Re: Nasal Polyposis: What Every Chest Physician Needs To Know

[Guest guest]

Thanks for this... I learned a lot! But omg... I could have done

without reading Hippocrates's surgical method. I'm still cringing!

Kim

> Technical - but worth the read...

>

> Nasal Polyposis: What Every Chest Physician Needs To Know

> By M. Szema, MD, FCCP; and C. Monte, MD

>

> To print for Mac press 'Cmd+p' on your keyboard.

> To print for Windows press 'Ctrl+p' on your keyboard.

>

> Objectives

> Learn how to diagnose and treat nasal polyps.

> Understand the background historical issues associated with nasal

> polyps.

> Learn about the epidemiology of nasal polyps.

> Be familiar with comorbid conditions and clinical symptoms.

> 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

>

> 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)

>

> 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,

> sson 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

>

> 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,

> 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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