Introduction
Background
Mucormycosis refers to several different diseases caused by infection with fungi in the order of Mucorales. Rhizopus species are the most common causative organisms. In descending order, the other genera with mucormycosis-causing species include Rhizomucor, Cunninghamella, Apophysomyces, Saksenaea, Absidia, Mucor, Syncephalastrum, Cokeromyces, and Mortierella. Most infections are life-threatening, and risk factors, such as diabetic ketoacidosis and neutropenia, are present in most cases. Severe infection of the facial sinuses, which may extend into the brain, is the most common presentation. Pulmonary, cutaneous, and Gi infections are also recognized. Successful treatment requires correction of the underlying risk factor or factors, antifungal therapy with amphotericin B, and aggressive surgery.
Pathophysiology
Mucoraceae are ubiquitous fungi that are commonly found in soil and in decaying matter. Rhizopus can be found in moldy bread. Given the ubiquitous nature of these fungi, most humans are exposed to these organisms on a daily or weekly basis. Nonetheless, they rarely cause disease because of the low virulence of the organisms and mainly affect individuals with immunocompromising conditions. Immunocompromised hosts with poorly controlled diabetes mellitus (especially with ketoacidosis), who are receiving glucocorticosteroids, who have neutropenia in the setting of hematological or solid malignancy, who have undergone transplantation, who have iron overload, and who have burns are at risk for disease.
The major route of infection is via inhalation of conida; other routes include ingestion and traumatic inoculation. For instance, nonsterile tape and contaminated wooden splints have caused wound infections. Such cases are associated with trauma, the presence of a pre-existing wound, or both. When spores are deposited in the nasal turbinates, rhinocerebral disease develops (see Rhinocerebral Mucormycosis); when spores are inhaled into the lungs, pulmonary disease develops. When the agents are introduced through abraded skin, cutaneous disease develops. Ingestion leads to GI disease, primarily among malnourished patients.
Mucoraceae are molds in the environment that become hyphal forms in tissues. Once the spores begin to grow, fungal hyphae invade blood vessels, producing tissue infarction, necrosis, and thrombosis. Neutrophils are the key host defense against these fungi; thus, individuals with neutropenia or neutrophil dysfunction (diabetes, steroid use) are at highest risk. Few cases of mucormycosis have been reported in patients with AIDS, suggesting that the host defense against this infection is not primarily mediated by cellular immunity.
Frequency
United States
Mucormycosis is extremely rare, and its incidence is difficult to calculate accurately. Rhinocerebral disease is the most common form, accounting for more than half of the cases. Other major syndromes include pulmonary, cutaneous, and disseminated diseases; rarer forms involve the GI tract and kidneys. Mucormycosis has been reported in immunocompetent individuals, mostly after traumatic inoculation of fungal spores, but this is extremely rare. A recent review of mucormycosis cases at one US cancer center found that 0.7% of patients were found to have mucormycosis at autopsy and that 20 patients per 100,000 admissions had the disease.1 The incidence of the mucormycosis appears to be increasing secondary to rising numbers of immunocompromised persons.
International
Mucormycosis was found in 1% of patients with acute leukemia in an Italian multicenter review.2
A related disease, entomophthoramycosis, is rare in the United States; it is most commonly found in Africa, Southeast Asia, Australia, and Central America. Entomophthoramycosis consists of 2 diseases: conidiobolomycosis (caused by Conidiobolus infection) and basidiobolomycosis (caused by Basidiobolus infection). The former presents as a painless, firm, subcutaneous mass that primarily involves the head and face, whereas the latter involves the trunk and/or extremities. In contrast with mucormycosis, entomophthoramycosis is associated with a lower mortality rate and usually affects immunocompetent hosts.
Mortality/Morbidity
Mucormycosis carries a very high mortality rate (50-85%). Pulmonary and GI diseases carry an even higher mortality rate because these forms are typically diagnosed late in the disease course. Rhinocerebral disease causes significant morbidity in patients who survive because treatment usually requires extensive, and often disfiguring, facial surgery.
Race
No racial factors that predispose people to mucormycosis exist.
Sex
Sex is not likely to affect the occurrence of mucormycosis because the underlying conditions are the major predisposing factors. Reviews of cases from single institutions show an equal sex distribution. However, a recent review of all published cases of pulmonary mucormycosis performed by Lee et al (1999) showed a male-to-female ratio of 3:1.3
Age
Mucormycosis is found in patients of a wide age range.
