A Pilot Study to Assess The Therapeutic Effectiveness Of Isotretinoin In Preventing Recurrences In Chronic Recurrent Dermatophytosis

Over the last couple of years, the major concern in dermatophytic infections has been the occurrence of recurrent infections. This, in spite of the patients being treated with gold standard drugs, namely, terbinafine, griseofulvin, and even azoles like itraconazole, in adequate doses. The world is experiencing a menace of recurrent and chronic dermatophyte infections in a magnitude that is unprecedented. Such cases are making up a large proportion of cases seen every day in the outpatient department. To make matters worse, there is as yet, no standard definition of the terms 'çhronic', 'recurrent', or 'resistant' tinea infections, although arbitrary definitions exist, like 'chronic dermatophytosis' being described in lay terms as "patients who have suffered from the disease for more than 6 months to 1 year duration, with or without recurrence, in spite of being treated", and recurrent dermatophytosis being defined as the reoccurrence of the dermatophyte infection within few weeks, after completion of treatment.

Alteration of immune pattern in dermatophytosis The development of antibodies (IgM, IgG, IgA and IgE) to dermatophyte infection seems not to substantially contribute to the elimination of fungal infections because highest antibody levels can be found in patients with chronic fungal infections. Studies by Jones in human volunteers suggested that cell-mediated immunity is the major immunologic defence mechanism in dermatophyte infection.Healthy volunteers infected with T. Mentagrophytes developed cell-mediated immunity resulting in mycologic cure. This was associated with intense inflammation due to T-cell mediated DTH, judging from the trichophytin skin test. A protective immunologic memory was indicated by elimination of T. mentagrophytes on re-inoculation and a continued positive trichophytin test. Impaired cell-mediated immunity in atopic persons is also believed to be the underlying mechanism for an increased susceptibility to T rubrum infections. Patients with allergic bronchial asthma or allergic rhinitis often develop chronic or recurrent fungal infections associated with high immediate-type hypersensitivity (high IgE levels) and low or waning DTH to trichophytin.

Green et al. showed that athymic rats that lack T-cell-mediated immunity could not clear T. mentagrophytes infection in contrast to their genetically matched euthymic control rats.

Chronic dermatophytosis is associated with a depression in cell-mediated immunity to dermatophytes. A selective antigen-specific immunodeficiency may be the underlying factor in such patients, and the continued presence of infecting dermatophytes or residual fungal elements may induce a tolerant state by flooding the host with antigenic material, resulting in a selective loss of cell-mediated immunity. Alternatively, fungal elements may interact with host skin to alter the cytokine milieu such that effective type I immune responses for eliminating organisms are suppressed. In a study done to evaluate immune response in T rubrum onychomycosis and to determine whether immune reactivity or nonreactivity can be a predictor of therapeutic outcome, a double-blind comparison was done of the effects of terbinafine with placebo tablets. Skin tests were performed using trichophytin antigen injected intradermally in the upper left arm. It was found that skin reactivity to trichophytin antigen decreases with increasing disease chronicity. Patients with longstanding disease demonstrated absent or significantly blunted skin reaction to trichophytin antigen compared with patients who had disease for less than 5 years. Patients who were reactive at baseline were the first to become mycologically negative in response to terbinafine treatment, and increases in skin reactivity were related to conversion to negative mycology. Subjects anergic at baseline who converted with treatment had a more favorable outcome overall than persistent nonconverters. It is already known that terbinafine and azoles eliminate the fungal elements and restore cellular immunity resulting in eradication of the oragnisms and cure of the infection. In our study, we plan to analyse if low dose oral isotretinoin has any role to play in the maintenance of the cure achieved by itraconazole by decreasing the number of relapses and whether it leads to an alteration of skin reactivity to trichophytin. If indeed we observe that isotretinoin does, in fact, reduce the number of relapses, it would be interesting to know if there is an immunological basis for this, given that isotretinoin is known to be an immunomodulator.

Probable antifungal Resistance Mechanisms in Dermatophytes In vivo, anti fungal resistance is also correlated with antifungal misuse because patients often fail to finish the full course of treatment. Thus, the inadequate use or dosage of drugs contributes to the failure in eliminating the disease agent completely, encouraging growth of the most resistant strains, which may lead to hard-to-treat fungal infections.