Conidiobolomycosis
Also known as: Rhinoentomophthoromycosis, Conidiobolus Infection
Conidiobolomycosis is a chronic, locally destructive infection of the nasal mucosa and facial subcutaneous tissue caused by Conidiobolus coronatus, in the order Entomophthorales. The characteristic syndrome is chronic rhinofacial disease in an otherwise healthy adult, with painless, woody swelling of the nose, upper lip and cheeks. Invasive, angioinvasive and disseminated disease is uncommon and occurs in immunocompromised hosts, mostly with Conidiobolus incongruus.
Epidemiology:
- Humid tropical rain forest regions of West and Central Africa (Nigeria, Ivory Coast, Cameroon, Uganda), India, Southeast Asia, and Latin America. Imported cases are rare.
- Adult men aged 20 to 40, working in forests and farms, are the main group.
- Sheep, horses and other animals are also infected.
| Species | Association |
|---|---|
| Conidiobolus coronatus | Commonest agent of chronic rhinofacial disease |
| Conidiobolus incongruus | Invasive and disseminated disease in immunocompromised patients; also rhinofacial disease |
| Conidiobolus lamprauges | Rare cause of subcutaneous disease and animal infection |
| Feature | Finding |
|---|---|
| Tissue form | Broad, sparsely septate hyphae, 6 to 25 micrometres wide, with irregular branching, surrounded by an eosinophilic sleeve of Splendore Hoeppli material |
| Staining | Haematoxylin and eosin shows the hyphae and sleeve; Grocott methenamine silver and periodic acid Schiff may stain poorly |
| Growth | Rapid on Sabouraud dextrose agar at 25 to 30 degrees Celsius, with growth often visible within 1 to 3 days |
| Colony | Flat, waxy to powdery, cream to tan, folded, with satellite colonies; forcibly discharged conidia coat the lid |
| Microscopy of culture | Globose primary conidia, 20 to 40 micrometres, with a prominent papilla, and in Conidiobolus coronatus a characteristic villose (hairy) surface; secondary conidia (microconidia) form from the primary conidia; thick walled zygospores |
| Cycloheximide | Inhibits growth |
The cell wall is chitin and chitosan rich, with little beta glucan. Echinocandins are inactive, and the beta D glucan assay is usually negative.
The fungus lives in soil, decaying vegetation and leaf litter, and in the gut of insects and some animals. Infection is believed to follow inhalation of spores into the nose, or traumatic inoculation of the nasal mucosa or facial skin, with insect bites implicated. Person to person transmission does not occur.
Spores germinate on the nasal mucosa, usually at the inferior turbinate, and hyphae grow into the submucosa and then subcutaneous tissue of the nose, lip and cheek. The reaction is chronic and granulomatous, with eosinophils, giant cells, fibrosis and Splendore Hoeppli material. Spread is by contiguity, with limited involvement of bone and brain. Lymphatic and haematogenous spread are uncommon.
Invasive disease in immunocompromised hosts differs. Conidiobolus incongruus and related species invade blood vessels, cause thrombosis and necrosis, and spread to the lung, sinuses, brain and other organs, resembling mucormycosis. Risk factors are neutropenia, transplantation, corticosteroids and haematological malignancy.
Chronic rhinofacial disease:
- Unilateral nasal obstruction, watery or mucoid rhinorrhoea, sneezing and sometimes epistaxis, with a submucosal nodule or swelling of the inferior turbinate.
- Painless, hard, "woody" swelling then spreads from the nose to the upper lip, cheek, forehead and periorbital area, and sometimes to the pharynx, with progressive facial deformity (the hippopotamus nose appearance).
- The skin is intact, shiny and sometimes erythematous, and it is fixed to the underlying mass. Ulceration, sinus formation and pus are unusual.
- Pain is minimal. Fever and systemic upset are absent.
- Regional nodes are not usually enlarged. Bone destruction, orbital invasion and cerebral spread are rare and mostly follow long delay.
- Untreated disease runs a chronic, slowly progressive course over months to years, with disfigurement and, rarely, airway compromise.
