Nasal Polyps

Etiology

Nasal polyps are classified into three groups: localized, diffuse, and systemic. Localized nasal polyps are typically reactive from either inflammatory processes or neoplastic processes. Diffuse nasal polyposis is often seen in patients with CRSwNP. CRSwNP has multiple etiologies. In the western hemisphere, nasal polyps are mostly the result of T-helper 2 (Th2) cell-driven eosinophilia, immunoglobulin-E (IgE) inflammation, with elevated interleukin-5 (IL-5), often associated with environmental and/or seasonal allergic triggers.  Patients with cystic fibrosis tend to have neutrophil-driven inflammation within their polyps, and can often have severe nasal polyposis without a distinct allergic trigger, though the clinical examination can be very similar. Cystic fibrosis should be in the differential of the young patient (pre-teen, teen, and young adults) with refractory nasal polyposis, particularly in patients of European ancestry. Prompt diagnosis is essential, as there are systemic and genetic/familial implications of a cystic fibrosis diagnosis. Additional proposed theories include a fungi-driven inflammatory process, as well as a massive inflammatory response triggered by exotoxins from Staphylococcus aureus infections. Finally, systemic nasal polyposis refers to patients suffering from systemic diseases with nasal manifestations. Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, and cystic fibrosis (CF) fall into this category.[3]

Epidemiology

CRS affects 10.9% of the European population.[4] Some researchers estimate the prevalence of CRS in the United States (US) to be around 2.1% (i.e., those who meet the criteria of two major symptoms), while 13.0% of individuals report only one symptom.[5] Of all patients with CRS, about 25%-30% have CRSwNP.[4] In the United States, CRSwNP typically affects patients between 40 to 60 years old. Males are more likely to have CRSwNP, with one study showing a 38% prevalence in females and 62% prevalence in males. Yet, females are more likely to have severe disease.[2]

Pathophysiology

The pathophysiology of nasal polyps can be varied. As we age, there are a series of anatomical and functional changes that occur in the human body that lead to stasis of thick mucus and impaired clearance of irritants and biologic offenders (viruses, bacteria, fungi), making patients more prone to develop polyps. These changes include decreased ciliary beat frequency with impaired mucociliary clearance, sinonasal mucosa atrophy with decreased vasculature, and diminished mucus secretion. These all potentially result in increased permeability of the epithelial basement membrane and distortion in the normal osmotic regulation between cells. Overall edema and resultant chronic inflammation results, leading to a localized increase in cell and tissue size. Hereditary factors have also been proposed (cystic fibrosis being but one of the hereditary factors, there are many others).

One study showed a 4.1-fold increased risk in first-degree relatives of patients with CRSwNP. Lastly, impaired innate and adaptive immunity rendering patients to the colonization of bacteria has been implicated. It has been found that patients with Staphylococcus aureus colonization have higher levels of IgE and eosinophils in nasal polyps.[6][7] Also, hyperimmune responses in the presence of fungal elements are believed to play a role in the formation of nasal polyps.[8]

Histopathology

The histopathology of nasal polyps depends mainly on the endotype classification. Polyps in patients with CRSwNP tend to have higher tissue eosinophilia, plasma cells, macrophages, edema, IL-5, and IgE. In contrast, in patients without nasal polyps, the collected specimens do not share this abundance of Th2 inflammatory markers. In the same cohort of patients, those who suffered from aspirin sensitivity (AERD) also had a generous amount of eosinophils and mast cells.[9]

Another study confirmed increased tissue eosinophilia in patients with CRSwNP and patients with AERD; however, there was no statistically significant relationship between their asthma and tissue eosinophilia. Charcot-Leyden crystals can be found in nasal polyps specimens. The authors describe that the presence of these crystals typically correlates with worse endoscopic findings.[10]

History and Physical

Nasal polyposis should be suspected in patients with progressive nasal obstruction, nasal and/or facial congestion, rhinorrhea, and decreased sense of smell (cardinal symptoms of CRS). Patients should be inquired about sensitivity to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and the presence of asthma (Samter's triad). Unilaterality of symptoms, history of the epistaxis, history of chronic otitis media, recurrent bronchitis, and/or pneumonia should alert the clinician about other possible etiologies.

