Objectives

1. Learn how to diagnose and treat nasal polyps.
2. Understand the background historical issues associated with nasal polyps.
3. Learn about the epidemiology of nasal polyps.
4. Be familiar with comorbid conditions and clinical symptoms.
5. Understand the histology, putative pathogenesis, and grading system for nasal polyps.

Key words

allergy; nasal polyposis; polyp; sinus surgery; steroids

Abbreviations

AFS = allergic fungal sinusitis; CF = cystic fibrosis; COX-2 = cyclooxygenase-2; NSAID = nonsteroidal anti-inflammatory drug;

Nasal polyps are nasal epithelial outpouchings incited by inflammation.¹ Nasal polyposis, a disease of the upper respiratory tract, can lead to symptoms of a perceived inability to breathe secondary to nasal obstruction—“stuffiness.” The presence of nasal polyps may predispose to recurrent episodes of bacterial sinusitis.² Patients may develop headaches, postnasal drip, facial pain, and possibly cough.³ Anosmia, hyposmia, and dysgeusia are common. Other symptoms include rhinorrhea,⁴ snoring,⁵ and mouth breathing. Nasal polyposis may be associated with diseases of the lower respiratory tract, including asthma,^6,7 Kartagener’s syndrome,⁸ and cystic fibrosis.⁹ Therefore, a chest physician who improves his or her clinical acumen regarding nasal polyps will be better able to treat his or her patients afflicted with this condition.

Historical Background

Nasal polyps were recognized as an illness in Egypt at least 3,000 years ago. Hippocrates developed two surgical methods of nasal polypectomy in 400 BC: (1) extraction by pulling a sponge through the nasal passages; and (2) cauterization (loop technique) [Fig 1]. The former method utilized a round sponge tied with a cord passed through the loop end of a flexible tin curette. Polyps were removed by avulsing them through the mouth by pulling these threads. The latter method, so-called cauterization, involved using powder of black hellebore—a scarforming, escharotic, caustic substance—for destroying tissue. Irons were inserted into a syringelike device used as a protective tube to avoid burning the surrounding tissue.10

Paul of Aegina, in the 7th century, wrote a book chapter called “About Polyps,” wherein he noted that a polyp “is a tumor which is created in the nose and which takes its name from the marine animal (named ‘polyp’) because it resembles the flesh of this creature and its behavior; as the animal protects itself with its tentacles, so the polyp reacts and extends itself in the nose of a sufferer, obstructing the nostrils and provoking dysfunction in breathing and talking.” He described a polypodic sword (polypus knife) and polypoxestes (polypus eradicator) [Fig 2].¹⁰

Epidemiology

Nasal polyps occur in all races and social classes. They affect 1 to 2% of the adult population in Europe. The male:female ratio is between 2:1 and 4:1. A hereditary association has been described. Symptoms usually manifest after the age of 20 years. Nasal polyposis is rare in healthy children (0.1% prevalence) but is common in patients with cystic fibrosis (CF). CF must be excluded in any child with nasal polyps, even in the absence of overt pulmonary disease.^11,12 Figure 3 shows the CT appearance of polyps.

Comorbid Medical Conditions

Ten disease entities associated with nasal polyps are important to the chest physician: IgE-mediated disease, asthma, aspirin and nonsteroidal antiinflammatory drug (NSAID) intolerance, Kartagener’s syndrome, CF, allergic fungal sinusitis (AFS), Churg-Strauss syndrome, Young’s syndrome, nonallergic rhinitis with eosinophilia syndrome, and sarcoidosis.

IgE-Mediated Disease

The incidence of allergies in patients with nasal polyps, as detected by allergy skin tests, a measure of specific IgE from epidermal mast cells, is no higher than that of the general population. However, some authors suggest that a subgroup of patients with nasal polyps have IgE-mediated disease with IgE in nasal secretions equivalent to those patients with allergic rhinitis. It remains to be determined why some patients develop allergic rhinitis and others may have superimposed nasal polyposis.¹³ One study showed that 29.4% of patients with nasal polyps had allergic rhinitis.¹²

Asthma

Roughly 70% of patients with nasal polyps have asthma.^11,12 Nasal polyps typically occur 10 years after the diagnosis of asthma.¹⁴ The Rhode Island Hospital allergy group reviewed several thousand records and noted that 6.7% of their asthmatic patients had nasal polyposis.¹⁵ These authors tested patients for skin-prick reactivity to “trees, grasses and ragweed pollen extracts, animal danders, and selected molds.” Of asthmatics with negative skin tests, 12.5% had nasal polyps, whereas 5% of asthmatics with positive skin tests had polyps.¹⁵ A recent Israeli series of 34 asthmatics with massive nasal polyps determined that functional endoscopic sinus surgery improved symptoms of nasal breathing and quality of life, but did not alter the clinical course of asthma postoperatively.¹⁶

