Chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory condition of the nasal cavity and paranasal sinuses persisting for 12 weeks or longer.[1] The disease is classified as primary or secondary, and further subtyped by the presence or absence of nasal polyps (CRSwNP vs. CRSsNP) and by inflammatory endotype (type 2 vs. non–type 2).[2] Pathogenesis involves a complex interplay of epithelial barrier dysfunction, mucociliary impairment, microbial colonization, and dysregulated immune responses.[3] The maxillary sinuses are most commonly affected, and the condition is frequently encountered as an incidental or symptomatic finding on dental radiographs and CBCT. The signature imaging pattern is mucosal thickening and variable opacification of the paranasal sinuses, with or without ostiomeatal complex obstruction.[4] Management ranges from topical corticosteroids and saline irrigation to endoscopic sinus surgery and biologic therapy.[2][5]

The preferred term is chronic rhinosinusitis (CRS), reflecting the near-universal concurrent involvement of the nasal mucosa.[1] The older term "chronic sinusitis" remains in common clinical use but is considered less precise. CRS is subdivided into:

• CRS with nasal polyps (CRSwNP) — polyps visible on endoscopy or imaging in the middle meatus or nasal cavity[6][7]
• CRS without nasal polyps (CRSsNP) — inflammatory disease without visible polyposis[6]

Endotype-based classification recognizes type 2 (T2, eosinophilic-predominant), type 1 (T1, IFN-γ–driven), and type 3 (T3, IL-17–driven) inflammatory patterns.[3][8] The term aspirin-exacerbated respiratory disease (AERD) designates the triad of nasal polyps, asthma, and NSAID hypersensitivity.[2] Secondary CRS encompasses odontogenic sinusitis, fungal ball, immunodeficiency-related disease, and mucociliary disorders such as cystic fibrosis and primary ciliary dyskinesia.[2]

CRS affects approximately 1% to 7% of adults, with symptom-based surveys reporting prevalence as high as 11%.[2][7] The condition accounts for over 30 million annual diagnoses in the United States, with direct management costs exceeding $11 billion per year.[1] CRSwNP represents roughly 25% to 30% of CRS cases. Males are more likely to have diffuse sinus opacification patterns, and comorbid asthma or allergic rhinitis increases the likelihood of diffuse disease.[9] CRS is associated with significant comorbidity, including bronchial asthma (20–45% of cases), depression, obstructive sleep apnea, and COPD.[5] Odontogenic sources account for 25% to 40% of chronic maxillary sinusitis cases and represent the most common cause of unilateral maxillary sinus disease.[10][11]

Symptoms and Presentation

Diagnosis requires at least two cardinal symptoms persisting for ≥12 weeks plus objective confirmation by endoscopy or imaging:[1][2]

• Nasal blockage, obstruction, or congestion
• Anterior or posterior nasal drainage (often mucopurulent)
• Facial pain or pressure
• Hyposmia or anosmia

Additional symptoms include headache, fatigue, halitosis, cough, dental pain, and sleep disturbance.[1][7] Olfactory loss and nasal obstruction tend to be the most severe symptoms in CRSwNP.[12]

Examination Findings

Nasal endoscopy may reveal mucosal edema, mucopurulent discharge from the middle meatus, and nasal polyps.[1] Anterior rhinoscopy in the primary care setting can identify gross polyposis but has limited sensitivity for subtle disease.

Tempo and Complications

CRS follows a relapsing course with acute exacerbations. Complications are uncommon but include orbital cellulitis, subperiosteal abscess, and rarely intracranial infection.[7] Odontogenic sinusitis may progress to orbital or intracranial abscess if unrecognized.[11]

Red Flags

Alarm symptoms warranting urgent referral include periorbital swelling, diplopia, reduced visual acuity, severe headache, new neurologic symptoms, and uncontrolled epistaxis.[2] Unilateral disease with epistaxis, a visible mass, or bony erosion raises concern for neoplasia.[1][13]

Location and Distribution

CRS most commonly involves the maxillary sinuses, followed by the anterior ethmoid air cells, with variable involvement of the posterior ethmoid, frontal, and sphenoid sinuses.[14] Disease may be localized to a single functional drainage unit (e.g., isolated ostiomeatal complex disease) or diffuse across multiple sinuses bilaterally.[9][15] Unilateral maxillary sinus opacification should prompt consideration of odontogenic sinusitis, fungal ball, antrochoanal polyp, or neoplasm.[13][16]

Periphery and Shape

• Mucosal thickening appears as a band of soft-tissue density lining the sinus walls, typically smooth and uniform in CRSsNP. Thickening >3 mm is generally considered pathologic, though this threshold is somewhat arbitrary and must be interpreted in clinical context.[17][18]
• Polypoidal thickening produces lobulated or irregular mucosal contours, most conspicuous in the middle meatus and ethmoid infundibulum.[19]
• Mucous retention cysts present as well-defined, dome-shaped, homogeneous soft-tissue opacities arising from the sinus floor or walls, with a smooth convex superior margin. These are common incidental findings (up to 12% of sinuses on CBCT) and should be distinguished from true mucosal disease.[19][20]

