Rhinocerebral Mucormycosis

What is Rhinocerebral Mucormycosis?

Rhinocerebral mucormycosis, also called zygomycosis, is a rare disease caused by a type of fungus known as filamentous fungi. This condition affects the nose, areas around the nose (paranasal sinuses), and the brain. Filamentous fungi are types of disease-causing organisms that typically affect people who have weakened immune systems. Because these fungi usually infect individuals that have weaker immune defenses, they grow rapidly and aggressively. This leads to a severe and potentially life-threatening condition. It’s really important to intervene as quickly as possible to save lives and avoid permanent damage to the brain.

In most people, this condition appears as a sudden fungal infection, but in some cases, it can occur more slowly as a chronic infection. Chronic forms of this condition are slower and progressive, taking several weeks to develop.

This disease often appears in people with certain medical conditions like diabetic ketoacidosis (a severe form of diabetes), severe burns, people on certain medications like steroids, solid organ transplant recipients, people with iron overload disease (hemochromatosis), HIV-positive patients, people with neutropenia (a decrease in a type of white blood cell), malnourished individuals, and those with blood cancers.

However, it’s important to note that just because these conditions are not present, it doesn’t mean that mucormycosis can’t occur. Studies have shown that about 9% of rhinocerebral mucormycosis cases occur in patients without any identifiable contributing factors.

What Causes Rhinocerebral Mucormycosis?

Rhinocerebral mucormycosis, a serious infection of the sinuses and brain, is caused by a type of fungus found in soil or organic matter. These fungi belong to a group known as Phycomycetes and include specific types like Apophysomyces elegans, Mucor, Rhizopus, Absidia, and Cunninghamella. The most common way this fungus enters our body is by breathing in its spores, particularly in people whose immune systems are weakened.

This type of infection tends to flourish in individuals with a weakened immune system or conditions such as high blood sugar levels or excess iron in the body. It’s also known as an “opportunistic infection” – meaning it takes advantage of situations where the body’s defenses are weak. This infection is more common in hot and humid climates and areas, especially in tropical regions and during the summer season.

Risk Factors and Frequency for Rhinocerebral Mucormycosis

Mucormycosis is a disease whose occurrence varies greatly, depending on the number of at-risk individuals in various populations. This makes it difficult to accurately measure how common it is. In the United States, the most common type of mucormycosis is known as the rhinocerebral form. In India, the leading cause of mucormycosis is uncontrolled diabetes. Roughly, for every 100 patients with types of blood cancer, about 4 will get mucormycosis. The type of blood cancer known as Acute myeloid leukemia makes up 62% of all these cases.

• The rate of mucormycosis can vary a lot depending on the number of people at high risk.
• It’s hard to accurately figure out how common this disease is.
• The most common type of mucormycosis in the US is the rhinocerebral form.
• In India, uncontrolled diabetes is the main cause of mucormycosis.
• For every 100 patients with types of blood cancer, about 4 will have mucormycosis.
• Out of all the blood cancer cases, Acute myeloid leukemia makes up 62%.

Signs and Symptoms of Rhinocerebral Mucormycosis

Rhinocerebral mucormycosis is a condition that can be hard to diagnose early on as its symptoms aren’t very specific. This medical condition primarily impacts the head and comes with symptoms like one-sided headaches and fatigue. Other common symptoms include:

• Nausea
• Fever
• Nasal congestion
• Nasal dripping
• Nose bleeding
• Nasal numbness
• Facial pain or numbness
• Black nasal discharge
• Sinusitis
• Eye pain
• Vision loss
• Double vision
• Blurred vision
• Convulsions
• Dizziness
• Changes in thinking
• Unsteady walk
• Breathing difficulty
• Coughing
• Spitting blood
• Vomiting
• Abdominal pain

Physical exams can reveal other symptoms of rhinocerebral mucormycosis such as red and swollen nasal and orbital cellulitis, which can darken over time due to tissue death. In severe cases, a black scar might be visible on the nasal or mouth roof, in addition to the bleeding nose. Eye issue symptoms can include bulging of the eye, impaired eye movement, vision loss, nystagmus (rapid involuntary eye movement), and a non-responsive pupil.

