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Editor: Farah Zahra Updated: 1/29/2024 12:18:36 AM


Entomophthoromycosis is a group of rare subcutaneous and mucocutaneous fungal infections predominant in tropical and subtropical areas. Entomon in Greek means "insect," reflecting the initial recognition of these fungi as parasites infecting insects. This gradually advancing infection commonly arises from the traumatic implantation of plant material or the inhalation of spores. The 2 distinct types of entomophthoromycosis include basidiobolomycosis and conidobolomycosis. Soil, insect, reptile, and amphibian excreta harbor Basidiobolus and Conidiobolus.

Conidobolomycosis, most commonly caused by Conidiobolus coronatus, is usually a chronic rhinofacial subcutaneous infection that originates in the nasal sinuses and subsequently spreads to the subcutaneous tissues of the face. Infection can lead to disfigurement, primarily affecting immunocompetent hosts.[1][2] Some Conidiobolus spp are found in immunocompromised hosts. Basidiobolomycosis is a chronic subcutaneous infection caused by Basidiobolus ranarum, which affects the limbs, trunk, buttocks, and gastrointestinal system.[1][2] The symptoms of gastrointestinal basidiobolomycosis (GIB) closely resemble those of more common illnesses, such as malignancy and inflammatory bowel disease, thereby challenging accurate diagnosis. Basidiobolomycosis affects both immunocompetent and immunocompromised patients.

With early treatment, the prognosis is favorable. However, in untreated cases or patients with compromised immune systems or systemic illness, disfigurement and death may occur. Accurate diagnosis necessitates a high index of suspicion. The gold standard for diagnosis involves a wet mount, cultures, and molecular methodologies using DNA probes and polymerase chain reaction (PCR). Advanced imaging using magnetic resonance imaging (MRI) or computed tomography (CT) may be necessary in some cases. Histologically, the Splendore-Hoeppli phenomenon may be apparent. Although typical antifungals are the standard treatment, the fungi display resistance, requiring prolonged combination therapy. Surgical debridement and reconstruction may also be essential.[3][4][5] Healthcare professionals should consider entomophthoromycosis in patients with classic symptoms, especially those who lived in or traveled to tropical or subtropical climates, due to its potential for disfigurement and mortality.


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Entomophthoromycosis is a group of infections caused by members of the order Entomophthorales, which comprises 6 families— Ancylistaceae, Basidiobolaceae, Completoriaceae, Entomopthoraceae, Meristacraceae, and Neozygitaceae. Within the Basidiobolaceae family, there is 1 genus with 4 species, and the most common species is B ranarum, commonly found on the skin or dung of frogs. Various species of Conididobolus from the family Ancylistaceae are saprobes found in soil. Notably, C coronatus and B ranarum are the primary species associated with medical cases of entomophthoromycosis.[3][4]

Certain Conidiobolus spp reproduce within their host insects and destroy them as hyphae disperse, thereby becoming airborne. Following the invasion of the insect's abdomen, a systemic infection ensues. Upon the insect's death, sporophores develop between the individual segments of the abdomen, generating a new generation of spores. Basidiobolus spp inhabit the gastrointestinal tract of amphibians and reptiles.


Entomophthoromycosis exhibits a high prevalence in tropical and subtropical regions. Basidiobolus spp are endemic in various countries, including India, Pakistan, Uganda, Kenya, the Ivory Coast, Myanmar, Ghana, and South America.[6] In addition, cases have been identified in the southeastern United States, particularly in Arizona.[7] This condition predominantly affects 80% of patients younger than 20, with a 3:1 male-to-female ratio.[4]

Conidiobolus spp lives in soil and decaying plant material, mainly in high-humidity areas, such as the beaches of the United Kingdom, the eastern coast of the United States, India, and the western region of Africa. Most cases of conidiobolomycosis are in the African continent, mainly Nigeria. The male-to-female ratio is 10:1, and the disease is predominantly seen in young adults.[3][4]


The fungi are unable to penetrate the intact skin of the human host. A traumatic wound on the skin or mucosa serves as a site of attachment for the conidia and facilitates the formation of a germ tube to penetrate with the help of lipolytic and proteolytic enzymes. Although the host's immune system cannot completely neutralize the fungus, it generally restrains the hyphae to the subcutaneous tissue. As a result, the fungi can remain in subcutaneous tissues as chronic granulomas for extended periods, lasting for years.

