Male genital fixed drug eruption: a systematic review

Fixed drug eruption (FDE) is a common cutaneous adverse reaction characterized by recurrent, well-demarcated lesions appearing at the same site upon re-exposure to a causative drug. Genital involvement represents one of the most frequent mucosal localizations in men but remains poorly described in the literature, often leading to diagnostic confusion with sexually transmitted infections. We aimed to systematically review the epidemiological, clinical and etiological characteristics of male genital FDE.

A systematic review was conducted according to PRISMA 2020 guidelines. Medline, Google Scholar, Embase and the Cochrane Library were searched for articles published between 1970 and 2024, using predefined keywords relating to FDE and male genital involvement. Eligible publications included case reports and case series describing genital FDE in adult male patients. Data on demographics, clinical presentation, drug triggers, diagnostic methods and extragenital involvement were extracted. Weighted medians and means were calculated when applicable.

Seventy studies were included, encompassing 262 male patients. The weighted median age was 35.5 years. Genital lesions were most commonly located on the glans penis (72.9%), followed by the shaft (17.6%), foreskin (12.2%), and scrotum (4.2%). Erythema (85.9%) was the predominant clinical presentation, while erosions (36.3%), bullae (26.7%), and post-inflammatory pigmentation (26.2%) were variably reported. In 79% of cases, genital involvement was isolated. Among extragenital sites, the oral mucosa was most frequently affected (54.5%). A causative agent was identified in 93.1% of patients. The most commonly implicated drugs were trimethoprim-sulfamethoxazole (27.9%), cyclines (20.9%), and NSAIDs (12.3%). The weighted median time to onset was 48 hours. Diagnosis relied solely on clinical history in 56.1% of patients, with oral provocation tests most frequently used when further allergy workup was performed.

This review represents the largest synthesis of male genital FDE to date. The condition predominantly affects the glans and is most commonly induced by antibiotics and NSAIDs. Recognizing its characteristic presentation and drug associations is essential to differentiate it from sexually transmitted infections and avoid recurrent episodes.