In a RCT, a 3% chlorhexidine shampoo was reported to be more than 50% effective in 18 of 22 treated dogs268 (Table 6; LoE 1; SoR B‐moderate) and was judged not inferior to 2% miconazole and 2% chlorhexidine. No statistical analyses, 5 mg/kg once daily for two consecutive days/week, Transient vomiting [n = 2], inappetence [n = 1], 6/13 dogs: transient vomiting [n = 4], vomiting and soft stool [n = 1], diarrhoea [n = 1]. Eine Breite von topischen und systemischen Therapien ist als wirksam bekannt, vor allem wenn prädisponierende Faktoren identifiziert und korrigiert werden. The studies were included if presented in full or abstract form in a peer‐reviewed journal; studies presented only in conference proceedings were not evaluated due to likely infrequent availability to the wider veterinary dermatology community. Development. The skin lesions in dogs with Malassezia dermatitis can be localised or generalised.70, 264, 387-389 Regional dermatitis commonly occurs on the muzzle, lips, ventral neck, axillae, ventral abdomen, medial hindlimbs, interdigital skin, perineum and in the external ear canal and intertriginous areas. Amongst the various treatments utilised for Malassezia dermatitis in dogs, strong evidence (SoR A) is available only for the use of a 2% miconazole and 2% chlorhexidine shampoo, used twice weekly (two RCT with LoE 1). In 2008, the Clinical and Laboratory Standards Institute published the most recent document (CLSI M27‐A3) in its’ series of reference standards for susceptibility testing of yeasts.331 However, these focused on invasive human pathogens such as Candida and Cryptococcus spp. These mature dendritic cells are excellent antigen presenting cells and are capable of presenting peptides on MHC molecules to T cells.185 Dendritic cells have also been shown to be activated by interaction between Malassezia antigens and various members of the C type lectin class of receptors such as Mincle, Dectins 1 & 2, and Langerin.175 This results in the production of pro‐inflammatory cytokines such as IL‐1, IL‐6, IL‐8 and TNF‐α.175 A recombinant Mala f 1 gene fragment upregulated the production of IL‐6, TNF‐Alpha and IL‐10, but not IL‐12, from human leukaemia‐derived dendritic cells.184 Interestingly, dendritic cells that have been stimulated by Malassezia antigens appear to be resistant to lysis by Natural Killer cells, a mechanism that likely favours survival of the cells in order to maintain antigen presentation.186. Skin colonization by Malassezia species in full term healthy newborns has been also investigated.464 Malassezia pachydermatis was not isolated from the skin of human neonates, while M. sympodialis and M. globosa colonisation begins at birth and increases in the first weeks of life. in skin diseases of the dog and cat. thérapeutiques pour la dermatite à Malassezia chez le chien..... 46 Deuxième partie : Évaluation de l’efficacité d’un shampooing dans le cadre du traitement de la dermatite à Malassezia chez le chien 1. Furthermore, the same study was unable to detect any significant differences in the relative abundance of Malassezia yeasts between healthy and allergic dogs.118 In a similar metagenomic analysis performed in healthy and allergic cats, the most abundant fungal sequences were identified as filamentous contaminants from the environment (Cladosporium and Alternaria spp.) The basset hound and WHWT in particular demonstrate clinically distinctive conditions characterized by generalized seborrhoea (basset hound)98, 145 or generalized, severely pruritic dermatitis with marked lichenification and hyperpigmentation.243 It is noteworthy that all of these breeds are recognized to be at increased risk for developing ether atopic dermatitis or primary idiopathic seborrhoea. The histopathological features in skin biopsy specimens from lesions of Malassezia infection in dogs and cats commonly represent an amalgamation of features reflecting both the host response to the yeast as well as the concurrent, underlying disease. (reviewed in Section 10). Elevated ALT in 1 dog. Of these cats, four received ketoconazole 10 mg/kg for 14–42 days either alone (2/4 cases) or with concurrent antibiotics (two of four cases). However, enhanced IgG responses can be seen in dogs with Malassezia dermatitis and in humans and dogs with atopic dermatitis. Adhesive tape can be applied to deeply folded or recessed areas that are not readily accessible for direct slide application, often with minimal animal restraint. