Mucormycosis

Mucormycosis is most often an acute surgical emergency, however, some cases display chronic symptoms that gradually develop over time (weeks or months). Symptoms depend heavily on which form of the disease patients have.

Symptoms of rhino-orbito-cerebral mucormycosis include acute sinusitis, fever, eye swelling and protrusion, dark nasal scabbing, cellulitis, facial pain, retinal artery thrombosis, redness of skin around sinuses and nasal congestion with black discharge. Diplopia and blindness may be observed in later stages of the disease, which indicates the infection has spread to the orbital nerves and vessels, and prognosis for these patients is poor.

Symptoms of pulmonary mucormycosis are nonspecific and may include fever, cough, rales, shortness of breath and possibly hemoptysis if tissue necrosis is present. Symptoms of GI mucormycosis include abdominal pain and distension, nausea, vomiting blood, tenderness upon palpation and hematochezia [5]. Presentation of cutaneous mucormycosis is marked by a single area of skin that is painful, hardened and may have a necrotic (blackened) central area [11]. If the mucormycosis infection has disseminated to the central nervous system patients will present with decreased consciousness and focal neurological symptoms, such as cranial nerve deficits.

Diagnosis is achieved through a variety of factors including patient’s history, risk factors and physical exam, however, a definitive diagnosis is hard to reach. The extent of infection or necrosis may be assessed through magnetic resonance imaging (MRI) or computerized tomography (CT) scan but these findings are nonspecific [12]. Biopsies can be stained with Grocott methenamine-silver stain or periodic acid-Schiff (PAS) stain and others to identify the fungus, but the specific fungal species is hard to determine [13]. More complicated cultivation and imaging techniques must be performed to identify structures unique to mucormycosis and distinguish this from other fungal infections like candidiasis and histoplasmosis. Therefore, the diagnosis of mucormycosis may be used without definitive evidence since the supportive care and treatment for many fungal infections are similar.

Mucormycosis is treated with antifungal medications (conventional or lipid formulations of amphotericin B) administered orally or IV [14] [15]. Infected areas of skin may require surgical resection to remove infected and dead tissues [15]. Patient survival relies on proper debridement of necrotic tissue when applicable. Surgical care of rhino-orbito-cerebral infection may include repeated surgeries to excise orbital contents and infected brain tissue along with drainage of sinuses.

There are a number of potential adjunct therapies to treat mucormycosis. Hyperbaric oxygen after surgery is thought to improve neutrophil function and wound healing and inhibit fungal growth. However, the effectiveness of hyperbaric oxygen for mucormycosis has not been studies extensively and this is not a currently approved use of hyperbaric oxygen. Administration of colony stimulating factor (CSF) or interferon-gamma (IFNγ) may be done to enhance immune response in neutropenic patients and white blood cell transfusions, respectively. However, the effectiveness of these treatments is unclear. Case reports on the use of iron chelators without xenosiderophore activity, such as deferasirox, indicated that adjunct use of deferasirox leads to increased mortality rates although only a small patient sample was investigated [16].

The mortality rate for mucormycosis is extremely high (at least 50%). Due to the late diagnosis associated with pulmonary and GI mucormycosis infections, the mortality rate in these forms is relatively higher. Transplant patients that contract mucormycosis may experience mortality rates of 80%. An Italian study indicated that 65% of diagnoses were made postmortem [10]. The lifesaving surgery associated with rhino-orbito-cerebral mucormycosis often leaves survivors with severe facial disfigurements.

The primary risk factor for murcormycosis is a compromised immune system. Patients with particularly high risk include those with uncontrolled diabetes mellitus, especially with ketoacidosis. Cancer patients receiving broad-spectrum antibiotics that display neutropenia, hematologic cancer patients with herpetic infection (eg. Cytomegalovirus) and graft versus host disease and individuals on immunosuppressive drugs, such as steroids and tumor necrosis factor (TNF) blockers are also at high risk for contracting murcormycosis infection.

The GI form of murcormycosis infection is linked to extreme malnutrition. The cutaneous form of murcormycosis is associated with trauma, the use of contaminated medical supplies, burns and intravenous (IV) drug use. Not all patients that develop murcormycosis will exhibit risk factors [2] [4].

Chemicals that increase chances of developing murcormycosis include iron, which is a growth stimulant for Mucorales, and deforoxamine, which is a siderophore that delivers iron to Mucorales [2] [3].

Compared to other fungal infections, Mucorales infections occur much less frequently (10 to 15 fold less) [5]. Annually in the United States (US) there are an estimated 1.7 cases per million people which equates to about 500 cases per year [5].

