Mucormycosis is a fatal fungal infection occuring most commonly in immunocompromised and diabetic patients. Impairment of host defense mechanisms leads to development of the fungus within the human body. Iron is important for growth of the mucorales fungus. Thrombosis with eventual necrosis is the end point in mucormycosis infection. Glucose regulated protein 78 receptor plays a vital part in helping the organism attach to endothelial cells and for subsequent vascular invasion and dissemination. On microscopic examination, the hyphae of mucorales are found to have few septations, are non-pigmented and branch at right angle.

• Fungi of the order Mucorales (class Zygomycetes) are causes of mucormycosis, a life-threatening fungal infection affecting immunocompromised hosts (transplant recepients, diabetics, leukopenic, acidotic patients and patients on dialysis who receive deferoxamine– an iron chelator) in either developing or industrialized countries. ^{[1] [2] [3] [4] [5]}
• Species belonging to the family Mucoraceae are isolated more frequently from patients with mucormycosis.
• Among the Mucoraceae, Rhizopus oryzae (Rhizopus arrhizus) is by far the most common cause of infection. Increasing cases of mucormycosis have been also reported due to infection with Cunninghamella spp.

• The skin represents a major barrier to fungi causing mucormycosis. The agents of mucormycosis are typically incapable of penetrating intact skin.
• However, burns, traumatic disruption of the skin or implantation of contaminated soil or water, and persistent maceration of skin enables the organism to penetrate into deeper tissues and cause infection.
• In addition, contaminated surgical dressings and nonsterile adhesive tape have been shown to be the source of primary cutaneous mucormycosis.
• Ingestion is the mechanism of transmission for gastrointestinal mucormycosis.
• Inhalation of Mucorales sporangiospores by immunocompromised patients leads to development of pulmonary mucormycosis and eventual hematogenous dissemination.

• Neutrophils play a major part in destroying fungal hyphae, once spores germinate.
• Macrophages and monocytes also play part in host defense mechanisms against fungi causing mucormycosis (specifically alveolar macrophages prevent germination of spores).^[6]
• Consequently, mucormycosis develops exclusively in immunocompromised patients who lack these defense mechanisms.
• Hyperglycemia, acidosis and corticosteroid treatment have also been known to hinder immunity (specifically the actions of phagocytic cells), which also puts patients with diabetes and DKA at an increased risk of acquiring mucormycosis.^[4]
• In order to cause disease, the agents of mucormycosis must acquire from the host sufficient iron for growth, must evade host phagocytic defense mechanisms, and must access vasculature to disseminate.
• In immunocompromised hosts (including diabetics), iron is released from sequestering proteins making it available to fungi for growth within the body.^[7]
• Acidotic conditions decrease the iron-binding capacity, suggesting that acidosis per se disrupts the capacity of transferrin to bind iron, probably by proton-mediated displacement of ferric iron from transferrin.^[8]
• Fungi can obtain iron from the host by using high-affinity iron permeases or low-molecular-weight iron chelators (siderophores). ^[9]
• This process along with a reduced number of neutrophils and phagocytes leads to fungal proliferation.^[10]
• Damage to the endothelial cells by fungi causing mucormycosis leads to vascular invasion, subsequent dissemination and tissue necrosis.
• R. oryzae spores but not germlings (i.e., pregerminated spores) have the ability to attach themselves to subendothelial matrix proteins including laminin and type IV collagen.^{[11] [12]}
• Glucose regulated protein 78 (GRP78) serves as a receptor that promotes the ability of Mucorales to penetrate endothelial cells.
• Increased concentrations of glucose and iron, consistent with those seen during diabetic ketoacidosis, increase GRP78 expression and resulting invasion and damage of endothelial cells in a receptor-mediated manner.^[13] These findings likely explain the unique susceptibility of diabetic ketoacidosis to mucormycosis.

• The lesions in cutaneous or rhinocerebral mucormycosis appear varied in size, and ranging from raised red nodules or plaques, which sometimes produce purulent material, to ulcerated lesions with central cavitation, red exuding centres and raised epidermal margins.
• Older lesions may be covered either partly or fully by thickened and irregular epidermis. There may be a black eschar indicating necrosis and ischemia.^[14]

• Histological examination of skin biopsies reveal discrete, poorly encapsulated granulomas, or more commonly a diffuse granulomatous or pyogranulomatous inflammationInflammatory infiltrate consists of neutrophils or eosinophils, few plasma cells and lymphocytes, numerous macrophages and occasional multinucleated giant cells. Fibrovascular tissue is diffusely and irregularly scattered in the granulomatous areas.^[14]
• Nonpigmented, wide (5- to 20-μm), thin-walled, ribbon-like hyphae with few septations (pauciseptate) and right-angle branching^[15]
• In lesions exposed to air, thick-walled spherical structures can form at the ends of the hyphae.