Primary and Secondary Grzybowski’s Generalized Eruptive Keratoacanthoma: A New Perspective on Management, Clinical Features, and Prognosis

Grzybowski's generalized eruptive keratoacanthoma (GEKA) is a rare variant of keratoacanthomas, characterized by hundreds to thousands of lesions, accompanied by pruritus, mucosal involvement, and comorbidities. Our aim was to analyze the clinical presentation, associated comorbidities, treatment strategies, and outcomes of GEKA. We conducted a literature review of all published cases between 1950 and 2024, following the Preferred Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. A total of 143 articles were screened; 58 were included, yielding 64 cases. Of these, 24 were associated with severe comorbidities, while 40 were not. Cases without associated conditions were more likely to exhibit a worse prognosis, greater therapeutic resistance, and distinct clinical features. In contrast, cases associated with malignancy, systemic diseases, or other comorbidities tended to show better treatment responses and fewer complications. Pruritus remained the predominant symptom in both groups, with similar lesion morphology. The rarity of GEKA leads to a paucity of literature. Reporting bias and limited cases may lead to less generalizability. Based on our review and considering the differences in clinical presentation, demographics, associated comorbidities, complications, and prognosis, GEKA may be classified as primary or secondary to a malignancy, systemic disease, or other comorbidity, encouraging clinicians to have a high index of suspicion during evaluation and treatment for an underlying trigger.