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Official reprint from UpToDate®

www.uptodate.com © 2022 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Chronic rhinosinusitis: Clinical manifestations,

pathophysiology, and diagnosis
Authors: Daniel L Hamilos, MD, Eric H Holbrook, MD
Section Editors: Anju T Peters, MD, MSCI, Daniel G Deschler, MD, FACS
Deputy Editor: Anna M Feldweg, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: May 2022. | This topic last updated: Nov 30, 2020.

INTRODUCTION

Chronic rhinosinusitis (CRS) may be broadly defined as an inflammatory disorder of the

paranasal sinuses and linings of the nasal passages that lasts 12 weeks or longer. More
precisely, it is a heterogeneous group of related disorders that share certain clinical and
pathologic features. In the past, CRS lacked a clear definition and was approached differently by
various specialties. However, multidisciplinary expert panels have been established to
determine how these disorders should be defined, evaluated, and managed [1-5].

The definition, epidemiology, clinical manifestations, pathologic features, evaluation, and

diagnosis of CRS will be discussed here. Treatment is presented separately. The complex role of
microbes and antimicrobial therapy in CRS is reviewed elsewhere. (See "Chronic rhinosinusitis:
Management" and "Microbiology and antibiotic management of chronic rhinosinusitis".)

DEFINITION

CRS is defined as an inflammatory condition involving the paranasal sinuses and linings of the
nasal passages that lasts 12 weeks or longer [1,6]. The diagnosis requires objective evidence of
mucosal inflammation.

In some iterations of the definition, the phrase "despite attempts at medical management" is
included to eliminate the possibility that CRS simply represents untreated acute rhinosinusitis.

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However, it is problematic to include this phrase, since there is no definitive standard of

treatment [2,3,5,6].

The term "chronic rhinosinusitis" replaced the term "chronic sinusitis" in most publications on
the subject since 2004 [7].

EPIDEMIOLOGY

Prevalence — Estimates of the prevalence of CRS worldwide vary significantly, in part because
of differences in the diagnostic criteria used (eg, symptom-based diagnosis versus inclusion of
objective rhinoscopy or imaging findings). Studies from the United States and Europe, South
America, the Caribbean, and China estimate the prevalence of CRS to be between 5 and 12
percent of the general population [6,8-14]. Somewhat higher estimates have been reported by
studies of Middle Eastern populations [15].

CRS occurs in both children and adults, although it is typically diagnosed in young or middle-
aged adults [16]. In several studies of adults, the mean age at diagnosis was 39 years of age
[13,17]. Women were disproportionately affected in some studies, although this finding is not
consistent [13,17].

Economic burden — CRS is a chronic disorder with a considerable economic burden resulting
from the costs of diagnostic tests, medical and surgical therapies, lost and reduced school and
work productivity, and detrimental impact on physical and emotional health [18]. Estimates of
the direct and indirect costs associated with CRS in the United States have ranged from $13 and
60 billion annually [10,11,19]. A Canadian study found the out-of-pocket costs to be
approximately $607 Canadian dollars per patient per year, even in a single-payer system [20]. In
one study, the average total days of work missed was 18.7 per patient per year [18].

CLINICAL MANIFESTATIONS

CRS may present abruptly, begin as a nonspecific upper respiratory infection or acute sinusitis
that fails to resolve, or develop slowly and insidiously over months or years. Occasionally, the
first manifestation of CRS may be the relatively acute onset of a “danger sign,” such as severe
headaches or facial pain or visual changes (such as diplopia). (See 'Danger signs and
complications' below.)

Signs and symptoms — There are four cardinal signs/symptoms of CRS in adults:

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● Anterior and/or posterior nasal mucopurulent drainage

● Nasal obstruction/nasal blockage/congestion
● Facial pain, pressure, and/or fullness
● Reduction or loss of sense of smell

In children, the fourth cardinal sign/symptom is cough (rather than reduction/loss of smell) [6].
Except when noted, the material in this topic review is applicable to both adults and children.

Several other symptoms are reported by patients with CRS, including fatigue, malaise, cough,
sleep disturbance, ear pain or pressure, dizziness, halitosis, dental pain, dysphonia, or nasal or
throat irritation. However, none of these are specific enough to be clinically useful in diagnosis.

The four cardinal symptoms of CRS may be present with any subtype of disease and do not
differentiate among the subtypes of CRS. (See 'Features of specific subtypes' below.)

Useful observations about the four leading signs/symptoms include the following:

● Anterior and/or posterior nasal mucopurulent drainage – The typical anterior and/or
posterior nasal drainage of CRS is usually opaque white or light yellow, although there is
considerable variability among patients. Thick yellow, green, or brown mucus can occur,
although it is more characteristic of recurrent acute rhinosinusitis, allergic fungal
rhinosinusitis, and eosinophilic mucin rhinosinusitis (also called eosinophilic nonfungal
rhinosinusitis). (See "Acute sinusitis and rhinosinusitis in adults: Clinical manifestations
and diagnosis".)

● Nasal obstruction/nasal blockage/congestion – "Nasal congestion" is a term that may

be used by patients to describe different sensations. It is helpful to clarify what congestion
means to each patient. It may mean nasal blockage, nasal stuffiness, a sense of pressure,
or the presence of excessive secretions that need to be cleared frequently (ie, "need to
blow nose"). The differential diagnosis of nasal congestion includes various forms of
rhinitis: allergic rhinitis, chronic nonallergic (idiopathic) rhinitis, rhinitis associated with
medication use, and secondary atrophic rhinitis (ie, "empty nose syndrome"). (See "An
overview of rhinitis" and "Chronic nonallergic rhinitis" and "Atrophic rhinosinusitis".)

Congestion in CRS is bilateral, although patients may find congestion on one side to be
more bothersome or noticeable than the other. Congestion is also affected by the “nasal
cycle” which is a physiologic process regulating nasal patency through neuronal
mechanisms [21]. However, truly unilateral nasal congestion/blockage raises the question
of a local anatomic problem, septal deviation, or tumor such as a benign antral choanal
polyp or malignant growth. (See "Etiologies of nasal symptoms: An overview".)
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● Facial pain, pressure, and/or fullness – Facial pressure and headache are reported by
most patients with CRS (83 percent in one series) [22]. These symptoms may be seen in all
subtypes of CRS, but they are less common in CRS with nasal polyposis (CRS with NP)
because the mucosal thickening in this condition is generally not associated with chronic
infection [23]. (See 'CRS with nasal polyposis' below.)

Facial symptoms are common in patients with CRS, although they are the least specific of
the cardinal symptoms. Facial pain can be caused by various nonrhinogenic conditions,
including migraine headaches (sometimes with accompanying nasal congestion), tension
headaches, cluster headaches, temporal mandibular joint problems, dental issues, and
other poorly understood facial pain syndromes [24]. In addition, the presence of facial
pain and/or pressure is less reliable for predicting the presence of objective findings of
rhinosinusitis compared with the symptoms of nasal obstruction or posterior nasal
drainage [25]. One study comprehensively examined the differential diagnosis of 211
patients presenting to the otolaryngologist for symptoms of sinus pressure, pain, or
headache [26]. Although 71 percent of patients met criteria for the presence of sinusitis or
rhinologic disease and 56 percent were suspected to have CRS, nearly one-half (49
percent) of patients were also diagnosed as having a primary headache disorder. This
study highlights the potential pitfalls in diagnosing CRS on the basis of symptoms of sinus
pressure, pain, or headache.

The mucosal linings of the paranasal sinuses are poorly innervated, which probably
contributes to the nonspecific nature of facial pain in CRS [27]. Most patients describe
vague discomfort, fullness, or pressure in the cheeks above or below the eyes or across
the bridge of the nose. Many patients point to an area on the face that anatomically
localizes to the ostiomeatal complex on one or both sides ( figure 1). Obstruction of the
nasofrontal recess may be associated with facial pain, pressure, or headache above the
eyes or in the forehead.

Focal and sharp facial pain over one or more sinus area(s) is less characteristic of CRS and
is typically not associated with radiographic evidence of sinus disease. Evaluation of these
sharp, localized pains usually does not identify a precise explanation, and the pains are
often ultimately diagnosed as "neurogenic" or "causalgic" in nature. (See "Overview of
craniofacial pain".)

