nodes/nodules was also observed. The right pararenal gutter contained masses ranging from 3 to 6 cm in diameter. Bowel from the ligament of Treitz to the ileocecal valve was grossly normal, but cecum and the lymph nodes around this area were involved. Multiple biopsies were taken.
The histopathology of the biopsy specimens revealed an exuberant necrotizing granulomatous inflammatory reaction with predominant diffuse eosinophilic infiltrate. The granulomas had sparsely scattered fungal hyphae in the necrotic center and within the giant cells. The fungal hyphae were highlighted with periodic acid-Schiff and silver stains (Fig. 1). A sheath of eosinophilic material was also identified around the hyphae, which has been described as Splendore-Hoeppli phenomenon. Fungal culture on Sabouraud agar grew colonies within 5 days at 30°C. These were waxy, flat, thin colonies. Smears of colony stained with lactophenol cotton blue showed irregular, broad, sparsely septate hyphae. Zygospores with beaks attached to one side were also identified. After this morphologic confirmation of basidobolus infection, oral itraconazole 200 mg once daily was started. CT scan of chest and brain did not reveal lesions.
The patient underwent a repeat laparotomy with right hemicolectomy, appendectomy and removal of retrohepatic masses, mesenteric lymph nodes and the terminal ileum. Resected intestine revealed widespread ulceration in the colon and thick walled cecum. Multiple large nodules were found occupying the adventitia and mesenteric fat. Histologically the lesions presented the same features as described for the biopsies. Mucosal ulcerations were a prominent feature with extensive necrotic slough at the surface and granulation tissue underneath with granulomas and eosinophilic infiltrate. It was a transmural inflammatory reaction but adventitia and serosal fat were maximally involved. The ileum was spared. Postoperatively the patient continued to receive total parenteral nutrition and iv itraconazole (5 mg/kg/day) for 2 days, shifting thereafter to oral therapy. The patient remained stable and was discharged after 7 days with oral itraconazole 200 mg in the morning and 100 mg in the evening (8 mg/kg/day). Repeat CT before discharge showed the persisting liver mass.
One month later the patient had gained 2 kg. His appetite, oral intake and bowel habits were normal. Repeat CT scan of the abdomen revealed marked reduction in the size of the liver mass, and no new lesions were detected in the abdominal viscera. It was decided to continue with the oral itraconazole for a further 9 months. Follow-up after 6 months revealed complete disappearance of the remaining liver lesions.
Invasive gastrointestinal B. ranarum infection is rare. A total of 13 authentic cases of such infection have been reported in the literature to date, ours being the 14th. Interestingly 9 of these 13 cases were reported during the last 5 years, the present case being the 10th. Our case presented clinically with features of acute abdominal condition which even at the time of surgery favored malignancy more than an inflammatory condition. This highlights the nonspecific clinical presentation of B. ranarum infection mimicking several diverse conditions ranging from inflammatory bowel disease, tuberculosis and lymphomas to simple appendicitis. 2–4
Morphologically the present case revealed mucosal ulcerations of resected intestine. However, the muscularis adventitial and periadventitial lesions with granulomatous inflammation outnumbered the mucosal involvement. Most of the previous studies report none or minimal involvement of mucosal layer. 3, 4 The presumptive route of infection for gastrointestinal infection is ingestion of fungal spores followed by mucosal transgression with subsequent spread and extensive intraabdominal disease. This cannot explain localization of inflammatory reaction predominantly in the muscularis, adventitia and periadventitial tissues of gastrointestinal tract.
In the present case no predisposing cause for acquiring this infection is defined. No previous history of any surgical procedure was present in our case. Two of the previously reported cases encountered the invasive B. ranarum infection after appendectomy and repair of inguinal hernia.
The factors responsible for progressive infection are not clearly defined. Our patient was immunocompetent clinically as well as on laboratory investigations. In none of the reported cases to date has any immunodeficiency state been identified except for two cases with history of insulin-dependent diabetes mellitus. 4, 6
No standardized appropriate treatment for basiobolomycosis has been defined. Surgical resection of any obstructing masses is essential, although surgery has been debated for fear of spreading the infection. 1 The role of adjunctive systemic antifungal therapy is established. The efficacy of amphotericin B in visceral infections has been unsatisfactory with resistance observed in >50% cases. 7 Prolonged treatment with itraconazole is the best option. 8 Our case had an excellent response to itraconazole therapy after surgical debulking.
In conclusion we report the second case of culture-proved invasive intestinal basidiobolomycosis in an immunocompetent child. At the time of presentation the disease had already advanced to liver, lymph nodes and abdominal cavity. This case was confirmed morphologically with demonstration of fungi in the resected tissues followed by positive culture. The rarity of this disease warrants for a high index of suspicion by the clinicians especially in endemic regions and developing world countries.
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