Abstract

Dermatophytosis has been increasingly recognized in children. Various topical antifungal agents are available for the treatment of localized tinea corporis – dermatophytosis of the body. Some areas of the body are more susceptible to fungal infections. The pathogenesis of dermatophyte infections involves complex interaction between the host, agent and the environment. Low immune status is one of the most common contributors.

M. praecox is a geophilic dermatophyte – morphologically resembling M. gypseum. Horses are often the source of infection; in humans, M. praecox can cause tinea corporis and tinea capitis. Topical ciclopirox olamine (CPO) has been found to be effective in ameliorating tinea corporis lesions due to M. praecox. It can be used as an adjunct to oral antifungal drugs to treat tinea corporis in adults and children and to prevent its recurrence.

This case study reports itchiness of the right lower arm in a 10-year-old girl. On examination, erythematosquamous and centrifugal growing, sparse itching lesions were observed over her right lower arm. Fluorescence optical preparation from skin scrapings revealed fungal hyphae suggesting tinea corporis. Sabourauds dextrose agar culture rendered fast growing dermatophyte forming flat, peripheral radiating and convolved colonies with white, slightly yellowish to beige brown stained granular and powdery surface. The dermatophyte species M. praecox, was confirmed via sequencing analysis of the ribosomal ITS-region (18 S rRNA, ITS1, 5.8 S rRNA, ITS2, 28 S rRNA) and of the translation elongation factor 1 alpha (tef-1-alpha) gene. The child was successfully treated with topical application of CPO cream along with oral terbinafine therapy. This treatment attenuated her symptoms; continued use of CPO helped in the prevention of recurrence of the lesions.

Introduction

Fungal infection of the nails has been increasingly recognized disease in infants and children. Trichophyton rubrum is among the most common isolate with tinea corporis and cruris in India. Various topical antifungal agents are available for the treatment of localized tinea corporis – dermatophytosis of the body.

The pathogenesis of dermatophyte infection involves complex interaction between the host, agent and the environment—the contributing factors being underlying diseases such as diabetes mellitus, lymphomas, immunocompromised status, Cushings syndrome and older age. Some areas of the body are more susceptible to the development of dermatophyte infections such as intertriginous areas – web spaces and groins, where excess sweating, maceration and alkaline pH favor the growth of the fungus. After inoculation into the host skin, the infection may adhere through penetration mediated by proteases, serine-subtilisins and fungolysin.

M. praecox is a geophilic dermatophyte – morphologically resembling M. gypseum. Horses are often the source of infection; in humans, M. praecox can cause tinea corporis and tinea capitis. For oral treatment of dermatomycosis due to M. praecox, griseofulvin and terbinafine can be used.¹ Topical CPO has been found to be effective in ameliorating tinea corporis lesions due to M. praecox. It can be used as an adjunct to oral antifungal drugs to treat tinea corporis in adults and children and to prevent its recurrence.

CPO is a hydroxypyridone derivative that differs in structure and mechanism of action from the other known antifungal agents – like azoles and allylamines. The molecule exists in its free acid form known as ciclopirox and in its salt form as CPO. Its 1% formulation is equivalent to 0.77% ciclopirox, which remains the active compound with no additional antifungal contribution by the olamine group. It is a broad-spectrum antifungal agent with additional antibacterial and anti-inflammatory properties.

CPO acts through the chelation of polyvalent metal cations, such as ferric (Fe3+) and aluminum (Al3+), thereby causing inhibition of metal-dependent enzymes – cytochromes, catalase and peroxidase, leading to disruption of cellular activities such as mitochondrial electron transport processes, energy production and nutrient intake across cell membrane. Furthermore, it alters membrane permeability causing blockage of intracellular transport of precursors.²

Case Report

A 10-year-old girl complained of itching over her right lower arm.

Physical examination disclosed erythematosquamous and centrifugal growing, sparse itching lesions on her right lower arm.

Fluorescence optical preparation from skin scrapings revealed fungal hyphae suggesting tinea corporis. Sabourauds dextrose agar culture rendered fast growing dermatophyte forming flat, peripheral radiating and convolved colonies with white, slightly yellowish to beige brown stained granular and powdery surface. The reverse side of the colonies was smooth with luminous yellow color.

Direct uniplex-PCR-EIA of the strains showed negative results for T. rubrum, T. interdigitale, T. anamorph of Arthroderma benhamiae and M. canis. Sequencing analysis of the ribosomal ITS-region (18 S rRNA, ITS1, 5.8 S rRNA, ITS2, 28 S rRNA) and of the translation elongation factor 1 alpha (tef-1-alpha) gene confirmed the dermatophyte species M. praecox.

The girl was successfully treated with topical application of CPO cream along with oral terbinafine therapy. This treatment attenuated her symptoms; continued use of CPO helped in the prevention of recurrence of the lesions.

Discussion

CPO is also available as a topical cream formulation, as well as a nail lacquer formulation—used for the treatment of onychomycosis. The pleiotropic effects and certain unique properties of CPO make it an effective topical antifungal. A phase III study on the use of 1% CPO cream in the pediatric population reported excellent safety profile in 95% of the children enrolled. Interestingly, 92% cases showed clinical improvement within a week of application. Therefore, CPO cream is a safe and feasible treatment option for superficial cutaneous mycotic infections, especially Candida spp. infection, in children aged between 3 months and 10 years.³

Local adverse events reported are minor and have rarely led to discontinuation of therapy or an allergic contact dermatitis. CPO compares very well with oral antimycotic agents in terms of the benefit/risk ratio because of its excellent tolerability and complete absence of serious adverse effects. It is a pregnancy category B drug and safe to use in patients over 10 years of age.²

Conclusion

CPO cream is effective in the treatment of tinea corporis and can be deemed as an ideal choice in the management of recurrent lesions in children. This agent can be used along with oral antifungals and is safe and well tolerated in adults and children.

The advantages of CPO include – unique mechanism of action; in vitro and in vivo efficacy; broad-spectrum antimycotic coverage; anti-bacterial and anti-inflammatory activity; well-established safety and excellent tolerance; lack of drug resistance and an extremely low likelihood of the development of resistance in future; and cost-effectiveness. Hence, CPO cream is considered as an ideal topical antifungal for superficial cutaneous mycoses.

CPO has shown efficacy against recalcitrant superficial fungal infections. This agent can be instrumental in reducing steroid-abuse and can be used as the drug of choice in the management of treatment-refractory dermatophytic infections, tinea incognito, mixed infections and recurrent VVC.

References

1. Sahoo AK, Mahajan R. Management of tinea corporis, tinea cruris, and tinea pedis: A comprehensive review. Indian Dermatol Online J. 2016;7(2):77-86. doi:10.4103/2229-5178.178099
2. Sonthalia S, Agrawal M, Sehgal VN. Topical Ciclopirox Olamine 1%: Revisiting a Unique Antifungal. Indian Dermatol Online J. 2019;10(4):481-485. doi:10.4103/idoj.IDOJ_29_19
3. Gómez-Moyano E, Hiraldo Gamero A, Vera Casaño Á, et al. Estudio fase III de la seguridad y la eficacia de ciclopirox olamina crema en niños afectados de dermatomicosis [Phase III study of the efficacy and safety of ciclopirox olamine cream in small children with dermatomycosis]. Rev Iberoam Micol. 2015;32(3):164-169. doi:10.1016/j.riam.2014.04.002