Fungal Microflora on the Hair and Skin

Dogs and cats harbor many saprophytic molds and yeasts on their haircoats and probably on their skin as well.32a,243a The most common fungi isolated from the haircoats of clinically healthy cats are Alternaria, Aspergillus, Cladosporium, Penicillium, Rhizopus, and Trichoderma.^187,188,188 From dogs, the same fungi are isolated with somewhat different frequencies.²³²

It has been proposed that cats are reservoirs of pathogenic dermatophytes (M. canis, M. gypseum, Microsporum vanbreuseghemii, Trichophyton verrucosum, T. mentagrophytes, Trichophyton rubrum, Epidermophyton spp.). To investigate this possibility, many populations (pet, stray, or cattery) of cats from various geographic areas have been surveyed by culture of haircoats.94,177,232,247 The prevalence of dermatophyte isolation, specifically that of M. canis, varied among the populations, depending on the geographic region, whether or not the cat was a stray or pet cat, and the presence or absence of skin disease at the time of sampling. M. canis was most commonly isolated from stray cats or those in multiple cat facilities and from warm geographic regions.

In surveys of clinically healthy pet cats from the United States, Belgium, and United Kingdom, the prevalence of M. canis isolation in 172 cats was 0%, in 467 was 2.1%, and in 181 cats was 2.2%, respectively.¹⁷⁷ In the study from the United Kingdom, all 4 cats with positive culture results were from multiple-cat households and were allowed to roam freely outside. Interestingly, in the United States study, T. rubrum was isolated from 14 cats; this organism is the human pathogen associated with tinea pedis (athlete’s foot).⁹⁴ These findings highlight the importance of fomite carriage by the haircoats of clinically healthy dogs and cats of potentially pathogenic dermatophytes; however, T. rubrum infection is rare in cats.

In catteries, the isolation of M. canis depends greatly on whether or not the cattery has a history of dermatophytosis. In one study of cats from catteries in temperate regions of the United States, cats without clinical dermatophytosis had negative culture results, compared to cats in clinically affected catteries, where virtually all cats had positive culture results.¹⁸⁸ These findings were identical to those of a smaller study from a warmer region of the United States where M. canis was not isolated from the haircoats of cattery cats from facilities that were free of the disease.²⁷²

In surveys of stray and shelter cats, the prevalence of M. canis isolation was higher in shelters in warmer climates. In the United States, the isolation of M. canis from animal shelters in a subtropic climate was 17.5% compared with 4% from a temperate climate.²⁰¹ Both isolations were performed at the same time of the year. In a study conducted in Belgium, the haircoats of 134 cats were cultured and M. canis was isolated from 15.7%.¹⁷⁷ In a study from the southeast of England the prevalence in 169 cats was 2.16%.²²² Results from these two studies emphasize the impact of climate and geography on the prevalence of M. canis. In a study involving stray cats (n = 40) in India, the prevalence was 42.5%.²⁵¹ In Italy,²⁴⁷ 173 stray cats without skin disease were sampled, and 47% had positive culture results for M. canis. These studies surveying the fungal flora of dogs and cats highlight several important points. First, pathogenic dermatophytic fungi (e.g., M. canis) should not be considered part of the normal fungal flora of cats or dogs. If these species were indigenous flora, they would have been isolated routinely from clinically healthy dogs and cats regardless of geographic region, lifestyle (indoor or outdoor), or domicile status (pet or stray). Second, isolating pathogens from clinically healthy animals is possible. The isolation of a known potentially pathogenic fungal organism indicates either infection (obvious or subclinical) or fomite carriage from exposure to a contaminated environment. However, if the animal is lesion free, distinguishing between these possibilities is often impossible. Finally, animals with positive culture results should be treated because dermatophytosis is an important zoonotic disease and there is evidence that in some areas of the world animal pathogens are emerging zoonoses. Data from a study on the epidemiology of dermatophyte infections in Europe have indicated that there has been a shift from Microsporum audouinii, Epidermophyton floccosum, and T. rubrum to M. canis as the most common dermatophytes causing infections in humans.²⁵⁷

