Retinoids in Fungal Infections: From Bench to Bedside

Abstract

Retinoids—a class of chemical compounds derived from vitamin A or chemically related to it—are used especially in dermatology, oncohematology and infectious diseases. It has been shown that retinoids—from their first generation—exert a potent antimicrobial activity against a wide range of pathogens, including bacteria, fungi and viruses. In this review, we summarize current evidence on retinoids’ efficacy as antifungal agents. Studies were identified by searching electronic databases (MEDLINE, EMBASE, PubMed, Cochrane, Trials.gov) and reference lists of respective articles from 1946 to today. Only articles published in the English language were included. A total of thirty-nine articles were found according to the criteria. In this regard, to date, In vitro and In vivo studies have demonstrated the efficacy of retinoids against a broad-spectrum of human opportunistic fungal pathogens, including yeast fungi that normally colonize the skin and mucosal surfaces of humans such as Candida spp., Rhodotorula mucilaginosa and Malassezia furfur, as well as environmental moulds such as Aspergillus spp., Fonsecae monofora and many species of dermatophytes associated with fungal infections both in humans and animals. Notwithstanding a lack of double-blind clinical trials, the efficacy, tolerability and safety profile of retinoids have been demonstrated against localized and systemic fungal infections.

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

“…Studies support the antifungal and immunomodulatory properties of retinoic acid, pointing to the possible therapeutic role of systemic retinoids in onychomycosis. [7][8][9][10][11][12][13] In the present study, we evaluated the efficacy of combined pulsed itraconazole/ acitretin therapy versus either agent alone in the treatment of different types of onychomycosis. The results of the present work revealed that 51.1% of the itraconazole only group (group A) showed mycological clearance.…”

“…However, in nail psoriasis, acitretin does not accelerate the already enhanced nail growth by the pathological process of psoriasis, instead it normalises psoriatic hyperproliferation of nail bed keratinocytes, decreases subungual hyperkeratosis, and hence increasing access by antifungals, besides its immunomodulatory and fungistatic functions. [7][8][9][10][11][12][13][14][15]24 Therefore, patients having nail psoriasis with concomitant ony-…”

“…6 The observation of decreased total episodes of fungemia when ATRA was administered for the treatment of acute promyelocytic leukaemia, 7 had led to more research in the use of retinoids as potential fungistatic agents. [8][9][10][11][12][13] Campione et al reported that tazarotene, a topical retinoid, can inhibit the growth of T rubrum, T mentagrophytes, and C albicans and demonstrated a successful use of topical 0.1% tazarotene gel in the treatment of onychomycosis. 8 Studies support the antifungal role of retinoic acid that has been found to control both innate and adaptive immune responses.…”

“…11 Thereafter, ATRA paved the way for its systemic use against these opportunistic agents. 12,13 Moreover, systemic retinoids, especially acitretin, increases nail growth rate through increasing the epidermal turnover and is specifically effective in the treatment of severe nail psoriasis, which is often affected by onychomycosis. 14,15 The observation that onychomycosis is rare in children due to rapid nail growth, together with the proven immunomodulatory and fungistatic activity of retinoids against both dermatophytes and C albicans, drives us to think of the possible role of systemic retinoids, whether as monotherapy or as a candidate for novel combined antifungal strategies in onychomycosis.…”

Pneumocystis Pneumonia: Pitfalls and Hindrances to Establishing a Reliable Animal Model

“…Animal models can circumvent these limitations [17][18][19]. Therefore, various animal models of Pneumocystis pneumonia have been developed in attempt to address pathogenesis, virulence, immune response, diagnosis, or therapy concerns [19][20][21][22][23][24]. However, a single model cannot answer all the aforementioned questions, which explains in part the great multiplicity of supports that have been developed so far.…”