REVIEW

published: 28 February 2020

doi: 10.3389/fcimb.2020.00079

Malassezia Yeasts in Veterinary

Dermatology: An Updated Overview
Jacques Guillot 1* and Ross Bond 2
1
École Nationale Vétérinaire d’Alfort, BioPôle Alfort, EA Dynamyc, UPEC, EnvA, Maisons-Alfort, France, 2 Department of
Clinical Sciences and Services, Royal Veterinary College, Hatfield, United Kingdom

Lipophilic yeasts of the genus Malassezia are important skin commensals and
opportunistic skin pathogens in a variety of animals. The species M. pachydermatis was
first isolated from the skin of a captive Indian rhinoceros with an exfoliative dermatitis
in 1925, recognized as an important otic pathogen of dogs in the 1950’s, and finally
accepted, after several years of controversy, as a common cause of canine dermatitis
in the 1990’s. Since then, there has been considerable research into the biology of
Malassezia yeasts and their interaction with their animal hosts. In dogs and cats,
M. pachydermatis is associated with ceruminous otitis externa and a “seborrhoeic”
dermatitis, wherein pruritic, erythematous skin lesions, often with brown/black greasy,
malodourous material matting hairs, preferentially develop in intertriginous areas. Skin
disease is favored by folds, underlying hypersensitivity disorders, endocrinopathies,
defects of cornification, and in cats, various visceral paraneoplastic syndromes.
Edited by: Diagnosis is based on detecting the yeast in compatible skin lesions, usually by cytology,
Thomas Dawson,
Skin Research Institute of Singapore
and observing a clinical and mycological response to therapy. Treatment normally
(A∗ STAR), Singapore comprises topical or systemic azole therapy, often with miconazole—chlorhexidine
Reviewed by: shampoos or oral itraconazole or ketoconazole. Management of concurrent diseases is
Rui Kano, important to minimize relapses. Historically, wild-type Malassezia isolates from dogs and
Nihon University, Japan
Courtney Meason Smith, cats were typically susceptible to azoles, with the exception of fluconazole, but emerging
Texas A&M University, United States azole resistance in field strains has recently been associated with either mutations
*Correspondence: or quadruplication of the ERG11 gene. These observations have prompted increased
Jacques Guillot
[email protected]
interest in alternative topical antifungal drugs, such as chlorhexidine, and various essential
oils. Further clinical trials are awaited with interest.
Specialty section: Keywords: Malassezia, dog, cat, diagnosis, treatment
This article was submitted to
Fungal Pathogenesis,
a section of the journal
Frontiers in Cellular and Infection
INTRODUCTION
Microbiology
The genus Malassezia is comprised of a group of lipophilic yeasts that have evolved as
Received: 02 January 2020
skin commensals and opportunistic cutaneous pathogens in a variety of mammals and birds
Accepted: 17 February 2020
(Guého-Kellerman et al., 2010). The transition from commensal to pathogen is frequent in dogs in
Published: 28 February 2020
particular, and in cats to a lesser extent, such that cases of Malassezia otitis externa and Malassezia
Citation:
dermatitis are commonly presented to veterinarians in small animal practice (Moraru et al., 2019).
Guillot J and Bond R (2020)
Malassezia Yeasts in Veterinary
For example, the prevalence of otitis externa amongst dogs presenting to primary care practices
Dermatology: An Updated Overview. is around 10% (O’neill et al., 2014), and up to 70% of such cases may be associated with M.
Front. Cell. Infect. Microbiol. 10:79. pachydermatis (Forster et al., 2018). These cases are seldom straightforward to manage, because
doi: 10.3389/fcimb.2020.00079 clinical disease often reflects yeast proliferation due to a disturbance in the normal homeostatic

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Guillot and Bond Malassezia Yeasts in Veterinary Dermatology

balance of host immunity, on the one hand, and yeast virulence, TABLE 1 | Malassezia species and main mammalian hosts.
on the other (Ashbee and Bond, 2010). Thus, successful case
Malassezia Synonyms Presence on Presence in lesions
management is often dependent upon both treating yeast (and species healthy skin
any concurrent bacterial) overgrowth with topical or systemic
antimicrobial treatments, as well as identifying and correcting M. furfur Pityrosporum ovale In humans In humans (PV, FG)
where possible, predisposing factors. Commonly identified Sometimes
factors include concurrent allergic or endocrine skin disease, in animals

defects in cornification, or anatomical defects such as skin M. pachydermatis P. pachydermatis, In dogs, cats, In dogs, cats, others
P. canis many others (SD, OT)
folds or stenosed ear canals (Bond et al., 2010). By contrast, (mostly canids) Sometimes in
there are only sporadic reports of Malassezia associated with Sometimes in humans (FG)
skin disease in large animal species. For example, Malassezia humans (dog
overgrowth in the intermammary region and preputial fossa has contact)
been implicated in tail-head pruritus and localized dermatitis in M. sympodialis M. furfur serovar A In humans and In humans (AD, SD)
horses (White et al., 2006). Goats may present with Malassezia- animals Sometimes in cats (OT)

