Mucormycosis overview
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Mucormycosis Microchapters |
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Diagnosis |
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Treatment |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]
Overview
Mucormycosis is a fatal fungal infection occuring usually in immunocompromised and diabetic patients. Impairment of host defense mechanisms leads to development of the fungus within the human body. The causative agents of mucormycosis include fungi from the phylum Zygomycota, which includes the sub-phylums Mucorales and Entomophthorales. Mucorales subphylum contains the main agents causing mucormycosis. Clark, in 1968, supported use of the term “mucormycosis” for the diseases caused by species of Mucorales, to distinguish them from “subcutaneous phycomycosis” caused by fungi belonging to Entomophthorales. Species of Mucorales are distributed worldwide. The pathogenic species of Mucorales cause an acute angioinvasive infection mainly in immunocompromised patients. Mucormycosis may involve various organ systems including brain, lungs, skin, GIT, bones, liver, spleen and can be classified based on the organ system involvement. Disseminated infection is associated with high mortality. The prognosis of mucormycosis is poor and has varied mortality rates depending on its form and severity. In the rhinocerebral form, the mortality rate is between 30% and 70%, whereas disseminated mucormycosis presents with the highest mortality rate in an otherwise healthy patient with a mortality rate of up to 100%. An established criteria exists which can help in diagnosing mucormycosis. Prompt amphotericin B therapy should be administered due to the rapid spread and mortality rate of the disease. Amphotericin B (which works by damaging the cell walls of the fungi) is usually administered for a further 4-6 weeks after initial therapy begins to ensure eradication of the infection. Posaconazole has been shown to be effective against mucormycosis. Surgical therapy can be very drastic for mucormycosis, and in some cases of rhinocerebral disease removal of infected brain tissue may be required. If we reduce the risk factors, the chance of getting the disease is decreased significantly. Posaconazole has been found to be an effective agent for secondary prevention of mucormycosis.
Historical Perspective
Mucormycosis in humans was was first reported in 1885 by a German pathologoist named Paltauf. Since its discovery, it has been known to be a lethal infection that mainly affects immune compromised and debilitated individuals. Recently, there has been an increase in its incidence across the world possibly due to increased incidence of diabetes, which is a major risk factor for development of the disease. Diagnosing mucormycosis has been a challenge since its discovery and early diagnosis is one of the keys to successful treatment. Much needs to be done regarding the early diagnosis and optimal treatment for this lethal infection. Thrombosis with eventual necrosis is the end point in mucormycosis infection. Patient history is an important part of the diagnosis and aids in ruling out other differentials
Classification
Mucormycosis may involve various organ systems including brain, lungs, skin, GIT, bones, liver, spleen and can be classified based on the organ system involvement. Disseminated infection is associated with high mortality.
Pathophysiology
Mucormycosis is a fatal fungal infection occuring usually in immunocompromisedand 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 is found to have few septations, non-pigmented and branches at right angle.
Causes
Rhizopus and mucor species are by far the most common causes of mucormycosis but there may be other fungi that lead to development of the disease.
Differentiating mucormycosis from other diseases
Mucormycosis can be difficult to diagnose and a high degree of clinical suspicion is required. Mucormycosis should be differentiated from diseases like invasive aspergillosis, orbital cellulitis, extra nodal T cell lymphoma and cutaneous anthrax. Patient history is an important part of the diagnosis and aids in ruling out other differentials. Other features which help differentiate conditions with similar presentations are radiological and histopathological appearance.
Epidemiology and Demographics
Mucormycosis has limited data which outlines the epidemiology and demographics of the disease. It has a high case-fatality rate.
Risk Factors
In humans mucormycosis is most prevalent in immunocompromised patients (HIV/AIDS, the elderly,SCID, etc) and patients in acidosis (diabetes, burns), particularly after barrier injury to the skin or mucus membranes, malignancies such as lymphomas and leukemias, renal failure, organ transplant, long term corticosteroid and immunosuppressive therapy, cirrhosis, burns and energy malnutrition. Some 50-75% of patients diagnosed with mucormycosis are estimated to have underlying poorly controlled diabetes mellitus and ketoacidosis.
