Mucormycosis

Dr. Ajay Mohan (AIIMS)MBBS

December 21, 2020

May 31, 2021

Mucormycosis
Mucormycosis

Mucormycosis—also known as zygomycosis—is a type of fungal infection that can affect the sinuses and brain, the lungs, the skin or the stomach and intestines. A “disseminated” form of the infection may also affect different parts of the body at once.

Normally, the fungi that cause this infection exist in our environment without causing disease—these fungi can be present in the soil, in rotting leaves or wood, or in compost piles. However, in people who are immunocompromised by another illness, mucormycosis may develop aggressively and even turn fatal if not detected early.

Lately, cases of mucormycosis in COVID-19 patients across India have come to light.

Diagnosis may involve a mix of physical examination, tests like fungal culture test and bronchoalveolar lavage and in some cases, a biopsy of the affected tissue.

Since mucormycosis is an opportunistic infection, treating the underlying cause and improving immunity are important to the treatment. Antifungals, especially amphotericin B, are the mainstay of treatment with adjuvant treatments (additional, supporting the main treatment) with hyperbaric oxygen under research.

Research has shown that mucormycosis-causing fungi need to scavenge or take iron from the body. For this reason, chelation therapy to remove excess iron (but not with deferoxamine) could also be useful for treating the infection.

Further, treatment may involve surgery on the part of the body affected by the fungus. For example, in the case of rhinocerebral mucormycosis which affects the sinuses and the brain, a nasal endoscopy may be done to check for necrotic or dead tissue and to guide its removal through surgical debridement. 

The prognosis varies, depending on the type of mucormycosis and the patient’s overall health. Generally, the prognosis is poor. For patients with pre-existing HIV/AIDS and for people with the disseminated form of this infection, there is a very high risk of mortality.

Read on to know all about the types, symptoms, causes, diagnosis and treatment of this opportunistic fungal infection:

Mucormycosis types

Based on which part of the body is affected, this fungal infection is classified into six forms:

  • Rhinocerebral: Affects the sinuses and brain
  • Pulmonary: Affects the lungs
  • Cutaneous: Affects the skin
  • Gastrointestinal: Affects the stomach and gut
  • Disseminated: Affects different parts of the body like the sinuses, brain, lungs, skin, inner lining of the heart chambers, heart valves and sometimes the kidneys
  • Uncommon presentations: Comprises all other presentations

There is some evidence of a relationship between the predisposing condition (or the condition that puts one at risk of the infection) and the type of mucormycosis that one may develop. The findings are reproduced here, though they date back to the early 2000s:

Condition that makes one prone to infection

Type of mucormycosis

Diabetic ketoacidosis

Rhinocerebral

Neutropenia

Pulmonary or disseminated

Use of corticosteroids

Pulmonary, disseminated or rhinocerebral

Use of deferoxamine (an iron chelator)

Disseminated

Nutritional deficiencies (vitamin B12, B9 or copper deficiency)

Gastrointestinal

Trauma or skin maceration; catheter or injection site 

Cutaneous or subcutaneous (under the skin)

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Mucormycosis symptoms

This fungal infection may present with different symptoms depending on which part of the body it affects:

Rhinocerebral (sinuses and brain) symptoms

Unless treated at this stage, the infection could spread and cause a lot of damage to the tissues of the face. Further symptoms to watch out for include:

  • Necrosis (tissue death) in the roof of the mouth (palate)—this can be seen as black spots or lesions inside the mouth
  • Disintegration of the nasal septum, or the wall separating the nostrils
  • Swelling around the nose (perinasal area)
  • The skin over the sinuses and eye socket become red (erythema), or occasionally, blue (cyanosis) from lack of enough oxygen. Black lesions could also appear on the bridge of the nose
  • Blurry vision or double vision

If the infection reaches the brain, the symptoms could be:

  • Lethargy
  • Seizures
  • Slurred speech
  • Partial paralysis
  • Cranial neuropathy (problems with the nerves of the face and eyes)
  • Brain abscess
  • Altered consciousness
  • Coma

Eye symptoms

  • Swollen eyes due to fluid buildup (periorbital edema)
  • Bulging or displacement of the eye (proptosis)
  • Vision loss or even blindness
  • Difficulty or pain while moving the eyes due to weakness or paralysis in the muscles that move the eyes (ophthalmoplegia)

