Recent Patents on Inflammation & Allergy Drug Discovery 2011, 5, 241-252 241

Nasal Polyposis: An Overview of Differential Diagnosis and Treatment

Cemal Cingi1, Duygu Demirbas2 and Ahmet Ural3,*

1
Osmangazi University, Medical Faculty, Department of Otorhinolaryngology, Eskisehir, Turkey, 2Acibadem Hospitals,
Department of Otorhinolaryngology, Istanbul, Turkey, 3 Karadeniz Technical University School of Medicine, Depart-
ment of Otorhinolaryngology, Trabzon, Turkey

Received: October 21, 2010; Accepted: July 8, 2011; Revised: July 11, 2011

Abstract: Nasal polyposis is a chronic inflammatory disease of the nasal and paranasal sinus mucosa. Etiology remains
unclear, but allergy, asthma, aspirin sensitivity, cystic fibrosis, and infection have been associated with the disease. Clini-
cally, nasal obstruction, anosmia/hyposmia, rhinorrhea, postnasal drainage, headaches, facial pain, and sleep disorders
constitute the main symptoms. Intranasal examination reveals bilateral, mobile, grey, smooth and semi translucent poly-
poid masses that usually originate in the ethmoid sinuses or the middle meatus. Differential diagnosis is important to rule
out congenital anomalies, as well as benign or malignant tumors. In the evaluation of nasal polyps, computerized tomo-
graphy is helpful especially in determining the extent of the disease and in planning the surgical approach. Management of
nasal polyposis consists of medical therapy and surgery. Surgical treatment is performed in cases that are refractory to
medical therapy. Recurrence of nasal polyps is quite common and medical therapy after surgery is often necessary for
avoiding recurrences. This paper aims to summarize the current trends in the diagnosis, management of nasal polyposis
and relevant patents.
Keywords: Diagnosis, nasal polyposis, pathopysiology, treatment.

INTRODUCTION indicate cystic fibrosis. There is a male predominance, with a

ratio of 2-4:1 [2].
Nasal polyposis has been known for more than 4000
years, and inteersitngly it is the first disease in history where
both the doctor and patient names had been recorded [1]. ETIOPATHOGENESIS
Nasal polyposis is often associated with systemic diseases Historically, allergy had been supposed to paly role in
and is characterized by nasal obstruction, anosmia/hyposmia, nasal polyposis is allergy; due to the increased number of
rhinorrhea, postnasal drip, headache, facial pain, and im- eosinophils in nasal secretions and similarity of clinical
paired quality of life [2, 3].In case of a unilateral nasal polyp, symptoms. Contemporarily, polyps are considered to occur
other possibilities such as benign or malignant tumors and as a consequence of chronic inflammation that may be initi-
congenital abnormalities should be ruled out. Due to the ated by both infectious and noninfectious causes. Several
obscure etiology and high rate of recurrence; treatment of hypotheses have been proposed to explain the pathogenesis
nasal polyps has always been a challenge in ENT practice. of nasal polyps.
There is no consensus for a standard therapy, approach, or
algorithm; and the management of nasal polyposis remains ALLERGY
primarily medical. Topical steroids can be combined with
systemic corticosteroids in severe cases [4]. Surgery is indi- In the past, nasal polyps were associated with allergic
cated in patients who are refractory to medical management diseases, because of the high concentration of eosinophils in
or in whom complications occur. Postoperative care needs to polyp tissue and similarity of clinical symptoms to allergic
be meticulous to avoid or at least to delay recurrences. rhinitis. Recently, studies have suggested that polyps are, in
fact, more likely to be linked to non-allergic inflammation
EPIDEMIOLOGY rather than allergic disease [9] Table 1.
Some studies have shown that the incidence of allergic
The prevalence of nasal polyposis in the general popula-
disease and rates of prick test positivity among the patients
tion has been estimated at 1-4% [2]. In autopsy studies, this
prevalence has been shown to be as high as 40% [5-8]. Nasal with nasal polyps are not higher than the general population.
Allergic disease in nasal polyp patients appears to be a coin-
polyps are usually present between the ages of 20 and 60
cidence [10]. Patients with nasal polyps have specific IgE
years. Nasal polyposis in children under 10 years of age may
manifested nasal mucosal allergy with no sign of systemic
allergy. This suggests that local allergic mechanisms, in the
absence of systemic features, could play role in the patho-
*Address correspondence to this author at the Medical Faculty, Department
of Otorhinolaryngology Karadeniz Technical University, Trabzon, Turkey; genesis [11]. Total and specific IgE levels have correlated
Tel: 0090 462 3775884; Fax: 00 90 462 3250518; with levels of eosinophils but not with prick test positivity
E-mail: ahmetural2001@yahoo.com [12].

1872-213X/11 $100.00+.00 © 2011 Bentham Science Publishers

242 Recent Patents on Inflammation & Allergy Drug Discovery 2011, Vol. 5, No. 3 Cingi et al.

Table 1. Prevalence of Nasal Polyposis in Different Popula- BERNOULLI PHENOMENON

tion Subgroups [9].
The Bernoulli phenomenon is based on the decreasing
pressure throughout a narrowing passage. When such a
Aspirin intolerance 36-72% change occurs in the nasal passage, the resulting pressure
Adult asthma 7% difference sucks the mucosa outward. Thus, it appears that
the negative pressure induces the inflamed mucosa to project
IgE mediated 5% into the nasal cavity, resulting in polyp formation [10].
Non-IgE mediated 13%
NITRIC OXIDE
Chronic sinusitis in adults 2%
Nitric oxide is a free radical that is kept in balance by the
IgE mediated 1% antioxidant defense system, which includes superoxide dis-
mutase (SOD), catalase, and glutathione peroxidase. In-
Non-IgE mediated 5%
creased levels of nitric oxide and decreased SOD were found
Childhood asthma/sinusitis 0.1% in patients with nasal polyps compared to controls, suggest-
ing the presence of free radical damage in nasal polyps [17].
Cystic fibrosis

