Cutaneous Mucormycosis (Mucormycosis/Zygomycetes)

Cutaneous Mucormycosis

Are You Confident of the Diagnosis?

What you should be alert for in the history

Cutaneous mucormycosis tends to occur in patients who have significant contamination of skin wounds. Due to the angioinvasive nature of this fungus, infection can spread rapidly from the skin to deep tissue and bone. Invariably, untreated skin infection will result in tissue infarction and necrosis as a consequence of vascular invasion and thrombosis.

Characteristic findings on physical examination

Cutaneous mucormycosis begins as erythema and induration at the site of inoculation. Tissue infarction may ensue rapidly, which is manifested typically as a black eschar with central ulceration (Figure 1, Figure 2). Necrotizing fasciitis is a severe complication of cutaneous mucormycosis, and can present as rapid expansion of tissue erythema, induration, pain, and eschar formation.

Figure 1.

Rapidly progressive lesion of cutaneous mucormycosis with classic eschar.

Figure 2.

Infection of surgical wound with extensive necrosis from vascular invasion.

Expected results of diagnostic studies

Diagnosis of cutaneous mucormycosis is confirmed by biopsy and culture of the affected area. Biopsies should be taken in the center of the necrotic lesion and include the subcutaneous tissue. Histopathologic evaluation reveals characteristic broad, irregular, ribbon-like, mostly aseptate hyphae that exhibit wide-angled branching (Figure 3). Surrounding tissue necrosis and angioinvasion of fungi may also be present. A significant portion of the biopsy should be cultured on fungal media to confirm the diagnosis of mucormycosis. Fungal blood cultures are usually negative, and there are no serologic blood tests that are currently available to confirm infection.

Figure 3.

Histopathology of mucormycosis: note the aseptate, irregular, ribbon-like hyphae, with wide angle branching.

Diagnosis confirmation

Cutaneous mucormycosis can be mistaken for other invasive fungal infections, such as aspergillosis, fusariosis, and infection with scedosporium. However, the rapidity of disease progression tends to set cutaneous mucormycosis apart from these other entities. Ecthyma gangrenosum (EG) can also present in a similiar manner as cutaneous mucormycosis; typical lesions of EG begin as hemorrhagic papules that progress to necrotic ulcers with erythematous bases, and echar formation . However, EG tends to occurs in severely ill patients with Pseudomonas sepsis; and less likely from direct inoculation.

Who is at Risk for Developing this Disease?

Generally, cutaneous mucormycosis occurs in hosts who have a significant disruption in skin integrity, such as burn victims and patients who have sustained soft tissue trauma. Rarely, cutaneous disease has also been attributed to contaminated surgical dressings and vascular catheter insertion sites. In these patients, infection tends to occur due to contamination of the skin, coupled with impaired local host defenses which are unable to contain infection.

Cutaneous disease may also occur in hosts with impaired immune defenses; such hosts include diabetics, transplant recipients, and patients on chronic steroids, those receiving deferoxamine, and those with iron overload (Figure 4, Figure 5). Although local cutaneous disease may occur in these patients due to breaks in skin integrity from trauma or instrumentation, rhinocerebral and pulmonary disease are more commonly encountered in this particular population. Cutaneous extension of rhinocerebral disease can manifest as erythema and/or eschar in the periorbital and paranasal area. Hematogenous spread of mucomycosis to the skin is rarely encountered; however, untreated skin infection may cause deeper infection and can eventually lead to hematogenous infection.

Figure 4.

Figure 4 (left panel) shows an immunocompromised host with rhinocerebral mucormycosis and secondary ecchymotic skin lesions.

Figure 5.

There was rapid progression within hours despite antifungal therapy as noted in the right panel (Figure 5)

What is the Cause of the Disease?


The group of organisms that typically cause mucormycosis belong to the order Mucorales. They are ubiquitous in nature, and are saphrophytic and thermotolerant. They are able to utilize carbohydrates for spore formation, and grow fairly rapidly (in 2-5 days). Mucorales are further classified into six families, of which the family Mucoraceae/Absidiaceae represents the majority of human disease. The most common species that are encountered in invasive disease include Rhizopus arrhizus (Rhizopus oryzae), Rhizopus microsporus var. rhizopodiformis, and Rhizomucor pusillus (Table I).

Table I.

Most common causative agents of mucormycosis
Rhizopus arrhizus (Rhizopus oryzae)
Rhizopus microsporus var. rhizopodiformis
Rhizomucor pusillus
Rhizopus stolonifer
Cunninghamella bertholletiae
Apophysomyces elegans
Saksenaea vasiformis
Absidia corymbifera


Infection occurs when there is inhalation, ingestion, or direct inoculation of sporangiospores. Phagocytes are the principal host defense against fungal invasion and dissemination. Conditions that inhibit phagocytic function, such as hyperglycemia and acidosis, enable the spores to escape host defenses. Iron is also essential for the growth of Mucorales; patients with iron overload, receiving deferoxamine-based therapy or have metabolic acidosis are especially susceptible to invasive disease. Once Mucorales are able to evade host defenses and acquire iron for growth, angioinvasion, tissue necrosis, and dissemination of infection occur.

Systemic Implications and Complications

If left untreated, cutaneous mucormycosis can cause deep tissue infection involving muscle, bone, and fascia. A severe complication of cutaneous mucormycosis is necrotizing fasciitis; despite aggressive surgical debridement and antifungal therapy, this diagnosis portends a poor prognosis. Hematogenous spread to other organs can occur, especially in immunocompromised hosts. When this occurs, overall mortality is near 100% .

Treatment Options

Surgical Therapy

Immediate aggressive surgical debridement.

