BLACK FUNGUS (RHINOCEREBRAL MUCORMYCOSIS): CAUSES, SYMPTOMS, TREATMENT AND MORE
Medically Reviewed by Dr. Sony Sherpa (MBBS)
Rhinocerebral mucormycosis (RCM), commonly called black fungus, is a dangerous fungal infection that affects the nasal passages, sinuses, and brain. While these fungi are typically harmless to healthy individuals, they can cause severe infections in people with weakened immune systems.
During the pandemic, there was a surge in cases of RCM among COVID-19 patients in India, leading to increased awareness and concern about this condition.
This article will explore what RCM is, its prevalence, risk factors, symptoms, diagnosis, treatment, and prevention.
What is Rhinocerebral Mucormycosis[1]?
Rhinocerebral mucormycosis is a rare but potentially life-threatening fungal infection that affects the nasal passages, sinuses, and brain. It is caused by fungi known as mucormycetes, which belong to the Mucorales order.
Several types of mucormycetes fungi can lead to severe infections, including:
- Rhizopus
- Mucor
- Rhizomucor
- Cunninghamella
- Apophysomyces
Mucormycetes fungi are often found in the environment, including plants, soil, and decomposing organic materials. They can enter the body in different ways, including ingestion, inhalation, and through skin wounds or cuts.
Most people come into contact with them daily without experiencing any adverse effects. However, in those susceptible, these fungi can cause severe infections. Individuals with compromised immune systems are the most prone, such as those with uncontrolled diabetes, COVID-19, cancer, or HIV/AIDS.
Global Prevalence
The number of mucormycosis cases is estimated to have risen to 910,000 globally. The prevalence is the highest in India, with multiple Indian ICUs finding mucormycosis in 14.4% of patients. Cases are noted elsewhere worldwide, including in Asia, Europe, and the US, with a prevalence ranging from 0.43-1.75 people per million per year.[2]
Infection Routes and Affected Areas
The most common route of infection for RCM is through the inhalation of fungal spores. These spores can infiltrate the body through the nose and travel to the paranasal sinuses, which are air-filled spaces behind the nose, cheeks, and forehead. Mucous membranes that line the sinuses give the fungi a warm and humid environment in which to grow.
Once the fungi reach the sinuses, they can invade the surrounding tissues, causing inflammation and damage. If left untreated, the infection is left to infiltrate the brain, eyes, and other nearby structures, leading to severe complications.
Types of Mucormycosis
Rhinocerebral mucormycosis is one of several types of mucormycosis, explicitly affecting the nasal passages, sinuses, and brain. The other types of mucormycosis include[3]:
- Cutaneous mucormycosis: This type affects the skin, mainly through wounds or punctures in the skin.
- Pulmonary mucormycosis: This version affects the lungs and often presents in individuals with weakened immune systems.
- Gastrointestinal mucormycosis: This type targets the digestive system, particularly the stomach and intestines.
- Disseminated mucormycosis: This is a severe form of the infection that spreads (disseminates) through the bloodstream and affects various organs in the body.
- Other rare forms: These may include mucormycosis, which affects bones or joints, the heart, and the central nervous system.
Each type of mucormycosis presents unique challenges and symptoms, with rhinocerebral mucormycosis being specifically concerning due to its potential impact on the nasal passages, sinuses, and brain.
Can RCM be Contagious?
Mucormycosis infection is neither contagious nor transmissible from person to person.
Risk Factors and Causes
As mentioned above, RCM is caused by exposure to Mucormycetes spores, which can be found in the environment and are particularly dangerous for individuals with weakened immune systems.
Studies reveal that the fungus typically infects those with erratic blood sugar levels and hypoxia (a state of low oxygen).
While anyone can develop RCM, certain factors can increase the risk of developing the infection. These include[4]:
- Uncontrolled diabetes
- COVID-19 and possibly other respiratory infections that target body tissue oxygenation
- Cancer
- HIV/AIDS
- Stem cell or organ transplantation
- Neutropenia (low white blood cell count)
- Iron excess and related conditions such as hemochromatosis
- Long-term use of immunosuppressive medications
- Malnutrition
- Trauma or surgery
- Use of contaminated medical equipment or medications
- Premature birth (for neonatal infections)
Lessons Learned: COVID-19-associated Mucormycosis in India
The rise in mucormycosis cases witnessed in India during the COVID-19 pandemic offers valuable lessons for healthcare professionals and the public.
- Diabetes Connection: The high prevalence of diabetes in India might be linked to a higher susceptibility to fungal infections like mucormycosis.
- Climate Considerations: Warm and humid environments, common in many parts of India, favor the growth and spread of fungi that cause mucormycosis. Other regions with similar climates may also face an increased risk.