Pain in the upper teeth is suggestive of nerve irritation caused by an inflammatory process
adjacent to tooth roots. In patients with CRS, this symptom is typically intermittent and
associated with an increase in other symptoms, such as nasal purulence. Dental pain was
reported by 50 percent of patients in the series mentioned previously [22]. However, in our
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experience, a much lower percentage of patients with CRS complain of tooth pain (eg, 5 to
10 percent). Even when this is reported, an "odontogenic" cause for the pain is not
commonly found.

● Decreased sense of smell – Disturbance in sense of smell may be perceived as a reduced

or completely absent sense of smell (hyposmia or anosmia, respectively). Anosmia is often
associated with mucosal thickening or opacification of the olfactory cleft between the
septum and middle turbinate and is much more common in CRS with NP than in CRS
without NP [28,29]. Patients with anosmia also frequently report a reduced ability to taste
foods.

Danger signs and complications — The following symptoms and signs are suggestive of other
conditions or complications that require immediate evaluation: high fever, double or reduced
vision, proptosis, dramatic periorbital edema, ophthalmoplegia, other focal neurologic signs,
severe headache, meningeal signs, or significant or recurrent epistaxis [30]. Urgent
involvement of an otolaryngologist/head and neck surgeon, ophthalmologist, and/or
neurosurgeon may be indicated.

Impact on quality of life — CRS can have significant adverse effects on quality of life,
particularly during exacerbations [31-34]. One early study documented that patients with CRS
had significantly lower quality of life scores for social functioning as well as physical and overall
health compared with the general population, with decrements similar to chronic lung or heart
illnesses [35]. (See 'Risk factors and associated conditions' below.)

FEATURES OF SPECIFIC SUBTYPES

CRS can be divided into three distinct clinical syndromes. The characteristics of each are
summarized in the table ( table 1). Subtype distinctions are clinically relevant, since risk
factors, contributing disorders, and response to medical or surgical management are
substantively different among the three conditions [3,28].

The three subtypes of CRS are:

● CRS with nasal polyposis (CRS with NP) – Accounting for 20 to 33 percent of cases

● Allergic fungal rhinosinusitis (AFRS) – accounting for <5 percent of cases in most series but
more prevalent in some geographic areas (see 'Allergic fungal rhinosinusitis' below)
● CRS without nasal polyposis (CRS without NP) – 60 to 65 percent

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The pathophysiology of the different subtypes remains incompletely understood, although it is

an area of intense multidisciplinary study [1,36,37]. Data on the pathophysiology of each
subtype is discussed in this section.

CRS with nasal polyposis — CRS with nasal polyposis (CRS with NP) is characterized by the
presence of bilateral nasal polyps in the middle meatus [1]. Nasal polyps are translucent,
yellowish-gray to white, glistening masses composed of gelatinous inflammatory material,
which may form in the nasal cavity or paranasal sinuses ( picture 1 and picture 2). The
gray-white color is due to the relatively avascular nature of the polyp tissue. One to 4 percent of
the general population has nasal polyps, and most are believed to be symptomatic [6,38,39].

Presentation — The characteristic presentation of CRS with NP is gradually worsening nasal

congestion/obstruction, sinus fullness and pressure, fatigue, posterior nasal drainage, and
hyposmia or anosmia. In contrast, fever and severe facial pain are uncommon.

On physical examination, large polyps are often visible with anterior rhinoscopy, while smaller
polyps require nasal endoscopy or imaging. Nasal polyps lack sensation. Swollen nasal
turbinates are sometimes mistaken for nasal polyps, but turbinates are pink in color, similar in
appearance to the rest of the nasal mucosa, and very sensitive to touch ( figure 2).

Nasal polyps generally begin to form around the ostiomeatal complex, although they may
eventually be found throughout the nasal cavities and sinuses [2]. The initial trigger for their
development is probably variable. Nasal polyposis in CRS with NP should be bilateral [1].
Unilateral polyps are relatively uncommon. If confirmed by imaging of the sinuses, this finding
should prompt consideration of other diagnoses, including inverting papilloma or nasal tumors
[40,41]. (See "Etiologies of nasal symptoms: An overview".)

CRS with NP affects immunocompetent patients. In a subset of patients, nasal CRS with NP is
associated with asthma and adverse reactions to aspirin and other nonsteroidal anti-
inflammatory drugs (NSAIDs) that inhibit cyclooxygenase-1 (COX-1). Reactions involve some
combination of rhinitis, conjunctival irritation, and/or asthmatic symptoms occurring within one
to four hours after ingestion of a COX-1-inhibiting NSAID. The combination of asthma, CRS with
NP, and aspirin sensitivity is called aspirin-exacerbated respiratory disease (AERD). Other terms
for this combination of disorders include "triad asthma" or "Samter's syndrome." Among
patients with CRS with NP, between 30 and 40 percent report wheezing and respiratory
discomfort, and about 15 percent have aspirin-associated respiratory disease ( table 1)
[39,42].

The diagnosis and management of AERD is reviewed in more detail elsewhere. (See "Aspirin-
exacerbated respiratory disease".)
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Imaging — On imaging with computed tomography (CT), mucosal thickening is

characteristically marked and bilateral. The CT density of polyps is similar to that of thickened
mucosa, although polyps are differentiated from nonpolypoid mucosal thickening by their
shape and contours ( image 1). Polyps appear as rounded mucosal protrusions into the nasal
or sinus cavities.

Sinus opacification in the absence of facial pain/pressure/headaches is typical of patients with

CRS with NP and is unlikely to represent chronic bacterial infection. When multiple polyps are
present, sinus secretions may become entrapped within the crevices between the polyps. The
CT attenuation values of the secretions can increase, and the polyp tissue itself might show
mixed CT attenuation values with areas of increased density, simulating focal or diffuse
dystrophic calcifications. When further information is required to clarify the nature of the
findings, the combination of sinus CT plus sinus magnetic resonance imaging is usually helpful
[43]. (See 'Sinus MRI' below.)

Histologic findings — Biopsy of mucosal tissue characteristically shows edematous tissue and
a paucity of submucosal glands and stromal fibrosis. Mixed infiltrates of mononuclear cells and
eosinophils are usually present, with a predominancy of eosinophils. CRS with NP and asthma
share eosinophilic histopathologic features [28,44,45]. This probably reflects a common
mucosal susceptibility to environmental exposures and allergic-type inflammation that is
shared by the upper and lower airways [46]. An increase in epithelial goblet cells may also be
present, although this does not distinguish CRS with NP from CRS without NP [1,47].

Pathophysiology — Polyp tissue typically contains high levels of the T helper type 2 cytokines
interleukin (IL)-5 and IL-13, as well as high levels of histamine [48].

There is evidence for localized allergic hyper-responsiveness to colonizing Staphylococcus aureus

in particular, as evidenced by the local production of specific immunoglobulin (Ig)E antibodies
against staphylococcal enterotoxins [49-51]. Enterotoxins act as superantigens and broadly
activate T lymphocytes [49]. Anti-enterotoxin antibodies can be measured in sinus tissues from
patients with CRS with NP, although levels in the blood may be undetectable. In contrast,
patients with CRS without NP do not appear to produce IgE to staphylococcal enterotoxins [49].

Allergic fungal rhinosinusitis — Allergic fungal rhinosinusitis (AFRS) has mostly been reported
in young patients from the southern United States. The disorder is believed to result from
chronic, intense allergic inflammation directed against colonizing (ie, noninvasive) fungi.
Patients with AFRS are immunocompetent and show evidence of allergy to one or more fungi (
table 1). AFRS typically presents subtly over years, with symptoms similar to CRS with NP,
since these patients usually have NP. Fever is uncommon. In occasional patients, AFRS presents

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dramatically with complete nasal obstruction, gross facial asymmetry, and/or visual changes
[52]. Children may present with proptosis more commonly than adults [53]. AFRS is
distinguished from CRS with NP by the presence of allergic mucin that contains viable fungal
hyphae (as demonstrated by fungal staining or culture) and evidence of IgE-mediated allergy to
one or more fungi. This disorder is discussed in detail separately. (See "Allergic fungal
rhinosinusitis".)

