Diagnosis and management of chronic rhinosinusitis

KEY POINTS

• Patients with chronic rhinosinusitis typically present with long-term nasal congestion, rhinorrhea, facial pressure, and altered sense of smell.

• A definitive diagnosis requires objective findings on endoscopy or computed tomography; sinus radiography is of limited value.

• First-line treatments include the long-term use of topical saline and intranasal corticosteroids.

• Endoscopic sinus surgery is effective but sometimes requires subsequent revision.

• Monoclonal antibody therapies are a treatment option for patients with severe chronic rhinosinusitis with nasal polyps recalcitrant to first-line therapies.

Chronic rhinosinusitis refers to symptomatic inflammation of the nose and paranasal sinuses that has been present for a minimum of 3 months.¹ Its true prevalence is difficult to determine because of diagnostic challenges, but estimates range from 2.1%² to 15%.³ It most commonly affects adults in middle age,³ with females affected slightly more often than males.^3,4 Although the condition may be perceived as a minor inconvenience compared with other chronic diseases, it can be associated with impaired sleep,^5,6 severe fatigue,⁷ and depression,^8,9 which can interfere substantially with activities of daily living. In Canada, patients lose an average of 20.6 work days per year because of symptoms as well as time off for surgeries and medical appointments related to the condition, leading to substantial economic costs.^10–12

Treatment options for patients with chronic rhinosinusitis have recently expanded and improved. We review the evidence related to chronic rhinosinusitis, including the evolving understanding of the condition and treatment modalities (Box 1).

Box 1: Literature review .

We conducted a literature review of PubMed from inception until Nov. 1, 2024. The search terms included “chronic rhinosinusitis,” “sinusitis,” and “CRS,” which we searched in combination with “epidemiology,” “pathophysiology,” and “treatment.” We excluded non-English literature. We emphasized recent clinical practice guidelines and systematic reviews, although we did not restrict article types. We also searched the reference lists of included articles for relevant articles that may have been missed by our search strategy. We focused on treatment guidelines and evidence from 2019 onward.

What are the risk factors for chronic rhinosinusitis?

The cause of chronic rhinosinusitis is not yet fully understood. Contributing factors likely include genetic predisposition, microbial pathogens, environmental factors, and allergy, although none of these factors appears to be solely causative. The rate of asthma among people with chronic rhinosinusitis is estimated to be 25%, 5 times higher than in the general public. The unified airway theory proposes that these 2 conditions share many of the same etiological factors, given their similar cellular biology and known triggers.¹

What is the pathophysiology of the condition?

Chronic rhinosinusitis is understood to be predominantly an inflammatory condition rather than an infectious process.^1,13–15 The underlying pathophysiology likely involves a combination of epithelial barrier insults (e.g., microbes, allergens) and dysregulation of inflammatory pathways (Figure 1). Both the innate and adaptive immune system show dysfunction at the level of the sinus mucosa, leading to goblet cell hyperplasia, impaired mucociliary clearance, and a proinflammatory state.^1,14,15

Figure 1:

Pathophysiology of chronic rhinosinusitis. Note: IFN = interferon, IL = interleukin, ILC1 = innate lymphoid cell type 1, ILC2 = innate lymphoid cell type 2, ILC3 = innate lymphoid cell type 3, NK = natural killer, Th0 = naive T cell, Th1 = T helper 1 cell, Th2 = T helper 2 cell, Th17 = T helper 17 cell, TNF = tumour necrosis factor, TSLP = thymic stromal lymphopoietin. Created in BioRender and adapted from Xu et al¹⁵ with permission from John Wiley and Sons. See Related Content tab for accessible version.

With the advent of targeted therapeutics and increased recognition that certain patients respond better to treatment, chronic rhinosinusitis has increasingly been classsified into endotypes rather than broad phenotypes. The type 2 endotype involves activation of the type 2 inflammatory pathway, whereby T helper 2 cells and type 2 innate lymphoid cells produce the inflammatory cytokines interleukin 4, interleukin 5, and interleukin 13.^14–16 In the non–type 2 endotype, both type 1 and type 3 inflammatory pathways have been seen (Figure 1).

How is chronic rhinosinusitis diagnosed?

The diagnostic criteria for chronic rhinosinusitis are sinonasal inflammation persisting for at least 12 weeks with at least 2 symptoms, as well as 1 sign on clinical examination (Table 1).

Table 1:

Diagnostic criteria for chronic rhinosinusitis^*

Criterion	Symptom or sign
At least 2 symptoms	Nasal obstruction or congestion
	Anterior or posterior nasal drainage
	Decreased sense of smell
	Facial pressure, pain, or fullness
At least 1 sign	Polyps, edema, or mucopurulence on nasal endoscopy or anterior rhinoscopy
	Sinus mucosal thickening on computed tomography

^*Sinonasal inflammation persisting for more than 12 weeks.

