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Vitalitys.chVeterinary Dermatology 2004, 15, 99 –107
Treatment of dermatophytosis in dogs and cats: review of
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, (Received 31 January 2003; accepted 24 July 2003) Abstract
The recent literature on the treatment of dermatophytosis in dogs and cats was reviewed. Based upon in vitro studies using isolated infected hairs and controlled or field in vivo studies, the following topical treatmentswere consistently found to be antifungal (i.e. antidermatophyte): lime sulfur (1:16), 0.2% enilconazole rinses, anda combined 2% miconazole/chlorhexidine shampoo. Animals or hairs were either bathed or rinsed once or twiceweekly. Itraconazole, griseofulvin and terbinafine were evaluated in controlled or field studies, most commonlyinvolving cats. Griseofulvin (50 mg kg−1) was reported to cure infected animals in 41–70 days. Itraconazole(10 mg kg−1 once daily or in a combined daily/pulse therapy 10 mg kg−1 once daily for 28 days and then week on/week off ) was reported to cure infected animals in 56 –70 days. Low-dose itraconazole (1.5 –3.0 mg kg−1) in 15-day cycles required 1–3 cycles (15 – 45 days). Various doses of terbinafine (5 – 40 mg kg−1) were reportedly usedto treat dogs or cats. The higher doses of terbinafine (> 20 mg kg−1) were required to achieve a mycological cure;the number of treatment days to cure varied from 21 to > 126 days. Lufenuron was reported anecdotally to bean effective cure, however, this was not substantiated in controlled studies. Finally, fungal vaccines were not foundto be effective against challenge exposure, however, there is evidence that they may be useful in treatment protocols.
Keywords: antifungal, cat, dermatophytosis, disinfectant, dog, lufenuron, Microsporum, treatment, Trichophyton,vaccine.
I N T RO D U C T I O N
However the most commonly isolated pathogens areMicrosporum canis, M. gypseum and Trichophyton ment- Dermatophytosis is a superficial infection of the kerat- agrophytes. Infection occurs via direct transmission of inized tissues including nails/claws, hair and stratum infective spores to a susceptible host. Reservoirs of corneum of the skin. The fungi that cause these infec- infection for both people and animals include cont- tions are known as dermatophytes. There are three aminated environments and objects, animals with sub- genera that comprise the dermatophytes: Microspo- clinical or clinical infections, and animals that are rum, Epidermophyton and Trichophyton. Microsporum mechanical carriers of the spores on their hair coat.
and Trichophyton spp. are usually separated on the Disease prevalence is unknown as this is not a report- basis of host preference and natural habitat.1 Anthro- able disease in most countries in the world. It has been pophilic species infect people and, less commonly, ani- estimated that dermatophytosis accounts for ≈ 2% of all mals. Zoophilic species are usually animal pathogens skin infections;2 however, prevalence of the disease tends but are capable of infecting people. Geophilic species to be more common in warm tropical /subtropical climates inhabit the soil and serve as a source of infection for and /or where there are large numbers of feral animals.4 both animals and people. The purpose of this article is Any age, sex, or breed of animal is susceptible to to briefly review the key clinical aspects of the disease infection. However, the disease tends to be more com- and summarize recent studies on treatment options.
mon in young, sick, debilitated and old animals. Thepresence of other diseases may also affect susceptibilityto infection; dermatophytosis is three times more prev- O VE R V I EW O F T H E D I S E A S E
alent in cats with feline immunodeficiency virus than inuninfected cats.5 There is a strong clinical impression that longhaired animals are more susceptible to infec- Over 20 different species of dermatophytes have been tion. This may be due to hereditary factors and/or the reported to cause clinical disease in dogs and /or cats.2,3 simple fact that long hairs trap spores and are a ‘fungusfriendly’ environment. Studies with experimental mod-els of dermatophyte infections have reported difficul-ties in the establishment of infection when cats were Correspondence: Karen A. Moriello, Department of Medical Sciences, allowed to groom.6 It is possible that grooming may be School of Veterinary Medicine, 2015 Linden Drive West, Madison,WI 53706 USA. E-mail: firstname.lastname@example.org an under recognized host defence mechanism.
2004 European Society of Veterinary Dermatology Mere exposure to dermatophyte spores does not screening tool and is helpful for identification of hairs guarantee infection. An unknown but ‘critical mass’ of for direct examination and/or culture; a negative test spores must come into contact with a susceptible host.
does not rule out infection. Direct examination of hairs The spores must evade host defence mechanisms that and scales looks for the presence of fungal hyphae include mechanical removal, competition with normal and/or ectothrix spores. This procedure can be done bacterial and fungal flora, exposure to fungistatic with mineral oil, but is facilitated by the use of clearing properties of epidermal lipids, low humidity of the skin agents such as potassium hydroxide 10 or 20%, 0.5% surface and acquired host immunity.7 Factors that calcofluor white, or chlorphenolac. Definitive diagno- favour infection include any pre-existing disease that sis can be made via skin biopsy, but it is not as sensitive will cause an increase in surface humidity, cause micro- as a fungal culture. Skin biopsy is helpful in the diag- trauma to the skin and/or compromise host immune nosis of kerion reactions and granulomatous infections surveillance.7 Once a nidus of infection has been estab- because cultures are often negative.2 Histological lished, the fungal species proceeds to invade the keratin examination of shaved, clipped or surgically removed of hairs and skin and establish and infection. Recovery samples of claws may be the test of choice in cases from infection is dependent upon a competent cell- fungal paronychia, onychorrhexis or onychomadesis.2 Fungal culture is considered the ‘gold standard’ fordiagnosis and can be accomplished via toothbrushing the hair coat and embedding the bristles in fungal cul- Dermatophytosis in dogs and cats is primarily a follic- ture plates or via plucking hairs for culture.2,3,8 Tooth- ular disease and clinical signs are essentially a reflection brush fungal culturing is favoured in the US, where as of hair follicle damage and subsequent inflammation.