Aspirin and NSAID Intolerance

Both aspirin and NSAID intolerance are associated with nasal polyps. For example, the antiphlogistics indomethacin and ibuprofen are cited as culprit medications. About 36% of patients with aspirin intolerance have nasal polyps.¹⁷ Although Widal described a triad of nasal polyps, aspirin intolerance, and asthma in 1922, it was not until 1967 that Samter and Beer promoted this clinical observation we now know as Samter’s triad. This entity occurs in 36 to 39% of patients with nasal polyps.¹⁸ For those patients with Samter’s triad, desensitization to aspirin helps. Approximately 65% of patients who receive nasal steroids and aspirin desensitization have improvement in hypersecretion and nasal blockage, while 74% show shrinkage of nasal polyps and improvement in symptoms of hyposmia or anosmia.⁶

Kartagener’s Syndrome

This is a rare ciliary dyskinesia syndrome (1/20,000 births) that involves bronchiectasis, situs inversus, and sinusitis. These patients may have nasal polyps.⁷ The original description by Kartagener noted a mirror-image organ arrangement (situs inversus), bronchiectasis, and sinusitis. Electron microscopic abnormalities in sperm tails from infertile men are a result of structural ciliary abnormalities. A dyskinetic beat pattern of cilia is seen, while 10% have a beat frequency within the normal range.^18a

Cystic Fibrosis

One of the most common hereditary diseases in Caucasians is CF, which often arises from an autosomal recessive defect of the cystic fibrosis transmembrane regulator (CFTR) gene on chromosome 7. This gene codes for a chloride channel on respiratory-tract epithelium. This defect causes these patients to have thick, inspissated secretions, which predisposes them to infections in both the lungs and the sinuses. The classic bacterial culprits are Pseudomonas spp. CF is also associated with digestive malfunction (pancreatic exocrine gland dysfunction/meconium ileus).¹⁹ In one study, 37% of patients with CF had nasal polyps.²⁰

Allergic Fungal Sinusitis

Nasal polyposis, crust formation, and sinus cultures growing Aspergillus were first noted in 1976 by Safirstein,²¹ who observed the similarity to allergic bronchopulmonary aspergillosis. There is currently no consensus regarding the diagnostic criteria for AFS. The most recently published criteria are from Bent and Kuhn²² in 1994. These include the presence of (1) Gell and Coombs type I hypersensitivity (IgE-mediated), (2) nasal polyps, (3) characteristic radiographic findings on sinus CT and MRI, (4) eosinophilic “allergic” mucin without fungal tissue invasion, and (5) positive fungal stain. The characteristic CT findings are serpiginous areas of increased attenuation within the sinuses.²³ Bony erosion with disease extension is present in approximately 20% of cases.²⁴ The characteristic MRI findings are hypointense regions with surrounding enhancement on T1-weighted images, as well as decreased signal intensity with surrounding enhancement on T2-weighted images.^25,26 Grossly, the eosinophilic mucus is rubbery and tenacious, like peanut butter or axle grease, and can range from green to brown.^22,27 It may be difficult to remove with usual suctioning.

Histologically, there are sheets of eosinophils, Charcot-Leyden crystals, and scarce fungal hyphae that will require a silver stain for identification.²² This eosinophilic mucus is sent for both pathologic and microbiologic examination, and is very important for making the diagnosis.²⁸ The mucosa and polyps removed at surgery will show chronic inflammation, but need to be examined to rule out fungal tissue invasion.²⁸ The dematiaceous fungi (Bipolaris, Curvularia, etc.) are the more predominant causative fungi, not Aspergillus.^29-31 This condition is most common in the Southwest and Southeast United States.³² It appears that atopy, as well as specific T-cell human leukocyte antigen receptor expression, fungal exposure, and abnormal mucosal immunity, may play a role in its pathogenesis.³³

The treatment of choice consists of (1) surgical drainage of the sinuses, ie, functional endoscopic sinus surgery, to ensure complete removal of all fungal mucin; followed by (2) immunomodulation in the form of topical and systemic steroids and/or immunotherapy; and (3) antifungal medications, either topical or systemic.³³

Currently, no guidelines exist as to the optimal steroid regimen after surgery.³³ Immunotherapy is recommended after surgery so that the allergic load is reduced.^34-37 Patients who receive immunotherapy after surgery for AFS have a better clinical outcome than those who have received immunotherapy before surgery.³⁸ Multiple fungal antigen immunotherapy, as well as immunotherapy to all other positive allergens, is advocated.^38-40

Cultures are not uniformly positive, and culture techniques may miss certain “mold” subtypes.³¹ Skin testing for reactivity to several locally pervasive molds is suggested. Systemic antifungal agents have many known negative side effects, and because there are no good studies to prove their effectiveness in this disease, their usefulness is limited.⁴¹ Topical antifungals may be of benefit; studies are underway to prove this.^42,43 AFS recidivism is well recognized, and a combination of both medical and surgical management is the best way to treat this difficult disease.³³