Eosinophilic mucin rhinosinusitis (EMRS), also called allergic eosinophilic mucin without fungus,
is a disorder that shares some clinical features with AFRS but is a distinct clinical entity. In some
areas of the US, EMRS is more prevalent than AFRS (eg, northeastern United States) [54,55].
Similar to AFRS, EMRS is characterized by the presence of nasal polyps and allergic mucin in the
paranasal sinuses. However, in EMRS, the allergic mucin does not contain fungal hyphae, and
fungal allergy is usually not present. EMRS is an important subset of CRS with NP, because it is
often associated with refractory or recurrent nasal polyps and AERD. It is also quite responsive
to treatment with dupilumab (see "Chronic rhinosinusitis: Management"). EMRS is discussed in
greater detail elsewhere. (See "Allergic fungal rhinosinusitis", section on 'Eosinophilic mucin
rhinosinusitis'.)

CRS without nasal polyposis — CRS without nasal polyposis (CRS without NP) is the most
common form of CRS, accounting for 60 to 65 percent of cases [28,56]. CRS without NP
describes the presence of CRS without the specific findings that define the other two
syndromes (eg, nasal polyposis or allergic mucin with fungal hyphae).

Presentation — A typical presentation of CRS without NP is that of persistent symptoms with

periodic exacerbations characterized by increased facial pain/pressure and/or increased
anterior or posterior drainage. Fatigue is a frequent accompanying symptom. Fever is usually
absent or low grade. A subset of patients has recurrent acute rhinosinusitis symptoms, which
respond well to antibiotic treatment. Such patients may have persistent symptoms between
episodes, in which case they could be classified as CRS without NP. Alternatively, they may be
completely symptom-free between episodes, in which case they have been described as having
"recurrent acute rhinosinusitis" or "chronic recurrent rhinosinusitis" [57].

CRS without NP is heterogeneous and may include patients with allergic and nonallergic
rhinitis, structural abnormalities, and/or immunodeficiency. (See 'Risk factors and associated
conditions' below.)

Imaging — CT imaging of CRS without NP usually shows sinus opacification or sinus ostial
obstruction, with nonpolypoid mucosal thickening of the associated sinus cavity ( image 2).

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Histology — Biopsy of mucosal tissue characteristically shows an infiltration of mixed

mononuclear cells and neutrophils, with an increase in submucosal glands and stromal fibrosis.
Epithelial goblet cell hyperplasia may be present. Eosinophils may be present but generally
represent <10 percent of the infiltrating inflammatory cells [1,47].

Pathogenic bacteria may or may not be present in the mucus. Allergic mucin is present in some
cases, although patients with CRS without NP lack one or more criteria for AFRS, such as a
positive mucus stain for fungi or evidence of fungal-specific IgE by skin tests or in vitro IgE
immunoassays. Thus, these patients do not fulfill all the criteria of AFRS.

Pathophysiology — In most cases, the disease process probably starts with obstruction of a
sinus ostium leading to acute bacterial rhinosinusitis. If the obstruction fails to resolve, a
chronic inflammatory process ensues. Antibiotic treatment and/or the host immune response
may clear or reduce the evidence of infection. The contribution of chronic infection at this point
is variable and controversial (see 'Role of bacterial infection' below). In some cases, there is little
clinical evidence of infection. However, studies have demonstrated the presence of bacterial
biofilm in sinus tissue in 45 to 80 percent of cases [58-61].

Histopathologic analysis typically reveals chronic inflammation with variable numbers of

mononuclear cells, neutrophils, and some eosinophils (typically much fewer than seen in CRS
with NP), and bacterial colonization or biofilm may contribute to the chronic inflammatory
process. This remains an active area of investigation.

More recent studies have examined tissue cytokine profiles as "endotypic" correlates to
histopathologic and clinical findings in CRS patients [62,63]. These studies have demonstrated
that CRS without NP is quite heterogeneous with distinct subsets of patients manifesting either
a T1 endotype (with expression of IFN-gamma), a T2 endotype (with expression of eosinophil
cationic protein and Charcot-Leyden crystal galectin), a T3 endotype (with expression of IL-17A)
or a mixed endotype profile (such as T2 + T3). This work confirms the previously well-known
observation that some CRS without NP patients have significant tissue eosinophilia whereas
others have a more neutrophilic predominance. It is likely that tissue endotyping in CRS may be
useful in guiding selection of targeted biologic cytokine blocking therapies. (See "Chronic
rhinosinusitis: Management".)

Certain risk factors have been identified for the development of CRS without NP. (See 'Risk
factors and associated conditions' below.)

Role of bacterial infection — CRS is a complex inflammatory disorder and not a simple
infectious process or anatomic problem. However, bacterial colonization or infection may
contribute to CRS in several ways:
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● Acute bacterial rhinosinusitis may fail to resolve, leading to a chronic infection in one or
more sinuses.

● Bacteria may form biofilms on the sinus epithelium. Sequestration of bacteria within
biofilms allows them to resist antibiotic treatment and persist as a low-grade infection
within the sinus mucosa [30,58-61,64].

● Bacterial colonization with enterotoxin-producing S. aureus is found with increased

prevalence in CRS with NP and is associated with local production of enterotoxin-specific
IgE antibodies [49]. (See 'CRS with nasal polyposis' above.)

IgE antibodies specific to S. aureus enterotoxin (SAE-IgE) are typically only detectable in the
serum of patients with severe concomitant asthma. In these cases, the presence of serum
SAE-IgE is strongly associated with the presence of an elevated total serum IgE
independent of allergic sensitization to common airborne allergens, suggesting that the
elevation may be attributable to SAE-IgE [65].

● Drug-resistant infection may occur with gram-negative bacteria or methicillin-resistant S.

aureus [66]. Infection with drug-resistant bacteria should be considered in patients with
nosocomial infections and in individuals who work in health care settings.

● Acute bacterial infection may lead to osteitis of the underlying bone and persistent
infection in some cases, although actual invasion of the bone has not been conclusively
demonstrated [67].

The microbiology and antimicrobial therapy of CRS are reviewed in more detail separately. (See
"Microbiology and antibiotic management of chronic rhinosinusitis".)

RISK FACTORS AND ASSOCIATED CONDITIONS

There are multiple associated conditions and risk factors that should be considered in each
patient with CRS ( table 2).

● Allergic rhinitis – Among CRS patients undergoing sinus surgery, the prevalence of
positive skin prick tests ranges from 50 to 84 percent, of which the majority of patients (60
percent) have multiple sensitivities [68-70]. By definition, all patients with allergic fungal
rhinosinusitis have IgE-mediated allergy to fungi. (See "Allergic fungal rhinosinusitis".)

CRS patients are typically sensitized to perennial rather than seasonal (ie, pollen) allergens
[71]. Important perennial allergens include house dust mites, fungal spores from indoor
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and/or outdoor sources, animal danders, cockroaches, and sometimes feathers. Perennial
allergens are generally present at higher levels for longer periods of time compared with
pollen allergens. Furthermore, fungal spores can germinate in sinus mucus, thereby
increasing the allergenic stimulus.

● Asthma – Approximately 20 percent of patients with CRS have concomitant asthma.

Conversely, approximately two-thirds of patients with asthma, including both children and
adults, have evidence of chronic sinus mucosal thickening or sinus opacification in cross-
sectional studies [46]. A cross-sectional study in multiple European centers consistently
found a strong association between the presence of asthma and the presence of CRS [72].
There is a higher prevalence of CRS in patients with severe asthma compared to milder
asthma [73]. CRS has been associated with an increased frequency of asthma
exacerbations in exacerbation-prone asthmatics [74]. Asthma is much more strongly
associated with CRS with nasal polyposis than CRS without nasal polyposis [28,56].

● Aspirin-exacerbated respiratory disease – The combination of asthma, CRS with nasal

polyposis, and aspirin sensitivity is called aspirin-exacerbated respiratory disease. These
three disorders are believed to be linked by an underlying biochemical abnormality in
airway tissues, namely overproduction of cysteinyl leukotrienes. (See 'CRS with nasal
polyposis' above and "Aspirin-exacerbated respiratory disease".)