in UK Denman brushes are used and in France carpet Pruritus may vary from none to severe.
squares are preferred. The basic theory is similar; a In dogs, lesions may consist of any combination of sterile object that is likely to trap spores is mechanically papules, pustules, focal to wide spread areas of alo- brushed over the coat. The two most commonly used pecia, variable erythema, and variable scaling and fungal culture media include Sabouraud’s dextrose crusting.2,3 Kerion reactions (nodular lesions), partic- agar and dermatophyte test medium. Recently, a study ularly on the face, may mimic areas of deep pyoderma was published that showed that increased incubation and/or furunculosis or even autoimmune skin dis- temperature (24 –27 °C) resulted in a more rapid colour eases.2 These reactions are common in M. gypseum change on a commercial dermatophyte test media and Trichophyton spp. infections. Involvement of foot- (DTM) developed for animals (Rapid Vet D, dms Lab- pads, nails, and ungual folds may occur alone, or in oratories, Inc. Flemington, NJ, USA) and improved combination with lesions on the trunk. Onychomyco- sporulation of fungi in that study.9 This study also sis may lead to chronic nail fragility and deformity.
suggested that incubation at room temperature might Dermatophytosis is less common in dogs than in cats.
account for false negative culture results.
It is often over-diagnosed; it is common for superficial In the early 1900’s when many dermatophyte species pyoderma to be misdiagnosed as dermatophytosis.
were first being described, it was not recognized that Dermatophytosis, demodicosis and bacterial pyo- strains transmitted from animals might change derma can be clinically indistinguishable in dogs.
considerably after several host-to-host transfers. As a In cats, lesions may consist of any combination of result of these transfers, a species may lose its typical scaling and crusting with or without alopecia; focal, morphology. This resulted in the description of a large multifocal or generalized alopecia; erythema; miliary number of species and variants of dermatophytes, dermatitis and onychomyhcosis.2,3 Dermatophytosis is especially within the Microsporum genus. With the one of the few skin diseases of cats in which hyperpig- advent of molecular technology, it has been possible to mentation may be seen.2,4 Focal pruritic lesions mimicking compare the molecular and conventional taxonomy of areas of eosinophilic plaques may be seen. Longhaired dermatophyte species.10 In a recent study, morpholog- cats may present with breakage and the complaint of ical and physiological features of various species and ‘excessive shedding’. Ingestion of larger than normal strains of the genus Microsporum were compared amounts of hair may result in owner complaints of with the results of molecular testing and DNA constipation, weight loss, anorexia and vomiting; in sequencing resulting in seven species being reclassified the author’s experience these are more common in or synonymized with M. canis, M. ferrugineum and longhaired cats. Cats may also develop granulomatous M. audouinii.11 As this technology becomes more lesions (kerions, mycetomas, pseudomycetomas) of the widespread, the microbiological community will skin and subcutaneous tissues. This is a rare clinical undoubtedly reclassify or rename many dermatophyte presentation with a poor prognosis for cure.
species or strains. The application of molecular tech-nology has not been limited to the reclassification of organisms. Polymerase chain reaction-based assays Diagnostic methods associated with dermatophytosis and chitin synthase 1 (Chs 1) assays have been devel- have been reviewed in detail elsewhere.8 Wood’s lamp oped that can reliably identify dermatophyte infections examination looks for fluorescence on the hair shafts in the skin and tissue.12–14 Although these tests will not of M. canis-infected hairs. This examination is a likely replace conventional testing, their value will be in 2004 European Society of Veterinary Dermatology, Veterinary Dermatology, 15, 99 –107
the identification of infections or strains in clinical involved Persian cats.20–26 Chlorhexidine solution used situations where typical morphological characteristics as dip was evaluated as a sole topical therapy in a con- are not present and/or in tissue specimens.
trolled study using an experimental M. canis infectionmodel.25 In that study, infected cats were dipped twiceweekly for 150 days after the hair coat was clipped. At RE V I EW O F D R U G T RE A T M E N T
the end of therapy there was no significant difference between the chlorhexidine treatment group and thecontrols. Chlorhexidine was found to be ineffective.
Unless otherwise stated, the reader should assume that In two studies, enilconazole was evaluated as a sole M. canis is the pathogen being discussed.
topical therapy (post whole body clipping) for thetreatment of naturally occurring M. canis infection in Persian cats.23,24 In one study, cats were either dipped Topical antifungal treatments for dermatophytosis in 0.2% enilconazole (n = 10) twice weekly or in luke- have been evaluated both in vitro using isolated infected warm water (n = 4) for 8 weeks.23 In the enilconazole- hairs and in various in vivo studies.4,15–26 Currently, treated cats, fungal cultures were culture negative as topical treatments are recommended as adjuvant to remained negative to the end of the 10-week monitor-ing period. In contrast, 3/4 control cats were still In vitro studies using isolated infected hairs or spores culture positive at end of 10 weeks of monitoring; There are five reports of studies using isolated infected previous studies have shown that dermatophytosis is a hairs or spores to evaluate topical antifungal therapies self-limiting disease with cats self-curing somewhere and one using a agar dilution method,4,15–19 four of between 12 and 17 weeks post infection.25 In the sec- these also reported on topical compounds used as ond study, 22 Persian cats in a cattery were treated with both on-animal and environmental treatments.15–18 The 0.2% enilconazole every 3 days for a total of eight advantages of isolated infected hairs or spores for applications.24 All of the cats improved clinically and testing include removal difficulties encountered when were culture negative by day 28 of therapy. In both trying to treat live animals, insurance of appropriate studies, cats were observed for adverse effects and contact with the antifungal agent, and elimination of serum chemistry panels were monitored. Enilconazole the problem of continued spore production on the was well tolerated but may have been associated with host. Problems with this model include an inability hypersalivation, anorexia, weight loss, emesis, idio- to quantify and standardize the amount of infective pathic muscle weakness and slightly elevated serum material being tested, maceration of hairs causing the alanine aminotransferase (ALT) concentrations.
release of spores within hairs leading that can result In three additional studies, topical therapy was evalu- in negative fungal cultures becoming ‘positive’ after ated but in combination with systemic therapy (lufenuron repeated soakings, and loss of material from stocki- or griseofulvin).20–22,26 In one study, 14 Persian cats nettes or other testing containers. Nevertheless, this with naturally occurring dermatophytosis were treated technique has provided valuable information on the with griseofulvin alone (n = 7) or with griseofulvin and efficacy of various commonly used antifungal com- concurrent twice-weekly shampoo (n = 7) with a com- pounds and this testing method is a useful screening bined 2% miconazole/2% chlorhexidine product.20 tool for potential commercial products.