Virulence Factors

The process by which infection occurs is complex; findings at the molecular level have been reviewed.²⁷⁹ The infection process has three stages: adhesion of arthroconidia to corneocytes; conidial germination; and fungal invasion of the keratin network. Little is known about the molecular aspects of these stages; however, studies using a reconstituted feline epidermis have shown that adherence to skin is time dependent, beginning within 2 hours and still increasing after 6 hours. Keratolytic proteases and fungal virulence factors were found to be important in the first stage of infection.¹⁷³ Other proteolytic enzymes (keratinase, elastase, and collagenase) have been isolated from dermatophyte fungi and are likely involved in all three stages of the establishment and progression of an infection.^1,33,34,82 These enzymes are produced under in vitro culture conditions and can be detected in infected skin biopsies.¹⁷⁸ The number and quantity of enzymes produced varies from strain to strain and may, in part, explain variability in clinical findings.¹

Immunologic Factors

The overall immunologic status of the host influences development of infections. Various innate factors, distinct from the specific immunologic responses acquired as a consequence of infection, are involved in protection. Infections are more easily established in very young, very old, or immunocompromised animals and humans. Some factors are inherent in the defenses provided by healthy skin. Normal serum inhibits growth of dermatophytes, as do fungistatic fatty acids present in sebum. Physical occlusion leads to increased hydration of the normally dry skin surface, with subsequent maceration and easier infection. Dermal trauma facilitates development of infection. Concurrent immunosuppression, as with feline immunodeficiency virus infection, can result in an increased frequency of isolation of M. canis.¹⁵⁰

Cat

Dermatophytosis can seemingly mimic almost any described feline skin disease. M. canis infection is not generally a localized disease, despite appearances to the contrary. Clinical lesions maybe focal or multifocal, but spores or areas of inapparent infection, or both, will be present throughout the haircoat. Pruritus varies from none to self-mutilation. Hyperpigmentation of the skin is rare in cats but is most likely seen in cats with dermatophytosis. Scaling may be limited or generalized and diffuse or multifocal. Because hair loss is a common finding, a usual owner complaint is excessive shedding. Cats with generalized dermatophytosis often ingest large amounts of hair while grooming and may have a history of vomiting, constipation, hair ball problems, or any combination of these. Erythema and scaling of the inner or outer pinnae (or both) is another common presentation in adult cats. Patches of scale with minor alopecia or hair breakage is one of the most common presentations in longhaired cats. Feline skin reaction patterns when dermatophytosis should be considered as a differential diagnosis include miliary dermatitis, symmetrical alopecia, eosinophilic plaques, and indolent ulcers. Ulcerative lesions are especially unilateral in young cats.

Dermatophyte lesions in kittens tend to consist of areas of hair loss and scaling; erythema is variable and is often difficult to detect in dark-haired cats. Lesions are often first seen as areas of hair loss on the muzzle, face, ears, and forelegs (Fig. 56-1). Depending on the overall health of the kitten, lesions may be focal, multifocal, or generalized. Kittens with limited dermatophyte lesions that develop upper respiratory infections or gastrointestinal diseases, or both, are at increased risk for the development of generalized lesions. M. canis can cause comedone-like lesions (i.e., chin acne) in young cats.

Uncommon presentations of feline dermatophytosis include an appearance clinically identical to pemphigus foliaceus, with scaling and crusting over the bridge of the nose and the face or crusting exudative paronychia, or both. Unilateral or bilateral pinnal pruritus is another underrecognized presentation of M. canis. In the cats examined by the author (KAM), infected hairs were limited to the ear margin or long hairs within the “bell” of the ear, or both. M. canis is uncommonly a cause of recurrent otitis externa.¹⁰⁷ Rarely, diffuse alopecia with hyperpigmented patches of long hair has been observed.²⁴⁴

Granulomatous dermatitis, in the form of well-circumscribed, ulcerated dermal nodules, is infrequently recognized in cats (Fig. 56-2). The lesions occur on cats afflicted with more generalized typical M. canis infections. Interestingly, one report described different strains of M. canis isolated from the granulomatous lesions and from the surface infections of the same cat.^178a,179 These lesions have been called mycetomas, pseudomycetomas, and Majocchi’s granulomas. This form of disease carries a poor prognosis for resolution.^215a,245

Dog

Lesions in puppies usually consist of focal or multifocal areas of hair loss and are clinically indistinguishable from other common causes of focal hair loss in a puppy, specifically demodicosis and bacterial pyoderma. As in kittens, the overall health of the puppy is an important factor in the severity of the infection.