Children 10% Conditions Associated with Nasal Polyposis

Adults 50% Asthma and Aspirin Intolerance
Allergic fungal sinusitis 66-100% Nasal polyposis has been related to aspirin (ASA) intol-
erance and asthma, with an eosinophilic inflammatory
Primary ciliary dyskinesia 40% mechanism [2]. Seven% of asthmatic patients were found to
have nasal polyps [6], while 20-40% of patients with nasal
INFECTION polyps have asthma. Among patients with ASA intolerance,
36% have nasal polyps [6,7].
Many patients with nasal polyps have a history of chronic
rhinosinusitis; the pathogens isolated were common patho- The combination of nasal polyps, ASA intolerance, and
gens in rhinosinusitis such as Staphylococcus aureus, Strep- aspirin-induced-asthma was described by Samter in 1967 and
tococcus pneumoniae, and Bacteroides fragilis. In addition later named as Samter’s Triad. Inhibition of the cyclooxy-
to these, Pseudomonas aeruginosa may be isolated in nasal genase enzymes (COX1 or COX2) with aspirin shunts ara-
polyposis patients with cystic fibrosis [13]. S. aureus is de- chidonic acid metabolism towards the leukotriene pathway.
tected in the mucin of 60-70% of patients with nasal poly- This leads to decreased levels of PGE2 and increased levels
posis Enterotoxins (SEA, SEB) excreted by Staphyloccus of cysteinyl leukotriene (Cys-LT), which may lead to serious
aureus may act as superantigens and cause clonal expansion inflammatory responses and chronic inflammation [8].
of lymphocytes. Increased levels of Th1 and Th2 cells may Genetic Predisposition
lead to mucosal damage [14]. Nasal polyps occurring secon-
dary to infections exhibit a predominance of, neutrophils and Cystic fibrosis (CF) is caused by an autosomal-recessive
lymphocytes rather than an eosinophilic infiltration [13]. defect of the CFTR gene on the long arm of chromosome 7.
Typical features of CF patients are high concentration of
Fungal infections may contribute to the development of chloride in sweat, recurrent pulmonary and paranasal sinus
nasal polyps, since eosinophils attack fungal elements and infections, nasal polyposis, pancreatic insufficiency, and
release toxic mediators, resulting in secondary mucosal in- infertility [18]. Among patients with CF, 10% of the children
flammation and polypoid changes [15]. Aspergillus sp. is the and 50% of the adults have concomitant nasal polyps [9].
most common fungal species found in paranasal sinuses. In
one study, 45% of patients with nasal polyps had a positive Nasal polyps are encountered in patients with other ge-
skin prick test with mold extracts and 40% had a positive netic syndromes, such as primary ciliary dyskinesia, an auto-
skin prick test for Candida albicans. In contrary, only 11% somal recessive disorder in which patients are plagued with
of control subjects were positive on skin prick test with mold recurrent upper respiratory tract infections including chronic
extracts [16]. To our knowledge, no viral etiology has been sinusitis. The maximal manifestation of the illness is known
demonstrated in the development of nasal polyposis yet. as Kartagener’s syndrome.
Young’s Syndrome is another disease characterized by
VASOMOTOR IMBALANCE recurrent respiratory infections, azoospermia and nasal pol-
yps. Churg-Strauss Syndrome is a granulomatous vasculitis
In recent years, due to the fact that most of the nasal
and one third of patients had been reported to suffer from
polyposis patients were found to be not atopic; the vasomo-
nasal polyps. Another study reported a genetic link in the
tor imbalance theory has been postulated as a cause of nasal
immune function through a significant association shown
polyposis, This theory is based on the idea of impaired vas-
between HLA-A74 and nasal polyps [18].
cular regulation with increased vascular permeability, that
may subsequently cause edema and polyp formation [9].
Nasal Polyposis Recent Patents on Inflammation & Allergy Drug Discovery 2011, Vol. 5, No. 3 243