Cats were not clipped prior to therapy in this study. At Lime sulfur (1:16) and enilconazole have been shown the end of the study, the lesion scores in the group to be consistently effective against M. canis in isolated receiving concurrent topical therapy decreased signifi- infective spore models.4,16–18 Miconazole shampoo was cantly more quickly than in the group receiving sys- evaluated in two studies. In one it was tested as a sole temic therapy alone. The investigators reported no agent using isolated infective spores and in the second statistically significant difference between the two it was tested combination with chlorhexidine using an groups with respect to time to mycological cure; all agar dilution technique in another.4,19 In both studies, treated cats were ‘cured’. They concluded that topical miconazole was found to be an effective antifungal agent.
concurrent therapy was beneficial and that, based Captan, chlorhexidine (as a single agent), and povi- upon the results of this study, clipping of the hair coat dine iodine have been consistently ineffective anti- is not always necessary. The authors admit that results fungal agents when tested using isolated infective spores from this study are hard to interpret. The investigators and/or hairs.4,15–18 Sodium hypochlorite has shown report that at the end of the study ‘none of the cats in mixed results when used at a dilution of 1:10;4,15–18 either group was positive for M. canis’; however, they however, this product is not licensed nor recommended also report that four cats from one group and two from as an on-animal treatment and is more appropriately the other had positive coat cultures suggestive of ‘con- tamination’ (not defined). Environmental contamina-tion and owner compliance were complicating factors.
In the second study, four groups of cats from a cat- There are seven published studies on the efficacy of tery with naturally occurring dermatophytosis were topical antifungal therapy in cats; five of these studies treated with oral griseofulvin and one of four concurrent 2004 European Society of Veterinary Dermatology, Veterinary Dermatology, 15, 99 –107
topical treatments twice weekly: water (placebo), 2% time was 41 days for 9 dogs and 3 cats with 100% of miconazole, 2% chlorhexidene, 2% miconazole and animals treated being cured. In the fourth study, the chlorhexidene.21 The investigators found that the com- authors reported that the cats were considered ‘cured’ bination shampoo was superior to the miconazole but indicated that small numbers of M. canis colonies shampoo alone; cats receiving twice weekly shampoos consistent with coat contamination were isolated from and griseofulvin began showing negative cultures as 4 of 7 making it unclear how to evaluate these results.20 early as 2 weeks after starting therapy. Miconazole In four studies, griseofulvin was evaluated in conjunc- shampoo was superior to chlorhexidine; chlorhexidine tion with topical therapies (enilconazole, miconazole, alone was no better than placebo; cultures did not start chlorhexidine or 2% miconazole/chlorhexidine sham- becoming culture negative until 4 weeks after starting poo)21–22,26 or lufenuron.22 Again the total daily dose was 50 mg kg−1. When combined with enilconazole or In the third study, 100 Persian and other breed cats lufenuron, mycological cure was not reported in any of from two different catteries with naturally occurring the cats after 5 weeks of therapy.22 However, it is dermatophytosis were divided into two groups.22 The important to note that 46 of the cats were Persians and first group (n = 36) was treated concurrently with once none of the 100 cats in the study was clipped prior to weekly topical 0.2% enilconazole rinses for 4 weeks therapy; the investigators noted marked environmental and twice-daily microsized griseofulvin (25 mg kg−1 for contamination. In the second study, unclipped Persian 5 weeks). The second group of cats (n = 64) was treated cats were also the focus; the authors reported a cure at concurrently with once weekly topical 0.2% enilcona- the end of 70 days of griseofulvin and shampoo therapy, zole rinses for 4 weeks and with two oral doses of lufen- but as mentioned previously two cats had ‘M. canis uron (60 mg kg−1 at day 0 and 30). None of the cats in coat contamination’ making it difficult to draw conclu- this study were clipped prior to, or during, therapy. ‘In sions. In one, griseofulvin was combined with 2% both catteries and in both groups, the mean number of miconazole/2% chlorhexidine twice-weekly shampoo fungal colonies decreased rapidly in the first 15 days of therapy. Cats were reported as mycologically cured at therapy, remained stable for the next 45 days, and then the end of 42 days.26 In the last study, griseofulvin ther- increased from day 60 until the end of therapy (day apy was combined with twice weekly shampoos with 90).22 No cures were reported in this study in either either chlorhexidine, miconazole or a combined sham- group or cattery. This study was complicated by heavy poo.21 The authors reported an improvement in all environmental contamination in the face of efforts to groups; however, the combined group ‘was superior’ to disinfectant the environment; it is impossible to know the other groups with this group showing negative cul- if positive cultures post day 60 represented infection or In the fourth study, 21 cats experimentally infected Itraconazole. Itraconazole is triazole derivative that with M. canis were divided into three groups: control, works by altering fungal cell membrane permeability systemic therapy alone and systemic therapy combined through inhibition of ergosterol synthesis.41 At low with twice weekly topical therapy with a 2% micona- doses it is fungistatic and at higher does fungicidal.
zole/2% chlorhexidine shampoo.26 The investigators Itraconazole’s antifungal activity against M. canis did not report clipping the cats prior to treatment. In infection in cats has been reported in three studies all this study, cats treated with both griseofulvin and twice of which were different.27–29 In first study, five cats with weekly miconazole/chlorhexidine shampoo showed a an experimental infection received 10 mg kg−1 once significantly faster mycological and clinical cure than daily and were reported to be mycologically cured after in cats treated with just griseofulvin alone. Cats receiv- 56 days.29 In the second study, 15 cats with naturally ing combined therapy were cured at the end of 9 weeks occurring M. canis infections were treated with low- of therapy compared with 11 and 12 weeks for single dose itraconazole (1.5 – 3.0 mg kg−1) for once daily for agent and control groups, respectively.