Unlike cats, dogs are more likely to develop the classic foci of alopecia with follicular papules, scales and crusts, and a central area of hyperpigmentation (see Table 56-1). Dermatophytosis should be considered in any papular or pustular eruption. Facial folliculitis and furunculosis, superficially mimicking an autoimmune skin disease, can develop (Fig. 56-3). Nodular skin lesions called kerion reactions may occur on the face and legs (Fig. 56-4). These lesions appear as areas of deep pyoderma and are most often caused by M. gypseum or Trichophyton spp. infections.^59a More generalized, widespread lesions should prompt a search for a potential underlying systemic cause predisposing to the infection.⁴⁹ Onychomycosis may be exhibited by chronic ungual fold inflammation, with or without footpad involvement, or the claw alone may be infected, which causes claw deformity and fragility. Dermatophytic granulomas have been reported rarely in dogs.¹⁰ One of the authors (DJD) has seen several shorthaired dogs with histories of recurrent urticaria and papular eruptions caused by dermatophytosis.

Demodicosis and dermatophytosis can be clinically indistinguishable but can be reliably differentiated by a skin scraping. Superficial folliculitis, especially when accompanied by the spreading rings of erythema and exfoliation that have been characterized as staphylococcal hypersensitivity or superficial spreading pyoderma, is more often mistaken for dermatophytosis. Staphylococcal skin lesions of spaniels with seborrhea are also often misdiagnosed as dermatophytosis.

Wood’s Light Examination

Examination of the haircoat with a Wood’s lamp (ultraviolet light, 320 to 400 nm wavelength) is a quick and easy initial screen for presence of certain dermatophyte infections but clearly is not definitive. Perhaps only half of all strains of M. canis will show fluorescence, and other animal dermatophyte species will not, rendering the Wood’s lamp an insensitive test. The fluorescence results from a fungal metabolite produced only when the organism is growing on hair and not on scale or claw material. Thus, true fluorescence is bright “apple green” in color and occurs only along hair shafts, never in scale (Fig. 56-5). Debris, scale, lint, and topical medications commonly produce false fluorescence. Because of these pitfalls, suspected fluorescing hairs should always be cultured or examined microscopically, or both, to confirm presence of the infection. Compared with culture, the Wood’s lamp examination was found to have a sensitivity of approximately 50% for M. canis infection.²⁶¹ Wood’s lamp examination is most useful when monitoring infection status in a cattery or multiple-animal facility where endemic infection with a fluorescing strain is involved. In examining a patient with a Wood’s lamp, make sure that the lamp has been allowed to warm up for a few minutes before the examination, and spend several minutes (with room lights out) examining the haircoat slowly and closely both to allow sufficient time for dark adaptation and to avoid missing small areas of fluorescence.¹⁹¹ The authors find that the larger, more powerful lamps that operate on household current are superior to smaller, battery-operated models.