Natural History, Complications and Prognosis
In most cases, the prognosis of mucormycosis is poor and has varied mortality rates depending on its form and severity. In the rhinocerebral form, the mortality rate is between 30% and 70%, whereas disseminated mucormycosis presents with the highest mortality rate in an otherwise healthy patient with a mortality rate of up to 100%. Patients with AIDS have a mortality rate of almost 100%. Possible complications of mucormycosis include the partial loss of neurological function, blindness and clotting of brain or lung vessels.
Diagnosis
An established criteria exists which can help in diagnosing mucormycosis. The criteria is provided by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. It is based on microscopic findings, clinical criteria and characteristics of the fungus.
History and Symptoms
Signs and symptoms of mucormycosis differ according to the organ system involvement. Severe infection of the facial sinuses, which may extend into the brain, is the most common presentation leading to proptosis, redness of skin above sinuses, mental status changes, dark scabbing in nasal cavities, fever and headache. Pulmonary mucormycosis may lead to development of cough, hemoptysis with or without chest pain and fever. Gastrointestinal mucormycosis presents as abdominal pain, hematemesis, diarrhea or constipation.
Physical Examination
Patients with mucormycosis usually appear lethargic, weak and debilitated owing to its development in immune compromised patients. Physical examination of patients with mucormycosis is usually remarkable for skin necrosis with a black eschar, fever, chills, myalgias, sore throat, non-productive cough, abdominal pain.
Laboratory Findings
When a clinician suspects invasive mucormycosis infection, an early diagnostic procedure performed within 16 days from the onset of symptom and early initiation of antifungal therapy will lead to successful management of this highly fatal disease. Biopsy with H&E staining of the specimen and PCR may confirm the diagnosis in suspected cases.
Chest X-ray
Chest xray in pulmonary mucormycosis may show cavitation, hilar adenopathy, pleural effusion, lobar or multi-nodular consolidation and nodules.
CT scan Findings
CT scan should be done immediately if mucormycosis is suspected because it can help in delineating the extent of the disease. In rhinocerebral disease, the lesions are isodense to muscle and bone with a rim of soft tissue thickness around the paranasal sinuses if there is sinus involvement. There may be air fluid levels or complete sinus opacification. The reverse halo sign is an important radiographic finding on CT scan which indicates vascular invasion.
MRI Findings
MRI in mucormycosis tends to show isotense or hypointense in all sequences. The black turbinate sign is an important finding in rhinocerebral involvement.
Treatment
Medical Therapy
If mucormycosis is suspected, prompt amphotericin B therapy should be administered due to the rapid spread and mortality rate of the disease. Amphotericin B (which works by damaging the cell walls of the fungi) is usually administered for a further 4-6 weeks after initial therapy begins to ensure eradication of the infection. Posaconazole has been shown to be effective against mucormycosis, perhaps more so than amphotericin B, but has not yet replaced it as the standard of care. After administration the patient must then be admitted to surgery for removal of the "fungus ball".
Surgery
Surgical therapy can be very drastic for mucormycosis, and in some cases of rhinocerebral disease removal of infected brain tissue may be required. In some cases surgery may be disfiguring because it may involve removal of the palate, nasal cavity, or eye structures. Surgery may be extended to more than one operation. It has been hypothesised that hyperbaric oxygen may be beneficial as an adjunctive therapy because higher oxygen pressure increases the ability of neutrophils to kill the organism.
Prevention
Mucormycosis may be prevented by avoiding the conditions leading to its development. If we reduce the risk factors, the chance of getting the disease is decreased significantly. Posaconazole has been found to be an effective agent for secondary prevention of mucormycosis.