The page number in the footer is not for bibliographic referencingwww.tandfonline.com/ojfp 20 Introduction Chronic sinusitis is currently recognised as an inflammatory disease of the upper airways, associated with a multifactorial aetiology.1 Although chronic rhinosinusitis (CRS), with and without nasal polyposis (NP), falls under the umbrella term of chronic rhinosinusitis, these separate disease entities are likely to have different pathogeneses, and can be distinguished individually by their unique inflammatory characteristics.2 In addition to common presenting symptoms, CRS is associated with a reduction in the patient’s quality of life, daily productivity and quality of sleep.1 Definition CRS can be defined as a complex inflammatory condition which persists for 12 weeks or longer, and can be subdivided into CRS, either with or without NP or allergic fungal rhinosinusitis.1-4 It involves the lining of the nasal passages, as well as the paranasal sinuses.3-5 Diagnosis Besides documented inflammation of the paranasal sinuses or nasal mucosa, the presence of at least two of the important clinical symptoms listed in Table I (one of the two symptoms must be either obstruction or discharge) lasting for 12 weeks or longer1-4 is required in order for a diagnosis of CRS to be made. Other symptoms may include fatigue, headaches, ear pain or fullness, toothache and difficulty sleeping.1 A diagnosis of CRS must be confirmed by at least one of the following objective findings: • Nasal endoscopy:6 The presence of nasal polyps.1 • Computed tomography (CT ):5,6 Demonstrating inflammation in the paranasal sinuses.1 • Purulence or oedema within the middle meatus.1 In general, bacterial culture from patients with CRS is unnecessary.3,6 Nasal swabs are not representative of the sinus contents. Thus, they are not useful when making a decision about antibiotic treatment.4 However, endoscopic culture of the middle meatus may be recommended in situations of serious complications, e.g. intracranial extension and orbital infection, or for patients with nosocomial sinusitis.5,6 Invasive fungal sinusitis should be considered in immunocompromised patients.6 Contributing factors to the development of chronic rhinosinusitis The following factors may contribute to the development of CRS: asthma, allergic and non-allergic rhinitis, immune and ciliary dysfunction, cystic fibrosis, lost ostia patency, defective mucociliary clearance, exacerbated respiratory disease relating to acetylsalicylic acid, and structural abnormalities and/or immunodeficiency.4,6 Indications for referral Indications for referral include the following: • The presence of a persistent crust, i.e. in conditions such as Wegener granulomatosis; irregular surfaces; diffuse haemorrhagic areas; and vascular malformations of ectasias and bleeding from minor trauma on physical examination. All of these should raise red flags .6 • The presence of “red flag” symptoms, such as unilateral symptoms, blockage, bleeding or bloodstained discharge, proptosis, diplopia, cacosmia, epiphora and neurological symptoms.2 Chronic rhinosinusitis (CRS) has a substantial effect on the patient’s quality of life. It has recently been accepted that CRS has multiple distinct components, e.g. infection and inflammation, which has led to changes in the therapeutic approach. In addition, it is no longer considered practical to manage CRS as a prolonged version of acute rhinosinusitis. A CRS diagnosis is based on the type and duration of symptoms, together with an objective finding of inflammation of the nasal mucosa or paranasal sinuses. Differences in treatment are based on the presence or absence of nasal polyps. Keywords: chronic rhinosinusitis, nasal polyps, inflammation, nasal mucosa, paranasal sinuses S Afr Fam Pract ISSN 2078-6190 EISSN 2078-6204 © 2015 The Author(s) REVIEW South African Family Practice 2015; 57(5):20-25 Open Access article distributed under the terms of the Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 Chronic rhinosinusitis Stephani Schmidt* Amayeza Info Centre *Corresponding author, email: stephani@amayeza-info.co.za Table I: Important clinical features of chronic rhinosinusitis • Pain and pressure or fullness (facial)1,2,4,6 • Obstruction or blockage (nasal)1,2,4,6 • Anterior or posterior purulent nasal drainage1,2,4,6 • Anosmia or hyposmia6 (reduced smell)1,2,4 Chronic rhinosinusitis 21 The page number in the footer is not for bibliographic referencingwww.tandfonline.com/ojfp 21 • Patients with refractory CRS or those who did not respond to treatment may be referred for an alternative diagnosis.6,7 • When mucous recirculation syndrome is suspected.7 • Patients with allergic fungal rhinosinusitis.4 Surgery Surgery should not be the first intervention4 in most cases of CRS, with the possible exception of allergic fungal rhinosinusitis (AFRS). A trial of medical treatment should be provided to patients with large polyps before surgery, except when the nature of the polyps is in doubt.7 Pharmacological treatment options Suggested adult dosages have been included in this article in instances where pharmacological treatment options are provided. Reference should be made to the package inserts for additional prescribing and safety information. Before initiating CRS treatment, contributing factors need to be identified and treated.6 CRS cannot be “cured” in most people, and the