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Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis

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
Literature review current through: Feb 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. 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:

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".)

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 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

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".)

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 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).

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:

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 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].

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 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 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

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].

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 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].

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".)

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).

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]:

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 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 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".)

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 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 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.)

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.)

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  48. Drake-Lee AB, McLaughlan P. Clinical symptoms, free histamine and IgE in patients with nasal polyposis. Int Arch Allergy Appl Immunol 1982; 69:268.
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  56. Benjamin MR, Stevens WW, Li N, et al. Clinical Characteristics of Patients with Chronic Rhinosinusitis without Nasal Polyps in an Academic Setting. J Allergy Clin Immunol Pract 2019; 7:1010.
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  58. Cryer J, Schipor I, Perloff JR, Palmer JN. Evidence of bacterial biofilms in human chronic sinusitis. ORL J Otorhinolaryngol Relat Spec 2004; 66:155.
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  71. Berrettini S, Carabelli A, Sellari-Franceschini S, et al. Perennial allergic rhinitis and chronic sinusitis: correlation with rhinologic risk factors. Allergy 1999; 54:242.
  72. Jarvis D, Newson R, Lotvall J, et al. Asthma in adults and its association with chronic rhinosinusitis: the GA2LEN survey in Europe. Allergy 2012; 67:91.
  73. Moore WC, Bleecker ER, Curran-Everett D, et al. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program. J Allergy Clin Immunol 2007; 119:405.
  74. Denlinger LC, Phillips BR, Ramratnam S, et al. Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations. Am J Respir Crit Care Med 2017; 195:302.
  75. Schlosser RJ, Gage SE, Kohli P, Soler ZM. Burden of illness: A systematic review of depression in chronic rhinosinusitis. Am J Rhinol Allergy 2016; 30:250.
  76. Lieu JE, Feinstein AR. Confirmations and surprises in the association of tobacco use with sinusitis. Arch Otolaryngol Head Neck Surg 2000; 126:940.
  77. Reh DD, Higgins TS, Smith TL. Impact of tobacco smoke on chronic rhinosinusitis: a review of the literature. Int Forum Allergy Rhinol 2012; 2:362.
  78. Pinto JM, Naclerio RM. Environmental and allergic factors in chronic rhinosinusitis. Clin Allergy Immunol 2007; 20:25.
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  80. Carr TF, Koterba AP, Chandra R, et al. Characterization of specific antibody deficiency in adults with medically refractory chronic rhinosinusitis. Am J Rhinol Allergy 2011; 25:241.
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  85. Schwitzguébel AJ, Jandus P, Lacroix JS, et al. Immunoglobulin deficiency in patients with chronic rhinosinusitis: Systematic review of the literature and meta-analysis. J Allergy Clin Immunol 2015; 136:1523.
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  90. Baroody FM. Mucociliary transport in chronic rhinosinusitis. Clin Allergy Immunol 2007; 20:103.
  91. Jang YJ, Kwon HJ, Park HW, Lee BJ. Detection of rhinovirus in turbinate epithelial cells of chronic sinusitis. Am J Rhinol 2006; 20:634.
  92. Cho GS, Moon BJ, Lee BJ, et al. High rates of detection of respiratory viruses in the nasal washes and mucosae of patients with chronic rhinosinusitis. J Clin Microbiol 2013; 51:979.
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  94. Goggin RK, Bennett CA, Bialasiewicz S, et al. The presence of virus significantly associates with chronic rhinosinusitis disease severity. Allergy 2019; 74:1569.
  95. Lohrmann C, Uhl M, Warnatz K, et al. Sinonasal computed tomography in patients with Wegener's granulomatosis. J Comput Assist Tomogr 2006; 30:122.
  96. Alobid I, Guilemany JM, Mullol J. Nasal manifestations of systemic illnesses. Curr Allergy Asthma Rep 2004; 4:208.
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  104. Jones NS, Strobl A, Holland I. A study of the CT findings in 100 patients with rhinosinusitis and 100 controls. Clin Otolaryngol Allied Sci 1997; 22:47.
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  108. Tichenor WS, Adinoff A, Smart B, Hamilos DL. Nasal and sinus endoscopy for medical management of resistant rhinosinusitis, including postsurgical patients. J Allergy Clin Immunol 2008; 121:917.
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  127. Asero R, Bottazzi G. Hypersensitivity to molds in patients with nasal polyposis: A clinical study. J Allergy Clin Immunol 2000; 105:186.
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Topic 7528 Version 32.0

References

1 : International Consensus Statement on Allergy and Rhinology: Rhinosinusitis.