Cellular Composition and Chemical Mediators Small polyps arising from the middle meatus may block the
outflow tract of the sinuses and cause chronic or recurrent
Nasal polyps are characterized by an edematous stroma,
acute sinusitis symptoms [7]. Mucocele, which may be
pseudostratified ciliated columnar epithelium, thick epithe-
caused by nasal polyps in the frontoethmoidal sinus, can
lial basement membrane, and few blood vessels with poor
displace the globe laterally, inferiorly and anteriorly; result-
vasoconstrictor innervation [19]. The most common type is ing in diplopia [27].
an edematous eosinophilic polyp; 85-90% of nasal polyps
are of this type [7]. Eosinophils are the major inflammatory
cells of nasal polyps found in 80-90% of all polyps. They Physical Examination
release inflammatory products that directly damage the epi- Careful examination of the nose is mandatory. Anterior
thelium of the upper and lower respiratory tract [2]. rhinoscopy mostly reveals bilateral, single or multiple, mo-
Increased inflammatory cell infiltration causes increased bile, grey, smooth and semi-translucent polypoid masses in
expression and production of numerous mediators in nasal the nasal cavity. Nasal polyps most frequently arise from the
polyps. High concentrations of free histamine have been middle meatus, but also the mucosa of the ostia, anterior and
found in fluid extracted from nasal polyps [20]. Th1 and Th2 posterior ethmoidal clefts, frontal and sphenoethmoidal re-
type cytokines are up-regulated in polyp tissue, but in atopic cesses may be the site of origin [28]. Nasal endoscopy may
patients, polyps exhibit a predominance of Th2 cells and be performed with or without decongestion. Decongestion
eosinophils in comparison to nonatopic patients [21]. and endoscopic examination provides excellent visualization
of the small polyps in the middle meatus, but is not essential
IL-1, IL-3, and IL-5 have been regularly found in polyp for gross polyps [29]. Endoscopic visualization of the polyps
stroma. IL-5 plays a key role in eosinophil migration, while and adjacent regions of the nasal and sinus cavities is neces-
IL-8 can induce neutrophil infiltration [14]. IL-5 is the major sary for correct diagnosis and staging of the disease. The
eosinophil survival factor, and treatment of eosinophil - most commonly used staging system, based on the endo-
infiltrated polyp tissue with neutralizing anti-IL-5 mono- scopic appearance of the sinonasal cavity, was described by
clonal antibody resulted in eosinophil apoptosis [22]. Lildholdt [29, 30] Table 2.
Increased levels of GM-CSF (granulocyte/macrophage Table 2. Grading of Nasal Polyps [29, 30].
colony-stimulating factor), RANTES (regulated upon activa-
tion, normal T-cell expressed and secreted), and VCAM-1
Endoscopic Appearance Score
(vascular cell adhesion molecule 1) have strong eosinophil
chemotactic, activating effects and are regularly detected No polyps 0
within the polyp stroma [23]. VPF/VEGF (vascular perme-
ability/vascular endothelial growth factor) may contribute to Polyps restricted to middle meatus 1
the edema, with induction of vascular hyperpermeability Polyps below middle turbinate 2
[24]. Immunoreactivity for IGF-I (insulin-like growth fac-
tor I) immunoreactivity was found at high levels in patients Massive polyposis 3
with nasal polyps [25]. The complement system was shown
to be involved in the pathogenesis of nasal polyposis; sig-
Radiology
nificantly higher concentrations of C3a desArg and C5a
desArg were found in nasal secretions of patients with nasal Plain sinus X-ray, sinus computed tomography (CT)
polyps compared to controls [26]. scanning, and magnetic resonance imaging (MRI) can be
In antrochoanal polyps, eosinophilia can be found in 20- used for the diagnosis of nasal polyposis. X-rays have a
65% of cases. Mucus glands, which are common in nasal limited value in the diagnosis of nasal polyposis [31]; be-
polyps, are almost never found in antrochoanal polyps. cause they show generalized opacification of all sinuses, but
the true nature of an opaque sinus cannot be demonstrated.
The polyp stroma regularly contains neutrophils, lym- Therefore, a plain radiograph cannot determine the nature of
phocytes, monocytes, plasma cells, and macrophages, in lesion resulting in the opacification of the paranasal sinus
addition to eosinophils and mast cells [19]. [7].
In patients with cystic fibrosis, primary ciliary dyskinesia Computerized tomography scanning is not a primary
syndrome or Young’s syndrome, neutrophils are the domi- method in the diagnosis of nasal polyposis. It must be util-
nant cells in polyps [2]. ized in cases for which surgical treatment (especially revi-
sion surgery) is considered and in cases of unilateral disease.
DIAGNOSIS A CT scan with 2-3 mm direct coronal sections is adequate
for diagnosis and before limited surgery for maxillary and
History
anterior ethmoid sinuses, complete CT (2 mm direct and
The evaluation of nasal polyps begins with a history. The 3 mm axial cuts) is useful if the disease extends beyond the
most common symptom is nasal obstruction, which depends ground lamella into the posterior ethmoids and sphenoid to
on the size of the nasal polyp. Nasal polyps can cause watery define the relationship of the optic nerves and carotid arteries
rhinorrhea, purulent postnasal drainage, hyposmia/anosmia, prior to the surgery. Because of the poor resolution of bony
headache, facial pain, and affect the quality of the voice and tissue, MRI is only preferred to differentiate meningocele or
sense of taste. Epistaxis does not occur with benign multiple encephalocele and to distinguish a tumor from retained se-
polyps and may suggest a more serious nasal cavity lesion. cretions and secondary inflammatory disease [32].
244 Recent Patents on Inflammation & Allergy Drug Discovery 2011, Vol. 5, No. 3 Cingi et al.

Other Tests Table 3. Differential Diagnosis of Nasal Polyposis.

Anterior rhinomanometry, acoustic rhinometry and nasal
inspiratory peak flow are other measures that can be used to Adults
quantify the restriction in the nasal airway [7]. Allergy test- Inverted papilloma
ing, pulmonary function tests, biopsies, sweat chloride test,
or genetic testing for the detection of cystic fibrosis, aspirin Tumors
intolerance test, fungal stains and cultures, and quantitative
Squamous cell carcinoma
tests of smell, such as by UPSIT [University of Pennsylvania
Smell Identification Test), can be used to assess the response Nasal lymphomas
to treatment or to the evaluate the efficacy of the treatment as
well as to diagnose the accompanying diseases [7]. Nasal melanoma

Esthesioneuroblastoma
Differential Diagnosis
Hemangiopericytoma
Presence of unilateral nasal polyp in a patient must arise
the suspicion of other clinical entitites. The similarities of Children
benign and malignant disorders at initial presentation lead to Turbinate hypertrophy
a significant delay in the diagnosis of malignancy. Sinonasal
symptoms unresponsive to medical treatment, intranasal Congenital
bleeding or crusting, orbital symptoms, cranial neuropathies,
Nasolacrimal duct cysts
severe and unilateral frontal headache, signs of meningitis or
focal neurological signs must remind the other possibilities Nasal gliomas
to the physician.
Encephaloceles
Any benign or malignant tumor can mimic or coexist
with nasal polyps. All polyp tissue removed surgically or Tumors
biopsies obtained from polyp tissue must be examined his- Juvenile nasopharyngeal angiofibroma (JNA)
tologically to exclude the possibilty of neoplasia [7]. When a
dermoid, glioma, or encephalocele is presumed, a biopsy Rhabdomyosarcoma
should not be performed unless an intracranial connection is Hemangioma
ruled out. Otherwise, a surgical intervention may bring about
the risk of meningitis or cerebrospinal fluid (CSF) leak. Chordoma

