Nasal Polyps

Etiology

Nasal polyps are classified into 3 groups: localized, diffuse, and systemic. Localized nasal polyps are typically reactive and arise from either inflammatory or neoplastic processes. Diffuse nasal polyposis is often observed in patients with CRSwNP, which has multiple etiologies. In the Western Hemisphere, most cases of nasal polyps are the result of T-helper 2 (Th2) cell-driven eosinophilia and immunoglobulin E (IgE) inflammation, characterized by elevated interleukin-5 (IL-5). This pattern is often associated with environmental or seasonal allergic triggers.

Patients with cystic fibrosis tend to exhibit neutrophil-driven inflammation within their polyps. These individuals may present with severe nasal polyposis in the absence of a clear allergic trigger, although the clinical appearance may closely resemble allergic disease. Cystic fibrosis should be considered in the differential diagnosis of refractory nasal polyposis in young patients, particularly preteens, teenagers, and young adults, which is especially relevant in patients of European ancestry. Prompt diagnosis is critical due to the systemic and genetic implications of cystic fibrosis.

Additional proposed mechanisms include a fungi-driven inflammatory process and an exaggerated immune response to exotoxins from Staphylococcus aureus. Systemic nasal polyposis refers to patients with systemic diseases that have nasal manifestations. Eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg-Strauss syndrome, and cystic fibrosis fall under this category.[3]

Epidemiology

CRS affects approximately 10.9% of the European population. Prevalence estimates vary in the U.S. Around 2.1% of individuals meet the diagnostic criteria based on 2 major symptoms, while 13.0% report only 1 symptom.[4] Among all patients with CRS, 25% to 30% are diagnosed with CRSwNP. In the U.S., CRSwNP typically presents between the ages of 40 and 60. Male individuals are more frequently affected, accounting for 62% of cases in a study, while female individuals represented 38%. Despite the lower prevalence, female patients are more likely to experience severe disease.

Pathophysiology

The pathophysiology of nasal polyps is varied. Aging leads to anatomical and functional changes that promote the stasis of thick mucus and impair the clearance of irritants and biological offenders, such as viruses, bacteria, and fungi, thereby increasing susceptibility to polyp formation. Changes include a decrease in ciliary beat frequency, resulting in impaired mucociliary clearance, atrophy of the sinonasal mucosa with reduced vasculature, and diminished mucus secretion. These changes contribute to increased permeability of the epithelial basement membrane and disruption of normal osmotic regulation between cells. Resultant edema and chronic inflammation cause localized increases in cell and tissue size. Hereditary factors have also been proposed, with cystic fibrosis as one example among many.

A study demonstrated a 4.1-fold increased risk of CRSwNP among 1st-degree relatives. Impaired innate and adaptive immunity, leading to bacterial colonization, has also been implicated. Patients with Staphylococcus aureus colonization exhibit higher levels of IgE and eosinophils in nasal polyps.[5][6] Hyperimmune responses triggered by fungal elements are believed to contribute to the formation of polyps.[7]

Histopathology

The histopathology of a nasal polyp depends mainly on endotype classification. Polyps in patients with CRSwNP tend to exhibit elevated tissue eosinophils, plasma cells, macrophages, edema, IL-5, and IgE. In contrast, specimens from patients without nasal polyps do not exhibit the same abundance of Th2 inflammatory markers. Within the same cohort, patients with AERD also demonstrated a high presence of eosinophils and mast cells.[8]

Another study confirmed tissue eosinophilia in patients with CRSwNP or AERD. However, no statistically significant association was found between asthma and tissue eosinophilia. Charcot-Leyden crystals may be observed in nasal polyp specimens, and their presence often correlates with more severe endoscopic findings.[9]

History and Physical

Nasal polyposis should be suspected in patients with progressive nasal obstruction, nasal or facial congestion, rhinorrhea, and a decreased sense of smell—the cardinal symptoms of CRS. Patients should be asked about sensitivity to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and the presence of asthma (Samter triad). Unilateral symptoms, a history of epistaxis, chronic otitis media, recurrent bronchitis, or pneumonia should raise suspicion for other possible etiologies.