Entomopthorales thrive in fatty substances, displaying a predilection for areas with adipose tissue. Basidiobolomycosis is most likely to propagate through the traumatic implantation of the fungus into the subcutaneous tissues of the thighs, buttocks, or trunk. In contrast, conidiobolomycosis is transmitted by inhaling fungal spores, affecting the nasal tissue, paranasal sinuses, and facial soft tissues. These fungi release chemical compounds that degrade substances such as cellulose—a feature uncommon among most fungi. The invading hyphae trigger the migration of numerous inflammatory cells, including numerous eosinophils, cytotoxic lymphocytes, giant cells, mast cells, mononuclear macrophages, natural killer cells, plasma cells, and a few neutrophils, to the infection site, resulting in a chronic granulomatous reaction.[3][5]

Infections Caused by B ranarum 

  • Infections are common in decaying vegetation, soil, and the intestinal contents of various insectivorous reptiles, amphibians, and mammals. 
  • This fungal species penetrates the skin through insect bites, scratches, and minor cuts.
  • This condition is most commonly observed in young children and particularly involves the thigh and buttock areas.
  • Affected patients rarely report a history of previous trauma.

Infections Caused by Conidiobolus Spp

  • Infection occurs through percutaneous or submucosal inoculation of soil-borne spores, typically resulting from minor trauma, insect bites, or the inhalation or ingestion of spores.
  • Only 3 species are indicated in human infection—C coronatusC incongruus, and C lamprauges.


Entomophthoramycotina are distinguished from other fungi by their characteristic hyphal morphology. The hyphae exhibit a broad, thin-walled, ribbon-like structure, predominantly aseptate, and display right or wide-angle branching. Characteristic findings in infected tissues include extensive fibrosis and an inflammatory response that gives rise to eosinophilic granulomas, along with the Splendore-Hoeppli phenomenon.

The Splendore-Hoeppli phenomenon involves inert material, such as fungi, surrounded by radiating eosinophilic material. This results in a star-like or asteroid configuration due to the deposition of antigen-antibody complexes and debris from host inflammatory cells on hematoxylin and eosin–stained sections. This finding may be absent in immunocompromised patients. The Splendore-Hoeppli phenomenon is not pathognomic of entomophthoromycosis, as it may be seen in other infections such as sporotrichosis, blastomycosis, and schistosomiasis. Histologically, no evidence of angioinvasion, necrosis, or tissue infarction exists.[4][5] 

History and Physical


Conidiobolomycosis typically manifests with symptoms such as nasal drainage, obstruction, and paranasal sinus pain. This condition generally remains confined to the rhinofacial area, and affected patients often delay medical care until they experience significant swelling of the upper lip or face. The swelling is typically firm and painless, gradually extending into the nasal bridge, upper and lower face, and orbit. Notably, angioinvasion is absent, and intracranial extension is uncommon. Case reports of invasive forms of the disease in immunocompromised hosts exist, where the organism acts as an opportunistic pathogen, leading to complications such as endocarditis and fatal dissemination.[4][8][9]

C coronatus: The characteristics of this fungal species are mentioned below. 

  • This fungal species primarily infects the subcutaneous tissues of the face, leading to predominantly bilateral symptoms. 
  • In the early stages, the disease exhibits symptoms such as rhinitis, intermittent epistaxis, sinus pain, and painless swelling around the nose.
  • Intermediate disease, occurring after about 1 month, presents with coryza, epistaxis, nasal obstruction, redness, nasal and nearby tissue swelling, and enlarged lymph nodes.
  • If left untreated, the progression may result in extreme facial deformity and facial elephantiasis. 

C incongruus: The characteristics of this fungal species are mentioned below. 

  • This fungal species affects healthy and immunocompromised hosts, with a higher likelihood of being associated with systemic infections.
  • The infection typically initiates with mild swelling at the site of infection.

C lamprauges: The characteristics of this fungal species are mentioned below. 

  • This fungal species exhibits a tendency to grow toward blood vessels.
  • Notably, the condition does not display the Splendore-Hoeppli phenomenon


Basidiobolomycosis is a chronic subcutaneous infection caused by B ranarum, which is the most prevalent species affecting young children. This infection affects the limbs, trunk, buttocks, and gastrointestinal system of the host.

B ranarum: The characteristics of this fungal species are mentioned below. 

