Feline Dermatophytosis: Topical and Systemic Treatment Recommendations
Vet Med 98[10]:877-884 Oct'03 Symposium 37 Refs
Karen A. Moriello, DVM, DACVD
Dept of Medical Sciences, SVM, University of Wisconsin-Madison, Madison, WI 53706

ABSTRACT:
Since dermatophytosis is highly contagious and zoonotic, treatment must be effective, or the disease will continue to spread. These guidelines will help you formulate the best therapeutic protocol for each case.

FULL TEXT:
In the first article of this symposium, I reviewed key aspects in the pathogenesis of feline dermatophytosis. In the second article, I described practical diagnostic testing. This article presents treatment strategies for single or multiple cats with dermatophytosis. The key points from the first and second articles to keep in mind when making treatment decisions with clients are:

• Dermatophytosis is the most common infectious skin disease in cats.
  
  
• Any cat that comes into contact with infective material is at risk for developing dermatophytosis, but it is most likely to be encountered in at-risk groups: cats from multicat facilities, stray or feral cats, young or old cats, and debilitated cats.
  
  
• Dermatophytosis is highly contagious and can be transmitted by direct and indirect contact with contaminated environments.
  
  
• The clinical signs of feline dermatophytosis are extremely variable, making it a reasonable differential diagnosis in almost any cat with skin disease
  
  
• The gold standard for diagnosis is a fungal culture. Wood's light examinations are only screening tools, and direct hair examinations, although inexpensive, are only practical when infected hairs fluoresce on Wood's light examination. Finding these hairs allows you to rapidly diagnose the infection and start therapy. However, if the hairs are not present, this tool is time-consuming and not cost-effective in practice.
  
  
• A toothbrush culture cannot distinguish between a cat with a subclinical infection and a cat that is mechanically carrying spores on its coat. But because of the highly contagious nature of this zoonotic disease, both groups require veterinary attention.
  
  
• Dermatophytosis will spontaneously resolve in most healthy cats, but treatment is recommended because the disease is zoonotic and highly contagious.

Endpoint of therapy

I find it helpful to give clients a perspective on what the desired outcome of treatment is before launching into a discussion on how to get there. Throughout the last decade, I have defined the endpoint of therapy to be a mycological cure; however, I would like to propose that veterinarians consider the endpoint to be both a mycological cure and a decontaminated environment. Both are required to prevent reinfection in cats and exposure of people to this zoonotic disease. It may help clients to grasp therapy concepts if you compare treating this disease to treating fleas: Both diseases are treatable and curable, require treatment of all in-contact animals, require treatment of the host and the environment, and are highly contagious and of zoonotic importance.

Cats will attain a clinical cure before a mycological cure. A mycological cure is defined as two or three consecutive negative toothbrush fungal culture results at weekly or biweekly intervals, and treatment should continue until all these negative culture results are obtained. Two negative results are usually sufficient in single-cat situations. Three negative results are preferred when multiple cats are involved.
As for environmental decontamination, infective material can remain viable in the environment for up to ¹⁸ months under optimal conditions of temperature and humidity. In addition, cats shed infected hairs and spores into the environment throughout treatment. Contact with infective material will increase the risk of reexposure, reinfection, and prolonged treatment. Decontaminating the environment involves aggressive and thorough cleaning and regular disinfectant application. The more cats involved in an outbreak, the longer the treatment and decontamination periods will last.

Overview of treatment strategies

A cat that has a positive Microsporum canis culture result requires medical care, whether it has clinical signs or is simply a mechanical carrier of the fungus. Treating dermatophytosis, especially in multicat situations, involves an individually tailored plan that includes some combination of clipping the coat, topical therapy that the client is able and willing to do, systemic antifungal therapy that the cat can tolerate and the client can afford, reasonable suggestions for environmental decontamination, and a case-by-case plan for monitoring for and preventing reinfection.
Two questions are commonly encountered when antifungal therapy is discussed: Is it absolutely necessary to treat cats topically (i.e. is systemic therapy alone effective)? And, can cats be successfully treated with topical therapy alone (i.e. is topical therapy alone effective)?

