LAS VEGAS — A mycologic mystery has been brewing in the desert Southwest of the United States.
During the past dozen years, there have been 16 cases of gastrointestinal infection with Basidiobolus ranarum, a filamentous fungus previously associated almost exclusively with skin and soft tissue infections in Africa and Southeast Asia, Dr. Jerry D. Smilack said. Fifteen of the 16 cases occurred in Arizona, and 1 occurred just across the state line in St. George, Utah.
B. ranarum is present throughout the world and was first isolated more than 100 years ago from frog and lizard intestines and other environmental sources such as decaying vegetable matter. The first human infections were reported in Indonesia during the 1950s.
Basidiobolus infection, which usually occurs in children after inoculation secondary to trauma, is typically characterized by a gradually enlarging subcutaneous mass or nodule that ultimately may ulcerate.
There have been anecdotal reports of treatment with saturated solution of potassium iodide, trimethoprim-sulfamethoxazole, and antifungal agents. Skin or soft tissue infection with this pathogen has not been reported in the United States, Dr. Smilack noted at a meeting on fungal infections sponsored by Imedex.
Prior to 1995, only six cases of gastrointestinal basidiobolomycosis had been reported in the literature: one in Florida, one in Nigeria, and four in Brazil. Only two of the affected patients survived.
Cases began appearing in Arizona during the late 1990s. Typical of them was a 79-year-old man seen by Dr. Smilack at the Mayo Clinic in Scottsdale, Ariz.
The patient had experienced 4–5 weeks of anorexia, left-sided abdominal pain, and diarrhea with a 35-lb weight loss, but he reported no fever, chills, nausea, or vomiting. He had been seen at another hospital, where the work-up showed narrowing of the descending colon and a possible inflammatory or neoplastic mass. Many years earlier, he had undergone sigmoid resection for diverticular disease; he was presumed to have recurrent diverticulitis and was given antibiotics but did not respond.
On physical examination, a palpable mass was discerned in the left upper quadrant, Dr. Smilack said. The patient's vital signs were normal, as were laboratory tests with the exception of a slight elevation in blood glucose; he had type II diabetes and was taking glyburide.
On plain film x-ray, gas bubbles were seen in the left upper quadrant, displacing the colon medially, and on CT, a considerable accumulation of inflammatory material was seen in the lumen of the colon as well as external to the colon.
The patient was taken for surgery, where a large inflammatory mass was found adherent to the small bowel, spleen, kidney, and lateral abdominal wall. A partial colon resection with end-to-end anastomosis was performed.
Histopathologic evaluation of the mass revealed marked inflammation and the Splendore-Hoeppli phenomenon, in which eosinophils are deposited around the fungus. “The histopathologic appearance is virtually diagnostic,” Dr. Smilack said.
The main clinical features reported with gastrointestinal Basidiobolus infection are abdominal pain and weight loss; fever is unusual. The infection was formerly thought to be limited to the sigmoid colon, but multiple extraintestinal sites of involvement have now been reported, including the liver, stomach, and mesentery. There have been five cases of disseminated infection as well.
All the Arizona patients have been treated with surgery and itraconazole, and all have survived, Dr. Smilack said. In vitro susceptibility data suggest that ketoconazole is active against this fungus, but that fluconazole and flucytosine are inactive.
The diagnosis should be suspected in a patient who has abdominal pain, possibly with a palpable mass, especially if there is radiographic evidence of bowel wall thickening, he said. This pathogen is found in the bowel wall itself, rather than in the mucosa, so a full-thickness histopathologic examination of the bowel wall is needed. Cultures also should be done if possible. In at least two-thirds of the cases, peripheral eosinophilia also has been present, Dr. Smilack said.
Important questions about this cluster of infections remain unanswered. “The mystery is why does this infection occur? Why in Arizona? Why, in the United States, is it only a gastrointestinal infection? What is the source—something in food or water? We assume it is something ingested, but other than that, I wish I knew,” he said.
A case-control study performed by the Centers for Disease Control and Prevention sought to identify potential host and risk factors, and there was some suggestion that prior use of ranitidine was a possible risk factor (MMWR 1999;48[32]:710–3). “I personally don't think it is a risk factor. We just don't know,” he said.