Fungal Infections of the Oral Mucosa

What is Fungal Infections of the Oral Mucosa?

The mouth is home to a complex mix of microorganisms including fungi such as Candida, Aspergillus, and Rhizopus. While these fungi are usually harmless, they can cause infections under certain conditions. Fungal infections have been increasing, particularly among COVID-19 patients, due to factors like weakened immune systems, high blood sugar due to diabetes, long hospital stays, extended use of steroids, and certain types of cancer.

New treatments for various diseases have also contributed to the increase in fungal infections. Diagnosing a fungal infection in the mouth is based primarily on symptoms and examination of affected tissue. Symptoms can include a burning sensation, unpleasant taste, white patches, sores, redness, and pain. Common types of fungal infections in the mouth include conditions known as candidiasis, aspergillosis, mucormycosis, histoplasmosis, blastomycosis, cryptococcosis, paracoccidioidomycosis, and geotrichosis.

There have been advances in detecting fungal organisms, such as rapid DNA tests like PCR. Fast assessment of any oral lesions is important to identify the problem, start treatment, and track progress. Managing a fungal infection generally involves good oral hygiene, addressing the factors that make a person more susceptible, and using the right antifungal drug. Occasionally, surgery may be needed to remove infected tissue. The key steps in dealing with fungal infections in the mouth are evaluating oral lesions, identifying and addressing risk factors, and using an effective antifungal medication.

What Causes Fungal Infections of the Oral Mucosa?

Oral Candidiasis, also known as thrush, is mainly caused by a fungus called Candida albicans. Around 95% of these mouth infections are due to this type of fungus. Recently, however, there have been more cases caused by other types of Candida. Factors like age, having the presence of cancer, the use of certain antifungal medications, having a tube placed in the body, and advancements in how we test for this illness may be contributing to this increase.

Some other types of Candida that can cause thrush include Candida glabrata, Candida tropicalis, Candida parapsilosis, Candida dubliniensis, Candida guilliermondii, Candida krusei, and Candida kefyr. Apart from Candida albicans, Candida glabrata and Candida dubliniensis are most likely to be found causing oral infections in people with HIV. One particular strain, Candida auris, has been causing multi-drug resistant outbreaks in healthcare settings, especially amongst those who have had COVID-19.

Aspergillosis is an infection caused by the Aspergillus species. These organisms typically grow on dead and decaying matter. Aspergillus fumigatus is the most common cause of this infection because its size allows it to easily enter the air sacs in our lungs. Aspergillus flavus can cause infections that are restricted to the sinus area.

Mucormycosis, or zygomycosis, is caused by the Zygomycetes group of fungi which includes Rhizopus, Mucor, Absidia, and Rhizomucor species. The fungus known as Rhizopus causes 90% of an uncommon infection, rhinocerebral mucormycosis, which affects the brain and nervous system.

Histoplasmosis is caused by the Histoplasma capsulatum, an environmental fungus that flourishes in soil contaminated by bird or bat droppings. There are two types of histoplasmosis in humans, American histoplasmosis and African histoplasmosis, caused by different strains of this fungus.

Blastomycosis is caused by a fungus called Blastomyces dermatitidis, which exists as a spore in the environment. This fungus usually lives in acidic, moist, and sandy soil. Two other species, Blastomyces helicus and Blastomyces percursus, also cause blastomycosis.

Cryptococcosis can be caused by the Cryptococcus species, for instance, Cryptococcus neoformans which can be found in bird droppings, environmental organisms like amoebas, and tree hollows.

Paracoccidioidomycosis, or South American blastomycosis, can be caused by various strains of the Paracoccidioides brasiliensis fungus.

Geotrichosis is a rare infection caused by the Geotrichum candidum fungus. Strains like Geotrichum capitatum and Geotrichum clavatum can affect the lungs.

Risk Factors and Frequency for Fungal Infections of the Oral Mucosa

Oral candidiasis is the most common oral fungal infection, largely affecting newborns and older adults. Roughly 5% to 7% of infants get oral candidiasis. Factors that can increase the risk include weakened immune system, diabetes, malnutrition, long-term use of steroids or antibiotics, and wearing dentures. This infection is especially common among individuals with AIDS, cancer, or those undergoing radiation or chemotherapy.