The core symptoms include nasal congestion (synonymous with nasal obstruction), anterior or posterior nasal discharge, an altered sense of smell, and facial pain or pressure.¹⁷ Facial discomfort lacks specificity, and some experts believe it should be omitted from diagnostic criteria.^1,13

Additional symptoms include ear fullness, cough, headache, fatigue, dental pain, an altered sense of taste, and halitosis.¹⁸ These symptoms are individually quite sensitive but not specific.¹⁹ Notably, although patients can present with acute rhinosinusitis (i.e., infection on top of their chronically inflamed baseline), they more often appear to have a lingering upper respiratory tract infection.

An overview of the workup and management algorithm is shown in Figure 2. Red-flag signs or symptoms should elicit an urgent referral to an otolaryngologist to rule out more serious pathology, as should failure to respond to standard medical therapy (Table 2). Unilateral symptoms should prompt an expedited referral to rule out other pathologies as chronic rhinosinusitis is typically bilateral in nature.

Figure 2:

The workup and diagnostic algorithm for chronic rhinosinusitis (CRS). Note: CT = computed tomography. *Common symptoms include nasal congestion or obstruction, nasal discharge (anterior or posterior), facial pressure, and loss of smell. †Red-flag signs and symptoms are described in Table 2. See Related Content for accessible version.

Table 2:

Important signs or symptoms in rhinosinusitis for which an alternate diagnosis should be considered

Clinical indicator	Potential condition
Proptosis	Neoplasm, acute infection
Paresthesia	Neoplasm, central neurologic disease
Unilateral, persistent, salty, or metallic-tasting rhinorrhea	Cerebrospinal fluid leak
Recurrent or persistent epistaxis	Neoplasm, nasal dryness or irritation
Diplopia	Neoplasm, central neurologic disease, acute infection
Severe pain	Acute infection, neoplasm, migraine, bruxism, tension or cluster headache
Fever	Acute infection

Differential diagnosis

The differential diagnosis of chronic rhinosinusitis includes allergic rhinitis, septal deviation, and neoplasms of the sinonasal cavity.

Nasal congestion is often seen with allergic rhinitis, but patients do not typically have facial pressure as they do in chronic rhinosinusitis. Furthermore, the secretions in allergic rhinitis are often clear and thin, in contrast to the thicker mucous seen in chronic rhinosinusitis.²⁰ A deviated septum can lead to nasal obstruction and congestion, but does not typically affect sense of smell or cause substantial nasal discharge. Nasal neoplasm may also cause new onset of facial pressure and nasal obstruction but usually in a unilateral pattern, which should prompt an expedited referral to an otolaryngologist.

Clinical examination

The diagnosis of chronic rhinosinusitis requires objective findings of sinonasal inflammation (Table 1). The phenotypic distinction of whether or not the patient has polyps can guide treatment. Nasal polyps may be suspected on anterior rhinoscopy or computed tomography (CT), but endoscopy by an otolaryngologist is currently considered the gold standard, particularly for detecting smaller polyps.²¹ Figure 3A shows nasal polyps arising from the middle meatus in the nose. When compared with the nasal turbinates, nasal polyps often have a watery, edematous, translucent quality. Patients with nasal polyps will often have a hyponasal (i.e., stuffy) quality to their voice and frequently sound as one would expect if they were recovering from an upper respiratory tract infection. In contrast, those without polyps more often have thick, mucopurulent secretions on examination (Figure 3B). Given the high rate of association between chronic rhinosinusitis and asthma, screening for lower airway inflammatory disease and chest auscultation are important.

Figure 3:

(A) Intraoperative endoscopic view of an inflammatory nasal polyp (NP) in the left nasal cavity, characteristic of chronic rhinosinusitis with nasal polyposis. (B) Intraoperative endoscopic view of purulent discharge (D) in the right nasal cavity, characteristic of chronic rhinosinusitis without nasal polyposis. Note: IT = inferior turbinate, MT = middle turbinate, S = septum.

Rarely, chronic rhinosinusitis can expand beyond the nasal sinuses and start to involve the orbital structures. These patients may present with proptosis, which is usually unilateral and readily apparent. This finding would warrant urgent CT to confirm the diagnosis of complicated rhinosinusitis and help guide treatment (Figure 2).

