eMedicine Specialties > Infectious Diseases > Fungal Infections

Mucormycosis

Author: Nancy F Crum-Cianflone, MD, MPH, Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Naval Medical Center at San Diego; HIV Research Physician, Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences
Contributor Information and Disclosures

Updated: Jul 1, 2008

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

More on Mucormycosis

Overview: Mucormycosis
Differential Diagnoses & Workup: Mucormycosis
Treatment & Medication: Mucormycosis
Follow-up: Mucormycosis
Multimedia: Mucormycosis
References

References

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  2. 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. Nov 1997;99(2):331-6. [Medline].

  3. Lee FY, Mossad SB, Adal KA. Pulmonary mucormycosis: the last 30 years. Arch Intern Med. Jun 28 1999;159(12):1301-9. [Medline].

  4. Szalai G, Fellegi V, Szabo Z, et al. Mucormycosis mimicks sinusitis in a diabetic adult. Ann N Y Acad Sci. Nov 2006;1084:520-30. [Medline].

  5. Mohindra S, Mohindra S, Gupta R, et al. Rhinocerebral mucormycosis: the disease spectrum in 27 patients. Mycoses. Jul 2007;50(4):290-6. [Medline].

  6. Gelston CD, Durairaj VD, Simoes EA. Rhino-orbital mucormycosis causing cavernous sinus and internal carotid thrombosis treated with posaconazole. Arch Ophthalmol. Jun 2007;125(6):848-9. [Medline].

  7. Keating GM. Posaconazole. Drugs. 2005;65(11):1553-67; discussion 1568-9. [Medline].

  8. Greenberg RN, Mullane K, van Burik JA, et al. Posaconazole as salvage therapy for zygomycosis. Antimicrob Agents Chemother. Jan 2006;50(1):126-33. [Medline].

  9. Sedlacek M, Cotter JG, Suriawinata AA, et al. Mucormycosis peritonitis: more than 2 years of disease-free follow-up after posaconazole salvage therapy after failure of liposomal amphotericin B. Am J Kidney Dis. Feb 2008;51(2):302-6. [Medline].

  10. Rickerts V, Atta J, Herrmann S, et al. Successful treatment of disseminated mucormycosis with a combination of liposomal amphotericin B and posaconazole in a patient with acute myeloid leukaemia. Mycoses. 2006;49 Suppl 1:27-30. [Medline].

  11. van Well GT, van Groeningen I, Debets-Ossenkopp YJ, et al. Zygomycete infection following voriconazole prophylaxis. Lancet Infect Dis. Sep 2005;5(9):594. [Medline].

  12. Trifilio SM, Bennett CL, Yarnold PR, et al. Breakthrough zygomycosis after voriconazole administration among patients with hematologic malignancies who receive hematopoietic stem-cell transplants or intensive chemotherapy. Bone Marrow Transplant. Apr 2007;39(7):425-9. [Medline].

  13. Al-Abdely HM. Management of rare fungal infections. Curr Opin Infect Dis. Dec 2004;17(6):527-32. [Medline].

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  15. Maertens J, Demuynck H, Verbeken EK, et al. Mucormycosis in allogeneic bone marrow transplant recipients: report of five cases and review of the role of iron overload in the pathogenesis. Bone Marrow Transplant. Aug 1999;24(3):307-12. [Medline].

  16. McAdams HP, Rosado de Christenson M, Strollo DC, et al. Pulmonary mucormycosis: radiologic findings in 32 cases. AJR Am J Roentgenol. Jun 1997;168(6):1541-8. [Medline].

  17. O'Neill BM, Alessi AS, George EB, et al. Disseminated rhinocerebral mucormycosis: a case report and review of the literature. J Oral Maxillofac Surg. Feb 2006;64(2):326-33. [Medline].

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  19. Sugar AM. Agents of mucormycosis and related species. In: Mandell GL, Bennett GE, Dolin R, eds. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. 5th ed. Philadelphia, Pa: Churchill Livingstone; 2005:2973-2984.

  20. Tobon AM, Arango M, Fernandez D, et al. Mucormycosis (zygomycosis) in a heart-kidney transplant recipient: recovery after posaconazole therapy. Clin Infect Dis. Jun 1 2003;36(11):1488-91. [Medline].

  21. Van Cutsem J, Boelaert JR. Effects of deferoxamine, feroxamine and iron on experimental mucormycosis (zygomycosis). Kidney Int. Dec 1989;36(6):1061-8. [Medline].

  22. Walsh TJ, Hiemenz JW, Seibel NL, et al. Amphotericin B lipid complex for invasive fungal infections: analysis of safety and efficacy in 556 cases. Clin Infect Dis. Jun 1998;26(6):1383-96. [Medline].

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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

Contributor Information and Disclosures

Author

Nancy F Crum-Cianflone, MD, MPH, Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Naval Medical Center at San Diego; HIV Research Physician, Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences
Nancy F Crum-Cianflone, MD, MPH is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

Maria D Mileno, MD, Assistant Professor, Department of Internal Medicine, Division of Infectious Diseases, Brown University
Maria D Mileno, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, International Society of Travel Medicine, and Sigma Xi
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Ronald A Greenfield, MD, Professor, Department of Internal Medicine, Section of Infectious Diseases, University of Oklahoma College of Medicine
Ronald A Greenfield, MD is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Central Society for Clinical Research, Infectious Diseases Society of America, Medical Mycology Society of the Americas, Phi Beta Kappa, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology
Disclosure: Pfizer Honoraria Speaking and teaching; Gilead Honoraria Speaking and teaching; Ortho McNeil Honoraria Speaking and teaching; Wyeth Honoraria Speaking and teaching; Abbott Honoraria Speaking and teaching; Astellas Honoraria Speaking and teaching; Cubicin  Speaking and teaching

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
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