Aspergillosis is another oral fungal infection, more common in males. While it’s rare for it to start in the mouth, it can spread there from the nose or sinuses. Patients with uncontrolled diabetes, weakened immune system or undergoing chemotherapy are more prone to it. The most commonly affected areas are the gums, followed by the hard palate and the maxillary sinus.

Mucormycosis, being the third most common oral fungal infection, can turn deadly especially in people with diabetes, blood cancers, or those receiving deferoxamine therapy. It rarely affects healthy individuals. This infection has increased among COVID-19 patients due to uncontrolled diabetes, long-term use of corticosteroids, and other factors. Mucormycosis typically occurs in individuals aged between 40 to 60, and up to half of these patients have diabetes.

Histoplasmosis is the most common overall fungal infection in the U.S, and it’s more common in men. It affects the lungs mainly while oral lesions are rare. It can affect the oral cavity in disseminated form, localized lesion, or as the only manifestation. The most commonly affected oral areas are the tongue, palate, and lips.

Blastomycosis is more common in Central and Southern North America. It usually affects healthy individuals and often causes oral lesions. Men aged 20 to 50 who work outdoors are particularly at risk.

Cryptococcus neoformans infection can occur in both individuals with healthy and weakened immune systems, but Cryptococcus gattii mainly infects healthy ones. About 95% of cryptococcal infections are caused by C. neoformans and 4% to 5% by C. gattii. More than 80% of cryptococcosis cases are among HIV patients. It mainly affects the central nervous system and lungs, while oral lesions are rare.

Paracoccidioidomycosis is more prevalent in Latin America and in males. The reason behind its lower prevalence in females is due to beta-estradiol in female hormones which prevents the conversion of hyphal to yeast form.

Geotrichosis is rare in the nails, skin, and oral cavity. The most common form of the disease is a pulmonary infection.

Signs and Symptoms of Fungal Infections of the Oral Mucosa

The diagnosis of an oral fungal infection is generally based on what the infection looks like and the results of tests on a small sample of the infected tissue. Different types of fungi can cause different symptoms and signs.

Oral Candidiasis

People with oral candidiasis usually complain of a burning sensation or bad taste in their mouth that persists for weeks, months, or even years. Some symptoms of oral candidiasis, or thrush, include:

• White patches on the cheeks, tongue, or roof of mouth, which can be wiped or scraped off, showing a red inflamed area underneath.
• These patches are often seen in babies who are more susceptible due to their developing immune systems.
• Use of steroid inhalers, mouth rinses, gels, and ointments, or dry mouth may increase the risk of developing oral candidiasis.
• Red inflamed areas with loss of normal tongue texture and color, known as erythematous candidiasis, can also happen. Long-term use of broad-spectrum antibiotics can trigger this condition.
• Other forms of oral candidiasis can cause inflamed red areas at the corners of the mouth, sores on the palate of people who wear dentures, and a red inflamed area in the middle of the tongue

Aspergillosis

The symptoms of aspergillosis vary according to a person’s immune health. People with a healthy immune system may experience allergic sinusitis. Pain or discharge from the nose may signal a low-level infection in the upper jaw sinus, which can be caused by damage to the tissue following tooth extraction or root canal. Aspergillosis in the mouth appears as painful swelling and ulcers, which may become necrotic or decayed. In people with compromised immune systems, aspergillosis can spread to the sinuses and lungs.

Mucormycosis

There are six clinical types of mucormycosis, resulting in symptoms such as nasal blockage, nasal discharge, facial pain and swelling. It most commonly affects the palate in the mouth, causing, at first, swelling of the upper jaw and later, a black, decaying ulcer and perforation of the palate.

Other Conditions

There are other types of oral fungal infections such as histoplasmosis, blastomycosis, cryptococcosis, and geotrichosis, which exhibit symptoms ranging from painful ulcers, swelling, non-healing extraction sockets, non-healing ulcers, to pseudomembranous white plaques and red, inflamed plaques or granulomas.

Testing for Fungal Infections of the Oral Mucosa

If you are suspected to have oral candidiasis, a type of yeast infection, doctors will look into potential risk factors. These could be things like using topical steroids, having dry mouth, wearing dentures all the time, or using tobacco. It could also be related to problems with your immune system, poor nutrition, or use of certain medications, like chronic steroids or antibiotics.

To diagnose oral candidiasis, doctors mainly look at your symptoms. For confirmation, they may take a swab or smear from the infected area and check for Candidal hyphae (yarn-like structures of the Candida fungus) using a specific staining method. In some cases, a biopsy may need to be done, especially when chronic hyperplastic candidiasis is suspected, to make sure it’s not cancer.

