it is an infection caused by various fungal species of trichophyton , epidermophyton , and microsporum genera , together known as dermatophytes belonging to order onygenales .
terbinafine was added to this list of antifungals in the early 1990s and has since then shown good efficacy in widespread tinea infections .
it is the only orally available allylamine antifungal . with a favorable mycological and pharmacokinetic profile ,
terbinafine is considered to be a first - line drug for the treatment of tinea corporis and cruris .
squalene epoxidase is an enzyme responsible for synthesis of ergosterol , an important component of fungal cell membrane .
this ultimately results in fungal cell wall disintegration allowing terbinafine to exert its fungicidal action .
the side effects include gastrointestinal side effects such as nausea , vomiting , and abdominal pain .
the drug has shown consistent efficacy against dermatophytes achieving more than 90% cure rates at a dose of 250 mg / day when administered for 2 weeks . however , recently , we have observed decreased efficacy terbinafine in patients with tinea infections .
this study is aimed at documenting these cases of terbinafine therapy failure in patients of tinea corporis and/or tinea cruris .
we also tried to see the correlation of this resistance with the species involved as well as the percentage of body surface area involved .
the study was carried out in northern part of india during spring and summer season with an average humidity of 70% and an average temperature of 28c .
patients diagnosed to have tinea corporis and/or tinea cruris on clinical examination and involving more than 1% body surface area were taken up for the study .
the diagnosis was made by clinical examination followed by 10% koh smear and culture in all the patients .
only culture positive patients were included in the study and culture negative patients were excluded from the study .
patients who had taken any treatment , had any previous history of intolerance to the drug under study , had any abnormality in the laboratory investigation or who were immune compromised , pregnant or lactating , were excluded from the study .
moreover , patients with a history of tinea infections in family , friends , or close contacts were also excluded from the study .
a total of 100 patients satisfying all the inclusion criteria were included in the study .
culture was performed simultaneously on sabouraud 's dextrose agar ( sda ) medium with chloramphenicol and sda with chloramphenicol and cycloheximide .
all the enrolled patients were put on oral terbinafine 250 mg once daily for 2 weeks . no antacids or antihistamines were prescribed , and the patients were advised to take the medication at bedtime . no topical antifungals or antifungal steroid combination agents were allowed during the study . clinical examination and fungal culture
were repeated at the end of treatment period to document clinical and mycological cure , respectively .
residual pigmentation was present in some cases but was not taken as suggestive of incomplete cure .
patients who had a persistent clinical disease on clinical examination were given alternate oral treatments and were excluded from further analysis .
cases , in whom the disease was seen to be cured clinically , were advised to go for repeat cultures from the initial involved sites only .
in addition , these clinically cured patients were asked to come for follow - up every 2 weeks .
relapse was defined as the appearance of lesions seen clinically and confirmed on culture subsequently .
in this study , a total of 100 culture positive patients of tinea corporis and/or tinea cruris in age group of 1662 years were included in this study .
the disease was found to be more common in males , the male : female ratio being 1.63:1 ( 62 males and 38 females ) .
the majority of patients , i.e. , 63% were in the age group 2030 years .
the most common causative organisms grown on culture were trichophyton rubrum and trichophyton tonsurans [ table 1 ] .
the percentage distribution of various causative organisms involved at the end of oral terbinafine therapy , only 70 cases out of 100 were clinically cured while the rest ( 30/100 ) had signs of persistent infection at the treated site ( persisters ) . on repeat fungal culture ,
five cases out of the seventy clinically cured patients had a positive culture with the same organism that was grown initially .
thus , out of a total of 100 cases enrolled , only 65% could achieve both clinical and mycological cure after 2-week terbinafine therapy ( cured ) . over the 12-week follow - up ,
clinical relapse was seen in 22 of the 65 clinico - mycologically cured patients ( relapse ) .
relapse was confirmed on culture as the repeat cultures grew primary pretreatment isolates in all cases .
thus , at the end of 12 weeks , there were only 43 cases out of the total 100 cases enrolled who were able to maintain a long - term clinical and mycological cure after 2 weeks of oral terbinafine treatment [ table 2 ] .