Churg-Strauss Syndrome

Churg-Strauss syndrome is a vasculitis characterized by asthma, 10% peripheralblood eosinophilia, pulmonary infiltrates, and paranasal sinus abnormalities (1990 criteria). Extravascular eosinophils may be seen. Fifty percent of patients with Churg-Strauss syndrome have nasal polyps.^45,46 In recent years, leukotriene modifiers used for the treatment of asthma, with the potential benefit for allergic rhinitis, were of concern because of a possible correlation between Churg-Strauss syndrome and the use of these agents. However, a review in CHEST noted no such correlation.⁴⁷ Conventional wisdom suggests that underlying Churg-Strauss vasculitis is unmasked when a patient’s steroid therapy for asthma is tapered as a result of leukotriene modifier use.

Young’s Syndrome

Young’s syndrome is a triad of chronic sinusitis, azoospermia, and nasal polyposis.⁴⁸

Nonallergic Rhinitis With Eosinophilia Syndrome

This entity is found in patients who have rhinorrhea but negative skin-prick test reactions to allergens. Yet, nasal lavage indicates the presence of eosinophils. These patients respond to nasal corticosteroids. Nineteen percent of these patients have nasal polyps.⁴⁹ Nonallergic rhinitis with eosinophilia syndrome is not IgE-mediated in a manner consistent with allergic rhinitis. A careful clinician should determine that antihistamines and topical corticosteroids have been discontinued prior to skin-prick testing to avoid a false-negative result.⁴⁹

Sarcoidosis

Although not a classic common finding on physical examination, there are three articles in the literature describing nasal polyp resection yielding a diagnosis of sarcoidosis from histologic examination. On occasion, systemic sarcoidosis was later diagnosed.^50-52

Clinical Symptoms

Patients with nasal polyposis may visit a physician because of a chief complaint of an inability to breathe through the nose.⁵³ They may have a hyponasal voice (rhinophonia clausa).⁵⁴ Hyposmia or anosmia is common as well, as is dysgeusia. Snoring can occur as a result of upper airway obstruction, as can postnasal drip/rhinorrhea, cough, and/or headache.^3-5

Physical examination of the anterior nares with a standard office speculum may miss a nasal polyp, especially when it only occupies the middle meatus. A diagnostic nasal endoscopy may be necessary. Nasal polyps are often pearly, glistening, pale gray, smooth and semitranslucent (Fig 4). They attach from a pedicle and arise from the ostiomeatal complex, most often from the uncinate process of the ethmoid bone and the middle turbinate.⁵⁶

The differential diagnosis of nasal polyps in adults includes benign tumors such as inverting papilloma or antrochoanal polyp, and malignant tumors such as squamous cell or adenocarcinoma (Table 1). Diamantopoulos et al⁵⁷ reviewed 2,021 nasal polyps biopsied from 1991 to 1999 and noted that 22 cases (1.1%) had a different ultimate diagnosis based on histology. In children, the presence of nasal polyps automatically requires a sweat test to rule out cystic fibrosis.⁵⁸ The differential diagnosis of nasal polyposis in children also includes meningocele, encephalocele, and glioma.^12,59-60

Histology, Pathogenesis, and Grading

Typically, histologic analysis of tissue from nasal polyps shows edema and eosinophilia. In a series of 95 resected nasal polyps, Davidsson and Hellquist⁵ found that 82 polyps displayed the usual edema/eosinophilia pathology (Fig 5), 7 were neutrophilic/fibroinflammatory, 5 had hyperplasia of seromucinous glands, and 1 indicated atypical stroma. Tissue eosinophilia is seen in 80 to 90% of cases.⁶² Regulated on activation, normal T-cell expressed and secreted (RANTES) is a chemokine that, along with eotaxin and interleukin-5, mediates migration of eosinophils into the lamina propria of nasal polyps.^62,63 There is hyperplasia of sebaceous glands. Nasal washings show neutrophilia in 7% of cases, especially in patients with CF, primary ciliary dyskinesia, or Young’s syndrome. Mast cells are present. Often, as mentioned above, the histology points to a non-IgE-mediated mechanism.^5,12(p1026)

Basic fibroblast growth factor has been localized to nasal polyps and may contribute to the pathology of the disease.⁶⁴ Similarly, matrix metalloproteinase-1 and matrix metalloproteinase-9 have been noted to be expressed in areas of matrix degradation in nasal polyp fibroblasts.^65,66 Glucocorticoid receptors and cyclooxygenase-2 (COX-2) are present in nasal polyps; therefore, they suggest a role for steroids (and perhaps COX-2 inhibitors) in modulating inflammation in patients with this disease.⁶⁷ Not surprisingly, nuclear factor kappa beta, a socalled final common pathway of inflammation as a transcriptional promotor of inflammation, has been determined to be constitutively expressed in nasal polyps.⁶⁷ Although some authors postulate a role for food allergy in causing nasal polyps (intradermal skin tests to food are positive in 85% of those with polyps, compared with 11% in healthy control individuals) there has been a lack of evidence indicating that food challenges can cause a dose-dependent increase in nasal polyp number and size.⁶⁸

A nasal polyp grading system is shown in Table 2.

