INTRODUCTION — Chronic rhinosinusitis (CRS) is defined as an inflammatory condition involving the paranasal sinuses and linings of the nasal passages, which persists for 12 weeks or longer [1-5]. CRS can be divided into three subtypes:
●CRS without nasal polyposis (CRS without NP)
●CRS with nasal polyposis (CRS with NP)
●Allergic fungal rhinosinusitis (AFRS)
The diagnosis requires at least two of four cardinal signs/symptoms (mucopurulent drainage, nasal obstruction, facial pain/pressure/fullness, and decreased sense of smell). In addition, objective documentation of mucosal inflammation (on imaging or direct visualization) is required. (See "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis".)
There are different strategies for treating each subtype. The management of patients with CRS with and without NP will be discussed here. AFRS is discussed in detail separately. The microbiology and antimicrobial therapy of this disorder and the clinical manifestations and diagnosis of the different types of CRS are also reviewed separately. (See "Microbiology and antibiotic management of chronic rhinosinusitis" and "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis" and "Allergic fungal rhinosinusitis".)
GOALS OF THERAPY — CRS cannot be "cured" in most patients, and therapy is intended to reduce symptoms and improve quality of life. Thus, the goals of CRS therapy include the following:
●Control of mucosal inflammation and edema
●Maintenance of adequate sinus ventilation and drainage
●Treatment of colonizing or infecting micro-organisms, if present
●Reduction in the number of acute exacerbations
In many respects, management of CRS resembles that of asthma, in which patients are treated initially to reduce symptoms as much as possible and then transitioned to maintenance therapy and followed over time for periodic adjustments in medications and treatment of acute exacerbations. Mucosal remodeling, similar to that believed to occur in severe asthma, has been increasingly studied as a cause of irreversible chronic sinus disease. It is not clear to what extent treatment can slow or prevent this process [6]. In keeping with the concept of overlapping pathogenesis involving both the upper and lower airways, medical management of CRS can lead to improvements in asthma control in patients with both disorders [7].
Smoking cessation — A cross-sectional study demonstrated that among patients with CRS (of all types) who stop smoking, each year since cessation is associated with improvements in CRS symptoms, quality of life, and CRS-related use of oral corticosteroids [8]. The authors estimated that the negative effects of smoking could be expected to resolve 10 to 20 years after cessation. Active smoking also negatively impacts outcomes following functional endoscopic sinus surgery (FESS) [9,10]. A general approach to smoking cessation and pharmacologic therapies to assist in smoking cessation are reviewed separately. (See "Overview of smoking cessation management in adults" and "Pharmacotherapy for smoking cessation in adults".)
REFERRAL — Initial management of a patient with CRS is often supervised by a generalist. However, treatment of refractory CRS and management of allergic fungal rhinosinusitis (AFRS) usually requires the input of a specialist. (See "Allergic fungal rhinosinusitis".)
●Otolaryngology specialists can obtain culture material directly from the sinuses, visualize mucosal abnormalities with nasal endoscopy, and perform surgical procedures. They can also diagnose and manage associated otologic problems. Patients with stable CRS who develop changes to suggest a complication of CRS, such as orbital cellulitis, cavernous vein thrombosis, mucocele formation, or erosion into the frontal sinus (Pott's puffy tumor) or central nervous system, should be urgently evaluated by an otolaryngologist [11-13].
●Allergy/immunology specialists can direct medical therapy, diagnose and treat associated allergy, immunodeficiency, and asthma, and perform aspirin desensitizations in patients with aspirin intolerance and nasal polyps (ie, aspirin-exacerbated respiratory disease).
OVERVIEW OF MEDICAL THERAPIES — Multiple therapies are used in the management of CRS with or without nasal polyposis (NP), including saline washes and sprays, intranasal and systemic corticosteroids, antibiotics, antileukotriene agents, and biologics in some cases. The approach described in this topic review is consistent with recent international guidelines [14]. (See "Society guideline links: Chronic rhinosinusitis".)
At present, there is significant variability in the management of CRS. Most therapies for CRS have not been evaluated in randomized trials, although, in 2006, a consensus group identified areas in which trials were needed, as a first step in strengthening the evidence base of the field [15]. In 2016, several systematic reviews evaluated the main therapies discussed in this review and concluded that the evidence supporting most of them was of low quality, further emphasizing the need for more rigorous research in these disorders [16-22]. An overview of each therapy is provided in this section. The subsequent sections describe the specific ways in which these therapies are combined to manage different types of CRS. (See 'CRS without nasal polyposis' below and 'CRS with nasal polyposis' below.)
Intranasal saline — Irrigating the nasal cavities with saline reduces postnasal drainage, removes secretions, and rinses away allergens and irritants. Saline irrigations can be used immediately prior to administration of other intranasal medications, so that the mucosa is freshly cleansed when the medications are introduced. We encourage patients with CRS to perform nasal irrigation in preference to using saline nasal sprays, based on our clinical impression and limited data that irrigation is the more effective technique [17,23,24]. Systematic reviews of studies employing various forms of saline sprays and irrigation (performed one to four times daily) found that nasal saline is an effective adjunctive treatment for CRS although is less effective as monotherapy than intranasal corticosteroids [17,25].
A variety of over-the-counter devices including squeeze bottles, syringes, and pots are available. Patients can make their own saline solutions (table 1) or buy commercially prepared products. Nasal lavage (with at least 200 mL warmed saline per side) can be performed as needed only, daily, or multiple times daily, depending on the severity of symptoms. Care should be taken to ensure that the irrigation bottles do not become contaminated. This can be accomplished by periodically microwaving or replacing the bottles and using water that is either distilled or boiled and cooled [26].
Intranasal corticosteroids — Intranasal corticosteroids, which can be administered either as nasal sprays or as solutions for instillation, are the cornerstone of maintenance treatment for many types of rhinitis and have been shown in randomized trials to be helpful as a maintenance therapy for CRS, although a 2016 systematic review rated the overall quality of evidence in CRS specifically as very low [1,18,27-32]. These agents remain underutilized in CRS [33]. For patients with persistent nasal congestion or blockage despite consistent use of corticosteroid nasal sprays, we suggest changing to nasal corticosteroid instillations.
Nasal sprays — Nasal corticosteroid sprays include budesonide, fluticasone propionate, mometasone furoate, triamcinolone acetonide, ciclesonide, beclomethasone dipropionate, and fluticasone furoate (table 2). Note that the dose of mometasone shown to be effective for NP (two sprays per nostril twice daily) is double what is typically used for treatment of allergic rhinitis. The efficacy of intranasal corticosteroid sprays in CRS is supported by randomized trials and is reviewed in more detail subsequently [28,31]. There is no compelling evidence that any one agent is more effective than another or that sprays are more or less effective than aerosol products [19]. (See 'Maintenance treatment' below and 'Intranasal corticosteroids' below.)
To optimize effectiveness and patient compliance with nasal sprays, we suggest the following:
●Preparations with once-daily dosing are convenient and can help optimize compliance. These include triamcinolone acetonide, budesonide, fluticasone propionate, mometasone furoate, or fluticasone furoate. Most intranasal corticosteroids are used at a dose of one to two sprays in each nostril once or twice per day.
●If obvious mucus or crusting is present, patients can clean the nose with saline nasal sprays or irrigation before the nasal corticosteroid is applied.
●Patients should be instructed to keep their head pointed slightly downward during spraying and avoid tilting the head back, as this can cause drainage of the medicine from the nose to the throat. In addition, they should avoid pointing the tip of the bottle at the septum to minimize septum irritation and bleeding.
Exhalation-delivered fluticasone — An exhalation-driven delivery system for fluticasone (EDS-FLU; brand name Xhance) is available for use in CRS with NP at a dose of one to two sprays per nostril twice daily and has been shown to be beneficial in both CRS with and without NP [34-37]. This delivery system is proposed to result in more thorough distribution of medication within the nasal cavity and sinuses without increased adverse effects compared with conventional sprays, although head-to-head studies of clinical outcomes have not been published [38]. It might be particularly helpful for patients who experience Eustachian tube congestion with nasal irrigation. It is US Food and Drug Administration (FDA) approved for treatment of NP. Studies are ongoing for use in CRS without nasal polyps.
Instillations/drops — Instillation of corticosteroid solutions into the nose can reach the middle meatus (where polyps often form) more reliably than nasal sprays [39-41]. In the United Kingdom and some areas of Europe, solutions of either betamethasone or fluticasone propionate are commercially available as nasal drops [42]. In the United States, mometasone aqueous solution is not available by prescription but can be used off-label for this purpose. Similarly, budesonide aqueous solution is commercially available for nebulization and can be used for sinus irrigation. The authors have used both solutions.