Doctors may also perform antifungal testing if you don’t respond to the usual treatments or if your infection keeps coming back. There are also specialized tests like the germ tube test or using certain cultures that can isolate and identify the Candida species causing the infection. They might also test for specific antigens and antibodies in your blood if you are immune-compromised and it’s hard to get deep samples. Lastly, they could use a method called MALDI-TOF mass spectrometry, which is really helpful in identifying the specific Candida species quickly.

Aspergillosis is diagnosed based on your symptoms, lab tests, and tissue examination. Findings that point towards aspergillosis include a specific type of fungal structure and evidence of necrosis or granulomatous inflammation. There are also special stains that can be used to confirm the diagnosis. Another marker for Aspergillus, a type of fungus, is galactomannan, which can be found in your blood.

Mucormycosis is a rare fungal infection that can occur in people with diseases like diabetes, AIDS, and cancer, or those who’ve had a bone marrow transplant or are receiving specific medications. It can also occur after dental procedures such as tooth extraction or periodontal surgery. Diagnosis includes taking samples and examining them under the microscope, checking fit fungal growths on specific agar plates, and using PCR, a type of DNA testing.

Diagnosis of histoplasmosis, caused by a specific type of fungus, is based on understanding your symptoms, tissue examination, and the growth of the fungus in cultures. A classic sign would be findings of fungal elements inside specific cells of your body (histiocytes).

Diagnosis of blastomycosis involves visualization of Blastomyces, the causing fungus, using various methods, including some special stains. Look for yeast-like cells with bud attachments.

Cryptococcosis, a fungal infection mainly affecting the nervous system can be diagnosed by staining with India ink or by testing samples for a specific antigen. In some cases, tissue staining with special dyes can be helpful.

Paracoccidioidomycosis is diagnosed based on tissue examination. The fungus looks like ‘Mickey Mouse ears’ or a ‘steering-wheel’ appearance.

Geotrichosis is diagnosed based on findings of specific cells (rectangular arthroconidia) in tissue examination or in KOH mounts. Culture is essential for the diagnosis.

Treatment Options for Fungal Infections of the Oral Mucosa

Oral candidiasis, or a yeast infection in the mouth, can be managed by maintaining good oral and denture hygiene, checking for and addressing contributing factors, and using an appropriate antifungal medicine. Topical clotrimazole is the usual treatment for adult candidiasis, while nystatin suspension is often used for infants. In some serious cases, medications like fluconazole or itraconazole may need to be taken internally. Posaconazole oral solution can be used in patients with weakened immune systems and drug resistance.

Aspergillosis refers to various diseases caused by a type of fungus called Aspergillus. In people with normal immune systems, non-invasive aspergilloma (a fungal ball in the lungs) can be treated with surgical removal alone. However, allergic fungal sinusitis, a type of sinus infection, is usually treated with surgical removal and corticosteroid therapy (a type of anti-inflammatory medicine). In certain localized aspergillosis cases, treatment involves surgical removal and administration of a medicine called voriconazole. In patients with weakened immune systems and invasive aspergillosis, aggressive surgical removal and systemic antifungal therapy with medicines like voriconazole, itraconazole, or amphotericin B may be necessary.

Mucormycosis is a severe fungal infection often affecting the sinuses, brain, or lungs. Management involves surgical removal of the dead tissue followed by using systemic antifungals such as liposomal amphotericin B. In patients with a communication between the mouth and nose, a prosthetic obturator (a dental device to close the opening) or surgical closure may be necessary. Additional supportive measures like hyperbaric oxygen can help new blood vessels form and reduce acidity in the body.

For histoplasmosis, a fungal infection that primarily affects the lungs, the disease often resolves itself in patients with normal immune systems. However, in those with weakened immune systems, intravenous amphotericin B is recommended for lung histoplasmosis. Additionally, itraconazole can be used for localized infections, mild to moderate cases, and to prevent a relapse.

Blastomycosis, a fungal infection that can affect the skin, bones, and other parts of the body, can be treated with itraconazole in non-life-threatening conditions. However, systemic administration of amphotericin B may be needed in patients with weakened immune systems.