Physical examination should include an anterior rhinoscopy, where polyps and other neoplasms can be readily visible at times. Nasal polyposis is a clinical diagnosis based on anterior rhinoscopy or a nasal endoscopic examination. Imaging studies, such as computed tomography of the paranasal sinuses (PNS CT scan), are sometimes necessary to assess the severity of the disease, and can aid in surgical planning, if indicated. The presence of nasal polyps with two cardinal symptoms confirms the diagnosis of chronic rhinosinusitis with nasal polyposis. Presentation ranges from asymptomatic persons to patients with severely affected QOL. The latter may require the services of an otolaryngologist, as surgery may be required to begin their definitive treatment.[2][3][4][5][11]

Evaluation

A careful history and physical exam are crucial. Patients that meet the criteria of CRS should always receive an endoscopic exam 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. Unilateral "nasal polyps" should always raise the suspicion of an alternate diagnosis. Inflammatory polyps are almost universally bilateral. While there are benign unilateral polyp etiologies such as an antrochoanal polyp, the suspicion for malignancy should be high and a referral to an otolaryngologist is indicated for a biopsy.

Usually, the diagnosis of CRSwNP is confirmed at this time, and the patient should be directed towards adequate 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 be evaluated with 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.[4][12]

Treatment / Management

The different endotypes and phenotypes of nasal polyps will determine further management. For patients with chronic rhinosinusitis with nasal polyposis, initial therapy with intranasal corticosteroids and nasal saline irrigations for approximately 2-3 months should be attempted. High-volume, low-pressure nasal saline irrigations are safe and non-expensive and increase the clearance of antigens, biofilms, and inflammatory mediators. Intranasal corticosteroids improve nasal congestion and decrease polyp size. When CRSwNP is refractory to adequate medical treatment, functional endoscopic sinus surgery (FESS) is planned; however, there is still some debate among otolaryngologists on when surgery should be implemented. Topical intranasal steroids form an essential part of CRSwNP treatment postoperatively. Surgery removes the anatomic obstruction and restores more normal mucosal drainage, but the underlying allergic etiology must be addressed. Topical nasal steroids +/- topical antihistamines are a mainstay, together with formal allergic testing and targeted immunotherapy if available.

At a more specialized level, biodegradable steroid-eluting stents can be implanted during surgery. These stents keep the sinuses open while releasing steroids over the subsequent 30 or more days, thereby decreasing inflammation and recurrence. As a result, there is a decrease in post-operative interventions and oral steroid use. It is mandatory to continue nasal saline irrigations and intranasal corticosteroids even after surgery, as this will improve the likelihood of long-term success. The role of surgery is to decrease the inflammatory burden of the disease and to enhance the effects of local medications in the post-surgical sinus cavities.

If a patient continues to be symptomatic despite the aforementioned strategies, oral corticosteroids are occasionally used. The mindful use of systemic steroids should be implemented to avoid unwanted side effects. Aspirin desensitization is another strategy that might be beneficial for patients with AERD (nasal polyps, asthma, and aspirin sensitivity). Antibiotics are typically used if there is evidence of an acute bacterial exacerbation. The role of antifungals in the treatment of CRSwNP is controversial.

Lastly, biologic drugs (monoclonal antibodies) can be used in refractory disease. Candidates for biologic drugs must have bilateral nasal polyps and three of the following criteria: severe anosmia, severe QOL, diagnosed asthma, need for systemic steroids or a contraindication to these, or evidence of type II inflammation (eosinophilia >250 cells/microliter, blood IgE >100 UI/mL, or tissue eosinophils >10 HPF). For patients with a systemic disease with nasal polyps such as EGPA or CF, the underlying condition should be treated. For instance, patients with CF may be treated with ivacaftor, a CFTR potentiator, which has been shown to improve QOL in patients with rhinologic disease.[1][2][3][12][13][14](A1)

Differential Diagnosis

The differential diagnosis of nasal polyps can be extensive. Therefore, histologic confirmation of nasal growths is mandatory in most instances. The diagnosis might include:

