How to win the war with skin infections: Part II (Proceedings)

Malassezia Dermatitis - Disease Characteristics & Treatment Principles

Malassezia pachydermatis is a yeast organism most commonly recognized as an associated cause of otitis externa. Cutaneous malassezia is a condition more commonly recognized now and most often encountered in geographic areas characterized by high humidity or non-arid climates. The disease is considered to be a secondary problem to an underlying disease in almost all cases. Recognition of this component is necessary for acceptable control of the accumulative problem. Local factors that contribute to the proliferation of the yeast include wax and sebum production, moisture and disruption of the epidermal barrier. Greasy skin, secondary to pruritic dermatoses such as allergy are often associated with the condition. It has also been shown that staphylococci will enhance the growth of malassezia in culture. Combinations of underlying diseases in addition to the individuals tendency to develop oily skin and hair are important in the development of cutaneous malassezia. The organism is categorized as a facultative pathogen with opportunistic characteristics.

Clinical Disease

The clinical manifestations of cutaneous malassezia is often overshadowed by the primary disease or by the similar manifestations of other conditions. Malassezia has most often been seen in conjunction with allergic dermatoses, in particular atopy and food allergy although it may be associated with any condition. Metabolic/endocrine dysfunctions are another group of associated problems. Keratinization defects (West Highland White Terrier) have been the underlying problem in some cases. Breeds recognized with possible predilection include the West Highland white terrier, basset hound, cocker or springer spaniel, poodles, silkie terriers, maltese, Australian terrier and Shetland sheepdog.

Among the postulated underlying causes of cutaneous malassezia is the chronic use of antibiotics in cases of recurrent pyoderma. A concern was expressed for the impact of antibiotic therapy on modifying the normal microflora of the skin thereby leading to the over production and proliferation of an opportunist such as Malassezia pachydermatitis. Although the concern is a legitimate one, there has not been any documentation of disease from malassezia organisims as a direct result of antibacterial topical or systemic therapy

Bacterial pyoderma is also a very important differential diagnosis for malazzezia dermatitis and often the two have such similar appearances as to lead to a misdiagnosis. Antibiotic failure has been interpreted in cases with persistant dermatitis when in actuality the dermatitis was due to malassezia. The occurrence of both bacterial infection and malassezia is common.

The clinical features include dermatitis in either a regionalized pattern or may be generalized. The hallmark of the disease is usually pruritus that typically has a limited response to standard anti-inflammatory doses of glucocorticoids. Clinical symptoms may mimic canine scabies or food allergy with convincing similarities. The lesions observed may be variable but usually includes erythema with a variability of scale and/or greasy buildup. The scale may have characteristic plaques appearing grey to white in color. A papular dermatitis is often seen but may represent the co-existance of bacterial pyoderma. Distribution areas often include the face, pinnae, head, ventrum, perianal region and extremities of the animal.

Diagnosis

The diagnosis of cutaneous malassezia is accomplished by cytological examination of material collected from the surface of the skin. This is best accomplished by using an acetate tape to collect scale/crust from the skin surface. The tape that is best suited is the clear 2" strapping tape packaged with a dispensing apparatus. Tearing off a small strip equal to the width of a standard microscope slide will aid in the transfer to the slide for examination. The tape is applied repeatedly to the skin surface until it has lost its "stickiness". Several drops of the blue stain (DiffQuick #3) is placed on the slide and the tape is placed over the stain with the sticky side down making a sandwich. The slide is ready for viewing. Since yeast organisms tend to adhere to the keratinocytes this is the place to focus the search for organisms. Ultimately, examination must be performed under oil immersion. Slides are available commercially that have a sticky surface which are also useful to collect material difficult to keep on the slide. Heat fixing is not necessary when using tape or sticky slides. If lesions are greasy or sticky, a dry scalpel blade or cotton applicator stick may be used to "harvest" sufficient specimen to place on a slide for examination. In this instance, heat fixation will be necessary to preserve the specimen on the slide. Always examine under immersion oil (100 X objective). Occasional yeast organisms may be found on normal animals. Numbers of malassezia identified is variable and is often influenced by the extent of bathing and topical medication being used by the pet owner. Greater than 2-3 per HPF is consistent with the diagnosis of cutaneous malassezia if the lesion characteristics of the condition. Always take into consideration what the pet owner or other veterinarians have been using to treat the problem. Aggressive shampoo therapy may remove substantial amount of organisms leaving few for identification on cytology. In this instance only a few organisms may be quite relevant. Dermatohistopathology may demonstrate organisms and aid in the diagnostic confirmation but should not be relied upon. Fungal cultures are often acquired as part of the minimal data base and frequently reveal malassezia organisms. This should be interpreted cautiously and may only demonstrate carriage of the organism as found on normal individuals. Lesion correlation is important when interpreting laboratory data.

Treatment

Treatment of cutaneous malassezia usually involves both topical and systemic medications. Shampoo treatment alternatives include chlorhexidine, benzoyl peroxide, selenium sulfide or specific antifungal products such as ketoconazole or miconazole nitrate. Focal lesions may be treated with miconazole containing products such as ConofiteR . Bathing should be performed for 10-15 minute treatments once or twice a week initially followed by weekly applications following the first two weeks of treatment. When the pinnae are involved, the animal should be examined for coexisting mycotic otitis externa.

