The latest in diagnosis and management of Malassezia dermatitis

Malassezia is a genus of lipophilic yeast found as a commensal of the skin and mucosal surfaces that may cause skin disease in a variety of mammalian species. In healthy dogs, these organisms are present in small numbers on the skin (fold areas/lip, vulvar, axillae, interdigital), oral and anal mucosal surfaces, in the ear canals, and the anal sacs. In contrast to Candida, Malassezia dermatitis (MD) has not been associated with recent antibiotic administration; in fact, there appears to be a symbiotic relationship between the surface staphylococcal organisms and the yeast. It is theorized that the organisms produce growth factors and microenvironmental changes (eg, inflammation) that are beneficial to each, so it is not uncommon to see concurrent infections with Malassezia and staphylococcus.

Malassezia dermatitis. (Photo by Todorean Gabriel)

Why do animals develop MD? There have been numerous studies comparing the strain of Malassezia organisms found on the skin of affected dogs vs the skin of unaffected dogs. It was previously believed that there is no difference in virulence and/or adhesion in Malassezia organisms found on the skin of affected dogs vs the skin of unaffected dogs, but this belief has recently been challenged.¹ One study found that phospholipase activity of Malassezia was highest in dogs with generalized disease as opposed to dogs with localized disease or healthy patients. This finding suggests that phospholipase activity may play a pathogenic role in the occurrence of skin lesions caused by Malassezia, thus contributing to its virulence. Despite this study, virulence alone doesn’t appear to completely explain MD. Both type I and type IV hypersensitivity reactions to Malassezia have been found in dogs with MD. It seems that the host response is the crucial factor for the development of MD. With Malassezia overgrowth, there are a variety of events that occur that can contribute to cutaneous inflammation. The metabolism of the surface free fatty acids by lipases produced by Malassezia leads to the production of inflammatory eicosanoids, changes in the cutaneous pH, and decreases in the normal cutaneous barrier function. Because of the percutaneous absorption of the Malassezia antigen, complementary activation may occur. Disorders that affect the barrier function of the skin (eg, pruritus) or the cutaneous lipid content (eg, hypothyroidism) are risk factors for developing MD.

Signalment

There is no age or sex pledilection.

History

MD is always secondary to another skin disease. A clue that MD may be present is a change in the clinical features and/or the previously effective therapy of the underlying disease becomes ineffective. For example, seasonal pruritus becomes nonseasonal; the distribution of the pruritus changes to involve areas atypical for atopic dermatitis (eg, ventral neck), becomes poorly responsive to a previously effective antibiotic, and/or the effectiveness of glucocorticoid therapy is decreased. Any allergic animal whose pruritus (intensity or distribution) or the therapeutic responsiveness of the pruritus changes suddenly should be evaluated for MD, pyoderma, and ectoparasites.

Clinical findings

On physical examination, lichenification, erythema, greasy exudate, dry scale, papules, plaques, alopecia, follicular casts, paronychia, hyperpigmentation, or alesional, intense muzzle pruritus may be present. Moist dermatitis with a musty odor is not an uncommon clinical finding. Pruritus may vary from mild to intense, and erythema may be present with minimal pruritus, especially interdigitally.

The lesions may be focal or generalized, and the distribution of the lesions overlap with other pruritic diseases. Any area may be affected, but some of the more common areas include interdigital, intertriginous areas, face, nail folds, perioral (lateral muzzle), pinna, and flexor surface of the elbow.

Diagnosis

MD may cause folliculitis that is clinically identical to staphylococcal pyoderma. Therefore, if there are follicular papules, epidermal collarettes, or lichenification, one cannot assume there is a bacterial component to the skin disease without performing skin cytologies. Remember to include skin scrapings for ectoparasites as part of your minimum database, as demodicosis is also a follicular-oriented disease.