Internal Architecture

• Partial opacification ranges from subtle mucosal thickening to near-complete sinus filling. The Lund-Mackay scoring system grades each sinus as 0 (clear), 1 (partial opacification), or 2 (complete opacification), with a maximum bilateral score of 24.[14][21]
• Complete opacification of a sinus produces a homogeneous radiopacity replacing the normal air-filled lucency. In the maxillary sinus, increasing opacification correlates with a higher likelihood of an odontogenic source.[10]
• Air-fluid levels appear as a straight horizontal radiopaque line within the sinus and suggest acute bacterial superinfection or recent hemorrhage rather than chronic disease alone.[18]
• Foci of high density (hyperattenuation) within opacified sinuses suggest inspissated secretions, calcification, or fungal concretions, as seen in allergic fungal rhinosinusitis (AFRS) or fungal ball.[14]

Effects on Adjacent Structures

• Sinus wall sclerosis and thickening — reactive osteitis with increased bone density of the sinus walls is a hallmark of chronicity, distinguishing CRS from acute disease.[4][14][18]
• Bony demineralization and expansion — prolonged mucocele formation or AFRS may cause pressure-related thinning and outward bowing of sinus walls.[14]
• Bony erosion — true cortical destruction is uncommon in uncomplicated CRS and should raise suspicion for invasive fungal disease or neoplasia.[1][13]
• Dental relationships — periapical pathology, periodontal bone loss, or iatrogenic factors (extractions, implants, displaced endodontic materials) adjacent to the sinus floor are key findings suggesting odontogenic sinusitis. Localized mucosal thickening overlying a periapical lesion is the most frequent sinus abnormality associated with dental disease.[22][23]

Ostiomeatal Complex and Drainage Pathways

Obstruction of the ostiomeatal complex (OMC) — comprising the maxillary sinus ostium, ethmoid infundibulum, and hiatus semilunaris — is a central feature of CRS pathophysiology and is well demonstrated on coronal imaging.[14] Anatomic variants that may predispose to OMC obstruction include concha bullosa, paradoxical middle turbinate, Haller cells, and nasal septal deviation.[4][17] CBCT demonstrates high accuracy for evaluating OMC patency and shows strong agreement with endoscopic findings.[4]

Extent and Cortical Involvement

The Lund-Mackay system provides a standardized method for quantifying disease extent across all sinus compartments and the OMC.[14][21] A score ≥4 has been associated with disease severity warranting surgical consideration.[21] Latent class analysis of CT opacification patterns identifies three clinically relevant groups: no/mild, localized, and diffuse, with diffuse opacification correlating with nasal blockage and anosmia.[9]

Recognized Variants

• Silent sinus syndrome — chronic OMC obstruction leads to negative intrasinus pressure, maxillary sinus atelectasis, inward bowing of sinus walls, and enophthalmos. Osseous thinning and lateralization of the uncinate process are characteristic.[4]
• Odontogenic sinusitis — typically unilateral maxillary disease with mucosal thickening or opacification overlying a dental source. CBCT is the preferred modality for identifying the causative tooth and evaluating the sinus floor integrity.[24]

Limitations of Two-Dimensional Dental Radiography

Panoramic radiography has poor sensitivity (approximately 37%) for detecting mucosal thickening compared with CBCT, though specificity is high.[25][26] A systematic review confirmed that CT/CBCT is significantly more effective than panoramic radiography for assessing maxillary sinus pathology (RR = 0.19, p = 0.01).[26] Periapical radiographs are limited by superimposition of multi-rooted teeth and the sinus floor, reducing diagnostic accuracy in the posterior maxilla.[27] Two-dimensional sinus radiographs (Waters and Caldwell views) are no longer considered adequate for evaluating paranasal sinus disease.[17]

MRI: Differentiating Retained Secretions, Fungal Disease, and Neoplasia

MRI is not a first-line diagnostic modality for CRS and is discouraged for routine confirmation due to higher cost and false-positive rates.[1] However, MRI plays a critical role when CT demonstrates findings suspicious for neoplasia, invasive fungal disease, or extra-sinus extension:[1][4]

• Tumor vs. retained secretions — on T2-weighted images, inflammatory secretions and edematous mucosa appear hyperintense, whereas sinonasal tumors show intermediate, heterogeneous signal intensity, allowing differentiation from obstructed secretions.[4][28]
• Fungal sinusitis — allergic fungal mucin demonstrates characteristic T2 hypointensity (signal void) due to high protein and low water content, with peripheral mucosal enhancement on post-gadolinium T1 images. This pattern helps distinguish AFRS from eosinophilic mucin rhinosinusitis and neoplasia.[14][29][30]
• Perineural and intracranial extension — MRI is superior to CT for detecting perineural tumor spread, dural involvement, and orbital invasion, which are critical for staging sinonasal malignancies.[4]

Maxillary sinus opacification on dental radiographs or CBCT has a broad differential. The clinical context — unilateral vs. bilateral disease, presence of dental pathology, bony integrity, and symptom profile — guides discrimination among entities.

