What is the pathophysiology of mucormycosis (zygomycosis)?

Updated: Jul 06, 2021
  • Author: Avnish Sandhu, DO; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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Answer

Mucorales are ubiquitous fungi that are commonly found in soil and in decaying matter. Rhizopus can be found in moldy bread. The major route of infection is via inhalation of conidia; other routes include ingestion and traumatic inoculation (see the images below). Ingestion leads to GI disease and occurs primarily among malnourished patients but can also occur after ingesting non-nutritional substances (pica).

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. 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 ingested, GI disease ensues; and when the agents are introduced through interrupted skin, cutaneous disease develops.

The virulence factor involved in the pathogenesis of Mucorales is high affinity iron permease (FTR1), allowing Mucorales survival in iron-poor environments. [13, 14, 15]  Spore coat protein (Cot H) present on the surface of Mucorales results in impaired host defense [13] ; ADP-ribosylation factor plays a significant role in the growth of Mucorales. [13]  Neutrophils are the key host defense against these fungi; thus, individuals with neutropenia or neutrophil dysfunction (eg, diabetes, steroid use) are at highest risk. [16] Few cases of mucormycosis have been reported in patients with acquired immunodeficiency syndrome (AIDS), suggesting that the host defense against this infection is not primarily mediated by cellular immunity.

Mucormycosis should be considered in the differential diagnosis of a necrotic-appearing wound or one with an inadequate response to antibiotic treatment. [17, 18, 19]  External factors, such as toxins produced by bacterial endosymbiosis, can lead to endothelial disruption, resulting in fungal virulence. [13, 20, 21]  Additionally, voriconazole exposure by a unknown mechanism and not due to selective pressure, allows for invasive mucormycosis. [13, 22]

The right eye of an immunocompetent man who sustai The right eye of an immunocompetent man who sustained a high-pressure water jet injury, resulting in rhinocerebral mucormycosis. Traumatic inoculation of Apophysomyces elegans was the pathogenetic mechanism. Note the proptosis. Courtesy of A Allworth, MD, Brisbane, Australia.
The right eye of an immunocompetent man who sustai The right eye of an immunocompetent man who sustained a high-pressure water jet injury, resulting in rhinocerebral mucormycosis. Traumatic inoculation of Apophysomyces elegans was the pathogenetic mechanism. Chemosis is shown in this photograph. Internal and external ophthalmoplegia, no light perception, and afferent pupil defect were present, which is consistent with orbital apex syndrome. Courtesy of A Allworth, MD, Brisbane, Australia.

Brain MRI (sagittal view) in a patient with uncontrolled diabetes who presented with progressive right eye pain and facial swelling. He underwent multiple surgeries to control rhinocerebral Mucor infection, including partial right frontal lobectomy and right orbital exenteration. He was treated with amphotericin B and his diabetes mellitus was controlled. The disease did not progress, and long-term isavuconazole therapy was initiated for salvage/maintenance therapy.

Brain MRI (sagittal view) in a patient with uncont Brain MRI (sagittal view) in a patient with uncontrolled diabetes who presented with progressive right eye pain and facial swelling. He underwent multiple surgeries to control rhinocerebral Mucor infection, including partial right frontal lobectomy and right orbital exenteration. He was treated with amphotericin B and his diabetes mellitus was controlled. The disease did not progress, and long-term isavuconazole therapy was initiated for salvage/maintenance therapy.

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