15-day cycles of therapy.28 Eight of 15 cats were cured.
Six of eight cats required only one cycle of therapy, whereas the remaining two cats needed prolonged There are 17 studies that report on the efficacy of gri- treatment (two 15-day cycles and three 15-day cycles).
seofulvin, itraconazole, terbinafine, or lufenuron alone In the third study, nine cats with naturally occurring or in combination with other therapies.20–22,26–39 dermatophytosis were treated with itraconazole com-bined continuous /pulse therapy protocol.27 All cats Griseofulvin. Griseofulvin is a fungistatic antifungal received itraconazole 10 mg kg−1 once daily for 28 days agent that inhibits nucleic acid synthesis and cell mito- and then on ‘week on /week off’ basis. Eight of nine cats sis metaphase by interfering with the function of spin- were considered cured after 56 days and one cat was dle microtubules.40 Griseofulvin was evaluated in several studies;20–22,26,29 four studies identified treat-ment groups where it was used as a sole therapy as at a Terbinafine. Terbinafine is an allylamine antifungal dose of 50 mg kg−1.20,26,29,39 Mycological cure was sol- agent that suppresses the biosynthesis of ergosterol idly achieved in two of these studies in 63–70 days for via inhibition of the fungal enzyme squaline epoxid- cats. In the study by Balda et al.39 the mean treatment ase. The drug is considered to be fungicidal against 2004 European Society of Veterinary Dermatology, Veterinary Dermatology, 15, 99 –107
dermatophytes.42 The use of terbinafine to treat feline reported a recommended drug dose of 80–100 mg kg−1 M. canis dermatophytosis has been reported in four once every two weeks until mycological cure.36 The studies;30–34 two studies reported on different aspects authors reported that the time to cure ranged from 6 to of the same experimental infection.30,31 In one study, 37 days (mean 13.7 days) in dogs and cats with dermat- three groups of cats were experimentally infected with ophytosis. In a large retrospective survey conducted in M. canis and monitored for 120 treatment days.30,31 In Italy, veterinarians were asked about their clinical this experiment, two doses of terbinafine were com- observations with lufenuron as a treatment dermato- pared with each other and an untreated control group.
phytosis in mammals.43 It is difficult to interpret the The investigators reported that there was no difference results of this study accurately as diagnosis of cases when low dose terbinafine (10 –20 mg kg−1) was compared could include documented infection or suspected with the untreated control group. The cats receiving infection. Furthermore, criteria for ‘cure’ were equally high dose terbinafine (30 – 40 mg kg−1) were considered variable; ‘cure’ could be defined as clinical resolution cured after > 120 days (126 days) of therapy. In one of of signs or mycological cure. In cases where mycologi- the studies, serum and hair concentrations of terbin- cal cure was determined, the mean time to recovery was afine were reported. There was no significant difference 34.7 days (range 12–90 days). There are two reports of in plasma concentrations between the low and high controlled blinded studies evaluating the efficacy of doses of terbinafine; however, the high-dose terbin- lufenuron to prevent or alter the course of experimen- afine group had a significantly higher concentration of tally induced M. canis infections in cats.37,38 In one terbinafine in hair compared to the low dose.31 In a study, lufenuron was used as a pretreatment prior to second study, 41 dogs and 24 cats were treated with ter- challenge exposure and infection.38 Two oral doses of binafine at a dose of 10–30 mg kg−1 once daily.32 No lufenuron were evaluated (30 or 133 mg kg−1); after adverse effects were noted and the mean length of ther- 2 months of pretreatment the kittens were challenged apy for mycological cure for dogs was 53 days (21–126) with infective M. canis spores. In this study, neither and 63 days (28–84 days) for cats. In the third study, dose of lufenuron prevented infection nor altered the 35 dogs or cats were treated with either griseofulvin course of infection; however, it is important to note (see above) or with one of two doses of terbinafine that the challenge was markedly larger than what (5 mg kg−1 and 20 mg kg−1)39 were used to treat dogs would occur under field exposure. In a follow-up study, or cats with naturally occurring dermatophytosis. Ter- two groups of cats were pretreated with either oral or binafine at either dose was effective in 81.3% of animals injectable lufenuron prior to exposure to a subclinically treated; animals responding to treatment required a infected cat.37 Cats received four doses of lufenuron at mean of 33 days of therapy. In a fourth study, 15 cats monthly intervals prior to exposure to the infected cat with naturally occurring dermatophytosis were treated and monthly treatments thereafter for an additional with terbinafine 30 mg kg−1 once daily for 14 days; 12 5 months. In this study, lufenuron did not prevent cats completed the study.34 Cats were followed for a infection in either treatment group. In addition, infec- total of 90 days and at the end of this time 11 of 12 cats tions in the control and two treatment groups resolved were mycologically cured. None of the cats was culture at about the same time. What was noticed in this study negative at the end of 14 days of therapy. The first was that infections were established more slowly in the mycological cures were noted at day 60 days. In the last lufenuron-treated groups when compared with the study, 9/20 laboratory cats were found to be culture control group. In a final study involving 100 cats in two positive for M. canis, but lesion free. All of the cats catteries with naturally occurring dermatophytosis, were treated with terbinafine 8.25 mg kg−1 once daily lufenuron was used in conjunction with topical enilco- for 21 days.33 Cats were reported to be mycologically nazole.22 Although the investigators reported a decrease cured at end of monitoring, 63 days. All of these stud- in fungal culture counts over 90 days and clinical reso- ies reported the drug to be well tolerated with vomiting lution of signs, cures were not reported.