Imaging modalitites should be considered prior to biopsy

in order to avoid the distortion of tumor margins as well as to Inverted papilloma (Cylindrical cell papilloma, Schnei-
assess the lesion in terms of vascularity and intracranial derian cell papilloma) is a true epitelial neoplasm character-
connection. The advantage of CT scans is the detection of ized by hyperplastic epithelium inverted into the underlying
bone erosion. Magnetic resonance imaging provides excel- stroma. It occupies approximately 0.5% of the nasal tumors
lent delineation of tumor from surrounding inflammatory and 4% of all nasal polyps. The typical presentation is a
tissue and secretions within the sinuses. Typically, edema of unilateral polyp. Malignant transformation is possible. Early-
the inflamed tissue and retained secretions would be of low stage and limited tumors can be managed with endoscopic
intensity on T1 sections and of high intensity on T2 sections excision. For widespread, recurrent and rapidly growing
secondary to the increased fluid content. In contrary, 95% of tumors; lateral rhinotomy with medial maxillectomy is the
sinonasal tumors are highly cellular with less fluid content treatment of choice. Close postoperative follow up is manda-
giving low to an intermediate signal intensity on both T1 and tory not to skip the recurrences [34].
T2 sections.
Squamous cell carcinoma is the most common malig-
A unilateral nasal polyp should raise the suspicion of an nant tumor of the paranasal sinuses (80%). In In %70 of
inverted papilloma or a tumor (nasal squamos cell carci- cases, the tumor arises from the maxillary sinus, followed by
noma, nasal lymphoma, melanoma, esthesioneuroblastoma, nasal cavity (20%), and ethmoid sinuses (10%). The presen-
and hemangiopericytoma) in adults, or congenital anomalies tation is variable and the complaints may include a nasal
like nasolacrimal canal cyst, gliomas, encephaloceles, or mass or obstruction, rhinorrhea, epistaxis, cranial neuropa-
tumors like juvenile nasopharyngeal angiofibroma, rhabdo- thies, or pain. 90% of cases exhibit local invasion at presen-
myosarcoma, hemangioma and chordomas in children Table tation. Surgical resection followed by postoperative radio-
3. therapy is recommended in resectable cases [35].
Antrochoanal polyp was initially described by Professor In general, non-Hodgkin lymphomas are primarily found
Gustav Killian in 1906. It represents 4-6% of all nasal pol- in patients at 6th and 7th decades. Clinically, symptoms of
yps. It is a benign lesion originating from the mucosa of the nasal obstruction may be accompanied by rhinorrhea and
maxillary sinus, growing through the accessory ostium into epistaxis. After the identification of the tumor, radiotherapy
the middle meatus and subsequently protruding posteriorly to and chemotherapy may be utilized. The prognosis is
the choana and nasopharynx. Incomplete excision of antro-
choanal polyp almost always leads to recurrence [33].
Nasal Polyposis Recent Patents on Inflammation & Allergy Drug Discovery 2011, Vol. 5, No. 3 245

variable, depending on the type and stage. Median survival ingocele) or they may communicate with a ventricle (en-
time ranges from 1 year to 5 years in 80% of cases. cephalomeningocystocele). Twenty percent of all encephalo-
celes occur in the cranium. Of these, 15% are nasal. Nasal
Melanomas are arising from melanocytes and those
encephaloceles can be divided into 2 types: syncipital (60%)
arising in the nasal cavity or paranasal sinus are relatively
rare. The incidence of melanomas arising from the mucosal and basal (40%). Syncipital encephaloceles typically present
as soft compressible masses over the glabella. Basal en-
surface of the aerodigestive tract varies from 0.4 to 4%. The
cephaloceles may remain clinically dormant. Both CT scan
majority of these lesions arise in the nasal cavity or paranasal
and MRI are useful in diagnosis and a treatment modality
sinuses. The peak incidence is between the fifth and eighth
involving craniotomy is necessary to provide sufficient ex-
decades. They are more common in malesi and age and sex
posure for the encephalocele [38].
do not affect the prognosis [35]. Immunogenic peptides
derived from the Melanoma antigen recognized by T lym- Juvenile nasopharyngeal angiofibroma (JNA) is a rare,
phocytes (MART-1) had been developed recently. Hope- benign, vascular neoplasm that accounts for less than 0.5%
fully, they are expected to serve as a vaccine to prevent or of all head and neck tumors. They are classically present
treat melanoma [36]. with unilateral nasal obstruction, epistaxis, and a naso-
pharyngeal mass in adolescent males. Treatment options
Esthesioneuroblastoma is a rare and malignant tumor
originating from the olfactory neuroepithelium in the nasal include surgery, radiation therapy, chemotherapy, and hor-
mone therapy. Surgery is the gold standard of treatment [39].
cavity. Esthesioneuroblastoma is the term used most com-
monly. Tumor may invade the nasal cavity, paranasal si- Rhabdomyosarcoma originates in the soft tissue and it
nuses, the orbit and the cranial cavity. Nasal obstruction appears as a nasal mass resembling a polyp. The tumor is
(65%) and epistaxis (55%) are the common symptoms. Pa- slightly more common in males than females. Early presenta-
tients with esthesioneuroblastoma are older than 40 years in tion of head and neck lesions allows early diagnosis, which
most cases [37]. in turn facilitates complete surgical resection and effectivity
of chemotherapy, thereby reducing the mortality and avoid-
Hemangiopericytoma is an uncommon vascular tumor
ing recurrence. Increased alertness for a nasal mass and thor-
originating from the pericytes of Zimmerman. Less than one-
ough clinical assessment is the key to diagnosis [38].
third of these tumors occur in the head and neck, while a
minor proportion can involve the sinonasal tract. Sinonasal Hemangiomas are benign vascular tumors originating
hemangiopericytomas are borderline tumors which clinically from the skin, mucosa, bones, muscles and glands. Although
appear as pale, gray-white, well-circumscribed masses with a hemangiomas are common lesions of the head and neck,
soft, rubbery consistency. Nasal obstruction with epistaxis is those of the nasal cavity and paranasal sinuses are relatively
common. The mean age of onset is 55, and the gender distri- rare. Neoplasms arising in the nasal cavity are predominant
bution is roughly equal. Treatment is a complete surgical capillaries and they may be attached to the nasal septum. On
resection followed by radiation if the surgical margin is the other hand, cavernous hemangiomas are more likely to
positive [35]. be found on the lateral wall of the nasal cavity [39].
Nasal duct cysts occur in advance to the congenital ob- Chordomas are malignant, nonepithelial neoplasms de-
struction of the nasolacrimal drainage system. It is common, rived from notochordal tissue. Primary chordoma of the
but symptomatic cases are rare. The most common site of paranasal sinuses or nasal cavity is extremely rare. The pre-
obstruction is the most distal part of the duct beside its exit senting signs and symptoms of chordoma are related to the
into the nose. The obstruction is usually unilateral. A bluish- site of origin and the area of extension. Intranasal chordoma
gray cyst can appear beneath the inferior turbinate. A large presents with nasal obstruction caused by the mass effect of
nasolacrimal duct cyst filingl the nasal cavity may lead to the tumor. Radiographically, chordomas are associated with
nasal obstruction and inferior turbinate may be pushed medi- bony destruction and an extraosseous soft-tissue mass with
ally toward the nasal septum. Because infants are preferen- intralesional destruction. Treatment of the lesion depends on
tially nose breathers, this displacement can cause significant the location and pattern of extension. An anterior lesion
respiratory distress, ending up with cyanotic spells and poor appears to be amenable to wide local excision, ending up
feeding, these symptoms usually subside with crying. The with good results. Clival or sphenoid lesions are usually
treatment of choice for symptomatic cases is endoscopic more advanced on presentation and are treated with debulk-
marsupialization or resection. Outfracturing of a medially ing and postoperative radiation. New therapeutic agent
displaced inferior turbinate might further improve the “Gamma-secretase inhibitor”, that has intramembranous
patency of the nasal airway [38]. proteolytic activity, has been patented for treatment of chor-
doma and other solid tumors [40, 41].
Nasal gliomas are rare, benign, congenital masses which
are actually sequestered glial tissue. Of the gliomas, 60% are
extranasal, 30% are intranasal, and 10% are both intra and TREATMENT
extranasal. Extranasal gliomas are mobile and usually do not Management of nasal polyps involves medical, surgical,
swell upon crying or Valsalva maneuver. Extranasal gliomas or a combination of medical and surgical therapy. Better
appear near the nasion. The overlying skin may be discol- knowledge on the cause and pathogenesis of nasal polyposis
ored or telangiectatic [38]. is mandatory in the treatment of nasal polyps Medical treat-
Encephaloceles are herniation of the neural tissue ments include topical or systemic steroid regimens, as well
through a defect in the skull. They may contain meninges as nasal saline lavage and allergen immunotherapy. The
(meningocele) or brain matter and meninges (encephalomen- current consensus among specialists is that benign nasal
246 Recent Patents on Inflammation & Allergy Drug Discovery 2011, Vol. 5, No. 3 Cingi et al.

