Zygomycosis

MeshName = Mucormycosis
MeshNumber = D009091

Zygomycosis is the broadest term to refer to an infection caused by fungi of the zygomycetes order. Zygomycosis can refer to mucormycosis,cite journal |author=Toro C, Del Palacio A, Alvarez C, "et al" |title=Cutaneous zygomycosis caused by Rhizopus arrhizus in a surgical wound |language=Spanish; Castilian |journal=Rev Iberoam Micol |volume=15 |issue=2 |pages=94–6 |year=1998 |pmid=17655419 |doi= |url=http://www.reviberoammicol.com/pubmed_linkout.php?15p94 |accessdate=2008-05-19] phycomycosis and basidiobolomycosis [cite web |url=http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4832a3.htm |title=Gastrointestinal Basidiobolomycosis -- Arizona, 1994-1999 |accessdate=2008-06-07] , rare yet serious and potentially life-threatening fungal infections, usually affecting the face or oropharyngeal cavity.cite web |url=http://www.emedicine.com/med/topic1513.htm |title= Mucormycosis |author= Nancy F Crum-Cianflone, MD MPH |publisher=eMedicine|accessdate=2008-05-19 |format= |work=] Zygomycosis 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.cite web |url=http://www.nlm.nih.gov/medlineplus/ency/article/000649.htm |title=MedlinePlus Medical Encyclopedia: Mucormycosis |format= |work= |accessdate=2008-05-19] As such, it usually infects those who are immunocompromised.cite book|author=Ettinger, Stephen J.;Feldman, Edward C.|title=Textbook of Veterinary Internal Medicine|edition=4th ed.|publisher=W.B. Saunders Company|year=1995|id=ISBN 0-7216-6795-3]

The condition can be caused by several fungi including "Mucor", "Rhizopus", "Apophysomyces", "Absidia", "Mortierella", "Cunninghamella", "Saksenaea", "Syncephalastrum" and "Cokeromyces", although the spectrum is much wider and can also contain "Entomophthorales", "Basidiobolus ranarum" or "Mucorales".cite book|author=Ettinger, Stephen J.;Feldman, Edward C.|title=Textbook of Veterinary Internal Medicine|edition=4th ed.|publisher=W.B. Saunders Company|year=1995|id=ISBN 0-7216-6795-3]

Occasionally, when caused by "Pythium" or 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.cite journal |author=Auluck A |title=Maxillary necrosis by mucormycosis. a case report and literature review |journal=Med Oral Patol Oral Cir Bucal |volume=12 |issue=5 |pages=E360–4 |year=2007 |pmid=17767099 |doi= |url=http://www.medicinaoral.com/medoralfree01/v12i5/medoralv12i5p360.pdf |accessdate=2008-05-19] Common symptoms include thrombosis and tissue necrosis. Treatment consists of prompt and intensive antifungal drug therapy and surgery to remove dead tissue. The prognosis varies vastly depending upon an individual patient's circumstances.

igns and symptoms

Zygomycosis frequently involves the sinuses, brain, or lungs as the sites of infection. While oral or cerebral zygomycosis are the most common types of the disease, this infection can also manifest in the gastrointestinal tract, skin, and in other organ systems. In rare cases, the maxilla may be affected by zygomycosis. The rich vascularity of maxillofacial areas usually prevents fungal infections, although more prevalent fungi, such as those responsible for zygomycosis, can often overcome this difficulty.

There are several key signs which point towards zygomycosis. One such sign is fungal invasion into the vascular network which results in thrombosis and death of surrounding tissue by loss of blood supply. If the disease involves the brain then symptoms may include a one-sided headache behind the eyes, facial pain, fevers, nasal stuffiness that progresses to black discharge, and acute sinusitis along with swelling of the eye. 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.cite journal |author=Spellberg B, Edwards J, Ibrahim A |title=Novel perspectives on mucormycosis: pathophysiology, presentation, and management |journal=Clin. Microbiol. Rev. |volume=18 |issue=3 |pages=556–69 |year=2005 |pmid=16020690 |doi=10.1128/CMR.18.3.556-569.2005| url=http://cmr.asm.org/cgi/content/full/18/3/556 PMC|1195964] In other forms of zygomycosis, such as pulmonary, cutaneous, or disseminated zygomycosis, symptoms may also include dyspnea (difficulty breathing), and persistent cough; in cases of necrosis, symptoms include nausea and vomiting, coughing blood, and abdominal pain.

Diagnosis

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 phycomycosis is through a biopsy or culture, although an ELISA test has been developed for "Pythium insidiosum" in animals.cite journal |author=Hensel P, Greene C, Medleau L, Latimer K, Mendoza L |title=Immunotherapy for treatment of multicentric cutaneous pythiosis in a dog |journal=J Am Vet Med Assoc |volume=223 |issue=2 |pages=215–8, 197 |year=2003 |pmid=12875449 |doi=10.2460/javma.2003.223.215] Computerised imaging techniques such as MRIs, CT scans and X-rays may be useful in the diagnosis of specific areas.cite web|title=Mucormycosis|author=Rebecca J. Frey, PhD|url=http://www.healthatoz.com/healthatoz/Atoz/clients/haz/general/custom/default.jsp|publisher=Health A to Z|accessdate=2008-05-19]

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 faded streaks on the film) surrounded by eosinophilic material. Basidiobolomycosis is usually a superficial infection of skin, but may very rarely cause lesions of the bowel or liver, mimicking bowel cancer, [cite journal | title=A fatal pseudo-tumour: Disseminated basidiobolomycosis | author=Van den berk GEL, Noorduyn LA, van Ketel RJ, "et al." | journal=BMC Infect Dis | year=2006 | volume=6 | pages=140 | doi=10.1186/1471-2334-6-140 ] or Crohn's disease.cite journal | journal=Clin Infect Dis | year=1999 | volume=28 | issue=6 | pages=1244–8 | title=Gastrointestinal zygomycotic infection caused by "Basidiobolus ranarum:" case report and review | author=Zavasky DM, Samowitz W, Loftus T, Segal H, Carroll K | doi=10.1086/514781 ] In patients with deep involvement, the eosinophil count may be raised, falsely suggesting a parasitic infection. Zygomycosis also has similar symptoms to other diseases including anthrax, aspergillosis and cellulitis.