Lufenuron. Lufenuron is a benzoylphenylurea drug There are three studies reporting on the use of fungal that disrupts chitin synthesis and is used for flea con- vaccines in cats to prevent dermatophytosis.44–47 In trol. Chitin is a critical component of the outer cell wall addition, a killed dermatophyte vaccine for treatment of fungi and it possible drugs that disrupt chitin syn- of M. canis in cats is available in the United States (Fel- thesis might also have antifungal activity. The use of O-Vax, MC-K, Fort Dodge Laboratories, Fort Dodge lufenuron in the treatment of dermatophytosis has IO, USA). This product is licensed for use for the treat- been described in several studies.35–38,43 In 2000, a ret- ment and prevention of lesions, but not disease. In rospective study suggested that lufenuron treatment Russia, there is also a live attenuated vaccine for both was strongly associated with recovery in a large treatment and prevention of small animal dermatophy- number of dogs and cats with a number of fungal infec- tosis; however, there is also limited information avail- tions, including dermatophyte infections.35 In that able on this vaccine.47 In two of studies, an experimental report, dogs and cats received lufenuron at doses com- killed cell-wall vaccine was evaluated first in a direct patible with the manufacturer’s recommended dose for application challenge exposure model and then in a less routine flea control. In a follow-up study, the authors intense cohabitant challenge model.44,45 In neither 2004 European Society of Veterinary Dermatology, Veterinary Dermatology, 15, 99 –107
study was the vaccine protective against challenge for use. Topical therapy should be used in conjunction exposure. In a third study, an experimental combined with systemic therapy; if cost constraints do not allow live-inactivated dermatophyte vaccine and a killed for concurrent systemic therapy, twice weekly applica- commercially available dermatophyte vaccine (Fel-O- tions of either lime sulphur or enilconazole can be used Vax) were evaluated for prophylactic immunity and until a mycological cure (2–3 negative consecutive fun- any therapeutic benefit.46 Neither vaccine prevented infection or provided a more rapid cure when com-pared with each other or untreated controls. However, vaccination was associated with a slightly reduced Systemic antifungal therapy is the treatment of choice severity of initial infection when compared with con- for dermatophytosis. Griseofulvin, itraconazole and trols. Interest in vaccination as a treatment or prophy- terbinafine are all effective systematic antifungal laxis continues to be an area of intense interest, primarily because of success in farmed foxes.48,49 Griseofulvin. Griseofulvin therapy is rapidly beingreplaced by itraconazole and terbinafine therapy but it C O N C L U S I O N S
is still an effective antifungal agent. The most com-monly used dose regimen is daily Based upon the current information available for thetreatment of dermatophytosis I have made the follow- • micro size 50 mg kg−1 orally every 24 h or divided ing treatment conclusions based upon my interpreta- tion of the studies. Other clinicians may have differing • ultramicro size 10–15 mg kg−1 orally every 24 h or Itraconazole. Based upon the studies reviewed, itraco- The endpoint of treatment in all studies was two or nazole therapy is flexible. The most commonly effective three negative consecutive fungal cultures obtained at dose was 5–10 mg kg−1 and the following dosing sched- weekly or bi-weekly intervals. This recommendation ules are recommended as treatment options: • daily dosing: itraconazole 5–10 mg kg−1 orally
The optimum treatment protocol for dogs or cats with • combined continuous/pulse therapy: itraconazole 5 –
dermatophytosis involves a combination of clipping of 10 mg kg−1 orally every 24 h for 28 days and then on the hair coat, twice weekly topical antifungal therapy, an alternate week regimen (1 week off and 1 week on); concurrent systemic antifungal therapy and environ- • cycle therapy: itraconazole 5–10 mg kg−1 orally
mental decontamination. Fungal culture monitoring every 24 h for 15 days, followed by fungal cultures should be performed every 2– 4 weeks until mycological Terbinafine. Terbinafine is the newest systemic anti- Although no controlled study exists that proves that fungal agent to be used in dogs and cats. This drug is clipping of the hair coat shortens the duration of infec- well tolerated by cats and dogs. When this drug is used tion, clinical studies strongly support the recommen- at 30–40 mg kg−1 significantly higher concentrations of dation that cats with long hair and/or generalized drug are found in hairs when compared to lower doses.
dermatophytosis should be clipped. Although not nec-essary in all cases of dermatophytosis, clipping of the • Terbinafine 30 – 40 mg kg−1 orally every 24 h.
It may be possible to use terbinafine (30–40 mg kg−1 orally) as a substitute for itraconazole in continuous/ In vitro and in vivo studies have documented that lime sulphur, enilconazole, and miconazole have consistentantifungal activity in the treatment of dermatophyto- sis. The most commonly recommended treatment In placebo-controlled studies, lufenuron did not pre- schedule is twice weekly whole-body applications of vent or alter the course of infection. Controlled studies one of these products. Lime sulfur and enilconazole did document that cats receiving lufenuron had infec- should not be rinsed from the hair coat and a contact tions were established more slowly in the lufenuron- time of 10 min for miconazole shampoos is recom- treated groups when compared with the control group, mended for efficacy. Captan, chlorhexidine (as a single but a difference in treatment outcome was not noted.
agent), and povidine iodine have been consistently Whether this benefit justifies the cost of lufenuron ther- ineffective antifungal agents when tested using isolated apy or can be ‘manipulated’ into a therapeutic advan- infective spores and/or hairs and are not recommended tage is not known. At this time, lufenuron therapy is 2004 European Society of Veterinary Dermatology, Veterinary Dermatology, 15, 99 –107
not recommended for the treatment or prevention of chitin synthase 1 gene. Microbiology and Immunology 2000; 44: 605 –7.