In a randomized trial of adults treated after sinus surgery, a dilute corticosteroid sinus rinse was more effective in controlling the symptoms and signs of CRS than the combination of nasal saline irrigation plus nasal corticosteroid spray [43]. Patients were randomized one day post-sinus surgery to receive either a corticosteroid nasal irrigation with a placebo nasal spray or a placebo nasal irrigation and corticosteroid nasal spray. All patients performed both a nasal irrigation followed by a nasal spray daily. Groups were defined by corticosteroid (2 mg mometasone) delivered by either spray or irrigation. Over 12 months, CRS patients in both groups improved significantly, but the corticosteroid nasal irrigation group had greater improvement in nasal blockage, Lund-Mackay sinus computed tomography score, and greater improvement on total visual analog scale scores.
●In some patients, use of a dilute corticosteroid sinus rinse provided inadequate improvement in the signs and symptoms of CRS. In such cases, use of a "concentrated budesonide rinse" may be beneficial. This is usually prepared by mixing one 0.5 mg budesonide respule (in 2 mL volume) with 1 teaspoon (5 mL) of saline solution in a small container (such as a cup) to provide a mixture containing 0.5 mg budesonide in 7 mL volume (71.4 mcg/mL). Lesser concentrations can be made, such as 250 mcg in 7 mL volume, depending on what is deemed most appropriate for the patient. To instill the concentrated budesonide rinse into the nostril, a syringe with a specialized nasal tip is very helpful. This syringe is used to first draw up the solution from a cup, and then it is used to instill the solution into the nostril.
●In rare cases, a 0.5 mg budesonide respule (in 2 mL volume) can be used undiluted as a "nasal drop" (250 mcg/mL). This "fully concentrated budesonide rinse" is typically only used for short periods of time to avoid risk of side effects from systemic absorption of the budesonide.
A technique for distributing the medication to different areas of the paranasal sinuses has been developed (figure 1) [44].
Efficacy and safety — Studies have evaluated the efficacy of corticosteroid nasal drops and nasal instillations [40-42,45-48]:
●The efficacy of fluticasone propionate nasal drops was demonstrated in 54 patients with severe CRS with and without NP who had refractory disease despite treatment with intranasal corticosteroid sprays and were awaiting functional endoscopic sinus surgery (FESS) [42]. Subjects received therapy with either fluticasone propionate (400 mcg per 0.4 mL, divided between the nostrils, once daily) or placebo for three months. Those treated with fluticasone experienced significantly more improvement in symptoms, polyp volume, and nasal airflow. In addition, FESS was no longer required in 13 of 27 patients treated with fluticasone, compared with 6 of 27 in the placebo group.
●The budesonide solution available in the United States has not been evaluated in controlled trials, although we have found it to be very helpful for patients who are unable to control CRS symptoms with standard corticosteroid nasal sprays.
The long-term safety of corticosteroid nasal instillations has not been established, although it has been demonstrated that very little of the instilled solution is retained [45]. Still, we periodically evaluate patients using this therapy for possible systemic effects of budesonide, particularly an increase in intraocular pressure.
●One study of 60 patients treated with "dilute" budesonide irrigation (0.5 mg diluted in 120 mL saline per nostril twice daily for one year) found no clinically significant changes in intraocular pressure or unstimulated plasma adrenocorticotropic hormone (ACTH) levels over the study duration [46]. However, this study was unable to demonstrate any clinical benefit from the "dilute" budesonide solution relative to saline solution alone.
●Another analysis of budesonide nasal irrigations showed a possible effect of cortisol stimulation test results [47]. This effect was most notable when the patients were receiving concomitant corticosteroids as nasal sprays and inhalers for asthma.
●A smaller study involving nine patients treated with a "concentrated" budesonide solution (0.25 mg per nostril diluted in 5 mL saline once per nostril daily for 30 days administered with head tilting maneuvers) demonstrated a clinically significant improvement in sinonasal outcome measures and found no significant change in adrenal response to cosyntropin stimulation [48].
Nasal nebulized solutions — Solutions of corticosteroid can also be administered by nasal nebulization, and the authors have found budesonide 0.5 mg per nostril daily to be an effective treatment in patients who cannot perform nasal instillation due to difficulties with the instillation technique [49].
Efficacy and safety were evaluated in a randomized trial of 60 patients with eosinophilic CRS with NP, treated with either a budesonide solution (containing 0.5 mg/nostril) or placebo twice daily for 14 days [49]. The active treatment resulted in significant improvement in the primary outcomes of reduction in polyp size and subjective symptoms. There was no evidence of adrenal suppression based on morning plasma cortisol over the two weeks of the study, although the short duration of active treatment could have minimized such an effect. It is noteworthy that this study used a dose of budesonide (1 mg/nostril/day) and concentration (500 mcg/mL versus 71.4 mcg/mL) higher than typically employed by the authors for nasal instillation. However, nasal nebulization at this high dose was not proposed for long-term use, and the dose and concentration of budesonide could certainly be reduced for chronic use.
Oral corticosteroids — Oral corticosteroids, such as prednisone, may be administered to patients with CRS for the following purposes:
●Relieving severe and refractory mucosal edema in CRS without NP
●Reducing the size of polyps in CRS with NP
●Minimizing mucosal inflammation in allergic fungal rhinosinusitis (AFRS)
Doses for specific situations are discussed below:
●For treatment of CRS without NP (see 'Short-term antibiotics and oral corticosteroids' below)
●For treatment of CRS with NP (see 'Oral corticosteroids' below)
Antibiotics — Expert consensus reports from otolaryngology and allergy/immunology groups have concluded that there is limited evidence for antibiotics in the treatment of CRS, except for management of acute exacerbations [2,50,51]. Evidence for the efficacy of antimicrobials as monotherapy is limited and of low quality [20]. The goal of managing CRS has now shifted to controlling the inflammation that predisposes patients to obstruction, thus minimizing the incidence of infections.
Despite this, all forms of CRS are associated with poor sinus drainage and secondary bacterial infections from time to time. Some patients require systemic antibiotics to clear infections at the outset of therapy and intermittently thereafter to treat acute exacerbations of CRS. The role of systemic antimicrobial agents beyond these indications remains an area of investigation.
The use of both systemic and topical antimicrobials in CRS, including choice of agent and dose, is discussed in detail separately. (See 'Treating exacerbations of CRS' below and "Microbiology and antibiotic management of chronic rhinosinusitis", section on 'Antimicrobial therapy'.)
Antileukotriene agents — Cysteinyl leukotrienes are inflammatory mediators that cause mucus secretion, increased vascular permeability, and mucosal edema in the upper and lower airways. Antileukotriene agents include the leukotriene D4 (LTD4) receptor blockers montelukast or zafirlukast and the 5-lipoxygenase inhibitor zileuton. Antileukotriene agents may be used as an adjunct therapy to intranasal corticosteroids in patients with CRS with concomitant allergic rhinitis or in patients with NP and may have additional advantages in patients with aspirin-exacerbated respiratory disease. (See 'Antileukotrienes' below.)
Of note, montelukast carries a boxed warning about adverse effects on mood that must be discussed with patients. Studies of adverse mood effects are discussed in more detail separately. (See "Antileukotriene agents in the management of asthma", section on 'Adverse effects'.)
Unproven therapies — Unproven therapies include oral or topical antifungal medications and probiotics.
●Surfactants to disrupt biofilms – The addition of surfactants, such as baby shampoo, to saline irrigations has been proposed to prevent the formation of bacterial biofilms on the sinus mucosa and to increase mucociliary clearance rates [52,53]. Possible adverse effects include discomfort and decreased sense of smell [54]. An uncontrolled study examined the effects of a 1% solution of baby shampoo in physiologic saline, which was used to irrigate the sinuses twice daily for four weeks in 18 postsurgical patients [52]. Sixty percent of patients reported subjective thinning of mucus and less postnasal drainage. However, no objective measures of mucosal disease or biofilm were measured. Based on these preliminary findings and in vitro studies [55], surfactants warrant further study in the management of CRS.
●Oral or intranasal antifungals – Fungal colonization has been implicated in the pathophysiology of CRS, most clearly in AFRS (see "Allergic fungal rhinosinusitis", section on 'Antifungal agents'). Accordingly, antifungal medications in both systemic and topical forms have been studied in clinical trials of CRS, with mostly unpromising results [56-61]. A systematic review and a meta-analysis, which pooled studies of antifungal therapy for all types of CRS, found no statistically significant benefit of intranasal or systemic antifungals over placebo and higher rates of adverse events in the antifungal groups [62,63].
