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TABLE O F CONT E NT S
Introduction
History and taxonomy of the genus Malassezia
Biological characteristics of Malassezia organisms
Structure
Reproduction
Biochemistry
Distribution of Malassezia organisms on the host
Immunological and epidermal responses to
Malassezia organisms
The immune response to Malassezia organisms
Antigen release, penetration and presentation
Cell-mediated immune responses
IgG, IgM and IgA responses to Malassezia
organisms
IgE responses to Malassezia organisms
Mast cell responses
Epidermal responses associated with Malassezia
dermatitis
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I N TRO D U CTI ON
The genus Malassezia is now known to include seven
species of yeast, many of which have been associated
with various diseases in humans and dogs. Malassezia
pachydermatis is a lipophilic budding yeast that colonizes the skin and mucosal sites of healthy dogs.1,2
Despite being part of the normal cutaneous microflora, it is now known that the yeast may become a
pathogen under certain circumstances. Malassezia dermatitis, an inflammatory dermatosis associated with
elevated populations of M. pachydermatis on the skin
of dogs, has been recognized with increasing frequency.
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Its importance in canine dermatology can be illustrated by the continuous rise in the number of articles
on this condition in the literature since it was first
described by Dufait in 1983.3
The interaction between Malassezia yeasts and their
host species has been studied extensively in humans but
less widely in dogs. In this article, we describe the basic
taxonomy and biology of Malassezia yeasts and review
current knowledge on the interplay between the organism and the skins protective responses. These include
cutaneous and systemic immune responses and the
protective barrier afforded by the epidermis. Failure of
these mechanisms to protect the host against proliferation of the organism can lead to pathogenicity and various disease states. In some cases, these responses are
actually deleterious and can lead to hypersensitivity
reactions or epidermal pathology. We end the review by
describing the clinical aspects of diseases associated
with Malassezia organisms in humans and animals and
2005 European Society of Veterinary Dermatology
B IO LO G IC A L C H A R AC T E R IST ICS
O F M A L A S S E Z IA O RG A N ISM S
Structure
The microscopic appearance of Malassezia organisms
is well known to veterinary dermatologists who visualize it regularly in samples obtained from clinical cases.
Malassezia pachydermatis is oval to peanut-shaped and
is approximately 23 m in width and 45 m in
length.1 Other species may differ slightly from this in
shape and size. A characteristic feature of the genus
Malassezia is its cell wall structure. Ultrastructurally,
the cell wall of Malassezia species is relatively thick (up
to 0.25 m) compared to other yeasts and is multilayered.2426 It constitutes 2637% of the cell volume.27
Reproduction
The proliferation of Malassezia yeasts is of clinical relevance because it is often overgrowth of the organism
that leads to disease. Yeasts of the genus Malassezia
reproduce by unipolar or sympodial (M. sympodialis)
budding and the budding process described for P.
ovale, P. orbiculare and M. pachydermatis is very similar.19,24,25,27 However, the budding base of M. pachydermatis (0.91.1 m in diameter) is broader than that
of P. ovale and P. orbiculare (0.50.7 m).25,27
Nishimura et al.25 precisely described the budding
process of M. pachydermatis in stages. The budding
yeast first forms an ear-like structure separating from
the cell wall. This structure grows outwards followed
by protrusion of the cytoplasm and dimpling of the cell
wall. The cell wall of the daughter cell then becomes
thicker, layered and serrated as it grows. When the
daughter cell is as long as the mother cell, a narrow
lumen forms in the cross-wall and fission takes place.
The bud is then completely released leaving the ear-like
structure as a bud scar.