  • Disc-shaped, rubbery, mobile, nodular lesions on the buttocks, thighs, and limbs of the affected individuals are the characteristics of basidiobolomycosis.
  • Although the condition is typically painless, the overlying skin exhibits erythema and warmth, accompanied by nonpitting edema of the involved area.
  • In some cases, there may be skin ulcerations and local lymphadenopathy.
  • Lesions evolve over months to years.

GIB presents with diarrhea containing blood and mucous, epigastric abdominal pain, intermittent low fever, intestinal bleeding, vomiting, and the development of tumor-like masses involving the stomach and intestinal tissues. These symptoms can mimic those of colon cancer and inflammatory bowel disease. In tropical and subtropical regions, GIB should be considered a possibility for patients with a gastrointestinal mass exhibiting subacute onset of abdominal pain, weight loss, and fever, as well as eosinophilia in their lab results.[7][10][11][12]


Clinicians and histopathologists need a high index of suspicion for the diagnosis. A comprehensive examination aids in localizing the extent of the lesion. A definitive diagnosis relies on demonstrating fungal elements and diagnostic culture findings. Leukocytosis with eosinophilia can be present.[13] The preferred diagnostic approach involves obtaining a biopsy specimen from an advancing edge of a lesion to reveal fungal elements on potassium hydroxide preparations and fungal cultures. The gold standard approach utilizes histological examinations and mycological cultures. A fluorescent dye wet mount preparation with fluorescent microscopy is used to increase the sensitivity of diagnosis.

Inoculation of culture specimens should be performed soon after specimen collection and transported at 4 °C.[14] Suitable culture media include Sabouraud dextrose agar, potato dextrose agar, or cornmeal agar. Colonies exhibit dense, radially furrowed, and waxy appearance, with rapid growth at 37 °C. The propulsion of conidia is noticeable as they adhere to the petri dish lid, clouding the view. Culture also helps in determining the susceptibility of antifungal agents. Often, culture results turn out negative due to potential damage to hyphae during tissue processing. In cases where cultures yield negative results, molecular identification can be used through DNA probes, fungal primers, and PCR to confirm diagnosis. This can be done using either freshly frozen or paraffin-embedded tissue.[4]

Imaging with CT or MRI should be performed for additional evaluation to assess the extent of infection, monitor therapeutic response, and plan the precise site of specimen collection. In cases where gastrointestinal disease is suspected, a colonoscopy enables visualization of the lesions and facilitates the collection of biopsies.[3] Potential findings on CT and MRI are tissue thickening, infiltrates, or tumor-like masses. In C coronatus infection, infiltration of the maxillary sinus, tumor-like masses, and opacities are observed frequently. In cases of GIB, thickening of the intestine and the presence of tumor-like masses in the colon and rectum are expected. Patients with disseminated infection may exhibit masses in the liver, gallbladder, pancreas, and kidney. 

Treatment / Management

Treatment involves medical management with prolonged antifungal therapy and consideration of surgery. Potential treatments include potassium iodide (KI), cotrimoxazole, amphotericin B, imidazoles, and hyperbaric oxygen, each with varying success rates. The standard treatment typically involves KI and triazoles, particularly itraconazole. Due to relative resistance to antifungals, higher doses than standard are necessary for adequate treatment, and prolonged daily therapy spanning several months is recommended.[15] Monotherapy is typically not successful. Interestingly, in vitro studies indicate that entomophthoralean fungi display resistance to KI. Researchers suspect that KI works in vivo through fungal cell wall degeneration and the activation of an immunological response. (B3)

Surgery alone has a limited role due to the high risk of recurrence. Therefore, surgery and antifungal therapy are recommended for treating entomophthoromycosis. Early-stage surgery for nasofacial conidiobolomycosis can help minimize severe cosmetic damage. Facial reconstructive surgery may be necessary in advanced stages due to persistent extensive fibrosis, even after eradicating the fungus. Antifungal treatment and surgical excision contribute to the improvement of nasal symptoms and central facial swelling. Cryotherapy shows limited success. In GIB, resection of the affected bowel followed by prolonged antifungal therapy is crucial.[16]

Hyperbaric oxygen increases the fungicidal activity of neutrophils, reduces the formation of reactive oxygen species, and causes vasodilation, thereby increasing perfusion to affected tissues. Although hyperbaric oxygen may aid in the healing process, additional studies are required for a comprehensive understanding.[17][4](B2)

