Dermatophytosis in cats

 

Introduction

Fungal dermatoses frequently occur in veterinary medicine, and dermatophytosis represents one of the most common causes of infectious superficial folliculitis in cats. Dermatophytes are keratin-loving organisms that invade skin and hair shafts, leading to clinical signs of folliculitis. The most common dermatophyte species affecting cats is Microsporum canis, and the cat serves as its environmental reservoir. 

Dermatophytosis is both contagious and zoonotic, therefore rapid diagnosis and treatment will prevent propagation within the environment and spread of disease, which is especially important in multi-cat households, catteries, and shelter environments. The traditional means of diagnosis (including Wood’s lamp, trichography, and dermatophyte culture) remain widely accepted, and PCR is a useful tool to shorten time to treatment and clinical resolution. Although the disease is self-limiting, treatment is recommended to prevent spread of infection.

 

 

Prevalence and predispositions

While dermatophytosis is recognized as a common fungal dermatosis in cats, the true prevalence is unknown 1. Disease occurs worldwide, and research trends suggest that animals living in warm environments, group housing, free-roaming cats, young cats, immunodeficient animals, and cats with clinical lesions more commonly culture positive for dermatophyte 1 2 3. There are no known predispositions, although evidence suggests that Persian cats are over-represented, especially for the subcutaneous form of dermatophytosis (mycetoma or pseudomycetoma) 1 4. 

Pathogenesis

Most fungi are opportunistic pathogens that invade the body if there is failure of the host’s innate immune defense system. This can be defined as the non-specific, naturally present component of the immune system which is not dependent on prior antigen sensitization – e.g., the physical skin barrier, temperature, pH, and antimicrobial peptides. The innate immune system includes cells (e.g., natural killer cells, macrophages, and neutrophils) which recognize conserved regions on pathogens (known as pathogen-associated molecular patterns, or PAMPs) and mount an immune attack. 

Dermatophytes invade the superficial layers of skin, the hair shaft/follicle, and the claws, quickly infecting the host while bypassing the innate immune defenses by producing fungal proteases (e.g., fungalysins, lipases, ceramidase, adhesins) that promote penetration into the keratinous tissue 5 6 7. Arthrospores released from the skin, hair, and claws of infected cats into the environment form the infectious stage of the lifecycle. These infective arthrospores develop when fungal hyphae fragment, and directly or indirectly (via clippers, brushes, bedding, etc.) make contact with a new host and create infection within hours of exposure. Once in contact with the skin, arthrospores create germ tubes to penetrate the stratum corneum and hair 5. Fungal invasion is more likely to occur in animals with microtrauma to the skin (e.g., scratches from allergies, clipper blade trauma), ectoparasites, and increased humidity 7. Clinical signs of infection develop 2-4 weeks after exposure, but infected cats shed infectious spores before signs appear 8. Infected hairs and spores remain viable in the environment for 12-18 months, but rarely serve as a source of reinfection 1. 

The host immune response to the presence of dermatophytic hyphae and arthrospores, mediated by neutrophils, macrophages and cytokine release, eventually leads to spontaneous resolution of infection over a course of weeks to months; however, infection may persist in cats with a compromised immune system. This could happen for numerous reasons, such as physical trauma to the skin barrier, surgery, poor husbandry, underlying disease (e.g., allergic dermatitis, endocrinopathy, neoplasia), and immune-compromising medications (e.g., steroids, chemotherapeutics).

Clinical appearance

Dermatophytes need keratin to survive, so lesions occur in areas of the skin with the most keratin: epidermis, hair follicles and claws. Folliculitis is the hallmark of infection, and clinical lesions include papules, pustules, alopecia, broken hairs, scales, crusts, follicular casts (keratin plugs), and skin hyperpigmentation (Figures 1-3). Infected claws will become misshapen and are prone to fracture and break. Most affected cats are not pruritic. Cats with subcutaneous forms of the disease may present with nodules in the deep dermis and subcutis that develop fistulae and ulcers with purulent exudate. As is typical of most infectious dermatoses, clinical lesions are asymmetrically distributed over the body; they may be single or multifocal in nature, and the severity of clinical presentation is usually dependent upon the cat’s immune response to infection. 

