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Rhizopus sps: Rhinocerebral zygomycosis

A 53-year old man with uncontrolled diabetes (keto-acidosis) who was admitted in the hospital developed retro-orbital pain, black eschar of nasal mucosa and palate, black nasal discharge, proptosis, high fever.On examination, the palates were blackened.

What is your diagnosis?
It is a case of rhinocerebral zygomycosis (craniofacial zygomycosis). Previously, it was called mucormycosis. Differential diagnosis include actinomycosis, aspergillosis, brain abscess, cryptococcosis, nocardiosis etc.

What is the specimen collected?
Nasal or sinus discharge is scraped or collected into a sterile container without exposing them to air. Biopsies may also be taken for histopathology.

Which the necessary investigations to be performed?
The discharge is subjected to a KOH mount. The specimen is subjected to staining for fungal elements as well as fungal culture. CT scans or MRI may be used to study the extent of invasion. Tissue sections are stained by Hematoxylin & Eosin, Grocott methenamine silver (GMS) stain or periodic acid-Schiff (PAS). The specimen is inoculated on Sabouraud's dextrose agar without cycloheximide and incubated at room temperature for 1-2 days. Sterile bread in a test tube may recover Zygomycetes when other media fail. An uninoculated tube of sterile bread is necessary for quality control.

What is your observation?
KOH mount revealed broad, aseptate hyphae branching at right angles. Tissue stains also revealed broad aseptate hyphae. Fungal hyphae may also be demonstrated using immunofluorescence. Swollen cells (up to 50 um) and distorted hyphae may be present.

Describe the culture findings.
The colonies, which are initially white, turn grayish-brown with a characteristic 'salt and pepper' appearance. A lacto-phenol tease mount preparation shows aseptate hyphae with rhizoides and sporangiophores arising opposite to rhizoides. The sporangiophores end in sporangia containing sporangiospores. The isolate is identified as Rhizopus arrhizus (Rhizopus oryzae). Isolation of fungus in most cases is not known to be highly successful. Since Rhizopus is a common contaminant, culture interpretations must always be made on clinical grounds.

Which are the various predisposing factors for this condition?
Organ transplant recipients, those with haematological malignancies, granulocytopenic and acidotic patients, bone marrow transplant recipients, persons with renal failure; persons on chelation therapy for iron or aluminium overload, patients on glucocorticoid therapy and those who had previous splenectomy also are at risk. Rare cases have been reported with HIV infection.

What is the pathogenesis of this condition?
Certain zygomycetes members (e.g., Rhizopus & Mucor) are ubiquitous, their spores are suspended in air. These cause opportunistic infections in people with certain predisposing conditions. Inhalation of air-borne spores results in infection of the susceptible person. While Rhizopus species are the agents most commonly isolated in this condition, other members such as Rhizomucor species, Absidia corymbifera, Apophysomyces elegans, Cunninghamella bertholletiae, Mucor species, and Saksenaea vasiformis may also produce infection. The keto-acidotic state and the resulting low pH as well as the presence of large amounts of glucose in a diabetic patient allows the fungus to proliferate. At low plasma pH the ability to transferrin to bind to iron also diminishes and Rhizopus can chelate the iron for its own growth. Their multiplication goes unchecked due to diminished function of phagocytes at low pH. Serum inhibitory activity is also diminished in such patients. Initially, the fungus infects nasal turbinates and paranasal sinuses and spread by direct extension to nose, eyes and bain and invades cranial nerves. These organisms have a particular predilection to invade major blood vessels, with ensuing ischemia, necrosis, and infarction of adjacent tissues; resulting in the production of black pus. Opacification of sinuses, bone destruction and osteomyelitis may also be noted.

How do you treat this condition?
Aggressive treatment include surgical debridement of the necrotic tissue, restoration of acid-base balance, correcting the glucose levels and treatment with antifungal agents such as Amphotericin B. If the condition is not aggressively treated, it may become fatal.

Which are the other infections/diseases caused by this fungus?
Zygomycosis presents as a spectrum of diseases, depending on the portal of entry and the predisposing risk factors of the patient. The 5 major clinical forms are as follows: (1) rhinocerebral, (2) pulmonary, (3) abdominal-pelvic and gastric (gastrointestinal), (4) primary cutaneous, and (5) disseminated.

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