Zygomycosis

Overview
Mucormycosis (also known as zygomycosis or phycomycosis ) is a rare yet life threatening and serious infection of fungi, usually affecting the face or oropharyngeal cavity. Occasionally, when caused by Pythium or other similar fungi, the condition may affect the gastrointestinal tract or the skin. It usually begins in the nose and paranasal sinuses and is one of the most rapidly spreading fungal infections in humans. The most common fungi responsible for mucormycosis in humans are Mucor and Rhizopus. Other fungi include Apophysomyces, Absidia, Mortierella, Cunninghamella, Saksenaea, Syncephalastrum and Cokeromyces, although the spectrum is far wider and can also contain Entomophthorales or Mucorales. It usually affects patients who are immunocompromised.

Basidiobolomycosis is a rare disease caused by the fungus Basidiobolus ranarum, member of the class Zygomycetes, order Entomophthorales, found worldwide. Usually basidiobolomycosis is a subcutaneous infection but it has been associated with gastrointestinal disease.

Cause
Mucormycosis is often caused by common fungi which can be found in soil and decaying vegetation. While most individuals are exposed to the fungi on a regular basis those with immune disorders are more prone to an infection.

Signs and symptoms
Mucormycosis frequently involves the sinuses, brain, or lungs as the sites of infection. Whilst orbitorhinocerebral mucormycosis is the most common type of the disease, this infection can also manifest in the gastrointestinal tract, skin, and in other organ systems. The clinical hallmark of mucormycosis is vascular invasion resulting in thrombosis and tissue infarction/necrosis.

If rhinocerebral disease is the cause of the infection, symptoms may include unilateral, retro-orbital headache, facial pain, fevers, nasal stuffiness that progresses to black discharge, acute sinusitis, and eye swelling along with protrusion of eye orbit. In addition, affected skin may appear relatively normal during the earliest stages of infection. This skin quickly progresses to an erythemic (reddening, occasionally with edema) stage, before eventually turning black due to necrosis. However, in other forms of mucormycosis (such as pulmonary, cutaneous or disseminated mucormycosis), symptoms may also include dyspnea, persistent cough, hemoptysis (in cases of necrosis and nausea/vomiting), coughing blood, and abdominal pain..

Rarely, maxilla may be affected by mucormycosis. The lack of case reports regarding maxillofacial mucormycosis lies in the rich vascularity of the maxillofacial areas preventing fungal infections, although this can be overcome by more prevalent fungi, bacteria or viruses such as those responsible for mucormycosis.

Predisposing factors for mucormycosis include AIDS, malignancies such as lymphomas and leukemias, renal failure, organ transplant, long term corticosteroid and immunosuppressive therapy, cirrhosis, burns and energy malnutrition.

Possible complications of mucormycosis include the partial loss of neurological function, blindness and clotting of brain or lung vessels.

Basidiobolomycosis is usually a superficial infection of skin, but may very rarely cause lesions of the bowel or liver, mimicking bowel cancer, or Crohn's disease. In patients with deep involvement, the eosinophil count may be raised, falsely suggesting a parasitic infection.

Diagnosis
As swabs of tissue or discharge are generally unreliable, the diagnosis of mucormycosis tends to be established by a biopsy specimen of the involved tissue. Computerised imaging techniques such as MRIs, CT scans and X-rays may be useful in the diagnosis of specific areas. Differentials to consider in diagnosis of the infection include anthrax, aspergillosis and cellulitis.

Diagnosis for phycomycosis is through a biopsy or culture, although an ELISA test has been developed for Pythium insidiosum in animals.

Diagnosis for basidiobolomycosis is by laboratory culture of the organism, usually from pieces of tissue taken from the patient. It grows easily on most media, but risks being discarded as irrelevant or being reported as a contaminant because laboratory staff are unfamiliar with it.

Diagnosis is often difficult because basidiobolomycosis is a rare disease and therefore often not recognised. The lesions often look like tumours rather than infection, so often no sample is sent for microbiology, however, the histopathology is characteristic: the Splendore-Hoeppli phenomenon describes the presence of fungal hyphae (which may exist only as ghosts on the slide) surrounded by eosinophilic material.

Treatment
If mucormycosis is suspected, prompt amphotericin B therapy should be administered due to the rapid spread and mortality rate of the disease. Amphotericin B (which works by damaging the cell walls of the fungi) is usually administered for a further 4-6 weeks after initial therapy begins to ensure eradication of the infection. Posaconazole has been shown to be effective against mucormycosis, perhaps more so than amphotericin B, but has not yet replaced it as the standard of care. After administration the patient must then be admitted to surgery for removal of the "fungus ball". The disease must be monitored carefully for any signs of reemergence.

Surgical therapy can be very drastic, and in some cases of Rhinocerebral disease removal of infected brain tissue may be required. In some cases surgery may be disfiguring because it may involve removal of the palate, nasal cavity, or eye structures. Surgery may be extended to more than one operation. It has been hypothesised that hyperbaric oxygen may be beneficial as an adjunctive therapy because higher oxygen pressure increases the ability of neutrophils to kill the organism.