The answers to both questions are yes and no, depending on the cat, the severity of infection, finances, and available drugs. The answers also depend on how many cats are involved in the outbreak, whether the cat's coat has been clipped, and how much environmental contamination is involved. After discussing the required endpoint of therapy with clients, I ask the clients two questions before discussing treatment options.

1. Does any risk of environmental contamination pose a serious risk to people or other cats? The risk of environmental contamination is an obvious concern, but in some situations it may be an overriding concern. For example, for an at-home daycare provider that acquires a new kitten with dermatophytosis, all potential risk of environmental contamination must be minimized.
   
   
2. Does the cat live with or frequently come into contact with children, elderly people, immunocompromised people, or other people with special physical, health, or occupational (e.g. nurse, physician) concerns who would be seriously compromised if they contracted dermatophytosis? Children, elderly cat owners, and people receiving chemotherapy are obviously special at-risk populations. But so are human healthcare workers, hairstylists, veterinarians, teachers, and more. These people cannot risk contracting the disease from or transmitting the disease to anyone.

If the answer to either question is yes, I recommend aggressive therapy for dermatophytosis regardless of the cat's hair length or severity of lesions. This recommendation includes clipping all the hair on the body and administering topical and systemic therapy until a mycological cure is attained. If the cat is part of a multicat household, additional measures need to be taken (Figure 1).
Identifying animals at risk

Any treatment plan will fail if the at risk population is not properly identified. Once a positive culture result is found in a cat, immediate consideration needs to be given to other animals that the cat is living with or has contact with on a daily basis. In this situation, one or more of the following actions are needed:

• Using a toothbrush fungal culture, screen animals not living with the cat but recently exposed to it. Topical lime-sulfur dips may or may not be indicated, depending on the degree of prior exposure.
• Perform a toothbrush fungal culture in all fur-bearing animals living with the cat, and treat these animals topically pending culture results. I recommend lime-sulfur sponge-on dips twice a week pending the results. Hold cultures for 21 days to ensure negative results. This also ensures that animals in daily contact with the infected cat will have received at least six topical treatments before culture results are finalized. If the infection is incubating in these animals, this treatment will prevent spreading or worsening of the infection during this screening period. Once the culture results are known to be positive, institute appropriate systemic therapy. If the initial fungal culture result is negative, this topical treatment will protect the animals from infection from infected cats during this period.
• Contact owners or operators of the facility where the cat was obtained (e.g. cattery, cat rescue agency, shelter, private home) or returned from (e.g. boarding facility), and inform them of the diagnosis so other in-contact animals can receive treatment.

Figure 1: Guidelines for Treating Dermatophytosis in Cats

Step 1: Determining whether clipping the coat is necessary

Clients often have a much greater emotional attachment to hair than do veterinary dermatologists. I find it ironic that clients fret over the aesthetics of clipping a cat's coat when they are faced with treating a disease that causes, among other signs, hair loss. Clipping the coat is not necessary in every case of feline dermatophytosis, but it is optimal in every case. When dermatophytes invade hairs, they make them fragile and easily fragmented. When hair shafts break, infected hair fragments and spores are shed into the environment and onto the coat. This shedding increases the risk of spreading the disease and increases the probability that the cat may become reexposed to spores in the environment and continue to have positive culture results.

Clipping the coat removes infected hairs and minimizes continued shedding of hair fragments and spores. It also makes topical therapy application easier and allows for more thorough penetration of the topical antifungal agent. In addition, clipping helps shorten the duration of therapy and ultimately decreases the cost of treatment.

However, clipping the coat may require sedating the cat and is time-intensive. It may temporarily worsen the infection by causing microtrauma to the skin. And it may result in environmental contamination if appropriate efforts to capture infected hairs and spores are not taken.

Any cat with dermatophytosis that lives with children, elderly people, or anyone with immunosuppression must have its coat clipped, because it is important to eradicate the infection as quickly as possible in these situations. Clipping the coat is also necessary in shorthaired cats with generalized dermatophytosis and in all longhaired cats with dermatophytosis, regardless of the severity of the lesions.
Clip the coat with a No. 10 electric clipper to a length less than 2 cm. In shorthaired cats with focal lesions, children's metal blunt-tipped scissors can be used to clip and remove infected hairs from around individual lesions. Be sure to clip a wide margin around the lesion. If the strain of M. canis is strongly fluorescent, a Wood's light can be used during treatment to monitor resolution of the infection and locate hairs for removal.

