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Mucormycosis

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Related Terms
  • Absidia,acidosis, AIDS, antifungal, Apophysomyces, central nervous system mucormycosis, Cokeromyces, Cunninghamella,cutaneous mucormycosis, diabetic ketoacidosis, fungal hyphae, fungal infection, fungi, fungus, gastrointestinal mucormycosis, HIV, hyperglycemia, hyphae, immune disorders, infection, Mortierella, Mucor,opportunistic fungal infection, opportunistic infection, pulmonary mucormycosis, renal mucormycosis, rhinocerebral mucormycosis, Rhizomucor, Rhizopus, Saksenaea, Syncephalastrum.

Background
  • Mucormycosis, also known as zygomycosis, is an aggressive, opportunistic fungal infection of the sinuses, skin, gastrointestinal tract, brain or lungs that usually affects individuals who are immunocompromised.
  • Mucormycosis, first described in 1885, refers to several different diseases that are caused by the fungi in the order of Mucorales. Rhizopus species are usually the cause of mucormycosis. In descending order, the other genera with mucormycosis-causing species include Rhizomucor, Cunninghamella, Apophysomyces, Saksenaea, Absidia, Mucor, Syncephalastrum, Cokeromyces and Mortierella.
  • Depending on where the fungal spores are deposited, mucormycosis may affect the sinuses, lungs, gastrointestinal tract, brain or skin. Most mucormycosis infections are life threatening. Most patients who have mucormycosis experience severe infections of the facial sinuses, which may extend into the brain. Pulmonary, cutaneous and gastrointestinal infections also occur. Complications may include loss of neurological function, blindness or blood clots in the brain or lung vessels (thrombosis).
  • Conditions most commonly associated with mucormycosis include diabetes, chronic steroid use, metabolic acidosis, organ transplantation, leukemia/lymphoma, AIDS and treatment with deferoxamine (a chelating agent that removes excess iron from the body).
  • Diabetic patients are predisposed to mucormycosis because of the decreased ability of their neutrophils to phagocytize (engulf pathogens) and adhere to endothelial walls. In addition, the acidosis and hyperglycemia provide an excellent environment for the fungus to reproduce.
  • Until the 1950s, mucormycosis was almost always a fatal disease. Researchers estimate that about 25-80% of cases today are fatal, depending on where the infection is. Successful treatment requires correction of the underlying risk factor(s), antifungal therapy (usually with amphotericin B) and aggressive surgery. Permanent residual effects of the disease, such as blindness and cranial nerve damage, occur up to 70% of the time.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. Baylor College of Medicine. .
  2. National Library of Medicine. .
  3. Natural Standard: The Authority on Integrative Medicine. . Copyright © 2008.

Causes
  • The Rhizopus species are usually the cause of mucormycosis. In descending order, the other genera with mucormycosis-causing species include Rhizomucor, Cunninghamella, Apophysomyces, Saksenaea, Absidia, Mucor, Syncephalastrum, Cokeromyces and Mortierella.
  • Most people are exposed to these fungi on a daily basis. However, individuals who have a compromised immune system are most likely to develop an infection. In most cases, the infection occurs after fungus spores are inhaled, but an infection can also develop after ingestion. There have also been reports of infection developing after wounds were exposed to non-sterile medical tape or wooden splints.
  • When spores are deposited in the nasal cavity, rhinocerebral disease develops. When the spores are deposited into the lungs, pulmonary disease develops. When the fungus is exposed to open sores on the skin, cutaneous disease develops. Ingestion leads to gastrointestinal disease, especially in patients who are malnourished.
  • Once the spores are in the body, they begin to grow, and fungal hyphae invade the blood vessels, which produces tissue infarction, necrosis (cell death) and thrombosis (blood clots). In a healthy person, neutrophils would destroy the fungus. However, in an immunocompromised person there are not enough neutrophils to destroy the fungus and prevent infection.

Symptoms
  • Most cases of mucormycosis are acute surgical emergencies. However, cases may also be chronic, with symptoms gradually developing over the course of four weeks or longer.
  • Rhinocerebral mucormycosis: Common symptoms of rhinocerebral mucormycosis include acute sinusitis, fever, eye swelling, protrusion of eye orbit, dark nasal eschar (scabbing), progressive cellulitis, facial pain, retinal artery thrombosis, redness of skin overlying sinuses and nasal stuffiness that progresses to black discharge.
  • Late symptoms such as diplopia (double vision) and visual loss indicate that the infection has spread to the orbital nerves and vessels. Patients with these symptoms usually have a poor prognosis.
  • Pulmonary mucormycosis: The symptoms of pulmonary mucormycosis are nonspecific. Symptoms often include fever, cough, rales (bubbling or rattling sounds when air moves through fluid-filled airways) and shortness of breath. Hemoptysis (blood in the sputum) may occur if necrosis is present.
  • Gastrointestinal mucormycosis: Some patients with gastrointestinal mucormycosis experience tenderness to palpation, abdominal pain, distension (bloating), nausea or vomiting blood. Hematochezia (blood in stools) may also occur.
  • Central nervous system: If the infection affects the central nervous system, symptoms may include decreased consciousness and focal neurologic signs, such as cranial nerve deficits.
  • Cutaneous mucormycosis: Cutaneous mucormycosis causes a single, painful, hardened area of skin that may have a blackened central area.

