Clinical Features and the Management of Drug-Induced Eruptive Keratoacanthoma and Squamous Cell Carcinoma: A Review of 172 Cases

May 2025 | Volume 24 | Issue 5 | 476 | Copyright © May 2025


Published online April 28, 2025

doi:10.36849/JDD.8986

Eric R. Bray MD PhDa, Lea Tordjman BSb, Keyvan Nouri MD MBAa

aDr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL
bUniversity of Miami Miller School of Medicine, Miami, FL

Abstract
Background: The sudden appearance of keratoacanthomas (KA) and squamous cell carcinomas (SCC) is a serious complication of several oncologic and immunomodulatory medications. The development of numerous lesions can cause significant morbidity. It remains unclear how these eruptive neoplasms vary by drug-induced etiology.
Objective: This study aimed to identify clinical features of eruptive KA/SCC linked to different medication classes.
Methods: PubMed was queried for cases describing drug-induced eruptive KA/SCC.
Results: Among the 172 cases identified, kinase inhibitor-associated eruptive KA/SCC affected younger patients, resulted in fewer lesions, favored the head and neck, and were more likely to be treated with excision. In contrast, immune checkpoint inhibitor (ICI)-associated lesions occurred in older individuals, often presented with multiple lesions, favored the lower extremities, and were usually pruritic. Treatment of ICI eruptive KA/SCC was more likely to include intralesional and topical corticosteroids, oral retinoids, and oral niacinamide.
Conclusions: Significant differences in the clinical presentation of eruptive KA/SCC between drug etiologies were identified. These findings indicate that different underlying cellular mechanisms may be responsible for the rapid growth of these lesions, further suggesting that different treatments may be appropriate depending on the causative medication.

Citation: Bray ER, Tordjman L, Nouri K. Clinical features and the management of drug-induced eruptive keratoacanthoma and squamous cell carcinoma: a review of 172 cases. J Drugs Dermatol. 2025;24(5):476-481. doi:10.36849/JDD.8986

INTRODUCTION

Eruptive keratoacanthomas (KAs) and squamous cell carcinomas (SCCs) are recognized side effects of monotherapy with BRAF inhibitors.1 These adverse effects have also been observed with other kinase inhibitors (KI), immune checkpoint inhibitors (ICI), and immunosuppressant medications.2 The emergence of these eruptive lesions can lead to significant morbidity and may often necessitate interruption of oncologic therapy. The mechanism of KI-induced lesions has been thoroughly characterized. However, the mechanisms underlying the variation in clinical features of these eruptive neoplasms based on other drug-induced etiologies remain unclear.

KA is a well-differentiated epithelial neoplasm frequently occurring on sun-exposed skin and characterized by rapid growth and potential spontaneous regression.3 Its etiology is complex and multifaceted, involving genetic susceptibilities, environmental factors,3 and, notably, pharmacological agents. KA and cutaneous SCC, both keratinocyte-derived neoplasms, present diagnostic challenges due to their overlapping clinical and histological features.4,5 This ambiguity fuels ongoing debates about whether KA should be classified as a benign lesion, a precursor to SCC, or a well-differentiated variant of SCC.4,5

This study examines the clinical characteristics and management strategies of drug-induced eruptive KA and SCC, aiming to delineate the variability of these lesions across different medication classes. Enhancing our understanding of these eruptive phenomena and their etiological differences is essential for improving diagnostic and therapeutic strategies for this intriguing dermatological condition.

MATERIALS AND METHODS

A literature review was conducted using PubMed with the search terms "eruptive" and "keratoacanthoma" or "squamous cell carcinoma". Articles were screened for cases of drug-induced eruptive KA or SCC. Those that did not include case-level data were excluded.

Data extraction was performed independently by two authors (ERB and LT). Collected information included inciting drug class, patient age, history of prior nonmelanoma skin cancer (NMSC), including basal cell carcinoma or squamous cell carcinoma, immunosuppressant use, and time to lesion eruption. Number, anatomic location, and associated pain or pruritus of lesions, as well as details of attempted and successful treatments were also extracted. Spontaneous resolution of lesions was considered only when the inciting drug was not discontinued. Lesions were categorized by number as "single" (1 lesion),