15. Rycroft, A.N., McLay, C. Disinfectants in the control of small animal ringworm due to Microsporum canis. Veter- Interest in the development of a fungal vaccine for pre- inary Record 1991; 129: 239 – 41.
16. Moriello, K.A., DeBoer D.J. Environmental decontami- vention and/or therapy of M. canis dermatophytosis nation of Microsporum canis: in vitro studies using iso- continues to be the focus of a great deal of research. To lated infected cat hair. In: Kwochka, K.W., Willemse, T., date, neither experimental nor commercial vaccines von Tscharner, C., eds. Advances in Veterinary Dermat- have been shown to be protective against challenge ology, Vol 3. Oxford: Butterworth Heinemann, 1998: exposure. Vaccination was associated with a slightly reduced severity of initial infection when compared 17. White-Weithers, N., Medleau, L. Efficacy of topical ther- with controls in cats. At this time, vaccination for apies for the treatment of dermatophyte-infected hairs M. canis is not recommended for prophylaxis, but may from dogs and cats. Journal of the American Animal Hos- be beneficial as an adjuvant to conventional therapy.
pital Association 1995; 31: 250 –3.
18. Moriello, K.A., DeBoer, D.J., Volk, L. Determination of strain variability of Microsporum canis to disinfectants
(Abstract). Veterinary Dermatology 2002; 13: 225.
RE F E RE N C E S
19. Perin, N., Bond, R. Synergistic inhibition of the growth in vitro of Microsporum canis by miconazole and chlo- 1. Beneke, E.S., Rodgers, A.L. Medical Mycology and rhexidine. Veterinary Dermatology 2003; 14: 99 –102.
Human Mycoses. Belmont, CA: Star Publishing, 1996: 20. Paterson, S. Miconazole/chlorhexidine shampoo as an adjunct to systemic therapy in controlling dermatophy- 2. Foil, C.S. Dermatophytosis. In: Greene, C.E., ed. Infec- tosis in cats. Journal of Small Animal Practice 1999; 40:
tious Diseases of the Dog and Cat. Philadelphia: W.B.
21. Mason, K.V., Frost, A., O’Boyle, D., Connole, M.D.
3. Scott, D.W., Miller, W.H., Griffin, C.E., eds. Fungal skin Treatment of a Microsporum canis infection in a colony diseases. In: Muller and Kirk’s Small Animal Dermatol- of Persian cats with griseofulvin and a shampoo contain- ogy, 6th edn. Philadelphia: W.B. Saunders, 2001: 336–61.
ing 2% miconazole, 2% chlorhexidine, 2% miconaozle 4. Moriello, K.A., DeBoer, D.J. Feline dermatophytosis: and 2% chlorhexidine or placebo. Veterinary Dermat- recent advances and recommendations for therapy. In: ology 2000; 12 (Suppl. 1): 55.
Kunkle, G.A., ed. Veterinary Clinics of North America: 22. Guillot, J., Malandain, E., Jankowski, F. et al. Evalu- Small Animal Practice. Philadelphia: W.B. Saunders, ation of the efficacy of oral lufenuron combined with topical enilconazole for the management of dermatophy- 5. Mancianti, F., Giannelli, C., Bendinelli, M. et al. Myco- tosis in catteries. Veterinary Record 2002; 150: 714 –18.
logical findings in immunodeficiency virus infected cats.
23. DeJaham, C. Eniloconazole emulsion in the treatment of Journal of Medical and Veterinary Mycology 1992; 30:
dermatophytosis in Persian cats; tolerance and suitabil- ity. In: Kwochka, K.W., Willemse, T., Von Tscharner, C., 6. DeBoer, D.J., Moriello, K.A. Development of an exper- eds. Advances in Veterinary Dermatology, Vol. 3. Oxford: imental model of M. canis infection in cats. Journal of Butterworth Heinemann, 1998: 299 –307.
Veterinary Microbiology 1994; 42: 289 –95.
24. Hnilica, K.A., Medleau, L. Evaluation of topically applied 7. Ogawa, H., Summerbell, R.C., Clemons, K.V. et al. Der- enilconazole for the treatment of dermatophytosis in a matophytes and host defence in cutaneous mycoses.
Persian cattery. Veterinary Dermatology 2002; 13: 23 – 8.
Medical Mycology 1998; 36 (Suppl. 1): 166 –73.
25. DeBoer, D.J., Moriello, K.A. Inability of topical treat- 8. Moriello, K.A. Diagnostic techniques for dermatophy- ment to influence the course of experimental feline tosis. Clinical Techniques in Small Animal Practice 2001; dermatophytosis. Journal of the American Veterinary 16: 219 –24.
Medical Association 1995; 207: 52–7.
9. Guillot, J., Latié, L., Manjula, D. et al. Evaluation of the 26. Sparkes, A.H., Robinson, A., MacKay, A.D. et al. A dermatophyte test medium Rapid Vet-D. Veterinary Der- study of the efficacy of topical and systemic therapy for matology 2001; 12: 123 –7.
the treatment of feline Microsporum canis infection.
10. Kac, G. Molecular approaches to the study of dermato- Journal of Feline Medicine and Surgery 2000; 2: 135 – 42.
phytes. Medical Mycology 2000; 38: 329 –36.
27. Colombo, S., Cornegliani, L., Vercelli, A. Efficacy of 11. Gräser, Y., Kuijpers, A.F.A., Fari, M. et al. Molecular itraconazole as combined continuous/pulse therapy in and conventional taxonomy of the Microsporum canis feline dermatophytosis: preliminary results in nine cases.
complex. Medical Mycology 2000; 38: 143 –53.
Veterinary Dermatology 2001; 12: 347–50.