Biochemistry
Lipid-dependent Malassezia species have been reported to elaborate a range of enzymes. These enzymes
have been the subject of recent interest because they
may be involved in the pathogenesis of clinical disease
states. Lipase activity has been demonstrated within
the cell wall and at the membrane sites of the yeast
in vitro using histochemical techniques and electron
microscopy. This suggests that this enzyme is synthesized intracellularly and exported to the cell surface.29
It has also been found that the fatty acid composition
of the cell varies depending on the lipid supplementation present in the medium, indicating that fatty acids
are required for membrane synthesis.30 The lipoxygenase activity of the yeast has been proposed to be
involved in the pathological changes associated with
pityriasis versicolor.31,32 Increased levels of lipoperoxides were detected in lipids from lesional but not nonlesional skin of patients with pityriasis versicolor.32
The by-products of lipoperoxidation induced by lipoxygenase activity of the yeast were considered to cause
damage to melanocytes, resulting in the hypopigmentation seen in pityriasis versicolor.31 In vitro, M. furfur
also produces phospholipases,33,34 the activity of which
was demonstrated to cause the release of arachidonic
acid from human epithelial cell lines, a mechanism by
which Malassezia organisms may trigger inflammation
in the skin.35 In addition to the enzymes described above,
Malassezia organisms produce azelaic acid in cultures
supplemented with oleic acid.36 Azelaic acid is an inhibitor of tyrosinase, an enzyme involved in the production of melanin, indicating that the production of azelaic
acid by Malassezia organisms may also play a role in
the pathological changes of pityriasis versicolor.36
M. pachydermatis has also been demonstrated to
produce various enzymes in vitro, including alkaline
and acid phosphatase, chondroitin-sulphatase,
esterase, esterase lipase, galactosidase, glucosidase,
hyaluronidase, leucine arylamidase, lipase, lecithinase,
peroxidase, phosphoamidase, phospholipase, phosphohydrolase, protease and urease.1,2,3740 Lipase was
found to be predominantly associated with the cell
membrane of M. pachydermatis, whereas protease is
secreted by the yeast.40 No significant difference was
found in the production of chondroitin-sulphatase,
hyaluronidase, phospholipase and protease by M.
pachydermatis strains isolated from dogs with otitis or
dermatitis.37 When cultured in liquid media, the activities of alkaline phosphatase and esterase lipase in the
culture supernatants from M. pachydermatis were significantly greater than that in the cell suspension. Furthermore, significantly greater activity of C4 esterase
was detected in cell suspensions of M. pachydermatis
strains obtained from healthy dogs compared to those
from dogs with dermatitis.2
D IST R IBU T IO N O F M A L A SS E Z IA
O RG A N IS M S O N T H E H O S T
Unlike many bacteria and other fungi, Malassezia
yeasts are rarely found in the environment.1,14 Their
habitat is primarily the skin and mucosae of mammals
and birds.1,14 Lipid-dependent Malassezia organisms
are frequently isolated from human skin. In a study
involving 200 healthy volunteers, Bandhaya41 isolated
Malassezia furfur from 10 different skin sites in every
individual, with the highest counts being on the head
and upper trunk. M. pachydermatis was only isolated
from 12% of the subjects.41
In healthy dogs, M. pachydermatis can be isolated
from the ear canal, anus, rectum, oral cavity and, less
commonly, the nose and vagina.4245 On normal canine
skin, carriage of the yeast is most common in the interdigital areas and around the mouth but uncommon
on the axilla, groin or dorsum.45,46 Interestingly, the
cells (APCs) and T cells takes place in the skin. An infiltration of CD4+ T cells has been detected at 24 h at
patch test sites in P. orbiculare patch test-positive,
atopic dermatitis patients, but was more pronounced at
72 h.63 The expression of intercelluar adhesion molecule (ICAM)-1 and human leucocyte antigen (HLA)DR in the dermis of these patients was also upregulated. At 24 h post-test, the former correlated with
the scale of the dermal CD3+ lymphocytic infiltrates,
with the majority being CD4+.63
To date, the release, penetration and presentation of
Malassezia antigens in the skin of dogs has not been
studied. However, it has been demonstrated that application of M. pachydermatis suspensions on healthy dog
skin can induce skin lesions similar to those observed
in naturally occurring Malassezia dermatitis.64 This
indicates that Malassezia antigens and/or organisms
may be able to penetrate into the skin, thus inducing
pathogenic effects. Also, there are some data providing
indirect evidence for a transepidermal route of antigen
penetration in dogs with atopic dermatitis. Higher
numbers of Langerhans cells have been detected in
lesional atopic skin compared to clinically normal
atopic or normal control canine skin.65,66 These cells
were present in clusters in lesional skin of dogs with
atopic dermatitis.67 Expression of surface IgE has also
been observed on epidermal Langerhans cells in
lesional atopic canine skin,66 and these cells are responsible for allergen capture and presentation.67 Moreover, eosinophils can be seen below the stratum
corneum in lesional atopic canine skin, but not in clinically normal atopic skin.68 Canine atopic skin also
exhibits hyperplasia of T lymphocytes expressing the
gamma-delta T-cell receptor.68 Furthermore, transepidermal penetration of staphylococcal antigens has
been demonstrated in dogs.69 Taken together, these
findings indicate it is likely that M. pachydermatis may
be able to release antigens that would penetrate the
skin of dogs, particularly those suffering from atopic
dermatitis, where they are captured by epidermal
APCs and thus initiate the process of antigen presentation to T cells and a cascade of immunological
responses.