● Depression – In a systemic review, the prevalence of possible or likely depression was 11

to 40 percent among patients with CRS, depending upon the depression screening
instrument used [75]. No reliable CRS-specific factors were found that predicted the
presence of depression. Patients with both depression and CRS improved with treatment
but did not attain the same degree of improvements in quality of life as those without
depression.

● Smoking – Active cigarette smoking is an important risk factor for CRS [76,77].

● Irritants and pollutants – Sustained exposure to other environmental noxious or

ciliostatic substances, such as formaldehyde, may also contribute to nasal and sinus
mucosal inflammation and decreased mucociliary function, thereby predisposing to sinus
infection [78].

Studies have demonstrated associations between common air pollutants, such as carbon
monoxide, nitrogen dioxide, sulfur dioxide, and particulate matter [79], although the
evidence supporting a pathogenic role for poor air quality in contributing to the
development of CRS is relatively weak [78].

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● Immunodeficiency – Defective or deficient antibody production is found in some children

and adults with CRS [28,80-82]. The specific disorders that are associated with CRS include
various forms of hypogammaglobulinemia and specific antibody deficiency [80,83-85].
Most patients with defective or deficient antibody production have a pattern of recurrent
acute episodes of purulent infection. They may also have a history of concomitant
pulmonary infections or recurrent otitis media. Such patients should be evaluated for an
underlying immune defect. (See "Primary humoral immunodeficiencies: An overview" and
"Specific antibody deficiency".)

There are more limited data about CRS risk in patients with defects in the innate immune
system. Innate immunodeficiency is difficult to diagnose owing to limited testing
capabilities. Mannose-binding lectin (MBL) deficiency is one of the most prevalent innate
immunodeficiencies, but there is little evidence for an increased prevalence of MBL
deficiency in children or adults with CRS [86]. The nasal and sinus epithelium produce a
variety of antimicrobial proteins, such as lactoferrin, lysozyme, defensins, collectins, and
cathelicidins. Little is known about functional defects in production of these proteins in
CRS, although this is an area of active research [87-89].

● Defects in mucociliary clearance – Defects in mucociliary clearance, such as those found

in cystic fibrosis and primary ciliary dyskinesia, dramatically increase the risk of developing
CRS. All children diagnosed with nasal polyposis should be evaluated for cystic fibrosis. In
comparison, these rare syndromes combined account for less than 1 percent of all adult
CRS cases [90]. (See "Cystic fibrosis: Clinical manifestations and diagnosis" and "Primary
ciliary dyskinesia (immotile-cilia syndrome)".)

● Viral infections – In a small number of cases, patients appear to develop CRS after a
period of repeated exposure to viral upper respiratory infections. This is characteristically
seen in patients exposed to health care settings, daycare centers, schools, or homes with
small children. A role for common respiratory viruses in the persistent phase of CRS has
also been suggested. One study found that 21 percent of CRS patients had detectable
rhinovirus in their nasal epithelial scraping compared to 9 percent of healthy controls [91].
Another study found a higher prevalence of rhinovirus detection in nasal lavage and nasal
epithelial scrapings from CRS patients compared with healthy controls, with odds ratio of
detection of 3.2 in lavage and 3.4 in scraping samples [92]. However, a similar study found
no difference in the prevalence of respiratory virus detection in nasal lavage and nasal
epithelial scrapings from CRS patients compared to healthy control subjects [93].

Viral infections may be more significant in the pathogenesis of CRS without NP (CRSsNP).
One study found that common respiratory viruses were more prevalent in nasal epithelial
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brushings from patients with CRSsNP patients than in controls, and that there was no
increase in the prevalence of respiratory virus detection in CRS with NP (CRSwNP) patients.
This study also found a significant association of virus detection with more severe
radiological and endoscopic disease in virus‐positive CRSsNP patients but not virus‐
positive patients with CRSwNP [94].

● Systemic diseases – CRS may be the presenting feature of an underlying systemic

vasculitic syndrome, such as granulomatosis with polyangiitis (GPA) or eosinophilic
granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss vasculitis)
[95,96]. Nasal polyps are associated with EGPA, whereas bony destruction and septal
erosion are much more commonly associated with GPA [2,97]. Rarely, sarcoidosis may
present with CRS [98].

Signs and symptoms that suggest the presence of these conditions include fever, other
signs of vasculitis, visual or other neurologic symptoms, severe headaches, or signs of
meningeal inflammation. Sinonasal findings that should raise suspicion include unilateral
sinus disease, persistently bloody nasal discharge, nonhealing nasal lesions, nasal septal
perforation with bleeding and crusting, and collapse of the nasal bridge. (See
"Granulomatosis with polyangiitis and microscopic polyangiitis: Clinical manifestations
and diagnosis" and "Epidemiology, pathogenesis, and pathology of eosinophilic
granulomatosis with polyangiitis (Churg-Strauss)" and "Clinical manifestations and
diagnosis of pulmonary sarcoidosis".)

● Dental infections – The relationship between dental infections and sinusitis is well known
but often difficult to establish. Both disorders are common and only occasionally related.
"Odontogenic sinusitis" should be considered in patients with maxillary sinusitis who have
had dental infections, dentoalveolar surgery, periodontal surgery, or who have recurrent
or chronic maxillary sinusitis refractory to standard treatment [99]. Sinus computed
tomography (CT) reports will occasionally note the presence of an oroantral fistula, apical
(also known as "periapical") abscess, periodontal disease, or a projecting tooth root into
the maxillary antrum. Of these, oroantral fistula or apical abscess are the most likely to be
associated with maxillary sinusitis, and they merit further evaluation. Dental abscesses
can be overlooked or missed on routine sinus CT images unless the image extends to
beyond the floor of the maxillary sinus and includes the maxillary teeth [100,101]. Early
stages of bony loss due to a periapical abscess can also be missed on conventional dental
radiographs but may be detected on sinus CT scans [100].

● Anatomic abnormalities – Certain anatomic variants, such as septal deviation, concha

bullosa, or a displaced uncinate process, have been suggested to predispose to
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obstruction of the ostiomeatal unit. However, there is little evidence that these play a role
in most cases of CRS [1,27,102-105]. (See "Etiologies of nasal symptoms: An overview".)

Repeated and/or overly aggressive sinus surgeries occasionally result in anatomic

abnormalities or replacement of normal sinus mucosal tissue with scar tissue that may
impair normal mucociliary clearance (ie, secondary atrophic rhinitis). (See "Atrophic
rhinosinusitis".)

● Indoor dampness and mold exposure – Whereas some studies have suggested a
possible relationship between indoor dampness or mold exposure and rhinosinusitis, an
Institute of Medicine report in 2004 concluded that there was no convincing epidemiologic
evidence of such an association [106].

EVALUATION

The evaluation of CRS involves a clinical history, objective documentation of mucosal disease,
allergy evaluation, and consideration of immunologic defects and infectious complications (
algorithm 1).

History — The initial history should include information about the following:

● Presence of the four cardinal symptoms (see 'Clinical manifestations' above)

● Duration of symptoms
● Presence of causative/contributing conditions and factors, as discussed in the preceding
section ( table 2)
● Previous treatment
● Previous imaging
● Previous surgical interventions
● Potential exposure to indoor allergens at home, school, or work

Demonstration of mucosal disease — The diagnosis of CRS requires objective documentation

of mucosal inflammation, as evidenced by one or more of the following findings [3]:

● Purulent (not clear) mucus or edema in the middle meatus or ethmoid regions

● Polyps in the nasal cavity or the middle meatus

● Radiographic imaging demonstrating mucosal thickening or partial or complete

opacification of the paranasal sinuses

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Clinicians with training in anterior rhinoscopy (with decongestion) or nasal endoscopy can
directly visualize the nasal cavities and sinuses, which has the advantage of limiting the
patient's radiation exposure [107]. Clinicians without such training most often obtain sinus
computed tomography (CT) scans.