Identifying Malassezia organisms (budding yeast) from the affected area is necessary to establish a diagnosis of MD. Tape impression or direct impression smear are the most common methods used for sampling affected areas. Because of the ease of collection, the former may be preferred. If the skin is dry, a scalpel blade or the edge of a glass slide is used to scrape the surface for sampling. If using slides for an impression smear, there is no need to heat fix the sample nor to use all 3 stains that are part of the Diff-Quik procedure.^2,3 Using just the third stain (methylene blue) is adequate and will make processing the slide faster. A faster approach would be to take a tape impression, place a drop of the methylene blue Diff-Quik stain on the slide, then lay the tape on top of the stain. Use the tape as a coverslip and examine the sample after placing oil immersion on top of the tape.

The question is: How many is too many organisms? An earlier report found that healthy dogs had 1 yeast per 27 oil fields.⁴ In my experience, MD is diagnosed when a dog has clinical signs compatible with MD and has on cytology, any field that has more than 1 organism, or if there is 1 organism every 5 to 10 fields (1000x). The American College of Veterinary Dermatology task force on atopic dermatitis discussed MD as a complication of atopic dermatitis. The task force states that “surface cytology of the skin and ear is useful to determine whether Malassezia or Staphylococci are present at lesional sites. Making antimicrobial treatment decisions based solely on microbe numbers is incorrect and inappropriate.” The article goes on to discuss that the host response to these normal organisms determines the severity of clinical signs. Their recommendation was “the result of cytology might better be limited to the sole report of presence or absence of detectable bacteria or yeast.” This is because of the reported poor repeatability and reproducibility of microscopic examination of adhesive tape strip cytology for counting Malassezia organisms.⁵

The interesting question is: Why can’t I find yeast when I’m sure the dog has MD? Site selection has a significant impact. Because Malassezia is a surface organism whose numbers may be decreased by the animal’s licking, multiple
sites must be sampled, and because even small numbers of organisms can be significant, numerous fields must be examined. Lastly, interpretation of the number of organisms from skin cytology is very different than interpreting ear cytologies, in which 1 or 2 organisms may be interpreted as negative or rare and is of no clinical significance. This interpretation is not correct when evaluating skin cytologies.

Treatment

To prevent the recurrence of MD, the underlying cause must be identified and treated. As previously mentioned, any disease that disrupts the barrier function, the lipid content of the skin surface, the cutaneous microclimate, or host defense mechanisms may predispose the animal to MD. These include hypersensitivities (atopy, cutaneous adverse food reactions), ectoparasites (Demodex, Sarcoptes, and fleas), endocrinopathies (hypothyroidism, hyperadrenocorticism), metabolic diseases (metabolic epidermal necrosis), neoplasia (cutaneous T-cell lymphoma), and excessive skin folds. Genetic factors, as seen in Basset Hounds, predispose them to maintain a higher number of Malassezia organisms on their skin, putting them at higher risk for developing MD.

Unless the MD is very focal, both topical and systemic therapy may be preferred. This combination will be the most successful treatment for MD. Determining how much of the pruritus is from the MD and how much is from the underlying hypersensitivity is important in helping direct the next step. If treatment of the MD completely resolves the pruritus without any concurrent antipruritic therapy, either the dog has seasonal atopic dermatitis and the season has changed from the allergy season to the nonallergy season, or the dog has an underlying endocrinopathy. On the other hand, if the pruritus continues despite the resolution of the MD, then the dog has atopic dermatitis (nonseasonal environmental triggered, food triggered, or both).

There are a variety of active topical agents, including selenium sulfide, miconazole, ketoconazole, clotrimazole, and chlorhexidine. A review article revealed convincing evidence of the effectiveness of the shampoo combination miconazole/chlorhexidine (Malaseb). More studies are needed to further evaluate the value of some of the other available topical products. In my experience, any shampoo that contains at least 3% chlorhexidine or has 2% chlorhexidine combined with an azole is effective. If these shampoos are ineffective, selenium sulfide–containing shampoo has been beneficial. More recently, when topical therapy with these previously listed ingredients occurs, I have been using a shampoo containing piroctone olamine (Keratolux). Piroctone olamine has reported antibacterial and antifungal properties. However, it is unclear how effective this ingredient is at this time due to the limited number of cases that have been treated with this product. In a recent consensus guideline on the treatment of MD,⁶ piroctone olamine products were listed as having insufficient evidence to recommend because no randomized controlled studies had yet been done.