Differential Diagnosis

Differential Diagnosis for Basidiobolomycosis

Conditions to consider in the differential diagnosis include tuberculosis, localized elephantiasis, onchocerciasis, scleroderma, Burkitt lymphoma, and granulomatosis with polyangiitis.[4]

Differential Diagnosis for Gastrointestinal Basidiobolomycosis

Conditions to consider in the differential diagnosis include gastrointestinal tumors and colon cancer, chronic granulomatous diseases such as Crohn disease, tuberculosis, and schistosomiasis, as well as lymphoma and rhabdomyosarcoma.[4]

Differential Diagnosis for Conidiobolomycosis

Conditions to consider in the differential diagnosis include mucormycosis, cellulitis, rhinoscleroma, lymphoma, and sarcoma.[4]


Entomophthoromycosis is a slowly progressive disease, and although the primary concerns may be cosmetic, it can become life-threatening if disseminated or involves the gastrointestinal system. Typically, patients with early or intermediate disease respond well to combination therapies. However, individuals affected by late or atypical disease, elephantiasis, or those with an absence of the Splendore-Hoeppli phenomenon may experience worse outcomes and increased mortality.[3][18]


Cosmetic injury occurs due to progressive disfigurement caused by intractable fibrosis and scarring. The fibrosis and scarring can lead to lymphatic obstruction and lymphedema, causing additional disfigurement with the loss of function in the affected area. Facial elephantiasis may complicate persistent or progressive rhinofacial conidiobolomycosis due to obstruction of lymphatic vessels.[3] In GIB cases, inflammatory obstruction may occur, and death may result from disseminated disease. Misdiagnosis may contribute to a delay in proper treatment, leading to increased morbidity and mortality.[10][4]

Deterrence and Patient Education

Entomophthoromycosis is a group of rare subcutaneous and mucocutaneous fungal infections predominantly affecting the skin of the buttocks, thighs, and trunk, as well as the gastrointestinal tract, sinuses, and facial tissues. These fungi, present in soil and the droppings of insects, reptiles, and amphibians, typically cause infections when individuals inhale spores through their noses or undergo inoculation via an insect bite or thorn prick. 

Initial symptoms of rhinofacial disease are redness or swelling at the infection site, followed by rhinitis, intermittent nose bleeds, sinus pain, and painless swelling around the nose. Patients develop nasal obstruction, increased swelling, and facial deformities without treatment. Patients affected by other cutaneous forms develop painless, disc-shaped, rubbery, mobile, nodular lesions on the buttocks, thighs, and limbs. As these lesions progress, they may ulcerate, and significant nonpitting edema may develop around the area. Gastrointestinal infection often mimics other gastrointestinal disorders, such as inflammatory bowel disease and colon cancer, making the diagnosis challenging.

Entomophthoromycosis typically exhibits a favorable response to treatment when addressed in the early stages using combination therapy. Medication compliance is crucial, as prolonged treatment is required. Sometimes, 2 medications or a combination of medication and surgery may be indicated.[18] Noncompliance can be a potential cause of poor outcomes. 

Enhancing Healthcare Team Outcomes

As entomophthoromycosis is a rare infection, it requires a high index of suspicion. Given the increased frequency of global travel, healthcare professionals must consider this unique condition. This involves broadening their understanding of the etiology, presentation, diagnosis, and management of entomophthoromycosis. Early treatment correlates with a favorable prognosis. Clinicians should contemplate entomophthoromycosis in patients who have traveled to or resided in tropical or subtropical climates, particularly if they present with characteristic cutaneous findings or new-onset gastrointestinal symptoms and eosinophilia.

To provide the best possible care to patients, it is crucial to have a healthcare team that works together effectively and efficiently. This requires coordination and collaboration among all the healthcare professionals involved in a patient's care, including physicians, nurses, therapists, pharmacists, and other support staff. Collaborating with the laboratory technician and histopathologist is crucial to ensure accurate specimen collection and testing. Engaging in discussions about the patient's symptoms and the potential differential diagnosis is essential to assist the radiologist in interpreting any ordered imaging studies. As various surgical specialties may be involved in reconstructing or removing infected tissues, a gastroenterologist may be necessary if a patient develops gastrointestinal disease. In addition, pharmacists are crucial in managing drug interactions and ensuring patient compliance. Although each specialty contributes its expertise, effective communication within the healthcare team is paramount to guarantee that the affected patient receives optimal care, thereby reducing morbidity and mortality.



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