polyps should initially be treated conservatively, as many supine position has been shown to be both comfortable and
patients may not require surgery. Surgery has a role when effective [44, 46].
themedical treatment fails [42]. Treatment should be deter-
Many studies have been performed to evaluate the effects
mined on an individual basis. Surgery is considered when
of topical steroids in nasal polyposis. Beclomethasone
medical therapeutic options fail. The goal of surgery is to dipropionate (BDP) has provided significant improvement in
reduce of the size of the nasal polyp, Ito improve sinus
nasal symptoms, but no significant difference could be ob-
drainage, restoration of the ventilation of sinuses and restora-
served in the size of polyps [46].
tion of olfaction and taste and also to remove the fungal
debris in cases with Allergic Fungal sinüsitis and to prevent Budesonide was shown effective for not only reducing
the complications in cases with erosion of the lamina pa- the symptom scores and polyp size, but also improving ol-
pyracea and the skull base.The surgical approach alone is not factory function [47].
entirely curative, and usually repeated procedures and addi- Fluticasone propionate (FP) has provided relief in nasal
tional long-term medical treatment is essential. However, it blockage and improved peak nasal respiratory flow. Impact
must be kept in mind that polyps cannot be compeletely on the size of polyps was not significant compared to pla-
eradicated and main aim of surgery is mostly to provide a cebo. In terms of side effect, only a few epistaxis cases were
nasal passage for airway and drainage [7, 43] Fig. (1). reported [48].
Nevertheless, for all nasal polyposis patients, recurrences Mometasone furoate (MF) was found to be effective in
still comprises of a serious problem and neither option pro- improving nasal congestion, polyp size, sense of smell, peak
vides the ideal solution. In recent years a change in treatment nasal inspiratory flow, and quality of life [49].
strategy has lead to greater use of medication, with good
evidence of the eficacy of nasal corticosteroids The effects of these steroid regimens have been com-
pared in the literature. However no obvious superiority of
MEDICALTREATMENT one compound over the other could be demonstrated [31].

