Case Report: Gastrointestinal Basidiobolomycosis with Multi-Organ Involvement Presented with Intussusception

ABSTRACT.

Gastrointestinal basidiobolomycosis (GIB) is a rare, life-threatening fungal infection affecting immunocompetent individuals in tropical and subtropical regions. A diverse presentation of GIB has been reported, but no report has yet been published on intussusception. We describe a 23-month-old immunocompetent boy from a subtropical area in Iran who presented with intussusception. Prolonged fever, an abdominal mass, hepatomegaly, high erythrocyte sedimentation rate, and peripheral eosinophilia strongly suggested GIB. Accordingly, GIB was diagnosed based on the characteristic histopathology (the Splendore-Hoeppli phenomenon) detected in a liver sample taken via biopsy. Exploratory laparotomy showed several organs, including the colon, gall bladder, liver, and abdominal wall, were involved. Antifungal therapy with trimethoprim/sulfamethoxazole, liposomal amphotericin B, a saturated solution of potassium iodide, and surgical resection of involved tissues were used with improved outcome. The presence of non-septate fungal hyphal elements in the colonic mucosa led to the thickening of the bowel wall, leading to secondary intussusception.

INTRODUCTION

Gastrointestinal basidiobolomycosis (GIB), caused by Basidiobolus ranarum, is a rare and life-threatening fungal infection that is limited geographically to tropical and subtropical regions, and is observed in immunocompetent individuals. It is a saprophytic fungus belonging to the order Entomophthorales of the Zygomycetes family.¹ The mortality rate in a recent review has been reported as 18.6%.² Good outcomes for patients with GIB require timely diagnosis, and prompt and proper management, including effective antifungal therapy and surgical resection of the involved tissues.³ GIB involves most frequently the liver and intestinal tract, and usually presents with abdominal pain, intra-abdominal mass lesions, fever, weight loss, and diarrhea or constipation. It is usually accompanied by peripheral blood eosinophilia and a high erythrocyte sedimentation rate (ESR).^4,5 Therefore, GIB can mimic a wide range of diseases, such as amebiasis, colon cancer, lymphoma, inflammatory bowel disease, chronic granulomatous diseases, and sarcoidosis.^4–9 To the best of our knowledge, intussusception has not been reported as the presentation of GIB in the corresponding English literature. We report our experience with a 23-month-old immunocompetent child with GIB who presented with intussusception and appeared to have multi-organ involvement.

CASE PRESENTATION

The patient in question was a previously healthy 23-month-old boy, living in Bushehr Province, southern Iran. He was referred to a local hospital with the chief complaints of intermittent irritability and abdominal distension, with increasing severity for 2 days. There was also a 2-month history of mild, intermittent fever and irritability, constipation, poor appetite, and abdominal protrusion. Intussusception was reported in ultrasound imaging of the abdomen. Upon his parents’ request, he was referred and admitted to our hospital, Nemazee Teaching Hospital in Shiraz, affiliated with Shiraz University of Medical Sciences. His parents denied any significant past medical diseases. During the physical examination, an abdominal mass was palpated from the right upper quadrant to the right iliac fossa, and abdominal distension and hepatomegaly were detected. Emergency abdominal ultrasonography was in favor of intussusception, so a reduction using fluoroscopy was performed. Passage of contrast from the rectum to the colon to the cecum and then to a small bowel loop were seen (Figure 1). The next day, abdominal ultrasonography revealed no sign of intussusception. However, significant homogenous circumferential wall thickening (10 mm) in the distal terminal ileum, cecum, and ascending colon until the hepatic flexure, with adjacent significant fat inflammation, multiple mesenteric lymph nodes in the right side of the abdomen, and hepatomegaly were evident. The same findings were also noted via abdominal computed tomography (CT) (Figure 1).

Figure 1.

(A) Barium enema using a water-soluble contrast agent demonstrates an intraluminal mass surrounded by a contrast agent representing the head of the intussuscept (thick arrow). (B) Upon the successful reduction of intussusception, luminal irregularity and narrowing of the ascending colon are visualized (thin arrow). (C) Axial computed tomographic scan shows circumferential wall thickening and edema of both the distal ileum (thick arrow) and the ascending colon (thin arrow). Multiple prominent and enhancing lymph nodes are also evident in the para-aortic and right para-iliac regions (curved arrow). (D) Coronal computed tomographic scan in the same patient demonstrates more clearly the wall thickening and enhancement of the distal ileum (thick arrow) and the ascending colon (thin arrow), as well as prominent, enhancing lymph nodes (curved arrow). There is also loss of the fat plane between the thickened ascending colon and the right lobe of the liver, which represents direct invasion (black arrow).