Step 2: Selecting appropriate topical therapy

Topical antifungal therapy is recommended in all cats with positive fungal culture results and pending culture results in cats in contact with infected cats. The advantages of topical therapy are decreased overall length and cost of treatment, minimized spread of infective spores into the environment and removal of infective crusts, scales, and spores from the coat. The disadvantages are that cats hate to be bathed, dipped, or sprayed; topical and topical antifungal agents can be irritating to people and cats.

Whole-body topical antifungal therapy

The following recommendations for topical therapy are based on a review of both in vitro and in vivo studies.^1-13 In vitro studies involve exposing either mats of infected hair or isolated infected spores to known dilutions of topical antifungal agents for specific periods. The viability of fungal spores is then determined by routine fungal culture of infective material. This technique has provided valuable efficacy information about various commonly used antifungal compounds and is a useful screening tool for potential commercial products.

Effective products

Lime-sulfur, enilconazole, miconazole, and bleach have been shown to be antifungal in in vitro or in vivo studies or both. It is important to note that fungicidal efficacy does not imply that one application of any of these products is 100% fungicidal. These products are fungicidal with repeated application.

Lime-sulfur (LymDyp-DVM Pharmaceuticals; 8 oz/gal water) has consistently been found to be antifungal in in vitro studies.^2,3,6 In our facility, lime-sulfur has been used as the topical therapy of choice, and in some cases as the sole therapy, for treating research cats that are still infected or have positive culture results at the end of a study. I have found it to be consistently effective. Furthermore, I've supervised the eradication of dermatophytosis in a pet store with more than ³⁰ infected kittens and cats. Financial constraints resulted in lime-sulfur being used as the sole therapy in most cats. Diligent environmental decontamination and twice-weekly sponge-on dips performed by the owner eradicated the infection. Lime-sulfur is administered twice a week and is the preferred treatment when enilconazole is not available or licensed for use. Lime-sulfur stains the coat of white cats yellow-green. It can be irritating to mucous membranes, and cats should be prevented from grooming the wet solution. Clients and cats tend to dislike the odor, but the odor rapidly diminishes once a cat dries. Owners should wear protective clothing, gloves, and a mask and should apply the dip in a well-ventilated area. It is important that clients do not rinse this product off the coat.

Enilconazole topical solution (Imaverol Janssen Pharmaceutica) 10% concentrated solution (100 mg/ml) is effective against M. canis. Unfortunately it is not available in the United States, nor is it approved for use in cats. A different formulation of enilconazole, licensed for use as an environmental disinfectant, is available in the United States (Clinafarm EC, 0.2% emulsion Janssen Pharmaceutica). This formulation has been used off-label to treat dermatophytosis at a dilution of 55.6 ml/gal water as a topical antifungal.^8-11 It is important to note that using this product off-label is illegal since this is an EPA licensed product in the United States.

Because of the efficacy of enilconazole in treating canine and equine dermatophytosis, it has been the subject of many studies evaluating its safety and efficacy in cats ^8-10 In two studies, it was used as the sole therapy for dermatophytosis; cats required at least 10 weeks of twice-weekly topical therapy before being cured, but fungal culture results were reported to be negative as early as five weeks into therapy. Enilconazole was well tolerated by all the cats but may have been associated with hypersalivation, anorexia, weight loss, emesis, idiopathic muscle weakness, and slightly elevated serum alanine aminotransferase activity. Longhaired cats made up most of the cats in these studies.

Miconazole (Malaseb-DVM Pharmaceuticals), as a sole therapeutic agent or in combination with chlorhexidine, has been shown to be an effective antifungal agent in both in vitro and in vivo studies.^4,5,7,12,14 It is important to note that in the in vivo studies it was used twice a week as an adjuvant to systemic therapy. Miconazole shampoo needs a contact time of 10 minutes; this is essential for a therapeutic effect. This product can be irritating to the eyes and can cause skin irritation.