Clinical
History
Manifestations of mucormycosis depend on the location of involvement.
- Rhinocerebral disease may manifest as unilateral, retro-orbital headache, facial pain, numbness, fever, and nasal stuffiness that progresses to black discharge. Initially, mucormycosis may mimic sinusitis.4 Late symptoms that indicate invasion of the orbital nerves and vessels include diplopia and visual loss. These late symptoms indicate a poor prognosis and are usually followed by reduced consciousness. Most patients with rhinocerebral disease have diabetes (especially with ketoacidosis) or have malignancies in combination with neutropenia and who may be receiving broad-spectrum antibiotics.
- Pulmonary mucormycosis manifests nonspecifically as fever, dyspnea, and cough. Hemoptysis may occur in the presence of necrosis. Most patients with pulmonary disease have malignancies and a history of neutropenia.
- Cutaneous disease manifests as cellulitis that progresses to dermal necrosis and black eschar formation. Patients with skin disease may have had prior trauma or have been exposed to contaminated medical equipment, such as bandages. Rare cases have occurred at catheter sites or insulin injection sites.
- GI mucormycosis usually affects severely malnourished individuals. Some case reports have described GI mucormycosis in transplant patients (eg, renal transplant). This may occur throughout the GI tract but most commonly affects the stomach, ileum, and colon. Again, the presentation is nonspecific, with abdominal pain, distension, nausea, and vomiting. Hematochezia may occur.
- CNS disease manifests as headache, decreasing consciousness, and focal neurologic symptoms. Patients with CNS involvement may have a history of open head trauma, drug use, or malignancy.
- Other disseminated forms may involve the kidneys, bones, and heart, with symptoms attributed to these organ systems.
Physical
The physical signs of mucormycosis depend on the location of involvement.
- Rhinocerebral
- Orbital swelling and facial cellulitis are progressive. Black pus discharges from the necrotic palatine or nasal eschars.
- Proptosis, ptosis, chemosis, and ophthalmoplegias indicate retro-orbital extension. Cranial nerves V and VII are the most commonly affected. Loss of vision can occur with retinal artery thrombosis.
- A reduced conscious state denotes brain involvement.
- Pulmonary: The signs of pulmonary disease are nonspecific. Fevers are often noted. Lung examination may reveal decreased breath sounds and rales.
- Cutaneous: The progressive black necrotic lesion of cutaneous mucormycosis reflects the vessel invasion characteristic of all forms of the disease.
- Gastrointestinal: These manifestations are nonspecific; some patients have tenderness to palpation or a mass; rupture may lead to signs of peritonitis.
- Central nervous system: This manifests as decreasing consciousness and focal neurologic signs, including cranial nerve deficits.
Causes
Immunocompromising conditions are the main risk factor for mucormycosis. Patients with uncontrolled diabetes mellitus, especially with ketoacidosis, are at high risk. Patients with cancer, especially those who are neutropenic and have received broad-spectrum antibiotics, are also at risk. Patients receiving immunosuppressive agents, including oral or intravenous steroids, as well as tumor necrosis factor (TNF)–alpha blockers, are at risk. Extreme malnutrition is also linked to mucormycosis, especially the GI form. Iron is a growth stimulant for Mucorales, and deferoxamine acts as a siderophore that delivers iron to the fungi. Deferoxamine therapy and all causes of iron overload are additional risk factors for mucormycosis. Trauma and the use of contaminated medical supplies over wounds are associated with cutaneous mucormycosis. In addition, patients with burns and those who use intravenous drugs are at a higher risk.
Some patients with mucormycosis have no identifiable risk factors.5
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References
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Further Reading
Keywords
Rhizopus species, mucormycosis, zygomycosis, phycomycosis, Mucorales, Rhizopus mucormycosis , Rhizomucor mucormycosis , Cunninghamella mucormycosis , Apophysomyces mucormycosis , Saksenaea mucormycosis , Absidia mucormycosis , Mucor mucormycosis , Syncephalastrum mucormycosis , Cokeromyces mucormycosis , Mortierella mucormycosis, conidiobolomycosis, entomophthoramycosis, basidiobolomycosis, pulmonary mucormycosis, rhinocerebral mucormycosis, cutaneous mucormycosis, gastrointestinal mucormycosis, disseminated mucormycosis