percentage of causative organisms viz - a - viz the cured , persisters and relapse groups majority of the relapses ( 16/22 ) were seen after 8 weeks of completion of treatment .
this was followed by 3 more cases at the end of 4-week while further 2 , 6 , 3 , and 7 patients relapsed at 6 , 8 , 10 , and 12 weeks , respectively .
the mean percentage body surface area involvement in the cured , persistent , and relapse groups was 3.23  1.2% , 3.65  1.73% , and 3.182  1.46% , respectively .
thus , there was no significant difference in the body surface area involvement when compared with the cured and the persistent disease groups ( mann  whitney u - test , p : 0.3908 ) .
furthermore , there was no significant difference between the cured and the relapse group as far as the body surface area involvement is concerned ( mann  whitney u - test , p : 0.5952 ) .
dermatophytosis , being among the most common dermatologic conditions , does not spare people of any race or age . according to the world health organization , about 20% of the world population are affected by cutaneous dermatophytic infections .
dermatophytes are related fungi capable of causing skin infection of the type known as ringworm or dermatophytosis .
the ringworm species belong to three asexual genera : microsporum , trichophyton , and epidermophyton , which attack the keratinized tissue and cause a wide spectrum of clinical manifestations , of which the most predominant type of infection is tinea corporis followed by tinea cruris , tinea pedis , and onychomycosis .
tinea corporis accounts for about 70% of the dermatophytic infection . in this study , which was limited to cases with tinea corporis and/or tinea cruris we found tinea cruris with corporis was the predominant type seen in 52% of cases followed by tinea corporis only ( 28% ) and tinea cruris only ( 20% ) . in this study ,
. and kumar et al . reported male : female ratio 1.86:1 and 1.36:1 , respectively , in patients with tinea infection .
the predominance of males is usually thought to be a result of increased physical activity and thus increased perspiration .
the patients belonged to the age group of 1462 years , with the mean age being 29.06  10.76 years .
the maximum number of patients , i.e. , 63% was in the age group 2030 years .
in a recent study by surendran et al . from south india , a similar age statistics was seen .
moreover , multiple authors from various parts of india have reported comparable data on age distribution .
tinea corporis and tinea cruris are most commonly caused by trichophyton species of which t. rubrum is most common infectious agent in the world accounting for around 50% of tinea corporis cases . in this study ,
the most common causative organism isolated after culture was t. rubrum , followed by t. tonsurans , trichophyton mentagrophytes , trichophyton verrucosum , and microsporum gypseum in that order . within the genus trichophyton ,
even one study from northeast india reported t. tonsurans as the most common etiological agent in dermatophytosis .
diagnosis of tinea corporis and/or tinea cruris is mostly done clinically . to avoid a misdiagnosis , important for successful treatment , identification of dermatophyte requires both a fungal culture on sabouraud 's agar media and a mycological examination , consisting of a 1015% koh preparation , from skin scrapings . in our patients , koh slide test was positive in 94% of cases .
however , much lower percentages of culture positivity in dermatophytosis have been reported by some authors .
the treatment is based on the infection site , an area involved etiological agent , and penetration ability of the drug .
although topical antifungals may be sufficient for treatment of tinea corporis and/or tinea cruris , lesions which are widespread or fail to respond to topical therapy need systemic therapy . among the several systemic antifungal drugs used to treat dermatophytosis ,
terbinafine 's fungicidal action , combined with its excellent pharmacokinetic properties , makes it an ideal systemic drug for the purpose .
it exhibits its action on fungi by inhibiting the enzyme squalene epoxidase , thus causing an ergosterol deficiency which is important for fungal cell wall integrity .
terbinafine is particularly effective against the species in trichophyton , microsporum , and epidermophyton genera , which in fact are the most common causative agents for tinea infections .
historically griseofulvin was considered the drug of choice for tinea infections for a pretty long time .