A 1:10 dilution of household bleach in water is an effective antifungal agent, but it is not recommended as a topical antifungal agent. It is too irritating to be used safely on cats and is not licensed for use in animals as a topical agent. Furthermore, at this concentration it presents a human health hazard because of its potential irritancy.
In general, the most consistently effective antifungal topical agents are lime-sulfur, enilconazole, and miconazole. Twice-weekly application as a whole-body rinse or shampoo (depending on the formulation) is recommended. Topical therapy is best used in conjunction with systemic antifungal drugs. If topical therapy is used as a sole therapy, clip the coat and use lime-sulfur. Do not allow cats to lick or groom off the antifungal solutions.

Ineffective products

Captan, povidone-iodine, and chlorhexidine have been consistently found to be ineffective against M. canis in in vitro and in vivo studies.³ Chlorhexidine solution used as a dip was evaluated as the sole topical therapy in a controlled study using an experimental M. canis infection model. ¹³ In that study, infected cats received the dip treatment twice a week for 150 days after their coats were clipped. At the end of therapy, there was no significant difference between the chlorhexidine treatment group and the control group.

Local topical therapy

Topical antifungal ointments and lotions are not recommended for treating feline dermatophytosis. The efficacy of these products is unproved in feline dermatophytosis. Furthermore, studies in guinea pigs revealed that topical antifungal agents were only successful in eliminating the infection when it was confined to the glabrous skin.¹⁵ Using these products was also associated with the development of chronic dermatophytosis. From a more practical perspective, these lotions and ointments are messy, easily groomed off, and tempt clients to do spot therapy. Given the fact that infective spores are present throughout the coat, applying local topical agents is not effective or practical therapy.

Step 3: Selecting appropriate systemic therapy

Systemic therapy is the treatment of choice for feline dermatophytosis. The efficacy of griseofulvin, itraconazole, terbinafine hydrochloride, and lufenuron alone or in combination with other therapies has been studied. ^{5,7,9,10,12,16-29} I am not aware of any age-related studies, but I do not use any of the systemic antifungal agents in kittens less than 8 weeks of age unless the alternative is euthanasia.

Griseofulvin

Griseofulvin is a fungistatic antifungal agent that inhibits nucleic acid synthesis and cell mitosis metaphase by interfering with the function of spindle microtubules. Griseofulvin has variable absorption from the digestive tract; its absorption is enhanced by administering it with fatty meat or by using formulations containing polyethylene glycol.

This drug is teratogenic and should not be given to pregnant animals. There are also anecdotal reports of its interfering with spermatogenesis, so it is best avoided in breeding males.¹⁴ The most common adverse effects are anorexia, vomiting, and diarrhea, which can be managed by dividing the dose into twice-daily administrations. Bone marrow suppression and neurologic side effects are most likely idiosyncratic reactions. Do not use griseofulvin in cats that have feline immunodeficiency virus (FIV) infections, because severe neutropenic reactions have been seen in cats with FIv.²⁰

The most commonly used dosing regimen is daily: griseofulvin microsize at a dosage of 25 to 50 mg/kg given orally once a day or divided twice a day; griseofulvin ultramicrosize at a dosage of 5 to 10 mg/kg given orally once a day or divided twice a day. Higher doses may be needed in refractory cases. Itraconazole is rapidly replacing griseofulvin as the drug of choice for treating dermatophytosis.
Itraconazole

This drug is currently my first choice for treating feline dermatophytosis. Itraconazole (Sporanox Janssen Pharmaceutica, Ortho Biotech) is a triazole derivative that alters fungal cell membrane permeability by inhibiting ergosterol synthesis.³⁰ At low doses it is fungistatic, and at higher doses it is fungicidal. In general, itraconazole is well-tolerated by cats at the doses used to treat dermatophytosis. vomiting and anorexia are the most common adverse effects and, in my experience, are dose-related.

Itraconazole's antifungal activity against M. canis has been documented in people and guinea pigs for some time. Three studies involving multicat situations provide some interesting insights regarding effective flexible dosing schedules. ^16,17,19 Based on these studies, the following dosing regimens can result in a mycological cure, provided they are accompanied by concurrent clipping, topical therapy, and environmental decontamination procedures.

