Skin Allergy to Azole Antifungal Agents for Systemic Use: A Review of the Literature.

BACKGROUND Antifungal azoles are the first-line agents used to treat topical and, above all, systemic mycosis. The latter could be life-threating infections in immunocompromised patients. Chemotherapeutic antibiotics, including antifungal azoles, may induce hypersensitivity reactions; however, such immunologic adverse reactions have not been as well defined and carefully investigated. OBJECTIVE To provide an update on the evaluation and diagnosis of skin allergy to azole antifungal agents. METHODS This is a systematic review performed on PubMed and Google Schoolbarusing the key term "allergy, hypersensitivity, anaphylaxis, immediate-type reaction, delayed-type reaction, ketoconazole, fluconazole, posaconazole, voriconazole, itravuconazole, triazoles, imidazoles, antifungals, antimycotics"The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, reviews and case reports. RESULTS One hundred twenty-four articles matched our search terms. The most common adverse events reported were T-cell mediateddelayed-type hypersensitivity reactions, such as fixed drug eruptions,localized, generalized and exhantematous dermatitis, Steven Johnson syndrome, toxic epidermal necrolysis and acute generalizedexhanthematouspustulosis. Rarely a drug rash, eosinophilia systemic symptoms has been described Also immediate-type reactions such as urticaria-angioedema or anaphylaxis have been reported following administration of antifungal imidazoles, although not so frequently. CONCLUSION Despite their widespread use, triazoles seem to induce rare cutaneous hypersensitivity reactions, but the pathomechanisms, risk factors, diagnostic and management strategies, including skin tests and challenge tests, are little known and poorly investigated.