Physical examination should include anterior rhinoscopy, where polyps and other neoplasms may be readily visible. Nasal polyposis is a clinical diagnosis based on anterior rhinoscopy or nasal endoscopic examination. Imaging studies, such as paranasal sinus computed tomography (PNS CT) scans, may be necessary to assess disease severity and aid in surgical planning. The presence of nasal polyps, accompanied by 2 cardinal symptoms, confirms the diagnosis of CRSwNP. Presentation ranges from asymptomatic disease to severely impaired QOL. People with the latter condition may require consultation with an otolaryngologist, as surgery may be needed for definitive treatment.[10]

Evaluation

A careful history and physical examination are crucial. Patients who meet the criteria for CRS should always undergo an endoscopic examination in the clinic. If nasal polyps are present, the endoscopic exam will reveal either unilateral or bilateral, mobile, smooth, grey, and semi-translucent masses originating from the middle meatus or sphenoethmoid recess. Nasal polyps supposedly presenting unilaterally should always raise suspicion for an alternate diagnosis, as inflammatory polyps are almost universally bilateral. While benign unilateral polyp etiologies, such as an antrochoanal polyp, exist, the suspicion for malignancy should remain high, and a referral to an otolaryngologist for a biopsy is indicated.

Typically, the diagnosis of CRSwNP is confirmed at this stage, and the patient should be directed toward appropriate medical management. Patients whose symptoms do not improve with adequate medical therapy will need further evaluation with a PNS CT scan. Furthermore, patients with unilateral symptoms or findings should undergo imaging studies as soon as possible. Surgery is considered an alternative for patients with an established diagnosis of CRSwNP who are refractory to medical management.[11]

Treatment / Management

The different endotypes and phenotypes of nasal polyps determine the appropriate management. For patients with CRSwNP, initial therapy with intranasal corticosteroids and nasal saline irrigations for approximately 2 to 3 months should be attempted. High-volume, low-pressure nasal saline irrigations are a safe and inexpensive method that increases the clearance of antigens, biofilms, and inflammatory mediators. Intranasal corticosteroids help alleviate nasal congestion and reduce polyp size.

When CRSwNP is refractory to adequate medical treatment, functional endoscopic sinus surgery (FESS) is planned. However, some debate persists among otolaryngologists on when surgery should be performed. Topical intranasal steroids form an essential part of CRSwNP treatment postoperatively. Surgery removes the anatomic obstruction and improves outflow tract drainage, but the underlying allergic etiology must be addressed. Topical nasal steroids, with or without topical antihistamines, are a mainstay, together with formal allergic testing and targeted immunotherapy if available.

At the procedural level, biodegradable steroid-eluting stents can be implanted during surgery. These stents keep the sinuses open while releasing steroids over the subsequent 30 days or more, thereby decreasing inflammation and reducing the likelihood of recurrence. Consequently, postoperative interventions and oral steroid use decrease. Continuing nasal saline irrigations and intranasal corticosteroids after surgery improves the likelihood of long-term success. Surgery aims to reduce the inflammatory burden of the disease and enhance the delivery of local medications in the postsurgical sinus cavities.

If a patient remains symptomatic despite the strategies above, oral corticosteroids may be used. Systemic steroids should be used mindfully to avoid unwanted side effects. Aspirin desensitization may benefit patients with AERD, characterized by nasal polyps, asthma, and aspirin sensitivity. Antibiotics are appropriate if evidence of an acute bacterial exacerbation is elicited. The role of antifungals in CRSwNP treatment remains controversial.

Lastly, biologic drugs, such as monoclonal antibodies, may be considered for patients with refractory disease. Candidates for biologics must have bilateral nasal polyps and meet 3 of the following criteria: severe anosmia, severe QOL impairment, diagnosed asthma, need for systemic steroids or a contraindication to these agents, or evidence of type 2 inflammation (eosinophilia > 250 cells/μL, blood IgE > 100 UI/mL, or tissue eosinophils > 10 HPF). Different immunotherapy treatments and regimens may be implemented in these patients. Dupilumab, omalizumab, and mepolizumab are among the most common options, with Dupilumab, an IL-4Ra antagonist, showing increasing efficacy compared to other biologics.

