Ever since the introduction of griseofulvin as a specific treatment for dermatophytosis (ringworm), there have been reports of nonresponding to antifungal drugs in a patient subset. However, this may be due to underlying disease affecting immunity or inaccessible location for drug penetration in some patients, who do not respond to therapy or relapse rapidly afterward. 

Investigators have confirmed the presence of increased minimum inhibitory concentrations to griseofulvin in dermatophytes isolated from these cases, indicating drug resistance. Fortunately, oral azole antifungals, such as ketoconazole, emerged as a solution to this problem. Yet, before long, therapeutic failure and in vitro resistance occurred with azoles used to treat these infections. Azoles act differently from griseofulvin. They inhibit the α-demethylase enzyme in the fungal cell membrane, thereby blocking the biosynthesis of ergosterol biosynthesis.

Until recently, there have also been reports describing the development of resistance to terbinafine, thus causing a recent and progressive increase in cases of widespread and treatment-unresponsive tinea corporis/cruris.

Resistance cases started as a sporadic nuisance, with the odd case of tinea corporis/cruris not responding to antifungals, but this is now evolving into a global public health crisis. This situation is raising many questions like what is the relationship, if any, between the old cases and the new emerging strains in India with evidence of resistance to terbinafine and, in some instances, azoles? Where did the new epidemic arise, and how far has it spread globally? What can be the treatment options? 

Evidence suggests overexpression of a transmembrane drug transporter, TruMDR3, in some cases of azole resistance dermatophytes. And these effects can be countered by milbemycins, a drug family used in veterinary medicine as antiparasitics. Some research has also identified a mutation in the squalene epoxidase gene itself rather than a defect in transmembrane drug transport. 

These new issues, like the transcontinental spread of resistant infections, the different resistance mechanisms, and the emergence of a new dermatophyte strain, need urgent investigations.

Source: Hay RJ. The spread of resistant tinea and the ingredients of a perfect storm. Dermatology. 2022;238(1):80-1.