You might find patients in a coma or showing stroke-like symptoms when the brain is affected or when blood flow is blocked. A neurological examination may reveal issues with the second to seventh cranial nerves, which could look like muscle weakness or loss of sensation.

Testing for Rhinocerebral Mucormycosis

When a medical condition presents with symptoms that don’t point to a specific diagnosis, high suspicion is critical, especially when certain risk factors exist. In these cases, doctors often take a small sample of tissue (biopsy) from the necrotic (dead) tissue in the antrum, a part of the stomach, to study its microscopic structure (histopathology). The comparison between what the doctor sees clinically and the microscopic structure of the tissue has a significant role in making the diagnosis.

Some doctors may choose to get a computed tomography scan, also known as a CT scan, before performing a biopsy, because a biopsy can take time. The CT scan allows doctors to assess the extent of the disease and gives a quick view of the condition. The scan often reveals bone erosion and blocked sinuses. Another type of imaging, magnetic resonance imaging (MRI), can be used to view changes in soft tissue very clearly. However, it’s more costly than a CT scan.

A CT scan is the preferred tool for quickly detecting infections because it can show thickened mucous membranes and dense areas. In the chronic phase of invasive sinusitis, a disease that causes inflammation and swelling of the sinus, a CT scan typically shows opacification (blocking of light) in the sinuses and bone erosion. These findings can help determine the best surgical procedure, if surgery is needed. However, CT scan results aren’t specific to any one condition. False positives, or diagnosing a disease when it isn’t present, can occur. Similarly, false negatives, or failing to identify a disease that is present, can also occur, including on seemingly normal sinus CT scans.

Nasal scraping and fine-needle aspiration cytology, which is collecting cells or tissue through a thin needle, can help doctors make a diagnosis. This typically reveals the presence of fungal structures known as hyphae. Blood cultures, which involve growing bacteria or other microorganisms from a blood sample, are not preferred because they rarely show positive results. Similarly, swab samples taken from the sinuses often don’t show any positive results. Cerebrospinal fluid, a clear fluid found in the brain and spinal cord, is also often negative for fungal hyphae. In these cases, an endoscopic examination of the sinuses, using a thin tube with a light to see inside the body, can help identify dead tissue and aid in collecting a tissue sample for a biopsy.

Treatment Options for Rhinocerebral Mucormycosis

Rhinocerebral mucormycosis is a severe and fast-spreading infection. The ideal treatment is currently undefined, making it necessary to establish clear and effective therapeutic strategies through extensive clinical trials. In the meantime, patients suspected of this fungal infection are given a drug called amphotericin B, over a duration of 4 to 6 weeks to eliminate the infection. The exact dosage of this medication isn’t established yet, but according to some studies, patients tolerated a daily dosage of 50 mg well.

Although amphotericin B is able to fight the fungus effectively, it may cause kidney damage. To reduce this risk, a modified form of the drug known as liposomal amphotericin B is preferred because it’s less harmful to the kidneys and can be given in higher doses. However, its use may be limited due to cost and availability constraints in certain regions. Patients receiving this treatment are regularly monitored to check their kidney function and may be given a medication called warfarin to prevent blood clotting, especially in cases where blood vessels are blocked by clots.

After the medical treatment, surgical removal of the fungal mass is generally recommended. However, some studies suggest immediate surgical removal as soon as the disease is diagnosed, with subsequent use of amphotericin B. This surgery is an invasive procedure that involves removing the affected body tissue and the fungal growth, followed by draining and rinsing of the sinuses. Depending on the location and extent of the disease, the configurations of body parts like the palate, eyes, and nasal cavity might be changed. The surgical procedure employed may differ based on the sinuses affected. Procedures like maxillectomy or ethmoidectomy, which involves the removal of disease-affected parts of the mouth or nose respectively, could be performed. The extent of these procedures depends on the degree of bone and surrounding tissue involvement.