Rhinoscopy and endoscopy — Anterior rhinoscopy can be performed with a nasal speculum
or otoscope, but apart from assessing the state of the nasal mucosa or documenting polyps
that protrude into the nasal cavity, this technique provides limited visualization of key
structures and therefore limited capacity to document CRS. The nasal cavities can be sprayed
with a solution of oxymetazoline or phenylephrine to shrink the turbinate tissue.

In contrast to rhinoscopy, nasal endoscopy can allow for visualization of the entire nasal cavity,
occasionally assess the patency of sinus ostia when anatomically possible, assess surgical
openings to the sinuses, document purulent drainage from the ostia, facilitate obtaining
bacterial or fungal cultures from the sinuses, or identify polyps within the sinuses [108].
Performance of nasal endoscopy requires a nasal endoscope and appropriate training. The
endoscope can only enter the maxillary, ethmoid, frontal, and sphenoid sinuses if the patient
has had prior sinus surgery. Otherwise, sinus imaging is required to evaluate these areas. In a
patient who has not undergone previous surgery, the nasal endoscope provides excellent
visualization of the septum, inferior and middle turbinates with their respective inferior and
middle meatus, the sphenoethmoidal recess (the drainage site for the sphenoid and posterior
ethmoid sinus) and occasionally the sphenoid ostium, and the nasopharynx.

Features consistent with CRS include mucopus (purulent mucus) emanating from the middle
meatus ( picture 3), edematous hyperemic mucosa, polypoid mucosal changes, or frank
polyposis ( image 1).

Sinus imaging — Either sinus CT without contrast (most common) or magnetic resonance
imaging (MRI) can be used to demonstrate mucosal disease, but CT is the preferred modality
due to better resolution of mucosal disease and sinus ostial occlusion. MRI is preferred if soft
tissue resolution is required or when there is concern for disease extension beyond the sinus
cavities [109,110]. Potential disadvantages of MRI are excessive sensitivity, leading to possible
overdiagnosis, and increased cost compared with CT [3]. Other forms of imaging are not
considered adequate:

● Standard radiographs (plain films) of the nasal cavity and paranasal sinuses are not
adequate to diagnose CRS, because abnormalities detected on plain films are neither
sensitive nor specific for sinusitis [1].

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● Transillumination and ultrasound imaging of the sinuses are considered outmoded and
have not been recommended for diagnostic purposes by consensus groups due to lack of
sensitivity and specificity for rhinosinusitis [1,111].

Sinus CT — Multiplanar sinus computed tomography (CT) scan is the preferred imaging
modality for evaluating CRS ( image 3) [112]. However, the number of scans performed on an
individual patient with sinus disease over time should be minimized, as there is growing
recognition that the cumulative radiation exposure from repeat CT scans can be clinically
significant [113]. (See "Radiation-related risks of imaging", section on 'CT examinations'.)

Sinus CT scans are generally not recommended for evaluation of acute rhinosinusitis or acute
flares of CRS, as common respiratory viral infections can cause extensive mucosal thickening,
sinus ostial occlusion, and air-fluid levels that may persist for weeks [114]. There are rare
circumstances, however, where a sinus CT scan can be helpful to rule out CRS in patients with
atypical symptoms. CT scan is also necessary for surgical planning and evaluation of unique
patient anatomy to prevent complications.

In children, sinus CT is generally not performed during the initial diagnostic evaluation in an
effort to minimize radiation exposure [115,116]. In a consensus document regarding
appropriate use of CT in the management of CRS, the majority of otolaryngology experts
believed that CT in children should be reserved for evaluation of those who have failed medical
treatment and/or adenoidectomy or are experiencing complications [117].

The anterior ethmoid air cells, in particular, are a common focus of persistent infection or
inflammation [118]. Coronal sinus CT images provide excellent visualization of the ethmoid
sinuses but may occasionally be difficult to interpret because of the small size of ethmoid air
cells and the existence of ethmoid septae that orient in the coronal plane. Multiplanar images in
the coronal, axial, and sagittal planes facilitate a more detailed examination of questionable
ethmoid opacification and analysis of the frontal sinus drainage pathway.

The most common findings in CRS are sinus mucosal thickening, sinus ostial obstruction,
polyps, and sinus opacification:

● Mucosal thickening – Mucosal thickening is suggestive of mucosal inflammation,

mucosal infection, and/or obstruction of a sinus ostium (the distinct bony opening
through which each sinus drains).

● Obstruction of the ostiomeatal complex – Variable degrees of sinus ostial obstruction

are common in CRS. The ostiomeatal complex (or ostiomeatal unit) is an area where
several structures interface, through which the anterior ethmoid and maxillary sinuses
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drain ( figure 3). Obstruction of the ostiomeatal complex predisposes to recurrent sinus
infections and chronic mucosal thickening.

● Sinus opacification – Sinus opacification is complete filling of a sinus with inflammatory

material or fluid. Opacification may be seen with persistent inflammation or bacterial
infection, purulent secretions, mucus inspissation, polypoid mucosal thickening, or an
accumulation of allergic mucin. Examining CT images in "bone" versus "soft tissue"
windows can be helpful in recognizing hyperdensities ( image 4). CT combined with MRI
is useful in differentiating among the different causes of sinus opacification [43]. (See
'Sinus MRI' below.)

A number of other findings may also be seen on sinus CT:

● Mucus retention cysts – Mucus retention cysts are most often seen in the maxillary sinus.
These result from obstruction of the ducts of mucosal serous and/or mucinous glands.
They are usually small and clinically silent, although they rarely enlarge sufficiently to fill a
sinus cavity. Mucus retention cysts are of no clinical significance unless they are large
enough or in position to obstruct the sinus outflow tract.

● Mucoceles – Mucoceles are epithelium-lined cysts filled with mucus, which may also
appear as cystic lesions on sinus CT. (See "Etiologies of nasal symptoms: An overview",
section on 'Mucoceles'.)

● Bony changes – Less common findings include sclerosis of the wall of the sinus, unusual
bony septations, bony erosions, and bowing of bony structures associated with sinus
opacification.

● Isolated sphenoid involvement – Uncommonly, patients present with symptoms of CRS

and are found to have isolated sphenoid sinusitis on sinus CT. Such patients typically have
symptoms of retro-orbital or frontal headache or visual disturbance, but they may have
less common symptoms, such as occipital or vertex headaches [119-122]. Isolated
sphenoid abnormalities may be found incidentally on sinus or brain imaging studies [122].

Because the symptoms of sphenoid sinus involvement are atypical and sometimes
insidious, there is a risk that the patient will present with a more advanced disease
process. Bony erosion and extrasinus extension of disease or infection may be present
[120,122]. Lesions that cause anatomic distortion of a sinus wall or erosion of bone on CT
scan warrant evaluation by MRI scan [122].

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In isolated sphenoid disease, pathologies other than acute or CRS are present in a
significant number of cases. Disorders such as fungal rhinosinusitis, fungus ball,
mucocele, fibrous dysplasia, meningoencephalocele, inverted papilloma, epidermoid
carcinoma, liquor fistula, rhabdomyosarcoma, chordoma, and carotid artery
pseudoaneurysm should be considered [119,120]. Following medical treatment of isolated
sphenoid sinusitis, repeat imaging to ensure that there is no evidence of persistent
pathology is suggested.

Sinus MRI — Data about the use of magnetic resonance imaging (MRI) to diagnose CRS is
limited, although sinus MRI correlated well with CT in one study of 89 patients [123].

The combination of CT and MRI imaging techniques can provide a more precise differentiation
of mucus accumulation and mucosal thickening within sinus cavities [1,111]. Combined imaging
is particularly useful for distinguishing the allergic mucin of allergic fungal rhinosinusitis (AFRS)
from other material in an opacified sinus (such as infected fluid or trapped secretions). Allergic
mucin produces characteristic hyperdensities on CT, which appear as hypoattenuated (or
hypointense) areas on T2-weighted MRIs ( image 4) [1]. These radiographic phenomena may
correspond to accumulations of calcium and heavy metals within the mucin [124,125].