●Probiotics – Oral probiotic therapy was evaluated in a randomized trial of 77 patients with different types of CRS, treated with either Lactobacillus rhamnosus R0011 strain (500 million active cells per tablet) or placebo for four weeks [61]. There were no differences between the two groups in sinonasal quality-of-life scores.
●Complementary and alternative therapies – Many patients try alternative and complementary therapies, either instead of or in combination with conventional therapies [64,65]. Most of these therapies, including use of herbal tea, botanicals and other herbal medicines, vitamins, homeopathy, massage, reflexology, yoga, diet modifications, chiropractics, and acupuncture, have not been studied in controlled clinical trials but rather discussed in open treatment trials [64-69]. Given the limited reports and lack of rigorously controlled studies, it is not possible to ascribe better results to any one type of treatment.
CRS WITHOUT NASAL POLYPOSIS — CRS without nasal polyposis (NP) is the most common form of CRS, accounting for approximately two-thirds of cases. Factors contributing to chronic sinus inflammation may include allergic and nonallergic rhinitis, structural abnormalities, and/or immunodeficiency. Patients with this condition do not have NP, by definition. (See "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis".)
Initial therapy — "Initial treatment" may be defined as the treatment given to a patient upon establishing the diagnosis of CRS. In many cases, the patient has already received treatment in the weeks preceding the diagnosis, and this should be considered when deciding how long to try initial measures before moving on to additional interventions.
Intranasal corticosteroids and saline lavage — The focus of initial treatment is on saline nasal lavage and topical corticosteroids. These interventions should be tried for a period of one to three months.
We initially treat all patients with the following:
●Intranasal saline irrigations or saline nasal spray [17,25]. (See 'Intranasal saline' above.)
●Intranasal corticosteroid spray or nasal instillations, which were shown to be beneficial in the treatment of CRS without NP in a systematic review [18]. (See 'Intranasal corticosteroids' above.)
If this results in satisfactory control of symptoms, these therapies can be continued as maintenance. (See 'Maintenance treatment' below.)
For patients who fail to achieve adequate symptom control following one to three months of saline nasal lavage and topical corticosteroids, a trial of use of a dilute corticosteroid sinus rinse may be beneficial. (See 'Instillations/drops' above.)
Persistent symptoms — For symptoms that persist despite corticosteroid instillations or drops, there are two other medical approaches that can be tried, both of which are supported only by low-quality evidence, or the patient can be referred for sinus surgery. (See 'Endoscopic sinus surgery' below.)
Choosing among medical therapies — If nasal endoscopy is possible, material can be obtained from the interior of the sinus cavities and cultured to determine if infection is present and identify organisms and antibiotic sensitivities. If this information is not available, an expert panel of allergists and otolaryngologists advocated the combination of systemic antibiotics plus a brief course of oral corticosteroids as a treatment option in patients with CRS without NP [51]. The authors and editors of this topic favor this approach in most cases. Another option is the prolonged administration of low-dose macrolide antibiotics, which has mainly been studied in CRS without NP and is included in European and British guidelines and has also been examined in some systematic reviews [1,20,27,32,70]. Macrolide antibiotics, which have both anti-inflammatory and antimicrobial properties, are combined with various topical therapies [71-74]. However, the authors and editors of this topic believe that the efficacy of macrolides has not been adequately demonstrated.
Short-term antibiotics and oral corticosteroids — A course of oral antibiotics combined with oral corticosteroids can be given for patients with refractory symptoms:
●The duration of antibiotics usually ranges from two to four weeks. (See 'Antibiotic selection' below.)
●Oral corticosteroids are given for 10 to 15 days, as a single morning dose or divided twice daily. We prefer prednisone, 40 mg daily for five days, followed by 20 mg daily for five days (adult dosing).
Although this approach is common in clinical practice and often results in at least short-term relief in the experience of the authors and editors of this topic, there is only low-level published evidence to support it, including a retrospective chart review in adults [75] and a small randomized trial in children [76]. Of note, it may be important that CRS in children is often associated with adenoiditis, which may account for greater responsiveness to antibiotics [77,78]. Thus, the evidence in support of this common practice approach is largely limited to clinical experience.
In the small pediatric trial, the combination of antibiotics and oral steroids was evaluated in 48 children (ages 6 to 17 years) with CRS without NP, who had previously failed at least three 10- to 14-day courses of broad-spectrum antibiotics [76]. Subjects were treated with 30 days of amoxicillin-clavulanate (at weight-appropriate doses), combined with either placebo or a 15-day course of methylprednisolone (1 mg/kg daily for the first 10 days, then tapered over five days). Adverse events were minimal in both groups. Children treated with antibiotics plus corticosteroids had significantly greater reductions in total symptom scores and in computed tomography (CT) scores, compared with those given antibiotics plus placebo. Complete clinical recovery occurred in 17 and 7 patients in the combined treatment and antibiotic-only groups, respectively. Relapse rates over the ensuing six months were lower in the combined treatment group (25 versus 43 percent), although the difference was not significant.
Antibiotic selection — Whenever possible, the choice of antibiotic treatment should be guided by cultures of purulent mucus that is visualized and sampled endoscopically from the middle meatus or another accessible sinus ostium [79-81]. Surveillance swabs and nasal swabs are not helpful. Choice of antimicrobial agent is made empirically if endoscopy is not feasible. Recommendations for empiric antibiotics in CRS are reviewed separately. (See "Microbiology and antibiotic management of chronic rhinosinusitis", section on 'Empiric regimen selection' and "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis", section on 'Sinus cultures'.)
Empiric antibiotic treatment is not recommended in the following clinical settings:
●If the patient has recently failed antibiotic treatment with a similar regimen
●If the patient has a history of infection with gram-negative or methicillin-resistant Staphylococcus or another highly drug-resistant bacteria
●If the patient is highly immunosuppressed and therefore at risk for invasive fungal rhinosinusitis
Patients with these characteristics should undergo nasal endoscopy to obtain reliable material for culture.
Macrolides — A 2017 systematic review included studies of patients with CRS both with and without NP, as well as patients both pre- and post-surgery [70]. It concluded that the quality of the evidence for use of macrolides in CRS is low in general but looked most promising for patients with NP who had already undergone surgery. Subsequently, the MACRO trial, a multicenter randomized clinical trial designed to compare long-term macrolide therapy to endoscopic sinus surgery in patients who failed initial therapy, has been initiated in the United Kingdom [82]. Results are pending.
Earlier studies included the following:
●In a randomized trial of 64 patients with CRS without NP, subjects were treated with roxithromycin (150 mg daily; not available in the United States) or placebo for three months and demonstrated some short-term benefit [71]. Outcome measures included the 20-item Sinonasal Outcome Test (SNOT-20), measurements of peak nasal inspiratory flow, saccharine transit time, olfactory function, nasal endoscopic scoring, and nasal lavage assays for inflammatory markers. In the group receiving macrolides, significant improvements were seen in SNOT-20 score, nasal endoscopy, saccharine transit time, and some inflammatory markers but not in olfactory function, peak nasal inspiratory flow, or other inflammatory markers. Better responses were seen in the subset of patients with a normal serum immunoglobulin (Ig)E level. However, benefit was not sustained 12 weeks after completion of therapy.
●In another randomized trial with negative results, 60 patients with CRS with or without NP who had not responded to previous medical or surgical interventions were randomized to receive azithromycin (500 mg daily for three days, then 500 mg weekly for 11 weeks) or placebo [83]. Outcomes were symptoms scores (SNOT-22), quality-of-life assessments, rigid nasal endoscopy, peak nasal inspiratory flow, and endoscopically guided middle meatus cultures. No significant differences were found between groups at the end of treatment. It is possible that inclusion of patients with elevated IgE levels or CRS with NP may have contributed to the negative results of this study.
●In a case-control study of 28 consecutive patients with CRS who underwent endoscopic sinus surgery after failing topical corticosteroid therapy, response to subsequent treatment with three months of low-dose clarithromycin was evaluated [84]. Patients were defined as a macrolide responder if endoscopy was nearly normal after a three-month period of clarithromycin treatment. There were 19 responders and 9 nonresponders. Responsiveness to macrolides was associated with a lack of tissue eosinophilia (fewer than 10 eosinophils per high-power field) and lower serum eosinophilia. Neutrophil expression was similar in tissue and serum.