Laboratory tests revealed hemoglobin, 9.5 g/dL; mean corpuscular volume, 69 fL; peripheral white blood cell count, 26,100 cells/µL; neutrophils, 69%; bands, 6%; lymphocytes, 10%; monocytes, 2%; eosinophils, 13%; and platelets, 768,000 platelets/µL. Both C-reactive protein and ESR levels were high (150 mg/L and 60 mm/h, respectively). Other test results including liver function and coagulation tests, blood urea nitrogen, and creatinine were within the normal range. A Tru-Cut biopsy from the liver mass was acquired and, during the microscopic examination, a granuloma formation and fungal hyphae surrounded by extensive eosinophilic infiltration (Splendore-Hoeppli phenomenon) were noted (Figure 2). Unfortunately, no tissue was sent for fungal culture to the microbiology laboratory from the operating room. Based on characteristic pathological and clinical features, a diagnosis of GIB was made. We started our routine antifungal treatment of GIB, including trimethoprim/sulfamethoxazole (/SMX) (8 mg trimethoprim/kg/d intravenously every 12 hours), liposomal amphotericin B (AmBisome, Gilead UK and Ireland) (5 mg/kg/d by intravenous infusion), and a saturated solution of potassium iodide (30 mg/kg/d, orally once a day).¹⁰ Vancomycin (60 mg/kg/d, intravenously every 6 hours) and meropenem (60 mg/kg/d, intravenously every 8 hours) were also prescribed on the suspicion of a secondary bacterial infection for 14 days. One week after starting antifungal therapy, exploratory laparotomy with the resection of a huge abdominal mass, right hemicolectomy, right lateral hepatectomy, cholecystectomy, and resection of the involved part of abdominal wall muscles were performed. The abdominal mass measured 11 × 10 × 7 cm and was attached to the colon, liver, and abdominal wall; the mass was sent to the pathology laboratory. If no fungal cultures had been done on these specimens, the potentially positive specimens might have been missed by performing only a histopathological examination. Cut sections showed colonic loops attached to each other by a firm, white solid mass (Figure 3). Histopathological examination of the colon, liver, and abdominal wall mass revealed the same findings from the previous Tru-Cut biopsy from the liver mass (Figures 2 and 3). The patient improved gradually and was discharged from the hospital 3 weeks after the operation. During the outpatient follow-up, a combination of itraconazole (5 mg/kg/d every 12 hours), potassium iodide (30 mg/kg/d once a day), and trimethoprim/sulfamethoxazole (10 mg/kg/d every 12 hours) was administered orally for 4 months. The patient tolerated treatments well without any adverse effects. After a 6-month outpatient follow-up, the patient was symptom free without any evidence of recurrence on serial abdominal ultrasound performed every other month.

Figure 2.

(A) Tru-Cut biopsy from the liver mass shows a granuloma formation and fungal hyphae surrounded by extensive eosinophilic infiltration (Splendore-Hoeppli phenomenon) (arrows) replaced hepatocytes (hematoxylin–eosin stain, ×200 magnification). (B) Cut section of the liver mass shows a firm, white solid mass. (C) Section from the liver mass shows granulom formation (arrow) and fungal elements (circle) (hematoxylin–eosin stain, ×100 magnification). This figure appears in color at www.ajtmh.org.

Figure 3.

(A) Histopathological section from the abdominal wall mass shows the Splendore-Hoeppli phenomenon between skeletal muscles and many eosinophils (hematoxylin–eosin stain, ×400 magnification). (B) Gross examination of the colonic mass shows a large mass attached to colonic loops. (C) Section of the colonic mass shows submucosal infiltration of inflammatory cells with granuloma formation (hematoxylin–eosin stain, ×40 magnification). (Inset) Granuloma formation and fungal hyphae (hematoxylin–eosin stain, ×200 magnification). This figure appears in color at www.ajtmh.org.