Sinus cultures — In patients with persistent symptoms despite previous antibiotic treatment,
the possibility of infection with either gram-negative or drug-resistant bacteria should be
considered. Documenting the presence of such an infection requires obtaining bacterial and/or
fungal cultures directly from the sinus ostia, either endoscopically or by sinus puncture. Nasal
swabs are not reflective of sinus contents and should not be used to guide treatment. (See 'Role
of bacterial infection' above and "Microbiology and antibiotic management of chronic
rhinosinusitis".)

Allergy evaluation — The prevalence of allergic sensitization in patients with CRS ranges from
60 to 84 percent [28,126]. Sensitization to perennial allergens, including dust mite, cockroach,
animal danders, and fungi, is more prevalent than sensitization to pollens [28,126,127]. Given
the overlapping symptoms of allergic rhinitis and CRS, a case can be made to evaluate any CRS
patient for the presence of allergies, especially to the perennial allergens, and this is our
approach. Diagnosing allergy to dust mite or animal dander may be beneficial, since reducing
exposure to these allergens may significantly improve the patient's symptoms. However,
studies specifically evaluating the impact of allergen immunotherapy on the clinical symptoms
of CRS are lacking. Practice guidelines concluded that testing for allergies in CRS patients was
"optional" [3]. (See "Allergic rhinitis: Clinical manifestations, epidemiology, and diagnosis".)

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Consider immune evaluation — In most patients with CRS, evaluation for immunodeficiency is
not warranted. The exception is the patient with a pattern of recurrent episodes of acute
purulent sinusitis. In addition, a history of concomitant pulmonary infections or recurrent otitis
media suggests possible underlying immunodeficiency. Patients with these presentations
should be evaluated for humoral (ie, antibody) immunodeficiencies. (See 'Risk factors and
associated conditions' above.)

Among patients with CRS who do prove to have a humoral immunodeficiency, most have CRS
without nasal polyposis (CRS without NP). One study found that among patients with CRS
without NP, the prevalence of humoral immunodeficiency was 12 percent [28]. By comparison,
humoral immunodeficiency is rare in patients with CRS with NP or AFRS.

Initial testing for humoral immunodeficiency includes measurement of serum levels of IgG, IgA,
and IgM. Evaluation of antibody function, in the form of measurement of the patient's response
to pneumococcal polysaccharide vaccine, is also important. The evaluation of antibody levels
and function is discussed in more detail elsewhere. (See "Laboratory evaluation of the immune
system" and "Assessing antibody function as part of an immunologic evaluation".)

Consider evaluation for systemic diseases — As discussed previously, CRS may be the
presenting manifestation of a disorder, such as granulomatosis with polyangiitis (GPA),
eosinophilic granulomatosis with polyangiitis (EGPA), or occasionally cystic fibrosis, sarcoidosis,
or primary ciliary dyskinesia. Certain signs and symptoms should raise suspicion for these
diseases. (See 'Risk factors and associated conditions' above.)

If concerning signs or symptoms are present, then initial laboratories should include the
following:

● Complete blood counts with differential.

● Erythrocyte sedimentation rate.

● Antineutrophil cytoplasmic antibodies, which are found in 40 to 60 percent of patients with

EGPA and 60 to 90 percent of those with GPA.

● Chest imaging studies and a sweat chloride measurement or genetic screening test for
cystic fibrosis in patients suspected of having cystic fibrosis.

● A chest radiograph and serum angiotensin-converting enzyme level (which is elevated in

75 percent of untreated patients with sarcoidosis).

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● For patients suspected of having primary ciliary dyskinesia, a nasal exhaled nitric oxide
measurement (which is typically low), lung imaging, and possibly a nasal or bronchial
biopsy for analysis of ciliary ultrastructure may be warranted.

The diagnosis of the systemic diseases that may present as CRS often requires histologic
confirmation in diseased sinus (or other) tissue. (See "Granulomatosis with polyangiitis and
microscopic polyangiitis: Respiratory tract involvement" and "Epidemiology, pathogenesis, and
pathology of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)" and "Clinical
manifestations and diagnosis of pulmonary sarcoidosis" and "Primary ciliary dyskinesia
(immotile-cilia syndrome)".)

DIAGNOSIS

The diagnosis of CRS is based upon the presence of suggestive symptoms in combination with
objective evidence of mucosal inflammation ( algorithm 1).

Suggestive signs and symptoms — The diagnosis of CRS is based upon the presence of at
least two of the four cardinal signs/symptoms [3,6,66]:

● Anterior and/or posterior nasal mucopurulent drainage

● Nasal obstruction/nasal blockage/congestion
● Facial pain, pressure, and/or fullness
● Reduction or loss of sense of smell

Some guidelines specify that patients must have drainage or nasal obstruction as one of the
two [6]. The cardinal signs/symptoms should be present for 12 weeks or longer despite
attempts at medical management.

Although symptoms must be present to consider the diagnosis, there is a poor correlation
between the symptoms of CRS and objective findings upon imaging or endoscopy of the
paranasal sinuses [107,128,129]. Thus, objective measures of mucosal inflammation are also
required for the diagnosis.

Objective evidence of inflammation — In addition, establishing the diagnosis requires

objective evidence of sinus mucosal disease on sinus computed tomography (CT) imaging or
direct endoscopic examination because symptoms alone are not sufficiently specific. (See
'Demonstration of mucosal disease' above.)

Objective evidence of mucosal inflammation requires demonstration of one or more of the

following findings using nasal endoscopy and/or CT imaging [3]:
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● Purulent (not clear) mucus or edema in the middle meatus or ethmoid regions (
picture 3)

● Polyps in the nasal cavity or the middle meatus

● Radiographic imaging demonstrating mucosal thickening or partial or complete

opacification of the paranasal sinuses

The performance of these diagnostic criteria was evaluated in a prospective study of 202
consecutive patients presenting to an otolaryngology practice for evaluation of possible CRS
[107]. Patients completed questionnaires about symptoms and then underwent rigid nasal
endoscopy by a clinician blinded to symptom scores. This was followed by sinus CT, which
served as the gold standard for determining the presence or absence of CRS. Within this
referral population, 178 had two or more of the four cardinal symptoms. Of these subjects, only
40 percent (71 of 178) had CRS based upon CT. Thus, symptoms alone had a sensitivity of 89
percent, a specificity of just 12 percent, and a positive predictive value (PPV) of only 40 percent
[107]. The addition of nasal endoscopy increased the PPV to 66 percent. Overall, the
combination of symptoms and endoscopy findings had a sensitivity of 47 percent and a
specificity of 84 percent for CRS. The primary advantage of nasal endoscopy compared with CT
is that it spares the patient some radiation, as discussed above. (See 'Rhinoscopy and
endoscopy' above.)

Determining the subtype of disease — Once the diagnosis of CRS has been established, the
subtype of disease present should be defined as clearly as possible. Findings on sinus CT (most
commonly) or tissue biopsy (if available) assist in differentiation among the three subtypes of
CRS ( table 1):

● CRS with nasal polyposis (CRS with NP) is characterized by the presence of bilateral nasal
polyposis [1]. Medical records documenting removal of bilateral nasal polyps during
previous surgery also satisfy this requirement. (See 'CRS with nasal polyposis' above.)

● Allergic fungal rhinosinusitis (AFRS) should be suspected when CT shows polypoid mucosal
thickening, one or more opacified sinuses despite extensive medical therapy, and
characteristic hyperdensities within the opacified sinuses ( image 4). Note that these
hyperdensities are not entirely specific for AFRS and are not required to make the
diagnosis [28].

Surgery is required to establish the diagnosis by confirming the presence of allergic mucin
containing degranulating eosinophils and fungal hyphae (as demonstrated by fungal
staining or culture) that do not invade the underlying mucosa. Evidence of IgE-mediated
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allergy to one or more fungi must be demonstrated, either with skin testing or IgE
immunoassays. Finally, diabetes mellitus or other immunodeficiency states should be
excluded, and there should be no evidence of invasive fungal disease. All of these
elements are required to make the diagnosis of AFRS. (See 'Allergic fungal rhinosinusitis'
above.)