Medical treatment should be determined on an individual Topical administration of corticosteroids can rarely cause
basis. Treatment options in nasal polyposis include topical epistaxis and nasal septal perforation [50]. Long term use
and systemic steroids, nasal lavage, antibiotic therapy, anti- (>1 year) of steroids have been accused for suppressing
fungal therapy, antihistamines, antileukotrienes, and aspirin growth via affecting the hypothalamic-pituitary-adrenal axis
desensitization. Despite this long list, topical and oral sys- in children [51, 52].
temic corticosteroids constitute the mainstay of contempo- All in all, topical corticosteroid sprays are effective on
rary medical management. While the other approaches may polyp size and nasal symptoms associated with nasal poly-
offer alternatives to corticosteroid treatment or surgery, at posis, but the impact on olfaction is limited [44].
present largescale controlled trials are lacking and further
evaluation is required before they could be considered a Systemic Corticosteroids
viable alternative to steroids.
Systemic corticosteroids are effective in reducing the size
Several studies have demonstrated the clinical efficacy of of polyps, alleviating nasal symptoms like sneezing, nasal
corticosteroids in patients with nasal polyps [43-51]. blockage, secretion and improving olfaction. They are usu-
ally preferred in extensive nasal polyposis for preparing the
CORTICOSTEROID TREATMENT patient for surgery or in refractory cases especially when
Corticosteroids have a broad anti-inflammatory activity allergy co-exists. Systemic corticosteroids can be adminis-
and are most effective drugs in the medical treatment of tered either in the form of depot injections or tablets pero-
nasal polyposis. Corticosteroids bind the cytoplasmic gluco- rally in tapered doses. There is no standard protocol regard-
corticoid receptors in the target tissue. They exert their effect ing the systemic corticosteroid treatment. Prednisolone is the
by reducing the acting on both the secretion of chemotactic most preferred corticosteroid in systemic therapy. Some
cytokines and inhibiting the activity of T cells and eosino- surgeons advocate use of 30 mg of prednisolone daily in
phils [43,44]. Corticosteroids may be used both as a primary reducing doses for 10-14 days prior to surgery. Short-term
treatment modality and as an adjunctive measure to prevent treatment with systemic corticosteroids can be used in con-
recurrence. junction with topical steroids. Such a regimen can reduce the
size of polyps preoperatively and the efficacy of the topical
therapy may be enhanced. This model is an effective method
Intranasal Corticosteroids
and has been named “medical polypectomy.”
The use of topical corticosteroids for several months in
Use of 50 mg prednisolone daily for 14 days was found
untreated nasal polyps,as well as in therapeutic attempts to
to be beneficial in terms of nasal symptoms (obstruction,
avoid surgery and for relapse prevention after surgical treat-
secretion, sneezing, and sense of smell), endoscopic findings
ment (6-12 months),is therefore to be recommended [45]
of polyp size, and MRI scores compared to placebo [39, 42,
Topical nasal steroids are delivered by drops or sprays. 43, 53].
Some patients with nasal polyps do not respond to topical
Oral steroids must be cautiously and very carefully used
steroids because of the complete nasal obstruction due to
in patients with diabetes mellitus, hypertension, psychiatric
gross polyps. Nasal drops deliver a higher dose of medica-
disorders, advanced osteoporosis, tuberculosis, glaucoma,
tion to the middle meatus and application of the drug in the
and peptic ulcer disease. Steroid injection into inferior
Nasal Polyposis Recent Patents on Inflammation & Allergy Drug Discovery 2011, Vol. 5, No. 3 247

One or more symptoms: Consider other diagnosis

 Nasal blockage  Unilateral symptoms
 Purulent discharge  Bleeding
 Smell disturbance  Crusting
 Rinoscopic or  Cacosmia
endoscopic nasal polys Orbital symptoms
 Periorbital edema
 Displaced globe
 Double or reduced
Severe vision
Nasal polyps Comorbidities
Mild  Ophtalmoplegia
 Asthma Severe frontal headache
 Anosmia Frontal swelling
 Severe nasal Signs of meningitis

Moderate blockage
Comorbidities
 Asthma
 Anosmia
 Nasal blockage

Saline douching Oral steroids

Topical steroid
Saline douching (short course)
spray Topical steroid drops Topical streoids

Review after 6 Review after 3 months

months

Test for aspirin sensitivity,

No improvement allergic fungal sinusitis. Treat
specifically if present
CT scan/ plan surgery

Topical steroids
Nasal irrigation
+/- oral steroids
Surgery +/- long term
antibiotics

Fig. (1). Management of chronic rhinosinusitis with nasal polyposis [42].

turbinates is not advised due to the risk of fat necrosis or involved in the recruitment of inflammatory cells and accela-
blindness [51,53]. rate the apoptosis of neutrophils. Macrolides have been
shıown to diminish the levels of IL-8 in nasal lavage and
NON-STEROIDAL TREATMENT reduce the size of nasal polyp. Roxithromycin has been re-
ported to inhibit fibrosis and prevent the progression of nasal
Antibiotic Therapy polyposis [54]. Trials of long-term oral antibiotics (12
Antibiotic therapy can be used if chronic or recurrent weeks), especially macrolides, have demonstrated sympto-
acute sinusitis due to the obstruction of the sinus ostiums matic and objective improvement similar to endoscopic
occurs. The treatment should be directed against the Staphy- sinus surgery. The improvement shown increases with time
lococcus species, Streptococcus species and anaerobes, as and may relate to anti-inflammatory reactions in macrolides
well as Pseudomonas aeruginosa, which is common in cys- [55].
tic fibrosis. Aggressive antimicrobial therapy in cystic fibro-
sis has also been reported to reduce the need for surgery in Antifungal Therapy
chronic sinusitis and polyposis. The effect of macrolides is
Fungi and their spores are present in the air at all times,
thought to be anti-inflammatory, rather than antimicrobial.
are naturally part of the respired air and can be detected in
Macrolides both inhibit the expression of adhesion molecules
the normal nose. it was suggested that immune response to
248 Recent Patents on Inflammation & Allergy Drug Discovery 2011, Vol. 5, No. 3 Cingi et al.