associated seborrheic dermatitis (Pin, 2004; Eguchi-Coe et al., M. globosa P. orbiculare In humans and In humans (PV, SD, AD)
M. furfur serovar B animals Sometimes in cats (OT)
2011). Malassezia otitis has been reported in fennec foxes (Guillot
M. obtusa In humans In humans
et al., 1994), ferrets (Dinsdale and Rest, 1995), pigs (Pinter et al.,
M. slooffiae In pigs, cats In humans
2002), and camels (Kuttin and Glas, 1985).
(claws)
Recently, the World Association of Veterinary Dermatology In humans
commissioned the development of clinical consensus guidelines M. restricta M. furfur serovar C In humans In humans (SD)
for the diagnosis and treatment of Malassezia dermatitis in dogs M. dermatis In humans In humans (AD)
and cats (Bond et al., 2020). A panel of specialists/diplomates M. japonica In humans In humans (AD, SD)
in veterinary dermatology and mycology prepared a detailed M. nana In cats, horses In cats, cattle (OT)
literature review of publications up to mid 2018, and made M. yamatoensis In humans In humans (SD)
recommendations on selected topics. The draft document was
M. caprae In goats
presented at international veterinary meetings and uploaded on
M. equina M. equi In horses In horses
the WAVD website for comment for a period of 6 months.
M. cuniculi In rabbits
The final version comprised a systematic review of published
M. arunalokei In humans In humans
therapeutic studies, and current information on the ecology,
M. brasiliensis In parrots –
pathophysiology, diagnosis, and prevention of skin diseases
M. psittaci In parrots –
associated with Malassezia yeasts in dogs and cats.
M. vespertilionis In hibernating bats –
In view of the free access availability of this recent very detailed
and wide-ranging review (Bond et al., 2020), the present article –, not reported; PV, pityriasis versicolor; FG, fungaemia; AD, atopic dermatitis; SD,
aims to provide the reader with a general background summary seborrheoic dermatitis; OT, otitis.

of current understanding of the roles of Malassezia yeasts in

animal skin disease, with emphasis on recent publications from routine media without lipid supplementation. Malassezia yeasts
mid 2018 to end of 2019 that expand upon previous knowledge. were further detected from different warm-blooded vertebrates
and several specific names were proposed according to the latin
names of the animals on which the yeasts were initially isolated:
THE GENUS MALASSEZIA: A GROWING M. pachydermatis (from a rhinoceros within Pachydermata,
NUMBER OF SPECIES IN A GROWING an obsolete nineteenth-century taxonomic order of mammals)
NUMBER OF ANIMAL HOSTS (Weidman, 1925), M. caprae from goats (Cabanes et al., 2007),
M. equina from horses (Cabanes et al., 2007), M. cuniculi
Originally thought as a single species, Malassezia yeasts are from rabbits (Cabanes et al., 2011), M. pstittaci from parrots
now known to form a unique cluster consisting of 18 species (Cabanes et al., 2016), and very recently M. vespertilionis from
living almost exclusively on the skin and mucosal sites of warm- bats (Lorch et al., 2018). Some Malassezia yeasts (especially
blooded vertebrates (Lorch et al., 2018; Theelen et al., 2018) M. pachydermatis) appear to have a broad host range, while
(Table 1). During the last decade, the analysis of the genome of others are more host-specific with a close adaptation to the
Malassezia yeasts suggested that their ancestors were plant or cutaneous ecosystem of a single animal species or a group
soil fungal residents which progressively managed to survive and of phylogenetically related animals (Table 1). The number of
develop in the cutaneous ecosystem (Xu et al., 2007). The genus currently described Malassezia species (n = 18) is likely limited
Malassezia (Baillon) was created in 1889 for a single species, due to a sampling bias toward humans and domestic animals. We
M. furfur, detected in cutaneous lesions in humans (Baillon, can imagine that the number of Malassezia species will increase
1889). Weidman was the first scientist to detect Malassezia yeasts when the skin microbiota of a broader range of wild animals
from the skin of an animal, an Indian rhinoceros (Rhinoceros is investigated.
unicornis) with a generalized exfoliative dermatitis (Weidman, Very recently, Lorch et al. were able to isolate a new Malassezia
1925). In contrast to M. furfur these yeasts cultivated readily on species from the skin of nine species of bats in the subfamily

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Guillot and Bond Malassezia Yeasts in Veterinary Dermatology