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. The taxonomy of the genus Malassezia is evolving. In a study of 24 M. pachydermatis isolates (urea broth dilution), mean MIC values of terbinafine were favourably comparable to those of itraconazole, although ranges or MIC90 values were not reported.349 Similar activity was found (supplemented RPMI 1640 medium) with a single M. pachydermatis strain.329 In a study of 62 canine derived M. pachydermatis strains (Christensen's urea broth, supplemented RPMI 1640), terbinafine was superior (based on MIC90) to fluconazole by six two‐fold dilutions but inferior to ketoconazole and itraconazole by three and five dilutions respectively.334 These values were barely exceeded in a pharmacokinetic study of skin concentrations achieved after oral dosing at 30 mg/kg sid.350 In another study (Sabouraud's broth with 1% Tween 80) of 216 colonies of M. pachydermatis obtained from 28 dogs with otitis (n = 25) or dermatitis (n = 3), terbinafine was superior (based on MIC90) to fluconazole by five two‐fold dilutions but inferior to ketoconazole and itraconazole by one and four two‐fold dilutions respectively.336 A similar relationship between terbinafine and ketoconazole susceptibility was noted in a study (supplemented Sabouraud's broth) of 51 M. pachydermatis strains from canine ears.351, The polyene cyclic macrolides, amphotericin B and nystatin, were amongst the earliest broad‐spectrum antifungals introduced for clinical use.352 The potential toxicity of amphotericin B generally limits its use in veterinary medicine to serious progressive or disseminated systemic mycoses, whereas nystatin is active when applied topically.353 Its mode of action is via altered cell membrane permeability mediated by preferential binding to ergosterol. Small group sizes and concurrent cefalexin therapy limits interpretation. Abundant ovoid to short cylindrical yeast cells with broad‐based budding amongst squames; modified Wright‐Giemsa stain (“Diff‐Quik”), x50. The internalisation was shown to occur via binding to the mannose receptor and pinocytosis. Small group sizes and concurrent cefalexin limits interpretation. Table S6. The history of the association between Malassezia yeasts and its animal hosts has been long mired in controversy. In 1990, Simmons and Guého described the new species M. sympodialis which was characterized by a sympodial budding process.19 In 1996, Guého et al.20 had the opportunity to collect and examine many isolates from humans and animals. Gustafson was able to induce a spontaneously‐resolving erythemato‐ceruminous otitis externa in healthy dogs by the application of a suspension of ‘P. Consequently, the concluding summary is a combination of evidence base and consensus of opinion.2. Some cases present with paronychia with claw fold erythema and swelling, waxy or crusty brown exudate, red‐brown claw staining, or frenzied facial pruritus with varying, sometimes subtle, cheilitis or erythema of chin/ perioral skin. Sabe‐se que uma variedade de terapias tópicas e sistêmicas é eficaz, especialmente quando fatores predisponentes são identificados e corrigidos. Important breed predispositions are discussed in Section 7.1.67, 240, 241 There is no sex predisposition. Malassezia dermatitis is now recognised as a common skin disorder in canine practice, although it is encountered more occasionally in feline practice. The World Association of Veterinary Dermatology (WAVD) Clinical Consensus Guideline committee provided guidance and oversight for this process. The relatively high cost of certain innovator‐formulated drugs such as itraconazole has stimulated the compounding of bulk powder formulations by pharmacists in an attempt to reduce costs to clients. Recent genomic studies have elucidated previously problematical aspects of taxonomy and indicated that genotypes and species of Malassezia are evolving as an adaptation to particular host ecological niches. A basic description of molecular methods is incorporated to aid the non‐specialist reader in understanding how these techniques are currently applied to yeast identification and epidemiology, and how in future they may change our diagnostic approach to the case. As Malassezia yeasts are part of the normal cutaneous microflora, complete elimination of the organism is unrealistic even with effective treatment.447 Relapsing infections are common where there is persistence of the underlying cause for the yeast overgrowth. Breeds with conformations that favour skin folds are also prone to infections at intertriginous anatomical sites. Conventional and modern spectrum techniques were employed to characterise these isolates, encompassing morphology, ultrastructure, physiology and molecular biology. On examination, skin lesions are characterised by diffuse erythema and variable amounts of kerato‐sebaceous scale that can be brown (Figure 4), yellow or grey in colour.326, 387 The skin and hair coat may become greasy and self‐induced alopecia can occur due to the pruritus. Recently, genome sequencing has confirmed that M. pachydermatis lacks a fatty acid synthase gene like the other members of the genus, but is uniquely able to utilise lipid fractions within the peptone component of Sabouraud's dextrose agar for growth. in chin acne,416 although two cases were reported in conference proceedings which responded poorly to antibiotics, had yeast organisms on both histopathology and cytology samples, and showed a good clinical and mycological response to a 30 day course of oral ketoconazole.74, Malassezia pachydermatis is the predominant Malassezia yeast isolated from cats’ ears; frequency of isolation is increased in cats with otitis externa.418 In addition, M. furfur has been isolated from the ear of a healthy cat, whereas M. sympodialis56, 76, 419 and M. nana 24, 116 have been recovered from both healthy cats and cats with otitis externa. 