1. Introduction

Basidiobolomycosis is a rare, uncommon, and invasive fungal disease associated with high mortality. It is distributed worldwide, but tropical areas are the most commonly involved such as Africa, the USA, and Southeast Asia. Unlike other fungal infections, it affects immunocompetent patients. Many reported cases were from Saudi Arabia, mainly found in the southern region. Most cases were under 20 years of age [1]. One member of the Zygomycetes family, Basidiobolus ranarum, is the causative agent of basidiobolomycosisIt is found in animals such as fish, frogs, bats, and reptiles [2]. Basidiobolus ranarum has a four-day incubation period [3]. It is a member of the phylum Entomophthoromycota, which also contains one of the largest groups of early-diverging terrestrial fungi that were previously categorized in the phylum Zygomycota [4]. Basidiobolomycosis is typically a subcutaneous infection that primarily affects young, male individuals and is spread by traumatic inoculation. It affects the gastrointestinal tract as well. The transmission of this organism to humans is not well understood, and there are three major routes of infection: skin penetration after injury to an infected source, ingestion of contaminated food, and inhalation of an infected agent. The first reported case was in 1956 in Indonesia, when the patient presented with a subcutaneous basidiobolomycosis infection [5]. Gastrointestinal basidiobolomycosis (GIB) is considered the most common presentation in tropical and subtropical areas.

Diagnosis of basidiobolomycosis is challenging because the clinical signs do not lead directly to fungal infection and due to nonspecific presentation of the disease and similarity with some malignant cases as well as inflammatory bowel disease (IBD) [6], which necessitate a high index of suspicion to reach the diagnosis. The most commonly affected abdominal organs are the colon (84%), the small intestine (32%), the liver (21%), and rarely other organs such as the stomach [7].

To confirm the disease, diagnostic workup is needed, such as radiological examinations and histological findings of a positive culture of Basidiobolus ranarum, which is considered the pathognomonic feature. This is one of the reported case series of GIB, including adult and pediatric, from Saudi Arabia. There has been one case series study aimed at describing five pediatric patients with basidiobolomycosis. In this case series study, we are describing the different clinical characteristics of the fifteen patients as well as the therapeutic plan and the outcome.

2. Method

This retrospective case series study was carried out at King Fahad Armed Forces Hospital (KFAFH) and King Abdulaziz Hospital and Oncology Center (KAHOC), both tertiary hospitals in Saudi Arabia. We used the microbiological and histopathological databases to identify basidiobolomycosis species from January 2010 to February 2023. The information of adult and pediatric patients who were diagnosed with basidiobolomycosis was collected. Our patients came from different cities in Saudi Arabia such as Jeddah, Al-Qunfudhah, and Abha, which are located at western and southern areas of Saudi Arabia (Tables 1 and 2). It is noticeable that fifteen patients’ records were collected, reviewed, and evaluated, and it was found that they had received empirical antibiotics initially until clinical workup and diagnosis became available. The empirical antimicrobial treatments administered ranged from a combination of ceftriaxone and metronidazole to a carbapenem (Table 3). The most commonly used antifungals for adjusted therapy were voriconazole and itraconazole. Voriconazole was used in the vast majority of our patients, and it was obtained in adults as 6 mg/kg intravenously twice daily on the first day, followed by 4 mg/kg twice daily as long as the patient had normal kidney function, then switched to an oral regimen of 400 mg twice daily on the first day, followed by 200 mg twice daily if the patient tolerated it. The recommended voriconazole dose administered to pediatric patients (cases 11, 12, and 13) was according to the body weight, and it was given as an intravenous loading dose of 9 mg/kg, followed by maintenance doses of 8 mg/kg according to kidney function, or as an oral dose of 9 mg/kg if tolerated. In cases 8 and 15, the patients developed hallucinations and visual disturbance on Day 3 of the voriconazole treatment, so the dose was reduced to 100 mg twice daily, but still the symptoms persisted, so the treatment was changed to oral itraconazole. Itraconazole was used in five adult patients, and it was given as an oral dose of 200 mg twice daily, as seen in cases 3, 4, 5, 7, and 15. One pediatric patient with orbital manifestation developed allergic fungal sinusitis and lacrimal duct obstruction, which was initially treated with empirical liposomal amphotericin. The antifungal was then changed to oral voriconazole and continued for three years. The duration of therapy was planned according to patients’ clinical response toward the treatment, which includes the disappearance of clinical and radiological symptoms associated with the infection.

3. Results

3.3. Radiology Findings

The diagnostic workup used in the investigation differed. Abdominal ultrasound (US), computed tomography (CT) scan, magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), and percutaneous transhepatic cholangiography (PTC) were required according to the clinical presentation. A CT scan was the main diagnostic tool in fourteen patients. It confirmed the site of organ involvement and the extent of disease infiltration. A CT-guided tissue biopsy (core needle biopsy) was also essential for diagnosis in those cases that failed to obtain an adequate tissue biopsy through colonoscopy. The common finding seen in an abdominal CT scan was the presence of colonic intraluminal fungating mass with severe thickening of the bowel wall and luminal narrowing, as well as local infiltration to adjacent organs, associated with diffuse mesenteric fat stranding and engorged vessels. These findings in the CT scan make the differentiation between basidiobolomycosis and malignancy so challenging (Figure 1). One patient (case no. 14) presented with obstructive jaundice and required further investigation by MRCP and endoscopic retrograde cholangiopancreatography (ERCP). ERCP was repeated twice but failed to intubate the ampulla of Vater due to severe outside compression, so PTC was the only way to drain the biliary system through an external and internal drain.