Myotinae in eastern and western United States (Lorch et al., 2020). The general conclusion from these studies is that the peri-
2018). Physiological features and molecular characterization at oral region and interdigital skin is frequently colonized (up to
seven additional loci clearly demonstrated that all of the bat 80%) by M. pachydermatis in healthy dogs of various breeds,
Malassezia isolates represented a single and new species which whereas the yeast is less-often (<25%) detected on the skin of
was designated as M. vespertilionis. Among other characteristics, the axilla, groin and dorsum. The skin of cats may be colonized
the new species is able to grow over a broad range of temperatures by several Malassezia species. Whilst M. pachydermatis remains
(7–40◦ C), with optimal growth occurring at 24◦ C. The authors most prevalent, as in dogs, the lipid-dependent species isolated
suggested that the wide thermal growth range may be an from cats include M. sympodialis, M. globosa, M. furfur, M. nana,
adaptation to survival on bat skin during both hibernation and and M. slooffiae (reviewed by Bond et al., 2020). M. nana is
active seasons (Lorch et al., 2018). the most common lipid-dependent species in cats, particularly
in the ear canal, and a particular M. nana genotype seem to
predominate in this animal host (De Bellis et al., 2009; Castella
RECENT RE-ASSESSMENTS OF
et al., 2011). M. slooffiae is primarily but not exclusively isolated
LIPID-DEPENDENCE IN MALASSEZIA from claw folds in cats (Åhman et al., 2007a).
PACHYDERMATIS Recently, methods based on next generation sequencing
(NGS) have allowed a better characterization of the complex
Malassezia species are lipid dependent due to an inability microbial communities occurring on animal skin and made it
to synthesize long-chained (C14 or C16) fatty acids de novo possible to detect Malassezia species that would otherwise be
(Shifrine and Marr, 1963). There are some differences in lipid missed using culture-based methods (Meason-Smith et al., 2017,
dependence among the species and this variability has been 2019; Korbelik et al., 2018; Older et al., 2019). Meason-Smith et al.
used for the development of specific tests for their identification reported that the cutaneous mycobiota in dogs was influenced by
(Guillot et al., 1996). Historically M. pachydermatis was regarded various factors including environmental exposure, cohabitation
as being “lipophilic but not lipid-dependent” because it was the with other pets and skin health status (Meason-Smith et al.,
only member of the genus to grow on Sabouraud’s dextrose 2015). Surprising, Malassezia yeasts were not the most abundant
agar (Guillot and Bond, 1999). Recently, genome sequencing fungal organisms on healthy canine skin. Furthermore, these
has confirmed that M. pachydermatis lacks a fatty acid synthase authors were unable to detect any significant differences in the
gene like the other members of the genus (Wu et al., 2015), relative abundance of Malassezia yeasts between healthy and
but is uniquely able to utilize lipid fractions within the peptone allergic dogs. The discrepancy between NGS results and culture-
component of Sabouraud’s dextrose agar for growth (Puig et al., dependent studies demonstrating increased populations of M.
2017). These observations explain its failure to grow on lipid- pachydermatis in allergic dogs (Bond et al., 1994; White et al.,
free defined media and thus M. pachydermatis should now also 1998) may be related to differences in methodology. Another
be regarded as being “lipid-dependent” (Puig et al., 2017). explanation would be that dysbiosis is present at Malassezia
species level (rather that at M. pachydermatis abundance) in
ECOLOGY OF MALASSEZIA YEASTS IN allergic dogs. This hypothesis was very recently investigated by
DOGS AND CATS: COMPLEMENTARY AND Meason-Smith et al. who collected skin samples from healthy,
naturally affected allergic, and experimentally sensitized atopic
CONFLICTING RESULTS FROM dogs (Meason-Smith et al., 2019). Using NGS (at species level
TRADITIONALLY CULTURE-BASED classification) and Malassezia species-specific quantitative real-
STUDIES AND MORE RECENT time PCR (qPCR), they demonstrated that M. globosa was
MOLECULAR INVESTIGATIONS significantly more abundant on healthy canine skin (by both
methods), M. restricta was significantly more abundant on
To better understand the ecology of Malassezia yeasts on healthy healthy skin (by NGS), and M. pachydermatis was significantly
skin and in cases of cutaneous lesions, culture-based studies more abundant on naturally-affected allergic skin (by NGS) and
have been carried out both in humans (Gaitanis et al., 2012) on allergen-induced atopic skin lesions (by qPCR).
and in animals, especially in dogs (reviewed by Bond et al., The NGS method was also recently applied to better
2020). Results vary between studies because of the use of understand the mycobiota in the external ear canal of dogs
different sampling procedures, culture media, and identification (Korbelik et al., 2018). Samples were collected from six dogs with
techniques. However, culture-based studies clearly demonstrate otitis externa and five clinically normal dogs. In cases of otitis
that M. pachydermatis is the predominant cutaneous yeast in externa, the mycobiota was largely dominated by Malassezia
both healthy dogs and dogs with Malassezia dermatitis or otitis yeasts. Fungal species diversity, richness and evenness were
(Gustafson, 1955; Dufait, 1985; Hajsig et al., 1985; Bond and all significantly reduced in samples from otitis externa when
Lloyd, 1997). M. pachydermatis is also most important in cats but compared to healthy ears.
in this host other Malassezia species are more frequently detected In cats, metagenomic analyses suggested that the skin is
(Hajsig et al., 1990; Hirai et al., 2004; Åhman et al., 2007a; Åhman inhabited by bacterial communities that are distinct to each
and Bergstrom, 2009; Volk et al., 2010). Several investigators body site (Older et al., 2017) whereas fungal communities seem
explored Malassezia colonization in various anatomical regions more unique to the individual level (Meason-Smith et al., 2017).
of different breeds of adult healthy dogs (reviewed by Bond et al., When samples from healthy and allergic cats were collected, the