Diagnosis
  • General: Mucormycosis should be suspected if symptoms appear in patients with compromised immune systems. A tissue biopsy is the standard diagnostic test for all types of mucormycosis.
  • Tissue biopsy: A tissue biopsy from the affected area of the body is the best way to definitively diagnose the condition. During the procedure a needle is inserted into the patient and a small piece of tissue is removed. The tissue sample is then analyzed to determine whether the infection is present.
  • Imaging studies: Depending on the site of involvement, Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) may be performed to detect infected tissue inside the body. These tests help healthcare professionals assess the tissue damage and determine whether surgery is necessary.
  • Lumbar puncture (spinal tap): A lumbar puncture (spinal tap) may be performed if it is suspected that the central nervous system is involved. During the procedure, the patient first receives a local anesthetic. Then a needle is inserted into the lower back and a sample of cerebrospinal fluid (CSF) is removed. Patients who have central nervous system mucormycosis may have elevated protein levels and modest mononuclear pleocytosis in the CSF. A CT scan should precede a lumbar puncture to ensure that this procedure is safe.

Treatment
  • The fatality rate ranges from 25-80%, depending on the site involved, and the underlying immunodeficiency. The most effective treatment for mucormycosis is early surgical intervention to remove all of the dead, infected tissue, in addition to antifungal treatment.
  • Antifungals: Antifungals like amphotericin B (Amphocin® or Fungizone®) have been administered intravenously to treat fungal infections. If the patient does not respond to amphotericin B or renal toxicity develops, liposomal amphotericin B (AmBisome®) may be administered intravenously. When the above amphotericin B formulations fail, but the patient still has renal function, amphotericin B lipid complex (Abelcet®) may be administered intravenously. In September 2006, the U.S. Food and Drug Administration (FDA) approved posaconazole (Noxafil®) as a prophylactic (preventative) treatment of invasive Aspergillus and Candida infections in high-risk patients.
  • Surgery: Dead, infected tissue should be surgically removed as soon as possible. In rhinocerebral disease, surgical care includes drainage of the sinuses and may require the removal of the eyes. Repeated surgery may be required, especially for rhinocerebral mucormycosis. Pulmonary lesions may be surgically removed if they are localized to a single lobe. Surgery may be disfiguring, especially if the palate, nasal structures or eye structures need to be removed.

Integrative therapies
  • Unclear or conflicting scientific evidence:
  • Bitter orange: One controlled clinical trial found promising results using oil of bitter orange (Citrus aurantium) as an antifungal agent. However, due to methodological weakness of the trial, further evidence is needed to confirm these results. Avoid if allergic to bitter orange or the Rutaceae family. Theoretically, bitter orange, which contains synephrine and octopamine, may cause hypertension (high blood pressure) and cardiovascular toxicity when consumed orally. Avoid with heart disease, narrow-angel glaucoma, intestinal colic and long QT interval syndrome. Avoid if taking anti-adrenergic agents, beta-blockers, QT-interval prolonging drugs, monoamine oxidase inhibitors (MAOIs), stimulants or honey. Use cautiously with headache, hyperthyroidism (overactive thyroid) or if fair-skinned. Avoid if pregnant or breastfeeding due to a lack of scientific evidence.
  • Cranberry: Limited laboratory research has examined the antifungal activity of cranberry. There are no reliable human studies supporting the use of cranberry in this area. Avoid if allergic to cranberries, blueberries or other plants of the Vaccinium species. Sweetened cranberry juice can increase blood sugar levels. Patients who are immunocompromised should use sweetened cranberry juice cautiously because hyperglycemia (high blood sugar) enhances fungal growth and impairs neutrophil (type of white blood cell that fights against disease and infection) function. Use cautiously with a history of kidney stones because it is unclear whether cranberries increase or decrease the risk of developing kidney stones. Avoid more than the amount usually found in foods if pregnant or breastfeeding.
  • Garlic: Several studies describe the application of garlic to the skin to treat fungal infections, including yeast infections. Use cautiously because garlic can cause severe burns and rash when applied to the skin of sensitive individuals. Avoid if allergic or hypersensitive to garlic or other members of the Lilaceae (lily) family (like hyacinth, tulip, onion, leek or chive). Avoid with a history of bleeding problems, asthma, diabetes, low blood pressure or thyroid disorders. Stop using supplemental garlic two weeks before dental/surgical/diagnostic procedures and avoid using immediately after such procedures to avoid bleeding problems. Avoid in supplemental doses if pregnant or breastfeeding.
  • Pomegranate: The extract of pomegranate was shown to be as effective as a commonly used oral gel when used topically to treat candidiasis associated with denture stomatitis in a randomized controlled trial. Pomegranate extract in combination with Centella asiatica extract was found to have a statistically significant benefit in plaque reduction compared with placebo. Avoid if allergic or hypersensitive to pomegranate. Avoid with diarrhea or high or low blood pressure. Avoid taking pomegranate fruit husk with oil or fats to treat parasites. Pomegranate root/stem bark should only be used under supervision of a qualified healthcare professional. Use cautiously with liver damage or disease. Pomegranate supplementation can be unsafe during pregnancy when taken by mouth. The bark, root and fruit rind can cause menstruation or uterine contractions. Avoid if breastfeeding due to a lack of scientific data.
  • Seaweed, kelp, bladderwrack: Laboratory study suggests anti-fungal and antibacterial activity of bladderwrack. However, there are no reliable human studies to support use as an antibacterial or anti-fungal agent. Avoid if allergic or hypersensitive to Fucus vesiculosus and iodine. Avoid with a history of thyroid disease, bleeding, acne, kidney disease, blood clots, nerve disorders, high blood pressure, stroke or diabetes. Bladderwrack is likely unsafe when taken by children or pregnant/breastfeeding women, due to its high iodine content and potential disruption of thyroid function.

