Persistent presumed allergic fungal rhinosinusitis during tezepelumab therapy with improvement after revision surgery: a case report.

Abstract

Allergic fungal rhinosinusitis (AFRS) is a clinically distinct subset of type 2 chronic rhinosinusitis with nasal polyps (CRSwNP), characterized by markedly elevated total IgE, fungal sensitization, and expansile disease with bony remodeling. Definitive diagnosis requires all five Bent and Kuhn criteria, including histopathological demonstration of eosinophilic mucin without tissue invasion and a positive fungal stain. Tezepelumab, a monoclonal antibody against thymic stromal lymphopoietin (anti-TSLP), has phase 3 evidence in severe CRSwNP but has not been evaluated specifically in AFRS. We report a 32-year-old woman with an AFRS-like CRSwNP phenotype, clinically and radiologically suspected but not histologically confirmed (total serum IgE 1,330 IU/mL; fungal polysensitization to Aspergillus, Alternaria, Penicillium and Candida) and severe asthma. During 11 months of tezepelumab prescribed for severe asthma rather than initiated for sinonasal disease, sinonasal disease was not controlled: the 22-item Sino-Nasal Outcome Test (SNOT-22) score remained severe (85→89/110) and imaging showed interval progression of maxillary disease, with persistence of a left posterior ethmoidal mucocele encroaching on the optic canal and orbit that had already been present on pre-biologic imaging. Revision endoscopic sinus surgery (FESS) was required; two months postoperatively the SNOT-22 improved markedly to 48/110 and asthma control improved partially (Asthma Control Test [ACT] 8→15/25). The temporal pattern is compatible with improvement following surgery rather than anti-TSLP therapy, although perioperative corticosteroids, continued medical treatment, changes in adherence and the natural course of disease may also have contributed. A single, uncontrolled observation with only two months of postoperative follow-up cannot establish that TSLP blockade is ineffective in AFRS; it does illustrate that fixed structural disease may not be addressed by biologic therapy alone. Dedicated prospective studies of anti-TSLP therapy in histologically confirmed AFRS are needed.