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Guillot and Bond Malassezia Yeasts in Veterinary Dermatology

most abundant fungal sequences were identified as filamentous in dogs and cats. All these processes should ideally result in a
contaminants from the environment and not Malassezia yeasts, delicately balanced homeostatic relationship. The presence of
which were identified in 30 and 21% of healthy and allergic Malassezia yeasts within the stratum corneum exposes the host
cat samples, but rarely accounted for more than 1% of the to an array of chemicals, immunogens and allergens, comprising
relative fungal abundance (Meason-Smith et al., 2017). The fungal cell wall-associated carbohydrates, proteins and lipids;
objectives of the recent study from Older et al. were to evaluate secreted enzymes that generate both substrates for nutrition, and
how genotype and environment can influence the bacterial and an array of irritant metabolic by-products (reviewed by Ashbee
fungal microbiota of feline skin (Older et al., 2019). Using and Bond, 2010; Sparber and Leibundgut-Landmann, 2017).
NGS and Malassezia qPCR, they demonstrated that M. restricta In a recent investigation, Czyżewska et al. compared the
and M. globosa were the most prevalent Malassezia species. protein profiles of M. pachydermatis isolates from 30 dogs
Sequences corresponding to M. slooffiae, M. furfur, M. nana, with clinical signs of otitis externa and 34 clinically normal
M. pachydermatis, M. dermatis, M. sympodialis, M. japonica, dogs (Czyżewska et al., 2019). The most significant finding was
M. obtusa, and M. yamatoensis were also detected. Malassezia the presence of nicotinamide adenine dinucleotide phosphate
abundance was significantly different between cat breeds with (NADP)-dependent mannitol dehydrogenase and ketol-acid
Devon Rex cats having the highest abundance. No significant reducto isomerase (an enzyme involved in the biosynthesis of
difference in abundance of any Malassezia species were found branched-chain amino acids) among M. pachydermatis isolates
between the different cat breeds or when comparing indoor and obtained from dogs with otitis externa. It is not clear whether
outdoor animals. these enzymes confer an advantage to the yeast or act as virulence
Taken together, these studies demonstrate significant disparity factors (Czyżewska et al., 2019).
between cultural and molecular studies in defining the Malassezia Malassezia cell wall carbohydrates are recognized as IgE
species component of the skin mycobiota in dogs and cats. binding epitopes in humans with atopic dermatitis but recent
Importantly in dogs, cultural methods seldom demonstrate work highlighted their importance in fungal cell recognition
Malassezia species other than M. pachydermatis in both health by host phagocytic cells. C-type lectins are proteins that bind
and disease, even when culture media reputed to support the carbohydrates in a calcium-dependent manner via highly-
growth of the more lipid-dependent species such as modified conserved carbohydrate-recognition domains (Tada et al., 2006).
Dixon’s agar are utilized (reviewed by Bond et al., 2020). By Mincle, a C-type lectin expressed by activated phagocytes that
contrast, molecular techniques indicate the frequent presence of binds glucosyl and mannosyl-glycolipids from M. pachydermatis
M. globosa and M. restricta, species that are seldom identified by and M. sympodialis, selectively recognizes Malassezia yeasts
culture (Meason-Smith et al., 2019), despite years of searching but not other fungi (Yamasaki et al., 2009). Recently, van
by the present and other authors (Guillot and Bond, 1999). der Peet et al. reported the total synthesis of a complex β-
Furthermore, the distinctive morphology of M. globosa (Guého- 1,2-mannosyloxymannitol glycolipid from M. pachydermatis,
Kellerman et al., 2010) is not systematically observed in clinical which was a potent agonist of human Mincle signaling; these
cytological specimens from dogs with dermatitis (Bond, R., observations may have relevance in the further understanding
personal observations). When presented with a clinical case, of antifungal immunity (Van Der Peet et al., 2019). Whilst it is
it may not be strictly necessary for the attending veterinarian intuitive that similar mechanisms may occur in dogs and cats,
to know the species identity of the Malassezia causing the species-specific studies are required to verify this.
disease, provided species variation in drug susceptibility is A recent study suggested that M. pachydermatis is able to
limited (Tragiannidis et al., 2010). Further developments in both activate the aryl hydrocarbon receptor (AhR), a nuclear receptor
diagnostic and antifungal drug susceptibility testing are urgently and transcriptional regulator with pleiotropic effects that
required to address these aspects. include down-regulation of immune stimulation, modification
of melanogenesis and epidermal cell function, and inhibition
of antagonistic microbes (Buommino et al., 2018). Since indole
PATHOGENESIS OF MALASSEZIA production was not detected in a study of 80 M. pachydermatis
DERMATITIS IN DOGS AND CATS: strains from canine otitis externa, AhR activation by M.
BACKGROUND AND RECENT ADVANCES pachydermatis might be associated with the release of compounds
other than indolic metabolites (Kiss et al., 1996).
There have been significant and recent advances in Experimental models have been used to better understand
understanding of the mechanisms of interaction between the pathogenesis of Malassezia dermatitis. Cutaneous responses
Malassezia yeasts and dogs and cats (reviewed by Bond to the application of viable and killed “lipid-dependent”
et al., 2020). The outcome of Malassezia growth on the skin Malassezia in laboratory animals (guinea pigs, mice, rabbits)
(commensal existence or inflammation and disease) is dependent generally comprised focal areas of scaling that most often
upon the metabolic activities of the yeasts (expression of cell resolve without treatment upon discontinuation of inoculation
wall and secreted virulence attributes) and the host’s innate and (Drouhet et al., 1980; Rosenberg et al., 1980; Faergemann
adaptive immune defensive responses. Interactions with other and Fredriksson, 1981; Van Cutsem et al., 1990). Similarly, in
skin commensals (especially staphylococci) may also play a role laboratory beagle dogs, application of M. pachydermatis was
in determining the outcome of colonization in animals, although associated histologically with epidermal hyperplasia, occasionally
this area is largely unexplored (Ianiri et al., 2018), especially with parakeratosis, superficial perivascular dermal inflammation

