Levurosis Asociada a DAC
This essay seeks to understand the importance of Malassezia as a disruptor agent and/or perpetuator of atopic crises in patients affected by canine atopic dermatitis (CAD), to establish adequate control, and to prevent recurrent episodes.
A common skin disease in dogs, CAD is a type I hypersensitivity reaction to environmental antigens (allergens) inhaled or present on the skin in genetically predisposed individuals. CAD has been defined as a disease mediated by antibodies - specifically IgE - but it is likely that other elements in the immune system are also important to its pathogenesis. In addition, it is presumed that there are different isotypes IgE with different pathogenesis.
For induction of high degrees of IgE, it is important that the antigen is presented in the first months of life through the next three to four. Parasitic infections, viral infections, vaccination with modified live virus may increase the production of IgE and therefore their response.
Canine atopic dermatitis animals are more prone to pyoderma and malassezial levurosis. They have a higher degree of IgE for Malassezia than unaffected animals.
A number of studies and researchers in veterinary dermatology have debated treatments and have done deep analysis of levurosis with good, evidence-based results.
A variety of active principles have been used to treat this dermatitis: enilconazole, itraconazole, ketoconazole, miconazole, terbinafine, chlorhexidine, selenium sulfide, piroctone olamine and benzalkonium chloride, as well as combinations and therapeutic modalities.
In systemic therapy oral azoles are recommended: ketoconazole and itraconazole. The lowest dose of 5 mg/kg of ketoconazole per day for three weeks is recommended since it is as effective as a higher dose of 5–10 mg/kg and has less likely adverse effects. The recommended dose of itraconazole is 5 mg/kg, once a day on two consecutive days, each week for 3–4 weeks.
In animals in which chronic therapy collapses, regular topical treatments or pulse therapies with itraconazole are recommended. Topical therapies are preferred because of their lower risk of toxicity.
Malassezia pachydermatis
Malassezia pachydermatis is a lipophilic yeast, non-lipodependent belonging to the class Deuteromycetes and to the same family as Cryptococcus spp. It is considered strictly zoophilous, isolated from domestic carnivores and farm animals. Malassezia sympodialis, of human origin, has recently been isolated in the skin of healthy cats. Germ forms are often found in shoeprints as a result of asexual binary fission in cytology. In cultures, small, pale yellow or cream-colored colonies form. It grows on agar Sabouraud, using short-chain fatty acids present in the medium. Malassezia pachydermatis is commensal, a normal resident in the skin whose presence inhibits colonization of other fungal agents. It is readily isolated from oral cavities, peri-oral areas, the external auditory canal, genitals, and interdigital spaces of healthy dogs.
Its overgrowth is inhibited by normal scaling of the skin, the fungistatic properties of the hydrolipidic film, immune mechanisms such as IgA in apocrine gland secretions and cell-mediated immunity. As it proliferates, it becomes pathogenic if this balance is disturbed or when the tegumentary balance is previously altered - CAD. There are no variations in the pathogenicity of strains; rather, overgrowth is stimulated by an increase in humidity, temperature and lipid substrate and/or decreased defenses in the host. Certain congenital problems such as immunodeficiency (sometimes inherited) or excess skin folds (intertrigo areas that cause skin maceration), and obesity predispose animals to yeast overgrowth.
Acquired problems favoring malassezial overgrowth include allergic disease and immunosuppression caused by hormonal disease, or use of corticosteroids.
Hypersensitive patients have reduced immune capacity and catch more pathogen - especially Malassezia, but also staphylococci, on the corneocytes. Excessive antibiotic therapy can reduce resident bacteria on the skin, favoring malassezial overgrowth. Qualitative and quantitative variation in sebaceous gland secretions provides an environment rich in lipids and proliferation of this microorganism.
Malassezia causes inflammation. While it does not invade the stratum corneum, it produces enzymes whose metabolites increase the inflammatory response and pruritus. For example, lipases (phospholipase and lipoxygenase) alter the nature of the hydrolipidic film, generating eicosanoid production.
Atopic dogs produce more IgE than normal dogs and exhibit superior mast cell responses, compared to malassezial intradermal challenges.
Released proteolytic enzymes can stimulate nerve endings directly, triggering or increasing pruritic responses. Its overgrowth can cause concurrent staphylococcal folliculitis, suggesting the existence of pathogenic synergy. Epidermal hyperplasia observed in Malassezia dermatitis can be caused by growth factors produced by the body itself, although it is more likely that the cause is a reaction to inflammation and self-trauma.