Prevention
  • Immunocompromised individuals are at an increased risk of developing mucormycosis. Therefore, the most effective preventative measure is to treat underlying immunodeficiencies.

Complications
  • Loss of neurological function can occurs when the infection affects the central nervous system.
  • Mucormycosis can cause blood clots in the brain or lung vessels (thrombosis).
  • If the infection spread to the optic nerve, it may result in permanent blindness.

Risk factors
  • Individuals who are immunocompromised are at the greatest risk of developing mucormycosis. Historically, patients with uncontrolled diabetes mellitus (especially with ketoacidosis) are at the greatest risk for infection. This is because funguses thrive in acidic environments. Immunocompromised patients, especially those who have cancer (particularly those who are neutropenic, have received broad-spectrum antibiotics or are undergoing chemotherapy or radiation therapy), liver problems, chronic renal failure, are taking immunosuppressive agents, are malnourished, have burns and recently suffered from trauma, are at an increased risk.

Types
  • Rhinocerebral mucormycosis: Rhinocerebral mucormycosis is an infection of the sinuses that spreads rapidly to the eye and brain. Rhizopus oryzae account for many cases of rhinocerebral mucormycosis.
  • Most patients with rhinocerebral disease have diabetes (especially with ketoacidosis) or have malignancies (cancerous tumors) and neutropenia and are receiving broad-spectrum antibiotics like tetracycline (Helidac Therapy®, Sumycin® or Sumycin® Syrup).
  • Seventy percent of patients diagnosed with rhinocerebral mucormycosis also have diabetes mellitus, although this percentage is declining with the use of chemotherapy and as the frequency of other immunocompromised states become more common. Fewer than four percent of cases occur without a recognized underlying condition. Hyperglycemia (high blood sugar) enhances fungal growth and impairs neutrophil (type of white blood cell that fights against disease and infection) function. Lactic acidosis prevents the white blood cells from performing phagocytosis (engulfing antigens).
  • Pulmonary mucormycosis: Pulmonary mucormycosis occurs when fungal spores are inhaled into the lungs. It is a rapidly progressive pneumonia that may spread to the chest, heart and brain. Immunocompromised patients, especially those who have malignancies and are neutropenic (low levels of neutrophils, which are the most common white blood cells in the bloodstream) are at an increased risk for developing pulmonary mucormycosis.
  • Gastrointestinal mucormycosis: Gastrointestinal mucormycosis occurs when the fungus is ingested. Gastrointestinal mucormycosis is most prevalent among individuals who are severely malnourished. The infection may occur throughout the gastrointestinal tract, but it is most likely to affect the stomach, ileum (lower end of the small intestine) and colon.
  • Cutaneous mucormycosis: Cutaneous mucormycosis occurs when the fungus enters the body through broken skin. Cutaneous mucormycosis causes cellulitis (inflammation of the connective tissue), which eventually results in dead skin and scabs. Patients who have cutaneous mucormycosis may have had prior trauma or have been exposed to contaminated medical equipment, such as bandages. Rare reports of cutaneous mucormycosis have occurred at catheter sites and insulin injection sites.
  • Central nervous system mucormycosis: Rhinocerebral mucormycosis can potentially spread to the central nervous system, causing central nervous system mucormycosis. Patients with central nervous system mucormycosis often experience headaches, loss of consciousness and focal neurologic symptoms. Patients with this form of mucormycosis may have a history of open head trauma or cancer.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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