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Guillot and Bond Malassezia Yeasts in Veterinary Dermatology

with primarily neutrophils and lymphocytes, and sometimes (Bond et al., 1996b). Skin folds commonly represent an important
mast cells (but not eosinophils); features were more severe local factor in favoring overgrowth by Malassezia and or bacteria;
at sites that were occluded (Bond et al., 2004). Histological this likely reflects local climatic differences involving factors
changes markedly reduced within 7 days of withdrawal of yeast such as reduced air movement, increased skin temperature and
challenge. Inoculation of suspensions of M. pachydermatis into humidity, retained secretions, and surface frictional trauma
the middle ear and dermis of immunosuppressed mice led to (Jenkinson, 1992). Although not specifically studied in the dog,
transient infection that resolved within 21 days (Schlemmer it is also generally recognized that Malassezia dermatitis is more
et al., 2018). Recently, Merkel et al. developed a minihost common in tropical climates, and during warm, humid months
(invertebrate) experimental model wherein the pathogenicity of in more temperate latitudes, reflecting external environmental
M. pachydermatis was evaluated in wild-type (WT) and Toll- effects on the skin microbiota (Theelen et al., 2018). This factor
deficient Drosophila melanogaster. WT flies were resistant to is well-documented in human medicine, with warm tropical
the infection, whereas Toll-deficient flies showed inoculum- climates favoring high positive culture rates and greater species
dependent mortality rates. Experimental models may prove diversity (Gaitanis et al., 2012; Leong et al., 2019).
valuable in the further elucidation of both yeast virulence and Predisposition to Malassezia dermatitis in cats parallels the
host immune factors that are important in disease processes in canine situation in many ways with one important exception.
various species. Whilst skin folds and allergic diseases are also commonly
The presence of Malassezia yeasts on the skin, both in normal identified as factors (Ordeix et al., 2007), feline Malassezia
and excessive numbers, is known to activate the skin immune dermatitis in older cats is occasionally associated with visceral
system in dogs and cats. Malassezia antigens can stimulate neoplasia, most commonly feline (pancreatic) paraneoplastic
innate, antibody and cell mediated immune responses, as well alopecia and thymoma-associated exfoliative dermatitis (Forster-
as triggering hypersensitivity reactions (Bond et al., 2010). In Van Hijfte et al., 1997; Mauldin et al., 2002).
animals in which an overgrowth of organisms has occurred, or Dog breeds identified to be at increased risk of Malassezia
in individuals that are predisposed to allergic sensitization, the dermatitis include West Highland white terriers (WHWT),
ensuing inflammatory response can lead to clinical signs such English setters, shih tzus, basset hounds, American cocker
as dermatitis and pruritus. Elevated IgE levels to Malassezia spaniels, boxers, dachshunds, poodles, and Australian silky
yeasts or Staphylococcus bacteria in human atopic dermatitis are terriers (Mason, 1992; Plant et al., 1992; Bond et al., 1996b;
related to the skin severity index. To assess whether a similar Mauldin et al., 1997). Devon rex and Sphynx cats, but not
association occurs in dogs, Khantavee et al. investigated levels Cornish rex cats, are prone to high carriage rates of Malassezia
of allergen-specific IgE, IgG1, and IgG2 directed against M. yeasts (defined by culture) and a generalized seborrhoeic
pachydermatis and S. pseudintermedius, with total IgG levels, dermatitis that responds to oral itraconazole (Åhman et al.,
and correlated them with lesion severity in dogs with atopic 2007a,b; Åhman and Bergstrom, 2009; Volk et al., 2010). These
dermatitis (Khantavee et al., 2019). They reported that specific breed predilections in dogs and cats are likely analogous to
IgE and total IgG against yeasts and bacteria were significantly the observed effects of ethnicity on Malassezia populations on
increased in atopic dogs of all ages. However, no significant human skin (Leong et al., 2019).
relationships were found between the clinical score and any A recent study that utilized next generation sequencing (NGS)
specific immunoglobulin levels for both microbe types. to study fungal populations on skin and mucosae in various cat
breeds also reported that Devon rex cats had a high abundance
of Malassezia species (Older et al., 2019). Interestingly, species-
PREDISPOSING FACTORS FOR SKIN level analyses of the sequences identified M. globosa and M.
DISEASE IN DOGS AND CATS restricta as the most abundant Malassezia species in the subject
cats (Older et al., 2019). In contrast, previous cultural studies
Ideally commensal Malassezia yeasts behave as “good citizens” typically identify M. pachydermatis as the most abundant species
and occupy their ecological niche within the “transitional mantel in cats, even when media (for example, modified Dixon’s agar)
zone” of the epidermal stratum corneum and follicular and temperatures (32–34◦ C) considered appropriate for the
infundibulae, influenced by host skin and the external cultivation of the more demanding species are adopted (Bond
environment (Theelen et al., 2018). Normally, continuous et al., 1996a, 1997, 2008; Volk et al., 2010). Further investigation
interactions with the host immune system will maintain low of these discordant results is warranted.
numbers of the yeast without generating a clinically-appreciable
inflammatory response (Bond et al., 2020). It is well-recognized
that Malassezia dermatitis in dogs and cats is most often CLINICAL PRESENTATIONS IN DOGS AND
associated with concurrent diseases that are likely associated with CATS
altered skin immune function and/or changes in the chemical
and micro-climatic conditions at the skin surface (Bond et al., Affected skin is usually erythematous, often with greasy
2020). Thus in dogs, hypersensitivity disorders (especially canine brown-black material matting the lower portion of hairs;
atopic dermatitis), defects of cornification and endocrinopathies intertriginous zones are frequently involved (Bond et al.,
are frequently recognized as underlying factors that must be 2010). Pruritus, whilst ranging from minimal to severe, is
corrected or managed as part of the therapeutic programme normally a dominant feature. Concurrent hyperpigmentation,