3.4. Colonoscopy Findings

Colonoscopy was done for nine cases who presented with gastrointestinal involvement. It showed severely inflamed mucosa with extensive widespread cobblestone-like lesions easily bleeding on touch with intraluminal narrowing mimicking IBD and/or malignancy (Figure 2, case no. 2). The biopsies were taken and were positive for basidiobolomycosis in four cases only.

3.5. Histopathology Findings

A tissue biopsy to confirm the diagnosis was obtained through either colonoscopy, interventional radiology (IR) using CT or US guidance, or surgical intervention. Nine patients underwent colonoscopy, and the biopsy was positive in only four cases. IR-guided biopsy confirmed the diagnosis in six cases; one case had CT-guided, while five had US-guided tissue biopsy (cases 1, 3, 10, 11, and 13). US-guided aspiration has been used in one patient, and it was not helpful because it failed to get enough fluid (case no. 7). Two patients had laparoscopic exploration with omental nodule excision (case no. 5) and lymph node biopsy (case no. 8), where the diagnosis was confirmed. Histopathology confirmed the diagnosis for the patient who underwent surgical resection, as shown in eight cases (cases 2, 4, 6, 7, 9, 12, 13, and 15). Figures 3(a), 3(b), and 3(c) show the gross appearance of the resected specimen in case no. 2 who had extended right hemicolectomy. The specimen showed a large fungating mass adherent to the surrounding tissue, with fat infiltrating mimicking adenocarcinoma. The cut surface of the specimen showed a cobblestone appearance mimicking Crohn’s disease (Table 2).

The microscopic examination of the specimen showed the fungal elements, which often appear as blank spaces, surrounded by a highly pigmented eosinophil. There was an abundant eosinophilic-rich transmutable inflammation admixed with neutrophils and a chronic granulomatous reaction with giant cells. The enormous cells, which are encircled by brilliantly eosinophilic amorphous detritus in a starburst pattern known as the “Splendore–Hoeppli phenomenon,” exhibit a broad, pauci-septate fungal hyphae. The fungal organism tests positive for Grocott methenamine silver (GMS) and periodic acid–Schiff (PAS) (Figures 4(a), 4(b), 4(c), and 4(d)).

4. Treatment Course and Outcome

All fifteen patients were treated either by surgical resection followed by antifungal therapy or by antifungal treatment alone. Ten cases (66.6%) underwent surgical intervention, and two (13.3%) had laparoscopic exploration and tissue biopsy only, while eight cases (53.3%) required surgical exploration and radical resection because of their acute presentation (Appendix 1) (cases 2, 4, 6, 7, 9, 12, 13 and 15). Four patients (26.6%) underwent right hemicolectomy; one patient had left hemicolectomy with limited ileocecal resection and anastomosis (case no. 6); one patient (6.6%) had subtotal colectomy with end ileostomy (case no. 15); one patient (6.6%) had transverse colectomy and enterocutaneous fistula excision (case no. 13); and the pediatric patient with orbital involvement had maxillectomy and orbital decompression (case no. 12) (Table 2). Ten patients (66.6%) showed good clinical response, and they finished their treatment course; only one case showed mild improvement and is still under treatment and follow-up.

Death has been reported in four cases (26.6%), three of them underwent surgery followed by itraconazole therapy, and one case was treated with voriconazole alone without surgery (Appendix 1) (cases 4, 5, 7, and 9). In case no. 4, the exact cause of death was uncertain, but we suspected that major cardiomyopathy and pulmonary hypertension were the probable cause of death. In case no. 5, the patient was started on itraconazole after laparoscopic exploration and omental nodule excisional biopsy. She was seen in the first visit after two months and showed a good clinical response, but she lost her follow-up. After calling the family, we have been informed that she died after six months from the diagnosis with no clear answer about the cause of her death. In case no. 7 (Appendix 1), the patient underwent extensive prolonged surgical procedure that included right hemicolectomy, rectosigmoid resection with end colostomy, debridement associated necrosectomy of abdominal wall, and urinary bladder repair with ureteric repair. Due to his critical condition, the patient was admitted to the critical care unit, where he passed away on the second day following surgery. In case no. 9 (Appendix 1), the patient underwent exploration laparotomy with partial gastrectomy and extended right hemicolectomy with ileocolic anastomosis. The patient did well and was discharged home after clinical improvement. Ten days from discharge, he reported to the emergency room complaining of a cough and fever with a wound infection; COVID-19 swap was positive; he was admitted to the intensive care unit (ICU), intubated, and ventilated; he developed respiratory failure and died with a COVID-19-related complication (Table 3).