Treatment for Phycomycosis is very difficult and includes surgery when possible. Postoperative recurrence is common. Antifungal drugs show only limited effect on the disease, but itraconazole and terbinafine hydrochloride are often used for two to three months following surgery. Humans with Basidiobolus infections have been treated with amphotericin B and potassium iodide. For pythiosis and lagenidiosis, a new drug targeting water moulds called caspofungin is available, but it is very expensive. Immunotherapy has been used successfully in humans and horses with pythiosis.

Treatment for skin lesions is traditionally with potassium iodide, but itraconazole has also been used successfully.

Prognosis
In most cases, the prognosis of mucormycosis is poor and has varied mortality rates depending on its form and severity. In the Rhinocerebral form, the mortality rate is between 30% and 70%, whereas disseminated mucormycosis presents with the highest mortality rate in an otherwise healthy patient with a mortality rate of up to 90%. Patients with AIDS have a mortality rate of almost 100%.

Pythiosis
Pythiosis is caused by Pythium insidiosum and occurs most commonly in dogs and horses, but is also found in cats, cattle, and humans. In the United States it is most commonly found in the Gulf states, especially Louisiana, but has been found in midwest and eastern states. It is also found in southeast Asia, eastern Australia, New Zealand, and South America. Pythiosis occurs in areas with mild winters due to the organism surviving in standing water that does not reach freezing temperatures. Pythium occupies swamps in late summer and infects dogs who drink water containing it. The disease is typically found in young, large breed dogs.

It is suspected that pythiosis is caused by invasion of the organism into wounds, either in the skin or in the gastrointestinal tract. The disease grows slowly in the stomach and small intestine, eventually forming large lumps of granulation tissue. It can also invade surrounding lymph nodes. Symptoms include vomiting, diarrhea, depression, weight loss, and a mass in the abdomen. Pythiosis of the skin in dogs is very rare, and appears as ulcerated lumps. Primary infection can also occur in the bones and lungs.

In horses, subcutaneous pythiosis is the most common form and infection occurs through a wound while standing in water containing the pathogen. The disease is also known as leeches, swamp cancer, and bursatti. Lesions are most commonly found on the lower limbs, abdomen, chest, and genitals. They are granulomatous and itchy, and may be ulcerated or fistulated. The lesions often contain yellow, firm masses of dead tissue known as kunkers. It is possible with chronic infection for the disease to spread to underlying bone.

In humans it can cause arteritis, keratitis, and periorbital cellulitis.

In cats pythioisis is almost always confined to the skin as hairless and edematous lesions. It is usually found on the limbs, perineum, and at the base of the tail. Lesions may also develop in the nasopharynx.

Pythium insidiosum is different from other members of the genus in that human and horse hair, skin, and decaying animal tissue are chemoattractants for its zoospores, in addition to decaying plant tissue.

Zygomycosis
Zygomycosis usually is a disease of the skin, but can also occur in the sinuses or gastrointestinal tract. In humans it is most prevalent in immunocompromised patients (HIV/AIDS, the elderly, SCID, etc) and patients in acidosis (diabetes, burns), particularly after barrier injury to the skin or mucus membranes. Zygomycosis caused by Mucorales causes a rapidly progressing disease of sudden onset in sick or immunocompromised animals. Entomophthorales cause chronic, local infections in otherwise healthy animals. The important species that cause entomophthoromycosis are Conidiobolus coronatus, C. incongruous, and Basidiobolus ranarum. Conidiobolus infections of the upper respiratory system have been reported in humans, sheep, horses, and dogs, and Basidiobolus has been reported less commonly in humans and dogs. Horses are one of the most common domestic animals to be affected by entomophthoromycosis. C. coronatus causes lesions in the nasal and oral mucosa of horses that may cause nasal discharge or difficulty breathing. B. ranarum causes large circular nodules on the upper body and neck of horses. Entomophthorales is found in soil and decaying plant matter, and specifically Basidiobolus can be contracted from insects and the feces of reptiles or amphibians.

Zygomycosis of the sinuses can extend from the sinuses into the orbit and the cranial vault, leading to rhinocerebral mucormycosis.

Lagenidiosis
The best known species of Lagenidium is Lagenidium giganteum, a parasite of mosquito larvae used in biological control of mosquitoes. Two different species cause disease exclusively in dogs: L. caninum and L. karlingii. Lagenidiosis is found in the southeastern United States in lakes and ponds. It causes progressive skin and subcutaneous lesions in the legs, groin, trunk, and near the tail. The lesions are firm nodules or ulcerated regions with draining tracts. Regional lymph nodes are usually swollen. Spread of the disease to distant lymph nodes, large blood vessels, and the lungs may occur. An aneurysm of a great vessel can rupture and cause sudden death. L. caninum is the more aggressive species and is more likely to spread to other organs than L. karlingii.

Epidemiology
Mucormycosis is a very rare infection, and as such it is hard to note histories of patients and incidence of the infection. However, one American oncology center revealed that mucormycosis was found in 0.7% of autopsies and roughly 20 patients per every 100,000 admissions to that center. In the United States, mucormycosis was most commonly found in the form of Rhinocerebral disease. In most cases the patient is immunocompromised, although rare cases have occurred in which the subject was not immunocompromised, most often due to a traumatic inoculation of fungal spores. Internationally, mucormycosis was found in 1% of patients with acute leukemia in an Italian review.

Some 50-75% of patients diagnosed with mucormycosis are estimated to have underlying poorly controlled diabetes mellitus and ketoacidosis.