In severe cases affecting the eyes, a procedure called orbital exenteration might be necessary, which implies removal of the eye and its connected tissues. However, if the eye contents aren’t affected, the base of the orbit (socket) might be preserved. If the disease spreads to the brain, surgical procedures like craniotomy and debridement, which involve removing a section of the skull and cleaning of the wound, might be required.

Thanks to technological advancements, endoscopic sinus surgery has become possible, which is especially beneficial in treating rhinocerebral mucormycosis. This surgical approach focuses on removing blockages and enhancing ventilation in the sinuses. It also offers improved visualization during the procedure. Prevention of this disease’s invasive progression by addressing an earlier stage of sinusitis (sinus inflammation) is thought to be more effective. This involves a thorough understanding of the disease development and focusing on ventilation and drainage to decrease the chance of recurrence.

Alternative treatments include hyperbaric oxygen therapy that enhances our body’s neutrophils to fight the fungus by providing them with enough oxygen. Another drug, Rifampicin, can also assist amphotericin B in treating this infection. Quick identification and treatment of the underlying cause, such as diabetes or an immune-suppressing condition, is important. Consulting with respective specialists is crucial, such as treating diabetic ketoacidosis with insulin under the instruction of physicians. Additionally, immunity can be increased by administering granulocyte colony-stimulating factors, which promote the production of a type of white blood cell called leukocytes. Some medications like azoles can serve as a rescue therapy, and iron chelators may be beneficial in cases where the cause is hemochromatosis, a condition that involves absorption of too much dietary iron.

What else can Rhinocerebral Mucormycosis be?

It can be quite challenging for medical professionals to distinguish between rhinocerebral mucormycosis and other diseases that show similar symptoms and affect the same parts of the body. The following are some of the conditions they need to consider:

• Bacterial Sinusitis and Allergic Fungal Sinusitis: In the early stages, mucormycosis causes sinusitis, which can be confused with other forms of sinusitis. When someone is diagnosed with mucormycosis, they should stop taking antibiotics for bacterial sinusitis. Allergic fungal sinusitis may lead to eye protrusion and a large mass in the nose and brain area. However, this is typically diagnosed in people with a history of recurring allergies and sinus infections, nasal polyps, and high levels of IgE (a type of antibody).
• Aspergillosis: This is a fungal sinusitis that can show similar symptoms to mucormycosis in people with weakened immune systems. Although it can be hard to tell these two infections apart, certain types of medical stains can help. Also, aspergillosis usually doesn’t cause the formation of a black scab, which is a common sign of mucormycosis.
• Nasal and Paranasal Malignancies: Mucormycosis is a very invasive disease and can sometimes be mistaken for cancers due to a nasal mass and bleeding.
• Proptosis: This is a common symptom of mucormycosis whereby the eye bulges out. Other conditions like Graves disease, orbital tumors, cellulitis, and subperiosteal hematoma can also cause protrusion and need to be ruled out.
• Brain Tumor and Pseudotumor Cerebri: These conditions share similar symptoms with mucormycosis like headaches, dizziness, nausea, and vision problems. Pseudotumor cerebri is a condition where the pressure inside the skull increases.
• Cavernous Sinus Thrombosis: Mucormycosis can cause this condition, which can also be due to infection spread from the nose, eyes, face, ear, and pharynx. This often affects both eyes, leading to proptosis, chemosis (swelling of the conjunctiva), and nerve damage.
• Migraine Headache: This is a condition is marked by recurring headaches that often accompany nausea, vomiting, and sensitivity to light. The one-sided nature of this headache can mimic the presentation of rhinocerebral mucormycosis.

What to expect with Rhinocerebral Mucormycosis

While most people diagnosed with this sickness don’t have a favourable outlook despite serious treatment, detecting the disease early and starting treatment right away can noticeably improve their chances of survival. How many people survive this sickness varies depending on how severe the disease is and how far it’s spread. For the variety of the disease that affects the nose and brain, about 30% to 70% of patients pass away. For the type that has spread throughout the body, the mortality rate can rise to 90%. If a patient has AIDS, they’re almost certainly going to pass away from this disease.

