Abstract

An elderly woman presented with a generalized, diffuse and progressive skin rash. These lesions had first appeared about of six-month back and were accompanied by itching at the site of the lesion, along with pain and burning sensation—which worsened with sweating. 

Use of a topical cream comprising clotrimazole 1% and betamethasone dipropionate 0.05% for several months rendered no improvement; the progression of the skin lesions could not be curtailed.

A detailed clinical history and lesion morphology and pathology findings led to a definitive diagnosis of tinea corporis. The patient was successfully treated with antifungal therapy – topical ciclopirox olamine cream 1% cream twice daily and systemic terbinafine 250 mg daily, for four weeks. This treatment helped in resolving her symptoms suppressed progression.

Introduction

Tinea corporis or ‘ringworm,’ is a superficial dermatophyte infection of the skin. It is most commonly caused by – Trichophyton rubrum, T. tonsurans and Microsporum canis. Other causative organisms include – T. interdigitale (or T. mentagrophytes), T. verrucosum, T. violaceum, T. concentricum, Epidermophyton floccosum, M. audouinii and M. gypseum.

The infection manifests as a well-demarcated, sharply circumscribed, oval or circular, mildly erythematous, scaly patch or plaque with a raised leading edge. The lesion starts off as a flat scaly spot that spreads centrifugally and clears centrally to form a characteristic annular ‘ring-shaped’ lesion. The central area becomes hypopigmented or brown and less scaly as the active border progresses outward. Occasionally, the border can be papular, vesicular, or pustular or the lesions may assume other shapes such as circinate and arcuate. Symptoms include – mild pruritus, and when multiple lesions are present, they may coalesce into polycyclic patterns. These lesions usually appear on is the trunk and are more common in children and adolescents.¹

Case Report

A 61-year-old woman complained of a generalized, diffuse skin rash of six-month duration. Her symptoms included itching at the site of the lesion, along with pain and burning sensation—which worsened with sweating. 

The lady reported that the rash had begun as a single lesion that continued to enlarge. Subsequently, new lesions appeared on her chest and axilla. She was initially prescribed a topical cream that consisted of an antifungal (clotrimazole 1%) and a high-potency corticosteroid (betamethasone dipropionate 0.05%), to be applied twice a day for several months. However, there was no improvement—the skin lesions continued to increase in size and number. 

The patient had Fitzpatrick skin type IV. On cutaneous examination, several large patches with raised scaly borders could be seen—which extended from the left axilla to left chest and left lower abdomen. The lesions spanned from her mid flank to her mid chest and umbilicus. The central portions of the lesions were flat and hyperpigmented – consistent with post-inflammatory hyperpigmentation.

Examination of a punch biopsy at the edge of her skin lesion revealed hyperkeratosis consisting of both, orthokeratosis and focal parakeratosis, acanthosis and spongiosis. Subepidermal oedema and superficial perivascular infiltration of lymphocytes were present in the dermis, without an evidence of a lymphoproliferative disorder.

In the differential diagnosis, gyrate erythema – such as erythema annulare centrifugum, mycosis fungoides – a variant of cutaneous T-cell lymphoma and tinea incognito – tinea corporis previously treated with corticosteroid, were considered.

Correlation of the clinical history, lesion morphology and pathology findings established a definitive diagnosis of tinea corporis. The patient was treated with antifungal therapy – topical ciclopirox olamine cream 1% cream twice daily and systemic terbinafine 250 mg daily. After four weeks of continued treatment, her symptoms resolved and the lesions stopped enlarging.

On follow-up after six-weeks, there was no itchiness or burning sensation. Residual faint macular brown areas could be observed at the site of the lesions – consistent with post-inflammatory hyperpigmentation. 

Discussion

The diagnosis of tinea corporis is usually clinical and the evaluation involves a detailed history ad thorough examination of the skin. Other mimicking skin conditions like tinea incognito must be ruled out before a definitive diagnosis is arrived upon. Tinea incognito is also a cutaneous fungal infection, wherein the lesions lose their classical morphological features because of the use of calcineurin inhibitors or corticosteroids. Compared to tinea corporis, lesions seen in tinea incognito are less erythematous and scaly, with a less defined border and is typically more widespread. Pruritus is usually mild or absent; the rash can be eczema-like, rosacea-like or discoid lupus erythematosus-like – especially on the face, and eczema-like or impetigo-like – on the trunk and limbs.¹

Ciclopirox olamine (CPO) 1% cream has demonstrated efficacy in treating tinea corporis/cruris with respect to the mycological and overall response rates. CPO is an effective antimycotic with broad-spectrum activity against dermatophytes, yeast and filamentous fungi. The drug has been approved by the US FDA for topical applications such as dandruff, seborrheic dermatitis and onychomycosis.²