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

All of the differentials mentioned above can be ruled out with biopsies in the operating room (OR), particularly if unilateral, which raises concern for neoplasia. For this same reason, polyps removed during endoscopic sinus surgery for chronic sinusitis need histopathologic confirmation. Careful examination of preoperative imaging studies is essential. For instance, encephaloceles might mimic inflammatory polyps during nasal endoscopy, while its true nature is identified in CT images. Biopsying an encephalocele will result in cerebrospinal fluid (CSF) fistula.[12]

In patients where you suspect malignancy in the preoperative setting, thorough evaluation with imaging is crucial. CT scan with intravenous (IV) contrast helps evaluate the bony contours, the vascularity of the lesions, as well as soft tissue invasion. Magnetic resonance imaging (MRI) helps to identify the perineural, orbital, and intracranial spread of neoplasms. It is also useful in cases of complicated sinusitis. Different pathologies of the nasal cavity have a different appearance on imaging. For instance, patients with nasal polyposis have smooth, convex, enhancing soft tissue masses on CT. In contrast, patients with squamous cell carcinomas may have bone erosion on CT and hypointense appearance on T2-weighted MRI with homogenous enhancement on contrasted MRI.[15]

Treatment Planning

Intranasal corticosteroids such as budesonide, fluticasone propionate, and mometasone furoate have been shown to reduce polyp size. These should be used twice daily for several weeks before optimal effects can be appreciated. In contrast, for more severe disease, oral corticosteroids can be given; these should be provided in pulses and in a tapered way. There is no clear consensus among otolaryngologists regarding the maximum daily dose of systemic steroids, nor the tapering regimen.[1] 

While antibiotics can be utilized for acute infection, the role of antibiotics in CRSwNP is controversial. There have been some reports of success in patients with CRSwNP with low IgE and neutrophilic diseases that receive macrolides. Current trials are underway to study further efficacy of this class of antibiotics. However, macrolides should be used judiciously since there are cardiovascular risks associated with them. Doxycycline has shown success in the literature, with one randomized control trial (RCT) revealing a small decrease in polyp size, post-nasal drip, and inflammatory markers.[10][11]

Toxicity and Adverse Effect Management

Intranasal corticosteroids are generally safe in the treatment of nasal polyps and rarely cause side effects. Occasional adverse reactions reported include epistaxis and nasal mucosa ulceration. Although more effective, oral steroids have a higher incidence of systemic side effects. They must be given cautiously to patients suffering from diabetes mellitus and hypertension, as these might trigger uncontrolled blood glucose levels and hypertensive crises in vulnerable individuals. Gastric ulcers, osteoporosis, and psychiatric conditions are relative contraindications for their use. They should also be avoided in patients with known tuberculosis as they might reactivate the disease.[12]

Prognosis

The prognosis of nasal polyps is influenced by the endotype of the disease process. According to an article by Guo M, et al., recurrence seems to be higher in patients with allergic fungal rhinosinusitis (AFRS) than patients with CRSwNP due to asthma or aspirin sensitivity.[16] However, when compared with CRSwNP patients, patients with aspirin sensitivity tend to have a more extensive disease and higher recurrence rates.[11][17] 

Other potential prognostic factors that are associated with the worst outcomes are younger age at presentation, higher Lund-Mackay scores, high global osteitis, and elevated tissue eosinophilia/neutrophilia, as noted by Kim JY et al.[18]

Complications

Nasal polyps are usually a manifestation of the underlying disease process; therefore, complications are usually determined by the underlying problem. Patients with nasal polyps have obstructive nasal symptoms with impaired sleep and, to a lesser extent, chronic fatigue. Nasal polyps can obstruct the paranasal sinuses drainage pathways facilitating the formation of mucoceles.

Mucoceles can be responsible for the compression of orbital structures, causing exophthalmos, diplopia, and unsightly appearance. Some patients may have such an extensive disease that their QOL is severely compromised. In such a scenario, nasal polyps might result in irreversible anosmia. Also, it has been described that nasal polyps contribute to obstructive sleep apnea (OSA).[2][19][20]