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Biology, diagnosis and treatment of Malassezia dermatitis in dogs and cats

2020; Wiley; Volume: 31; Issue: 1 Linguagem: Inglês

10.1111/vde.12834

1365-3164

R. Bond, Daniel O. Morris, Jacques Guillot, Emmanuel Bensignor, David Robson, Kenneth Mason, Rui Kano, Peter Hill,

Cutaneous lymphoproliferative disorders research

This short paper presents the main conclusions from each section of the Clinical Consensus Guidelines. Literature reviews underpinning each of these summaries and recommendations are presented in the full version; the open-access complete text can be found at https://doi.org/10.1111/vde.12809. Malassezia yeasts are unique in several ways, including their strict dependence on lipids, their cellular ultrastructure, and their dominance as eukaryotic residents on the skin of warm-blooded vertebrates. The taxonomy of the genus Malassezia is evolving. Eighteen species have been described to date but many other species are most probably present on the skin or mucosal sites of warm-blooded animals. Few phenotypic tests are available to differentiate Malassezia species and some of them may overlap. Consequently, DNA sequencing (or other techniques such as mass spectrometry) may be required for specific identification. The history of the association between Malassezia yeasts and their animal hosts has been long-mired in controversy. Having been previously overlooked, canine Malassezia dermatitis has evolved from a controversial to a now routine diagnosis in small animal practice, with very significant welfare benefits for many animals. Malassezia pachydermatis is a normal inhabitant of healthy canine skin and mucosae; it also predominates on the skin of the domestic cat, although other species are occasionally identified, particularly M. nana in the ear canal and M. slooffiae in the claw fold. Population sizes vary markedly between anatomical sites and between different breeds. These commensal Malassezia populations provide a reservoir of yeasts that might proliferate and or induce an inflammatory response under the influence of various host predisposing factors. There have been significant advances in understanding of the mechanisms of interaction between Malassezia yeasts and their hosts. The outcome of Malassezia growth in the stratum corneum is dependent upon the metabolic activities of the yeasts (expression of cell wall and secreted virulence attributes) and the host's innate and adaptive immune defensive responses; interactions with other skin commensals (especially staphylococci) may also play a role. All these processes should ideally result in a delicately balanced homeostatic relationship. Further studies are required to define fully the parameters that dictate transitions between commensalism and parasitism that may yield opportunities for novel preventative and therapeutic strategies. A range of immunological hyper-responsiveness can be present in dogs with Malassezia dermatitis (none, immediate, delayed, contact). Tests for immediate hypersensitivity (serology, intradermal) are relatively accessible (although not standardised) whereas delayed reactivity following intradermal testing is assessed infrequently and patch testing is technically challenging in the clinical environment. Serological and skin test reactivity is also seen in a proportion of unaffected dogs; thus immunological tests must be assessed in the context of clinical and cytological data; they should not be used as stand-alone 'diagnostic' tests. It is intuitive that evidence of immediate, IgE-mediated or cellular hypersensitivity might indicate the need for rigorous antifungal therapy to minimize allergen challenge in the sensitized host, although this remains to be proven by controlled therapeutic studies. Although evidence of immediate, IgE-mediated hypersensitivity provides a rationale for allergen-specific immunotherapy (AIT), to date, there is relatively limited evidence of beneficial effects of AIT against M. pachydermatis in dogs. More data is required before this can be systematically recommended. Whilst some laboratories offer serological testing for IgG reactivity to M. pachydermatis, the clinical utility of this test is uncertain as there is no evidence of any diagnostic or therapeutic value. Dog breeds identified to be at increased risk of Malassezia dermatitis include West Highland white terriers, English setters, shih tzus, basset hounds, American cocker spaniels, boxers, dachshunds, poodles and Australian silky terriers. Devon rex and sphynx cat breeds are also predisposed. The presence of skin folds is a common risk factor for localised disease. Dogs with Malassezia dermatitis often have concurrent hypersensitivity disorders, cornification defects or endocrinopathies. Cats without a breed predilection most often have an underlying hypersensitivity disorder, or visceral neoplasia or other serious internal disease. Routine cytological sampling of skin sites in the veterinary clinic is best achieved by light microscopical examination (usually x100 oil objective) of tape-strips or dry scrapes stained with modified Wright Giemsa stain (Diff-Quik [Harleco, NJ, USA] or generic equivalent) (Figure 1). Cytology using swabs is normally best restricted to use in the ear canal. Factors such as important variations in anatomical site, breed, sampling method and host