Direct Microscopic Examination

Mineral oil is often used to remove and suspend hairs for microscopic evaluation. However, the hair shafts are opaque, thereby reducing visualization of the fungal elements. Hair and scale may be wet mounted in 10% to 20% potassium hydroxide (KOH) overnight or heated gently in the same solution for 10 minutes for clearing of keratin and visualization of fungal elements. Mounting in chlorphenolac (50 g chloral hydrate, 25 mL liquid phenol, and 25 mL liquid lactic acid) solution accomplishes the same task in a few minutes without heating, but the solution is not commercially available and is cumbersome to prepare. Direct examinations can be performed using mineral oil; the author (KAM) recommends holding the Wood’s lamp over the glass slide to locate the glowing hairs. Even in experienced hands, direct examination is time-consuming and may be diagnostic in only a few cases; however, results of a study of animals with dermatophytosis found that it can be a reliable in-house test allowing for confirmation of infection and initiation of therapy pending fungal culture.⁵⁸ In that study, use of mineral oil skin scrapings of lesions instead of hair pluckings were found to be superior. The authors (KAM and DJD) recommend both plucking and scraping of suspect lesions to maximize identification of infection in highly suspect cases. Care must be taken, because this can still lead to misinterpretation if saprophytic fungal spores are present in the specimen; debris and the complex structure of normal hair shafts can be misinterpreted as fungal elements. Dermatophytes never form macroconidia in tissue, but rather form hyphae and arthroconidia (ectothrix spores) on hair and scale. One investigation has recommended hair examination with a solution of 0.5% calcofluor white stain (Beckton Dickinson, Franklin Lakes, NJ) and Evans blue dye (1:9 solution) in equal volume of 20% KOH for superior visualization of fungal elements.²⁶⁷ Direct microscopic examination is most useful when fluorescing hairs are located and can be directly plucked with a forceps under a Wood’s lamp. The Wood’s lamp can also be used as a light source for the microscope to aid in visualization. In this case, the finding of ectothrix spores along the hair or mycelium, or both, growing down the center of the hair shaft (Fig. 56-6, A and B) is justification for beginning treatment while awaiting more definitive culture identification of the pathogen. Compared with normal hairs, infected ones are thicker, frayed, and indistinct with a filamentous appearance.

Fungal Culture

Definitive diagnosis of dermatophytosis is made by culture, although it is neither perfectly sensitive nor always specific for the diagnosis.²⁶¹ Proper specimen collection techniques, regular examination of the growing cultures, and microscopic confirmation of the fungal species are all necessary for ideal performance of this test.

Histopathologic Findings

Biopsy examination is not as sensitive as culture in the diagnosis of dermatophytosis. When the significance of culture results is questioned, demonstration of the organism in biopsy specimens is more definitive. Histopathologic examination is most helpful in detecting the nodular forms of dermatophytosis (the kerion and granulomatous ringworm), especially because these lesions often have negative culture results. Shaved, clipped, or surgically excised specimens of claws may be submitted for histologic examination in cases of paronychia, onychorrhexis, or onychomadesis. If fungal organisms are present, they will be readily visible within the substance of the claw. When submitting such specimens to the pathology laboratory, indicate the suspicion of fungal disease so that special fungal stains may be performed if necessary.

Clipping of the Haircoat

Clipping of the haircoat will mechanically remove fragile hairs that will otherwise fracture and release spores into the environment and onto the haircoat. Furthermore, it allows for thorough penetration of topical medications, reducing the amount and duration of treatment. Clipping of the entire haircoat is the optimal treatment in all cases of dermatophytosis; however, this is not always possible or practical. Clipping is time consuming and often requires sedation and can be irritating to cats. If not done carefully, thermal burns from electric clipper blades can also occur. Clipping of localized lesions can be easily accomplished using children’s scissors, which are disposable. For more generalized lesions, clipping of the haircoat with a No. 10 clipper blade is usually adequate. One of the authors (KAM) has successfully treated shelter cats for mild to severe generalized dermatophytosis without clipping of the haircoat using a combination of twice weekly topical therapy and itraconazole (ITZ).198,215 However, success was only achieved with thorough application of the topical solution, concurrent use of a systemic drug, and confinement of the pet. In some cattery situations, it may be mandatory for successful eradication. Clipping of the haircoat may temporarily irritate the skin and exacerbate lesions; however, these complications should not be used as a reason to not clip the haircoat.

Topical Therapy

To date, no evidence has been found to support the use of localized or spot treatment for dermatophytosis in dogs or cats. In fact, evidence has been found suggesting that use of spot treatment products alone may predispose individuals to chronic subclinical infections.³¹ Rather, whole-body shampooing, dipping, or rinsing with topical antifungal agents is much preferred. General topical treatment recommendations are summarized in Box 56-1.

