Introduction
Background
Zygomycosis is an infection caused by fungi in the orders Mucorales and Entomophthorales. The Mucorales order contains 2 families exist—Mucoraceae and Cunninghamellaceae.1 Mucormycosis is another common name applied to this same group of diseases. This designation reflected the predominance of the Mucorales in causing disease in humans. However, this term ignored the role of the Entomophthorales (Conidiobolus species and Basidiobolus species).2 The currently accepted designation is zygomycosis, reflecting all disease processes caused by the members of the class Zygomycetes. During the past decade, the Zygomycetes have emerged as common causes of invasive fungal infections.3,4,5
The pathogens that cause zygomycosis are commonly found in the environment on fruit, on bread, and in soil and are common components of decaying organic debris.2 These organisms are ubiquitous and generally saprophytic, rarely causing disease in immunocompetent hosts, but they are the third-most-common cause of invasive fungal infection in immunocompromised patients, especially stem cell transplant recipients and patients with underlying hematologic malignancies.6,7,8,9
Fungi are ubiquitous in the natural world, often found in association with plants, mammals, and insects. Accordingly, humans are continually exposed to multiple genera of fungi via various routes, including the respiratory and gastrointestinal routes, which allow the possibility of colonization. Depending on the interaction between host mucosal defense mechanisms and fungal virulence factors, colonization may be transient or persistent, or local disease may ensue.
Pathophysiology
Overall, Rhizopus species from the Mucoraceae family are the most commonly identified etiologic agents of zygomycosis in humans. Of the Rhizopus species, the most common agent associated with zygomycosis is Rhizopus arrhizus (Rhizopus oryzae), followed by Rhizopus rhizopodiformis. Other causes include Mucor species, Cunninghamella bertholletiae, Apophysomyces elegans, Absidia species, Saksenaea species, Rhizomucor pusillus, Entomophthora species, Conidiobolus species, and Basidiobolus species.2,9
Zygomycosis caused by R arrhizus is acute and rapidly fatal despite early diagnosis and treatment. These organisms have a particular predilection for invading major blood vessels, with ensuing ischemia, necrosis, and infarction of adjacent tissues, resulting in the production of black pus. Persons at particular risk include those with granulocytopenia and acidosis. For unknown reasons, the Zygomycetes have a propensity to affect patients with acidosis, particularly those with diabetes. They also infect patients with acidosis secondary to renal insufficiency, diarrhea, and aspirin intake. Patients who are receiving glucocorticoids or deferoxamine and those who have undergone splenectomy also are at risk.10,9
Frequency
International
The distribution of the various forms of zygomycosis is uniform regardless of age, geography, or race.
Mortality/Morbidity
The overall mortality rate associated with zygomycosis is approximately 50% and has remained at this level for the past 50 years. Rhinocerebral zygomycosis carries a mortality rate of approximately 85%. Mortality rates are very high because, by the time zygomycosis is suspected and diagnosed, it has frequently spread diffusely and caused extensive tissue destruction. However, the risk of mortality varies depending on the characteristics of the host, the type of infection, the site of infection, and the use of surgical intervention. In general, antifungal therapy and surgical management independently decrease the likelihood of death.10,9
Sex
According to the latest epidemiologic surveys, approximately two thirds of all zygomycosis cases occur in males. The reason for this discrepancy is poorly understood.
Clinical
History
Zygomycosis manifests as a spectrum of diseases, depending on the portal of entry and the predisposing risk factors of the patient. The 5 major clinical forms include rhinocerebral zygomycosis, pulmonary zygomycosis, abdominopelvic and gastric (gastrointestinal) zygomycosis, primary cutaneous zygomycosis, and disseminated zygomycosis.10,3
- Rhinocerebral zygomycosis
- Rhinocerebral zygomycosis is the most frequently encountered form of the disease. Approximately 50% of zygomycosis cases in persons with diabetes are of the rhinocerebral type. Rhinocerebral zygomycosis is frequently observed in patients presenting with diabetic ketoacidosis. The typical presentation of rhinocerebral zygomycosis generally involves the nose, followed by the eyes, brain, and, occasionally, the meninges.
- Patients with rhinocerebral zygomycosis typically present with a history of fever, unilateral facial pain or headaches, nasal congestion, epistaxis, visual disturbances, and lethargy.
- Physical examination may reveal periorbital cellulitis, proptosis, and loss of extraocular muscle movement (as seen in the image below). These lesions are frequently accompanied by cranial nerve palsy of the II, III, IV, and VI nerves.
A 45-year-old woman with poorly controlled diabetes mellitus with facial and periorbital swelling due to zygomycosis. She was unable to open her right eye upon admission.
- Black necrotic lesions are generally observed on the hard palate or nasal mucosa of these extremely ill patients.
- Pulmonary zygomycosis
- Patients with pulmonary zygomycosis typically present with a history of fever, cough, hemoptysis, chest pain, and increasing shortness of breath.
- Physical examination may reveal pleuritic rub and rhonchi over the affected area.
- Primary pulmonary zygomycosis is the second-most-common form of zygomycosis and tends to occur in patients with hematological malignancy, those with profound neutropenia, stem cell transplant recipients, and in those who have been receiving high-dose steroid therapy.
