Entomophthoromycosis

What is Entomophthoromycosis?

Entomophthoromycosis is a collection of uncommon fungal infections that mainly occur in the skin and mucous membranes and are typically found in tropical and subtropical areas. The name, in Greek, suggests insects, as these types of fungi were first recognized as parasites in insects. This infection generally progresses slowly and usually starts from foreign matter, like plant debris entering the body, or by inhaling fungal spores. Entomophthoromycosis has two particular forms known as basidiobolomycosis and conidobolomycosis. Regions where these types of fungi thrive include soil and the waste of insects, reptiles, and amphibians.

Conidobolomycosis, often triggered by a fungus named Conidiobolus coronatus, is typically a chronic infection affecting the nasal passages and facial skin tissues. The infection can lead to facial disfigurement and predominantly affects individuals with a healthy immune system. There have been instances where Conidiobolus spp have been found in individuals with weakened immune systems. The other type, Basidiobolomycosis, is also a long-term skin infection caused by Basidiobolus ranarum, which usually affects the arms, legs, trunk, buttocks, and the digestive system. Its symptoms are similar to more common diseases such as cancers or inflammatory bowel disease, which can make identifying the condition difficult. This infection can affect both people with healthy and compromised immunity.

Treatment in the early stages can be successful. However, if left untreated or if the patient has a weakened immune system or another severe illness, disfigurement or even death may occur. Diagnosis requires vigilance due to the rarity of the disease. Anti-fungal medicines are the go-to treatment, but the fungi can be resistant, requiring longer treatment times or combined therapies. Confirming the infection involves different lab tests, and in some cases detailed imagery like MRI or CT scan may be required. Surgery may also be needed in certain situations.

Overall, healthcare providers should have entomophthoromycosis in mind for patients who show classic symptoms and, especially for those who have lived in or travelled to tropical or subtropical climates, due to its potential for causing serious disfigurement and even lead to death.

What Causes Entomophthoromycosis?

Entomophthoromycosis refers to a group of infections caused by fungi from the ‘Entomophthorales’ order, which includes six families. Among these families, one is the ‘Basidiobolaceae’ family and it has a single group with four species. The most commonly found type is ‘B ranarum’. This fungus is usually found on the skin or feces of frogs.

There are also several species of ‘Conididobolus’ fungus, which is from the ‘Ancylistaceae’ family. These fungi are usually found in the soil. The medically significant species of this fungus causing entomophthoromycosis are ‘C coronatus’ and ‘B ranarum’.

Certain species of ‘Conidiobolus’ reproduce within insects, killing them by spreading their filaments called hyphae, which can become airborne. After infecting the insect’s abdomen, the fungus causes a systemic infection, which affects the insect’s entire body. When the insect dies, the fungus continues to grow and creates a new generation of spores. The species of ‘Basidiobolus’ are found living in the digestive systems of amphibians and reptiles.

Risk Factors and Frequency for Entomophthoromycosis

Entomophthoromycosis is a disease that is most commonly seen in tropical and subtropical areas. Basidiobolus spp, a type of fungus that causes this condition, can be found in numerous countries such as India, Pakistan, Uganda, Kenya, Ivory Coast, Myanmar, Ghana, and South America. Cases have also been found in the southeastern United States, with Arizona being a noteworthy location.

This disease typically impacts young individuals with a staggering 80% of patients being under the age of 20. It also happens to affect males more than females with a 3:1 ratio.

Another fungus, Conidiobolus spp, responsible for the disease conidiobolomycosis, thrives in areas with high humidity. It can be found in soil and decaying plant matter, especially in locations like the beaches in the United Kingdom, the eastern coast of the United States, India, and the western parts of Africa. Nigeria, in particular, sees a high number of conidiobolomycosis cases.

This disease also affects males more than females, with a 10:1 ratio, and is commonly seen in young adults.

Signs and Symptoms of Entomophthoromycosis

Conidiobolomycosis manifests as symptoms like nasal blockage, drainage, and pain in the area near the sinuses. Generally, it remains restricted to the facial and nasal region. Patients usually don’t seek medical help until they experience sizeable painless swelling in the upper lip or face. The swelling often extends gradually into other facial areas. Invasive forms of the conditions can happen in people with weakened immune systems, potentially causing complications like endocarditis.

The different types of this condition caused by various fungal species include:

• C coronatus: This primarily causes infection in the tissue below the face skin, triggering bilateral symptoms. Initial symptoms can include rhinitis, occasional nose bleeding, sinus pain, and painless swelling around the nose. If not treated, it can cause severe facial deformation.
• C incongruus: This type affects both healthy and immunocompromised patients, often associated with systemic infections. It usually begins with mild swelling at the infection site.
• C lamprauges: This type tends to grow in the direction of blood vessels.