intention of therapy is to reduce the signs and symptoms, and to improve patients’ quality of life.4,6,7 Because CRS responds incompletely to treatment, it may be necessary to continue with long-term treatment.7 The objectives of treatment are to: • Reduce complications:6 Minimise or control mucosal oedema and inflammation;3,4,6 and control infection, if present.3,4,6 • Maintain adequate sinus drainage and ventilation.3,4 • Reduce the number of acute exacerbations.4 • Prevent disease progression or recurrence.7 Nasal saline Saline nasal irrigation reduces postnasal drainage, removes secretions, rinses away allergens and irritants, and assists in restoring normal mucociliary clearance.1,4 If obvious mucus or crusting is present, a saline spray or irrigation can be used immediately prior to the administration of other intranasal medications.4 Although nasal saline is an effective adjunctive treatment for CRS, it was indicated in studies to be less effective than topical glucocorticoids as monotherapy.1,4 Saline irrigation with a high volume (> 100 ml) is more effective than a saline nasal spray.1,4 Depending on the severity of symptoms, nasal irrigation may be performed as needed; daily or multiple times per day.1,4 Place in therapy Nasal saline should be used as adjunctive to intranasal corticosteroids in patients with and without nasal polyps.1,4 Intranasal corticosteroids Intranasal corticosteroids (INCS) are the cornerstone of maintenance treatment, and are helpful in all types of CRS.2,4 INCS suppress inflammation at multiple points in the inflammatory cascade, decrease vascular permeability and reduce glycoprotein release from the submucosal glands, i.e. thin mucus.1,7 INCS can be administered either as a nasal spray or as a solution for instillation. Treatment is usually initiated using a nasal spray.4 Table II contains information on which type of product to use, and Tables III and IV contain a list of INCS products. Place in therapy INCS is recommended for: • Chronic sinusitis, with and without nasal polyposis.1 • CRS with nasal polyps (CRSwNP): INCS reduces the size of nasal polyps, improves nasal symptoms,4,6 and may delay the re-growth of nasal polyps.4,7 INCS are the mainstay of maintenance treatment4 following the surgical removal of polyps. • CRS without nasal polyps (CRSsNP): INCS are recommended for their anti-inflammatory properties and because long-term adverse effects have not been reported.6 Table IV: Other intranasal corticosteroid products Other intranasal corticosteroid products Strength Frequency per nostril Prednisolone nasal drops 1% solution 2-4 drops, once or twice daily Budesonide nebulising solution Mix budesonide nebulising solution into a high-volume saline irrigation, using either: • 0.5 mg (2.0 ml of 0.25 mg/ml), or • 1.0 mg (2.0 ml of 0.50 mg/ml) Rinse the nasal cavities (both), once or twice daily Table III: A list of intranasal corticosteroid nasal sprays1 Intranasal corticosteroid nasal sprays Dosage per spray Sprays per nostril Frequency per day Mometasone furoate 50 μg 1 Twice Beclomethasone dipropionate monohydrate 42 μg 1 Twice Fluticasone propionate 50 μg 2 Once Fluticasone furoate 50 μg 2 Once Budesonide 32 μg 1-4 Once Ciclesonide 50 μg 2 Once Flunisolide Not listed 2 Twice Triamcinolone acetonide 55 μg 2 Once Table II: Choosing an intranasal corticosteroid product Drops Initiate treatment with INCS drops7 in patients with nasal polyposis, and in those with severe obstruction Sprays Nasal sprays with once-daily dosing are convenient, and can help optimise patient compliance4 Instillation Instillation is recommended in patients who have persistent symptoms, despite consistent use of INCS4 Can reach the middle meatus, where polyps often form4 INCS: intranasal corticosteroids S Afr Fam Pract 2015;57(5):20-2522 The page number in the footer is not for bibliographic referencingwww.tandfonline.com/ojfp 22 Special considerations Special consideration applies in certain circumstances. Some individuals may experience local nasal irritation, sore throat and epistaxis.7 Nasal sprays containing benzalkonium chloride may irritate the nose.7 If the risk of systemic absorption is high, i.e. with betamethasone and dexamethasone, short-term use only is recommended.7 Oral corticosteroids Currently, there is no consensus regarding the dose and duration of treatment of oral corticosteroids for CRS1,4 (Table V). However, the lowest effective dose should always be used to reduce the risk of serious adverse events.6 Treatment options include prednisone or prednisolone (5.0-60.0 mg once daily), methylprednisolone (7.5-60.0 mg once daily), or dexamethasone (0.5-4.5 mg twice daily).1 Place in therapy Oral corticosteroids should be used as follows: • As an intermittent short course (1-3 weeks) for symptomatic NP or the treatment of CRSsNP.1 • Use briefly in combination with, or prior to, the application of INCS.2,7 • Use for severe nasal obstruction,7 uncontrolled symptoms following conventional pharmacotherapy (as short-term rescue medication),7and as part of medical polypectomy for nasal polyps.7 Medical polypectomy A brief course of oral corticosteroids may be administered to patients with large polyps, nasal blockage or an impaired sense of smell.4 Oral corticosteroid therapy, i.e. prednisolone (0.5 mg/kg each morning for 5-10 days, is accompanied by instillations of betamethasone nasal drops4 (2 drops