Treatment of the underlying condition is essential for patients with a systemic disease associated with nasal polyps, such as EGPA or cystic fibrosis. For example, patients with cystic fibrosis may receive ivacaftor, a cystic fibrosis transmembrane conductance regulator potentiator, which has been shown to improve QOL in patients with rhinologic disease.[12][13][14](A1)

Differential Diagnosis

The differential diagnosis of nasal polyps is extensive and includes the following conditions:

• Antrochoanal polyps
• Inverted papillomas
• Schneiderian papillomas
• Squamous cell carcinoma
• Non-Hodgkin lymphoma
• Melanoma
• Esthesioneuroblastoma
• Hemangiopericytoma
• Nasal duct cysts
• Nasal gliomas
• Encephaloceles
• Juvenile nasopharyngeal angiofibroma
• RhabdomyosarcomaHemangiomas
• Chordomas

Histologic confirmation of nasal growths is recommended in most cases. All of the above differentials may be ruled out with biopsies, especially if unilateral, which raises concern for neoplasia. For the same reason, polyps removed during endoscopic sinus surgery for chronic sinusitis should undergo histopathologic confirmation. Careful examination of preoperative imaging is essential. For example, encephaloceles may mimic inflammatory polyps during nasal endoscopy, but their true nature is revealed in computed tomography (CT) images. Biopsying an encephalocele could result in a cerebrospinal fluid fistula.

Thorough evaluation with imaging is critical if malignancy is suspected in the preoperative setting. A CT scan with intravenous contrast helps assess bony contours, vascularity of lesions, and soft tissue invasion. Magnetic resonance imaging (MRI) is useful for identifying perineural, orbital, and intracranial spread of neoplasms, as well as complicated sinusitis. Different pathologies of the nasal cavity appear differently on imaging. For instance, nasal polyposis typically presents as smooth, convex, enhancing soft tissue masses on CT scans, whereas squamous cell carcinomas may exhibit bony erosion on CT scans and a hypointense appearance on T2-weighted MRI, with homogeneous enhancement on contrast-enhanced MRI.[15]

Treatment Planning

Intranasal corticosteroids, such as budesonide, fluticasone propionate, and mometasone furoate, effectively reduce polyp size. These agents should be used twice daily for several weeks to achieve optimal effects. For more severe disease, oral corticosteroids may be prescribed in pulses and tapered gradually. No clear consensus has been established among otolaryngologists regarding the maximum daily dose of systemic steroids or the tapering regimen.

While antibiotics can be used to treat acute infections, their role in CRSwNP remains controversial. Some reports suggest success with macrolide therapy in cases of CRSwNP associated with low IgE levels and neutrophilic inflammation. Current trials are exploring the efficacy of this antibiotic class. However, macrolides should be used cautiously due to associated cardiovascular risks. Doxycycline has also shown success, with one randomized controlled trial indicating a modest reduction in polyp size, postnasal drip, and inflammatory markers.

Toxicity and Adverse Effect Management

Intranasal corticosteroids are generally safe for treating nasal polyps and rarely cause side effects. Occasional adverse reactions include epistaxis and nasal mucosa ulceration. Although more effective, oral steroids have a higher incidence of systemic side effects. These medications must be used cautiously in patients with diabetes mellitus and hypertension, which may trigger uncontrolled hyperglycemia and hypertensive crises in susceptible individuals. Gastric ulcers, osteoporosis, and psychiatric conditions are relative contraindications for the use of oral steroids. These agents should also be avoided in patients with known tuberculosis due to the risk of disease reactivation.

Prognosis

The disease endotype influences the prognosis of nasal polyps. According to Guo M et al, recurrence is more common in patients with allergic fungal rhinosinusitis (AFRS) than in those with CRSwNP due to asthma or aspirin sensitivity.[16] However, patients with aspirin sensitivity tend to have more extensive disease and higher recurrence rates than individuals with CRSwNP.[17] Other prognostic factors associated with worse outcomes include younger age at presentation, higher Lund-Mackay scores, high global osteitis, and elevated tissue eosinophilia or neutrophilia, as noted by Kim JY et al.[18]

Complications

Nasal polyps typically manifest as part of an underlying disease process, so complications are often linked to the primary condition. Patients with nasal polyps often experience obstructive nasal symptoms, which can impair sleep and, to a lesser extent, cause chronic fatigue. The polyps can obstruct the paranasal sinus drainage pathways, facilitating the formation of mucoceles, which may compress orbital structures, leading to exophthalmos, diplopia, and an unsightly appearance. In severe cases, the disease can significantly compromise QOL, potentially resulting in irreversible anosmia. Nasal polyps have also been linked to the development of obstructive sleep apnea (OSA).[19][20]