Basidiobolomycosis is another chronic infection mainly caused by B ranarum. It tends to affect young children, impacting their limbs, trunk, buttocks, and digestive system. Its manifestations include:

• Rubbery, disc-shaped nodular lesions on the buttocks, thighs, and limbs. The skin over these lesions may be red and warm, and the area swollen.
• Having the skin ulcerations and local lymph node enlargement in some cases.
• Lesions that develop over months to years.

Gastrointestinal basidiobolomycosis (GIB) causes symptoms similar to those of colon cancer and inflammatory bowel disease. These symptoms include diarrhea with blood and mucus, abdominal pain, intermittent low fever, intestinal bleeding, vomiting, and formation of tumor-like masses in the stomach and intestine tissues. In tropical and subtropical regions, these symptoms along with weight loss, fever, eosinophilia, calls for the consideration of GIB.

Testing for Entomophthoromycosis

When doctors and histopathologists suspect a fungal infection, they must thoroughly examine you to determine the extent of the suspected infection. To confirm the diagnosis, they will look for fungal elements and perform diagnostic cultures. You might have more white blood cells than usual, particularly a type called eosinophils.

They usually take a tissue sample from the edge of the affected area to look for signs of the fungus under a microscope and perform fungal cultures. This is considered the gold standard, or the most reliable method, for diagnosing fungal infections. To better see the fungal elements, they often use a microscopic technique with a special fluorescent dye.

It’s important to test the tissue sample as soon as possible after collection, and they typically keep the sample cold during transportation. The sample is put onto special types of agar, a gel-like substance that helps fungus grow, such as Sabouraud dextrose agar, potato dextrose agar, or cornmeal agar. Under the right conditions, the fungus should grow rapidly and form dense, furrowed colonies with a waxy appearance. The fungus even sends out spores, which can make the inside of the petri dish lid look cloudy. These cultures can also help doctors determine which antifungal medications will be most effective against your specific fungus.

Sometimes, the sample doesn’t grow anything in culture because the fungus might have been damaged during processing. If this happens, your doctor can use techniques known as DNA probes, fungal primers, and PCR to identify the fungus in your tissue sample. This can be done using either fresh frozen or paraffin-embedded tissue.

Your doctor might also want to get a better look at the infection by using imaging techniques like computed tomography (CT) or magnetic resonance imaging (MRI). These can help them understand how far the infection has spread, monitor your response to treatment, and plan where to collect tissue samples in the future. In cases where the fungal infection might be affecting your digestive system, they might use a technique called a colonoscopy. This involves inserting a flexible tube with a camera into your rectum to view your colon.

Imaging might reveal things like thickened tissue, dense areas known as infiltrates, or tumor-like masses. In cases of C coronatus infection, they might see things like infection in your maxillary sinus (one of your sinuses located in your cheek), tumor-like masses, and dense areas in your sinuses. If the infection is in your gastrointestinal tract, they might see thickened areas in your intestine and tumor-like masses in your colon and rectum. If the infection has spread throughout your body, they might see masses in organs like your liver, gallbladder, pancreas, and kidney.

Treatment Options for Entomophthoromycosis

If you have a medical condition called entomophthoromycosis, your doctor typically uses a two-pronged approach, combining medicine and potential surgery to manage it. In simple terms, entomophthoromycosis is an infection caused by certain kinds of fungi.

The most commonly used treatments include certain types of antifungal medicines such as KI (potassium iodide), cotrimoxazole, amphotericin B, imidazoles, along with the use of hyperbaric oxygen, a treatment where you inhale pure oxygen in a pressurized room or tube.

The first choice of treatment tends to be a combination of KI and another group of medicines called triazoles, particularly one called itraconazole. Unfortunately, the fungus that causes this infection can be resistant to antifungal medicine, which means stronger-than-normal doses may be required. The treatment usually needs to be continued daily for several months. Using only one medicine (monotherapy) is usually not effective.

One interesting thing to note is that, although we know that the fungus causing this infection can resist the effects of KI in a lab setting, it still appears to work in the body. Scientists believe this is because KI helps break down the fungal cell wall and boosts the body’s immune response to fight the infection.

In addition to medicine, surgery might be necessary. But surgery alone usually isn’t enough because there’s a high chance the infection may return. In cases where the infection is in the early stages and affecting the face or nose (a condition called nasofacial conidiobolomycosis), surgery might be helpful to prevent severe cosmetic damage. In more advanced stages where scarring has happened even after the fungus has been eradicated, facial reconstructive surgery may be needed. Using a combination of antifungal treatment and surgical removal has been found to help improve nasal symptoms and reduce swelling in the central part of the face.