fungal elements may be the cause of most chronic sinusitis gery. The rate of polyp recurrences is higher in patients in-
and nasal polyposis [56]. tolerant to aspirin and NSAIDs [63].
Surgery has played an important role in the management Oral doses as low as 100mg daily may be effective and
of allergic fungal sinusitis (AFS). An aggressive surgical this could potentially prevent some of the adverse effects
procedure is needed because of a perceived risk of fungal including gastrointestinal bleeding associated with oral aspi-
invasion. Complete extirpation of all allergic mucin and rin [57]. In a study aspirin-sensitive patients were treated
fungal debris, permanent drainage and ventilation of the perorally for up to 6 years with aspirin. clinical reduction of
affected sinuses and postoperative access to the previously sinus infections and asthma exacerbations, as well as im-
diseased areas are the goals of the surgery proved nasal olfaction were experienced by the patients.
To minimize recurrence, for ameliorating the underlying Furthermore, the numbers of sinus and polyp operations
were clearly reduced[64].
inflammatory process the use of limited systemic and topical
steroid preparations are important. Postoperative care begins Saline nasal irrigation Nasal douching is a safe, inex-
immediately following surgery with nasal saline irrigation. pensive treatment commonly used in patients who suffer
Frequent clinic visits are required to allow regular inspection from hypersecretion or postnasal drainage. It improves nasal
of the operative site and debridement of crusts and retained mucociliary clearance measured by the saccharine test in
fungal debris. It recently was postulated that immunotherapy both NP and healthy volunteers [65]. In all patients the addi-
may be beneficial, rather than harmful, as a component of tion of simple saline nasal douching to help cleanse the nose
treatment for allergic fungal sinusitis (AFS). Clinical experi- prior to topical medications is beneficial [39]. But it is not
ence from a large practice suggests that if patients comply effective in the medical management of uncomplicated nasal
with their immunotherapy, they will need less systemic ster- polyposis [44].
oid usage and fewer revision surgeries [57,58].
Promising results have been reported with specific im- Other Therapies
munotherapy, effectivity of intranasal amphotericin in the Topical capsaicin application causes depletion of pep-
treatment of nasal polyposis remains obscure [58]. tides in the nasal mucosa and degeneration of non-
For invasive fungal rhinosinusitis; surgery is the main myelinated sensory C branches. A case study by Baudoin
treatment option; topical and systemic antifungal agents can et al. has demonstrated significant reduction of sinonasal
be used additionally [57,58]. polyposis after 5 consecutive days treatment with increasing
doses (30-100 mmol/L) of topical capsaicin in massive poly-
Antihistamines posis measured by CT scans at entry and after 4 weeks The
sensation of burning in nasal mucosa administration of cap-
Antihistamines are not the first line drug of choice in saicin can cause burning of the nasal mucosa, limiting its
nasal polyposis. However, when a patient with polyps also acceptability to patients [66].
suffers from seasonal or perennial allergic rhinitis, there is an
increased risk of exacerbations of polyps during allergen Topically administered lysine acetylsalicylate (LAS)
appears to be effective in nasal polyp patients with aspirin
exposure [59]. Exposure to allergen exacerbates the symp-
intolerance, especially those with the Samter’s triad (asthma,
toms in nasal polyposis patients with allergic rhinitis. These
aspirin intolerance and nasal polyposis). Reduction in fre-
patients benefit from antihistamines especially during expo-
quency of rhinosinusitis, and asthma attacks were observed
sure to allergens in the pollen season. In a placebo-controlled
in patients with aspirin sensitization treated with oral aspirin
study, an antihistamine, cetirizine, provided significant re-
duction in sneezing, rhinorrhea, and obstruction, but did not for 6 years [67]. Intranasal treatment with LAS after poly-
pectomy (2000 mcg weekly for 24 months) was effective in
affect the size or number of polyps [60].
aspirin intolerant patients [67]. In conclusion, intranasal
treatment with oral aspirin and topically administered LAS
Antileukotrienes appears to be effective in patients with aspirin intolerance,
Leukotriene receptor antagonists and leukotriene synthe- especially within the aspirin triad. Local treatment with LAS
sis inhibitors have been used for the therapy of nasal polyps. has no effect in patients without aspirin intolerance [68].
Parnes and Chuma found that zafirlukast and zileuton sig- Mucolytics can be used as adjuncts to antibiotics in acute
nificantly improves symptoms in 75% patients an objective sinusitis to reduce viscosity of sinus secretion but no clinical
stabilization of polyposis was detected by endoscopic ax- trials have tested their effects in NP [69].
amination in 50% of patients [61] Leukotriene antagonists
are showed to be effective in reducing the symptoms of se- IL-5 is the major eosinophil survival factor, and treat-
vere nasal polyposis and chronic sinusitis, but further inves- ment of eosinophil - infiltrated polyp tissue with neutralizing
tigations are needed [62]. anti -IL-5 monoclonal antibody resulted in eosinophil apopi-
tosis [22].
ASPIRIN DESENSITIZATION THERAPY
INVESTIGATIONAL THERAPIES
Apirin desensitization therapy can alleviate the symp-
toms in nasal polyposis patients with aspirin-exacerbated There are numbers of therapies which are investigational;
respiratory disease. Aspirin desensitization not only to re- Pilon described recombinant human CC10 for treatment of
duces the number of sinusitis episodes and decreases recur- nasal polyposis. It has anti-inflammatory and immunomodu-
rence rates; but also decreases the need for additional sur- latory effects. Intranasally administered rhCClO is found to
Nasal Polyposis Recent Patents on Inflammation & Allergy Drug Discovery 2011, Vol. 5, No. 3 249

be safe and well-tolerated for alleviating the symptoms of External Ethmoidectomy

nasal polyposis, rhinitis, nasal sinusitis [70].
The procedure is generally performed under general
Cyclosporin has been patented for the treatment of nasal anesthesia. External ethmoidectomy is performed through an
polyps it blocks the synthesis and secretion of certain lym- incision between the medial canthus and the midline of the
phokines. A 52- year- old male patient was treated with nose. The periosteum is elevated posteriorly into the orbit
topical cyclosporin (0.2% in a spray form, three times a day until the anterior ethmoidal artery is identified. Identification
for two weeks), and eventually the size of the nasal polyps of the basal lamella guides the limits of the dissection. The
was reduced that subsequently resulted in the resolution of skull base can usually be identified clearly in the posterior
the nasal blockage [71]. ethmoids. Once the ethmoids are opened, any diseased mu-
cosa, polyps, or tumors should be removed. All ethmoid cells
SURGICAL TREATMENT should be removed once the orbit has been displaced later-
ally [73].
Most authors primarily prefer conservative medical ther-
apy with steroids, but because of the side effects of systemic
steroids and the strong recurrence tendency of polyposis. Caldwell-Luc
Surgery is often necessary for complicated cases, persistant The Caldwell-Luc procedure is usually performed under
or recurrent infections, and unilateral nasal polyps. The aims general anesthesia. The incision is made in the gingivobuccal
of treatment are elimination or at least significantly reduction sulcus, above the canine fossa, and extended through the
of the size of the nasal polyp, improvement of sinus drain- periosteum over the maxilla. The periosteum is elevated
age, restoration of the ventilation of sinuses and restoration superiorly until the infraorbital nerve is identified. A 4-mm
of olfaction and taste. Patients with polyps and asthma may osteotome or a drill is used to outline a window into the
benefit from surgery by elimination of a contributory factor maxillary antrum. Once the window is opened, a punch for-
for asthma [7]. Surgical techniques have been signifi cantly ceps or a drill can be used to enlarge the window as required.
refined over the past 20 years with the advent of endoscopic Injury to the secondary dentition and the infraorbital nerve
sinus surgery (ESS). ESS is now the mainstay surgical must be avoided. The Caldwell-Luc operation was primarily
method of treatment for NP. It is important postoperatively designed for chronic maxillary sinusitis, but it can also be
to regularly douche the nasal cavity with saline to prevent used in generalized polypoid disease, fungal sinusitis, antro-
crusting and adhesions. Topical intranasal steroids are also a choanal polyps, pterygomaxillary space surgery, trauma,
routine part of aftersurgery care to prevent recurrence [72]. foreign bodies, and benign tumors [73].