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Table 1. Three allergens of Malassezia furfur and six allergens of Malassezia sympodialis that have been sequenced and expressed as recombinant
proteins
Allergen name
MW
(kDa)
Percentage of AD
patients reacting
Mal s 1
37
70
Mal f 2
21
72
Mal f 3
20
70
Mal f 4
35
83
Mal s 5
Mal s 6
18.2
17.2
48
48
Mal s 7
Mal s 8
Mal s 9
16.2
19.2
14
40
40
24
Identity
No homology to known proteins
Membrane or secreted cell wall protein
Homology to peroxisomal membrane proteins of
Candida boidinii and Aspergillus fumigatus (Asp f 3)
Homology to peroxisomal membrane proteins of
Candida boidinii and Aspergillus fumigatus (Asp f 3)
Showing 57% homology to mitochondria malate
dehydrogenase from Saccharomyces cerevisiae
No homology to known proteins
Showing 82% homology to cyclophilin from
Schizosaccharomyces pombe
No homology to known proteins
No homology to known proteins
No homology to known proteins
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pityriasis versicolor because of its predominant presence in populations of affected patients,127 it remains to
be determined whether M. globosa is also the predominant species in the lesions of individuals. Pityriasis
versicolor most often occurs on the trunk, neck and
proximal extremities. It is characterized by scaly hypoor hyperpigmented macules and patches with minimal
pruritus (Fig. 3).130 The diagnosis can be made by
potassium hydroxide preparations of skin scrapings
or tape strippings, which reveal typical clusters of
yeasts with hyphae.124,125 There are several therapeutic
options for treating pityriasis versicolor, such as
topical treatment with lotions or creams containing
selenium, sodium thiosulphate or specific antifungal
agents, or oral medication with ketoconazole, fluconazole or itraconazole. However, relapse is very common
and prophylactic treatment may be required.125
Malassezia folliculitis. Malassezia folliculitis is characterized by follicular papules and pustules localized to
the trunk, upper arms, neck, and, less often, the face
(Fig. 4). These lesions are generally pruritic.124 Diagnosis is based on clinical signs, cytology and culture in
combination with histopathology. Budding yeasts and,
rarely, hyphae can be found in cytological samples and
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suggested to trigger overgrowth of the yeast are alterations in host defence mechanisms and changes in the
cutaneous microenvironment.70,160 By causing these
changes, various diseases have been suggested as
underlying causes of Malassezia dermatitis.
As described earlier, a disrupted epidermal barrier
renders the skin more prone to bacterial and yeast
infections. Diseases that can cause a decrease in cutaneous barrier function and are commonly associated
with Malassezia dermatitis are hypersensitivity diseases (especially atopic dermatitis), parasite infestation
and keratinization disorders.160,161 Alterations in the
immune system caused by hypersensitivity and endocrine diseases are also thought to predispose to Malassezia dermatitis.160
The cutaneous microenvironment is generally
considered to be important in controlling Malassezia
populations. Malassezia dermatitis seems to be more
common in warm, humid climates and seasons, and in
certain anatomic sites such as skin folds, suggesting
that increased cutaneous humidity favours yeast
growth.161 Additionally, changes in lipids on the skin
surface, resulting in increased availability of nutrients
and growth factors for Malassezia organisms, may promote their proliferation. The diseases that can cause
changes in sebum production and that are associated
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C O N C LU SIO N S
Advances in molecular techniques have led to a clearer
classification of Malassezia yeasts. Certain species
within the genus Malassezia have been associated with
skin diseases, both in humans and animals. Current
research has revealed that Malassezia organisms can
induce immunological responses in normal and atopic
individuals. The identification of several major allergens of Malassezia organisms in atopic humans and
dogs has provided the potential for future development
of immunotherapy for chronically affected patients.
Although the characteristics of the dermatoses associated with Malassezia spp. such as greasy scales and
epidermal hyperplasia have been well recognized, the
interaction between Malassezia organisms and the epidermis remains incompletely understood. Future studies aiming to identify important factors which mediate
the initiation of inflammation or the formation of epidermal hyperplasia seen in Malassezia dermatitis, such
as cytokines and adhesion molecules, might also lead
to novel approaches to prevent or better control
Malassezia dermatitis in humans and dogs.
