Osimertinib, a Trigger of Subacute Cutaneous Lupus Erythematosus: Three-Patient Case Series and Literature Review

Background

Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is the standard first-line therapy for EGFR-mutant non-small cell lung cancer (NSCLC). While acneiform rash, pruritus, xerosis and paronychia are well-recognized cutaneous adverse events of EGFR-TKIs, drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) is an emerging and under-recognized complication that may be misdiagnosed as eczema, psoriasis or drug allergic reaction, potentially leading to inappropriate management and permanent discontinuation of life-prolonging targeted therapy. Case presentations: We report three female patients (aged 55-80 years) with EGFR-mutant NSCLC who developed DI-SCLE during osimertinib therapy, presenting with characteristic annular and polycyclic erythematous plaques in a photodistributed location 3-17 months after treatment initiation. Histopathological examination revealed irregularly thin epidermis with dyskeratotic keratinocytes, interface lymphocytic infiltrate and vacuolar degeneration of the basal layer in all cases corresponding to subacute cutaneous lupus erythematosus. Direct immunofluorescence demonstrated immunoglobulin and complement deposition along the dermoepidermal junction in two of three patients (positive lupus band test). All patients were managed with systemic corticosteroids and antimalarials (hydroxychloroquine or chloroquine) additionally used in two patients. This approach enabled continuation or resumption of osimertinib.