Disease name and synonyms

Mucormycosis (Zygomycosis)

Fungi responsible

Many fungi under the  order Mucorales cause mucormycosis. They include Rhizopus oryzae (the most common), Rhizopus microsporus, Lichtheimia corymbifera, Lichtheimia ramosa, Rhizomucor pusillus, Mucor circinelloides, Apophysomyces elegans, Cunninghamella bertholletiae and Saksenaea vasiformis

The less common manifestations of mucormycosis are:

The clinical presentation is similar to invasive aspergillosis with little fever and few clinical features. Clues to the diagnosis of mucormycosis include progression of the disease on voriconazole or echinocandin therapy, high white blood cell count and elevated inflammatory markers, palatal ulcer with eschar, pulmonary nodules, consolidation or cavitation with negative Aspergillus antigen (galactomannan), Aspergillus PCR and/or beta 1,3B-D glucan. Sometimes haemoptysis is the presenting feature.

Isolated renal mucormycosis presents abruptly with fever, loin pain, oliguria/anuria and haematuria, in previously well people.

Frequency and global burden

Up to 11% of filamentous fungal infections in leukaemia are mucormycosis, ~5,000 cases annually. In large series of patients with mucormycosis, about 15% of cases were related to malignancy and bone marrow transplantation, implying around 35,000 cases annually worldwide, probably a significant underestimate because of the difficulties in diagnosis. In 16-23% patients mucormycosis was reported as diabetes-defining illness.

 view Global Epidemiology of cutaneous zygomycosis

Underlying problems and at risk patients

•        Immunosuppression, especially haematological malignancy and transplantation
•        Poorly controlled diabetes
•        High dose corticosteroids
•        Desferrioxamine therapy for iron overload
•        Malnutrition and prematurity
•        Intravenous drug abuse
•        Contaminated wounds
•        Contaminated hospital air or dressings
•        Multiple risk factors may be seen in same patients
•       Though similar risk factors are also seen in other invasive fungal infections, metabolic       acidosis, and iron overload strikes out in mucormycosis
•      The anti-rejection agent tacrolimus appears to be protective against mucormycosis

Diagnostic testing

For pulmonary mucormycosis, a ‘reverse halo’ sign may an early radiographic feature of pulmonary mucormycosis. Most diagnoses of mucormycosis are made on direct microscopy and histology on a biopsy or sample collected from deep tissue. This is because there are no antigen tests or commercialized PCR and culture is positive in ~10% of cases only. Sometimes microscopy of respiratory fluids or surface swabs will reveal non-septate branching hyaline (not coloured) hyphae that are characteristic. In most cases, there are many fungal hyphae present, but being confident that they are not Aspergillus or another filamentous fungus, requires experience and enough material.

The individual fungi responsible can be identified using molecular tools or by conventional microscopic means.

Susceptibility testing is difficult and not validated for these fungi.

Treatments

Amphotericin B and posaconazole are the only active antifungal agents. Surgical debridement or resection is critically important in therapy, and antifungal therapy is secondary and moderately effective.  Reversal of the underlying disease is also and important step

Outlook and prognosis

Approximately 70% of patients survive mucormycosis in the short term. Disseminated disease, bilateral pulmonary infection, cerebral infection, burn wound, uncontrolled malignancy and severe malnutrition are all poor prognostic features.