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Topical antifungals for Tinea infections: What should be prescribed?: Prof. Dr. D.G. Saple

M3 India Newsdesk Oct 13, 2020

Superficial fungal infections caused by dermatophytes and yeasts can be successfully and safely treated with topical antifungal agents with proper counselling and guidance. In the next part of our Dermatophytosis series, Dr. DG Saple writes on topical agents that can be used for their antifungal action as well as for their anti-inflammatory properties.


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Practice pearls

  1. Tinea corporis and cruris infections are usually treated for two weeks, while Tinea pedis is treated for four weeks with an azole or for one to two weeks with allylamine medication.
  2. Treatment should continue for at least 2 weeks after clinical clearing of infection.
  3. The presence of inflammation may require the use of an agent with inherent anti-inflammatory properties or the use of a combination antifungal/steroid agent.
  4. The latter agents should be used with caution because of their potential for causing atrophy and other steroid-associated complications.

Indications for topical treatment

  • Localised disease of Glabrous skin
  • Infection in pregnant women
  • Infection in children
  • Infection in patients with serious systemic disease
  • Infection in patients with potential for interactions of oral antifungals

Advantages of topical antifungals

  • Absence of systemic side effects and complications due to limited systemic absorption
  • Reduce chances of drug interaction
  • Easy to use
  • Benefit of anti-inflamatory activity
  • Relatively low cost

Disadvantages of topical antifungals

  • Cannot be used for extensive lesions
  • Poor efficacy in onychomycosis

Instructions for application of topical antifungals

  1. Patients should be explained to apply the formulation one inch beyond the margin, twice a day for atleast 6 weeks.
  2. Choice of formulation should be according to the site involved:
    1. Lotions for hairy areas, intertriginous areas, eczematised lesions
    2. Creams for scaly lesions and glabrous skin
    3. Ointments for keratotic lesions
    4. Gels for the face
    5. Nail lacquer for onychomycosis
    6. Shampoo-based formulation for Tinea capitis

Treatment

Most Tinea corporis, cruris, and pedis infections can be treated with topical agents. Systemic treatment should be considered when lesions are covering a large body-surface area and fail to clear with repeated treatment using different topical agents. While treating dermatophytosis, the physician must also address environmental factors that lead to or exacerbate tinea infection and select an appropriate topical therapy for the infection.

The previous guidelines for treatment in western literature have lost their relevance with context to the current scenario. Thus, in today’s times, the management of tinea needs to be experience based.


Non-pharmacologic measures

Since tinea thrives in moist, warm environments, patients should be encouraged to wear loose-fitting garments made of cotton or synthetic materials designed to wick moisture away from the surface. Socks should have similar properties. Areas likely to become infected should be dried completely before being covered with clothes. Patients should also be advised to avoid walking barefoot and sharing garments.


Non-specific agents

A plethora of traditional agents without specific antimicrobial function are available for use, including Whitfield's ointment and Castellani's (carbolfuchsin solution) paint. The efficacy of these preparations has not been very well quantified and assessed.


Antifungal agents

The antifungal agents can be classified by structure and mechanism of action (table 1). The two main pharmacologic groups are the azoles and the allylamines.

Table 1: Classification of antifungals

Antifungal class Examples

Antibiotics

Polyenes

Amphotericin B (0.1% liposomal Cream)

Azoles

Imidazoles

Clotrimazole 1% cream/lotion

Ketoconazole 2% cream/gel/lotion

Econazole 1% cream

Miconazole 2% cream

Bifonazole 1 % cream

Oxiconazole 1% cream/lotion

Tioconazole 1% cream

Sertaconazole 2% cream

Luliconazole 1%cream

Eberconazole 1% cream

Fenticonazole 2% cream

Fluconazole 0.5% gel

Efinaconazole 10 % nail solution

Allylamines

Terbinafine 1%cream

Naftifine 1% cream
Benzylamines Butenafine 1% cream
Morpholines Amorolfine 5% nail lacquer/0.25% cream
Hydroxypridines Ciclopirox 8% nail lacquer/1% cream
Others

Tolnaftate 1% cream

Oxaboroles Tavaborole 5%
Non-specific agents Whitfields ointment/Castellani’s paint


The advantages of topical antifungals include – lack of systemic side effects and complications due to limited systemic absorption, very low incidence of drug interactions, ease of use, comparatively low cost of therapy, additional benefit of anti-inflammatory activity of several topical antifungals including azoles and allylamines.