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Guillot and Bond Malassezia Yeasts in Veterinary Dermatology

lichenification, malodour, traumatic alopecia, and otitis externa canal with a soft rubber feeding tube (Choi et al., 2018). In an
is common. In otitis externa, the discharge from the ear canal effort to improve upon the sensitivity of cytological sampling for
is commonly ceruminous and rarely purulent, and inflammation M. pachydermatis in the canine ear, Puig et al. have developed
commonly extends onto the pinnae. Cases of Malassezia a quantitative PCR method based on amplification of the single
paronychia present with claw fold erythema and swelling, waxy copy ß-tubulin gene (Puig et al., 2019). The authors judged that
or crusty brown exudate, red-brown claw staining, and may co- the results were accurate and showed improved sensitivity over
exist with a wider pododermatitis of haired skin. An occasional cytology; this method may have useful applications in diagnosis
presentation of frenzied facial pruritus in dogs with varying, and therapeutic monitoring, and in studies of pathogenesis and
sometimes subtle, erythema of chin / perioral skin, may be therapeutic product development.
misdiagnosed as neurological disease (Mason, 1992, 1993).
The signs of Malassezia dermatitis may mimic, or complicate,
those of canine atopic dermatitis. Features of concurrent diseases
ANTIFUNGAL DRUG SUSCEPTIBILITY
may be evident initially although they are commonly best TESTING FOR M. PACHYDERMATIS
appreciated once secondary Malassezia infection is removed.
Antimicrobial resistance has emerged globally as a serious
Malassezia dermatitis might feature in cats that present with a
threat to human and animal health (Fera et al., 2009). Recent
phenotype of allergic skin disease, idiopathic facial dermatitis
publications (Brilhante et al., 2018; Schlemmer et al., 2019a)
(Persian/Himalayan), feline acne, and serious internal medical
support previous observations that most wild-type Malassezia
disorders such as feline paraneoplastic alopecia and thymoma-
yeasts remain susceptible to the commonly-used azole drugs
associated exfoliative dermatitis (Bond et al., 2010). Client
such as itraconazole, ketoconazole and miconazole, although
expectation should be managed accordingly; residual skin disease
efficacy of fluconazole is more variable (Velegraki et al., 2004;
commonly remains despite successful antifungal therapy.
Cafarchia et al., 2012a,b; Weiler et al., 2013). In M. pachydermatis
isolates from canine otitis externa, synergistic interactions have
DIAGNOSTIC APPROACH IN THE been reported between between caspofungin and itraconazole or
VETERINARY CLINIC fluconazole (Schlemmer et al., 2019a), whereas amphoterecin B
antagonized the activity of itraconazole, but not fluconazole or
Following the original elegant description of tape-stripping in posaconazole (Alvarez-Perez et al., 2019).
human dermatology (Keddie et al., 1961), this method has In view of routine susceptibility and an absence of standard
gained wide acceptance in veterinary clinical practice as a rapid methods appropriate for the Malassezia genus, diagnostic testing
and versatile method for recovering stratum corneum cells and in veterinary practice tends to rely upon cytological rather
their attendant adherent microbes (Maynard et al., 2011). Light than cultural methods. However, laboratory studies of M.
microscopical examination (40–50 or 100x oil objectives) of tape- pachydermatis have previously demonstrated that it is possible to
strips, or dry scrapes, stained with modified Wright Giemsa stain select for resistance to terbinafine and azoles (Nakano et al., 2005;
(“Diff-Quik” or generic equivalents) is rapid and convenient for Jesus et al., 2011). Of greater concern are recent sporadic reports
assessment of the presence and numbers of Malassezia yeasts of therapeutic failure with azoles in canine M. pachydermatis-
(Moraru et al., 2019). Factors such as important variations in associated dermatitis that were associated with increased azole
anatomical site, breed, sampling method and host immune status tolerance in vitro; this might reflect the chronic and relapsing
commonly thwart the interpretation of the clinical significance of course of Malassezia dermatitis and otitis that often necessitate
an observed population (“XX yeasts in YY fields”); consequently frequent and lengthy treatment courses (Chiavassa et al., 2014;
a “treat what you see” trial therapy approach with topical or Watanabe et al., 2014).
systemic antifungal drugs is routinely required to establish the Angileri et al. isolated M. pachydermatis from an azole-
clinical significance of an observed population. A recent clinical unresponsive toy poodle that had MICs that were several
consensus guideline document presents a detailed diagnostic fold higher when compared with strains from untreated dogs
algorithm for use in the veterinary clinic (Bond et al., 2020). (Angileri et al., 2019). Kano et al. showed that an isolate of
The importance for investigating and correcting concurrent M. pachydermatis with MICs of itraconazole and ketoconazole
skin diseases and other predisposing factors, where possible, of >32 mg/L by Etest had mis-sense mutations in the ERG11
cannot be over-emphasized, if a chronic or relapsing course is to gene that encodes lanosterol 14 –alpha-demethylase, the target
be prevented. site for antifungal azoles (Kano et al., 2019b). Mutations in the
Cytology using swabs of lesions rolled onto glass slides same gene were described in field isolates with tolerance to
is normally best restricted to use in the ear canal, as the ravuconazole (Kano et al., 2019a) and in miconazole-resistant
yield of squames and yeast from the skin is inferior to that clones of CBS1879 (the neotype culture of M. pachydermatis)
obtained by tape strips and dry scrapes (Bond and Sant, 1993; selected by serial passage on miconazole supplemented media
White et al., 1998; Bensignor and Carlotti, 1999). In a recent (Kano and Kamata, 2019). Azole resistance in M. pachydermatis
randomized, blinded prospective study of 30 dogs with otitis has also been associated with quadruplication of the ERG11
externa, cytological specimens obtained using a conventional gene (Kim et al., 2018). By contrast, mutations in drug efflux
cotton-tipped swab contained comparable numbers of yeasts pumps, a common mechanism of azole resistance in Candida
and bacteria, but fewer inflammatory cells, when compared with species (Sanguinetti et al., 2005), has not yet been reported in
samples prepared by aspiration of material from the horizontal the genus Malassezia. The emergence of azole resistance amongst

Frontiers in Cellular and Infection Microbiology | www.frontiersin.org 6 February 2020 | Volume 10 | Article 79
Guillot and Bond Malassezia Yeasts in Veterinary Dermatology