Mucormycosis is commonly observed in immunosuppressed individuals but certain strains, such as those in the order Entomophthorales, have occurred in immunocompetent hosts. Individuals with the highest risk include those with diabetic ketoacidosis, hematologic malignancies, organ transplant recipients, chronic corticosteroid use and graft-versus-host-disease [5].

The most common form of mucormycosis is rhino-orbito-cerebral (44-49%) [7]. Cutaneous mucormycosis accounts for 10-16% of cases followed by pulmonary (10-11%), disseminated (6-11.6%) and GI (2-11%). Diabetic patients are more likely to present rhino-orbito-cerebral mucormycosis, while patients with hematological malignancies or transplants commonly present with pulmonary mucormycosis.

Outbreaks of mucormycosis have been reported including a nosocomial outbreak of GI mucormycosis that occurred in a hospital in Spain. This outbreak was linked to the use of wooden tongue depressors that were contaminated with Rhizopus and the mortality rate in this case was 40% [6].

The most common mode of entry of Mucorales is inhalation of fungal spores. Once spores enter a host they may germinate to produce hyphae that can enter blood vessels and cause thrombosis which may results in tissue necrosis. Experimentally, germinated fungal spores can adhere to the sub-endothelial matrix and cause damage to endothelial cells after phagocytosis [9]. This outcome occurs regardless of viability indicating that cidal antifungals will not be effective for the treatment of established disease [9]. Mucorales may be disseminated to other organs through the blood stream. An efficient host immune response to Mucorales infection requires normal mononuclear and polymorphonuclear phagocytes that can produce oxidative metabolites and definsins to kill fungi along with macrophages and neutrophils to inhibit spore germination and damage hyphae, respectively [8].

Factors that decrease the abundance or functioning of neutrophils, such as chemotherapy (induces neutropenia), corticosteroids, acidosis and hyperglycemia, increase the risk of developing mucormycosis [5]. Other conditions and factors that hamper the immune response to fungi include acidosis and hyperglycemia which hinder the ability of phagocytes to kill fungi and corticosteroids which prevent the ability of macrophages to stop germination [9]. Actions that result in better outcomes include early recognition and appropriate treatment along with reversal of acidosis (if it applies).

To prevent risk of mucormycosis infection, immunosuppressants, such as corticosteroids, should be used sparingly and patients should control their diabetes. Physicians and hospitals should use appropriate rooms equipped with high-efficiency particulate air (HEPA) filters and patients with immunosuppressive conditions should use masks [5].

Several different fungal species in the order Mucorales may cause murcormycosis infections. The organisms most commonly associated with murcormycosis infection are Rhizopus. Other disease causing genera include Mucor, Cunninghamella, Apophysomyces, Absidia, Saksenaea and Rhizomucor [1] [2]. Mucormycosis infections are serious and in most cases life-threatening with disorders such as diabetic ketoacidosis and neutropenia present in most cases. Patients commonly present with severe infection of the facial sinuses which may extend to the brain (rhino-orbito-cerebral). Other infections, including pulmonary, cutaneous, gastrointestinal (GI) and disseminated, are also observed. Effective treatment of murcormycosis requires rapid correction of underlying risk factors, administration of antifungals (liposomal amphotericin B) and aggressive surgery.

Mucormycosis is a serious and sometimes life-threatening fungal infection that may affect the sinuses, brain, lungs and skin. The fungi that cause mucormycosis are often found in soil, decaying plants and compost and can enter the body through cuts or inhalation. Once the fungus enters the body it can spread quickly. Individuals with healthy immune systems often destroy and eliminate the fungus, however, if the immune system is weak the fungus may go on to cause a severe infection. Symptoms of mucormycosis infection include fever, facial pain, swollen eyes, redness of skin over sinuses, bloody cough, shortness of breath, abdominal pain, vomiting blood, pain on side of the body between upper abdomen and back and a skin infection that starts with blisters and later becomes tender, red, swollen and black in the center.

Patients with a compromised immune system that display the symptoms above are often diagnosed with mucormycosis. Analysis of tissue biopsies (tissue removed using small needle) is required to obtain a definitive diagnosis. Doctors may also perform CT scan or MRI to determine the extent of infection within the body and whether surgery is needed. If the central nervous system is thought to be infected patients may receive a lumbar puncture (spinal tap), if it is safe, to assess protein levels in the cerebrospinal fluid (CSF). Aggressive treatment is required if mucormycosis is suspected and early treatment is associated with better outcomes. Oral or IV antifungal medication will be administered as soon as possible and surgery may be required to remove infected and dead tissue.

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