12. Faggi, E., Pini, G., Campisi, E. et al. Application of PCR 28. Mancianti, F., Pedonese, F., Zullino, C. Efficacy of oral to distinguish common species of dermatophyes. Journal administration of itraconazole to cats with dermatophy- of Clinical Microbiology 2001; 39: 3382–5.
tosis caused by Microsporum canis. Journal of the Amer- 13. Kano, R., Aihara, S., Nakamura, Y. et al. Chitin syn- ican Veterinary Medical Association 1998; 213: 993 –5.
thase 1 (Chs 1) gene sequences of Microsporum equinum 29. Moriello, K.A., DeBoer, D.J. Efficacy of griseofulvin and Trichophyton equinum. Veterinary Microbiology and itraconazole in the treatment of experimentally 2001; 78: 85 – 90.
induced dermatophytosis in cats. Journal of the American 14. Kano, R., Nakamura, Y., Watanabe, S. et al. Detection Veterinary Medical Association 1995; 207: 439 – 44.
of Microsporum canis in the skin scrapings and hairs of 30. Kotnik, T. Drug efficacy of terbinafine hydrochloride dogs with dermatophytosis based on sequences of the (Lamisil®) during oral treatment of cats, experimentally 2004 European Society of Veterinary Dermatology, Veterinary Dermatology, 15, 99 –107
infected with Microsporum canis. Journal of Veterinary 40. McNall, E.G. Biochemical studies on the metabolism of Medicine Series B 2002; 49: 120 –2.
griseofulvin. Archives of Dermatology 1960; 81: 657–61.
31. Kotnik, T., Erzuh, N.K., Kuzner, J., Drobniè-Kosorok, M.
41. Odds, F.C. Itraconazole-A new oral antifungal agent Terbinafine hydrochloride treatment of Microsporum with a very broad spectrum of activity in superficial and canis experimentally-induced ringworm in cats. Veteri- systemic mycoses. Journal of Dermatological Science nary Microbiology 2001; 83: 161–8.
1993; 5: 65 –72.
32. Chen, C. The use of terbinafine for the treatment of 42. Debruyne, D., Coquerel, A. Pharmacokinetics of anti- dermatophytosis. Veterinary Dermatology 2000; 12
fungal agents in onychomycoses. Clinical Pharmacoki- netics 2001; 40: 441–72.
33. Castañón-Olivares, L.R., Manzano-Gayosso, P., Lópex- 43. Schenker, R., Bucci, V., Strehlau, G. Use of lufenuron for Martínez, R. et al. Mycoses. Effectiveness of terbinafine the treatment of dermatophytosis in Italy. Proceedings of in the eradication of Microsporum canis from laboratory the World Small Animal Veterinary Association Congress, 34. Mancianti, F., Pedonese, F., Millanta, F. et al. Efficacy of 44. DeBoer, D.J., Moriello, K.A. The immune response to oral terbinafine in feline dermatophytosis due to Micro- Microsporum canis induced by a fungal cell wall vaccine.
sporum canis. Journal of Feline Medicine and Surgery Veterinary Dermatology 1994; 5: 47–55.
1999; 1: 37– 41.
45. DeBoer, D.J., Moriello, K.A. Investigations of a killed 35. Ben-Ziony, Y., Arzi, B. Use of lufenuron for treating dermatophyte cell-wall vaccine against Microsporum fungal infections of dogs and cats: 297 cases (1997–99).
canis infection with Microsporum canis in cats. Research Journal of the American Veterinary Medical Association in Veterinary Science 1995; 59: 110 –13.
2000; 217: 1510 –13.
46. DeBoer, D.J., Moriello, K.A., Blum, J.L. et al. Safety and 36. Ben-Ziony, Y., Arzi, B. Update information for the treat- efficacy and immunologica effects after inoculation of an ment of fungal infections in dogs and cats. Journal of the inactivated and combined live-inactivated dermatophy- American Veterinary Medical Association 2001; 218: 1718.
tosis vaccines in cats. American Journal of Veterinary 37. DeBoer, D.J., Moriello, K.A., Blum, J., Volk, L.M.
Research 2002; 63: 1532–7.
Effects of lufenuron treatment in cats on the establish- 47. Manoyan, M.G., Panin, A.N., Letyagin, K.P. Effective- ment and course of Microsporum canis infection follow- ness of Microderm vaccine against dermatophytosis ing exposure to infected cats. Journal of the American in animals. Veterinary Dermatology 2000; 12 (Suppl. 1):
Veterinary Medical Association 2003; 1216 –20.
38. Moriello, K.A., DeBoer, D.J., Volk, L., Blum, J. Preven- 48. Bredahl, L.K., Bratberg, A.M., Solbakk, I.T. et al. Effi- tion of Microsporum canis infection in a cat challenge cacy of an experimental Microsporum canis vaccine in model (Abstract). Veterinary Dermatology 2002; 13: 225.
farmed foxes. Veterinary Dermatology 2000; 12 (Suppl. 1):
39. Balda, A.C., Gamble, W., Otsuka, M. et al. Comparative efficacy of griseofulvin and terbinafine in the therapy of 49. Bredahl, L.K., Bratberg, A.M., Solbakk, I.T. et al. Safety dermatophytosis in dogs and cats. Proceedings of the of an experimental Microsporum canis vaccine in farmed World Small Animal Veterinary Association Congress, 2002.
foxes. Veterinary Dermatology 2000; 12 (Suppl. 1): 45.
Une revue de la littérature récente sur le traitement des dermatophytoses chez le chien et le chat est présentée. En se basant sur des études in vitro portant dur des poils infectés et sur des études controlées ou deterrain in vivo, les traitements topiques suivants peuvent être considérés comme antifongiques (i.e. antidermat-ophyte): lime sulfur (1:16), lotion d’enilconazole à 0.2% et shampooing à 2%miconazole/chlorhexidine. Les ani-maux ou des poils étaient soit baignés soit rincés une ou deux fois par semaine. L’itraconazole, la griséofulvineet la terbinafine ont été évalués dans des essais controlés ou des essais terrain, la plupart du temps chez le chat.