Medical Therapy

Systemic antifungal therapy

  1. Amphotericin B preparations: conventional or lipid based. Only FDA-approved treatment for mucormycosis.

  2. Posaconazole: not yet FDA-approved for treatment, but has been successful as salvage therapy in clinical trials. It is only available orally. Absorption is maximized by a high fat meal and when given in four divided doses.

Hyperbaric Oxygen

Case reports of successful outcomes, but no clinical trials to support routine use in treatment.

Optimal Therapeutic Approach for this Disease

Due to the aggressive nature of this infection, prompt surgical debridement is necessary to minimize deeper extension and dissemination. Patients may require serial surgical debridements to ensure adequate removal of infected and infarcted tissue.

Along with surgery, antifungal therapy should also be instituted. Currently, the only FDA-approved therapy for cutaneous mucormycosis is either amphotericin B deoxycholate at high doses (1.0-1.5mg/kg/day); or lipid formulations of amphotericin B. Generally, such high doses of conventional amphotericin B cannot be tolerated for very long and hence the lipid formulations of amphotericin B are preferred.

Posaconazole has been shown to be active against several Mucorales species, and has been shown to be successful as salvage therapy. It has also been used as step down therapy after a course of amphotericin B. Posaconazole does not currently have FDA approval for treatment of mucormycosis; In case reports, posaconazole was administered either 200mg four times daily or 400mg twice daily.

Reversal of conditions that foster growth and proliferation of mucormycosis is also important in containing disease. Correction of acidosis and hyperglycemia, restoration of the immune system, and if possible, discontinuation of immunosuppresive agents are interventions that will aid in halting disease progression. Hyperbaric oxygen treatment may also be used as an adjunctive therapy; however, there are no randomized clinical trials to support wide use of this modality.

Patient Management

Aggressive surgical debridement and starting antifungal therapy are crucial for treatment of cutaneous mucormycosis. Mortality rates are less than 10% if both treatment modalities are promptly instituted; conversely, mortality rates near 100% if no intervention is perfomed.

After sufficient surgical debridement, the patient will need to be maintained on antifungal therapy. Conventional amphotericin B, dosed at 1.0-1.5mg/kg/day, is the preferred treatment. Alternatively, lipid-based amphotericin B can be used, especially in patients who develop renal toxicity or severe adverse events from conventional amphotericin B. Length of therapy is highly individualized for each patient.

All formulations of amphotericin B are administered via the intravenous route. Amphotericin B deoxycholate is associated with several side effects, including infusion-related symptoms (fever, chills, rigors, headache, gastrointestinal (GI) upset), renal toxicity, electrolyte imbalance, hepatotoxicity, cardiac arrhythmias, and bone marrow suppression. The lipid formulations of amphotericin B are less likely to cause these toxicities, especially renal insufficiency.

Because amphotericin B can cause irreversible nephrotoxicity, careful review of concurrent medications should be done; other potential nephrotoxic agents that are not essential should be withheld while on amphotericin B. Frequent monitoring of electrolytes and renal function should be performed while on therapy; aggressive electrolyte supplementation is important to ensure that the patient is not at risk for cardiac disturbances.

Although not approved by the FDA, posaconazole is an option for patients unable to tolerate amphotericin B-based compounds and for completion of a course of therapy.

Consultation with an infectious diseases specialist is highly recommended in formulating treatment plans for these patients.

Unusual Clinical Scenarios to Consider in Patient Management

Outbreaks of necrotizing soft tissue infections with cutaneous mucormycosis have been reported in the setting of environmental catastrophies, such as earthquakes and tsunamis. Contaminated needles and bandages have also caused outbreaks.

What is the Evidence?

Kontoyiannis, DP, Lewis, RE. "Invasive zygomycosis: update on pathogenesis, clnical manifestations, and management". Infect Dis Clin N Am. vol. 20. 2006. pp. 581-607.

(A comprehensive review of mucormycosis, including epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment.)

Kontoyiannis, DP, Lewis, RE, Mandell, GL, Bennett, JE, Dolin, R. "Agents of mucormycosis and entomophthoramycosis". Mandell, Douglas, and Bennett’s principles and practice if infectiojus diseases. Churchill Livingstone Elsivier. 2010. pp. 2257-69.

(Another comprehensive review of mucormycosis, with excellent clinical and histopathologic images of mucormycosis. The most common species encountered in human mucormycosis (Table I) is extrapolated from this chapter.)

Chayakulkeeree, M, Ghannoum, MA, Perfect, JR. "Zygomycosis:the re-emerging fungal infection". Eur J Clin Microbiol Infect Dis. vol. 25. 2006. pp. 215-29.

(This review article includes an in-depth review of risk factors for mucormycosis infection, as well as disease manifestations.)

Spellberg, B, Edwards, J, Ibrahim, A. "Novel perspectives in mucormycosis: pathophysiology, presentation, and management". Clin Microbiol Rev. vol. 18. 2005. pp. 556-69.

(An excellent overview of mucormycosis, detailing mechanisms of host defense, the role of iron in disease, clinical manifestations of disease, and a comprehensive overview of antifungal therapy.)

Roden, MM, Zaoutis, TE, Buchanan, WL, Knudsen, TA, Sarkisova, TA, Schaufele, RL. "Epidemiology and outcome of zygomycosis: a review of 929 reported cases". Clin Infect Dis. vol. 41. 2005. pp. 634-53.

(Largest review of mucormycosis cases, which included 176 patients with cutaneous disease. Of the 35 patients with cutaneous disease that had disseminated mucormycosis to other organs, 33 patients died; this emphasizes the importance of prompt surgical intervention and antifungal therapy in patients suspected of having mucormycosis.)
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