Systemic Treatment for Cutaneous Malassezia

Systemic therapy has traditionally been reserved pending response to topical therapy and treatment of the underlying condition. It appears to be a more essential part of the treatment than previously recognized and hence is used earlier in the treatment program. It should be remembered that griseofulvin is NOT effective against malassezia.

Ketoconazole (Nizoral) at 5 mg/kg once or twice daily or 10 mg/kg once daily has been the systemic treatment of choice. The standard dosage I currently use is 5 gm/kg once or twice daily with higher dosages used in situations of poor response. Absorption is enhanced when administered with food and is ideal in an acid environment. Antacids or H2 blockers should not be administered concurrently. Side effects include gastroenteritis (vomiting), inappetence and malaise. Other side effects include hepatopathy, although this is an uncommon finding. Refractoriness to therapy has been observed particularly when ketoconazole has been used repetitively for recurrent malassezia. If refractoriness is observed and there is relative certainty of the infection, other systemic alternatives should be considered. Treatment for malassezia like pyoderma is required beyond the resolution of the problem. This usually equates to a minimum of 21-28 days. Recent evidence has shown that pulse therapy with ketoconazole may eliminate an active infection. Treatment is typically administered 3 days per week in lieu of every day therapy. Smaller dogs are more difficult to dose at the standard 5 mg/kg and may need to be compounded or utilize another drug for treatment. Higher doses of ketoconazole may be used (10-15 mg/kg) but increases the chance of side effects.

Itraconazole is a broad spectrum antifungal drug marketed under the brand name Sporanox and is produced in 100 mg size capsules and 10mg/ml liquid. Drug absorption is best when combined with food and is enhanced in an acid environment or in the presence of fat. The minimal inhibitory concentration of itraconazole, in general, appears to be less than ketoconazole. It is also tolerated in cats in contrast to ketoconazole which should not be used in cats. This drug may be used as a once a day regimen for the treatment of cutaneous malassezia at 5 mg/kg. or used in a pulse therapy approach three days per week. Adverse reactions are anorexia and may be related to hepatic toxicosis. Vasculitis has also been observed resulting in an ulcerative dermatitis. Drug reaction appears to somewhat dose dependent. Dosing smaller animals is easier with the liquid formulation. Several alternatives have been used to implement a more precise dosage. The capsule may be emptied and the granules mixed with an empirical amount of softened butter (e.g.2 tablespoons). The mixture is then placed on some wax paper and formed into a narrow linear mound of a predetermined length. The paper is then placed in the freezer to harden and individual doses are produced by cutting the ridge of butter at a specified length dependent upon the amount required and the length of the ridge. Although itraconazole is available as a commercial suspension it may be compounded using the capsules. To make 15 ml of 40 mg/ml, place the contents of 6 capsules in a glass mortar and soften the beads with a small amount of 95% ethanol (approx. 1.5 ml). Allow the alcohol to almost dry and then proceed to grind the beads into a fine powder. Add 5 ml of Ora Plus, an oral suspending vehicle (Paddock Labs, Inc., Minneapolis MN), to make a paste and then add 10 mls of Ora Sweet, an oral syrup vehicle (Paddock Labs., Inc., Minneapolis MN). The suspension will be stable for 35 days when refrigerated in an amber bottle. Shake well before pouring.

Fluconazole is another alternative for the systemic treatment of malassezia and is currently inexpensive since its availability as a generic. Fluconaazole is also well tolerated by the cat. The dosage is similar to itraconazole at 5mg/kg once daily but may be used at 8-10 mg/kg daily. The residual effect of fluconazole may provide some enhancement over the other choices. Some anecdotal reports of once or twice weekly treatment has demonstrated success in the treatment of cutaneous malassezia. The use of an every other day treatment has also been described. Using a higher dosage (10mg/kg) once or twice weekly may provide an alternative to other methods of therapy. Terbinafine (Lamisil) is a systemic antifungal used in veterinary dermatology and has shown some effectiveness for treatment of yeast. It is highly effective for the treatment of dermatophytosis. It is only supplied as 250 mg. tablets and is somewhat expensive. The dosage is quite variable at 10 mg/kg qd- 30 mg/kg qd-bid. It is tolerated much better than either ketoconazole and itraconazole and is currently available as a generic for reduced cost.

Chronic relapsing cases of cutaneous malassezia may be frustrating and have the limitation of financial fatique. Maintenance therapy has been successful when used on some cases to prevent the full exacerbation of the condition. Alternate day or every third day administration of ketoconazole has been used by the author as well as less frequent administration of itraconazole (weekly or twice weekly). Fluconazole would potentially be better for this type of treatment because of its residual tissue levels. Pulse therapy has also been employed with ketoconazole and itraconazole. A variety of schedules may be used such as one week on followed by one week off or one week on, two weeks off, etc. Administration of the drug the first 7-10 days of each month has apparently been helpful in selected cases. It is difficult to evaluate the benefits of this treatment approach when there are no recurrences to observe. Gradual withdrawl of the antifungal therapy should be attempted in the face of remission. Other effects of these drugs should be considered in the overall evaluation. Anti-inflammatory and anti-pruritic affects have been observed with ketoconazole. Exacerbation of pruritus at the termination of therapy with inflammation may not represent a recurrence of the cutaneous malassezia. Refractoriness to therapy has been observed and may represent some resistance.