- Healthcare Environment: Overcrowding as a result of rising COVID-19 cases was reported across healthcare systems globally. In many developing countries, such as India, the surge in cases and the consequent strain on resources affected sanitation practices in some healthcare facilities, which may have contributed to fungal exposure, potentially through contaminated equipment or environmental factors. Renovations may have also stirred up spores that were previously contained within infrastructure.
- COVID-19's Impact: The pandemic worsened the situation through several factors:
- COVID-19 itself weakens the immune system.
- Widespread use of corticosteroids for COVID-19 treatment in India might have unintentionally suppressed immunity and increased susceptibility to mucormycosis.
- The pandemic placed a heavy burden on the healthcare system, potentially increasing the risk of hospital-acquired infections.
What are the Symptoms of Rhinocerebral Mucormycosis?
The symptoms of RCM can vary depending on the stage of the infection.
The symptoms may be mild and nonspecific in the early stages, making diagnosis difficult. However, as the infection progresses, the symptoms become more severe.
Early Symptoms
The initial signs of black fungus infections resemble other respiratory illnesses or allergic rhinitis (nose congestion). These include:
- Nasal congestion with black discharge from the nose
- Facial pain or pressure
- Headache
- Fever
- Swelling or redness around the eyes or nose
- Black lesions on the nasal mucosa or palate
- Reduced sense of smell
Late-Stage Symptoms
As the disease progresses, it disseminates to surrounding structures via blood vessels and can infiltrate the brain, eyes, and bone.
Late-stage symptoms may include:
- Double vision
- Vision loss
- Dizziness
- Facial numbness or paralysis
- Difficulty opening the mouth
- Difficulty swallowing
- Necrotic bone surrounding the nose
- Seizures
- Altered mental status
- Difficulty maintaining balance or walking
- Coma
Rhinocerebral Mucormycosis Diagnosis
Diagnosing RCM can be challenging, as the symptoms can be similar to those of other conditions, such as sinusitis or a bacterial infection.[5] However, if RCM is suspected, the doctor will examine the nose, sinuses, and surrounding areas for signs of infection, such as black lesions, swelling, and redness.
They may also order several tests to confirm the diagnosis, including[6]:
- Biopsy: A small tissue sample may be taken from the affected area and examined under a microscope to confirm the presence of mucormycetes fungi.
- Imaging tests: A CT scan or MRI can identify the infection’s extent and determine if it has spread to other areas. However, these imaging tests overlook the degree of damage an infection causes.
How Is Rhinocerebral Mucormycosis Treated?
Early diagnosis and treatment are crucial for a successful outcome in RCM. The treatment approach may vary with respect to the infection’s severity, the patient's overall health, and the type of mucormycetes fungi causing the infection.
The treatment options may include:
- Antifungal medications: These medications kill the fungi and stop the infection from spreading. The most commonly used antifungal medications for RCM include amphotericin B and Isavuconazonium.
- Immunity-enhancing medications: If the patient has a weakened immune system, the doctor may prescribe immune-boosting medications such as granulocyte colony-stimulating factors to help fight the infection. In some cases, supportive therapies may be recommended to strengthen immune function.
- Surgical debridement: In severe cases, surgery may be necessary to eliminate the infected tissues and prevent the infection from spreading. Debridement may also make it easier to deliver medications to the site of the infection.[7] Milder cases may benefit from minimally invasive endoscopic procedures for early diagnosis and debridement.[8]
- Reconstructive surgery: In extreme cases, reconstructive surgery is necessary to rectify the damage to surrounding structures.[9]
Patients who struggle to breathe or are under-oxygenated can benefit from adjunctive therapy with mild hyperbaric oxygen. Hyperbaric oxygen therapy[10] can enhance oxygenation, support immune function, and create an environment that inhibits fungal growth, which may aid in controlling the black fungus infection.
Recent Advancements in Treatment
In recent years, significant advancements have been made in the treatment of RCM.[11]
Early Diagnosis
- Mucorales-specific PCR: This technique detects DNA specific to the fungi that cause mucormycosis directly from patient samples (blood, tissue). Faster and more sensitive PCR tests will enhance the speed and accuracy of diagnosis, allowing for earlier treatment intervention.
- Lateral-flow immunoassays for specific antigen detection: These assays are like rapid tests designed to detect proteins unique to Mucorales fungi. Their advantage is that they provide near-immediate results at the patient's bedside, offering a first line of diagnosis even in locations with limited lab facilities.
Novel Targeted Antifungal Therapies
- Spore coat proteins (CotH)[12]: These proteins are crucial for the fungus to invade host tissues. Research focuses on developing drugs that either block CotH directly or target the mechanisms that produce it. This approach could disrupt the infection process at a very early stage.
