‘End of the road for terbinafine’ in dermatophytosis: Is it a valid conclusion?

Rajsmita Bhattacharjee, Sunil Dogra

 Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Correspondence Address:
Sunil Dogra
Department of Dermatology, Venereology, and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
India

Sir,

We read with keen interest the article by Singh and Shukla on the effectiveness of terbinafine in dermatophytosis, and wish to draw attention to some points.^[1] There is no doubt that dermatophytosis has progressed from being an innocuous, easily treatable infection to one that is rapidly assuming gigantic proportions in India, with chronicity and multiple recurrences, although these terms have been only recently defined.^[2] Drugs such as terbinafine that were uniformly effective in treating dermatophytosis earlier are now seldom proving so in the duration conventionally considered to be sufficient. However, to conclude regarding a mainstay agent as abysmally ineffective would require consideration of some pertinent issues.

In this prospective cohort study, 500 patients of dermatophytosis were included and treated with oral terbinafine (5 mg/kg/day) for a maximum duration of 4 weeks. The number of patients following up at the end of 2 and 4 weeks were 357 and 362 and the cure rates at these time points were found to be 2 and 30.6%, respectively. Out of 500 patients, 42% had applied topical corticosteroids in the recent past, either alone or in combination creams as over-the-counter topical preparations.^[1] It is well known that the unregulated availability and use of such irrational corticosteroid–antifungal–antibacterial combinations causes a reduction in the local cellular immunity, thereby playing an important role in making the dermatophytosis notoriously recalcitrant.^[3] In such a scenario, to confer the recalcitrance to merely lack of effectiveness of a hitherto effective drug, such as terbinafine, would seem as jumping the gun a little too soon; more so because the use of terbinafine in this study has not been compared with any other standard drug such as itraconazole in a parallel arm. In this study, of the total patients enrolled, 243 (48.6%) had already taken some form of oral and/or topical treatment and hence were not treatment-naïve cases. There is also a marked difference in the cure rates of dermatophytosis in this study at the end of 2 and 4 weeks from 2 to 30.6%. Hence, the use of terbinafine for a duration of 4 weeks is perhaps not adequate to determine its effectiveness in causing cure, and treatment longer than 4 weeks would have perhaps improved the cure rates much further. This seems particularly relevant in today's scenario where the conventional regimens of mainstream drugs such as terbinafine and azoles no longer seem effective in the durations prescribed in standard textbooks. In this regard, it is also useful to remember that it has been recommended that minimum duration of treatment should be 2–4 weeks in naïve cases and >4 weeks in recalcitrant cases.^[2] The calculation of cure rates at the end of 4 weeks also seems fallacious (153 cured out of 362, giving a cure rate of 42.3% instead of 30.6% as mentioned in the article).

Two additional factors that do not seem to have been considered are the possibility of reinfection, because the family members were not screened; and information regarding demographic and socioeconomic variables and advice regarding hygiene were not provided. These, in all probability, could have played a role in determining the cure of infection with terbinafine. Recurrences may have been owing to reinfection from family members or the environment, or the duration of antifungal therapy given may be inadequate, as was the likely case in the index study. In a study on 150 patients of dermatophytosis from North India, the authors found high minimum inhibitory concentration (>2 μg/ml) for terbinafine in one Trichophyton interdigitale, four Trichophyton mentagrophytes and three Trichophyton rubrum isolates.^[4] They concluded that increase in minimum inhibitory concentration is not the only factor responsible for recurrence and most of the strains were not drug-resistant, thereby further consolidating our point that the dismal cure rate of terbinafine may not be explained by its effectiveness alone.

Hence, we conclude that further well-designed studies comparing the effectiveness of terbinafine with other standard drugs, such as itraconazole, should be conducted before concluding that it is the end of the road for terbinafine.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

1.	Singh S, Shukla P. End of the road for terbinafine? Results of a pragmatic prospective cohort study of 500 patients. Indian J Dermatol Venereol Leprol 2018;84:554-7. [Google Scholar]
2.	Rajagopalan M, Inamadar A, Mittal A, Miskeen AK, Srinivas CR, Sardana K, et al. Expert consensus on the management of dermatophytosis in India (ECTODERM India). BMC Dermatol 2018;18:6. [Google Scholar]
3.	Verma SB, Vasani R. Male genital dermatophytosis – Clinical features and the effects of the misuse of topical steroids and steroid combinations – An alarming problem in India. Mycoses 2016;59:606-14. [Google Scholar]
4.	Pathania S, Rudramurthy SM, Narang T, Saikia UN, Dogra S. A prospective study of the epidemiological and clinical patterns of recurrent dermatophytosis at a tertiary care hospital in India. Indian J Dermatol Venereol Leprol 2018 July (Epub ahead of print). [Google Scholar]