1 – On ne guérit pas l’atopie par un traitement d’une dizaine de jours : c’est une maladie génétique (donc, quand on l’a, on l’a), chronique, avec des rechutes, qui demandera dans la majorité des cas un traitement permanent pendant toute la vie du chien. The skin also presents gross topographical features that affect moisture and retain secretions such as the intertriginous zones and the interdigital spaces. In one RCT study, clinical efficacy was associated with marked reductions in skin population densities of both M. pachydermatis and total bacteria/ staphylococci, assessed using a detergent scrub technique.145 In the second RCT, yeast counts were assessed by tape‐strips whereas bacterial populations were not assessed.268 Adverse effects to miconazole/ chlorhexidine were not reported amongst the 48 dogs treated in these two studies,145, 268 although the UK data sheet of the product used mentions ‘very rare’ or ‘exceptional’ pruritic or erythematous reactions (http://www.noahcompendium.co.uk/?xml:id=-449936). According to a standard textbook,326 Malassezia may feature in cases of bacterial intertrigo, feline hypersensitivity reactions, acrodermatitis of bull terrier dogs, atopic dermatitis, congenital follicular parakeratosis, facial dermatitis of Persian and Himalayan cats, familial paw pad hyperkeratosis, feline acne, feline paraneoplastic alopecia, feline thymoma‐associated exfoliative dermatitis, female hyperoestrogenism, food allergy, hypothyroidism, ichthyosis, interdigital furunculosis, mucinosis, nasodigital hyperkeratosis, sarcoptic mange, seborrhoeic dermatitis, Sertoli cell tumour‐associated skin disease, superficial necrolytic dermatitis and zinc‐responsive dermatosis (Table S4). Several species of Malassezia yeast are known to colonize healthy people as part of the commensal microbiome of human skin.33, 121, 458, 459 Spatial distributions of the species most commonly identified (M. globosa, M. sympodialis and M. restricta) may vary according to the age, body site and geographical location of the subjects studied.88, 121, 460 The archetypal zoophilic species, M. pachydermatis, may also be isolated from healthy human skin by culture or detected by molecular techniques, especially from the face460, 461 and hands.461, 462 In a retrospective study of 32 Malassezia spp. SDA (preferably supplemented with 1% Tween 80) is an alternative for dogs 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. In the absence of standard methods appropriate for M. pachydermatis the CLSI M27‐A2 and A3 protocols have been adapted by various modifications of the process (Table S5).329, 330, 333-336 Technical specifics were usefully reviewed in detail, including a discussion of the effects of medium and conditions of incubation, lipid supplementation, inoculum preparation, end‐point determination and quality control aspects.337. Concurrent cefalexin therapy limits interpretation. Cytology using swabs is normally best restricted to use in the ear canal. Despite the undisputable value of this phenotypic identification scheme, ambiguous results are sometimes reported. 1928–1929: McLeod and Dowling part‐fulfilled Koch's postulates by isolation of M. furfur from humans with seborrhoeic dermatitis in an oleic acid broth.48, 49 They then inoculated lesion‐free skin of a person with seborrhoeic dermatitis and a normal human with the broth isolate and reproduced seborrhoeic lesions in both, from which they re‐isolated M. furfur. An unusual feature of this study was reported lack of relapse 150 days post‐treatment in all of the essential oil‐treated dogs. Activation of keratinocytes by Malassezia is suggested by studies in humans which demonstrated that M. furfur could invade keratinocytes and resist phagolysosome fusion.178, 179 Furthermore, M. sympodialis produces extracellular vesicles, enriched with the allergens Mala s 1 and s 7, that bind actively to and are internalised by human keratinocytes, potentially promoting sensitisation and maintenance of inflammation.180, Keratinocytes recognise Malassezia antigens via Toll‐like receptors,174 although they, along with other cells, can also be activated via the aryl hydrocarbon receptor following stimulation with Malassezia furfur‐derived indole alkaloids such as malassezin, indirubin and indolo carbazole.175 These tryptophan‐derived metabolites can trigger a variety of effects such as apoptosis of human melanocytes, but their precise role in cutaneous pathology remains to be determined. For canine Malassezia dermatitis, there is moderate evidence (SoR B) for the use of ketoconazole at 5–10 mg/kg orally once or twice daily (five studies of LoE ≥ 2); and itraconazole at 5 mg/kg orally once daily or two consecutive days per week (two studies of LoE ≥ 2). Systemic therapies