● Eosinophilic mucin rhinosinusitis should be suspected in patients with diffuse bilateral

nasal polyposis and bilateral sinus opacification with hyperdensities within the opacified
sinuses, especially in patients with asthma and aspirin-exacerbated respiratory disease (
image 5). In such patients, AFRS must also be ruled out. (See "Allergic fungal
rhinosinusitis".)

● CRS without NP is characterized by sinus opacification or sinus ostial obstruction with

nonpolypoid mucosal thickening of the associated sinus cavity ( image 2). Chronic
infection should be considered when these findings are present. (See 'CRS without nasal
polyposis' above.)

When purulent drainage is present, it may be helpful to obtain cultures from the middle
meatus or sinus cavities. Antral puncture of the maxillary sinus to obtain cultures is
typically reserved for research studies. (See 'Rhinoscopy and endoscopy' above.)

DIFFERENTIAL DIAGNOSIS

The symptoms of CRS overlap with those of other rhinogenic and nonrhinogenic conditions.
CRS can also coexist with these other conditions.

● Pain syndromes – Prominent facial pain can be seen with migraine headaches, tension
headaches, cluster headaches, and other poorly understood facial pain syndromes
[130,131]. In these conditions, pain overshadows other symptoms, and imaging does not
show sinus pathology. However, headaches and pain syndromes coexist with CRS in a
substantial proportion of patients. In coexistent disease, a careful review of the patient's
symptoms usually reveals more than one pattern of pain. Headache syndromes are
discussed separately. (See "Evaluation of headache in adults" and "Overview of craniofacial
pain" and "Headache in children: Approach to evaluation and general management
strategies", section on 'Primary headache'.)

● Rhinitis without sinusitis – Anterior or posterior nasal drainage may be a symptom of

seasonal or perennial allergic rhinitis, nonallergic vasomotor (or idiopathic) rhinitis, rhinitis
medicamentosa, and rhinitis associated with medication use. However, patients with these
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conditions do not fulfill the other criteria for CRS. Uncommon causes include cerebral
spinal fluid rhinorrhea, nasal and sinus secreting tumors, inverted papilloma, and nasal
foreign bodies. The nasal secretions in these disorders are not usually mucopurulent in
appearance. (See "An overview of rhinitis" and "Etiologies of nasal symptoms: An
overview".)

● Laryngopharyngeal reflux – Occasionally, the perception of mucus build-up in the throat

may be a symptom of laryngopharyngeal reflux (LPR), a variant of gastroesophageal
reflux, in which acidic gastric fluids reflux up into the larynx and/or pharynx. Other
associated symptoms include heartburn, chronic throat clearing, and hoarseness [132].
This disorder can both mimic CRS and contribute to the symptomatology of CRS in
patients with both conditions. LPR is reviewed elsewhere. (See "Laryngopharyngeal reflux
in adults: Evaluation, diagnosis, and management".)

● Disorders of olfaction – Nasal/paranasal sinus disease is one of the most common causes
of decreased sense of smell. Head trauma and loss of smell related to upper respiratory
tract infections or age are other possible causes. Cacosmia is not suggestive of CRS.
Disorders of olfaction are reviewed separately. (See "Taste and olfactory disorders in
adults: Anatomy and etiology", section on 'Olfactory dysfunction'.)

INCIDENTAL FINDINGS OF SINUSITIS ON IMAGING STUDIES

Occasionally, a computerized tomography (CT) or magnetic resonance image (MRI) done for
another reason (eg, stroke, trauma, mental status change) shows evidence of sinusitis or
mastoiditis in a patient who does not report symptoms, even upon careful questioning. A few
studies have addressed incidental findings and concluded that these are not uncommon and
should not warrant treatment unless there are suggestive symptoms:

● The presence of mucosal thickening in the paranasal sinuses and mastoid cells of 147
children who had undergone MRI of the head for reasons other than sinusitis or
mastoiditis was evaluated in a prospective analysis [133]. Mucosal swelling in the
maxillary, frontal, and sphenoid sinuses was characterized as absent, minor (<5 mm), or
major (≥5 mm). Involvement of the ethmoid cells and mastoid cells was characterized as
absent, minor (≤50 percent of cells), or major (>50 percent). On MRI, 61 percent of children
had one or more findings in their paranasal sinuses or mastoid cells, including 48 percent
with mucosal swelling in their paranasal cavities and 25 percent with abnormalities in the
mastoid cells. The prevalence was higher among children younger than 10 years of age
(60 percent in paranasal sinuses and 42 percent in mastoid cells) and among children with

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current upper respiratory tract infection (71 percent and 35 percent). No correlation was
found with a history of headache, snoring, asthma, allergies, gender, or place of
residence. The authors concluded that mucosal swelling in the paranasal sinuses and
mastoids is a frequent incidental finding in children.

● The prevalence and clinical relevance of findings of chronic sinusitis on head CT scans was
evaluated in a retrospective study of 500 adults presenting to an emergency department
with acute atraumatic headaches [134]. In this study, findings of "chronic sinusitis" were
defined as CT evidence of mucosal thickening, secretions, or opacification involving the
ethmoid, frontal, or maxillary sinuses. CT scans showing polyps, polypoid thickening, or
mucous retention cysts were considered indeterminate, whereas CT scans reporting an air
fluid level were considered possibly consistent with acute sinusitis (a potential etiology for
an acute atraumatic headache). A cohort of 234 patients with atraumatic headache was
compared with a control cohort of 266 patients with minor head injury. Findings of chronic
sinusitis (total of 19.8 percent of CT scans), indeterminate (total of 4.4 percent of CT scans),
or air fluid level (total of 4 percent of CT scans) were no more prevalent in the atraumatic
headache group than in the minor head injury group. The authors concluded that the
various CT findings of chronic sinusitis in patients with atraumatic headache may be
incidental and that these findings are rarely the cause of a patient's acute headache.

Based on these studies, it can be concluded that radiographic abnormalities in the paranasal
sinuses and mastoid cells are not uncommon in asymptomatic patients. The clinician who
encounters patients with asymptomatic findings should consider whether the findings may
relate to a recent viral upper respiratory infection (URI). If so, treatment is not warranted. In the
absence of a recent URI, the patient should be questioned further about symptoms suggestive
of chronic sinusitis (or mastoiditis). If symptoms are not present, treatment is not indicated.

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Chronic rhinosinusitis"
and "Society guideline links: Primary ciliary dyskinesia".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade

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reading level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer
short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading
level and are best for patients who want in-depth information and are comfortable with some
medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a
variety of subjects by searching on "patient info" and the keyword(s) of interest.)

● Basics topic (see "Patient education: Chronic sinusitis (The Basics)")

● Beyond the Basics topic (see "Patient education: Chronic rhinosinusitis (Beyond the
Basics)")

SUMMARY AND RECOMMENDATIONS

Chronic rhinosinusitis (CRS) is an inflammatory condition involving the paranasal sinuses and
the lining of the nasal passages, lasting 12 weeks or longer, despite attempts at medical
management. (See 'Definition' above.)

● The four cardinal symptoms of CRS are mucopurulent drainage, nasal obstruction, facial
pain and/or pressure, and decreased olfaction. In children, the fourth cardinal symptom is
cough. At least two of these four must be present to consider the diagnosis of CRS. These
symptoms are not specific for CRS, do not distinguish reliably among the different
subtypes, and do not correlate well with objective findings upon imaging. (See 'Clinical
manifestations' above.)

● CRS may be subdivided into three distinct clinical syndromes, with different contributing
factors and responses to medical or surgical management: CRS with nasal polyposis (CRS
with NP), CRS without nasal polyposis (CRS without NP), and allergic fungal rhinosinusitis (
table 1). (See 'Features of specific subtypes' above.)

● CRS, particularly CRS with NP, is strongly associated with asthma and with aspirin-
exacerbated respiratory disease. A variety of factors may contribute to the development of
CRS, independent of the subtype, including environmental allergies, aspirin sensitivity,
inhaled irritants, viral infections, immunodeficiency, systemic diseases, and anatomic
abnormalities ( table 2). (See 'Risk factors and associated conditions' above.)