 

 

Differential diagnoses

The prime differential in cats is superficial folliculitis, which occurs secondary to Staphylococcus spp. and Demodex spp. infections, as well as allergic dermatitis and eosinophilic granuloma complex. Less common considerations would include psychogenic alopecia, anagen/telogen defluxion, pemphigus foliaceus, pseudopelade, thymoma-associated exfoliative dermatitis, and cutaneous lymphoma.

Nodular forms of the disease may appear similar to other opportunistic bacterial (e.g., Mycobacteria spp., Nocardia spp.) or fungal (e.g., phaeohyphomycosis, hyalohyphomycosis, zygomycosis) infections, neoplasia, or sterile nodular panniculitis. 

Diagnosis

Many cats go undiagnosed for days to weeks after developing infection due to camouflaging of lesions within the hair coat, or misdiagnosis as another similar-appearing dermatosis such as pyoderma (bacterial dermatitis) or allergic dermatitis. Any delay in diagnosis leads to increased contamination of the environment and risk of spread within the population of cats, dogs and people. Rapid diagnosis is critical to eliminate infection as quickly as possible. Dermatophytosis is commonly over-diagnosed based on clinical lesions alone, so additional testing is required. Many diagnostic techniques are available but they vary in reliability; however, it is usually possible to accurately diagnosis infection through a combination of tests. 

The most important part of diagnosis is confirming the presence of infection at the onset of clinical signs, and the absence of infection at the end of treatment 1. Accurate diagnosis of dermatophytosis will be important when making decisions about which cats to treat, isolate, and re-test. Confirming the absence of infection ensures that animals can be reintroduced into the population without risk of spreading infection. Choosing the best tests to answer these questions is important to reliably diagnose and treat dermatophytosis. 

History

Clients may be able to provide information confirming multiple in-contact animals or people with suspicious skin lesions. While this information certainly increases the suspicion of dermatophytosis, it is not enough in itself to diagnose the condition. 

Wood’s lamp

Most M. canis isolates fluoresce bright green when ultraviolet light highlights a chemical reaction occurring between the dermatophyte and the water-soluble chemical metabolite, pteridine, located in the hair 1 9 (Figure 4). Data suggest that 91-100% of spontaneously infected cats fluoresce prior to initiation of antifungal treatment, but this may decrease to 39-53% after treatment 1. When examining the cat, be sure the hair shaft is glowing by looking through the magnification lens at a distance of 2-4 cm from the skin. Keep in mind that other things can fluoresce to create a false positive result, including medications, bacteria, scale/crust, soaps, petroleum, and fabric fibers, but these will lack the classic green coloring. Lack of fluorescence does not rule out dermatophytosis, so this method alone is insufficient to make the diagnosis; it is important to perform fungal PCR or culture to confirm the dermatophyte species causing infection. Note that Wood’s lamp examination can be very helpful for several reasons, from making a diagnosis to selecting the best hairs to sample for culture.

Dermatophyte test medium (DTM)

DTMs are specialized fungal agars for growing dermatophytes; they contain antibacterial and antifungal agents to inhibit contamination, along with phenol red, a pH indicator that causes a red discoloration when dermatophytes grow and release alkaline metabolites. DTMs should be examined daily for concurrent colony growth and color change. One study demonstrated that DTMs are as reliable as diagnostic laboratory fungal culture results when (i) manufacturer storage and incubation instructions are followed, and (ii) colony growth is evaluated microscopically to identify morphology of fungal reproductive structures (macroconidia and microconidia) 10. False positive color change is possible, so cytological evaluation of all growing colonies to identify the fungal species present is important. Cultures are negative if no growth occurs within 14 days 11 although false negative results may occur when non-infected hairs are sampled, with a small sample size, improper storage and incubation, and overgrowth of bacterial/fungal contaminants in culture 1. 

Collect skin and hair samples by hair plucking or via a toothbrush or sticky tape technique. When collecting hair and skin samples, pluck from the margin of lesions while using the Wood’s lamp to identify and select fluorescing hairs. Alternatively use a sterile toothbrush to brush over the top and margins of clinical lesions, or brush the entire cat if no clinical lesions are evident; brush for two to three minutes utilizing about twenty strokes, or until ample hair is collected within the bristles 1 12. The least-utilized technique involves using sticky tape pressed over skin lesions and then applied directly onto the fungal culture plate 13. 

Typically, culture is preferred when monitoring response to treatment and mycological cure. Current guidelines recommend that a combination of skin lesions, Wood’s lamp examinations, and number of colony forming units (cfu/plate) on culture is the best monitoring tool. Response to treatment is defined as a decrease in cfu/plate, and clinical cure is defined as two to three negative fungal cultures 1. 