Cryptococcosis, a fungal infection typically affecting the lungs or central nervous system, can be treated with oral fluconazole when the infection is localized and there’s no underlying immune system deficiency. Cryptococcal meningitis, an inflammation of the membranes covering the brain and spinal cord, is treated with amphotericin B and flucytosine in three phases: induction, consolidation, and maintenance.

Patients with oral paracoccidioidomycosis, a systemic fungal infection often affecting the mouth, are usually treated with oral itraconazole or ketoconazole.

Recommendations for treating oral geotrichosis, a rare fungal infection of the mouth, are similar to those for oral candidiasis.

What else can Fungal Infections of the Oral Mucosa be?

Fungal infections can appear to be a lot like other medical conditions based on the symptoms you’re experiencing. Here are a few examples:

• Oral candidiasis: This could be mistaken for conditions such as a white-coated tongue, leukoplakia (white spots on the mouth), lichenoid reactions (inflammation in the mouth), and secondary syphilis because they all cause changes in the mouth that resemble pseudomembranous candidiasis. You might also confuse it with conditions like thermal burns, erythroplakia (red patches in the mouth), anemia, and oral mucositis, which are similar to erythematous candidiasis.
• Aspergillosis: This is a type of fungal infection that causes inflammation that may look like other diseases such as tuberculosis, syphilis, Wegener’s granulomatosis, or leprosy when observed through a microscope.
• Mucormycosis: This condition might seem like other situations that can result in palatal necrosis such as bacterial infections (like actinomycosis), viral infections (like herpes zoster), radiation, and trauma. It can be challenging to distinguish Mucormycosis from Aspergillosis, but analyzing the appearance of the fungal hyphae under the microscope can help.
• Histoplasmosis: This is a lung infection that can lead to symptoms similar to tuberculosis such as fever, weight loss, cough, difficulty breathing, and chest pain. Oral histoplasmosis can often be mistaken for a malignancy (cancer).
• Blastomycosis: The lesions caused by this infection can resemble oral carcinoma (mouth cancer) both clinically and under a microscope. So, the careful examination of yeasts is crucial. Blastomycosis can also resemble bacterial infections such as syphilis, tuberculosis, actinomycosis, or autoimmune diseases like Crohn’s disease and systemic lupus erythematosus.
• Cryptococcosis: When it occurs in the mouth, this infection can seem similar to histoplasmosis, paracoccidioidomycosis (another fungal infection), tuberculosis, or malignancy.
• Paracoccidioidomycosis: The oral lesions caused by paracoccidioidomycosis can mimic malignancies and other granulomatous lesions (inflammations).
• Geotrichosis: An oral geotrichosis infection can appear similar to oral candidiasis (yeast infection).

Given the diversity of the symptoms and the way they can resemble other diseases, it’s essential to get a proper diagnosis for the effective treatment of fungal infections.

What to expect with Fungal Infections of the Oral Mucosa

Oral candidiasis, a fungus that develops in the mouth, generally has a positive outcome when treated correctly. However, the infection can come back if patients do not continue with their medication or if the cause of the condition is not addressed.

Aspergillosis, another type of fungal infection, generally has a poor outcome for those with weakened immune systems. Almost 58% of serious cases of Aspergillosis result in death.

Mucormycosis is another severe fungal infection that often has a high mortality rate, particularly for those with weakened immune systems. However, medications like oral posaconazole can help patients prone to the disease, such as those with a low white blood cell count or a graft-versus-host disease.

The outcome for those with Histoplasmosis, a fungal infection that affects the lungs, depends on the strength of the patient’s immune system. Particularly for those living with HIV, severe lung and kidney damage can lead to a bleak prognosis, and if the disease spreads throughout the body and it’s not treated, it could be lethal.

Blastomycosis, a fungus that can cause a variety of symptoms, has a mortality rate of roughly 2% to 6%. This rate increases with severe or widespread infection, especially in patients with weakened immune systems.

Cryptococcosis can be a severe threat to those with AIDS. Its consequence in HIV patients largely relies on their use of antiretroviral medications, which can control the HIV virus. However, these medications could potentially trigger a harmful immune response during antifungal therapy. Cryptococcal meningitis, an infection in the membranes surrounding the brain and spinal cord, comes with a bleak prognosis and a high mortality rate.

The prognosis for Paracoccidioidomycosis, a fungal infection primarily found in South and Central America, depends on how severe the disease is when diagnosed.