A D D IT IO NA L N O T E
Figure 15. Histopathology of canine Malassezia dermatitis.
(a) Irregular epidermal hyperplasia and hyperkeratosis (40).
(b) The epidermis shows marked spongiosis and orthokeratotic
hyperkeratosis with focal parakeratosis (250). Malassezia yeasts are
visible in the stratum corneum (thin arrow). Some keratinocytes
show multiple nucleoli, indicating mitotic activity (bold arrows).
(c) Budding yeasts showing characteristic morphology of Malassezia
spp. (thin arrows, 400). Scale bars for (a), (b) and (c) are 100, 10 and
10 m, respectively. H&E stain. Section courtesy of Dr S. Rhind,
University of Edinburgh.
R E FE R E N C E S
1. Guillot J, Bond R. Malassezia pachydermatis: a review.
Medical Mycology 1999; 37: 295306.
2. Bond R. Pathogenesis of Malassezia dermatitis. In:
Thoday KL, Foil CS, Bond R eds. Advances in
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22. Nell A, James SA, Bond CJ et al. Identification and distribution of a novel Malassezia species yeast on normal
equine skin. Veterinary Record 2002; 150: 3958.
23. Sugita T, Takashima M, Shinoda T et al. New yeast
species, Malassezia dermatis, isolated from patients
with atopic dermatitis. Journal of Clinical Microbiology 2002; 40: 13637.
24. Swift JA, Dunbar SF. Ultrastructure of Pityrosporum
ovale and Pityrosporum canis. Nature 1965; 206: 1174
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25. Nishimura K, Asada Y, Tanaka S et al. Ultrastructure
of budding process of Malassezia pachydermatis.
Journal of Medical and Veterinary Mycology 1991; 29:
38793.
26. Mittag H. Fine structural investigation of Malassezia
furfur. II. The envelope of the yeast cells. Mycoses 1995;
38: 1321.
27. Keddie FM, Barajas L. Quantitative ultrastructural
variations between Pityrosporum ovale and P. orbiculare
based on serial section electron microscopy. International Journal of Dermatology 1972; 11: 408.
28. Barfatani M, Munn RJ, Schjeide DA. An ultrastructural study of Pityrosporum orbiculare. Journal of
Investigative Dermatology 1964; 43: 2313.
29. Catterall MD, Ward ME, Jacobs P. A reappraisal of the
role of Pityrosporum orbiculare in pityriasis versicolor
and the significance of extracellular lipase. Journal of
Investigative Dermatology 1978; 71: 398401.
30. Nazzaro-Porro M, Passi S, Caprill F et al. Growth
requirements and lipid metabolism of Pityrosporum
orbiculare. Journal of Investigative Dermatology 1976;
66: 17882.
31. De Luca C, Picardo M, Breathnach A et al. Lipoperoxidase activity of Pityrosporum: characterisation of
by-products and possible role in pityriasis versicolor.
Experimental Dermatology 1996; 5: 4956.
32. Nazzaro-Porro M, Passi S, Picardo M et al. Lipoxygenase activity of Pityrosporum in vitro and in vivo. Journal of Investigative Dermatology 1986; 87: 10812.
33. Muhsin TM, Aubaid AH, Al-Duboon AH. Extracellular enzyme activities of dermatophytes and yeast
isolates on solid media. Mycoses 1997; 40: 4659.
34. Riciputo RM, Oliveri S, Micali G et al. Phospholipase
activity in Malassezia furfur pathogenic strains.
Mycoses 1996; 39: 2335.
35. Plotkin LI, Mathov I, Squiquera L et al. Arachidonic
acid released from epithelial cells by Malassezia furfur
phospholipase A (2): a potential pathophysiological
mechanism. Mycologia 1998; 90: 1639.
36. Nazzaro-Porro M, Passi S. Identification of tyrosinase
inhibitors in cultures of Pityrosporum. Journal of Investigative Dermatology 1978; 71: 2058.
37. Coutinho SD, Paula CR. Proteinase, phospholipase,
hyaluronidase and chondroitin-sulphatase production
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Rsum Le genre Malassezia comporte sept espces de levures, dont la plupart a t associe ) des maladies
varies chez lhomme et chez le chien. Malassezia pachydermatis est une levure lipophile, bourgeonnante, qui colonise la peau les muqueuses des chiens sains. Bien quil sagisse dun lment normal de microflore cutane, cette
levure peut dans certaines circonstances devenir pathogne. La dermatite Malassezia est une dermatose inflammatoire associe la prsence de population leves de M. pachydermatis sur la peau du chien, reconnue de plus
en plus frquemment. Son importance en dermatologie canine peut tre illustre par laugmentation continue
du nombre darticles publis sur cette maladie depuis sa premire description par Dufait en 1983.
