Cystic fibrosis

Acne adverse event with CF triple therapy


Isotretinoin treatment may be necessary in some patients who develop acneiform eruption as an adverse event associated with the cystic fibrosis (CF) drug combination of elexacaftor-tezacaftor-ivacaftor (ELX-TEZ-IVA).

A French case series, published in JAMA Dermatology [link here], comprised 16 patients with CF aged 22-38 years receiving triple therapy targeting the CFTR gene and presenting with an acneiform rash between July 2021 and June 2022.

Six patients (37.5%) had developed new-onset acneiform rashes, while five (31.3%) had a relapse of previous acne and five (31.3%) had worsening of preexisting acne during treatment with ELX-TEZ-IVA.

Eleven patients (68.7%) had facial hyperseborrhea, 15 (93.7%) had noninflammatory lesions (open and/or closed comedones), and 14 (87.5%) had inflammatory lesions (papules, pustules, and/or nodules).

Nine patients (56.2%) had postinflammatory hyperpigmentation and four (25.0%) had pitted scars.

The severity of these acneiform eruptions assessed using the Global Acne Severity Scale was mild to moderate (50.0% grade 2 and 18.7% grade 3)

The study said affected areas included facial seborrheic areas in 13 patients (81.2%), chest in 10 patients (62.5%), and back in 11 patients (68.7%).

“Of note, 4 patients (25.0%) described spontaneous improvement of acneiform lesions without discontinuation of ELX-TEZ-IVA,” it said.

Skin biopsy of inflammatory papules in four patients showed consistent evidence of acute folliculitis with a perifollicular inflammatory infiltrate of neutrophils occasionally.

“In addition, histopathologic features of necrotizing infundibular crystalline folliculitis (NICF) were observed in all 4 biopsies, showing dilated follicular ostia with birefringent crystalline material.”

“The pathogenesis of NICF remains largely unknown. However, polarizable crystals may result from esterification of cholesterol in sebum by gram-positive cocci bacteria, including Cutibacterium acnes and Pityrosporum species; NICF may represent aberrant differentiation of infundibular progenitors in response to destructive folliculitis,” the study said.

Topical treatments (monotherapy or retinoid and benzoyl peroxide combination) were prescribed for 15 patients (93.7%), while six patients (37.5%) were secondarily prescribed oral antibiotics and four (25.0%) were prescribed isotretinoin.

“Because isotretinoin safety profile was unknown in patients treated with ELX-TEZ-IVA, it was started at a low dose (0.1-0.2 mg/kg/day) and gradually increased with monthly biological monitoring.”

“The overall safety profile was good except for 2 cases of increased creatine kinase (CK) levels greater than 10 times the upper limit of normal that occurred at 0.3 to 0.5 mg/kg/day.”

Overall, partial or complete remission was achieved in 12 patients (85.7% of patients reevaluated). In those who achieved complete remission, the median delay was 90 days after treatment.

The investigators said the description of acneiform lesions on ELX-TEZ-IVA treatment suggests a potential role of CTFR in follicular and sebaceous homeostasis.

“The CFTR protein was previously shown to be expressed in sebaceous glands. Whether ELX-TEZ-IVA–associated acneiform eruption could also be related to changes of sweat composition is an interesting hypothesis that would require further exploration.”

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