Intranasal (Simple) Polypectomy Endoscopic Sinus Surgery (ESS)

Simple polypectomy is traditionally performed using a The mainstay of surgical treatment for nasal polyposis is
snare or forceps, removing the polyp by either avulsion or actually endoscopic sinus surgery (ESS), which requires a
cutting. Formerly, this technique was unsafe because of the high degree expertise to achieve optimum results without
lack of proper examination and surgical instruments. Intrana- complications [7].
sal polypectomy had become a more conservative method
Two approaches have been defined in ESS. In the “front-
after the development of endoscopes [73].
to-back” approach (Messeklinger technique), the procedure
begins with visualization with a 0-degree endoscope. The
Intranasal Ethmoidectomy operation starts with uncinectomy and afterwards removal of
Intranasal ethmoidectomy was described by Mosher in the ethmoid bulla, exposure of the frontal sinus ostium, and
1913. In 1929, he eventually concluded that the operation identification of the roof of the ethmoid are done. Once the
was theoretically easy, but in practice it had proven to be one skull base is identified, the dissection continues posteriorly
of the easiest interventions to kill the patient. Mortality oc- with removal of the anterior ethmoid cells and the posterior
curred due to the poor visualisation of anterior cranial fossa ethmoid cells, and finally opening of the sphenoid sinus. The
during surgery. Contemporarily, intranasal ethmoidectomies ostium of the maxillary sinus is identified with a 30-degree
have been replaced by endoscopic approaches. The proce- telescope, and this ostium may be widened if necessary [73].
dure is mostly performed under general anesthesia, but local In the “back-to-front” approach (Wigand technique), the
anesthesia with sedation can also be used. The eyes should sphenoid sinus is initially identified. Using the skull base and
be inspected during surgery. Subsequently, middle turbinate lateral wall as landmarks, the ethmoid sinuses are cleaned
is medialized, the bulla is opened with a small curette and from posterior to the anterior. early exposure to the skull
the anterior ethmoids are removed. A toal middle turbinec- base is the major advantage of this technique [74].
tomy is usually necessary to provide sufficient exposure to
the ethmoids. Great care must be taken to preserve the orbit A microdebrider may reduce the blood loss and improve
or the skull base. The safety of the intranasal ethmoidectomy the visualization due to the rapid removal of the nasal pol-
has been questioned. Most surgeons now do not perform this yps. The instrument also functions as suction, and it keeps
procedure [73]. the surgical field clear. In cases with extensive polyposis,
removal of the polyps may be performed anteriorly and infe-
riorly until the middle turbinate and other landmarks
250 Recent Patents on Inflammation & Allergy Drug Discovery 2011, Vol. 5, No. 3 Cingi et al.

are identified. Surgery should progress in parallel with the ases [77, 78]. Advanced oxidation protein products are found
identification of the orbit and skull base. Polyp recurrence to be significantly higher in patients with nasal polyposis;
tends to occur more in the upper frontal area. therefore efficacy of antioxidant therapy needs to be investi-
gated [79]. Recently, some tissue proteins such as Cu/Zn
Preoperative CT scans are necessary for planning the
surgical strategy [7]. Computer-assisted surgical navigation SOD and PLUNC are thought to be involved in airway in-
flammation. They may be utilized not only for exploring the
allows the sinus surgeon to more effectively remove disease
pathophysiology but also for monitoring disease progression
and preserve normal tissue and avoid vital structures, espe-
or response to treatment [80]. Possible role of biofilms in
cially in tumor and revision cases.
pathogenesis of nasal polyposis needs to be determined [78].
Sinus surgery should be reserved for patients who do not Weakening of desmosomal junctions in the nasal mucosa
respond to medical treatment [7]. due to exposure to the inflammatory cytokines may enhance
Several studies were performed to compare the efficacy the pathogenesis of nasal polyposis [81]. Molecules such as a
of surgical treatment to medical treatment. In a study, it was disintegrin and metalloproteinase 33 (ADAM-33) and metal-
proposed that olfaction improved better with systemic and lothionein were supposed to contribute to the pathogenesis of
topical steroids, whereas surgery had a more prominent polyps in nasal mucosa [82,83]. These issues can help devel-
beneficial effect on nasal obstruction and secretion [75]. oping new treatment options in the management of nasal
polyposis.
At 6 and 12 months, significant improvements in quality
of life, nasal symptoms, and polyp size were observed after CONFLICT OF INTEREST
both medical and surgical treatment [76].
Authors state that there is no conflict of interest for this
Functional endoscopic surgery is superior to minimal article.
conventional procedures such as polypectomy and antral
irrigations. But its superiority to inferior meatal antrostomy
ACKNOWLEDGEMENTS
or conventional sphenoethmoidectomy has not yet been
demonstrated [44]. Author has not made any acknowledgements.
Recurrence occurs in 5-10% of patients with severe dis-
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