La griséofulvine (50 mg kg–1) a permis une guérison des animaux infectés en 41 à 70 jours. L’itraconazole(10 mg kg–1 une fois par jour ou en traitement pulsé 10 mg kg–1 une fois par jour pendant 28 jours puis une semaineavec traitement, une semaine sans traitement) a permis de guérir les animaux infectés en 56 à 70 jours. L’utilisationde l’itraconazole à faible dose (1.5 à 3.0 mg kg–1) pendant des cycles de 15 jours a nécessité 1 à 3 cycles (15 à45 jours. Des doses variables de terbinafine ont été utilisées pour traiter des chiens ou des chats (5 mg kg–1 à40 mg kg–1). Des doses élevées (>20 mg kg–1) étaient nécessaires pour obtenir une guérison mycologique. Le nombrede jours de traitement variait de 21 à >126 days. Le lufenuron a également anecdotiquement été rapporté commeun traitement efficace bien que cet effet ne soit pas confirmé par des études controlées. Enfin, la vaccination anti-dermatophyte n’a pas prouvé son efficacité dans un modèle expérimental, bien qu’il existe des preuves qu’ellepuisse être efficace comme traitement adjuvant.
Se revisó la literatura reciente sobre el tratamiento de la dermatofitosis en perros y gatos. Basándonos en estudios in vitro utilizando pelos infectados aislados y estudios controlados o de campo in vivo, los siguientestratamientos tópicos fueron considerados antifúngicos (es decir, antidermatofitos): sulfuro de lima (1:16), 0.2%enjuagues con enilconazol, y un champú con una combinación de un 2% de miconazol/clorexidina. Los animaleso los pelos fueron bañados o enjuagados una o dos veces a la semana. El itraconazol, la griseofulvina, y la ter-binafina fueron evaluados en estudios de campo o estudios controlados, la mayoría implicando gatos. La grise-ofulvina (50 mg kg–1) curó animales infectados en 41 a 70 días. Se ha publicado que el itraconazol (10 mg kg–1una vez al día o en una combinación de terapia diaria/intermitente a 10 mg kg–1 una vez al día durante 28 díasy después semana sí/semana no) cura los animales infectados en 56 a 70 días. El itraconazol a dosis bajas (1.5 a 2004 European Society of Veterinary Dermatology, Veterinary Dermatology, 15, 99 –107
3.0 mg kg–1) en ciclos de 15 días requería de 1 a 3 ciclos (15 a 45 días). Se ha publicado el uso de varias dosis deterbinafina (5 mg kg–1 a 40 mg kg–1) para tratar perros y gatos. Las dosis más altas de terbinafina (>20 mg kg–1)eran necesarias para conseguir una curación micológica; el número de días de tratamiento para conseguir lacuración variaba de 21 a >126 días. Anecdóticamente se ha descrito que el lufenuron puede ser efectivo, aunqueesto no pudo ser confirmado mediante estudios controlados. Finalmente, las vacunas fúngicas no fueron efectivascontra la exposición, aunque existen pruebas de que pueden ser útiles en protocolos de tratamiento.
Neue Veröffentlichungen über die Behandlung der Dermatophytose bei Hunden und Katzen werden besprochen. Basierend auf in vitro Studien mit isolierten infizierten Haaren und kontrolliertenoder Feld-Studien in vivo erwiesen sich folgende topische Behandlungen übereinstimmend als antimykotisch(d.h. gegen Dermatophyten) wirksam: Schwefelkalk (1:16), 0,2% Enilkonazol Spülungen und ein Shampoo miteiner Kombination von 2%Miconazol/Chlohexidin. Tiere oder Haare wurden ein- bis zweimal wöchentlich geba-det oder gespült. Itraconazole, Griseofulvin, und Terbinafine wurden in kontrollierten oder Feld-Studien zumeistbei Katzen evaluiert. Griseofulvin (50 mg/kg) heilte infizierte Tiere innerhalb von 41 bis 70 Tagen. Itrakonazol(10mg/kg 1xtäglich oder in einer kombinierten Therapie mit täglicher Gabe und Pulstherapie mit 10mg/kg1xtäglich über 28 Tage und dann alternierend mit und ohne Therapie im wöchentlichen Wechsel) heilt Tiere inner-halb von 56 bis 70 Tage. Niedrig dosiertes Itrakonazol (1,5 bis 3,0 mg/kg) in 15-tägigen Zyklen erfoderte 1 bis 3Zyklen (15 bis 45 Tage). Verschiedene Dosierungen von Terbinafine (5 bis 40mg/kg) wurden zur Behandlungvon Hunden und Katzen eingesetzt. Es war die höhere Dosis von Terbinafine (>20mg/kg) nötig, um eine mykol-ogische Heilung zu erzielen. Die Anzahl an Behandlungstagen variierte von 21 bis >126 Tage. Es wurde gele-gentlich berichtet, dass Lufenuron erfolgreich zur Behandlung eingesetzt wurde, dies konnte durch kontrollierteStudien nicht untermauert werden. Zum Schluss erwiesen sich Pilz-Vakzine als nicht wirksam bei Belastungsex-position, es gibt jedoch Anzeichen, dass sie als Bestandteil von Behandlungsprotokollen nützlich sein könnten.
2004 European Society of Veterinary Dermatology, Veterinary Dermatology, 15, 99 –107
Pediatric Hematology and Oncology , 23:1–7, 2006Copyright C Taylor & Francis Group, LLCISSN: 0888-0018 print / 1521-0669 onlineDOI: 10.1080/08880010600803214 CONCURRENT DEVELOPMENT OF CROHN DISEASE AND MYELODYSPLASTIC SYNDROME IN A CHILD: Case Report and Literature Review Sergio Carlos Nahas, Caio Sergio Rizkallah Nahas, and Carlos Frederico Marques ✷ Colon and Rectum Su