• Daily dosing: Itraconazole 10 mg/kg given orally once a day¹⁷
  
  
• Combined continuous/pulse therapy: Itraconazole 10 mg/kg given orally once a day for 28 days and then on an alternate week regimen (one week off and one week on)¹⁹
  
  
• Short-term cycle therapy: Itraconazole 10 mg/kg given orally once a day for 15 days, followed by fungal cultures 10 to 15 days after treatment; this cycle is repeated until the cats are cured.¹⁶

It is important to point out that the study of short-term cycle therapy used a dose of 1.5 to 3 mg/kg given orally once a day.¹⁶ I recommend a higher dose of itraconazole (10 mg/kg orally), because only eight of 15 cats in that study were cured of dermatophytosis. I have found the 15 day treatment cycles to be very effective in multicat situations, provided a higher dose is used. I prefer the 10 mg/kg dose, but I have successfully treated dermatophytosis with doses of 5 to 10 mg/kg given orally.

Terbinafine

Terbinafine (Lamisil Tablets-Novartis) is the newest systemic antifungal agent to be used in treating dermatophytosis. It is an allylamine antifungal agent that suppresses the biosynthesis of ergosterol by inhibiting the fungal enzyme squalene epoxidase.³¹ The drug is considered to be fungicidal against dermatophytes.

Five recent reports describe its use in treating dermatophytosis in multicat situations; two of these studies report on different aspects of the same experimental infection.^18,21-25 In addition, this drug has been used in a recently completed study at the University of Wisconsin (DeBoer, D.J.; Moriello, K.A.: Unpublished data, 2003). As a result of these studies, it has been determined that terbinafine needs to be administered at a dose of 30 to 40 mg/kg given orally once a day. This dose results in significantly higher concentrations in hair when compared with lower doses. Terbinafine at this dose may be substituted for itraconazole in combined continuous/pulse or short-term cycle therapy. Terbinafine also appears to be equivalent to griseofulvin and itraconazole in
treating feline dermatophytosis (De= Boer, D.J.; Moriello, K.A.: Unpublished data, 2003).¹⁸ It is well-tolerated by cats; vomiting is the most common adverse effect. In my opinion, there is not an advantage in using terbinafine instead of itraconazole in cats.

Lufenuron

Lufenuron is a benzoylphenylurea drug that disrupts chitin synthesis and is used for flea control. Chitin is a critical component of the outer cell wall of fungi, and it is possible that drugs that disrupt chitin synthesis might also have antifungal activity. One retrospective study suggested lufenuron treatment was strongly associated with recovery in many dogs and cats with a number of fungal infections, including dermatophyte infections.²⁶ Since that report, the use of lufenuron has been a widely debated topic in both the lay and veterinary literature and has been the focus of numerous anecdotal and published reports.^9,27-29

Two controlled blinded studies have evaluated the efficacy of lufenuron in preventing or altering the course of experimentally induced M. canis infections.^28,29 In the first study, after two months of pretreatment with either 30 or 130 mg/kg lufenuron given orally, kittens received a markedly larger than field challenge with infective M. canis spores.²⁹ In the second study, cats received four doses of lufenuron (100 to 133 mg/kg orally or 40 mg/kg subcutaneously) at monthly intervals before being exposed to a subclinically infected cat.²⁸ They then received five additional monthly doses. In the second study, infections were established more slowly in the lufenuron-treated groups when compared with the control group, but the infections in all groups resolved at about the same time.²⁸ In both studies, lufenuron failed to prevent infection or alter the course of infection.^28,29

In a clinical field study involving 100 cats in two catteries with naturally occurring dermatophytosis, lufenuron (60 mg/kg orally once on Day 0 and again on Day 30) was used in conjunction with topical enilconazole. A second group of cats was treated with griseofulvin (25 mg/kg b.i.d.) and topical enilconazole. Although the investigators reported a decrease in fungal culture counts over 90 days and clinical resolution of signs, cures were not reported in either group. The authors did note that severe environmental contamination was present in the catteries ⁹ At this time, I do not recommend lufenuron for treating or preventing dermatophytosis.