When treating a tinea infection, it is unlikely that the dermatologist will be aware of the infecting species. Traditionally, Tinea corporis and Tinea cruris require twice-daily application for two weeks. Tinea pedis may require treatment for four weeks. However, all these gudelines are now being revisited and a duration of atleast 6 to 8 weeks is recommended. Treatment should continue for at least 2 weeks after symptoms have resolved.

The application area should include normal skin about 2 cm beyond the affected area. Ideally, an agent will provide clinical and mycologic cure, symptomatic relief, and low relapse rate, along with ease of use. In addition to specific anti-fungal properties, some preparations have antibacterial and anti-inflammatory properties that may influence their efficacy. Combination therapy (antifungal plus steroid) can be considered when inflammation is an issue. Combination agents should not be used when the diagnosis is in question because that may lead to their overuse or to adverse effects.

Some of the common antifungals used recently, include the following:

Luliconazole: It acts by inhibiting fungal ergosterol biosynthesis by inhibiting cytochrome P450 enzyme. It exhibits potent antifungal activity- against Trichophyton spp., Candida albicans, and Aspergillus fumigatus. It has the lowest MIC among a wide variety of drugs tested, including terbinafine, ketoconazole, clotrimazole, miconazole, bifonazole, and sertaconazole. Low binding affinity for keratin allows luliconazole to be released from the keratinous nail plate and be transported across the nail bed. In contrast with many other azoles, its potency remains unaffected by keratin.

  • Indications: Topical treatment of interdigital Tinea pedis, Tinea cruris,Tinea corporis
  • Off label indication: Onychomycosis

Luliconazole has strong fungicidal activity against Trichophyton spp., similar to that seen with terbinafine. Evidence from clinical trials, study done by Michael Gold et al, in Tinea pedis have shown once-daily application of luliconazole cream 1% for 14 days to be effective and well tolerated.

Ciclopirox: It is a broad-spectrum antifungal medication which also has antibacterial and anti-inflammatory properties. Its main mode of action is attributed to its high affinity for trivalent cations, which inhibit essential co-factors in enzymes. It appears to modify the plasma membrane of fungi, resulting in the disorganisation of internal structures. It exhibits either fungistatic or fungicidal activity in vitro against a broad spectrum of fungal organisms, such as dermatophytes, yeasts, dimorphic fungi, eumycetes, and actinomycetes. In addition, it also exerts antibacterial activity against many gram-positive and gram-negative bacteria. It also has anti-inflammatory effect by inhibiting the synthesis of prostaglandin and leukotriene. The most frequently reported adverse effect was skin-burning sensation on application, which subsided after sometime.

In a study by Gupta AK, Ciclopirox as 1% cream was shown to have an excellent anti-inflammatory and anti-bacterial effect apart from anti-fungal effect.


Recalcitrant cutaneous mycoses is a major epidemic across all South Asian countries. Nuisance of widespread failure of antifungal pharmacotherapy has become an ordeal. Treatment requires attention to exacerbating factors such as skin moisture and choosing an appropriate antifungal agent. Topical therapy is generally successful unless the infection covers an extensive area or patient has poor compliance. In these cases, systemic therapy may be required.


Click here to see references

This article is part of an exclusive series on Dermatophytosis by Dr. DG Saple. Click on the following links to read other articles in the series.

Emerging recalcitrant dermatophytosis in India

Diagnosis of Dermatophytosis- Dr. DG Saple

Resistance in Dermatophytosis- Dr. DG Saple

Tinea cruris & corporis: Current approach and management

 

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author, Dr. DG Saple is a Senior Consultant and Director of Dermatology at a Mumbai-based clinic.

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