The causative organisms of mucormycosis are of the class Phycomycetes, subclass Zygomycetes. The most commonly seen genera are from the Mucoraceae family,¹⁸,²³,²⁵,²⁸ but an increasing number of infections from the Cunninghamellaceae family are also being reported.²⁹,³⁰,³¹ The most commonly identified organisms are Rhizopus species in 44% of cases and Mucor species in 15%.²² These fungi are ubiquitous saprophytes commonly found in soil, decomposing vegetation, and in healthy human respiratory and digestive tracts.

Mucormycosis typically presents as rhino-orbital or rhinocerebral disease but also occurs as a disease involving
the lungs, skin, and gastrointestinal tract.³² Environmental fungal spores are inhaled and enter the sinuses where the fibrous mycelium and thin-walled aseptate or hyposeptate hyphae grow rapidly within the host tissues. Increased availability of soluble iron in the host is believed to play a role in promoting Mucorales growth, especially in patients receiving deferoxamine iron chelation therapy.³³,³⁴,³⁵ The infection progresses to soft tissues causing facial swelling, numbness, and pain. It may extend to the orbits and brain, causing vision loss and cerebral abscesses. Hematologic dissemination with seeding of visceral organs can follow.³⁶ As the hyphae grow, they invade the blood vessels leading to thrombosis and tissue necrosis.³⁷

For optimal growth in humans, Mucorales fungi require the host to have decreased levels of neutrophils.³⁸ In healthy individuals, neutrophils are a key defense against the fungi in the host tissue and phagocytize these pathogens, but in neutropenic individuals, the pathogens proliferate leading to infection.

Once the infection is initiated, mucormycosis has an affinity for arterial blood vessels,³⁹ where they adhere to the arterial wall and grow along the internal elastic lamina causing thrombosis, ischemia, and necrosis of the surrounding tissues.

During the COVID-19 pandemic, coronavirus disease-associated mucormycosis (CAM) has become a growing threat globally, especially in tropical regions. The emergence of CAM cases has been attributed to environmental, host, and iatrogenic factors.⁴⁰ In COVID-19 patients, virus-induced endothelial dysfunction, hyperglycemia, and immune dysfunction following corticosteroid use is believed to increase the risk of acquiring mucormycosis by the interaction of Mucorales spores with damaged epithelial cells, followed by endothelial invasion.⁴⁰ Corticosteroid treatment, frequently required by COVID-19 patients, further reduces or abolishes the innate immune functions of phagocytic cells contributing to the pathogenesis of CAM.⁴⁰

Mucormycosis commonly presents in five forms: it may affect the pulmonary, rhinocerebral, gastrointestinal, cutaneous, or central nervous systems.³⁷ Systemic dissemination, where infection affects two or more noncontiguous organ systems, may also occur due to the highly invasive nature of this fungus.³⁷ Of the five forms, pulmonary and rhinocerebral are the most common. Cases of rhinocerebral mucormycosis present with facial pain, periorbital cellulitis, proptosis, ophthalmoplegia (Figure 89.1A), visual deficiencies, black necrotic lesions, discharge from the nasal and palatal mucosa, and fever.⁴¹,⁴²,⁴³ CNS mucormycosis is not common by itself but is usually a result of dissemination of the fungal infection from pulmonary or rhinocerebral sources.⁴⁴

Cutaneous involvement by mucormycosis is most often seen on the face and extremities. Patients present with fever and rapidly progressive facial and eyelid induration, edema, and cellulitis (Figure 89.1B), with ulceration, purulent discharge, occasionally bleeding, and necrosis (Figure 89.1B and 89.2).²⁰,²⁷,⁴⁵,⁴⁶,⁴⁷,⁴⁸,⁴⁹,⁵⁰ There may be a history of trauma, burn, insect bite, uncontrolled diabetes, or hematologic malignancy. Chronic infections may sometimes persist for months or years.⁵¹