Chronic rhinosinusitis precipitated by tumor necrosis factor alpha inhibitors is the phenotype of chronic rhinosinusitis without nasal polyps

Abstract

BackgroundChronic rhinosinusitis (CRS) is a frequently observed condition in patients with immunodeficiency secondary to tumor necrosis factor alpha inhibitors (TNFαis). The histologic features of CRS caused by TNFαis have yet to be determined and may have important implications in understanding the pathophysiology of the disease process.MethodsA structured histopathology report was used to analyze sinus tissue removed during functional endoscopic sinus surgery (FESS). These structured histopathology variables were compared among patients with CRS on TNFαi (CRSαi), CRS without nasal polyps (CRSsNP) patients, and CRS with nasal polyps (CRSwNP) patients.ResultsEighteen CRSαi, 91 CRSwNP, and 113 CRSsNP patients undergoing FESS were analyzed. Compared to CRSsNP, CRSαi patients exhibited increased mucosal ulceration (16.7% vs 0.9%, p < 0.008), increased fibrosis (100% vs 34.5%, p < 0.001), and increased presence of Charcot‐Leiden crystals (16.7% vs 0%, p < 0.002). Compared to CRSwNP, CRSαi patients demonstrated increased fibrosis (100% vs 54.9%, p < 0.001), decreased presence of subepithelial edema (44.4% vs 69.2% p < 0.043), decreased eosinophil aggregates (22.2% vs 47.3% p < 0.042), and fewer eosinophils per high‐power field (44.4% vs 73.6%, p < 0.017).ConclusionCRSαi exhibits structured histopathology more similar to CRSsNP. In the appropriate clinical context, it may be reasonable that the medical regimen for these patients be focused on a more antineutrophilic, macrolide‐based approach. This study provides insight into the inflammatory environment of patients with CRSαi and may have implications for disease management.

International consensus statement on allergy and rhinology: rhinosinusitis 2021

“…The varied medical therapies to treat CRSsNP, including antibiotics and systemic corticosteroids, can also cause serious complications and add morbidity to the disease 1318–1323 . Interestingly, recent evidence suggests that CRSsNP can be precipitated by treatment with anti‐tumor necrosis factor‐alpha inhibitors for rheumatic conditions 1291,1324,1325 …”

Fractional Exhaled Nitric Oxide as a Marker of Mucosal Inflammation in Chronic Rhinosinusitis

“…30 Furthermore, ovalbumin-sensitized mice lacking TNFα show marked reduction in nasal symptoms and Th2 cytokine mRNA expression following intranasal allergen challenge. 31 Of note, systemic anti-TNFα therapy has been reported to cause CRS, 32 suggesting that strategies targeting TNFα in CRS may need to be either locally administered or selectively target a downstream effector of TNFα. TNFα is a known potent inducer of nitric oxide synthase expression in macrophages 33 and bronchial epithelial cells, 34 but whether TNFα directly regulates NO production in upper airway respiratory cells remains to be determined.…”

Characteristics of mucin hypersecretion in different inflammatory patterns based on endotypes of chronic rhinosinusitis

“…Polymorphism of the TNFα‐1031 gene might be significantly correlated with the incidence of atopic CRS 34 . Peter et al 35 . classified patients with CRS treated with TNF‐α inhibitors into a separate subtype and also found that CRS on TNF‐α inhibitors (TNFαis) significantly reduced the number of eosinophils when compared to patients with CRSwNP.…”