Treatment

Treatment modalities for nasal polyps include medical management alone or in combination with surgical intervention.⁷⁰ Despite advances in both medical and surgical treatment modalities, we do not have a cure for nasal polyps. These therapies are only able to delay the reformation of polyps. This is due to the fact that the etiology and pathogenesis of nasal polyps are not completely understood.⁷¹

Although the use of functional endoscopic sinus surgery along with glucocorticoids is a common treatment modality, a recurrence rate of at least 40 to 60% is common.^72,73 Indeed, nasal polyp recurrence rates are higher in patients with asthma or aspirin intolerance and negative skin tests.⁴⁵ Persistent nasal obstruction after a course of steroids may warrant surgery.⁷⁴

The mainstay of medical management is topical steroids,⁷⁵ which have been shown to be effective in the primary treatment of nasal polyps as well as in maintenance therapy to delay recurrence after surgery.⁷⁶ Systemic steroids can also be added, and are very helpful during the perioperative period.⁷⁷ For patients with small polyps that are not causing significant nasal obstruction, topical corticosteroids may be sufficient to shrink polypoid tissue and yield symptomatic improvement. For patients with large polyps, a short course of systemic corticosteroids combined with topical therapy may provide relief of nasal symptoms.⁷⁸

Medical treatment modalities that have been reported in the literature but are not yet accepted as the standard of care include the use of antileukotrienes,⁷⁹ longterm low-dose macrolide therapy,⁸⁰ topical capsaicin,⁸¹ topical furosemide,⁸² immune modification with interferon alfa-2a,⁸³ and, most recently, topical amphotericin B.⁸⁴

For many years, the surgical management of nasal polyps consisted of a simple intranasal snare polypectomy. The surgeon wore a headlight and used a wire snare to remove polyps from the nasal cavity only. This provided excellent relief of nasal obstruction, but the recurrence rate was very high because it did not address the abnormal tissue from within the sinuses themselves. Then in the late 1980s, David Kennedy introduced functional endoscopic sinus surgery to North America.⁸⁵ This revolutionized the surgical management of nasal polyposis. This surgery entails using a rigid telescope with both straight and varying angles that improve visualization within the sinuses. These are used along with grasping and/or cutting instruments to remove diseased tissue directly from the affected sinuses to create open drainage pathways. A coronal CT film is placed on a viewbox in the operating room to be used as a “road map.” The recurrence rate after this surgery is much lower than with the intranasal snare polypectomy, but it is still not a cure.^85,86

Another surgical advancement is the use of powered instrumentation, which has greatly improved dissection techniques.^87,88 Powered instruments suction and cut tissue precisely. This allows for a faster and more complete removal of the visualized abnormal tissue, while sparing the normal mucosa.^87,88

Most recently, the use of CT image-guided surgery has greatly improved the surgeon’s ability to do a more complete dissection (Fig 6).^90,91 Preoperatively, a special thin-cut sinus CT scan that allows the surgeon to orient the patient in space is obtained. At surgery, the patient is registered, and then the surgeon can point to an area within the sinus cavity to determine if it is safe and/or necessary to enter that particular air cell. The margin of error is approximately 1 to 2 mm, and therefore the surgeon still must know the complicated and varying anatomy of the paranasal sinuses.⁹⁰

Summary

Nasal polyps are nasal epithelial outpouchings incited and promoted by inflammation. Although some patients have IgE-mediated disease with positive skin tests, others do not. Symptomatic patients may have nasal stuffiness, perceived inability to breathe, postnasal drip, cough, headache, anosmia, and dysgeusia. Physical examination reveals pale, glistening lesions that sometimes require nasal endoscopy to be recognized. Despite surgery and steroids, there is still a high recurrence rate. Underlying disease processes—eg, IgE-mediated disease, AFS, Churg-Strauss syndrome, CF, Kartagener’s syndrome, Samter’s triad, or asthma—must be diagnosed and treated.

The pathogenesis of this eosinophilic yet avascular lesion is complex and still incompletely understood. As we come to better understand the etiology and pathogenesis of nasal polyps, new treatment modalities are sure to be found that will enhance our ability to treat this challenging disease entity. As chest physicians, we serve our patients’ health well by understanding the nuances of this ancient disease.

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