The highest-risk diagnostic pitfall is failing to recognize a sinonasal neoplasm masquerading as refractory CRS. Unilateral disease with bony erosion, extra-sinus extension, or epistaxis warrants urgent otolaryngologic referral with biopsy and MRI.[1][13]

Mucosal biopsy is not routinely required for CRS diagnosis but is essential when neoplasia or granulomatous disease is suspected. The histopathologic features of CRS vary by endotype and phenotype:[32]

CRSwNP (Type 2–Predominant)

• Edematous stroma with prominent subepithelial edema
• Dense eosinophilic infiltration, often with eosinophil aggregates
• Basement membrane thickening
• Goblet cell hyperplasia
• Epithelial damage with areas of squamous metaplasia
• Elevated tissue IgE and eosinophil cationic protein[33][34][35]

CRSsNP (Non–Type 2–Predominant)

• Submucosal fibrosis with collagen deposition
• Neutrophilic infiltration predominates
• Less prominent edema compared with CRSwNP
• Basement membrane thickening may be present but is typically less marked[32]

Radiologic-Pathologic Correlation

Eosinophilic (T2) CRS correlates with diffuse bilateral polypoid opacification, higher Lund-Mackay scores, and greater disease severity and recurrence risk.[36][37] Non-eosinophilic CRS tends toward localized disease following anatomic drainage pathways.[15] Cluster analyses incorporating both inflammatory and remodeling markers identify at least four to five distinct histopathologic subtypes with differing clinical behavior and recurrence profiles.[32][36]

Initial Medical Management

First-line therapy for all CRS subtypes comprises intranasal saline irrigation and intranasal corticosteroids (INCS), which reduce nasal symptoms and improve quality of life.[2][5] Oral corticosteroids may be considered for severe exacerbations but should generally be avoided due to systemic adverse effects.[2] Long-term low-dose macrolide antibiotics (>3 weeks) may benefit select patients with non-eosinophilic CRS, though evidence remains limited.[2]

Referral Indications

Patients with refractory symptoms despite 4 to 8 weeks of appropriate medical therapy, alarm symptoms, nasal polyps, or suspected odontogenic source should be referred to otolaryngology.[1][2] Odontogenic sinusitis requires coordinated care between dental providers and otolaryngologists, with treatment of the dental source being essential.[11][31]

Surgical Management

Functional endoscopic sinus surgery (FESS) is the standard of care for medically refractory CRS, restoring sinus outflow tract patency with symptomatic improvement in over 75% of patients.[4][38] Preoperative CT is critical for surgical planning, particularly for identifying anatomic variants that increase risk of orbital, intracranial, or vascular injury.[4]

Biologic Therapy

For CRSwNP refractory to INCS and surgery, biologic agents targeting type 2 inflammation are recommended:[39][40]

• Dupilumab (anti–IL-4Rα) — FDA-approved for CRSwNP; most effective biologic for polyp score reduction and quality-of-life improvement[40][41]
• Omalizumab (anti-IgE) — FDA-approved for CRSwNP with inadequate response to INCS[41]
• Mepolizumab (anti–IL-5) — FDA-approved for CRSwNP[41]

Recurrence and Prognosis

Recurrence after ESS is common, reported in approximately 39% to 54% of CRSwNP patients depending on follow-up duration.[12][37][42] Independent risk factors for recurrence include higher preoperative Lund-Mackay score, peripheral blood eosinophilia >5%, comorbid asthma or NSAID hypersensitivity, history of revision surgery, and poor adherence to postoperative INCS.[42][43][44] With optimized surgery and medication adherence, approximately 55% of patients achieve controlled status and 30% partial control.[12] Long-term follow-up with endoscopic assessment is recommended, as endoscopic outcomes at 3 to 18 months post-surgery are predictive of the need for revision.[38]

Aspirin-Exacerbated Respiratory Disease (AERD)

The triad of CRSwNP, asthma, and NSAID hypersensitivity defines AERD, a distinct clinical entity with aggressive polyposis and high recurrence rates. Aspirin therapy after desensitization (ATAD) is conditionally recommended in addition to standard CRS management.[2][39] NSAID hypersensitivity is an independent predictor of recurrence after ESS.[42][45]

Odontogenic Sinusitis

Odontogenic sinusitis is frequently underdiagnosed because dental pain may be absent and symptoms overlap with non-odontogenic CRS.[11][46] CBCT is the preferred imaging modality for identifying the dental source, as panoramic radiography cannot reliably exclude odontogenic disease.[26][46] Combined ESS with dental treatment yields significantly better outcomes (96% vs. 74% success) than ESS alone.[31]

Cystic Fibrosis

CRS is nearly universal in cystic fibrosis, with characteristic findings including diffuse sinus opacification, medial bowing of the lateral nasal wall, and demineralization of the uncinate process.[21] CFTR modulator therapy (e.g., elexacaftor-tezacaftor-ivacaftor) has demonstrated significant improvement in sinus CT scores.[21]