Secukinumab in Refractory Generalized Darier's Disease with a 40-Year Disease Duration: A Case Report

To report a rare case of refractory generalized Darier's disease (DD), also known as keratosis follicularis, with a disease duration exceeding 40 years and to explore the therapeutic effect of the interleukin-17A inhibitor secukinumab.

Clinical data were collected. Skin histopathological examination was performed using hematoxylin-eosin (HE) staining, and ATP2A2 gene mutation testing was conducted via whole-exome high-throughput sequencing. The patient was treated with secukinumab. The patient received subcutaneous secukinumab 300 mg once weekly for the first 5 weeks (loading phase), followed by 300 mg every 4 weeks as maintenance therapy.

The patient presented with generalized hyperpigmentation, widespread keratotic papules and plaques, some with an oyster-shell appearance, covered with greasy crusts. Histopathology examination further revealed characteristic suprabasal clefts, acantholysis, and dyskeratotic cells (corps ronds and grains). Genetic testing subsequently identified a heterozygous c.479C>T (p.P160L) mutation in the ATP2A2 gene. Following 9 months of secukinumab treatment, the patient experienced partial improvement in pruritus and skin lesions.

This case represents a severe form of generalized Darier's disease with well-defined clinical, pathological, and genetic features. Secukinumab treatment suggested partial clinical improvement, although complete clearance was not achieved. However, the patient discontinued treatment due to financial constraints, and long-term follow-up data are lacking, warranting further investigation. This report provides preliminary experience with biologic therapy for this condition, and the findings require confirmation through controlled studies.