5. Discussion

Gastrointestinal infections have been reported to affect immunocompetent hosts [8]. The southern region of Saudi Arabia has reported the highest number of cases of B. ranarum infection, which grows more quickly in warm, humid climates like those found in the southern region of Saudi Arabia, Arizona, West Africa, and Indonesia [9]. Most of the recorded reports showed that the young male age group was the most affected by basidiobolomycosis [10]. Our current data revealed the same results in addition to pediatrics.

Nonspecific symptoms are seen in the presentation of GIB. Abdominal pain, constipation, abdominal mass, loss of appetite, nausea, vomiting, and diarrhea are among the most typical symptoms of GIB [2, 11]. The lack of specificity in the symptoms could cause a delay in diagnosis and raise the patient’s risk of morbidity [11]. While the primary diagnostic method at the moment is the histopathological analysis of biopsy specimens, there are additional methods as well; these include molecular methods, fungal cultures, and serological testing, which, when available, can definitively determine the diagnosis [12]. Histopathology may reveal a dense eosinophilic reaction encircling thin-walled, irregularly branching hyphae with sporadic septate (Splendore–Hoeppli phenomenon) as seen in our cases (Appendix 1) [13, 14].

Eosinophilia in the peripheral blood can be a helpful adjunct to diagnosis [15]. The majority of study patients had elevated WBC counts, eosinophils, and CRP and low hemoglobin. The radiological examination varies according to the affected organ. CT is the most common radiological method used in investigation. The most common radiological findings are colonic masses, liver lesions, and involvement of the small intestine; less commonly affected are the gallbladder, kidneys, pancreas, and retroperitoneum [2]. Life-threatening consequences such as gastrointestinal perforation, intra-abdominal collections, obstruction, esophageal varices, duodenal-biliary fistula, and nephritis have been reported [16]. Bowel obstruction is the most common complication in most of our cases.

The treatment of choice for basidiobolomycosis remains a matter of debate [2]. The previously preferred treatment was the combination of surgical excision of affected organs followed by long-acting antifungal medication [17]. Vikram et al. showed that itraconazole and voriconazole were the most efficient therapies in most cases, and for those with obstructive symptoms or perforation, surgical intervention is indicated. Nevertheless, there has been a recent shift toward treating the patient with antifungal drugs alone, particularly with antifungals from the azole group [7]. Patients who had pre-existing risk factors like cardiac diseases were likely more susceptible to itraconazole’s harmful side effects on the heart since it was reported to produce impairment in cardiac function [18]. In any case, whether surgery is performed or not, a long-term antifungal treatment is recommended [13]. Without surgery, medical treatment for six to twelve months has been demonstrated to have positive effects in both adults and pediatric patients [2]. Thus, depending on the patient’s critical condition and response to medication, surgery may not be necessary [2]. In this series, the shortest period of antifungal therapy was 6 months, while the longest course was 26 months (the third patient) (Table 3). Since there is no prior local experience with the disease and it is uncommon, different medications were chosen with no clear indication of which was superior to the other. However, in any case, regular follow-up with periodic liver and renal functions is required, as was done in this series. Therefore, surgery may be avoided, depending on the patient’s critical condition and response to medications [2]. In our case series, azole-based antifungal demonstrated a beneficial effect in treating basidiobolomycosis with a low risk of complications. Surgical intervention was required in eight patients due to their acute critical presentation followed by antifungal treatment with a good response. GIB is considered a life-threatening condition if a delay in management occurs. Hence, high index of suspicion such as abdominal masses with early diagnosis, aggressive medical therapy, and surgical resection are considered the critical components of management. A mortality rate of 16% had been reported if not managed properly [11]. Pandit et al. reported that patients who undergo surgical resection without antifungal treatment have a high mortality rate [19]. In our case series, the mortality rate related to basidiobolomycosis was one out of fifteen.

6. Conclusion

In this report, we introduced the fifteen cases of basidiobolomycosis as a rare, invasive, and life-threatening disease that affects immunocompetent patients. A prompt and accurate diagnosis is needed to avoid fatal complications. Since its diagnosis is difficult, the presence of an abdominal mass associated with high eosinophilia should raise suspicion of GIB. Long-term azole antifungal therapy was effective in curing this illness and had shown to be a component of the treatment; nevertheless, in certain conditions, surgery is still required in conjunction with other treatments.

Ethics Statement

There is no identifiable information on the patients.

Consent

The data for the patients were obtained from the hospital’s electronic system.

Conflicts of Interest

The authors declare no conflicts of interest.

Funding

No financial funding was received for this work.

Supporting Information

Appendix 1 contains detailed documentation of fifteen medical conditions that form part of a comprehensive case series. Each case provides insights into specific clinical presentations, treatment approaches, and outcomes, contributing to a broader understanding of the conditions being studied. This appendix serves as a good resource for clinicians and researchers, offering a rich dataset for treatment efficacy and patient outcomes in the specific clinical context addressed in the case series.