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● The evaluation of CRS involves a clinical history and objective documentation of mucosal
disease with either sinus computed tomography (CT) imaging or rhinoscopy or nasal
endoscopy with decongestion. Allergy evaluation should be pursued in all patients, and
immunologic defects and infectious complications should be considered. (See 'Evaluation'
above.)

● The diagnosis of CRS requires the presence of at least two of the four cardinal symptoms
of CRS lasting 12 weeks or longer, despite attempts at medical management plus
objective evidence of sinus mucosal disease on sinus CT imaging or direct examination (
algorithm 1). Each subtype of CRS has characteristic findings on CT imaging. (See
'Diagnosis' above.)

● The differential diagnosis of CRS includes headache and facial pain syndromes, various
forms of rhinitis without sinusitis, laryngopharyngeal reflux, and disorders of olfaction.
(See 'Differential diagnosis' above.)

Use of UpToDate is subject to the Terms of Use.

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Topic 7528 Version 32.0

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GRAPHICS

Location of the paranasal sinuses and ostiomeatal complex

Schematic figure showing location of the frontal, ethmoid, maxillary, and sphenoid sinuses, as
well as the ostiomeatal complex (also called the ostiomeatal unit).

Graphic 67454 Version 4.0

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Types of chronic rhinosinusitis

Features AFRS CRS with NP CRS without NP

Bilateral nasal polyps Yes (in most cases) Yes - Required for No - Exclusion of
diagnosis* polyps is required for
diagnosis

Allergic mucin Yes - Required for May be present May be present

diagnosis

Aspirin-associated May be present Asthma present in Rare

respiratory disease approximately 40%

Aspirin intolerance and

asthma present in
approximately 15%

Evidence of IgE- Yes - Required for May be present May be present

mediated allergy to diagnosis
fungi

AFRS: allergic fungal rhinosinusitis; CRS: chronic rhinosinusitis; NP: nasal polyposis; IgE:
immunoglobulin E.

* Medical records documenting removal of bilateral NP during surgery would satisfy this
requirement.

Graphic 53734 Version 10.0

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Nasal polyps in nostril

Nasal polyps appear as glistening, gray or white, mucoid masses in

the nasal cavities.

Courtesy of Glenis Scadding, MD and Peter Andrews, BSc, FRCS.

Graphic 50105 Version 4.0

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Surgically removed polyp

This picture shows resected nasal/sinus polyp tissue. The bottom

portion of the specimen demonstrates the characteristic white (or
sometimes gray), avascular nature of polyp tissue.

Courtesy of Daniel L Hamilos, MD.

Graphic 53872 Version 6.0

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Internal examination of the nose

Graphic 52743 Version 3.0

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Radiographic and rhinoscopic features of CRS with

NP

A) Coronal sinus CT scan showing evidence of prior functional

endoscopic sinus surgery with persistence of polypoid mucosal
thickening in both maxillary sinuses and polypoid opacification of
the anterior ethmoid sinuses. B) Rhinoscopic photograph showing
the typical appearance of polypoid regrowth in the left anterior
ethmoid region.

CRS: chronic rhinosinusitis: NP: nasal polyposis; CT: computed

tomography.

Courtesy of Daniel L Hamilos, MD

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Radiographic features of CRS without NP

Sinus CT scan of a 35-year-old female with CRS without NP before (A) and
immediately following (B) intensive medical treatment.

(A) The pretreatment sinus CT scan shows near total opacification of both
maxillary and anterior ethmoid sinuses.

(B) The post-treatment sinus CT scan shows complete resolution of these

findings. The patient's CRS symptoms completely resolved.

CRS: chronic rhinosinusitis; NP: nasal polyposis; CT: computed tomography.

Reproduced with permission from: Subramanian HN, Schechtman KB, Hamilos DL. A retrospective
analysis of treatment outcomes and time to relapse after intensive medical treatment for chronic
sinusitis. Am J Rhinol 2002; 16:303. Copyright © 2002 Oceanside Publications.

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Disorders that may exacerbate and/or contribute to CRS

Allergic rhinitis

Chronic exposure to environmental irritants or ciliostatic substances (eg, tobacco smoke)

Immunodeficiency states (especially defects in antibody production or function)

Defects in mucociliary clearance (eg, cystic fibrosis and primary ciliary dyskinesia)

Recurrent viral upper respiratory tract infections

Systemic disorders (eg, granulomatosis with polyangiitis [Wegener's], eosinophilic granulomatosis

with polyangiitis [Churg-Strauss], sarcoidosis)

Anatomic abnormalities predisposing to sinus obstruction

Iatrogenic (due to complications of repeated sinus surgery)

CRS: chronic rhinosinusitis.

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Diagnosis of chronic rhinosinusitis (CRS) in adults

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CT: computed tomography; MRI: magnetic resonance imaging.

* Note that plain sinus radiographs are not adequate.

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Endoscopic view of the nose

Endoscopic view of the right nasal cavity showing purulent

discharge flowing from the maxillary and ethmoid sinuses onto the
middle meatus. The middle turbinate (MT), lateral nasal wall (L), and
nasal septum (S) are visible.

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CT scan of normal paranasal sinuses

This coronal CT image shows normal maxillary and ethmoid sinuses with the
ostiomeatal complexes widely patent bilaterally.

CT: computed tomography.

Courtesy of Daniel L Hamilos, MD.

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Paranasal sinuses: Anatomy of the ostiomeatal complex

Panel A shows a coronal view of the ostiomeatal complex (OMC). Arrows indicate the
direction of mucociliary flow, and circles mark areas that can become obstructed. Panel B, in
which the middle turbinate has been removed, shows the remaining structures that comprise
the OMC: the uncinate process, hiatus semilunaris, ethmoid bulla, and ostium of the
maxillary sinus.

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Sinus computed tomography scan of a patient with

allergic fungal rhinosinusitis

Sinus computed tomography scan of a patient with arrows showing

complete opacification of both anterior ethmoid (upper set of
arrows) and maxillary (lower set of arrows) sinuses and
hyperdensities within these same areas.

Courtesy of Daniel L Hamilos, MD.

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Sinus CT scan of a patient with eosinophilic mucin rhinosinusitis (EMRS)

Sinus CT scan of a patient with EMRS showing characteristic features of soft tissue thickening in the
upper nasal cavity consistent with nasal polyposis and extensive bilateral sinus opacification and
hyperdensities. Panel A demonstrates a bone window, which provides excellent delineation of bony
structures but only faintly demonstrates hyperdensities in the maxillary sinuses. In contrast, panel B
(same image as on the left) is a soft tissue window that demonstrates dramatic hyperdensities in
both maxillary sinuses. This patient underwent sinus surgery. The sinus pathology showed polypoid
chronic rhinosinusitis with stromal eosinophils and abundant allergic mucin. A Gomori-
methenamine silver (GMS) stain was negative for fungal organisms.

CT: computed tomography.

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Contributor Disclosures
Daniel L Hamilos, MD Consultant/Advisory Boards: AstraZeneca [Drug development, Nasal
polyposis];GSK [Drug development, Nasal polyposis]. All of the relevant financial relationships listed have
been mitigated. Eric H Holbrook, MD Consultant/Advisory Boards: Lyra Therapeutics [Rhinology]. All of
the relevant financial relationships listed have been mitigated. Anju T Peters, MD,
MSCI Grant/Research/Clinical Trial Support: AstraZeneca [Chronic rhinosinusitis with nasal
polyps];Merck[Cough];Optinose [Chronic rhinosinusitis];Sanofi Regeneron[Chronic rhinosinusitis with
nasal polys]. Consultant/Advisory Boards: AstraZeneca [Asthma, chronic rhinosinusitis with nasal
polyps];Genentech[Allergy/immunology];GSK [Respiratory diseases];Merck[Cough];Optinose [Chronic
rhinosinusitis with nasal polyps];Sanofi Regeneron [Chronic rhinosinusitis with nasal polyps]. All of the
relevant financial relationships listed have been mitigated. Daniel G Deschler, MD, FACS No relevant
financial relationship(s) with ineligible companies to disclose. Anna M Feldweg, MD No relevant financial
relationship(s) with ineligible companies to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.

Conflict of interest policy

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