immune status commonly thwart the interpretation of the clinical significance of an observed population ("XX yeasts in YY fields"); trial therapy is routinely required to establish this. Tape-strip impression from the lip fold of a dog with Malassezia pachydermatis dermatitis. Abundant ovoid to short cylindrical yeast cells with broad-based budding amongst squames; modified Wright-Giemsa stain ("Diff-Quik"), x50. A single report indicates that the sharp end of a tooth pick is the preferred method for sampling the dorsal claw fold in dogs. Routine cultures provide primarily qualitative data on presence / absence of yeast, although 'heavy' growth on primary isolation plates likely indicates a high population. Modified Dixon's agar is the preferred medium for the isolation and quantification for M. pachydermatis from canine skin, in view of the relatively rapid growth of colonies that are readily distinguished from cutaneous bacteria and its' potential for supporting the growth of lipid-dependent isolates; incubation should be aerobic at 32-37°C for at least three days. Sabouraud's dextrose agar (preferably supplemented with 1% Tween 80) is an alternative for dog samples if modified Dixon's agar is unavailable, although occasional more-lipid dependent isolates will be overlooked with this medium; temperatures below 32°C should be avoided and use of 5-10% carbon dioxide should be considered. For cats, samples should be grown on modified Dixon's agar at 32-34°C aerobically; cultures should be systematically extended to at least seven days in case of presence of slower growing Malassezia spp. Temperatures in excess of 34°C must be avoided because of the potential to inhibit the growth of thermo-sensitive species such as M. globosa known to inhabit feline skin. Contact plates allow convenient, rapid and inexpensive quantitative culturing of M. pachydermatis from canine and feline skin; they are suitable for both diagnostic and research purposes. Optimally sized plates for cats and dogs (typically 18-27 mm diameter depending on site sampled) containing the preferred medium (modified Dixon's agar) are not available commercially but are readily custom-made in mycology laboratories. Detergent scrub sampling is the 'gold standard' method for quantitative culture, although it is more suited to a research rather than diagnostic environment because it is suitable for only relatively flat skin on co-operative animals and rapid sample processing is required. This is the optimal technique for mycological assessment in therapeutic product development. Molecular techniques are pivotal in the accurate identification of many of the currently recognised Malassezia species with the usual exception of M. pachydermatis. In particular, sequencing of D1/D2 domain of the large subunit of the rRNA gene, ITS, IGS, CHS2 and ß-tubulin genes allows for accurate identification of species and recognition of genotypes that may have relevance for host-adaptation and virulence. Microbiome studies utilising next-generation sequencing have the potential to re-define the microbial ecology of mammalian skin. Multiplex PCR and MALDI-TOF MS hold promise for rapid and specific identification of Malassezia from skin and culture specimens, respectively. A diagnosis of Malassezia dermatitis cannot be made by histopathology alone. Histopathological features in dogs often comprise hyperkeratosis or parakeratosis, irregular epidermal hyperplasia and spongiosis that extends to the hair follicle infundibula, lymphocyte and granulocyte exocytosis, and a mixed, predominately lymphocytic, superficial perivascular or interstitial infiltrate with variable superficial dermal oedema. Yeast cells may or may not be observed in surface or infundibular stratum corneum (cytology or quantitative culture preferable for assessment of populations). In cats, histopathological features vary markedly according to the nature of the underlying disorder. Testing for resistance is hampered by the unsuitability of the current CLSI and EUCAST reference methods, lack of an agreed modified protocol optimized for M. pachydermatis and absence of clinical breakpoints for either systemic or topical therapies. Despite these critical limitations, current data suggest that the vast majority of field isolates of M. pachydermatis are routinely susceptible to most relevant azoles (miconazole, clotrimazole, itraconazole, posaconazole and ketoconazole). However, the evidence that reduced susceptibility of M. pachydermatis to commonly used antifungal drugs may develop under both field and laboratory conditions highlights the need for surveillance and vigilance for the emergence of clinically relevant resistance. This is especially important in cases of canine atopic dermatitis, seborrhoeic dermatitis and chronic otitis externa where repeated treatments are commonly utilized. Improved and agreed reference methods designed to overcome the specific growth requirements of Malassezia spp. are therefore urgently required. Erythema, usually with kerato-sebaceous scale ("greasy material") and pruritus (minimal, mild, moderate or severe) dominates the clinical presentation, often favouring intertriginous zones (Figure 2). There may be concurrent hyperpigmentation, lichenification (Figure 3), malodour, traumatic alopecia and otitis externa. Some cases present with paronychia with claw fold erythema and