Other antibiotics — In a small, open-label study of 16 adults with CRS without NP refractory to previous antibiotic treatment, subjects received either clindamycin (150 mg three times daily; 13 patients), amoxicillin-clavulanate (two patients), or doxycycline (one patient) for six weeks and underwent sinus CT scanning at baseline and after three and six weeks of treatment [85]. Improvement in the Lund-Mackay (LM) sinus CT score was noted comparing baseline (8.9) with week 3 (4.4) and week 6 (4.1). However, in six patients (38 percent), radiographic improvement only occurred between weeks 3 and 6. When just these six patients were considered, the average LM score at baseline, three weeks, and six weeks was 10.5, 5.7, and 2.8. Only one of these six patients was recommended for sinus surgery after six weeks of treatment. This small study suggests that some patients with CRS without NP may benefit from prolonged antibiotic treatment.
Endoscopic sinus surgery — In patients in whom medical treatment appears to help but does not result in sufficient improvement in symptoms or resolution of CT findings, the next logical step after failure of medical treatment is sinus surgery. (See 'Indications for sinus surgery' below.)
Treatment failure — There are several potential reasons for failure of medical therapy, including persistent sinus ostial obstruction, odontogenic sinusitis, problems with mucociliary clearance, incompletely treated sinus infection, underlying immunodeficiency, or "mucous recirculation syndrome."
●Odontogenic maxillary sinusitis – Periapical or periodontal infection is one cause of persistent and refractory CRS symptoms, usually affecting the maxillary sinuses unilaterally [86]. Patients may have a history of dental infection, oroantral fistula or other communication, tooth extraction, or dental implants, sometimes occurring several years before, as there can be a multi-year latency between the inciting event and presentation with CRS.
●Immunodeficiency – Immunodeficiency disorders are more commonly identified in patients with CRS without NP compared with those with NP. Typically, patients have humoral (ie, antibody) defects. Clues to the presence of immunodeficiency include a history of pneumonia, recurrent otitis media, or a history of recurrent acute sinus infections that resolve with antibiotic treatment. One study found a 12 percent prevalence of humoral immunodeficiency among patients with CRS without NP [87]. Immunodeficient individuals may continue to have recurrent infections despite appropriate medical management, and the addition of prophylactic antibiotics and/or immune globulin therapy may be necessary. Referral to an immunology expert (allergist or infectious diseases specialist) is appropriate for patients with uncontrolled CRS without NP despite therapy, particularly if there is a history of one or more episodes of pneumonia. Surgery is typically reserved for refractory cases where immune globulin therapy fails. In these cases, surgery can help assist in more effective sinus hygiene, reduce obstruction, and improve access for topical therapies. (See "Primary immunodeficiency: Overview of management".)
Measurement of serum levels of IgG, IgA, and IgM is an initial step in evaluation of the humoral immune system. If IgG is low, further evaluation is indicated. The finding of low IgG plus either low IgM or low IgA indicates a more significant antibody defect. The isolated finding of low IgA requires further evaluation to determine significance. If IgG is normal, the next step is assessment of the patient's response to pneumococcal polysaccharide vaccine, which provides a measure of antibody function. One of the milder humoral defects is defective function of IgG, with normal levels (ie, specific antibody deficiency). The evaluation of antibody function is reviewed in detail separately. (See "Assessing antibody function as part of an immunologic evaluation".)
●Mucous recirculation syndrome – Mucus recirculation syndrome is a condition in which mucus draining through a sinus ostium re-enters the sinus through a different ostium, rather than draining down the nasopharynx [88-94]. It is another potential explanation for persistence of rhinosinusitis symptoms despite medical and/or surgical management. The vast majority of cases involve the maxillary sinus [88]. In most cases, the problematic ostium was surgically created, although mucus recirculation may involve an accessory sinus ostia (which can be congenital or form spontaneously). Patients suspected of having this disorder should be evaluated by an otolaryngology specialist [90]. One group has proposed diagnostic criteria based on a series of 12 patients plus 44 collected from the literature: CRS not responding to oral or topical therapies, visualization of mucous recirculation between two or more ostia by rhinoscopy, and resolution of symptoms with surgical treatment [95]. Irrigation may sometimes resolve this problem. However, surgery to remove the tissue separating the two ostia and create a single ostium has been reported to be curative [88,95].
Maintenance treatment — Patients with CRS without NP who have achieved adequate symptom control with the interventions discussed above should be transitioned to maintenance treatment. The presence or absence of underlying allergic rhinitis or immunodeficiency has an impact on maintenance treatment recommendations, as there are several effective interventions for those conditions.
Intranasal corticosteroids and saline — We usually continue a maintenance regimen of a corticosteroid nasal spray and saline irrigation in all patients [27,31]. For patients who have persistent symptoms despite consistent use of corticosteroid nasal sprays, we advise them to change to instillations, as described previously. (See 'Instillations/drops' above.)
Treatment of underlying allergic rhinitis — In patients with CRS and concomitant allergic rhinitis, other therapies, including remediation of allergen exposure, allergen immunotherapy, and oral and topical antihistamines, may be helpful.
●Allergen remediation measures in the home or workplace and specific allergen immunotherapy to reduce sensitivity to specific allergens can help reduce mucosal edema over time. These interventions are discussed separately. (See "Allergen avoidance in the treatment of asthma and allergic rhinitis" and "Subcutaneous immunotherapy (SCIT) for allergic rhinoconjunctivitis and asthma: Indications and efficacy".)
●There are no randomized, controlled trials of allergen immunotherapy for CRS. An observational case series found that allergic CRS patients receiving immunotherapy following sinus surgery had less severe symptoms and better long-term prognosis than their nonallergic counterparts. However, the nonallergic patients also had more extensive initial sinus surgery, suggesting that their baseline disease was more severe [96]. A systematic review concluded that there is weak evidence to support the use of immunotherapy as an adjunctive treatment in CRS patients, particularly in the postoperative period [97].
●Antihistamines may be helpful in patients with CRS and concomitant allergic rhinitis, although their relative contribution has not been studied [98]. Antihistamines (oral and topical) are reviewed separately. Newer, minimally sedating oral antihistamines (such as cetirizine, fexofenadine, or loratadine) are preferred over older agents. (See "Pharmacotherapy of allergic rhinitis", section on 'Oral antihistamines' and "Pharmacotherapy of allergic rhinitis", section on 'Antihistamine nasal sprays'.)
Adjunctive therapies — Antileukotriene agents, such as montelukast and zafirlukast, may be useful in patients with allergic rhinitis and refractory nasal congestion and postnasal drainage [99]. Chronic use of oral decongestants, such as pseudoephedrine, is generally avoided for maintenance treatment.
CRS WITH NASAL POLYPOSIS — The typical patient with CRS with nasal polyposis (NP) reports nasal congestion, vague facial or sinus fullness, postnasal drainage, and anosmia/hyposmia and may lack features of acute or chronic infection. It is our approach to begin with medical therapies rather than surgery. A systematic review attempted to compare medical and surgical treatments of CRS with NP, but the quality of the evidence was sufficiently low that no firm conclusions could be drawn [100]. (See "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis".)
Initial therapy — "Initial treatment" may be defined as the treatment given to a patient upon establishing the diagnosis of CRS with NP. In many cases, the patient has already received treatment in the weeks preceding the diagnosis, and this should be considered when deciding how long to try initial measures before moving on to additional interventions.
In patients who do not have significant nasal blockage by polyps, intranasal saline (sprays or irrigations) and intranasal corticosteroids (sprays or instillations) may be administered for a period of one to three months. (See 'Intranasal saline' above and 'Intranasal corticosteroids' above.)
Oral corticosteroids — A brief course of oral corticosteroids may be administered if the patient is very uncomfortable with nasal blockage or impaired sense of smell or cannot use topical therapies because of obstructing polyp tissue. This is sometimes referred to as a "medical polypectomy," and, in most cases, it results in significant reduction in polyp tissue and clinical improvement, although the improvement is usually temporary. Still, reducing polyp size is an important first step for patients who are sufficiently obstructed that topical therapies cannot penetrate into the nasal cavities.
A 10- to 15-day course of oral corticosteroids is usually adequate. Doses are sometimes reduced for older adults or those with known side effects in the past:
●One suggested regimen for adults is oral prednisone 40 mg for 5 days, followed by 20 mg daily for 5 days (10 days of treatment).