Fungal vaccines

Intense interest in developing a fungal vaccine to prevent and possibly treat dermatophytosis continues. The only commercially available fungal vaccine licensed for use in cats is Fel-O-Vax MC-K (Fort Dodge Laboratories), and its current availability is uncertain. Several studies have evaluated either an experimental or commercial vaccine for treating and preventing dermatophytosis.^32-37 These studies have found that fungal vaccines are not protective against challenge exposure, but they are associated with a temporary reduction in the clinical signs of dermatophytosis. Fungal vaccines as sole therapy are not effective in treating dermatophytosis, but they may be a useful adjuvant therapy when combined with appropriate topical and systemic therapy and environmental control. Fungal vaccination may be a practical alternative to topical therapy in situations in which topical therapy cannot be used; this recommendation assumes that the coat is clipped and that appropriate systemic antifungal therapy and environmental decontamination procedures are used.

Treatment summary and follow-up

The treatment strategies described in this article are summarized in Table 1. Ridding cats of dermatophytosis for good requires intensive monitoring and environmental decontamination. The best way to go about these two important components of therapy, as well as how to prevent reinfection, is covered in the next article in this symposium.

References

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21. Chen, C.: The use of terbinafine for the treatment of dermatophytosis. Vet. Dermatol. 12 (suppl. 1):41; 2000.
    
    
22. Mancianti, F. et al: Efficacy of oral terbinafine in feline dematophytosis due to Micraporum canis. J Feline Med. Surg. 1(1):37Jt1; 1999.
    
    
23. Kotnik, T.: Drug efficacy of terbinafine hydrochloride (Lamisil) during oral treatment of cats, experimentally infected with Micro sporum canis. J. Vet. Med. B Infect. Dis. Vet. Public Health 49 (3):120-122; 2002.
    
    
24. Castanon-Olivares, L.R. et al.: Effectiveness of terbinafine in the eradication of Microsporum canis from laboratory cats. Mycoses 44 (3-4):95-97; 2001.
    
    
25. Kotnik, T. et al.: Terbinafine hydrochloride treatment of Microsporum canis experimentally induced ringworm in cats. Vet. Microbiol. 83 (2):161-168; 2001.
    
    
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28. DeBoer, DJ. etal.: Effects of lufenuron treatment in cats on the establishment and course of Micrmporum canis infection following exposure to infected cats. JA 014 222 (9):121(-1220; 2003.
    
    
29. Moriello, K.A. et al.: Prevention of Microsporum canis infection in a cat challenge model (abst.). Vet. Dermatol. 13:225; 2002.
    
    
30. Odds, F.C.: Itraconazole-A new ora antifungal agent with a very broad spectrum of activity in superficial and systemic mycoses. J. Dermatol. Sci. 5 (2):65-72; 1993.
    
    
31. Debruyne, D.; Coquerel, A.: Pharmacoki netics of antifungal agents in onychomycoses Clin. Pharmacokinet. 40 (6):441-472; 2001.
    
    
32. DeBoer, DJ; Moriello, K.A.; The immune response to Microsporum canis induced by a fungal cell wall vaccine. Vet. Dermatol. 5:4755; 1994.
    
    
33. DeBoer, DJ.; Moriello, K.A.: Investigations of a killed dermatophyte cell-wall vaccine against infection with Microsporum canis in cats. Res. Vet. Sci. 59 (2):110-113; 1995.
    
    
34. Manoyan, M.G. et al.: Effectiveness of Microderm vaccine against dermatophytosis in animals. Vet. Dermatol. 12 (suppl. 1):59; 2000.
    
    
35. Bredahl, L.K. et al.: Efficacy of an experimental Microsporum canis vaccine in farmed foxes. Vet. Dermatol. 12 (suppl. 1):39; 2000.
    
    
36. Bredahl, L.K. et al.: Safety of an experimental Microsporum canis vaccine in farmed foxes. Vet. Dermatol. 12 (suppl. 1):45; 2000.
    
    
37. DeBoer, D.J. et al.: Safety and immunologic effects after inoculation of inactivated and combined live-inactivated demnatophytosis vaccines in cats. AJVR 63 (11):1532-1537; 2002.
    
    

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