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Authors: Dr Sharnika Abeyakirthi, Dermatology Registrar, Waikato Hospital, Hamilton, New Zealand, 2007. Updated: Dr Parzhin Piran, Resident Doctor, Royal Darwin Hospital, Darwin, Australia; Dr Dev Tilakaratne, Dermatologist, Darwin, Australia. Copy edited by Gus Mitchell. September 2021


What is zygomycosis?

Zygomycosis is any infection caused by fungi in the class Zygomycetes commonly found in soil or decomposing vegetation and animal matter. There are two major orders of Zygomycetes that cause infection in humans — Mucorales and Entomophthorales.

Cutaneous mucormycosis

Image Credits: Figure 1 - Maleitze T, Stahnke K, Trampuz A, Märdian S. A case report of cutaneous mucormycosis of the hand after minor trauma in a patient with acute myeloid leukaemia. Trauma Case Reports. 2019;23:100221. Figures 2&3 - Wang Y, Zhu M, Bao Y, et al. Cutaneous mucormycosis caused by Rhizopus microsporus in an immunocompetent patient. A case report and review of the literature. Medicine. 2018;97:25(e11141)

Who gets zygomycosis?

Zygomycosis due to Mucorales is seen predominantly in immunocompromised individuals. Diabetes mellitus is the leading predisposing cause worldwide, followed by haematological malignancies and stem cell transplants. Other associations include immune compromise due to solid organ cancer or transplant, drug-induced immunosuppression, or HIV (rare), and iron overload. In up to 20% of cases, the patient is immunocompetent and infection may complicate impairment of the skin barrier such as following skin trauma, thermal burns, or toxic epidermal necrolysis, and has been reported in premature infants. Graft-transmission of infection is an important route of acquisition in some countries.

The annual incidence ranges from approximately 1/million in the US and Europe to 140/million in India. 

COVID-19-associated infection with Mucorales (‘black fungus’) has particularly affected diabetic males treated with systemic corticosteroids in India during the second wave of COVID-19 (April to July 2021), resulting in over 45000 cases and at least 4000 deaths.

Entomophthorales skin infection occurs in healthy individuals particularly around the tropical and subtropical humid areas such as in equatorial Africa and Southeast Asia.

What causes zygomycosis?


The order Mucorales is divided into many families of which the two major causes of infection are Mucoraceae and Cunninghamellaceae. Within these families there are three important genera that cause infection in humans — Rhizopus, Mucor, and Lichtheimia (formerly Absidia) account for 75% of infections. Mucormycosis is the opportunistic infection caused by members of the Mucoraceae family.

Primary cutaneous infection generally occurs due to direct implantation of fungal elements following major or minor skin trauma, such as skin abrasion, or tattoo, or in hospital following surgery, IV-line placement, or contaminated wound dressing. Secondary cutaneous involvement follows haematogenous dissemination.


Entomophthorales are insect pathogens. Two genera of the order Entomophthorales cause subcutaneous phycomycosis in humans, Basidiobolus and Conidiobolus.

What are the clinical features of zygomycosis? 


There are five major clinical forms of mucormycosis:

  • Rhinocerebral (34-39%)
  • Pulmonary (20-24%)
  • Cutaneous (19-22%)
  • Gastrointestinal
  • Disseminated
  • Other rare forms.

Cutaneous mucormycosis may be primary at the site of inoculation, or secondary in disseminated mucormycosis. Onset may be insidious or fulminant — acute and rapid in nature leading to gangrene.


'Red flag' warning signs for rhinocerebral mucormycosis in an at-risk patient include:

  • Cranial nerve palsy
  • Double vision
  • Sinus pain
  • Protruding eye (exophthalmos)
  • Swelling around an eye
  • Orbital apex syndrome — vision loss, inability to move the eye
  • Black necrotic ulcer on the palate.

Entomophthoromycosis/Subcutaneous phycomycosis

  • Slowly progressive painless subcutaneous swelling
    • Uniform, disc-shaped moveable lump under the skin
    • Hard, non-pitting consistency
  • Typically, solitary but can be multiple
  • Overlying skin usually normal
    • Hyperpigmentation, peeling sometimes seen
Conidiobolus coronatus/incongruous
  • Affects young adults, and is more common in males than females.
  • Face is the most common site of infection.
  • Fungi gain entry through the nasal mucosa and produce a subcutaneous swelling around the nose and perinasal region.
  • Infection can spread from the inferior turbinates to produce a generalised swelling of the face.
  • Patients may complain of nasal obstruction and discharge, and sinus pain.
  • Pulmonary and systemic infection has been reported.
Basidiobolus ranarum
  • Usually seen in children, and is more common in males.
  • Often presents with a slowly progressive subcutaneous mass in the limb or limb girdle area.

What are the complications of zygomycosis?

  • Haematogenous dissemination from primary site of infection
  • Invasion of adjacent tissues
  • Disfigurement particularly of the face

How is cutaneous zygomycosis diagnosed?

Diagnosis of cutaneous zygomycosis may be suspected clinically in an at-risk patient and confirmed on deep incisional skin biopsy with sufficient tissue for histology and culture.


  • Histology
    • Eosinophilic thick-walled nonseptate hyphae
    • Vasculotropic — hyphae invade vessel walls
    • See Mucormycosis pathology
  • Fungal culture
    • Negative in up to 50%
    • Allows identification of the genus and species, and antifungal agent susceptibility

Wet mount direct microscopy is a quick and inexpensive diagnostic test for mucormycosis on samples from usually sterile body tissues.

Entomophthoromycosis/Subcutaneous phycomycosis

  • Histology
    • Broad aseptate hyphae
    • Granulomatous inflammationlymphocytes, plasma cells, histiocytes, eosinophils, giant cells
    • Splendore-Hoeppli phenomenon — smudgy eosinophilic sleeves around the hyphae
    • Scattered abscesses, areas of necrosis
    • Lobular panniculitis
  • Fungal culture
    • Fast growing fungi at 30C
    • Conidiobolous species — white to greasy waxy colonies
    • Basidiobolous species — cream to yellow waxy colonies

What is the differential diagnosis for zygomycosis?

What is the treatment for zygomycosis?

  • Early suspicion of diagnosis
  • Reversal of underlying predisposing factors
  • Surgical excision — early extensive surgical debridement
  • Appropriate antifungal therapy — needs to be started early within days of first symptoms, and typically continues for many months


  • Amphotericin B (lipid-formulation or conventional) — high-dose IV — firstline therapy
  • Posaconazole — oral or IV — used if intolerant to amphotericin B or as maintenance therapy


What is the outcome for zygomycosis?

Zygomycosis can be difficult to treat despite the development of new antifungal agents. Treatment should be started within 6 days of symptom-onset for the most favourable outcome. Mucormycosis is often fatal although primary cutaneous disease has a lower mortality rate than gastrointestinal or pulmonary infection. In the past mortality rates were as high as 80% and even now the 90-day mortality rate is around 40%. Disseminated mucormycosis still has a mortality rate of over 90%. Rhinocerebral zygomycosis in solid organ transplant recipients is almost always fatal due to the high rate of CNS invasion.

Spontaneous resolution of entomophthormycosis has been reported. Recurrence is common even after surgical excision. The course is typically indolent.



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