CPO is the ethanolamine salt of ciclopirox; the therapeutic effect of 1% ciclopirox olamine cream is equivalent to that of 0.77% ciclopirox as the ethanolamine part of this agent does not add to the antifungal effect. This agent has a very broad spectrum of antifungal activity and inhibits nearly all clinically relevant dermatophytes, yeasts and molds, including the azole-resistant Candida species – Candida glabrata, Candida krusei, and Candida guilliermondii. Additionally, it can act against an array of bacterial pathogens—including many gram-positive and gram-negative species.³

Ciclopirox olamine has a unique mechanism of action compared to the commonly used allylamines and azoles. CPO is a hydroxypyridone derivative, which differs in structure and mechanism of action from the other known antifungal agents. Hydroxypyridones are the class of topical antifungal agents that have a completely different mechanism of action than other topical antifungals – azoles and allylamines. Ciclopirox – the active compound, acts as a broad-spectrum antifungal, with additional antibacterial and anti-inflammatory properties. It acts through the chelation of polyvalent metal cations, such as ferric (Fe³⁺⁾ and aluminum (Al³⁺). This leads to the inhibition of metal-dependent enzymes – cytochromes, catalase and peroxidase, leading to the disruption of cellular activities like mitochondrial electron transport processes, energy production and nutrient intake across cell membrane. This class of drugs can also alter membrane permeability resulting in the blockage of intracellular transport of precursors.

Its combined antifungal and antibacterial activity are of particular advantage in the treatment of macerated tinea pedis and “dermatophytosis complex,” – symptomatic intertriginous fungal affections secondarily infected by bacteria. The drug is available as a topical cream topical; its nail lacquer formulation is also used in for treating onychomycosis, tinea pedis, tinea corporis/cruris, pityriasis versicolor, seborrheic dermatitis, as well as vuvovaginal candidiasis (VVC).

CPO agent could aid in encountering the emerging antifungal resistance. Even after more than two decades of frequent use of ciclopirox for tinea, PV and VVC – clinical or in vivo resistance is yet to be reported. Dermatophytes exhibit extremely low potential for developing resistance to ciclopirox, both by biochemical or molecular means. The most accepted explanation behind the inability of superficial fungi (both dermatophytes and yeasts) of mounting or evolving mechanisms to resist this drug are its fungicidal mode of action, unique anti-fungal mechanism and a steep dose-response curve.⁴

Conclusion

Ciclopirox olamine 1% cream has wide-spectrum antifungal effect and has been successfully used for treating dermatophytic infections, as well as candidiasis. CPO also offres antibacterial properties. This agent is safe for use in children, adults and the elderly and its use reduces the chances of antimicrobial resistance. CPO is well-tolerated on long-term usage and can be used as an adjunct to oral antifungal agents like terbinafine, for treating superficial skin infections, such as tinea cruris or tinea cruris.

This case reports a generalized, diffuse and progressive skin rash in a 61-year-old lady. Her lesions had first appeared about of six-month back and were described as being itchy, painful and with burning sensation—which exacerbated on sweating. The woman was initially given a topical cream comprising clotrimazole 1% and betamethasone dipropionate 0.05% for several months, with no improvement. Lesion morphology and pathology findings aided in the definitive diagnosis of tinea corporis. She was prescribed topical ciclopirox olamine cream 1% cream twice daily and oral terbinafine 250 mg daily, to be used for four weeks. This therapy attenuated her symptoms and prevented progression of the lesions. On the six-week follow up, only residual faint macular brown areas – consistent with post-inflammatory hyperpigmentation, could be detected.

References

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2. Bernier KM, Morrison LA. Antifungal drug ciclopirox olamine reduces HSV-1 replication and disease in mice. Antiviral Res. 2018;156:102-106. doi:10.1016/j.antiviral.2018.06.010
3. Niewerth M, Kunze D, Seibold M, Schaller M, Korting HC, Hube B. Ciclopirox olamine treatment affects the expression pattern of Candida albicans genes encoding virulence factors, iron metabolism proteins, and drug resistance factors. Antimicrob Agents Chemother. 2003;47(6):1805-1817. doi:10.1128/aac.47.6.1805-1817.2003
4. Sonthalia S, Agrawal M, Sehgal V. Topical ciclopirox olamine 1%: Revisiting a unique antifungal. Indian Dermatol Online J. 2019;10(4):481. doi:10.4103/idoj.idoj_29_19