are often more expensive than topical therapies but may be necessary in cases where topical therapy is challenging for the owner/patient affiliation or otherwise ineffective. Ce qui est très interpellant aujourdhui cest que les symptômes de démangeaisons du chien (ou prurit du chien), liés à lirritation de la peau, sont de plus en plus graves jusquà donner des chiens qui nhésiten… Whilst one un‐blinded randomised study of 20 dogs suggested that there was no significant difference in efficacy between 5 and 10 mg/kg/day of ketoconazole administrated once daily for three weeks,428 there is insufficient evidence to comment specifically on the efficacy of the various doses used (5 or 10 mg/kg, once or twice daily). The perianal skin and anal mucosa is a frequent (~55% of 73 dogs) carriage site whereas nasal and oral carriage is less frequent. Cryptogamic Diseases], Uber das wesen des sogenannten Unnaschen Flaschenbazillus [The nature of the so‐called Unna's bottle bacillus], Exfoliative dermatitis in the Indian Rhinoceros (Rhinoceros unicornis) with description of a new yeast species, Pityrosporum pachydermatis, An experimental study of the pityrosporon of Malassez: its morphology, cultivation and pathogenicity, Epidermal infectiosn with yeast‐like organisms, An experimental study of the pityrosporon of Malassez: Its morphology, cultivation and pathogenicity, International Commision on the Taxonomy of Fungi (ICTF): name changes in fungi of microbiological, industrial and medical importance. Together, these studies indicated that the use of ketoconazole at an oral dosage of 5–10 mg/kg/day is most often either completely or partially effective, when given fasted, to improve both clinical signs and cytological or colony counts from dogs suffering from Malassezia dermatitis (Strength of Recommendation (SoR) B‐moderate). The role of this IgG response in the pathogenesis of skin disease is currently unclear, both in humans and dogs. The interactions between Malassezia yeasts and the skin of their hosts, and the factors which influence transition from commensal to pathogen, are the subject of intensive scientific endeavour, especially pertaining to the common pathogens of humans (M. globosa, M. sympodialis, M. restricta and M. furfur).33, 129 Comparative genomic studies following the sequencing of 14 Malassezia species have significantly advanced opportunities for understanding of the adaption of the genus to its limited ecological niches (mainly skin), elucidation of virulence attributes necessary for colonisation and infection, and identification of novel interventional targets for therapy.8 In particular, the novel description of Agrobacterium tumifaciens‐mediated transformation systems that allows for the insertion of transfer DNA and targeted gene deletion in M. furfur, M. sympodialis and M. pachydermatis, and thus analysis of individual gene function, is certain to revolutionise our understanding of the biology of this genus.130-132. Methods for microbiological assessment of skin populations have traditionally included impression (cytology using slides or tape; culture) and dispersal (primarily cup‐scrub or swab‐wash) methods.261 Impression culture methods tend to under‐estimate microbial populations whereas dispersal methods yield values closer to the true population.262, 263 Cytological examination without impression (scrapings, swab samples) are more recent developments. Few phenotypic tests are available to differentiate Malassezia species and some of them may overlap. The GP prepared a detailed literature review and made recommendations on selected topics. 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.18. Terbinafine: One study showed that oral terbinafine at 30 mg/kg orally once daily for 21 days reduced yeast counts (assessed by contact plates) in a group of seven basset hounds with high skin population densities of M. pachydermatis but without dermatitis; mycological efficacy was numerically but not statistically inferior to oral ketoconazole at 10 mg/kg once daily.281 This low‐powered study was not included in the SORT analysis because the outcome is disease‐orientated (yeast count) rather than patient‐oriented (no clinical scoring)(Level of evidence (LoE) 3).2 The efficacy of terbinafine was subsequently assessed in two clinical trials, either randomized and controlled by a different interval of dosing of terbinafine, or in a small study with concurrent cefalexin therapy (Table 5; SoR C‐weak).146, 432 Monitoring of serum hepatic enzymes has been recommended for dogs receiving daily oral terbinafine in view of reports of reversible, mild‐moderate elevations of alanine aminotransferase and serum alkaline phosphate.432, 433 A study designed to integrate pharmacokinetic data with previous MIC data in 10 healthy dogs treated with 30 mg/kg orally once daily for 21 days indicated that terbinafine does not achieve high stratum corneum and sebum concentrations compared with serum values; achieved concentrations barely exceeded previously reported in vitro MIC values.350 