Zygomycosis overview

# Overview
Zygomycosis 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.

# Pathophysiology
The clinical hallmark of Zygomycosis is vascular invasion resulting in thrombosis and tissue infarction/necrosis.

# Causes
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.

# Differentiating Zygomycosis from other Diseases
Zygomycosis needs to be differentiated from conditions like anthrax, aspergillosis and cellulitis.

# Epidemiology and Demographics
Zygomycosis 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 zygomycosis was found in 0.7% of autopsies and roughly 20 patients per every 100,000 admissions to that center. In the United States, zygomycosis 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, zygomycosis was found in 1% of patients with acute leukemia in an Italian review.

# Risk Factors
While most individuals are exposed to the fungi on a regular basis those with immune disorders are more prone to an infection. In humans zygomycosis 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, malignancies such as lymphomas and leukemias, renal failure, organ transplant, long term corticosteroid and immunosuppressive therapy, cirrhosis, burns and energy malnutrition. Some 50-75% of patients diagnosed with zygomycosis are estimated to have underlying poorly controlled diabetes mellitus and ketoacidosis.

# Natural History, Complications and Prognosis
In most cases, the prognosis of zygomycosis 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 zygomycosis 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%. Possible complications of Zygomycosis include the partial loss of neurological function, blindness and clotting of brain or lung vessels.

# Diagnosis

## Laboratory Findings
Diagnosis for phycomycosis is through a biopsy or culture, although an ELISA test has been developed for Pythium insidiosum in animals.  As swabs of tissue or discharge are generally unreliable, the diagnosis of zygomycosis tends to be established by a biopsy specimen of the involved tissue. 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 recognized.  The lesions often look like tumors 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.
In patients with deep involvement with Basidiobolomycosis, the eosinophil count may be raised, falsely suggesting a parasitic infection.

# Treatment

## Medical Therapy
If zygomycosis 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 zygomycosis, 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.
Treatment for skin lesions is traditionally with potassium iodide, but itraconazole has also been used successfully. Antifungal drugs show only limited effect on treatment of phycomycosis, 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. Immunotherapy has been used successfully in humans and horses with pythiosis.

## Surgery
Surgical therapy can be very drastic for zygomycosis, 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. For pythiosis and lagenidiosis, a new drug targeting water moulds called caspofungin is available, but it is very expensive. For pythiosis and lagenidiosis, a new drug targeting water moulds called caspofungin is available, but it is very expensive.

## Primary Prevention
Because the fungi that cause zygomycosis are widespread, the most appropriate preventive measures involve improved control of the underlying illnesses associated with zygomycosis.