Mucormycosis

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Mucormycosis
Periorbital fungal infection known as mucormycosis or phycomycosis
ICD-10 B46.0-B46.5
ICD-9 117.7
DiseasesDB 31759
eMedicine med/1513 
MeSH D009091

Template:DiseaseDisorder infobox

Basidiobolomycosis
ICD-10 B46
ICD-9 117.7
MedlinePlus 000649
eMedicine med/2735  med/1513
MeSH D009091

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Overview

Mucormycosis (also known as zygomycosis) is a rare but serious infection of fungi of the Mucorales order.[1] The most common fungi responsible for mucormycosis in humans are Mucor and Rhizopus.

Signs 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.[2] 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.[2] 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.

Presentation

It that frequently involves the sinuses, brain, or lungs and most commonly presents in immunocompromised patients.

While 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.

Associated conditions

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

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.[3] Computerised imaging techniques such as MRIs, CT scans and X-rays may be useful in the diagnosis of specific areas.[4]

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,[5] or Crohn's disease.[6] 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.

This photomicrograph reveals a mature sporangium of a Mucor sp. fungus, which can be responsible for zygomycosis

Treatment

Surgical resection of the "fungus ball" and intravenous amphotericin B is the recommended 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.

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,[7] but itraconazole has also been used successfully.[8][9]

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%.[2] Patients with AIDS have a mortality rate of almost 100%.[4] Possible complications of zygomycosis include the partial loss of neurological function, blindness and clotting of brain or lung vessels.

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.[4] In the United States, zygomycosis was most commonly found in rhinocerebral form, almost always with hyperglycemia and metabolic acidosis.[10] 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.[10]

Case Example: Carotid Artery Mucormycosis

Clinical Summary

A 63-year-old white male was in his usual state of good health until eight weeks before his death when he developed sudden onset of shortness of breath. A thoracotomy was performed for plication of ruptured emphysematous blebs.

Following improvement and discharge from the hospital he developed weakness, lethargy, and a left lower lobe lung infiltrate. The patient's condition soon deteriorated further, with almost every organ system having failed. The patient developed DIC and peripheral embolic phenomena, including gangrene of his extremities and face.

A single antemortem blood culture grew Staphylococcus aureus.

Postmortem Findings

Autopsy revealed severe emphysema, severe widespread abscessiform and necrotizing pneumonia, and bacterial endocarditis (Staphylococcus aureus) of the pulmonic valve. The right internal carotid artery was occluded by a thrombus and there were areas of necrosis (due to CVAs) in the brain.

Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology




Mucormycosis meningoencephalitis

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References

  1. "eMedicine - Mucormycosis : Article by Nancy F Crum-Cianflone, MD MPH". Retrieved 2007-09-30.
  2. 2.0 2.1 2.2 Spellberg B, Edwards J, Ibrahim A (2005). "Novel perspectives on mucormycosis: pathophysiology, presentation, and management". Clin. Microbiol. Rev. 18 (3): 556–69. doi:10.1128/CMR.18.3.556-569.2005. PMID 16020690. PMC 1195964
  3. Hensel P, Greene C, Medleau L, Latimer K, Mendoza L (2003). "Immunotherapy for treatment of multicentric cutaneous pythiosis in a dog". J Am Vet Med Assoc. 223 (2): 215–8, 197. doi:10.2460/javma.2003.223.215. PMID 12875449.
  4. 4.0 4.1 4.2 Rebecca J. Frey, PhD. "Mucormycosis". Health A to Z. Retrieved 2008-05-19.
  5. Van den berk GEL, Noorduyn LA, van Ketel RJ; et al. (2006). "A fatal pseudo-tumour: Disseminated basidiobolomycosis". BMC Infect Dis. 6: 140. doi:10.1186/1471-2334-6-140.
  6. Zavasky DM, Samowitz W, Loftus T, Segal H, Carroll K (1999). "Gastrointestinal zygomycotic infection caused by Basidiobolus ranarum: case report and review". Clin Infect Dis. 28 (6): 1244&ndash, 8. doi:10.1086/514781.
  7. Nazir Z, Hasan R, Pervaiz S, Alam M, Moazam F. (1997). "Invasive retroperitoneal infection due to Basidiobolus ranarum with response to potassium iodide—case report and review of the literature". Ann Trop Paediatr. 17 (2): 161&ndash, 4. PMID 9230980.
  8. Wasim Yusuf N, Assaf HM, Rotowa NA (2003). "Invasive gastrointestinal Basidiobolus ranarum infection in an immunocompetent child". Pediatr. Infect. Dis. J. 22 (3): 281–2. doi:10.1097/00006454-200303000-00017. PMID 12664879.
  9. Mathew R, Kumaravel S, Kuruvilla S; et al. (2005). "Successful treatment of extensive basidiobolomycosis with oral itraconazole in a child". Int. J. Dermatol. 44 (7): 572–5. doi:10.1111/j.1365-4632.2004.02419.x. PMID 15985026.
  10. 10.0 10.1 Roden MM, Zaoutis TE, Buchanan WL; et al. (2005). "Epidemiology and outcome of zygomycosis: a review of 929 reported cases". Clin. Infect. Dis. 41 (5): 634–53. doi:10.1086/432579. PMID 16080086. Retrieved 2008-05-19. Unknown parameter |month= ignored (help)

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