Nasal polyps are benign inflammatory and hyperplastic outgrowths of the sinonasal mucosa. Their most common manifestation is in patients with chronic rhinosinusitis (CRS). For this reason, the term chronic rhinosinusitis with nasal polyposis (CRSwNP) is frequently used when discussing the topic of nasal polyps. However, they are also associated with aspirin-exacerbated respiratory disease (AERD), certain systemic vasculitis, and cystic fibrosis, among others. Presentation ranges from asymptomatic persons to patients with significant nasal obstruction, nasal and facial congestion, anosmia, ageusia, and rhinorrhea. These symptoms decrease the quality of life (QOL) of affected individuals.
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). On the contrary, patients with cystic fibrosis tend to have neutrophil-driven inflammation within their polyps. 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.
CRS affects 10.9% of the European population. 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. Of all patients with CRS, about 25%-30% have CRSwNP. 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.
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. Hereditary factors have also been proposed.
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. Also, hyperimmune responses in the presence of fungal elements are believed to play a role in the formation of nasal polyps.
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.
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.
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. 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. Usually, nasal polyps are diagnosed with 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. 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 tend to visit the otolaryngologist seeking remediation.
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.
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.
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.
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. 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 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.
The differential diagnosis of nasal polyps can be extensive. Therefore, histologic confirmation of nasal growths is mandatory in most instances. The diagnosis might include:
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.
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.
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.
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.
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.
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. However, when compared with CRSwNP patients, patients with aspirin sensitivity tend to have a more extensive disease and higher recurrence rates.
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.
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).
Patients with nasal polyposis need to be evaluated by an otolaryngologist to investigate the underlying etiology and treat their disease state. Once an underlying etiology has been established and an endotype has been implicated, several consultations should be considered. For patients with AERD, CRSwNP, and allergic fungal rhinosinusitis, the allergist should be consulted; either immunotherapy, aspirin desensitization, or both might be indicated.
For patients with underlying CF, EGPA, or other systemic diseases, the role of the pulmonologist is imperative. In these cases, treating the underlying condition will most likely result in significant improvement of the nasal symptoms. An interprofessional team approach in patients with nasal polyposis should always be considered due to the complexity of this disease process and its associated comorbidities.
Since each patient is different, there is no way to predict how detrimental nasal polyps can be to someone's health and personal circumstances. In many situations, people live daily with nasal polyps without knowing it and do not seek medical care for their bothersome symptoms. Once identified, patients with nasal polyps should undergo a complete medical evaluation. Besides the improvement in their nasal breathing, patients should understand that the etiology of the nasal polyps should be narrowed down and that additional clinical evaluation by a pulmonologist and allergist will help in the management of the disease and in identifying and treating additional undiagnosed comorbidities such as asthma.
One important remark towards patient education is adherence to treatment. It has been shown that consistent use of high-volume low-pressure nasal saline irrigation, in addition to twice-daily intranasal corticosteroids, improve the QOL of those affected. Many patients with nasal polyposis will experience recurrence due to a lack of adherence to the daily nasal spray. It is important to follow-up with patients closely and reiterate the importance of compliance with the medication to see optimal results.
Like most diseases, medical management usually precedes surgery. Surgery for nasal polyps, although generally safe and well-tolerated, has multiple risks, including significant bleeding, epiphora, and rarely, damage to orbital or intracranial structures. Therefore, it is always important to start patients on intranasal corticosteroids and nasal saline irrigations, assess compliance, and follow their improvement.
Failure to respond to medical management or the presence of very severe symptoms might warrant surgery. Furthermore, patients should understand that although surgery will improve their quality of life significantly, it might not cure the disease. Patients should continue medical management to optimize surgical results. Close follow-up is indicated to ensure the patient’s quality of life is satisfactory. The 22-item sinonasal outcome test (SNOT-22) is a valuable instrument to assess a patient’s burden of disease and track improvement throughout the treatment period.
Primary care clinicians are the first to care for patients with nasal polyposis. Therefore, they must have the clinical knowledge to detect this disease and begin the patient on appropriate therapy before referring them to the otolaryngologist. Since impaired QOL might affect the patient’s emotional well-being, there are times psychiatric evaluation might be warranted. Cooperation between allergists, pulmonologists, and otolaryngologists is required to improve patient management and treatment outcomes. Pathologists help establish the etiology of nasal polyps and are valuable for ruling out neoplasia.
Diagnostic radiologists play an integral role in the care of nasal polyposis patients. The intricate anatomy of the paranasal sinuses with its anatomical variants may pose risks during endoscopic sinus surgery. Accurate interpretation of PNS CT scans may assist the otolaryngologist in avoiding surgical complications. Pharmacists involved in the care of patients with nasal polyposis should be familiar with drug compounding, as different medications can be added to nasal saline irrigations to help control the inflammatory process within the sinuses. Nurses play a pivotal role in educating patients regarding their condition and assist the clinician with treatment compliance. Excellent interprofessional communication is essential in the management of nasal polyposis patients.
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