Symptoms in lungs: Normally, if someone inhales the spores that cause mucormycosis, the spores would stick to the mucus and be expelled from the body with a sneeze or a cough (remember that coughing and sneezing are actually protective reflexes of the body). In a healthy person, the spores that are not cleared away with the mucus are destroyed by immune cells called neutrophils. However, in people with illnesses that result in neutropenia or low neutrophil count, the spores can enter the lungs and cause infection. In such cases, the symptoms of mucormycosis in the lungs (pulmonary mucormycosis) could be:

Skin symptoms (cutaneous mucormycosis)

  • Hardening of one area of the skin
  • Pain and inflammation in the tissue beneath this hardened area
  • Surrounding skin may become red, warm to the touch, swollen and painful: the four key signs of inflammation

Less common skin symptoms of this infection include:

  • Open sores
  • Blisters
  • Necrosis: Rarely, the affected tissue could turn black, indicating necrosis or tissue loss
  • Fever

Skin infection due to Zygomycetes family (Mucorales order) could develop slowly or set in and become severe suddenly (fulminant).

Stomach symptoms: Stomach- and gut-related symptoms can arise if the spores enter the body through the mouth or through contaminated food. The symptoms include:

  • Abdominal pain
  • Nausea and vomiting
  • Gastrointestinal bleeding
  • Vomiting blood (hematemesis)
  • Lesions that can lead to perforation of the stomach or intestines
  • Peritonitis or inflammation of the inner lining of the stomach and the lining of other organs in the abdomen
  • Bowel infarction: Loss of blood flow to the bowel, which is painful
  • Shock, in case of significant blood loss (hemorrhagic shock)

Disseminated mucormycosis symptoms: This is a rare form of the infection that is seen in people with heavily compromised immunity due to a preexisting condition. The symptoms can vary, as the infection spreads to multiple parts of the body including the brain, sinuses (sometimes the sinuses and the brain—known as rhinocerebral or rhino-cerebellar infection), skin, lungs, heart, kidneys and spleen, among other organs.

Causes and risk factors of mucormycosis

Mucormycosis is an opportunistic infection. It is caused by the zygomycetes family of fungi—mainly Mucor, Rhizopus, Absidia and Cunninghamella species—that normally exist in our surroundings without causing infection. However, in people with weak immunity or in those who are immunocompromised, mucormycosis can develop and even be fatal if not diagnosed and treated in time.

In India, researchers have found that the following fungi are increasingly responsible:

  • Apophysomyces elegans
  • Rhizopus homothallicus
  • Mucor irregularis
  • Thamnostylum lucknowense

The infection-causing agent can enter the body through:

  • The nose
  • Broken skin, due to a cut or burn, etc.
  • Less commonly through the mouth or through contaminated food

For infection to occur, a few things need to happen:

  • The causative agent needs to draw sufficient iron from the host’s body for growth
  • The causative agent needs to overcome the host body’s phagocytic mechanisms (a part of the immune system that destroys pathogens by eating them)—these mechanisms are already weakened in some immunocompromised people
  • The causative fungi need to gain entry to the vasculature (blood circulation) to spread/disseminate

In a healthy person, these fungi are unable to cause disease as:

  • The body can use special iron-binding proteins to sequester or tie-up the iron present in blood
  • Immune cells like phagocytes (including neutrophils) and macrophages, and endothelial cells (outermost cell layer of blood vessels) protect the vessels from invasion

In people who are susceptible to this infection, these defence mechanisms don’t work or don’t work properly. This, in turn, can happen for a number of reasons.

  • In diabetic ketoacidosis, for example, the low blood pH (acidic) makes it difficult for the body to bind iron using iron-binding proteins. The excess iron in blood creates conditions for the growth of the fungus.
  • In neutropenia—which can occur in some infections, nutritional deficiencies (like vitamin B12 deficiency), cancer or as a result of cancer therapies—the fungus can grow easily in the absence of enough neutrophils to eat/destroy it. Once the fungus damages the endothelial cells and gets into the blood vessels (angioinvasion) resulting in vessel thrombosis, tissue necrosis and dissemination (spread) of the infection throughout the body.