Treatment

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.

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, [cite journal | journal=Ann Trop Paediatr | year=1997 | volume=17 | issue=2 | pages=161–4 | title=Invasive retroperitoneal infection due to "Basidiobolus ranarum" with response to potassium iodide—case report and review of the literature | author=Nazir Z, Hasan R, Pervaiz S, Alam M, Moazam F. | pmid=9230980 ] but itraconazole has also been used successfully. [cite journal |author=Wasim Yusuf N, Assaf HM, Rotowa NA |title=Invasive gastrointestinal Basidiobolus ranarum infection in an immunocompetent child |journal=Pediatr. Infect. Dis. J. |volume=22 |issue=3 |pages=281–2 |year=2003 |pmid=12664879 |doi=10.1097/00006454-200303000-00017 |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0891-3668&volume=22&issue=3&spage=281] [cite journal |author=Mathew R, Kumaravel S, Kuruvilla S, "et al" |title=Successful treatment of extensive basidiobolomycosis with oral itraconazole in a child |journal=Int. J. Dermatol. |volume=44 |issue=7 |pages=572–5 |year=2005 |pmid=15985026 |doi=10.1111/j.1365-4632.2004.02419.x |url=http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=0011-9059&date=2005&volume=44&issue=7&spage=572]

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.

Pythiosis

Pythiosis is caused by "Pythium insidiosum" and occurs most commonly in dogs and horses, but is also found in cats, cattle, and humans. The disease is typically found in young, large breed dogs. "Pythium" occupies swamps in late summer and infects dogs who drink water containing it. "Pythium insidiosum" is different from other members of the genus in that human and horse hair, skin, and decaying animal and plant tissue are chemoattractants for its zoospores.

Pythiosis occurs in areas with mild winters because the organism survives in standing water that does not reach freezing temperatures.cite journal |author=Helman R, Oliver J |title=Pythiosis of the digestive tract in dogs from Oklahoma |journal=J Am Anim Hosp Assoc |volume=35 |issue=2 |pages=111–4 |year=1999 |pmid=10102178] In the United States it is most commonly found in the Gulf states, especially Louisiana, but has also been found in midwest and eastern states. It is also found in southeast Asia, eastern Australia, New Zealand, and South America.

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.cite journal |author=Liljebjelke K, Abramson C, Brockus C, Greene C |title=Duodenal obstruction caused by infection with Pythium insidiosum in a 12-week-old puppy |journal=J Am Vet Med Assoc |volume=220 |issue=8 |pages=1188–91, 1162 |year=2002 |pmid=11990966 |doi=10.2460/javma.2002.220.1188] 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".cite web | title=Oomycosis | work=The Merck Veterinary Manual | date=2006 | url=http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/51112.htm | accessdate=2007-02-03 ] It is possible with chronic infection for the disease to spread to underlying bone. [cite journal |author=Worster A, Lillich J, Cox J, Rush B |title=Pythiosis with bone lesions in a pregnant mare |journal=J Am Vet Med Assoc |volume=216 |issue=11 |pages=1795–8, 1760 |year=2000 |pmid=10844973 |doi=10.2460/javma.2000.216.1795] In humans it can cause arteritis, keratitis, and periorbital cellulitis.cite journal |author=Grooters A |title=Pythiosis, lagenidiosis, and zygomycosis in small animals |journal=Vet Clin North Am Small Anim Pract |volume=33 |issue=4 |pages=695–720, v |year=2003 |pmid=12910739 |doi=10.1016/S0195-5616(03)00034-2] 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.cite book|editor=August, John R. (ed.)|chapter=Opportunistic fungal infections|author=Wolf, Alice|title=Consultations in Feline Internal Medicine Vol. 5|publisher=Elsevier Saunders|year=2005|id=ISBN 0-7216-0423-4] Lesions may also develop in the nasopharynx.

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".cite journal | last=Todd-Jenkins | first=Karen | title=A new disease: clinically interesting for all the right reasons | journal=Veterinary Forum | volume=24 | issue=9 | pages=18–20 | publisher=Veterinary Learning Systems | date=September 2007 ]

Epidemiology

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 rhinocerebral form, almost always with hyperglycemia and metabolic acidosis. In most cases the patient is immunocompromised, although rare cases have occurred in which the subject was not; these are usually due to a traumatic inoculation of fungal spores. Internationally, zygomycosis was found in 1% of patients with acute leukemia in an Italian review.

Predisposing factors for zygomycosis include AIDS, malignancies such as lymphomas, renal failure, organ transplant, long term corticosteroid and immunosuppressive therapy, cirrhosis and energy malnutrition. Despite this, however, there have been cases of zygomycosis reported with no apparent predisposing factors present.cite journal |author=Roden MM, Zaoutis TE, Buchanan WL, "et al" |title=Epidemiology and outcome of zygomycosis: a review of 929 reported cases |journal=Clin. Infect. Dis. |volume=41 |issue=5 |pages=634–53 |year=2005 |month=September |pmid=16080086 |doi=10.1086/432579 |url=http://www.journals.uchicago.edu/doi/abs/10.1086/432579 |issn= |accessdate=2008-05-19]

References