swelling, waxy or crusty brown exudate, red-brown claw staining (Figure 4), or frenzied facial pruritus with varying, sometimes subtle, erythema of chin / perioral skin. Malassezia dermatitis in the neck fold of a bull mastiff. There is a localised and demarcated area of focally intense erythema of thickened skin, with mild alopecia and kerato-sebaceous material matting the remaining hairs. Malassezia dermatitis affecting the axillae of an atopic West Highland white terrier. These chronic lesions are characterised by symmetrical areas of intense hyperpigmentation, severe lichenification, erythema and tightly adherent crust. Erythema, usually with kerato-sebaceous scale ("greasy material") and pruritus (minimal, mild, moderate or severe) dominates the clinical presentation. There may be concurrent otitis externa and an observed breed predilection (Devon rex, sphynx). Malassezia dermatitis might feature in cats that present with a phenotype of allergic skin disease, idiopathic facial dermatitis (Persian / Himalayan), feline acne and serious internal medical disorders such as feline paraneoplastic alopecia and thymoma-associated exfoliative dermatitis. Yes Initiate trial therapy with appropriate topical and or systemic antifungal product. Amongst the various treatments utilised for Malassezia dermatitis in dogs, strong evidence is available only for the use of a 2% miconazole and 2% chlorhexidine shampoo, used twice weekly. This may be considered to be the topical treatment of first choice, where available and locally approved, and when owners are able to apply the product effectively. Moderate evidence is available for a 3% chlorhexidine shampoo. For canine Malassezia dermatitis, there is moderate evidence for the oral use of ketoconazole at 5-10 mg/kg once or twice daily; and oral itraconazole at 5 mg/kg once daily or two consecutive days per week. Based on current limited evidence, the use of either of these two azoles is justified in canine cases and the final choice may depend on geographical differences in availability, regulatory status and cost. Rationale for itraconazole instead of ketoconazole includes the potential for intermittent dosing and a perceived tendency for itraconazole to be better-tolerated. However, definitive statistical evidence of superior safety and/or efficacy is lacking and cost-benefit analysis makes ketoconazole a more practical choice in some countries. Compounded formulations must be avoided due to unreliable bioavailability. Evidence for oral fluconazole is limited to a single study where it was used at 5-10 mg/kg once daily conjunction with cefalexin. Thus fluconazole requires further assessment, especially since in vitro MIC values are routinely the highest amongst antifungal azoles utilised in veterinary medicine (section 10); this may correlate with intermittent anecdotal reports of treatment failures. Oral terbinafine warrants further evaluation due to partial beneficial effects in two trials and questionable stratum corneum concentrations in a pharmacokinetic study when given at the current dose of 30 mg/kg once daily. In cats, there is weak evidence only for the use of oral itraconazole at doses of 5-10 mg/kg daily; or 5 mg/kg on a seven days on / seven days off protocol. In view of this limited data, good safety profile and, in line with guidelines for feline dermatophytosis, itraconazole should be considered as the systemic azole of first choice in this species for Malassezia dermatitis. Topical chlorhexidine and azole products have not been evaluated although their use is intuitive as adjunctive or sole treatments where application is practicable and clinically appropriate, such as in localised infections. Treatment of chronic relapsing cases of Malassezia dermatitis in dogs and cats can be frustrating and may be limited by financial considerations. Identification and treatment of underlying causes is essential. When predisposing factors cannot be controlled, regular topical treatment or pulse oral therapy are reportedly useful in minimising relapses. Topical treatments are preferred to systemic treatments for long-term therapy because of a lower risk of toxicity. Topical prevention of Malassezia dermatitis in dogs might be achieved using 2% chlorhexidine / 2% miconazole or 3% chlorhexidine shampoo twice weekly, as has been previously recommended for treatment. Lesser frequencies may be useful in preventing relapse in some cases but there is currently no evidence to support this. Twice weekly application of three drops of topical hydrocortisone aceponate shows promise in the prevention of Malassezia otitis externa associated with allergic skin diseases. Pulsed therapy with itraconazole (5 mg/kg once daily, two days on / five days off for three weeks) has been shown to be efficacious in the treatment of Malassezia dermatitis (but not otitis externa) in dogs and thus should be effective as a preventative. There are only anecdotal reports of preventative efficacy of itraconazole for dermatitis at a once-weekly interval. Given the high prevalence of M. pachydermatis hand carriage by dog owners (as assessed by PCR) and the relative rarity of serious human infections by this organism, the overall risk for zoonosis is quite low, particularly among people who are immunocompetent. The need for good hand hygiene by individuals in contact with pet dogs and cats should be emphasised.