Invasive disease in immunocompromised hosts: fever, pneumonia with nodules or cavities, sinusitis, vascular thrombosis, and disseminated infection, with a high mortality.
| Feature | Conidiobolomycosis | Basidiobolomycosis |
|---|---|---|
| Organism | Conidiobolus coronatus | Basidiobolus ranarum |
| Typical site | Nose, face, paranasal tissue | Trunk, buttocks, limbs; gastrointestinal tract |
| Typical host | Adult men, rain forest workers | Children and young adults |
| Culture microscopy | Villose, papillate conidia | Zygospores with a beak like projection |
| Gastrointestinal disease | No | Yes |
| Angioinvasion | Rare in rhinofacial disease; frequent in immunocompromised hosts | Uncommon |
| Condition | Discriminating features |
|---|---|
| Rhinoscleroma (Klebsiella rhinoscleromatis) | Nasal induration with Mikulicz cells and Gram negative bacilli on biopsy |
| Rhinosporidiosis | Polypoid friable nasal mass with large sporangia containing endospores |
| Mucormycosis | Acute, necrotic, angioinvasive, in diabetes or immunocompromise |
| Nasal and sinus lymphoma (including NK/T cell lymphoma), carcinoma | Biopsy; destruction and ulceration |
| Granulomatosis with polyangiitis | Crusting, septal perforation, ANCA positive |
| Mucocutaneous leishmaniasis | Mucosal destruction, geography, amastigotes |
| Leprosy, tuberculosis, syphilis | Specific microbiology and serology |
| Allergic or inflammatory nasal polyps, angioedema | Soft, no hyphae, response to treatment |
| Burkitt lymphoma (facial) in African children | Rapid growth, jaw involvement, biopsy |
| Cellulitis and orbital cellulitis | Acute, painful, response to antibacterials |
- Specimen: deep biopsy of the nasal mucosa or facial mass. Swabs are inadequate. Tissue is minced and not ground.
- Histopathology: granulomatous inflammation with eosinophils and a broad, sparsely septate hyphal profile surrounded by an eosinophilic sleeve. A negative Grocott methenamine silver stain does not exclude the diagnosis.
- Culture: Sabouraud dextrose agar without cycloheximide at 30 degrees Celsius, held for 4 weeks. Growth is rapid, and villose, papillate primary conidia separate Conidiobolus from Basidiobolus.
- Molecular identification: sequencing of the internal transcribed spacer region.
- Serology: immunodiffusion in reference laboratories.
- Imaging: CT and MRI of the sinuses and face show soft tissue thickening of the nasal cavity and cheek, with bone remodelling or erosion in advanced disease. Orbital and intracranial extension is excluded by MRI.
- Immunocompromised patients: chest CT, blood tests for the underlying defect, and prompt biopsy of any necrotic lesion.
Evidence comes from case reports and small series, and response is variable. Treatment is prolonged, and relapse follows early cessation.
| Agent | Dose | Duration and comments |
|---|---|---|
| Itraconazole (first line) | Adults 200 to 400 mg orally daily; children 5 to 10 mg per kg daily, maximum 400 mg daily | 6 to 12 months, continued until clinical and imaging resolution and for several weeks to months afterwards; capsules with a full meal and an acidic drink; trough level where available |
| Voriconazole | Oral 400 mg every 12 hours for two doses, then 200 mg every 12 hours (adults 40 kg and above); trough 1 to 5.5 micrograms per mL | Alternative or salvage |
| Posaconazole | Delayed release tablets 300 mg every 12 hours on day 1, then 300 mg once daily; trough above 1 microgram per mL | Alternative or salvage |
| Isavuconazole | Isavuconazonium sulphate 372 mg (isavuconazole 200 mg) every 8 hours for six doses, then 372 mg once daily | Alternative or salvage |
| Co-trimoxazole | 960 mg orally twice daily | Several months; traditional agent where azoles are unavailable |
| Saturated solution of potassium iodide | 5 drops (0.25 mL) three times daily, increased by 1 drop per dose daily to the maximum tolerated, usually 40 to 50 drops three times daily | Several months; low cost; iodism and thyroid dysfunction |
| Liposomal amphotericin B | 5 mg per kg intravenously daily | Invasive, angioinvasive or disseminated disease, or failure of other agents |
| Echinocandins | Not used | Inactive |
Surgical measures:
- Surgical debulking or removal of infected tissue, combined with antifungal therapy, is used in extensive rhinofacial disease, but surgery alone has a high recurrence rate.
- Invasive disease in immunocompromised hosts needs urgent surgical debridement, reversal of immunosuppression and neutrophil recovery, with liposomal amphotericin B, followed by an oral azole.
Itraconazole needs liver tests at baseline, at 2 to 4 weeks and every 1 to 3 months, drug level checks and interaction review, and is avoided in heart failure and pregnancy.
There is no proven preventive measure beyond protective nasal and facial hygiene and avoidance of heavy exposure to decaying vegetation in immunocompromised patients. Chronic rhinofacial disease has a good prognosis when treated early. Late presentation leaves permanent facial deformity.