Oral Geotrichosis, a rare fungal infection in the mouth, generally responds well to treatment and has a promising prognosis.

Possible Complications When Diagnosed with Fungal Infections of the Oral Mucosa

Oral candidiasis, if not treated, can turn into a long-lasting infection, spread deeply into the body, cause severe mouth sores, and even reach the throat and esophagus. It can also lead to conditions like bronchitis, pneumonia, and heart inflammation.

Aspergillosis is a type of sinus infection that can affect the bone and blood vessels causing clots, tissue death due to loss of blood supply, and serious bleeding. It can also spread to distant parts of the body like the eyes, brain, skin, and digestive tract.

Mucormycosis is an infection that starts from the nasal cavity and quickly reaches the sinuses around the nose and the eye socket. It can lead to visual problems and facial paralysis due to affected nerves. If not managed in time, it can reach the brain through sinuses and the eye socket, potentially leading to death.

Histoplasmosis can lead to fractures due to ongoing bone destruction. This infection can spread to other parts of the body like the adrenal gland, spleen, liver, lymph nodes, and digestive tract.

Blastomycosis most commonly spreads to the skin. But it can also affect the bone, prostate, testicles, and central nervous system.

Cryptococcosis is common in individuals with weak immune systems and can affect the skin, prostate, eyes, and bone. Rarely, it can spread to the salivary glands.

Paracoccidioidomycosis often starts with an oral lesion, before it affects the lungs. Hence, an examination of the lungs is critical, even in patients without any symptoms related to the lungs.

Disease Complications:

• Oral candidiasis: ongoing infections, severe mouth sores, bronchitis, pneumonia, heart inflammation
• Aspergillosis: affects bones, blood vessels, can cause clots, tissue death, serious bleeding, and spread to eyes, brain, skin, and the digestive tract
• Mucormycosis: rapid spread to sinuses, eye socket, potential visual problems, facial paralysis, and possible death if it reaches the brain
• Histoplasmosis: fractures due to bone destruction, spreading to other parts of the body like the adrenal gland, spleen, liver, lymph nodes, and digestive tract
• Blastomycosis: commonly spread to the skin, can affect bone, prostate, testicles, and central nervous system
• Cryptococcosis: common in individuals with weak immune systems, can affect skin, prostate, eyes, bone, and rarely, salivary glands
• Paracoccidioidomycosis: starts with an oral lesion, affects the lungs, necessitates lung evaluation even without related symptoms

Preventing Fungal Infections of the Oral Mucosa

If you’re suffering from oral thrush, maintaining a clean mouth and using an antimicrobial rinse can help lessen the amount of these microorganisms in your mouth. If you wear dentures, remember to take them out at night, wash them, and soak them in a solution with 0.2% chlorhexidine, which is a type of antiseptic. Quitting tobacco use can also be beneficial. If you’re using inhaled steroids, rinse your mouth with water after each use to prevent a build-up of the medicine. Regular dental check-ups are important for an examination of your mouth and to ensure your dentures are still fitting comfortably and securely.

Aspergillosis is a type of lung infection that can be caused by inhaling certain fungal spores. If you work in environments where these spores are present, such as construction sites, you should wear a protective mask, specifically a N95/P2 type. If you have a sinus infection, try to avoid flying as the change in altitude can actually make your symptoms worse.

Mucormycosis is a serious fungal infection that can affect people with compromised immune systems or diabetes. If you have a tooth extraction site that doesn’t seem to be healing, it’s important to see a doctor as it could be a sign of this condition. People who survive mucormycosis often suffer severe damage to their facial structures, so rehabilitation is critical to regain a good quality of life.

Histoplasmosis, another type of fungal infection, can start in the mouth and then spread to other parts of the body. Regular check-ups can catch this sooner and help keep the disease under control.

Avoiding soil disturbance when doing outdoor activities like hunting, fishing or camping can reduce the risk of getting Blastomycosis, a disease often contracted in wooded areas.

Cryptococcosis is a disease that sometimes affects people with weakened immune systems. Regular screenings can help catch this condition sooner, and quick treatment can prevent it from spreading. If you’re diagnosed with oral cryptococcosis, follow-up check-ups are crucial to make sure it isn’t spreading to other parts of the body.

Paracoccidioidomycosis is a deep fungal infection that is treated with the drug ketoconazole. However, this drug can cause liver side effects, so regular check-ups help monitor your liver’s health whilst on this medication.