Malassezia species warrants careful surveillance and product et al., 2020). Recently, the clinical and cytological effects of a
stewardship to ensure ongoing utility of this important drug class. once daily application of a leave-on spray formulation containing
Further data are urgently required to establish whether topical zinc, ethyl lauroyl arginate, laureth-9, urea, panthenol, glycerine
therapies are preferable to systemic treatments in this context, and butylene glycol (Aptus R Derma Spot On ConcentrateTM ,
and to guide antimicrobial stewardship policies for antifungal Orion Pharma Animal Health, Sollentuna, Sweden) were
therapy in small animal practice. evaluated in a randomized, blinded, controlled study of 18
Concern over azole resistance has prompted heightened dogs with chronic pododermatitis associated with Malassezia
interest in alternative antifungal agents. There are reports of yeasts (Sjostrom et al., 2018). When compared with placebo
in vitro efficacy against M. pachydermatis of a honey-based treatment of the contralateral foot, reduced yeast counts from
gel (Oliveira et al., 2018), monensin and, to a lesser extent, the actively treated foot were associated with a reduction in
narasin (polyether ionophores originally marketed as anti- clinical scores.
coccidials and growth-promoting modifiers of the bovine rumen In dogs, persistent or recurrent Malassezia dermatitis
flora; Chan et al., 2018, 2019). Multiple recent publications are usually associated with failure to identify and correct
have explored the potential antifungal utility of essential oils, predisposing or perpetuating factors. However, the evidence that
complex mixtures of highly concentrated aromatic oils (primarily reduced susceptibility of M. pachydermatis to commonly used
terpenes and/or phenylpropanoids) extracted from plants by antifungal drugs may develop under both field and laboratory
steam distillation, hydrodiffusion or pressure (Manion and conditions highlights the need for surveillance and vigilance for
Widder, 2017; Bismark et al., 2019). A previous randomized the emergence of clinically-relevant resistance. Agreed reference
clinical trial reported persistent efficacy of a commercial essential methods to assess antifungal susceptibility of M. pachydermatis
oil product (Malacalm, Flora Slr Oli essenziali, Lorenzana, are required to assist veterinary practitioner for the management
Italy) applied twice daily for 1 month to dogs with Malassezia of chronic cases.
dermatitis (Nardoni et al., 2014), although the study is weakened
by incomplete data on randomization and clinical scores (Bond POTENTIAL TRANSMISSION OF
et al., 2020). Publications between 2013 and 2018 were usefully
MALASSEZIA YEASTS FROM ANIMALS TO
reviewed by Donato et al. (2019). Most of the recent studies
have been conducted in vitro and their utility in clinical practice HUMANS
remains largely untested. Comparisons between studies are
The zoonotic potential of Malassezia yeasts was first defined in
hampered by an absence of agreed standard testing methods
the context of a neonatal intensive care unit, where a cluster
that are not yet optimized, arbitrary assignment of interpretative
of low birth weight patients receiving lipid emulsions were
criteria, and likely batch variation in activities of essential oils
colonized by M. pachydermatis that was likely introduced on the
prepared by different methods (Bismark et al., 2019). Recently,
hands of health care workers transmitted by contact with pet dogs
anti-Malassezia effects have been observed in vitro using winter
(Chang et al., 1998). Once introduced to a facility, Malassezia