Boosting Immune Response
- Interferon-γ: This naturally occurring immune system stimulant is under investigation for enhancing the body's ability to fight mucormycosis. It might be used alongside antifungals as a combination therapy.
- Anti-PDR1: PDR1 is a protein in the fungus that helps it develop resistance to antifungal drugs. Blocking PDR1 could make existing antifungal medications more effective or restore sensitivity to those the fungus has become resistant to.
- Fungal-specific chimeric antigen receptor (CAR) T-cells: This highly specialized immunotherapy involves genetically modifying a patient's T-cells (immune cells) to recognize and attack the fungus causing mucormycosis specifically. It is still experimental but holds potential for severely immunocompromised patients.
Is there a Vaccine Available for Rhinocerebral Mucormycosis?
Currently, there is no vaccine available for RCM. However, researchers are developing a vaccine to help prevent the infection in high-risk individuals.
One vaccine under development targets two common mucormycosis-causing fungi and theoretically should stimulate a multi-pronged immune response against them. It will include variations of a transmembrane protein from each species to build immunity. This vaccine is still in the design phase, and the mechanism needs further scientific confirmation[13].
Complications and Prognosis
If left untreated, RCM can lead to serious complications, including[14]:
- Orbital apex syndrome: This is a rare yet severe complication of RCM that occurs when the infection spreads to the eye, causing vision loss and other symptoms.
- Brain infarction and hemorrhage: The fungus can block cerebral blood vessels, leading to strokes (infarction) and bleeding (hemorrhage).
- Meningitis: The infection can extend to the meninges, the brain’s protective membranes, causing inflammation (meningitis).
- Brain abscesses: Collections of pus can form in the brain tissue as the fungus invades.
- Facial and nasal deformities: Damage to facial tissues and structures by the fungus can cause permanent disfigurement.
- Garcin Syndrome[15]: In rare cases, RCM can progress to involve cranial nerves, causing Garcin syndrome. This condition is characterized by the progressive decline in function of multiple cranial nerves, often on one side of the face.
The prognosis for RCM is generally very poor. Without treatment, the mortality rate varies between 30% and 70%. In severe cases, the mortality rate for disseminated RCM is as high as 90-100%. With early diagnosis and prompt treatment, survival rates improve. Combined antifungal therapy and surgical treatment results in a 70% survival rate on average. Severely immune-compromised patients, such as those with HIV, are highly susceptible to mortality.
Prevention
While it may not be possible to prevent RCM completely, there are steps to take to lower the risk of developing the infection, including:
- Managing underlying health conditions, such as diabetes.
- Avoid contact with soil or decaying organic matter, especially if you have a weakened immune system. If gardening, wear gloves, waterproof boots, long pants, and other protective gear, and keep this gear away from your ordinary clothing, food, and other household goods.
- Practicing scrupulous hygiene, such as washing your hands regularly and keeping wounds clean and covered.
- Avoiding the use of contaminated medical equipment or medications.
- Seeking prompt treatment for any infections or wounds.
- Do not seek treatment at a hospital or clinic undergoing renovations, particularly if you live in a highly endemic area with a tropical or subtropical climate.
- If living in an endemic area, follow warnings for outbreaks and stay indoors if the weather promotes mold growth.
- Maintaining a healthy lifestyle by managing stress effectively, engaging in routine physical activity, and consuming a healthy diet. It is essential to emphasize stable blood sugar levels and to support immune function.
Living with Rhinocerebral Mucormycosis
Life after surviving rhinocerebral mucormycosis is not without challenges. The aggressive nature of the disease and its treatments can leave lasting consequences, demanding extensive rehabilitation and continuous medical care.
Depending on the severity of the infection, survivors may face:
- Facial disfigurement from tissue damage and surgical interventions.
- Vision loss or impairment due to eye involvement.
- Neurological deficits if the infection involves the brain or cranial nerves.
- The trauma of the disease, disfigurement, and potential disabilities can heavily impact mental health. Depression, anxiety, and struggles with self-image are common.
Regular monitoring is essential to:
- Manage any residual effects of the infection.
- Monitor for recurrence of mucormycosis.
- Screen for long-term complications of treatment.
- Address underlying conditions like diabetes that increase vulnerability.
Access to physical therapy, occupational therapy, reconstructive surgery, psychological counseling, and support groups for survivors can significantly improve their quality of life.
Conclusion
Rhinocerebral mucormycosis is a rare but serious fungal infection affecting the nasal passages, sinuses, and brain. While it is rare, knowing the risk factors, symptoms, and treatment options is crucial to ensure early diagnosis and prompt treatment. Through preventative measures and seeking swift medical treatment if you experience symptoms, you can lessen your odds of developing RCM and improve your chances of a successful.
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