●One author (DLH) prefers twice-daily dosing and a 15-day regimen (eg, 20 mg twice daily for 5 days, followed by 10 mg twice daily for 5 days, then 10 mg once daily for 5 days).
●Another regimen is 60 mg daily for 5 days, followed by 40 mg daily for 5 days, then 20 mg daily for 5 days (ie, total of 15 days of treatment).
Methylprednisolone can be used instead of prednisone (8 mg of methylprednisolone is equivalent to 10 mg of prednisone).
Systematic reviews and randomized trials have concluded that oral corticosteroids provide short-term (ie, several weeks) benefit in NP, although the majority of studies were either small or had significant limitations, and the quality of the evidence is generally low [21,22,28,32,101-104]. Among patients with CRS with NP, the short-term response to oral corticosteroids has been estimated at 60 to 80 percent [105]. In a study of approximately 250 patients with NP, a predominance of eosinophils in the pretreatment polyp tissue predicted a better response to corticosteroids, compared with a predominance of neutrophils or a mixed histology, although histology is generally not known prior to treatment [106]. However, higher peripheral blood eosinophil counts and concomitant asthma may be surrogate markers for tissue eosinophilia in patients with CRS with NP [107,108].
It is critical to avoid repeated administration of oral corticosteroids because of the potential long-term adverse health effects for an intervention that provides only temporary relief. In a study that illustrated the transient nature of the improvement, 60 adults with moderate-to-severe NP were randomly assigned to oral prednisolone (25 mg daily) or placebo for two weeks [109]. One-half of the subjects in each group had aspirin-exacerbated respiratory disease (AERD). Both groups subsequently received fluticasone nasal drops (400 mcg twice daily) for nine weeks, followed by fluticasone propionate nasal spray (200 mcg twice daily) for 18 weeks. Polyp size, olfaction, and several measures of corticosteroid toxicity were assessed after each phase of treatment. The group treated with oral corticosteroids experienced a significant reduction in polyp size and improvement in olfaction after the two-week oral tablet phase, which was preserved through the nasal drops phase but lost by the end of the nasal spray phase (approximately 28 weeks after completion of oral therapy). Evidence of adrenal suppression had resolved by the end of the nasal drops phase.
Biologic agents offer a safer alternative to repeated courses of oral corticosteroids and may be especially helpful for patients with concomitant asthma. However, the availability and cost of biologic therapies must also be considered. (See 'Biologic agents' below.)
Antibiotics for concomitant infection — Antibiotics for patients with CRS with NP are not recommended unless an infection is suspected. Clues to the presence of infection in such a patient include the presence of facial pain, the presence of an air fluid level on sinus CT scan, or the presence of purulent mucus in the middle meatus. When possible, an endoscopically obtained culture should be obtained to inform the antibiotic selection. (See 'Antibiotic selection' above.)
There has been interest specifically in treatment directed against Staphylococcus aureus in CRS with NP patients, but the available evidence does not support this approach. Mucosal colonization with S. aureus has been found in 64 percent of patients with CRS and NP, compared with roughly 30 percent in healthy individuals or patients with other forms of CRS. In addition, immunoglobulin (Ig)E antibodies directed against staphylococcal superantigens have been found in the tissues of a high percentage of colonized polyposis patients. However, studies were unable to show that use of antistaphylococcal antibiotic regimens (either a fluoroquinolone, amoxicillin-clavulanate, or co-trimoxazole) resulted in any clinically significant benefits in unselected patients with CRS with NP, and doxycycline caused only a slight reduction in NP size [103,110].
Options for refractory disease — If intranasal and oral corticosteroids fail to reduce polyp tissue sufficiently and the patient has persistent blockage or anosmia, we consider either sinus surgery or therapy with a biologic agent. Patient preferences and availability should be considered in the choice of approach, as comparative studies have not been performed.
The presence of eosinophilic granulomatosis with polyangiitis should be considered in patients with aggressive nasal polyposis if the peripheral blood shows eosinophilia in excess of 1500 cells/microL or if the patient has other worrisome symptoms, such as mononeuritis multiplex. (See "Clinical features and diagnosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)", section on 'Evaluation'.)
Endoscopic sinus surgery — Sinus surgery can provide rapid relief of symptoms. If not recently given, preoperative corticosteroids can reduce polyp burden, allow for better visualization of normal anatomy, and potentially reduce intraoperative bleeding [111]. Data comparing different surgical approaches for this disorder are limited [112]. It is important that surgery be followed by intranasal corticosteroids and other appropriate medical therapies (eg, aspirin desensitization in patients with AERD) to prevent the subsequent regrowth of polyps. (See 'Intranasal corticosteroids' below and 'Aspirin desensitization and therapy' below.)
Relapse is not uncommon, even with post-surgical medical therapy. Studies have estimated that approximately 40 percent of patients have regrowth of polyps within 18 months after surgery [113]. Longer-term follow-up was evaluated in a small prospective cohort study, in which 47 patients with CRS with NP underwent primary or revision endoscopic sinus surgery and were monitored for total nasal endoscopic polyp score and clinical symptoms [114]. At 12 years after surgery, 81 percent were still available for evaluation and reported improved polyps scores and symptom scores relative to their pre-surgery baseline. However, 80 percent developed recurrent polyposis during the follow-up period and 37 percent underwent revision surgery.
Biologic agents — Biologic therapies are another option for patients with recalcitrant disease [115]. Biologic agents that have been studied for the treatment of CRS with NP include dupilumab, mepolizumab, and omalizumab. In the United States, all three agents are approved for the treatment of CRS with NP. There are no biomarkers that help to select patients for therapy or predict benefit [116].
In a systematic review of biologics for CRS, 10 randomized trials of dupilumab, omalizumab, or mepolizumab were identified, which included a total of 1262 adults, nearly all of whom had CRS with NP [117]. The outcomes of interest were disease-specific health-related quality of life (HRQL) as measured by the 22-item Sinonasal Outcome Test (SNOT-22) score, disease severity, and serious adverse events (SAEs). HRQL improved 19.6, 15.6, and 13.3 points with dupilumab, omalizumab, and mepolizumab, respectively, with a minimal clinically important difference of 8.9 points. Dupilumab probably also reduced disease severity and may have reduced SAEs. The impact of omalizumab and mepolizumab on disease severity and SAEs was very uncertain.
In a review of available data from phase II and phase III trials of dupilumab, mepolizumab, and omalizumab for nasal polyps, the authors concluded that differences in study design limited the ability to directly compare the efficacy of these three biologics, but dupilumab demonstrated clearly significant effect sizes on both patient reported (nasal congestion, smell loss, and SNOT-22 scores) and objective measures (CT scan Lund-Mackay score, standardized smell test, and nasal polyp scores) [118]. Furthermore, dupilumab treatment had the most significant effect size on improvement in sense of smell.
●Dupilumab – Dupilumab (a monoclonal antibody to the alpha subunit of the interleukin [IL]-4 receptor) inhibits signaling of IL-4 and IL-13, cytokines important in the generation of inflammation mediated by T helper type 2 cells, and inhibits eosinophil migration into tissues. It was approved by the US Food and Drug Administration (FDA) for treatment of CRS with NP in 2019, at a dose of 300 mg given subcutaneously every other week. In two multicenter randomized trials including 724 patients with CRS with NP, dupilumab therapy for 24 or 52 weeks resulted in significant improvements in the primary endpoints of nasal polyp scores, nasal congestion/obstruction, and sinus Lund-MacKay CT scores compared with placebo and was well tolerated [119]. Dupilumab-treated patients also experienced improvements in olfaction and overall CRS symptoms as measured by SNOT-22. Patients with concomitant asthma or AERD also improved. Patients in the 52-week study were still improving at the end of the treatment period, and symptoms worsened again with time off therapy, so prolonged treatment will likely be required.
Although it is too early to know which nasal polyp patients to select for dupilumab treatment, a reasonable approximation is to consider dupilumab treatment for patients whose NP has failed to be controlled by a course of systemic corticosteroids and/or sinus surgery followed by topical corticosteroid treatment as outlined previously. Adverse effects of dupilumab in patients with severe atopic dermatitis include conjunctivitis that can be severe enough to require discontinuation [120]. However, in the large study above, conjunctivitis developed in only seven patients and was not severe.