These and other pharmacokinetic data might indicate preferential utility for systemic mycoses,434 or the need for further dose optimisation for superficial mycoses in dogs. The need for good hand hygiene by individuals in contact with pet dogs and cats should be emphasised. Feline facial acne, thought to represent an idiopathic disorder of follicular keratinization, may also result in Malassezia overgrowth.252, The skin surface presents a range of natural micro‐climates and several ecological niches with different moisture and nutrient levels may be recognised.253 The eyes, ears, nares, oral cavity, lip fold, prepuce, vagina and anus provide microenvironments that are moist with secretions and constitute unique ecological niches (Section 4). The histopathological features of skin diseases where Malassezia spp. Interaction with other commensal microbes might also influence pathogenicity and expression of virulence factors.138-140 Thus, these commensal yeasts are likely highly regulated by continuous interactions with the host immune system (Section 6)141 and these interactions ultimately determine whether the outcome is inflammation (i.e. En cas d’otite externe, la plus fréquente, la peau du pavillon externe de l’oreille est rouge et chaude. The clinical presentation of feline Malassezia dermatitis varies markedly depending on the underlying disease (Section 7). From work in Malassezia and other pathogens, reduced susceptibility to azoles may be caused by reduced affinity due to alterations in the drug target enzyme,375 by increased expression of the target gene (ERG11) encoding this enzyme, or by increased efflux by overexpression of genes encoding membrane transport proteins of the ABC transporter (CDR1/CDR2) or the major facilitator (MDR1) superfamilies.352 Induction of high fluconazole MICs in 30 strains of M. pachydermatis by prolonged exposure was associated with elevated MICs to other azoles, suggesting that the molecular basis for these effects may in some cases confer cross‐resistance to this drug class.376 Further studies are needed to define the molecular genetics of the reduced susceptibility to azoles, terbinafine and nystatin induced in M. pachydermatis by laboratory exposure at sub‐inhibitory drug concentrations and any implications for long‐term drug use in clinical practice. In routine cases, skin populations of the yeast are best assessed by cytology or quantitative culture (Section 8). 1846: Karl Ferdinand Eichstedt was the first to observe hyphal elements and blastoconidia in scale from his patients and attributed these to cause a human skin disease he called “Pityriasis versicolor”.38, 1853: Charles Robin named Eichstedt's fungus as Microsporon furfur, believing it to be a dermatophyte, and termed the associated skin disease “Tinea versicolor”.39, 1873: Sebastiano Rivolta, an Italian veterinarian, noticed a double‐contour budding yeast in human “psoriatic” scales and gave them the name Cryptococcus psoriasis.40, 1874: Frenchman Louis Charles Malassez41 suggested that Microsporon furfur caused dandruff and correctly differentiated the yeast into genus of single cell fungi (“Saccharomyces”) rather than the dermatophyte complex. La dermatite à Malassezia fait partie du diagnostic différentiel des dermatites qui associent alopécie et prurit chez le chien et dans une moindre mesure chez le chat. Other enzymes from Malassezia yeasts such as acid sphingomyelinases and chitin deacetylases may also influence host‐yeast interactions.162. The rhinoceros responded rapidly to topical therapy with 1% salicylic acid in lard. Certaines régions sont plus touchées comme : le conduit auditif, les plis, les babines, les espaces interdigités et la base des griffes, la face ventrale de l’abdomen…. O GP preparou uma revisão detalhada da literatura e fez recomendações sobre os tópicos selecionados. One study reported that most M. pachydermatis isolates from canine otitis externa cases were inhibited by clotrimazole, miconazole and thiabendazole, at concentrations of 2‐8 (clotrimazole), 1–4 (miconazole) or 16–32 (thiabendazole) μg/mL.341 MICs were higher in M. pachydermatis isolates from chronic otitis dogs that had been previously treated with various topical ear products containing miconazole and clotrimazole.356 Another study examined in vitro antifungal susceptibility of M. pachydermatis isolated from cases of canine otitis clinically nonresponsive to either topical miconazole or clotrimazole and recognized MICs above the limit of detection for miconazole and clotrimazole in some isolates.382 Another study reported that high MICs of itraconazole and ketoconazole in a strain of M. pachydermatis from canine dermatitis were associated with missense mutations in the ERG11 gene.375 An additive effect of itraconazole in combination with tacrolimus375 likely reflected calcineurin‐inhibitor binding to the immunophilin FKBP12, as shown previously for additive interactions with fluconazole in M. furfur and M. sympodialis.131.

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