Generalized topical therapy, in addition to clipping of the haircoat, will help decrease contamination of the environment by hairs and spores, decrease the chance of spread of the disease to other animals and humans, and help speed mycologic cure of the infection. The choice of topical antifungal treatment is important because studies have shown that many common topical agents are ineffective.42,70,191,197,282 The relative efficacies of various topical antifungal drugs is summarized in Table 56-4. In vitro and in vivo studies have shown that the most consistently effective topical antifungal whole-body treatments are lime-sulfur, enilconazole, and miconazole (the last with or without chlorhexidine).* Captan, povidone-iodine, and chlorhexidine are consistently ineffective against M. canis and should not be used in lieu of the following products listed.

Lime-sulfur has been extensively tested in in vitro infected spore models and, when used at concentration of 8 ounces/gallon of water (1:16 dilution), has shown superior antifungal activity.94,197 Lime-sulfur treatment alone, twice weekly at this concentration, has been used by one of the authors (KAM) to successfully treat dermatophytosis in single- and multiple-cat households when combined with or without whole-body clipping and appropriate environmental treatment. Lime-sulfur is very safe and can be used on newborn kittens and puppies. There are many formulations of lime-sulfur available, and no difference in the sporicidal efficacy against M. canis was found among them when tested in vitro.⁸⁴In one study involving cats (see under discussion of miconazole-chlorhexidine rinse below), lime-sulfur original formulation was more effective than a similar preparation with odor modification.^214a

Enilconazole topical solution is also an effective treatment; unfortunately, it is not available in the United States and is licensed only for use in dogs and horses. Because of its superior antifungal activity, the safety and efficacy of enilconazole have been evaluated in cats.115,122 In two studies, enilconazole was evaluated as a sole topical therapy (after whole body clipping) for the treatment of naturally occurring M. canis infection in Persian cats.^79,122 In one study, cats were dipped with either water (control) or 0.2% (2 mg/mL) enilconazole twice weekly for 8 weeks.⁷⁹ In the enilconazole-treated cats, results of fungal cultures were negative as early as 5 weeks after initiation of therapy and remained negative to the end of the 10-week monitoring period. In contrast, 75% of control cats still had culture-positive results at the end of 10 weeks of monitoring. In the second study, 22 Persian cats in a cattery were treated with 0.2% enilconazole every 3 days for a total of eight applications.¹²² All cats improved clinically and had culture-negative results by day 28 of therapy. In both studies, cats were observed for adverse effects, and serum biochemistry panels were monitored. Enilconazole was well tolerated but may have been associated with hypersalivation, anorexia, weight loss, emesis, idiopathic muscle weakness, and slightly elevated serum alanine aminotransferase activities. Anecdotal reports have surfaced of uncommonly severe toxicity, and even death, occurring in cats after topical application of enilconazole. These cases are thought to be associated with ingestion of the solution by the cat via grooming after application. Enilconazole appears safe for use on cats if the animals are fitted with an Elizabethan collar for a few hours after each treatment, to prevent grooming, until the cat is dry. See the Drug Formulary in the Appendix for further information.

Miconazole is also an effective topical antifungal in both in vitro and in vivo studies.158,229 Synergism between miconazole and chlorhexidine has been demonstrated in vitro,²²⁹ and shampoos with this combination of ingredients are documented to hasten mycologic cure.²⁶³ Using an isolated infected spore model, a miconazole (5.2%)–chlorhexidine gluconate (5.9%) commercial rinse was found to be as sporicidal as lime-sulfur.¹⁹⁹ In a nonrandomized study, cats were treated with oral ITZ with topical therapy of either lime sulfur, lime sulfur with odor modification, or miconazole-chlorhexidine commercial rinse with mycologic cure rates at 42 days after treatment of 87.1%, 59.2% or 52.6% respectively.^214a It is important to note that miconazole-based products are most effective when used as adjunct therapy and not as sole therapy.