- Gastrointestinal zygomycosis
- Patients with gastrointestinal zygomycosis typically present with a history of abdominal pain or distention, dyspepsia, nausea and vomiting, diarrhea, and hematochezia.
- Physical examination may reveal decreased bowel sounds, guarding or rebound tenderness, and localized-to-diffuse abdominal tenderness.
- Gastrointestinal zygomycosis is the least common form of the infection, accounting for less than 10% of all cases of zygomycosis.9
- Gastrointestinal zygomycosis tends to develop in malnourished individuals, low birth weight infants, or in patients with renal failure who are on peritoneal dialysis. Infection is caused by ingestion of the organism and results in necrotic ulcerations, with ischemia and gangrene of the stomach and colon. Gastrointestinal zygomycosis carries an extremely high mortality rate because of the high incidence of bowel perforation and the difficulty in establishing the diagnosis.11
- Cutaneous zygomycosis
- Cutaneous zygomycosis accounts for approximately 20% of all zygomycosis cases.
- Primary cutaneous zygomycosis is generally due to local trauma or inoculation, while secondary infection is due to hematogenous dissemination of the organisms to the skin.
- Patients with cutaneous zygomycosis typically present with a history of previous local trauma, with pain around the trauma site.
- Physical examination may reveal single skin lesions that begin with induration and erythema and gradually develop into a necrotic ulcer with a characteristic dark central area. The margins of the ulcer are sharply demarcated.
- Cutaneous zygomycosis may be primary, resulting from direct inoculation of the organism into disrupted integument. It also has been associated with the use of Elastoplast bandages over biopsy sites and in burn patients with prior colonization. Secondary cutaneous zygomycosis is generally observed with widely disseminated zygomycosis because of hematogenous seeding.
- Disseminated zygomycosis
- Disseminated zygomycosis generally arises from the lungs and spreads hematogenously to the central nervous system.
- Patients with disseminated zygomycosis typically present with a history of headaches, fever, visual disturbances, and changes in mental status.
- Physical examination may reveal lethargy, obtundation, coma, sudden onset of focal neurologic deficits, and necrotic ulcerations on the respiratory-tract mucosa or the skin.
- Deferoxamine therapy appears to be the most significant risk factor for disseminated zygomycosis. This underscores the importance of iron availability as a virulence factor for these infections.
- Disseminated zygomycosis in individuals with hematological malignancies begins in the lungs and spreads to the CNS, producing infarction and abscess. It also can spread to the liver, spleen, kidney, heart, and skin.
Physical
See History.
Causes
Most persons who develop zygomycosis are immunocompromised, although 15-20% of patients have no evidence of any underlying condition at the time of the diagnosis.10,5,9 Thus, sporadic cases in immunocompetent hosts are not uncommon. The most common risk factors include the following:
- Stem cell transplantation
- Poorly controlled diabetes mellitus, either type 1 or type 2
- Hematologic malignancy (eg, leukemias, lymphomas)
- Solid organ transplants
- Steroid use
- Metabolic acidosis
- Deferoxamine therapy
- Severe and prolonged neutropenia
- Intravenous drug use
- Renal failure
- Peritoneal dialysis
- Burns
- Penetrating trauma (rare)
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References
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Lass-Flörl C, Resch G, Nachbaur D, Mayr A, Gastl G, Auberger J, et al. The value of computed tomography-guided percutaneous lung biopsy for diagnosis of invasive fungal infection in immunocompromised patients. Clin Infect Dis. Oct 1 2007;45(7):e101-4. [Medline].
Sun QN, Fothergill AW, McCarthy DI, et al. In vitro activities of posaconazole, itraconazole, voriconazole, amphotericin B, and fluconazole against 37 clinical isolates of zygomycetes. Antimicrob Agents Chemother. May 2002;46(5):1581-2. [Medline].
Dannaoui E, Meletiadis J, Mouton JW, et al. In vitro susceptibilities of zygomycetes to conventional and new antifungals. J Antimicrob Chemother. Jan 2003;51(1):45-52. [Medline].
Herbrecht R. Posaconazole: a potent, extended-spectrum triazole anti-fungal for the treatment of serious fungal infections. Int J Clin Pract. Jun 2004;58(6):612-24. [Medline].
van Burik JA, Hare RS, Solomon HF, Corrado ML, Kontoyiannis DP. Posaconazole is effective as salvage therapy in zygomycosis: a retrospective summary of 91 cases. Clin Infect Dis. Apr 1 2006;42(7):e61-5. [Medline].
Further Reading
Keywords
zygomycosis, mucormycosis, phycomycosis, rhinocerebral zygomycosis, pulmonary zygomycosis, abdominopelvic zygomycosis, gastric zygomycosis, gastrointestinal zygomycosis, GI zygomycosis, primary cutaneous zygomycosis, disseminated zygomycosis , Rhizopus arrhizus, R arrhizus, Rhizopus oryzae, R oryzae, Rhizopus rhizopodiformis, R rhizopodiformis, Mucor species, Cunninghamella bertholletiae, C bertholletiae, Apophysomyces elegans, A elegans, Absidia species, Saksenaea species, Rhizomucor pusillus, R pusillus, Entomophthora species, Conidiobolus species, Basidiobolus species, Mucorales, Entomophthorales, Zygomycetes, Conidiobolus, Basidiobolus, Rhizopus species, Mucoraceae