●Omalizumab – Omalizumab (an anti-IgE monoclonal antibody) prevents the binding of IgE to inflammatory cells and downregulates Th2 inflammation. Although nasal polyp patients may be either "allergic" or "nonallergic" based on conventional skin testing and/or blood IgE tests, nasal polyp tissue typically contains a high level of locally produced IgE. This represents a form of "local allergy" believed to be driven by local factors, such as staphylococcal superantigens [121]. Omalizumab was shown to be effective for CRS with NP in two phase III randomized trials (POLYP 1 and POLYP 2) [122]. Considered together, 265 adults with severe symptoms inadequately responsive to intranasal corticosteroids were randomized to either omalizumab or placebo plus intranasal mometasone for 24 weeks. Primary endpoints were changes from baseline in nasal polyp score (NPS) and nasal congestion score (NCS). Omalizumab therapy resulted in improvements in both endpoints as well as improvements in measurements of nasal polyp-related quality of life. Improvements were similar in patients with and without AERD and were comparable in magnitude to those achieved with FESS [123]. A smaller, earlier trial was also positive [124].
Omalizumab was approved by the FDA in 2020 for add-on therapy for adults (>18 years) with CRS with NP inadequately responsive to intranasal corticosteroids [125]. The approved dosing is based on serum total IgE and body weight, although the upper limit of serum IgE (1500 kU/mL) and the maximum dose of Xolair (600 mg every two weeks) are significantly higher for nasal polyps compared with asthma using a formula provided by the manufacturer. It is also used in the treatment of inadequately controlled moderate-to-severe asthma and chronic urticaria, as discussed separately. (See "Anti-IgE therapy".)
●Mepolizumab – Mepolizumab (an anti-IL-5 monoclonal antibody preparation) reduces tissue eosinophilia by blocking the actions of IL-5 on eosinophil differentiation and survival. It was approved by the FDA in July 2021 for add-on therapy for adults (>18 years) with CRS with NP inadequately responsive to intranasal corticosteroids, at a dose of 100 mg subcutaneously every four weeks [126].
Mepolizumab at this dose was studied in a randomized, multicenter, 52-week trial of 407 patients with recurrent and symptomatic CRS with NP despite ≥8 weeks of intranasal corticosteroid and at least one surgery to remove polyps in the previous 10 years [127]. By the end of the trial, both co-primary endpoints improved: endoscopic polyp score (adjusted difference in medians -0.73, 95% CI -1.11 to -0.34) and nasal obstruction score (-3.14, 95% CI -4.09 to -2.18). Mepolizumab is also approved for severe asthma. (See "Treatment of severe asthma in adolescents and adults", section on 'Mepolizumab'.)
Two additional biologic agents, benralizumab (an anti-IL-5 receptor monoclonal antibody preparation) [128,129] and reslizumab (an anti-IL-5 monoclonal) [130] are considered investigational for the treatment of CRS with NP, but both are available for severe asthma. Preliminary data are encouraging.
Aspirin desensitization and therapy — Patients with the combination of CRS with NP, asthma, and aspirin/NSAID intolerance, a combination of features that is referred to as AERD, NERD, or Samter's triad, may be candidates for aspirin desensitization, followed by daily aspirin therapy. Note that aspirin therapy is not effective for patients with CRS with NP but without asthma or NSAID intolerance. Sinus surgery is often recommended prior to desensitization because the presence of extensive polyp tissue is associated with more severe symptoms during desensitization and because aspirin therapy slows the regrowth of polyps but minimally reduces existing polyps. In addition, sinus surgery would carry a lower risk of bleeding if pursued before the patient is taking aspirin.
A beneficial effect of aspirin desensitization and daily aspirin therapy on NP had been noted by several groups as far back as 1983 [131-134]. In contrast to patients with aspirin intolerance, those with CRS and NP who tolerate aspirin without developing characteristic flushing and nasal/respiratory symptoms do not appear to benefit from daily aspirin therapy, at least at moderate doses [135]. Aspirin desensitization requires close monitoring for bronchospasm and is usually conducted by a specialist in drug desensitizations. This is reviewed in detail separately. (See "Aspirin-exacerbated respiratory disease" and "Diagnostic challenge and desensitization protocols for NSAID reactions".)
Long-term aspirin therapy has been shown in retrospective studies to reduce upper and lower airway inflammation in some patients, although it is rarely sufficient as monotherapy. In addition, gastrointestinal side effects from daily oral aspirin therapy preclude long-term treatment in some patients, although preventative H2 antihistamines and proton pump inhibitors can be helpful. The initial maintenance dose of aspirin has traditionally been 650 mg twice daily, but studies recommend attempting to lower the dose to 325 mg twice daily for long-term maintenance [136]. (See "Aspirin-exacerbated respiratory disease: NSAID challenge and desensitization".)
A topical preparation of intranasal lysine-aspirin is available in many countries (not in the United States). Regular intranasal therapy with this agent is being studied for the purpose of treating CRS with NP in aspirin-intolerant patients but cannot be recommended [1,137].
Maintenance therapies — Once symptoms have been controlled to a level acceptable to the patient, therapies to minimize inflammation should be initiated or continued without interruption. Maintenance therapies for CRS with NP include intranasal corticosteroids and a trial of antileukotriene agents. Other therapies are of uncertain benefit but may help certain patients.
Intranasal corticosteroids — The mainstay of maintenance treatment is intranasal corticosteroids [138,139]. Several different intranasal corticosteroids have been shown either to reduce the size or prevent the regrowth of NP following surgical removal, including (in alphabetical order) beclomethasone dipropionate, budesonide, ciclesonide, flunisolide, fluticasone furoate, fluticasone propionate, mometasone furoate, and triamcinolone acetonide (table 2). Systematic reviews and randomized trials have demonstrated that these agents are effective, delivered either by intranasal spray [18,19,28,140] or intranasal instillation [44].
Intranasal corticosteroids may also be helpful in preventing the regrowth of nasal polyps following sinus surgery [140,141], although not all studies have demonstrated efficacy, and the effect may not be equal in all patient populations [46,142]. Specifically, polyp recurrence may be more difficult to prevent in patients with AERD or nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD). In a randomized trial of 60 patients with AERD who had undergone sinus surgery and polypectomy, intranasal corticosteroids did not prevent polyp regrowth [46]. The protocol compared three treatments: saline irrigation (60 mL/nostril twice daily), saline irrigation followed by intranasal budesonide spray (64 mcg/nostril), and saline irrigation with aqueous budesonide (250 mcg/60 mL/nostril), all administered twice daily. Treatment was continued for one year. The primary outcome variable was change in quality of life on the Sino-Nasal Outcome Test (QOL-SNOT-21) at six months and one year. Patients in each arm of the study experienced an improvement in QOL-SNOT-21, but the improvement was waning by one year. There were no statistically significant differences between groups.
Antileukotrienes — Antileukotriene agents may be used as an adjunct to intranasal corticosteroids in the treatment of CRS with NP [143-146]. We treat most patients with AERD with some form of long-term antileukotriene therapy. We usually administer a three-month trial of montelukast and continue it indefinitely in patients who experience clinical benefit. Small, randomized trials demonstrated modest benefit after one to two months of montelukast, either as monotherapy [143] or as adjunctive therapy to oral prednisolone and budesonide nasal spray [145]. The effect of antileukotriene agents is generally less than that of intranasal corticosteroids, but additive effects have been reported in some studies [147-149].
Antileukotriene agents may not benefit all patients with CRS with NP. They may be more effective in those with concomitant asthma and aspirin intolerance (ie, the syndrome of AERD) [150]. It is unclear whether the 5-lipoxygenase inhibitor zileuton is any more effective than leukotriene D4 (LTD4) receptor blockers (eg, montelukast or zafirlukast). (See "Aspirin-exacerbated respiratory disease", section on 'Leukotriene-modifying agents'.)
Therapies of uncertain benefit
●Antihistamines – One randomized, placebo-controlled trial examined the effect of cetirizine 20 mg once daily for three months as a treatment for 45 patients with residual or recurrent nasal polyps [151]. Both allergic and nonallergic patients were included. The use of intranasal corticosteroids was not mentioned, except to state that the study group had "tried topical steroids unsuccessfully." Inhaled corticosteroids for asthma were allowed up to 800 mcg per day. In this study, treatment with cetirizine had no effect on the number or size of nasal polyps or total nasal symptom scores. However, individual symptoms of rhinorrhea, sneezing, and nasal obstruction were improved on cetirizine treatment. Since there are no studies combining treatment with intranasal corticosteroids plus antihistamines (oral or intranasal), it is unclear whether antihistamines provide any additional benefit in patients already receiving intranasal corticosteroids. However, if persistent nasal symptoms are present despite use of intranasal corticosteroids, antihistamines may be worth trying.