2 : BSACI guidelines for the management of rhinosinusitis and nasal polyposis.

3 : Clinical practice guideline (update): adult sinusitis.

4 : EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists.

5 : The diagnosis and management of sinusitis: a practice parameter update.

6 : European Position Paper on Rhinosinusitis and Nasal Polyps 2020.

7 : Rhinosinusitis: establishing definitions for clinical research and patient care.

8 : Nasal and sinus symptoms and chronic rhinosinusitis in a population-based sample.

9 : Prevalence of chronic rhinosinusitis in the general population based on sinus radiology and symptomatology.

10 : Chronic rhinosinusitis: Epidemiology and burden of disease.

11 : Direct costs of adult chronic rhinosinusitis by using 4 methods of estimation: Results of the US Medical Expenditure Panel Survey.

12 : Chronic rhinosinusitis: a comparative study of disease occurrence in North of Scotland and Southern Caribbean otolaryngology outpatient clinics over a two month period.

13 : Prevalence of chronic rhinosinusitis in Sao Paulo.

14 : Epidemiology of chronic rhinosinusitis: results from a cross-sectional survey in seven Chinese cities.

15 : Epidemiology of chronic rhinosinusitis in Bushehr, southwestern region of Iran: a GA2LEN study.

16 : Chronic rhinosinusitis: contrasts between children and adult patients.

17 : Prevalence of the chronic sinusitis diagnosis in Olmsted County, Minnesota.

18 : The socioeconomic cost of chronic rhinosinusitis study.

19 : Cost of adult chronic rhinosinusitis: A systematic review.

20 : The personal financial burden of chronic rhinosinusitis: A Canadian perspective.

21 : Relationship Between Nasal Cycle, Nasal Symptoms and Nasal Cytology.

22 : The economic burden and symptom manifestations of chronic rhinosinusitis.

23 : Association of radiological evidence of frontal sinus disease with the presence of frontal pain.

24 : Midfacial segment pain: implications for rhinitis and sinusitis.

25 : Usefulness of patient symptoms and nasal endoscopy in the diagnosis of chronic sinusitis.

26 : Comprehensive management of patients presenting to the otolaryngologist for sinus pressure, pain, or headache.

27 : Lack of significant correlation between rhinosinusitis symptoms and specific regions of sinus computer tomography scans.

28 : Chronic rhinosinusitis patterns of illness.

29 : [Localization and distribution of human olfactory mucosa in the nasal cavities].

30 : Biofilms and chronic rhinosinusitis: systematic review of evidence, current concepts and directions for research.

31 : Functional limitations and workdays lost associated with chronic rhinosinusitis and allergic rhinitis.

32 : Impaired eating-related quality of life in chronic rhinosinusitis.

33 : Non-surgical chronic rhinosinusitis and quality of life: A Vietnamese perspective.

34 : Acute Exacerbations Mediate Quality of Life Impairment in Chronic Rhinosinusitis.

35 : The health impact of chronic sinusitis in patients seeking otolaryngologic care.

36 : Pathogenesis of chronic rhinosinusitis: inflammation.

37 : Pathophysiology of chronic rhinosinusitis.

38 : Prevalence of nasal polyps in adults: the Skövde population-based study.

39 : Prevalence of nasal polyposis in France: a cross-sectional, case-control study.

40 : Nasal polyps as immunoreactive tissue.

41 : Unexpected tumor incidence in surgically removed unilateral and bilateral nasal polyps.