In terms of risk factor, people with weak immunity are susceptible to this infection. According to medical evidence, the risk is known to high in case of

"(In India,) Rhino-orbito-cerebral presentation (sinus-eyes-brain symptoms) associated with uncontrolled diabetes is the predominant characteristic," explained researchers Arunaloke Chakrabarti and Rachna Singh in a 2014 article published in the journal Mycoses.

Mucormycosis fungal infection diagnosis

Research shows that there are five main mould infections (including mucormycosis) that can have a significant impact on our health. These are Aspergillus disease (caused by Aspergillus fumigatus) fusariosis (fusarium fungus), scedosporiosis (scedosporium fungus), Lomentospora-related infections and mucormycosis (mucormycete). Of these diagnostic tests and biological markers are well-established for Aspergillus diseases only. (Read more: Aspergillus galactomannan antigen test)

To diagnose mucormycosis, your doctor will check if you have a pre-existing condition that could have weakened your immunity. Lately, cases of mucormycosis have emerged among COVID-19 patients in India.

Next, your doctor will ask you about your symptoms. Make sure you tell them if you have any blue or black discolouration of the skin and psychological symptoms like an altered state of mind in addition to other symptoms. (Altered state of mind could manifest in a number of ways; if you feel or if someone has told you that you haven’t been behaving like your usual self, do let the doctor know).

The doctor may also order some tests like a fungal culture test like a KOH fungal smear test. He or she may also perform a bronchoalveolar lavage (a small amount of sterile fluid is introduced into a previously identified portion of the lungs; the fluid is then extracted for examination). In the case of lung infection, a sample of sputum or nasal discharge may be tested. For skin infection, a sample of the skin may be tested.

A tissue biopsy may be recommended in some cases.

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Mucormycosis treatment

There are three important steps in the treatment of mucormycosis:

  • Early detection
  • Treatment of the predisposing condition
  • And treatment of the infection with:
    • Liposomal amphotericin B: This is an antifungal medicine used to treat potentially life-threatening fungal infections only. The medicine is given as an intravenous injection, to kill the fungal cells with fewer side effects than the conventional form of amphotericin B (known as amphotericin B deoxycholate or DAmB).
      For the treatment of mucormycosis, high-dose liposomal (lipid-based) amphotericin B is given on its own or in combination with an echinocandin (antifungal medicine that inhibits a certain enzyme that is needed to make the fungal cell wall) and/or an azole (itraconazole). Treatment is usually continued for more than four to six weeks, to ensure that the infection has cleared completely.
    • The US Food & Drug Administration (FDA) has also approved the use of isavuconazole for invasive mucormycosis.
    • Surgery is often required to remove the infected tissue, including infected brain tissue. In some cases, the palate (roof of the mouth) or parts of the eye or nasal cavity may have to be removed.

Medical researchers are looking into additional therapies like using hyperbaric oxygen (high-pressure oxygen) to assist the neutrophils in killing the pathogenic fungus, and cytokine therapy to treat the infection.

Controlled and randomised trials need to be done to confirm the usefulness of these therapies, before making them available, according to the researchers. Having said that, researchers have also pointed out the difficulty of doing randomised controlled trials, given the seriousness and high mortality of this infection.



Mucormycosis FAQs

Question over 2 years ago

What is Black Fungus?

The truth is that we don’t know everything about it yet, but let’s start by calling it what it is – “Mucormycosis”. It's an aggressive and invasive fungal infection caused by a group of fungi called “mucormycetes”.

Question over 2 years ago

How does Black Fungus spread?

Dr. Ayush Pandey MBBS, PG Diploma , General Physician

“Mucormycetes” are ubiquitous – you can find them in soil, fallen leaves, compost, and air.

Most commonly, these are inhaled through the nose. Therefore, wearing a mask probably helps prevent it.

Question over 2 years ago

Is Black Fungus contagious?

Dr. B. K. Agrawal MBBS, MD , Cardiology, General Physician, Internal Medicine

No – you can’t get infected even if you’re in close contact with someone who has the disease.

Question over 2 years ago

What makes you more prone to Black Fungus?

Dr. Braj Bhushan Ojha BAMS , Gastroenterology, Dermatology, Psychiatry, Ayurveda, Sexology, Diabetology

By far, the most important reason is reduced immunity – and there are several reasons for this – diabetes, being on steroids, taking immunosuppressant drugs, chemotherapy, and so on.