Importance: A new treatment for cystic fibrosis combining 3 CFTR modulators-elexacaftor (ELX), tezacaftor (TEZ), and ivacaftor (IVA)-has recently been approved for cystic fibrosis treatment. The cutaneous adverse effects following treatment with this combination are poorly described in the literature.
Objective: To describe the clinicopathological features and treatment response of ELX-TEZ-IVA-associated acneiform eruptions in patients with cystic fibrosis.
Design, setting, and participants: This case series study was conducted in the Dermatology Department of Cochin Hospital, Paris, France, from July 2021 to June 2022 in collaboration with the Cochin Reference Center for Cystic Fibrosis. Referred patients were examined by senior dermatologists. All patients with cystic fibrosis treated with ELX-TEZ-IVA and referred for an acneiform rash were included.
Exposures: Treatment with ELX-TEZ-IVA.
Main outcomes and measures: Onset of acneiform rash, type of lesions, and degree of severity, as well as treatments initiated and response, were evaluated. When performed, skin biopsies were reviewed.
Results: This study included 16 patients (11 women [68.7%]) with a median (range) age of 27 (22-38) years. Six patients (37.5%) developed new-onset acneiform rashes, whereas 10 patients (62.5%) had a relapse (5 patients) or worsening (5 patients) of previous acne. The median (range) onset of acneiform rash was 45 (15-150) days. At inclusion, 11 patients (68.7%) had facial hyperseborrhea, 15 patients (93.7%) had noninflammatory lesions, and 14 (87.5%) had inflammatory lesions of seborrheic regions. Four patients (25.0%) had severe acne with deep inflammatory lesions and pitted scars. A specific pathological pattern of necrotizing infundibular crystalline folliculitis was observed in 4 patients. Topical acne treatments, antibiotics, and isotretinoin were used successfully in these patients, resulting in partial or complete remission in 12 patients (85.7% of patients reevaluated).
Conclusions and relevance: This case series study found that acneiform eruption is an adverse event associated with ELX-TEZ-IVA treatment in patients with cystic fibrosis. Most patients developed mild lesions. However, isotretinoin treatment may be necessary in some patients. The mechanism of ELX-TEZ-IVA-associated acneiform eruption is currently unknown, but the observation of necrotizing infundibular crystalline folliculitis in biopsied patients may guide further exploration.