DISCUSSION

GIB, a potentially life-threatening and rare fungal infection, occurs uniquely in tropical and subtropical regions of the world and has been mostly reported from the United States, Saudi Arabia, and Iran.^2,11 According to a recent review, only 102 cases have been reported from 1964 to 2017, with 20.6% of cases being from Iran. GIB was reported predominantly in males (74.5%) and immunocompetent children without any predisposing factors (41.2%).² Our patient was a 23-month-old boy from a subtropical area in southern Iran who presented with intussusception and was treated successfully with non-operative reduction. To the best of our knowledge, this is the first report of a child with GIB presenting with intussusception, and further investigations revealed the involvement of multiple organs, including the colon, gall bladder, liver, and abdominal wall. In a recent review of 102 cases, the colon or cecum has been the most common site of gastrointestinal involvement in GIB (84.2%), with liver and gall bladder involvement reported in 21.8% of cases. Abdominal wall involvement was not reported in a review by Pizzani et al.² Intussusception, mostly idiopathic, is the most common surgical emergency in children. In as few as 2% up to 25% of cases, an underlying disease may cause a pathological lead point for the intussusception.^12–14 In our patient, the presence of coenocytic fungal hyphal elements in the colonic mucosa ensued the thickening of the bowel wall, likely leading to secondary intussusception.

Given the rareness of the condition, lack of any predisposing factor, and diverse clinical presentations, a timely diagnosis of GIB needs a high index of suspicion. Most GIB cases were misdiagnosed as lymphoma, colon carcinoma, intestinal tuberculosis, sarcoidosis, amebiasis, and inflammatory bowel disease.¹⁴ Although our patient was referred to an emergency department as a result of acutely increasing irritability, abdominal protrusion, and a palpable mass caused by intussusception, other findings such as prolonged fever, abdominal pain, abdominal mass, hepatomegaly, and peripheral eosinophilia were suggestive of GIB. In a recent review of 102 patients with GIB, abdominal pain (86.3%) was found to be the most common presenting symptom, followed by abdominal mass (30.4%), fever (40.2%), weight loss (33.3%), constipation (22.5%), abdominal distension (16.7%), vomiting (15.7%), and diarrhea (13.7%). This finding was in line with the findings of a multicenter study in Saudi Arabia. Eosinophilia was also a prominent laboratory finding.²

GIB was diagnosed in our patient by detecting characteristic histopathological findings of fungal hyphae, and granulomatous inflammation with marked tissue eosinophilia (the Splendore-Hoeppli phenomenon). The isolation of B. ranarum in culture or molecular detection by polymerase chain reaction provides a definite diagnosis. However, the characteristic Splendore-Hoeppli phenomenon in healthy humans is almost equivalent to them.^11,15 In a recent review, characteristic histopathology was diagnostic in 100 of 101 cases with GIB (99%), and culture was positive in only 34 of 53 patients (64.2%).² The Splendore-Hoeppli phenomenon has also been reported in botryomycosis caused by some bacteria.^16,17 Cases with Pythium insidiosum, a pathogenic oomycete (also known as water mold), may also trigger the Splendore-Hoeppli phenomenon in the involved tissues, including cutaneous, vascular, ocular, or gastrointestinal organs. In contrast to the Entomophthorales, P. insidiosum hyphae do not stain well in hematoxylin and eosin.¹⁸ People living in swamps in tropical and subtropical areas suitable for the life cycle of P. insidiosum are more likely to contact the pathogen.¹⁹ All patients with disseminated pythiosis reported in a large case series from Thailand had underlying hematological disorders. We believe P. insidiosum was not the etiological agent in our patient because of the lack of history of exposure to a swampy environment, no hematological disorders, and the detection of the well-stained fungal elements using hematoxylin–eosin staining. In line with other reports, aggressive, prolonged antifungal therapy combined with surgical resection was successful in treating our patient.

Based on this report, diagnosis of GIB should be considered in any previously healthy child living in tropical and subtropical areas who presents with intussusception and has other clinical and laboratory diagnostic clues such as prolonged abdominal pain and/or fever, hepatomegaly, abdominal mass, elevated ESR level, and peripheral blood eosinophilia.