Investigations

No specific laboratory tests currently exist for the diagnosis of chronic rhinosinusitis. Biomarkers (e.g., serum eosinophil levels) may help with distinguishing the underlying endotype but no markers have yet been found to be useful in predicting treatment response or guiding management.²¹

The standard imaging modality used in chronic rhinosinusitis is noncontrast CT of the sinuses. Chronic inflammation appears as mucosal thickening or opacification (lack of aeration) of the sinuses on CT. A plain film radiograph of the sinuses lacks sensitivity for diagnosing chronic rhinosinusitis and should not be ordered.¹⁷

If a patient presents with symptoms of allergic rhinitis (bilateral clear rhinorrhea, itchy eyes, and sneezing), allergy testing can be helpful to identify and avoid potential triggers.

How is chronic rhinosinusitis managed?

Treatment of chronic rhinosinusitis is focused on reducing inflammatory burden and trying to restore normal mucociliary function. The presence of nasal polyps is relevant but does not change first-line approaches. Table 3 summarizes the standard treatment options.

Table 3:

Standard medical treatment for chronic rhinosinusitis

Treatment	Example agent	Common dosing regimen
Topical saline irrigation	Commercially available sinus rinse or saline mist	1–2 times daily
Topical steroid spray	Mometasone furoate, fluticasone furoate	2 sprays to both nostrils daily for minimum 8 wk
Oral steroids for nasal polyps	Prednisone	30 mg/d for 7 d
Oral antibiotics for acute flares	Amoxicillin–clavulanate	875 mg twice daily for 10 d

Pharmacologic treatment

Long-term topical intranasal corticosteroids are the first-line treatment. A Cochrane review of 18 randomized controlled trials (RCTs) compared intranasal steroids to placebo and concluded that intranasal corticosteroids improved patient symptoms, reduced inflammation in the sinonasal mucosa (including the reduction of nasal polyps), and addressed related conditions such as allergic rhinitis.²² Specifically, in 6 studies that reported severity of nasal blockage and rhinorrhea, patients treated with steroids had less severe symptoms (mean difference −0.31, 95% confidence interval [CI] −0.38 to −0.24) than those treated with placebo.²² With regard to polyp size, the relative risk of improvement in size was 1.77 (95% CI 1.06 to 2.95) for patients in the intranasal steroid group, again demonstrating the efficacy of steroids compared with placebo.²² Therefore, it is reasonable to start treatment when chronic rhinosinusitis is clinically suspected based on mild to moderate symptoms. These topical medications are considered safe with minimal systemic absorption. Meta-analyses have shown the risk of biochemical adrenal insufficiency, a feared complication from steroid absorption, to be low (around 0.70%); none of the included studies reported clinical symptoms of adrenal insufficiency (e.g., hypotension, fatigue, irritability).^23,24

Topical saline sprays and irrigations are effective adjuvant treatments for chronic rhinosinusitis (both with and without nasal polyps). A systematic review demonstrated that high-volume saline irrigations (squeeze bottle or pot) had greater distribution to the sinus cavities than saline sprays.²⁵ These solutions are typically mixed by the patient by adding a premixed packet (sodium chloride and sodium bicarbonate) to 240 mL of distilled water, which is then used to irrigate the nasal cavity. An RCT found a significant improvement in quality-of-life scores and symptom frequency (absolute risk reduction 0.20, 95% CI 0.02 to 0.38) in the nasal irrigation group, compared with low-volume saline sprays, with a number needed to treat of 5.²⁶ If high-volume irrigations are not well tolerated because of ear pressure or other symptoms, patients should continue to use saline sprays alone. Regardless of the delivery method, irrigation should be done before using an intranasal steroid spray to avoid washing out the medication.

Oral medications

Short bursts of oral steroids such as prednisone can reduce the size of known nasal polyps and provide rapid symptomatic relief, including improved sense of smell.^1,13,27 A Cochrane review that included 8 RCTs showed that the benefits of oral steroids were generally limited to a few months.²⁸ Specifically, the mean symptom score after 17 days of treatment was 2.84 standard deviations lower than baseline scores, but just 0.22 standard deviations lower at 3 months, highlighting the short-lived nature of the benefit.²⁸ Judicious use of steroids is recommended, given concerns of long-term adverse effects from systemic absorption.²⁷ The optimal dosage of oral steroids is unknown; a common regimen is provided in Table 3.