42 : Aspirin-exacerbated respiratory disease: burden of disease.

43 : Aspirin-exacerbated respiratory disease: burden of disease.

44 : Chronic hyperplastic sinusitis: association of tissue eosinophilia with mRNA expression of granulocyte-macrophage colony-stimulating factor and interleukin-3.

45 : Features of airway remodeling and eosinophilic inflammation in chronic rhinosinusitis: is the histopathology similar to asthma?

46 : Current thinking on the relationship between rhinosinusitis and asthma.

47 : Density of middle turbinate subepithelial mucous glands in patients with chronic rhinosinusitis.

48 : Clinical symptoms, free histamine and IgE in patients with nasal polyposis.

49 : Staphylococcus aureus colonization and IgE antibody formation to enterotoxins is increased in nasal polyposis.

50 : Superantigen hypothesis for the early development of chronic hyperplastic sinusitis with massive nasal polyposis.

51 : Further observations on the role of Staphylococcus aureus exotoxins and IgE in the pathogenesis of nasal polyposis.

52 : Optic neuropathy due to allergic fungal rhinosinusitis.

53 : Allergic fungal sinusitis in children.

54 : Eosinophilic mucin rhinosinusitis: a distinct clinicopathological entity.

55 : Fungal-specific humoral response in eosinophilic mucus chronic rhinosinusitis.

56 : Clinical Characteristics of Patients with Chronic Rhinosinusitis without Nasal Polyps in an Academic Setting.

57 : Chronic recurrent rhinosinusitis: disease severity and clinical characterization.

58 : Evidence of bacterial biofilms in human chronic sinusitis.

59 : Demonstration of biofilm in human bacterial chronic rhinosinusitis.

60 : Bacterial biofilms in surgical specimens of patients with chronic rhinosinusitis.

61 : The impact of biofilms on outcomes after endoscopic sinus surgery.

62 : Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers.

63 : Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis.

64 : Chronic rhinosinusitis and bacterial biofilms.

65 : Clinical and immunological determinants of severe/refractory asthma (SRA): association with Staphylococcal superantigen-specific IgE antibodies.

66 : Adult chronic rhinosinusitis: definitions, diagnosis, epidemiology, and pathophysiology.

67 : The incidence of concurrent osteitis in patients with chronic rhinosinusitis: a clinicopathological study.

68 : Chronic rhinosinusitis: allergy and sinus computed tomography relationships.

69 : Pediatric acute and chronic rhinosinusitis: comparison of clinical characteristics and outcome of treatment.

70 : Prevalence and risk factors of chronic rhinosinusitis in Korea.

71 : Perennial allergic rhinitis and chronic sinusitis: correlation with rhinologic risk factors.

72 : Asthma in adults and its association with chronic rhinosinusitis: the GA2LEN survey in Europe.

73 : Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program.

74 : Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations.

75 : Burden of illness: A systematic review of depression in chronic rhinosinusitis.

76 : Confirmations and surprises in the association of tobacco use with sinusitis.

77 : Impact of tobacco smoke on chronic rhinosinusitis: a review of the literature.

78 : Environmental and allergic factors in chronic rhinosinusitis.

79 : Air quality influences the prevalence of hay fever and sinusitis.

80 : Characterization of specific antibody deficiency in adults with medically refractory chronic rhinosinusitis.

81 : Immunologic defects in patients with refractory sinusitis.

82 : The prevalence of humoral immunodeficiency in refractory rhinosinusitis: a retrospective analysis.

83 : Clinical characteristics of adults with chronic rhinosinusitis and specific antibody deficiency.

84 : The Clinical Significance of Specific Antibody Deficiency (SAD) Severity in Chronic Rhinosinusitis (CRS).

85 : Immunoglobulin deficiency in patients with chronic rhinosinusitis: Systematic review of the literature and meta-analysis.

86 : A population-based study of morbidity and mortality in mannose-binding lectin deficiency.

87 : Nasal mucosa expression of lactoferrin in patients with chronic rhinosinusitis.