Other treatments, like cryotherapy (an approach that uses cold temperatures to treat disease), may also be used, but its success has been limited. For patients with GIB (a condition where the fungus affects your gut), removing the affected parts of the gut through surgery followed by antifungal therapy is extremely important.

Hyperbaric oxygen therapy can be another option, which increases the ability of cells that fight infection (neutrophils) to kill the fungus, reduces the formation of harmful substances known as reactive oxygen species, and causes blood vessels to widen (vasodilate), which increases blood flow to the infected tissues. While this therapy may help in the healing process, more research is needed to understand its full benefits.

What else can Entomophthoromycosis be?

When trying to identify Basidiobolomycosis, physicians also need to consider:

• Tuberculosis
• Localized elephantiasis
• Onchocerciasis
• Scleroderma
• Burkitt lymphoma
• Granulomatosis with polyangiitis

For Gastrointestinal Basidiobolomycosis, doctors should also think about:

• Gastrointestinal tumors and colon cancer
• Chronic granulomatous diseases like Crohn disease
• Tuberculosis
• Schistosomiasis
• Lymphoma
• Rhabdomyosarcoma

And when diagnosing Conidiobolomycosis, these conditions should also be considered:

• Mucormycosis
• Cellulitis
• Rhinoscleroma
• Lymphoma
• Sarcoma

What to expect with Entomophthoromycosis

Entomophthoromycosis is a disease that develops gradually, and though its impact is often related to physical appearance, it can turn out to be dangerous, even life-threatening, especially when it spreads throughout the body or affects the digestive system. Usually, patients who are diagnosed early or in the middle stages of the disease tend to respond positively to combined treatments. However, those with the disease in its late stages, experiencing elephantiasis (severe swelling), or lacking the Splendore-Hoeppli phenomenon (a particular pattern seen in some infections) may face poorer health outcomes and potentially a higher risk of death.

Possible Complications When Diagnosed with Entomophthoromycosis

Cosmetic injury can lead to an ongoing, progressive change in appearance due to tough scar tissue building up (fibrosis) and scarring. These can block lymphatic channels and result in lymphedema – swollen body parts – causing further changes in appearance and the loss of functionality in the affected area. In particular, facial swelling can occur in persistent or progressive cases of a fungal disease affecting the nose and face (rhinofacial conidiobolomycosis), due to the obstruction of lymphatic vessels.

In cases related to the gastrointestinal tract (GIB), inflammation can cause further obstruction, and untreated, the disease can spread, cause severe complications and potentially result in death. Wrong diagnosis or late detection may delay suitable treatment, leading to more severe health problems and increased risk of death.

Common Problems:

• Changes in appearance due to scar tissue and scarring
• Lymphedema – swollen body parts due to lymphatic obstruction
• Loss of functionality in the affected area
• Facial swelling in persistent cases of rhinofacial conidiobolomycosis
• Obstruction caused by inflammation in gastrointestinal tract cases
• Potential spread of disease resulting in severe complications and death
• Increased risk of health issues and death due to late or wrong diagnosis

Preventing Entomophthoromycosis

Entomophthoromycosis refers to a set of uncommon fungal infections that primarily target the skin areas like the buttocks, thighs, and trunk. It can also affect the insides of your body like the gastrointestinal tract, which is basically your stomach and intestines, as well as your sinuses and facial tissues. The fungi causing these infections are found in the soil and waste of insects, reptiles, and amphibians. The infection usually happens when someone breathes in fungal spores through their noses or gets infected through a bug bite or a prick from a thorn.

Early signs of the disease affecting your face and nose area include redness or swelling where the infection happened. Other symptoms include issues with your nose such as rhinitis (irritation and swelling inside your nose), occasional nosebleeds, sinus pain, and swelling around your nose that doesn’t hurt. If not treated, you may start to get blocked nose, more swelling, and changes to your face. If other parts of the skin are affected, patients may develop painless, disk-shaped, flexible lumps. These lumps can be moved around and appear on your buttocks, thighs and other parts of your body. As these lumps get worse, they might turn into ulcers, and a lot of nonpitting edema (swelling that doesn’t leave a dent when you press on it) may show up around the area. If your gastrointestinal tract gets infected, it often resembles other stomach and intestine disorders, such as inflammatory bowel disease and colon cancer. This imitation can make diagnosing the disease difficult.

Long-term treatment is a must have in case of Entomophthoromycosis. The right kind of treatment done on time can yield a positive outcome. Patients will need to stick to their medication schedule closely, as the treatment needs to be carried out over a long period of time. In some cases, two types of medicines or a combination of medicine and surgery might be needed. Not following the treatment properly can potentially lead to unsuccessful results.