Studies have shown that a blend of surgical treatment to remove diseased tissue and antifungal medication boosts the survival rate to 70%. That’s more than the 57% survival rate for surgery alone or the 61% for just using anti-fungal drugs.

Another study showed that starting treatment within 5 days of diagnosing the disease increased the survival rate to 85%. However, the survival rate dropped to 49% if treatment began more than 6 days after diagnosis. The mortality, or death, rate can range from 80% to 145%, impacted by patient-specific factors and when the diagnosis and treatment were made. Research findings conclude that patients with predisposing factors and cerebral (or brain) involvement tend to have a higher death rate than those without such factors.

Possible Complications When Diagnosed with Rhinocerebral Mucormycosis

Brain infarction, which is a type of stroke, and hematoma, a collection of blood outside of blood vessels, can both occur due to rhinocerebral mucormycosis. This condition often invades blood vessels, causing blockages that can lead to stroke in parts of the brain including the cerebrum, cerebellum, and brainstem. It can also weaken blood vessels, which can lead to swollen blood vessels known as aneurysms. If these aneurysms rupture, bleeding can occur, leading to the formation of a hematoma.

Ophthalmoplegia, or eye muscle weakness, and vision loss can also occur due to this condition. Eyelid drooping, or ptosis, can occur if there’s damage to a specific cranial nerve, and sensation in the cornea might also decrease. One might also notice proptosis, which is a bulging of the eye, due to a variety of reasons including vein congestion and lack of tone in the eyeball. Other eye-related complications can occur, too, such as excessive bleeding in the clear front surface of the eye, known as hemorrhage, as well as fluid buildup or edema. In some cases, orbital cellulitis, an infection behind the eyeball, can occur.

Meningitis, an inflammation of the protective membranes of the brain and spinal cord, occasionally occurs in rhinocerebral mucormycosis cases. This inflammation can be caused by either inflammation of the blood vessels or fungal infection of the protective layers of the brain.

Rhinocerebral mucormycosis can also cause problems with the brain tissue, resulting in abscesses, particularly in chronic cases. Sometimes, these abscesses can be complicated by bacterial infections, which can lead to paralysis on one side of the body, or hemiplegia.

Garcin syndrome might also occur, which is characterized by paralysis in cranial nerves without affecting sensory and motor tracts. This syndrome results due to direct invasion of the nerves or blood vessels surrounding the brain rather than a direct injury to the brain tissue.

Lastly, this fungal infection can lead to changes in the facial and nasal structure. Particularly, when the eye is removed, known as orbital exenteration, to control the infection, it can disfigure facial structures.

Complications of rhinocerebral mucormycosis can include:

• Brain stroke
• Hematoma in brain
• Eye muscle weakness and vision loss
• Eye bulging and eyelid drooping
• Corneal injuries
• Bleeding in the front of the eye and fluid buildup
• Infection behind the eyeball
• Meningitis
• Brain abscesses
• Garcin syndrome
• Changes to the facial and nasal structure
• Facial disfigurement due to removal of the eye

Preventing Rhinocerebral Mucormycosis

People with weaker immune systems are especially prone to a severe infection called mucormycosis, so it’s crucial for them to get medical help early on. Recognizing the symptoms of a specific form of this infection, rhinocerebral mucormycosis, can encourage people to seek medical help quickly. This early action can help doctors diagnose the condition faster, which can significantly improve a person’s chances of survival. Patients often feel more comfortable and well-informed when information about their illness is conveyed in a way they can easily understand.

Moreover, patients who have a higher level of education may be given more detailed information about their condition. Giving patients information about how to spot the symptoms of their disease can help them identify early signs of it. Patients have the right to choose how their condition is investigated and treated, which includes deciding to accept or decline suggested treatment options. However, it’s essential that patients receive thorough advice and clear instructions about their treatment options. This will put them in a better position to understand the pros and cons, as well as the necessity and potential risks associated with their treatment options.