Case Report: Olfactory loss as the sentinel manifestation of type 2 chronic rhinosinusitis without polyps: response to IL-4Rα inhibition with stapokibart - a case series.

Chronic rhinosinusitis without nasal polyps (CRSsNP) is traditionally associated with type 1 inflammation, but emerging evidence reveals a subset of patients with a type 2 endotype driven by IL-4 and IL-13, often presenting with prominent olfactory dysfunction and responding poorly to conventional therapy. We report three cases of type 2 CRSsNP with comorbid allergic rhinitis (aged 29-30 years, two males, one female) who presented with debilitating olfactory loss as the sentinel symptom. All had elevated type 2 biomarkers, absence of nasal polyps, and CT evidence of sinusitis. After failure of intranasal corticosteroids, they received stapokibart (600 mg loading dose, then 300 mg every two weeks for 16 weeks). Olfactory improvement occurred within two weeks and was sustained through week 16; SNOT-22 scores decreased by approximately 90%, and Lund-Mackay scores decreased to 0 (Cases 1 and 2) and 1 (Case 3). Serum total IgE decreased in all patients; eosinophil counts decreased in two but paradoxically increased in one. No serious adverse events occurred. Type 2 CRSsNP with prominent olfactory dysfunction is a distinct, treatable phenotype. Stapokibart rapidly improves olfactory function in patients refractory to conventional therapy, supporting an endotype-driven biologic strategy for CRS.