Sunday, January 24, 2010

What are Malassezia?


Definition


Malassezia are lipophilic, dimorphic fungi that
are found as normal flora on the skin of humans and other mammals. These
fungi can cause a variety of skin conditions and systemic infections in special circumstances.






Natural Habitat and Features


Malassezia are lipophilic yeasts. Most species depend upon saturated fatty acids for growth.
They are found as part of the normal flora of the skin of humans and other mammals
in areas where sebaceous glands secreting sebum are located. Sebum is composed of
triglycerides and esters. Malassezia
lipases degrade triglycerides into both unsaturated and saturated fatty acids. The
Malassezia consume the specific saturated fatty acids and
leave the unsaturated fatty acids on the skin.


Since discovery of the fungi in 1874, thirteen Malassezia sp.
have been described. Four species, caprae,
equina, nana, and
pachydermatis, are associated with animals, and the other
species are found as human commensals and as opportunistic pathogens. Human colonization begins
shortly after birth and is maintained throughout adulthood. Certain diseases, such
as diabetes
mellitus or human immunodeficiency virus infection,
may encourage the yeasts to grow, as may treatment with drugs, such as
corticosteroids or cancer chemotherapy, that impair the
immune system. Systemic infection may occur in association with vascular
catheters, particularly when intravenous lipids are administered.


While Malassezia are classified as yeasts, they are dimorphic fungi occurring as both saprophytic yeasts and parasitic mycelia. The yeast forms vary from spherical to ovoid and reach diameters of 8 micrometers (m). The yeasts multiply by monopolar budding. The presence of a prominent collarette at the budding site helps to distinguish them from Candida glabrata, which is otherwise similar in appearance. The hyphae are short and septate with occasional branching and are 2.5 to 4 m in diameter. Parker’s ink, Gomori’s methenamine silver, or periodic acid-Schiff (PAS) stains can all be used to aid in microscopic visualization of the organisms from specimens such as skin scrapings or punch biopsies.


The fungi are difficult to culture; a source of lipid must be added to meet their growth requirements. Sabouraud’s dextrose agar can be overlaid with sterile olive oil or other media, including Leeming-Norman, Dixon agar; Littman oxgall may be employed. Colonies comprising budding yeasts grow slowly, maturing in five days at 86° to 98.6° Fahrenheit (30° to 37° Celsius). They initially appear as small, smooth, creamy colonies and later become dull and wrinkled with a tan or brownish coloration. Colonial and microscopic morphology, growth requirements, biochemical tests, and molecular tests have all been used for the identification of various species.




Pathogenicity and Clinical Significance


Sebaceous
glands cover the human body, with the exception of the palms
of the hands and the soles of the feet. The secretion of sebum is under glandular
control. Activity begins at birth under control of maternal androgens and then
declines until puberty. Secretion remains steady until middle age, when androgens
decrease and sebum production declines. In women, the decline is linked to
menopause, but in men the decline occurs somewhat later.


Dandruff and seborrheic dermatitis are superficial infections with Malassezia species that are associated with the hyperproliferation of the cells of the epidermis, which results in flaking of the skin. When Malassezia shift the composition of sebum to a preponderance of unsaturated fatty acids, these fatty acids alter the skin barrier and create inflammation and ultimately hyperproliferation and flaking of the skin. These two conditions affect up to 50 percent of the population at some time in their lives, and they are most common during those years of highest sebaceous gland activity. While dandruff affects only the scalp, seborrheic dermatitis can involve the scalp, eyebrows, nose, external ears, and even the trunk and groin areas. M. globosa and M. restricta are the most common species identified. The diagnosis may be confirmed by microscopic examination of skin scrapings that reveal the round yeasts.


Pityriasis versicolor is a superficial infection of the skin covering the trunk and proximal extremities in young adults. The infection is associated with transformation of the yeast to the mycelial phase, but the factor or factors inciting the change is unknown. A fatty acid metabolite of Malassezia, azeleic acid, is responsible for the depigmentation of the skin lesions. M. globosa is the species found in the majority of infected persons. In most cases the diagnosis is made clinically, but confirmation can be obtained by observing round yeast forms accompanied by short hyphae elements on microscopic examination of skin scrapings.


Neonatal cephalic pustulosis, or
neonatal acne, occurs in about 3 percent of hospitalized neonates. The condition is a pustular eruption involving the face, neck, and scalp. Maternal hormones stimulate neonatal sebum production, facilitating Malassezia growth after being introduced to the fetus during pregnancy or passed on by health care workers. The diagnosis is made on the basis of the clinical appearance of the skin lesions, smears showing yeasts on microscopic examination, and response to topical antifungal therapy. M. sympodialis has been the species associated with more severe cases, while M. furfur is found in mild cases or in asymptomatic infants.


Severely ill neonates or adults receiving infusions of intravenous lipids to provide parenteral nutrition are at risk for systemic infection through the bloodstream by Malassezia. While the lipid emulsions are not intrinsically contaminated, they do support the growth of Malassezia by providing them with fatty acids. The impaired immune systems of severely ill persons may allow systemic spread of the infection.


Most conventional blood culture systems have poor cultural yields for these organisms. Lysis-centrifugation with subsequent culture onto lipid supplemented media, or the addition of lipids to the broth used for blood culture, may provide a higher yield. Blood cultures obtained through the central venous catheter used for hyperalimentation are more likely to be positive than are peripheral vein samples. Additionally, buffy coat smears have revealed yeast forms in the blood of some infants. M. furfur is the species usually found.


Domestic pets, especially dogs, are colonized and sometimes infected with Malassezia. Canine ear and skin infections are commonly observed and treated by veterinarians. M. pachydermatis is the usual species, and because this species is uncommon in human infections, canine transmission is thought to be of minimal importance.




Drug Susceptibility


Malassezia are uniformly susceptible to the azole class of
antifungal agents. Ketoconazole is the most commonly used azole in the treatment
of the various types of infection caused by these organisms. Ketoconazole shampoo
and cream are employed for superficial infections such as dandruff,
seborrheic dermatitis, and neonatal cephalic pustulosis. Ketoconazole cream may
also be successfully used for the treatment of pityriasis versicolor, but more
extensive or persistent cases should be treated with oral itraconazole or
fluconazole. In cases of systemic infection associated with lipid infusions, the
contaminated central venous catheter should be removed and intravenous antifungal
therapy with an agent such as fluconazole commenced.




Bibliography


Hibbett, David S., et al. “A Higher-Level Phylogenetic Classification of the Fungi.” Mycological Research 111 (2007): 509-547. A complete classification of fungi.



Inamadar, A. C., and A. Palit. “The Genus Malassezia and Human Disease.” Indian Journal of Dermatology, Venereology, and Leprology 69 (2003): 265-270. A short general review of diseases caused by Malassezia.



Larone, Davise H. Medically Important Fungi: A Guide to Identification. 4th ed. Washington, D.C.: ASM Press, 2002. A standard guide with illustrations.



Naldi, Luigi, and Alfredo Rebora. “Seborrheic Dermatitis.” New England Journal of Medicine 360 (2009): 387-396. Comprehensive review of effective treatments for dandruff and seborrheic dermatitis.



Ro, Byung In, and Thomas L. Dawson. “The Role of Sebaceous Gland Activity and Scalp Microfloral Metabolism in the Etiology of Seborrheic Dermatitis and Dandruff.” Journal of Investigative Dermatology Symposium Proceedings 10 (2005): 194-197. An excellent scientific explanation of the metabolic relationship of Malassezia to the skin.

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