Granulomatosis with polyangiitis presenting with isolated external genital and urethral manifestations: a case-based review

Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis primarily affecting the respiratory tract and kidneys, with external genital and urethral lesions (EGUL) being exceedingly rare. We present a case of a middle-aged man with relapsing proteinase 3-antineutrophil antibody-positive GPA who developed isolated granulomatous, ulcerative balanitis, and urethritis. His condition abruptly worsened after a prolonged indolent course, requiring treatment with glucocorticoids and rituximab, leading to successful remission. To better characterize EGUL in GPA, a systematic literature search was performed in PubMed, Scopus, and the NPO Japanese Society of Medical Abstracts databases using keywords related to GPA and EGUL. Cases meeting the American College of Rheumatology or Japanese Ministry of Health, Labor, and Welfare criteria for GPA and the 2012 Chapel Hill Consensus Conference definitions were included for analysis. Our review identified that EGUL often presents as an initial symptom and can be classified by the presence or absence of preceding urethritis. Cases with preceding urethritis had a higher risk of severe complications with extensive penile or urethral involvement. In contrast, penile lesions without preceding urethritis typically presented as characteristic mucosal lesions localized around the glans. In females, GPA-associated urethritis frequently led to periurethral mass formation, vaginal involvement, and significant sequelae. Given the potential for delayed diagnosis and serious complications, clinicians should be vigilant for EGUL in patients with suspected or diagnosed GPA. Future prospective studies with larger cohorts are needed to elucidate the prevalence, clinical spectrum, and optimal management of these rare but significant manifestations of GPA.