88 : Perspectives on the etiology of chronic rhinosinusitis.

89 : Proteomics of nasal mucus in chronic rhinosinusitis.

90 : Mucociliary transport in chronic rhinosinusitis.

91 : Detection of rhinovirus in turbinate epithelial cells of chronic sinusitis.

92 : High rates of detection of respiratory viruses in the nasal washes and mucosae of patients with chronic rhinosinusitis.

93 : Respiratory viral infection in the chronic persistent phase of chronic rhinosinusitis.

94 : The presence of virus significantly associates with chronic rhinosinusitis disease severity.

95 : Sinonasal computed tomography in patients with Wegener's granulomatosis.

96 : Nasal manifestations of systemic illnesses.

97 : Sinonasal imaging findings in granulomatosis with polyangiitis (Wegener granulomatosis): A systematic review.

98 : Clinical features of sarcoid rhinosinusitis.

99 : Sinusitis of odontogenic origin.

100 : Frequency of a dental source for acute maxillary sinusitis.

101 : Unrecognized odontogenic maxillary sinusitis: a cause of endoscopic sinus surgery failure.

102 : Anatomic variation in pediatric chronic sinusitis: a CT study.

103 : Paranasal sinus bony anatomic variations and mucosal abnormalities: CT analysis for endoscopic sinus surgery.

104 : A study of the CT findings in 100 patients with rhinosinusitis and 100 controls.

105 : [Influence of naso-sinusal anatomic variants on recurrent, persistent or chronic sinusitis. X-ray computed tomographic evaluation in 112 patients].

106 : [Influence of naso-sinusal anatomic variants on recurrent, persistent or chronic sinusitis. X-ray computed tomographic evaluation in 112 patients].

107 : Evaluating the diagnosis of chronic rhinosinusitis based on clinical guidelines and endoscopy.

108 : Nasal and sinus endoscopy for medical management of resistant rhinosinusitis, including postsurgical patients.

109 : Diagnosis and management of rhinosinusitis: a practice parameter update.

110 : Imaging of rhinosinusitis and its complications: plain film, CT, and MRI.

111 : EAACI position paper on rhinosinusitis and nasal polyps executive summary.

112 : The accuracy of computed tomography in the diagnosis of chronic rhinosinusitis.

113 : Projected cancer risks from computed tomographic scans performed in the United States in 2007.

114 : Computed tomographic study of the common cold.

115 : Computed tomography--an increasing source of radiation exposure.

116 : Chronic rhinosinusitis in children.

117 : Clinical consensus statement: appropriate use of computed tomography for paranasal sinus disease.

118 : Clinical consensus statement: appropriate use of computed tomography for paranasal sinus disease.

119 : Diagnosis and treatment of isolated sphenoid sinus disease: a review of 109 cases.

120 : Isolated sphenoid sinus pathology: spectrum of diagnostic and treatment modalities.

121 : Current management of isolated sphenoiditis.

122 : Isolated sphenoid sinus disease.

123 : Diagnostic and staging accuracy of magnetic resonance imaging for the assessment of sinonasal disease.

124 : Fungal sinusitis: diagnosis with CT and MR imaging.

125 : Allergic fungal sinusitis: CT findings.

126 : Nasal polyposis: a study of its association with airborne allergen hypersensitivity.

127 : Hypersensitivity to molds in patients with nasal polyposis: A clinical study.

128 : Relationship between patient-based descriptions of sinusitis and paranasal sinus computed tomographic findings.

129 : The Lund-Mackay staging system for chronic rhinosinusitis: how is it used and what does it predict?

130 : The prevalence of facial pain and purulent sinusitis.

131 : Headaches and facial pain in rhinology.

132 : Hoarseness and laryngopharyngeal reflux: a cause and effect relationship or coincidence?

133 : Incidental findings in paranasal sinuses and mastoid cells: a cross-sectional magnetic resonance imaging (MRI) study in a pediatric radiology department.

134 : Findings of chronic sinusitis on brain computed tomography are not associated with acute headaches.