Les interactions entre les levures Malassezia et leur hte ont t tudies de faon approfondie chez lhomme,
moins chez le chien. Dans cet article, nous dcrivons la taxonomie et la biologique des levures Malassezia ainsi
que les lments connus actuellement concernant les interactions entre le microorganisme et les moyens de dfense
de la peau. Ces derniers incluent les rponses immunitaires cutanes et systmiques, et la barrire pidermique.
Lincapacit de ces mcanismes de dfense ) protger lhte contre la prolifration des levures peut provoquer
leur pathognicit et lapparition dune dermatose. Dans certains cas, ces rponses peuvent mme tre dltres
et provoquer des ractions dhypersensibilit ou une anomalie pidermique. Nous terminons cette revue en
dcrivant les aspects cliniques des maladies associes Malassezia chez lhomme et lanimal et les moyens
thrapeutiques disponibles pour traiter ces maladies.
Resumen El gnero Malassezia incluye siete especies de levadura, muchas de las cuales se han asociado a enfermedades en humanos y perros. La Malassezia pachydermatis es una levadura lipoflica que se reproduce por
gemacin, que coloniza piel y mucosas de perros sanos.1,2 A pesar de formar parte de la microflora cutnea normal, actualmente se sabe que esta levadura puede comportarse como patgeno bajo ciertas circunstancias. La
dermatitis por Malassezia, una dermatosis inflamatoria asociada a una elevada poblacin de M. pachydermatis
en la piel del perro, se describe con frecuencia creciente. Puede ilustrarse su importancia en la dermatologa canina observando el continuo aumento en el nmero de artculos sobre esta presentacin en la bibliografa desde
que se describi por primera vez por Dufait en 1983.3
Se ha estudiado ampliamente la interaccin entre las levaduras de Malassezia y sus especies husped en el caso
de los humanos, pero menos en el perro. En este artculo, describimos la taxonoma bsica y biologa de las
levaduras Malassezia y presentamos una revisin de los conocimientos actuales sobre la interaccin entre el
organismo y las respuestas protectoras de la piel. stas incluyen las respuestas inmunitarias cutneas y sistmicas
y la barrera protectora proporcionada por la epidermis. Cuando estos mecanismos dejan de proteger el husped
contra la proliferacin del organismo, puede producirse patogenicidad y diferentes presentaciones clnicas. En
algunos casos, estas respuestas son en realidad perjudiciales y pueden llevar a reacciones de hipersensibilidad o
a patologa epidrmica. Finalizamos la revisin describiendo aspectos clnicos de enfermedades asociadas a
organismos del gnero Malassezia en humanos y animales, y las diferentes opciones teraputicas actuales para
el tratamiento de estas presentaciones.
Zusammenfassung Die Gattung Malassezia beinhaltet bekannterweise sieben Species von Hefepilzen, von
denen viele mit verschiedenen Erkrankungen beim Menschen und Hund assoziiert sind. Malassezia pachydermatis ist eine lipophile sprossende Hefe, die die Haut und die Schleimhute gesunder Hunde kolonisiert. Obwohl
sie Teil der normalen cutanen Mikroflora ist, wei man jetzt, dass die Hefe unter gewissen Umstnden Krankheitserreger werden kann. Malassezia-Dermatitis, eine entzndliche Dermatose, die mit erhhter Population von M.
pachydermatis auf der Haut von Hunden verbunden ist, wurde mit zunehmender Hufigkeit diagnostiziert. Ihre
Bedeutung in caniner Dermatologie wird durch den kontinuierlichen Anstieg der Anzahl an Artikeln zu dieser
Erkrankung in der Literatur seit ihrer ersten Beschreibung durch Dufait 1983 verdeutlicht.
Die Interaktion zwischen Malassezia-Hefen und ihrer Wirtsart wurde beim Menschen ausgiebig, beim Hund
jedoch in geringerem Umfang studiert. In diesem Artikel beschreiben wir die grundstzliche Taxonomie und Biologie
von Malassezia-Hefepilzen und den augenblicklichen Wissenstand bezglich des Wechselspiels zwischen dem
2005 European Society of Veterinary Dermatology, Veterinary Dermatology, 16, 426
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