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Synonyms include zygomycosis and phycomycosis
Mucormycosis is a rare, severe infection with fungi of the order Mucorales. Rhizopus are the most common species, with Rhizomucor, Cunninghamella, Saksenaea, and Apophysomyces species occurring less often.
These fungi are common environmental organisms that only cause disease when immunity is impaired. The spores grow, and fungal hyphae invade blood vessels and produce tissue infarction. The result can be invasive, life-threatening disease. Severe infection of the facial sinuses may extend into the brain. Less common manifestations are pulmonary, cutaneous and gastrointestinal (GI) infections.
The condition is very rare but often unrecognised. Invasive fungal infections have always been a problem in the immunocompromised, typically aspergillosis and candidiasis, but mucormycosis has also increased in incidence over the last decade. An estimate of annual incidence in the USA was 1.7 infections per million population.
Impaired immunity from various causes:
- Poorly controlled diabetes mellitus, especially diabetic ketoacidosis.
- Steroid use.
- Neutropenia, especially with haematological malignancy.
- Renal insufficiency.
- Organ or stem cell transplantation.
- Iron overload.
- Broad-spectrum antibiotics.
- Extremes of age.
- Intravenous drug abuse.
- Use of voriconazole for prophylaxis or treatment of aspergillosis.
Extremely rarely, trauma and the use of contaminated medical supplies over wounds are associated with cutaneous mucormycosis in non-immunosuppressed individuals, but not the disseminated form of disease.
- There is usually a fulminant course with considerable tissue necrosis.
- Pyrexia is usual.
- In rhinocerebral disease there is unilateral, retro-orbital headache and nasal stuffiness progressing to a black discharge.
- Late symptoms from invasion of the orbital nerves and vessels include diplopia and visual field loss.
- These are late symptoms with a poor prognosis and usually are followed by reduced consciousness.
- Pulmonary mucormycosis presents nonspecifically with fever, dyspneoa, and cough.
- Cutaneous mucormycosis produces cellulitis that progresses to dermal necrosis and black eschar formation.
- Gastrointestinal (GI) mucormycosis occurs with severe malnutrition and may occur throughout the GI tract. Presentation is nonspecific, with abdominal pain, abdominal distension, nausea, and vomiting.
Only the signs of rhinocerebral mucormycosis are characteristic:
- Cellulitis of the orbit and face progress with discharge of black pus from the palate and nose.
- Retro-orbital extension produces proptosis, chemosis, ophthalmoplegias and blindness.
- As the brain is involved, there are decreasing levels of consciousness.
Pulmonary and GI symptoms are nonspecific but black, necrotic lesions of the skin indicate cutaneous disease.
May include, dependent on presentation:
- Bacterial cellulitis
- Cavernous sinus thrombosis
- Rapidly growing orbital tumour
- Pulmonary embolism
- Bowel obstruction
- Renal function (high doses of amphotericin B will be required and it is nephrotoxic).
- Diabetic control (blood glucose, bicarbonate, and electrolytes, blood gases, HbA1c).
- Ferritin and studies of iron status.
- Imaging - both CT and MRI scans are useful to assess the skull, sinuses and brain (in general, CT is better for viewing bone and MRI gives better pictures of brain and soft tissues).
- CXR and chest CT (if chest disease is suspected).
- Abdominal CT (may show a mass by the gut).
- Tissue biopsy and microbiology (hyphae must be demonstrated to start treatment swiftly; culture is also required to determine the species but will take longer).
General principles of treatment:
- Early diagnosis and initiation of treatment - need to consider diagnosis early and for rapid diagnostic tests. Rapid polymerase chain reaction (PCR) based assays are being developed. Prompt initiation of polyene therapy improves prognosis.
- Reversal of underlying disease - eg rectify any poor control of diabetes, reduce immunosuppressant agents (where possible), stop deferoximine.
- Surgical management - debridement of necrotic areas improves antifungal penetration. The optimum timing of surgical debridement is not well defined. For rhinocerebral disease, surgery includes drainage of the sinuses and may require excision of the eye, other orbital contents, and involved brain. Surgery may be quite destructive and may need to be repeated. Pulmonary lesions can be excised if confined to a single lobe
- Primary antifungal therapy - usually high-dose liposomal amphotericin B for at least 4-6 weeks. A new oral antifungal is posaconazole: it appears to be useful for step-down or salvage therapy after initial amphotericin B treatment but it is unclear as yet if it is effective primary therapy. The use of combination regimes is being explored.
- Adjunctive therapy - agents such as hyperbaric oxygen, interferon-γ, granulocyte-macrophage colony stimulating factor and iron chelation with deferasirox may be beneficial but their use remains experimental.
There is massive invasion and infarction of local tissues.
Mucormycosis has a very high mortality rate of at least 50%. Mortality from pulmonary and gastrointestinal (GI) disease is even higher due to late diagnosis. In patients who survive rhinocerebral disease, treatment requires extensive and often disfiguring facial surgery. In an Italian study 65% of diagnoses were made postmortem although, in many, empirical antifungal treatment has already been given. Mortality in transplant patients can be 80%.
- Nasty, black discharge from the nose and palate.
- Cranial nerve involvement causing diplopia, restricted eye movements and visual field defects.
- Black discharge may also be seen in cutaneous variants.
- Predisposing factors such as diabetes, malignancy or disorders of iron metabolism.
Further reading and references
Chayakulkeeree M, Ghannoum MA, Perfect JR; Zygomycosis: the re-emerging fungal infection. Eur J Clin Microbiol Infect Dis. 2006 Apr25(4):215-29.
Rogers TR; Treatment of zygomycosis: current and new options. J Antimicrob Chemother. 2008 Jan61 Suppl 1:i35-40.
Mantadakis E, Samonis G; Clinical presentation of zygomycosis. Clin Microbiol Infect. 2009 Oct15 Suppl 5:15-20.
Safar A, Marsan J, Marglani O, et al; Early identification of rhinocerebral mucormycosis. J Otolaryngol. 2005 Jun34(3):166-71.
Spira A, Brecher S, Karlinsky J; Pulmonary mucormycosis in the setting of chronic obstructive pulmonary disease. A case report and review of the literature. Respiration. 200269(6):560-3.
Kara IO, Tasova Y, Uguz A, et al; Mucormycosis-associated fungal infections in patients with haematologic Int J Clin Pract. 2009 Jan63(1):134-9. Epub 2007 Mar 16.
Lee FY, Mossad SB, Adal KA; Pulmonary mucormycosis: the last 30 years. Arch Intern Med. 1999 Jun 28159(12):1301-9.
Crum-Cianflone NF; Murcomycosis, eMedicine, Jul 2008
Lass-Florl C; Zygomycosis: conventional laboratory diagnosis. Clin Microbiol Infect. 2009 Oct15 Suppl 5:60-5.
Malani AN, Kauffman CA; Changing epidemiology of rare mould infections: implications for therapy. Drugs. 200767(13):1803-12.
Pagano L, Valentini CG, Caira M, et al; ZYGOMYCOSIS: current approaches to management of patients with haematological Br J Haematol. 2009 Sep146(6):597-606. Epub 2009 May 18.
Tragiannidis A, Groll AH; Hyperbaric oxygen therapy and other adjunctive treatments for zygomycosis. Clin Microbiol Infect. 2009 Oct15 Suppl 5:82-6.
Pagano L, Ricci P, Tonso A, et al; Mucormycosis in patients with haematological malignancies: a retrospective clinical study of 37 cases. GIMEMA Infection Program (Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto). Br J Haematol. 1997 Nov99(2):331-6.
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