Hidradenitis suppurativa onset associated with gamma-secretase inhibitor (nirogacestat)

Summary: Abstract Body: Hidradenitis suppurativa (HS) is a chronic follicular disorder affecting apocrine-rich areas, characterized by painful nodules, abscesses, and sinus tracts, leading to scarring and impaired quality of life. Previous studies have linked gamma-secretase (GS) complex knockout mutations to HS. Here, we report a case of HS onset temporally associated with gamma-secretase inhibitor (nirogacestat) use. Objective: To describe a rare case of HS onset linked to nirogacestat treatment. A 47-year-old woman presented with a 4-month history of HS symptoms following initiation of nirogacestat for treatment of a right abdominal wall desmoid tumor diagnosed in December 2021. In early 2024, nirogacestat was initiated. After 5 months, inflammatory nodules of HS appeared on the right inner thighs. Concomitant side effects included diarrhea, fatigue, amenorrhea, and daily hot flashes consistent with menopause onset. HS remained localized while flares occurred monthly. Acute lesions were refractory to intralesional triamcinolone, Augmentin, and topical therapies. At presentation to our HS Center, four to five areas of post-inflammatory hyperpigmentation and scarring were observed in the right inguinal crease and upper medial thigh. Topical chlorhexidine wash and clindamycin gel with oral spironolactone 50 mg twice daily led to reduced HS activity. To our knowledge, this is one of the first reports of HS onset associated with a gamma-secretase inhibitor, accompanied by symptoms suggesting androgen excess and menopause, possibly hastened by nirogacestat. Careful monitoring of gamma-secretase inhibitor therapy as a trigger of HS is underscored by this case. Hansen Tai¹, Khyla Hill¹, Aarthi Parvathaneni¹, Steven Cohen¹ 1. Dermatology, Weill Cornell Medicine, New York, NY, United States. Clinical Research: Interventional Research