Dermatophyte PCR

PCR is a sensitive and rapid technique for the identification of fungal DNA within the skin and hair 14 15. The technique does not prove fungi are viable, since it is simply measuring the presence of DNA, so paired positive PCR results along with DTM culture are required for confirmation of living organisms, especially when cats are non-lesional. A positive PCR result could indicate any of the following: active infection, resolving infection, or contamination of hair coat (fomite carriage). A negative PCR result could indicate lack of infection or poor sampling technique 1. Dermatophyte PCR has the advantages of being fast, affordable, widely available, and sensitive (i.e., it can detect a small amount of DNA in a small sample size). Dermatophyte PCR is best used to make an initial, rapid diagnosis, while DTM cultures are more reliable for monitoring response to treatment in cases where PCR remains positive 14 15 16 17 18. A negative PCR in cats undergoing treatment is consistent with mycological cure 1. 

Skin cytology

Direct impression and acetate tape cytologies will reveal neutrophils and some macrophages with suitable staining. Occasionally, fungal arthrospores are identified in heavily infected animals. Fine needle aspirate of dermal nodules due to dermatophytosis reveals pyogranulomatous inflammation and occasionally fungal hyphae and/or arthrospores.

Dermoscopy

A specialized dermoscope magnifies skin and hair for evaluation of external changes in cats infected with dermatophyte, and typical changes include hairs that are opaque, slightly curved, broken, and thickened (“comma shaped”), and skin with brown to yellow crusts 19. 

Trichography

Microscopic evaluation of fluorescing and/or lesional hairs allows identification of fungal hyphae within the hair shafts and accumulation of arthrospores along or within hair shafts (Figure 5). Pluck suspicious hairs and scrape alopecic skin, place in mineral oil on a glass slide, apply a coverslip, and evaluate at x100-400 magnification. One study found that when using both hair plucking and skin scraping, positive identification occurred in 87.5% of infected cats 20.

 

Macerated tissue fungal culture and histopathology

Dermatophytes will rarely causes deep nodular lesions. These are termed pseudomycetoma or mycetoma, and they usually contain very few fungal elements, so histopathology may not reveal evidence of fungi in tissue, even with specialized stains such as periodic acid Schiff (PAS) or Grocott methenamine silver (GMS). If dermatophyte elements are identified on histopathology, culture or PCR is needed to determine the species of dermatophyte present. It is important to remember that in the case of pseudomycetoma, even tissue culture may result in false negative results 4 21. 

Treatment and prevention

Treatment of lesional, culture or PCR-positive cats is recommended in order to reduce the contamination of the environment and spread of disease. Treatment may be topical, systemic or both, but isolation of the affected animal during treatment is generally recommended. Prevention is best achieved be treating predisposing conditions and decontaminating the environment. Isolate infected cats into easily disinfected rooms away from non-infected cats. Cats are easily stressed when isolated, especially if completely alone, which may exacerbate disease, and clinical consensus guidelines suggest that the shortest possible confinement time should be employed 1. However, time to cure is highly variable and dependent on various factors (e.g., overall health status, age, environmental stresses, treatment compliance, etc.), although the time period involved is usually weeks to months. Infected hairs and spores are a source of reinfection of the same cat, or spread to other pets and people in the environment in rare circumstances 2 22. Frequent (twice weekly at least) vacuuming and disposal of contents helps to remove hairs, crusts, and scales from the environment. Washing bedding, steam cleaning, and cleaning with dust wipes, accelerated hydrogen peroxide, bleach, and enilconazole are effective environmental decontamination measures. Performing environmental cultures is not recommended, since environmental contamination is an expected finding when infected animals are present. 

Topical therapies

Topical therapy is important to reduce the infectious elements shed by the cat by physically removing infected hairs, scales, and crusts, and acting as a fungicidal agent. Options include: lime sulfur leave-on rinse, enilconazole leave-on rinse, miconazole/ketoconazole/climbazole formulations, terbinafine formulations, topical essential oils, and accelerated hydrogen peroxide formulations. However, not all of these are particular effective. The clinical consensus guidelines recommend the use of twice weekly applications of lime sulfur, enilconazole, or miconazole/chlorhexidine shampoo for generalized dermatophytosis, or the use of clotrimazole, miconazole, or enilconazole for localized disease in conjunction with other therapies 1. 