however , reports of higher relapse rates with griseofulvin pushed terbinafine to the forefront in treatment of tineacorporis and cruris . over the years
terbinafine slowly gained a first line drug status in the treatment of tinea infections particularly tineacorporis and cruris where clinical and mycological cure rates were reported to be around 90% .
even with an intermittent pulse dose therapy cure rates of around 90% have been reported with terbinafine .
however , these results are in contrast to what we experienced in our patients of tinea cruris and corporis treated with oral terbinafine .
we found a clinical efficacy of only 43% in our patients followed for a 12-week .
such a low clinical efficacy might be a result of the appearance of resistant strains of dermatophytes .
although resistance to terbinafine in dermatophytosis is very uncommon in clinical practice , it has been reported in clinical isolates which result from sequence variation in the gene for squalene epoxidase .
these mutations ultimately decrease the affinity of the terbinafine binding domain resulting in decreased susceptibility to the drug . the low clinical efficacy
as observed in this study could not be attributed to extensive body surface area involvement as there was no statistically significant difference between the cured , persistent and the relapsed cases . again
numerous authors have reported excellent results with oral terbinafine therapy in immunocompromised individuals who interestingly have extensive area involvement .
even 1 week short course oral therapy with terbinafine has shown good results in such individuals with extensive skin area involvement .
however , primary resistance to terbinafine in clinical t. rubrum strains has been reported long back .
thus , we need to seriously consider the appearance of resistance to terbinafine in dermatophytes as an upcoming challenge in dermatological practice .
our results demand further studies to characterize the resistant strains isolated , at a molecular and biochemical level and further test the susceptibility to various antifungals so that an alternate treatment could be proposed .
the main limitation of the study was the absence of calculation of mic in cases with failed cure and relapse .
incomplete cure is very common after a 2-week course of oral terbinafine therapy and recommendations about the daily dose and duration of oral therapy need to be changed and updated accordingly .
this article highlights the presence of resistance to terbinafine in our cases of tinea infections .
this article makes the dermatologists aware of the growing resistance to terbinafine and stimulates further microbiological studies in this respect .
this article highlights the presence of resistance to terbinafine in our cases of tinea infections .
this article makes the dermatologists aware of the growing resistance to terbinafine and stimulates further microbiological studies in this respect .
this article highlights the presence of resistance to terbinafine in our cases of tinea infections .
this article makes the dermatologists aware of the growing resistance to terbinafine and stimulates further microbiological studies in this respect .
 background : the incidence of recurrent tinea infections after oral terbinafine therapy is on the rise.aim:this study aims to identify the appearance of incomplete cure and relapse after 2-week oral terbinafine therapy in tinea corporis and/or tinea cruris.materials and methods : a total of 100 consecutive patients clinically and mycologically diagnosed to have tinea corporis and/or tinea cruris were included in the study . 
 the enrolled patients were administered oral terbinafine 250 mg once daily for 2 weeks . 
 all clinically cured patients were then followed up for 12 weeks to look for any relapse / cure.results : the common dermatophytes grown on culture were trichophyton rubrum and trichophyton tonsurans in 55% and 20% patients , respectively . at the end of 2-week oral terbinafine therapy , 
 30% patients showed a persistent disease on clinical examination while 35% patients showed a persistent positive fungal culture ( persisters ) at this time . 
 these culture positive patients included all the clinically positive cases . 
 rest of the patients ( 65/100 ) demonstrated both clinical and mycological cure at this time ( cured ) . over the 12-week follow - up , 
 clinical relapse was seen in 22 more patients ( relapse ) among those who had shown clinical and mycological cure at the end of terbinafine therapy . 
 thus , only 43% patients could achieve a long - term clinical and mycological cure after 2 weeks of oral terbinafine treatment . 
 majority of the relapses ( 16/22 ) were seen after 8 weeks of completion of treatment . 
 there was no statistically significant difference in the body surface area involvement or the causative organism involved between the cured , persister , or relapse groups.conclusions:incomplete mycological cure as well as relapse is very common after standard ( 2-week ) terbinafine therapy in our patients of tinea cruris / corporis . 