Treatment of refractory rhinosinusitis: a narrative review

Abstract

Purpose: Refractory chronic rhinosinusitis (CRS) refers to persistent or recurrent sinonasal inflammation despite guideline-directed medical management and anatomically complete endoscopic surgery. This review delineates the epidemiology, endotypic drivers, and current therapeutic options for refractory CRS to support individualized care and identify unmet research needs. Current Concepts: Epidemiological studies indicate that 10% to 20% of patients undergoing surgery for CRS experience relapse, with recurrence rates increasing to 60% in the presence of nasal polyps. The prognosis is further compromised by comorbid conditions such as asthma, aspirin-exacerbated respiratory disease, cystic fibrosis, and immunodeficiency. However, inflammatory endotype—particularly type 2 eosinophilic disease—remains the principal determinant of outcomes. Core medical therapies include daily intranasal corticosteroids, high-volume saline irrigation, and short courses of systemic steroids. The efficacy of antibiotics, macrolides, antileukotrienes, proton-pump inhibitors, mucolytics, antifungals, probiotics, and complementary remedies remains inconsistent or marginal. Revision endoscopic surgery is indicated for persistent adhesions, residual partitions, or obstructing polyps, but its success diminishes in type 2 disease. Biologics targeting immunoglobulin (Ig) E (omalizumab) or type 2 cytokines significantly reduce polyp burden, improve olfaction, and decrease systemic steroid requirements, with dupilumab supported by the most robust evidence. Discussion and Conclusion: Among non-surgical treatments, topical corticosteroids and saline irrigation have demonstrated the most consistent benefit, while alternative therapies show limited efficacy. Surgical intervention is considered when there is insufficient improvement despite appropriate medical therapy. Recently, biologic agents have emerged as effective alternatives for patients with eosinophilic chronic rhinosinusitis with nasal polyps, resulting in marked improvements in polyp size, olfactory function, and symptom control.