Different formulations of topical agents range from concentrated rinses, shampoos, sprays, lotions, mousses, or creams/ointments. Some studies suggest that clipping hair improves topical treatment efficacy and reduces environmental contamination; however, it may also increase stress to the cat and lead to spread of infection through skin microtrauma 1. Many factors will determine if topical therapy is the best route of treatment and which formulation to use, including patient tolerance, hair coat, owner compliance, cutaneous lesion characteristics, and product characteristics. Topical therapy has the advantage of avoiding systemic side effects of medications, so it is safe for use in almost all cats, including the young, old, and debilitated. Topical antifungal therapy can be used as an adjunctive therapy for subcutaneous dermatophytosis, but is not appropriate as sole therapy.

Systemic therapies

The purpose of systemic therapy is to inhibit proliferation of fungal infection within the hair and skin of the infected animal so that there is a decreased risk of lesion propagation throughout the infected animal, contamination within the environment, and contagion to other animals and people. Systemic therapeutic options include itraconazole, ketoconazole, fluconazole, terbinafine and griseofulvin 1. The current consensus guidelines recommend the use of itraconazole or terbinafine due to their wide safety profile and high efficacy rates, while ketoconazole and fluconazole are considered less effective treatment options 1. Griseofulvin is effective, but has the potential for severe adverse effects compared to itraconazole and terbinafine. Lufenuron is not an effective treatment, and fungal vaccines most likely are only useful as an adjunct therapy 1. 

Itraconazole is a triazole with a broad spectrum of activity. It inhibits ergosterol formation in the fungal cell membrane via the inhibition of the fungal cytochrome P450 enzyme, 14α demethylase. Itraconazole is considered fungistatic at low doses and fungicidal at high doses. It is highly lipophilic and concentrates in the skin and sebum at concentrations ten times that of plasma. The recommended dose for feline dermatophytosis is 5-10 mg PO q24H with food. Studies in cats demonstrate that weekly pulse dosing (5 mg/kg PO q24H, week on/week off) results in cumulative, increasing drug concentrations in hairs above the minimum inhibitory concentration (MIC) for M. canis (0.1 µg/mL) over a 35-day period 23. Repeated pulse dosing at this level for five weeks resulted in 97.5% cure of infected cats by nine weeks 24. Compounded formulations, while cheaper, are not reliable nor recommended for use in cats. Side effects may occur but are less likely compared to other azoles and triazoles; they include gastrointestinal disturbance, elevated liver enzyme activity, and hepatotoxicity.

Terbinafine is a synthetic allylamine with a broad spectrum of activity. It inhibits the fungal membrane-bound enzyme, squalene epoxidase, thereby preventing the conversion of lanosterol to ergosterol. Terbinafine has a very low MIC for M. canis (0.002-0.25 µg/mL) as compared to itraconazole. It is highly concentrated in the hair of cats at doses ranging from 10-40 mg/kg PO q24H, with drug concentrations in the hair ranging from 0.47-9.6 µg/g. In one study, cats maintained therapeutic drug concentrations in the hair follicle for 56 days after completing two weeks of terbinafine at 35-40 mg/kg PO q24H 25. Despite its reported high drug concentration in hairs well after the final dose, clinical studies show the best outcomes occur when terbinafine is dosed for a minimum of 21 consecutive days 25 26. Terbinafine is well tolerated and side effects (e.g., gastrointestinal disturbance, lethargy and weight loss) are uncommon and mild in nature. Elevation of liver enzymes may occur but rarely extends outside of reference intervals, even at high doses in cats 1.

Prognosis

Dermatophytosis carries a good prognosis for cure; however, treatment can be frustrating in multi-animal households where environmental contamination is prevalent. It is important to look for underlying causes of infection and initiate treatment if the disease is ongoing (e.g., allergies, stress, immunocompromise, etc.). 

Conclusion

Dermatophytosis is a common superficial fungal dermatosis that is highly contagious between cats and carries a zoonotic risk. Clinical lesions vary and tend to be both multifocal and asymmetrical in distribution. Diagnosis is achieved readily through a combination of history, physical exam and diagnostic tests, although false positive and negative results are possible. Topical and systemic treatments are recommended – despite the self-liming nature of this disease and the fact that the disease carries a good prognosis – in order to prevent contagion to the infected and noninfected animals, as well as people.