Malassezia dermatitis occurs mainly in adult dogs. There is no prevalence associated to gender or age, but there has been increased susceptibility to infection in certain breeds: West Highland white terrier, poodle, basset hound, Shi-tzu, Pekingese, cocker, Labrador, German shepherd, Shar Pei and Jack Russell terrier. This dermatitis is more common in seasons of the year with higher ambient temperature, the greater presence of ecto-parasites, pollen allergens and higher humidity. Without adequate therapy, it persists and is perpetuated in the coldest months.
It usually begins in the abdomen, extending to the inguinal, axillary and neck ventral regions. Pododermatitis shows interdigital erythema, melanotrichia - pigmentation (dark) brown from the nail bed and infection.
As with bacterial otitis, the primary causes of Malassezia otitis include allergy, endocrine disease (primarily hypothyroidism), parasites of the ear canal, dyskeratosis and abuse of antibiotics or topical or systemic corticosteroids. In cats, Malassezia pruritic dermatitis induces autotrauma, presents with alopecia, erythema, dry or oily seborrhea. Some have malassezial paronychia and infection emerges with immunosuppressive systemic diseases: diabetes, feline immunodeficiency virus (FIV), feline leukemia virus (FeLV), herpesvirus.
Differential diagnoses, such as CAD or HA, pyoderma and dyskeratosis, include diseases with pruritic dermatitis, erythematous, seborrhea, lichenification and hyperpigmentation. Almost all of the above can denote malassezial infection. The diagnosis is made by cytology. The isolation of the organism in culture does not mean infection, Malassezia being normal resident. The number of colonies, like in other opportunistic infections, can be an indicator of infection.
The organism does not invade the epidermis, so histology is not a sensitive diagnostic test. Occasionally, organisms are seen in the stratum corneum.
Effective treatment depends on the identification and control of the primary cause.
In extensive cases, itraconazole is recommended at 5 mg/kg/day or ketoconazole 5–10 mg/kg BID for 20 days along with weekly baths.
Doses greater than 10 mg/kg of itraconazole SID, have been associated with vasculitis.
Griseofulvin is ineffective against this yeast.
Topical treatment is effective by itself in many cases. Shampoos based on 02.04% Chlorhexidine, 2% miconazole, are highly efficient.
In recurrent cases, and after stopping the systemic treatment, a topical therapy with shampoo is very useful.
As Malassezia pachydermatis is easily controlled, we are under a good perspective, but if the underlying disease is not identified, levurosis tends to recur.
References
1. Bond R, Lloyd DH. Factors affecting the adherence of Malassezia pachydermatis to canine corneocytes in vitro. Veterinary Dermatology. 1996;7:49–56.
2. Bond R, Lloyd DH. Skin and mucosal populations of Malassezia pachydermatis in healthy and seborrhoeic Basset Hound. Veterinary Dermatology. 1997;8:101–106.
3. Bruner SR, Blakemore JC. Malassezia dermatitis in dogs. Veterinary Medicine. 1999;94:613–620.
4. Carlotti DN. Shampoo therapy in veterinary dermatology. In: Proceedings of the World Small Animal Veterinary Association (WSAVA) Congress, Rhodes, Greece; 2004.
5. Guillot J, Bond R. Malassezia pachydermatis: a review. Medical Mycology. 1999;37:295–306.
6. Lower K, Medleau L, Hnilica K. A dog with elephant-like skin. Veterinary Medicine. 2000;95:360–362.
7. Negre A, Bensignor E, Guillot J. Evidence-based veterinary dermatology: a systematic review of interventions for Malassezia dermatitis in dogs. Veterinary Dermatology. 2009;20(1):1–12.
8. Mason IS, Mason KV, Lloyd DH. A review of the biology of canine skin with respect to the commensals Staphylococcus intermedius, Demodex canis and Malassezia pachydermatis. Veterinary Dermatology. 1996;7:119–132.
9. Mauldin EA, et al. Malassezia dermatitis in the dog: a retrospective, histopathological and immunopathological study of 86 cases (1990–95). Veterinary Dermatology. 1997;8:191–202.
10. Medleau L, Hnilica KA. Chapter 7: Hypersensitivity disorders: canine atopy (allergic inhalant dermatitis). In: Small Animal Dermatology: A Color Atlas and Therapeutic Guide. 2nd ed.; 2006.
11. Locke PH, Harvey RG, Mason IS. Manual de Dermatología en Pequeños Animales. ed. Harcourt. vol. 1. British Small Animal Veterinary Association (BSAVA); 1999.
12. Scott DW, Miller WH Jr., Griffin CE. Skin immune system and allergic skin disease. In: Muller and Kirk's Small Animal Dermatology. Chapter 8. 6th edition. Philadelphia, PA: Saunders Elsevier;2001.