●Topical antifungal agents – Evidence for a beneficial effect of topical antifungal agents is mostly lacking, and this treatment is not recommended in recent consensus documents [51,98]. In one author's experience (DLH), topical antifungal therapy (ie, either amphotericin B or itraconazole) has been beneficial in a subset of patients with CRS with or without NP. The author reserves this therapy specifically for patients who have failed a trial of intranasal corticosteroid irrigations and have persistent mucosal thickening and mucus production, with no evidence of bacterial infection.
INDICATIONS FOR SINUS SURGERY — CRS is an inflammatory disorder of the sinonasal mucosa, and underlying structural abnormalities, such as septal deviation, do not occur with higher frequency in patients with CRS compared with controls [152]. Thus, surgery should not be the first intervention in most cases, with the possible exception of allergic fungal rhinosinusitis (AFRS) and for complications related to CRS. (See "Allergic fungal rhinosinusitis".)
Functional endoscopic sinus surgery, known by the acronym FESS, is intended to restore physiologic sinus ventilation and drainage, which can facilitate the gradual resolution of mucosal disease. However, because FESS does not directly treat the underlying inflammatory disorder, sinus surgery must be followed by medical management to control inflammatory processes or symptoms will invariably return [153]. This is particularly true for surgical polypectomy. Polyps usually reaccumulate within a few years without medical maintenance therapy [153,154].
Indications for surgical intervention include the following:
●Failure of medical treatment
●Restoration of sinus ventilation (ie, restoration of sinus ostial patency and removal of material from opacified sinuses)
●Improve penetration of topical medical therapies
●Debulking of severe polyposis (see 'Options for refractory disease' above)
●Bony erosion or extension of disease beyond the sinus cavities
In patients with both asthma and CRS, there is some evidence that medical management results in better long-term outcomes [7,155].
General effectiveness — A 2006 systematic review of FESS for CRS concluded that it was safe, although the procedures encompassed by that term did not clearly confer additional benefit over medical management [156]. However, this was based upon just three randomized trials.
A 2017 systematic review and meta-analysis was designed to compare surgery with continued medical treatment in patients who have already received some medical therapy, defined in the review as at least three weeks of antibiotics, with or without topical and/or oral corticosteroids [157]. This analysis included five studies (no randomized trials), and patients self-selected to surgery or continued medical therapy. The authors concluded that among patients who are refractory to medical therapy, those with lower quality-of-life scores tended to choose surgery, while those with higher scores chose continued medical management. Those who underwent surgery attained relatively greater benefit from it during the ensuing year, compared to those who continued medical therapy.
Another study prospectively followed a cohort of 59 adults (from a potential pool of 227) who had elected FESS for CRS, in order to assess whether improvements achieved as a result of surgery were durable [158]. The type of surgery performed and subsequent medical therapy was determined by the responsible surgeon. Approximately one-half of the cohort had nasal polyposis (NP), and data were collected through several validated survey tools. Mean follow-up was 10.9 years. Measures of quality of life and health utilization improved immediately and remained improved for most patients, although 17 percent required one or more revision surgeries, mostly due to recurrent NP. However, without the corresponding data on the remaining patients, it is difficult to draw firm conclusions about long-term outcomes overall [159,160].
Sinus ostial dilation (balloon ostial dilation) — Balloon ostial dilation (BOD) is a procedure in which the frontal, sphenoid, or maxillary sinus ostium is dilated using a balloon catheter. This procedure also goes by other names, including "balloon catheter sinusotomy," but "balloon ostial dilation" is the recommended terminology of the American Academy of Otolaryngology-Head and Neck Surgery [161]. The procedure does not involve surgical removal of tissue and can be performed in the office setting under local anesthesia. High-quality data comparing BOD and FESS for the management of CRS are limited and mostly sponsored by manufacturers of the balloon catheters:
●A 2011 systematic review of BOD for CRS identified only one study of 34 patients that met inclusion criteria and concluded that there was no convincing evidence supporting the use of this technique, compared with conventional surgical modalities, in the management of CRS refractory to medical treatment [162].
●Observational case series reported high success rates of BOD (85 percent or greater) with low rates of revision treatment (less than 10 percent of patients) in patients followed for 6 months [163] or 24 months [164].
●In a subsequent randomized, open-label, industry-sponsored trial, 92 subjects with uncomplicated CRS of the maxillary sinuses, with or without anterior ethmoid disease, were randomized to in-office BOD or FESS [165]. Patients with gross polyposis, AFRS, aspirin-exacerbated respiratory disease (AERD), previous surgery, or other complicating conditions were excluded. Primary endpoints were mean improvement in 20-item Sino-Nasal Outcome Test (SNOT-20) score at six months and need for postoperative debridement procedures. Both groups experienced significant clinical improvement and similar degrees of improvement in SNOT-20 scores (-1.67 and -1.6 points in the BOD and FESS groups, respectively, with -0.8 defined as a clinically meaningful improvement). Those treated with BOD required fewer postoperative debridement procedures to remove clots, scabs, crusts, and synechiae than those undergoing FESS, and the difference in number of debridement procedures was statistically significant. Thus, BOD was noninferior to FESS in this selected population without complicating disorders. Benefits were sustained at one year [166].
Although these reports are encouraging, the final decision regarding whether to perform BOD or FESS is considered the responsibility of the attending surgeon and must take into consideration the suitability of the case for BOD alone. Current technology does not allow the dilation of the ethmoid sinuses, where much of the more significant sinus disease is often located. "Hybrid" procedures involving BOD plus endoscopic sinus surgery have also been reported by some groups [164]. Alternatively, extensions of typical FESS may also be beneficial for extensive disease and include maxillary mega-antrostomy and frontal sinus drill-outs, which increase the maximal openings to the sinuses.
A 2018 consensus statement report agreed on the following clinical conditions in which sinus ostial dilatation (SOD) may be beneficial [167]:
●SOD can be appropriate as an adjunct procedure to FESS in patients with chronic sinusitis without nasal polyps.
●There can be a role for SOD in patients with persistent sinus disease who have had previous sinus surgery.
●There is a role for SOD in managing patients with recurrent acute sinusitis, as defined in the American Academy of Otolaryngology – Head and Neck Surgery (AAO-HNSF) guideline, based on symptoms and the CT evidence of ostial occlusion and mucosal thickening [168].
Studies of surgery in children — Both adenoidectomy and FESS have been performed in children with CRS, although neither has been formally studied, and the efficacy is not well defined. In most cases, surgery should be considered only after medical therapy has failed. Thus, decisions regarding surgery should be individualized according to the potential benefits and risks and the values and preferences of the family and child.
●Adenoidectomy – In young children with CRS and adenoidal hypertrophy, adenoidectomy is often suggested before other interventions. Enlarged adenoids are proposed to prevent normal mucociliary clearance, act as a reservoir for bacteria, and serve as a platform for biofilm formation [169,170]. However, high-level evidence addressing the efficacy of adenoid surgery in children with CRS is lacking. The available literature regarding adenoidectomy in children with CRS is reviewed separately. (See "Tonsillectomy and/or adenoidectomy in children: Indications and contraindications", section on 'Chronic sinusitis'.)
●FESS – A 2013 systematic review of the literature evaluating FESS for the treatment of CRS in children included 11 studies, with three prospective studies and no randomized, controlled trials [171]. Most studies reported subjective measures of improvement, and serious complications were rare, but the overall quality of the evidence was low.
●Balloon catheter sinuplasty – Balloon catheter sinuplasty (BCS) has been reported in prospective cohorts of children with or without ethmoidectomy or adenoidectomy [172,173]. Although BCS can be used to restore patency to the maxillary, sphenoid, or frontal sinuses, studies in children have focused on restoring patency to the maxillary sinus. The procedure appears to be safe and to result in significant improvement in symptoms beyond that afforded by adenoidectomy alone but comparable in magnitude with that previously published from adenoidectomy plus maxillary lavage [174]. One study compared BCS with ethmoidectomy to FESS and reported similar overall results in both groups but less postoperative use of antibiotics in the BCS with the ethmoidectomy group [173].
Medical adjuncts to sinus surgery — Several medical treatments have been developed as adjuncts to sinus surgery.
