impaginato piccolo - Società Italiana di Parassitologia (SoIPa)

86
A. Peano, M.G. Gallo - Treatment of Malassezia infection in the dog
repeated recurrences, and often require long-term antifungal
agent therapy. Therefore these “natural” compounds
showing in-vitro inhibition of the yeast growth
may be studied as “maintenance” topicals in case of
recurrent Malassezia infections. Moreover the appearance
of resistant strains of M.pachydermatis to available
antifungal agents is a concern (Nakano et al.
2005).
The clinical relevance of the in-vitro data is indirect
because many pharmacokinetic factors participate in
the final efficacy. For example penetration and accumulation
of the antifungals in the stratum corneum, as
well as synergism or counteracting effects mediated by
components of the stratum corneum (Piérard et al.
2004). An ex-vivo bioassay, based on studying yeast
growth on stratum corneum harvested by cyanoacrilate
skin surface stripping, has been developed to complement
the classic in-vitro tests (Rurangirwa et al. 1989).
In human medicine corneofungimetry has been used to
test antifungal compounds after applying them topically
(Arrese et al. 1995) or after oral intake (Piérard et al.
2004) by health volunteers. By this technique it was
possible to test the final formulations of the antifungals
as they are used in clinical practice and the fungal
strains tested, among which there were several
Malassezia species, were allowed to grow on human
stratum corneum, natural substratum for superficial
dermatomycoses (Rurangirwa et al. 1989; Piérard et al.
2004). Concerning Malassezia dermatitis of dogs similar
studies would permit to overcome in-vitro testing
drawbacks by testing the final product formulations
that, as above reported, have been shown to play a role
in the final efficacy of commercially available products
(Lloyd et al. 1999; Nebbia et al. 2008). In addition
Malassezia strains may be cultivated directly on their
natural substratum. Unlike many bacteria and other
fungi Malassezia yeasts are rarely found in the environment,
their habitat being primarily the skin and
mucosae of mammals and birds (Chen and Hill 2005).
Most in-vivo studies have been assessed on dogs with
spontaneous Malassezia dermatitis and/or otitis, while
a few have been carried out on dogs with induced infection
(Uchida et al. 1992; Nascente et al. 2005). Some
of the compounds showing in-vitro efficacy against
Malassezia are successfully used in clinical practice
either using systemic or topical approach. Different
treatment protocols are effective. The commonly used
systemic agents for Malassezia dermatitis in dogs are
the azoles. Ketoconazole and itraconazole are given at
5-10 mg/kg -1 per day per os for 3 or 4 weeks (Morris
et al. 1999; Matousek and Campbell 2002).
Itraconazole is also effective with a pulse regimen: 5
mg/kg -1 on 2 consecutive days per week for 3 weeks
(Pinchbeck et al. 2002). Recently oral terbinafine at 30
mg/kg -1 every 24 h has been shown to be a possible
alternative to azole derivatives (Guillot et al. 2003;
Rosales et al. 2005). The main advantages of this compound
are represented by its good oral tolerability with
no side effects demonstrated in man rodents, cats and
dogs (Gupta et al. 1994; Mancianti et al. 1999;
Castanon et al. 2001; Rosales et al. 2005) and its persistent
clinical effect after cessation of the treatment
due to residual tissue levels (Gupta et al. 1994).
Azoles, chlorhexydine, natural (Melaleluca alternifolia
oil) and miscellanous (selenium sulphide, lime sulphur)
compunds are used in various forms of topical commercial
products (shampoos, sprays, ointments, foams,
gels, ear drops), often as coadiuvants to systemic therapy
(Lloyd and Lamport 1999; Scott et al. 2001;
Nebbia et al. 2008). Topical therapy is sometimes used
prophylactically for recurring cases due to uncontrollable
underlying factors (Morris et. al 1999).
Although in-vitro anti-Malassezia activity of different
antifungals has repetitively been proved, commonly
used commercial formulations containing the same
principles often demonstrate lower in-vivo efficacy,
with maintenance of yeast abnormal overgrowth or
rapid recurrences. This is true especially for otologic
formulations. Actually in the dog in-vitro results on
strains isolated from clinical practice are not standardized
tools for prediction of in-vivo response to drugs of
M.pachyermatis. Poor responses to therapy and recurrences
confirm that many important factors which
mediate the initiation of inflammation or the developing
of histological changes depend on dog/yeast
immune relationship. Different evidences support, in
atopic dogs, the role of hypersensitivity to the yeast in
the pathogenesis of canine dermatitis/otitis by
Malassezia (Farver et al. 2005). Secondary microbial
infections can both initiate and perpetuate episodes of
atopic dermatitis in dogs and humans, and could even
participate in promotion of proallergic immunologic
responses (DeBoer and Marsella 2001). Atopic dogs
with Malassezia dermatitis show immediate skin test
reactivity to the yeast antigens whereas atopic dogs
without Malassezia overgrowth have generally negative
skin test results (Morris et al.1998). Some dogs with
typical cutaneous signs and low number of yeast at
cytological examination show a good clinical response
to antifungal therapy (Scott et al. 2001). Significantly
higher concentrations of Malassezia-specific IgE have
been detected in atopic dogs with or without yeast
overgrowth than either healthy dogs or non atopic dogs
with Malassezia dermatitis (Nuttall and Halliwell
2001). Hyposensitization to Malassezia by
immunotherapy has then been proposed as an alternative
to extended or repeated administration of antifungals
(Morris et al.1998; Morris et al. 2002; Morris et al.
2003). Actually Malassezia antigens are often either
included in skin test or IgE in-vitro panels for diagnosis
of canine atopy and consequently in “vaccines” used
to hyposensitize atopic dogs. Further investigations are
required to determine whether immunotherapy for
Malassezia type-1 hypersensitivity is really beneficial.
Actually cases for which immunotherapy appear to be
successful often receive concomitant other allergens
and/or topical and systemic antifungal compunds. It is
therefore questionable whether the positive response is
due to hyposensitization to Malassezia or either to successful
immunotherapy against other allergens and/or