savory, lemon grass, oregano, palmarosa and cinnamon leaf oils
yeasts can persist on incubator surfaces for prolonged periods
by agar disc diffusion and vapor assays (Bismark et al., 2019).
of time (Van Belkum et al., 1994). A subsequent case report
Oregano oil and thyme oil and their major phenolic components
described a facial granuloma caused by M. pachydermatis in a
(carvacrol, thymol) were fungicidal against M. pachydermatis
dog owner (Fan et al., 2006), and recently M. pachydermatis-
when tested using agar dilution (Sim et al., 2019). There are
associated fungemia has been reported in a small number
recent reports of synergistic interactions between essential oil
of adults with various predisposing factors (Choudhury and
components and azoles or nystatin against M. pachydermatis,
Marte, 2014; Roman et al., 2016; Lee et al., 2019). Since hand
including carvacrol and miconazole or nystatin, thymol and
contamination by M. pachydermatis is common amongst dog
nystatin (Schlemmer et al., 2019b), and between clotrimazole
owners, especially in owners of allergic dogs with Malassezia
and essential oils of Melaleuca alternifolia, Mentha piperita, and
overgrowth (Morris, 2005), there is a clear need for rigorous
Origanum vulgare (Bohmova et al., 2019).
hand hygiene by individuals in contact with pet dogs and cats,
especially when there is contact with immunocompromised
TREATMENT OF MALASSEZIA individuals (Bond et al., 2020).
DERMATITIS IN DOGS
AUTHOR CONTRIBUTIONS
A recent evidence-based review on the treatment of canine
Malassezia dermatitis reported “strong” evidence for the use JG and RB wrote, revised, edited and approved this manuscript
of a 2% miconazole and 2% chlorhexidine shampoo, used for submission in a collaborative process, agreed on the
twice weekly (Bond et al., 1995, 2020; Maynard et al., 2011). allocation of the review of these papers by topic, and circulated
“Moderate” evidence was available for a 3% chlorhexidine their draft reviews for the other author to edit and revise
shampoo (Maynard et al., 2011; Bond et al., 2020). For canine as appropriate. RB performed an initial electronic search
cases where topical therapy is ineffective or impractical, there was for recent relevant publications and led the development
“moderate” evidence for the use of ketoconazole at 5–10 mg/kg of the remaining sections. JG led the development of the
orally once or twice daily; and itraconazole at 5 mg/kg orally sections on the genus, ecology, and pathogenesis and uploaded
once daily or two consecutive days per week (reviewed by Bond the manuscript.

Frontiers in Cellular and Infection Microbiology | www.frontiersin.org 7 February 2020 | Volume 10 | Article 79
Guillot and Bond Malassezia Yeasts in Veterinary Dermatology

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physiology, and niche adaptation on human skin. PLoS Genet. 11:e1005614. Conflict of Interest: In the past 5 years, JG has received funding from or otherwise
doi: 10.1371/journal.pgen.1005614 collaborated with MSD Animal Health, Ceva Animal Health, Bayer Animal
Xu, J., Saunders, C. W., Hu, P., Grant, R. A., Boekhout, T., Kuramae, E. E., Health and Boehringer-Ingelheim. RB has received funding from or otherwise
et al. (2007). Dandruff-associated Malassezia genomes reveal convergent and collaborated with Dechra Veterinary Products, Bayer Animal Health, Ceva Animal
divergent virulence traits shared with plant and human fungal pathogens. Health, MSD Animal Health and Elanco.
Proc. Natl. Acad. Sci. U.S.A. 104, 18730–18735. doi: 10.1073/pnas.07067
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