Glucocorticoid-eluting sinus implants — Mometasone-eluting sinus implants are approved by the US Food and Drug Administration to maintain the patency of the ethmoid or frontal sinus openings following endoscopic surgery [175,176]. The approved implants deliver 370 mcg of mometasone furoate from a biodegradable, bioabsorbable polymer matrix over 30 days. Several published studies and a meta-analysis have examined the utility of these devices [177-181]. The meta-analysis included two randomized trials with a total of 143 patients and found that drug-eluting implants, compared with nondrug implants, significantly reduced postoperative interventions, lysis of adhesions, and the need for oral corticosteroids by 35, 51, and 40 percent, respectively [180]. Another study demonstrated that the implants could be inserted in-office into the ethmoid cavity for treatment of recurrent polyposis following endoscopic sinus surgery with resultant reduction in NP size, ethmoid sinus obstruction, and improvement in nasal obstruction symptom scores achieved for six months [182].
Glucocorticoid-impregnated nasal dressing — Another method of delivery of intranasal corticosteroid therapy is corticosteroid-impregnated dressing, although evidence in support of this approach is less robust. In a retrospective, case control study, 21 subjects with recurrent polypoid changes following surgery underwent placement of triamcinolone-impregnated (total dose 20 mg) absorbable nasal dressings in the middle meatus [183]. Patients with frank polyposis were not included. Compared with a control group of patients treated with oral methylprednisolone (24 mg initially, gradually reduced over six days and discontinued), improvements were similar at four and eight weeks. This approach represents another method of delivery of intranasal corticosteroid therapy, which should achieve high local concentrations while minimizing systemic exposure. The assistance of an otolaryngologist is required, and this technique should be studied further to better define optimal dose, duration of benefit, and patient selection. In a separate study using 20 mg per side of triamcinolone-impregnated dressings (equivalent to a daily dose of 17 mg prednisolone orally), serum cortisol was suppressed at day 2 after placement but had normalized by day 10 [184].
TREATING EXACERBATIONS OF CRS — Exacerbations of CRS may be precipitated by the following:
●Discontinuation or reduction of medications
●Acute viral upper respiratory tract infections
●Heavy exposure to allergens
●Exposure to noxious inhalants
●Worsening of inflammation secondary to bacterial infection or (perhaps) fungal colonization
A bacterial infection should be suspected if the patient has increased symptoms persisting greater than 7 to 10 days, purulent nasal discharge, and/or increased facial pain or pressure. However, the frequency of bacterial infection during acute exacerbations of CRS remains unknown and largely unstudied. The situation is even more complex in patients who have had S. aureus, gram-negative rod, or drug-resistant bacterial infections in the past.
In patients suspected of having uncomplicated bacterial infection, acute exacerbations of CRS are treated similarly to episodes of acute bacterial rhinosinusitis with a 10- to 14-day course of antibiotics. Repeated use of the same agent should be avoided, as there is risk of promoting a drug-resistant bacterial infection and perhaps greater fungal colonization. A culture from the sinus ostium should be obtained if an infection with S. aureus, gram-negative rods, or drug-resistant bacteria is suspected. (See "Microbiology and antibiotic management of chronic rhinosinusitis".)
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".)
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 email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Nasal polyps (The Basics)" and "Patient education: Chronic sinusitis (The Basics)" and "Patient education: Rinsing out your nose with salt water (The Basics)")
●Beyond the Basics topic (see "Patient education: Chronic rhinosinusitis (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Definition – Chronic rhinosinusitis (CRS) is an inflammatory condition of the paranasal sinuses and linings of the nasal passages that lasts 12 weeks or longer. In most cases, the disorder cannot be cured, and the goal of therapy is to reduce symptoms and improve quality of life. (See 'Goals of therapy' above.)
●General approach for different types of CRS – Multiple therapies are utilized in the management of CRS, including intranasal saline, intranasal and oral corticosteroids, antibiotics, antileukotriene agents, biologics, and endoscopic sinus surgery. These are combined in various ways to manage specific subtypes of CRS. (See 'Overview of medical therapies' above.)
●CRS without nasal polyposis
•Initial therapies – For patients with CRS without nasal polyposis (NP), we suggest initial treatment with one to three months of a combination of intranasal saline (sprays or irrigations) and intranasal corticosteroids (Grade 2C). (See 'Initial therapy' above and 'Overview of medical therapies' above.)
•Further interventions – For patients who do not achieve adequate relief with intranasal saline and corticosteroids, next steps depend upon available evaluation. If endoscopy can be performed to obtain material from the sinuses directly, we culture this to determine if infection is present and treat accordingly. If endoscopy is not available, we suggest an empiric course of oral corticosteroids plus oral antibiotics (Grade 2C). A representative regimen for adults is prednisone, 40 mg daily for five days, followed by 20 mg daily for five days plus two to four weeks of an antibiotic. An alternative approach is to initiate treatment with long-term, low-dose macrolide antibiotics (see 'Persistent symptoms' above and 'Oral corticosteroids' above). Empiric antibiotic selection is discussed separately. (See "Microbiology and antibiotic management of chronic rhinosinusitis", section on 'Empiric regimen selection'.)
•Endoscopic sinus surgery – In patients in whom these medical treatments do not result in sufficient improvement in symptoms, we proceed to endoscopic sinus surgery. (See 'Endoscopic sinus surgery' above.)
•Maintenance therapy – Any successful intervention for CRS without NP must be followed by maintenance therapy, because without ongoing treatment, symptoms will eventually return in most patients. For maintenance therapy, we suggest intranasal corticosteroid nasal sprays and intranasal saline (Grade 2B). For patients with persistent or increasing symptoms despite consistent use of corticosteroid sprays, we suggest changing to corticosteroid instillations (figure 1) (Grade 2C). (See 'Maintenance treatment' above.)
•Treatment of underlying allergic rhinitis – Patients with underlying allergic rhinitis who have sneezing or nasal pruritus may benefit from additional therapies targeting that condition, including minimally sedating second-generation oral antihistamines, intranasal antihistamine sprays or antileukotriene agents (eg, montelukast), and/or allergen immunotherapy. (See "Pharmacotherapy of allergic rhinitis".)
•Reasons for treatment failure – Potential explanations for refractory or recurrent symptoms include persistent sinus ostial obstruction, odontogenic sinusitis, problems with mucociliary clearance, incompletely treated sinus infection, underlying immunodeficiency, or mucous recirculation syndrome. (See 'Treatment failure' above.)
●CRS with nasal polyposis
•Initial therapies – For patients with CRS with NP, we suggest initial treatment with one to three months of a combination of intranasal saline (sprays or irrigations) and intranasal corticosteroids (Grade 2C). Patients with severe polyposis may not be able to use intranasal medications because the nasal passages are blocked. (See 'Initial therapy' above.)
•Short-term relief of severe congestion – For patients with CRS with NP who are seeking relief of nasal blockage or an impaired sense of smell, we recommend a course of oral corticosteroids initially to shrink nasal polyps (Grade 1B). A typical adult regimen is prednisone 40 mg for five days, followed by 20 mg daily for five days. Antibiotics are not recommended unless a concomitant infection is suspected. The benefit of oral corticosteroids is temporary, and this intervention must be followed by maintenance therapy. (See 'Oral corticosteroids' above.)
•Endoscopic surgery or biologic agents – For patients in whom intranasal and oral corticosteroids fail to reduce polyp tissue sufficiently and the patient has persistent blockage or anosmia, we suggest either sinus surgery or therapy with a biologic agent (Grade 2B). The choice of approach depends upon availability, cost, and patient preference. Available biologics include dupilumab, omalizumab, and mepolizumab. (See 'Options for refractory disease' above.)
•Maintenance therapy – Following reduction of polyps by oral corticosteroids or sinus surgery, maintenance therapy is necessary to help prevent regrowth of polyps. For patients who have relatively mild residual symptoms (eg, nasal patency and an intact sense of smell), we suggest intranasal corticosteroids (Grade 2B). Dilute corticosteroid sinus rinses are another treatment option. We advise patients to try these approaches initially, but if symptoms worsen despite consistent use, we change this to the concentrated corticosteroid instillations (figure 1). (See 'Intranasal corticosteroids' above and 'Maintenance therapies' above.)
•Patients with AERD – Some patients with CRS with NP also have asthma and intolerance to aspirin (or other nonsteroidal anti-inflammatory drugs [NSAIDs]), a condition called aspirin-exacerbated respiratory disease (AERD). Options for these patients include aspirin desensitization and daily aspirin therapy or dupilumab. Aspirin desensitization is a treatment option for these patients, but it requires access to an allergy specialist with experience in drug desensitizations and is often performed shortly after surgery to remove polyps. (See 'Aspirin desensitization and therapy' above and "Aspirin-exacerbated respiratory disease".)
