Acitretin: Could it be a new therapeutic player in the field of onychomycosis?

Abstract

Onychomycosis is a chronic fungal infection of the nail, characterised by nail discoloration, subungual hyperkeratosis and onycholysis.The involved pathogens are dermatophytes, yeasts (Candida spp.) and non-dermatophyte moulds (NDMs). 1 Dermatophytes such as Trichophyton rubrum and Trichophyton mentagrophytes are the most common agents of onychomycosis, with higher prevalence of the infection in toenails than in fingernails. Candida albicans affects almost exclusively the fingernails and accounts for 10% of toenail onychomycosis. 2,3 Onychomycosis represents a therapeutic challenge because of the high recurrence rate. Moreover, it requires long treatment duration and systemic rather than topical antifungal agent because onychomycosis-related subungual hyperkeratosis limits the penetration with topical antifungal drugs, in addition to the slow nail growth,

Combination Therapy Should Be Reserved as Second-Line Treatment of Onychomycosis: A Systematic Review of Onychomycosis Clinical Trials

“…By preventing hyphal germination necessary for biofilm formation, all-trans retinoic acid may also be effective against Candida biofilm-related infections, which are typically difficult to treat due to multidrug resistance [ 97 ]. In a study performed after our systematic search on 135 patients with toenail and/or fingernail onychomycosis receiving oral itraconazole pulse monotherapy, oral acitretin monotherapy, or combined pulsed itraconazole and acitretin for 3 months [ 98 ], mycological cure was 51.1%, 28.9%, and 80%, respectively, and complete cure was 20%, 28.9%, and 53.3%, respectively ( p ≤ 0.05). OSI scores significantly improved in the combination group compared to itraconazole monotherapy ( p = 0.005) and acitretin monotherapy ( p = 0.006) groups, with no difference observed between the monotherapy groups ( p = 0.95).…”

Vitamins for the Management of Nail Disease: A Literature Review

“…Retinoids have immunomodulatory and fungistatic activity against dermatophytes and Candida albicans [42] and increase nail growth rate via increased epidermal turnover [35]. It has been hypothesized that systemic retinoids may serve a therapeutic adjuvant role in the treatment of onychomycosis [35].…”

“…Mycological and complete cures were achieved in 51.1 and 20% of the itraconazole group, 28.9 and 28.9% of the acitretin group, and 80.0 and 53.3% in the combined itraconazole/acitretin group (mycological cure p ≤ 0.05 and clinical cure p = 0.007), respectively. Cheilitis was reported in 44.4% (20/45) of the oral acitretin group and 57.7% (26/45) of the combined itraconazole/acitretin therapy group [35].…”

“…Alessandrini et al’s [30] study on topical vitamin E yielded promising results with an almost 80% complete cure rate reported following 6 months of treatment. Nasr et al’s [35] study on oral acitretin similarly yielded promising results with 80.0% mycological cure rate with combination itraconazole/oral acitretin, compared to 28.9 and 51.1% with itraconazole and acitretin alone, respectively ( p ≤ 0.05). Acitretin may have innate antifungal activity, and/or it may have a beneficial effect on onychomycosis treatment by accelerating nail growth.…”

Voriconazole is superior to combined itraconazole/isotretinoin therapy and itraconazole monotherapy in recalcitrant dermatophytosis

“…[10][11][12][13][14] Additionally, Campione et al 15 reported the successful use of topical 0.1% tazarotene gel in the treatment of onychomycosis. Furthermore, Nasr et al 16 have recently demonstrated favourable clinical and mycological outcomes of acitretin (25 mg/day for 3 months) in onychomycosis, with significantly superior efficacy when combined with oral itraconazole pulse therapy. Similarly, isotretinoin has been found to be a good adjuvant treatment for recalcitrant dermatophytosis due to its keratolytic and immunomodulatory effects.…”