Shampooing should be followed by a leave-in conditioner containing an antifungal ingredient, such as miconazole, ketoconazole, terbinafine, or clotrimazole. Note for MD affecting the face folds of brachycephalic breeds of dogs, miconazole vaginal cream is a nice choice because it is safe even if it gets into the eyes (ophthalmologists use it for fungal keratitis in horses).⁷ Depending on the severity and extensiveness of the lesions, the frequency of application varies from daily to 3 times a week.

Ketoconazole (200-mg tabs) 7 to 10 mg/kg once daily (rarely twice daily) is the systemic drug of choice and is to be given with a small amount of fatty food for increased absorption. If the dog does not tolerate ketoconazole (eg, gastrointestinal disturbances), itraconazole 5 to 10 mg/kg (do not use doses > 10 mg/ kg, as it has been reported to increase the risk of adverse effects such as anorexia, hepatotoxicity, and vasculitis) given 2 consecutive days/week is also effec- tive. Do not use compounded itraconazole, as it has poor bioavailability.^8,9 Generic formulation is effective, but if compounded from bulk chemical, it is not. In cats or dogs, if using the capsule formulation, it should be given with a fatty meal. If using the liquid formulation, it is best to give without food to allow for optimal absorption. In cats, the liquid formulation is better absorbed than the capsule form, allowing a 50% reduction in dose. This is not true for dogs, in which the absorption is equal between the liquid and capsule formulations.¹⁰

I rarely use fluconazole 5 to 10 mg/kg once daily (rarely twice daily), except in small dog. Because it comes in a 50-mg tablet, it is more amendable for dosing small dogs. In contrast to ketoconazole and itraconazole, fluconazole does not require an acidic environment for oral absorption, therefore it can be given with or without food.

Terbinafine 30 to 40 mg/kg once daily may be useful in dogs who are on multiple medications because, in contrast to the azoles, terbinafine has fewer drug interactions. Treatment should be continued for 14 days beyond clinical resolution based on your examination (not a phone call) and cytology, with a minimum treatment time of 21 days. Please note that griseofulvin is ineffective against Malassezia.

Be sure to evaluate the dog for concurrent superficial bacterial pyoderma, as it is not uncommon to have both MD and superficial bacterial folliculitis present concurrently. In cases of concurrent superficial bacterial pyoderma, because the shampoo therapy that was discussed above is active against bacteria, antibiotic therapy may not be necessary.

Paul B. Bloom, DVM, DACVD, DABVP (Canine and Feline Specialty) is a practitioner at the Allergy, Skin, and Ear Clinic for Pets in Livonia, Michigan. He is also an assistant adjunct professor of small animal clinical sciences in the Department of Dermatology at Michigan State University in Lansing.

References

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2. Griffin JS, Scott DW, Erb HN. Malassezia otitis externa in the dog: the effect of heat-fixing otic exudate for cytological analysis.
   J Vet Med A Physiol Pathol Clin Med. 2007;54(8):424-427. doi:10.1111/j.1439-0442.2007.00938.x
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9. Mawby DI, Whittemore JC, Genger S, Papich MG. Bioequivalence of orally administered generic, compounded, and innova- tor-formulated itraconazole in healthy dogs. J Vet Intern Med. 2014;28(1):72-77. doi:10.1111/jvim.12219
10. Hasbach AE, Langlois DK, Rosser EJ Jr, Papich MG. Pharmacokinetics and relative bioavailability of orally adminis- tered innovator-formulated itraconazole capsules and solution in healthy dogs. J Vet Intern Med. 2017;31(4):1163-1169. doi:10.1111/ jvim.14779