Recent guidelines suggest antibiotics should be considered for only acute exacerbations of chronic rhinosinusitis (with and without nasal polyps), while clinicians should remain wary of the patient who presents with fever or severe pain (Table 2).^1,27 A 2016 Cochrane review found very little evidence for the efficacy of systemic antibiotics in patients with chronic rhinosinusitis, showing no meaningful improvement compared with placebo treatment.^1,29 Adverse effects, concerns over antibiotic stewardship, and the current understanding of chronic rhinosinusitis as an inflammatory process should also discourage antibiotic use. Although long-term, low-dose antibiotics may have some benefit in patients with non-type 2 inflammation, the literature on this topic is still conflicting and no definitive recommendations can be made at this time.^1,27

Surgical treatment

Endoscopic sinus surgery is known to be an effective and safe treatment for patients with chronic rhinosinusitis for whom standard medical therapy has not been beneficial. This minimally invasive procedure is done through the nostrils with endoscopes, without external incisions. Inflamed tissue, polyps, and small pieces of bone can be delicately removed to improve the drainage and ventilation of the sinus cavities. Several studies have demonstrated the ability of endoscopic sinus surgery to improve quality of life while reducing the inflammatory burden in the sinuses.³⁰ Perhaps most importantly, surgery facilitates an improved delivery of topical medications to the paranasal sinuses, which is an essential component of long-term management and symptom control.³¹

However, endoscopic sinus surgery cannot definitively change the underlying pathophysiology of this disease, and patients may require further procedures. Revision rates are estimated to be 10%–30% depending on the length of follow-up.³² One retrospective review found the time between surgeries was 4.39 years, on average.³² Most studies suggest that around 75% of patients will report significantly improved symptoms after endoscopic sinus surgery,³³ and patients who undergo revision surgery were found to have a similar improvement in quality-of-life scores as those having primary surgery.³⁴ Risk factors for symptomatic recurrence after surgery include those with severe polyp disease and those with comorbid asthma.³²

Monoclonal antibody therapy for chronic rhinosinusitis with polyps

Several monoclonal antibody therapies, also known as biologics, can improve both symptoms and signs among patients with severe chronic rhinosinusitis with polyps. These systemic agents target the type 2 inflammatory pathway.

A 2021 Cochrane review demonstrated the efficacy of biologics in the treatment of chronic rhinosinusitis with polyps.³⁵ Therapeutic effects include reduction in nasal congestion, reduction in polyp size, improvement in smell and disease-specific quality-of-life score, and minimization of the need for oral steroids and surgical revisions.³⁵

A 2021 Canadian Consensus Statement, based on a Delphi study, guides the use of biologics in patients with chronic rhinosinusitis. ²¹ Otolaryngologists must first confirm the presence of polyps by endoscopy to be considered for a trial of therapy. Oral and nasal steroids must not have been effective, and, in most circumstances, patients should have had previous endoscopic sinus surgery, without evidence they might benefit from further surgical revision. Dupilumab, mepolizumab, and omalizumab have been approved for use in Canada. These are administered by injection and are also used in other type 2 inflammatory conditions including asthma and atopic dermatitis.

Ongoing use is required to maintain a therapeutic benefit, and optimal duration of treatment is yet to be determined. Short-term risks of systemic biologic use include arthralgias, rash, and conjunctivitis.³⁶ In a retrospective review of real-world data, fewer than 10% of patients discontinued their biologic because of adverse effects, and most of these effects presented within the first 3 months of therapy.³⁶ A systematic review and meta-analysis found that patients on biologics had an increased risk of developing a rheumatic adverse event (risk ratio 2.53, 95% CI 1.29 to 4.94), compared with those on placebo, usually managed with treatment discontinuation.³⁷ Given that biologics are relatively novel therapies, high-quality, long-term data on adverse effects are not available, and patients should be counselled accordingly. Moreover, the cost of these medications will be prohibitive for many patients. A cost–utility analysis found that treatment with dupilumab cost more than surgery by a factor of 11 per quality-adjusted-life-year.³⁸ Use of biologics should therefore be reserved for the small percentage of patients for whom other treatment options have failed.²¹

Conclusion

Chronic rhinosinusitis is a common inflammatory condition with serious effects on individual functioning and quality of life. Diagnosis is clinical and depends on subjective symptoms and objective findings on imaging and physical examination. Diagnostic biomarkers may be avilable in the future. First-line treatment involves topical steroid therapy and saline irrigation, with consideration of endoscopic sinus surgery when necessary. Patients with chronic rhinosinusitis with polyps who do not achieve symptomatic relief with standard medical and surgical therapy can now be prescribed biologics, although the long-term effects of these agents are unknown. Future studies should investigate the optimal diagnostic techniques for individual patients based on underlying pathophysiology to better direct treatment and should assess the role of new therapies (Box 2).

Box 2: Unanswered questions .

• Will biomarkers be useful to guide diagnosis and treatment, and if so, which ones?

• How can clinicians identify which treatments will most benefit a patient?

• What is the optimal duration of treatment with biologics?

• What are the long-term adverse effects of biologics in the treatment of chronic rhinosinusitis?