per nostril, 3 times a day for 5 days, then twice daily until the bottle runs out).7 Since polyps tend to recur, fluticasone (drops or spray) or mometasone (spray) is recommended as maintenance therapy owing to their lower bioavailability. However, treatment efficacy varies in different patients.4 It should be noted that the initial use of betamethasone nasal drops only may be effective for smaller polyps.7 Antimicrobial agents Oral antimicrobial agents Compared to acute bacterial rhinosinusitis (ABRS), the bacteriology of CRS is different and not as well understood.5,8 The microbiology of rhinosinusitis in some patients with CRS may evolve through several phases.3,8 In addition, fungi may colonise the sinuses, and cause allergic fungal rhinosinusitis or invasive fungal sinusitis.3 Currently, there is only limited evidence that antibiotics are effective in the treatment of CRS. In addition, the duration of treatment has not been studied prospectively.3 The use of antibiotics may be considered in secondary care for the treatment of CRS.2 Initial antimicrobial treatment should be effective against the most likely bacterial aetiologies, including aerobic, anaerobic pathogens, methicillin-resistant Staphylococcus aureus (in case of risk of infection),3 as well as the most common encapsulated organisms associated with an ABRS, e.g. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella  catarrhalis.5 CRSsNP is often associated with a bacterial infection.6 Whenever possible, the endoscopic culture of purulent mucus obtained from the middle meatus or another accessible sinus ostium should guide the choice of antibiotic treatment.4 However, if this is not possible, the choice of antimicrobial agent is made empirically.3,4 Empiric antibiotic treatment is not recommended in patients: • Who have recently failed antibiotic treatment with a similar regimen.4 Table V: Place in therapy and suggested dosages of oral corticosteroids Place in therapy CRSsNP Relieves severe and refractory mucosal oedema4 CRSwNP Reduces the size of polyps1,4 AFRS Minimises mucosal inflammation4 Suggested adult dosage CRSwNP Oral prednisone, 20 mg twice daily for 5 days, followed by 10 mg twice daily for 5 days, then 10 mg once daily for 5 days4 British guidelines:* Prednisolone (0.5 mg/kg every morning for 5-10 days), and the instillation of betamethasone nasal drops4 As part of intensive medical management of CRSsNP Oral prednisone, 20 mg twice daily for 5 days, followed by 20 mg daily for 5 days4 Severe polypoid disease, unresponsive to INCS therapy A two-week course of prednisone may reduce the polyp size or grade, e.g. 30 mg/day for 4 days. Thereafter, reduce the dose by 5 mg every 2 days for 10 days6 INCS is recommended to maintain this improvement6 After endoscopic sinus surgery Systemic prednisone, e.g. 30 mg/day, given 5 days before and 9 days after, may provide benefit6 AFRS: allergic fungal rhinosinusitis, INCS: intranasal corticosteroids, CRSsNP: chronic rhinosinusitis without nasal polyps, CRSwNP: chronic rhinosinusitis with nasal polyps * British Society for Allergy and Clinical Immunology7 Chronic rhinosinusitis 23 The page number in the footer is not for bibliographic referencingwww.tandfonline.com/ojfp 23 • With a history of infection with Gram-negative or methicillin- resistant S. aureus or other highly drug-resistant bacteria.4 • Who are highly immunosuppressed, and therefore at risk of invasive fungal rhinosinusitis.4 If a patient was given an antibiotic in the past three months, a different class of antibiotic should be used.3 A second course of empiric intensive treatment may be initiated in patients for whom intensive medical treatment appeared to have helped, but did not result in a sufficient improvement in symptoms or the resolution of the CT findings. The second course may be initiated provided that there is no clear indication of surgical intervention, there are no signs or symptoms suggesting another condition, the patient does not appear to be severely ill, or prefers to continue with medical treatment in order to avoid surgery.4 Table VI contains a list of available antibiotic therapies, and Table VII information on short- and long-term antibiotic treatment. Systemic and topical antifungal therapy does not appear to be effective in the treatment of CRS. Therefore, it should not be used as an empirical treatment.3 Topical antimicrobial agents The routine use of topical antimicrobial agents is not recommended during the management of CRSsNP.1 Depending on antimicrobial susceptibility, topical antimicrobial agents, such as mupirocin, gentamicin or tobramycin, once or twice daily for four weeks, may be useful in patients who have undergone prior surgery.4 Topical aminoglycosides should be used for a defined treatment period and with caution. Owing to the potential risk of ototoxicity, the use of topical aminoglycosides is contraindicated in the sphenoethmoidal region.4 Antileukotrienes Antileukotrienes are generally less effective than the INCS, but some studies have reported additive effects.4 Treatment with antileukotrienes (Table VIII) may be more effective in those with concomitant asthma and aspirin intolerance.4 Table VIII: Treatment with antileukotrienes Product Dosage and treatment frequency Montelukast 10 mg, once daily1 Zafirlukast 20 mg, twice daily1 Zileuton 600 mg, four times daily1 Place in therapy Anitleukotrienes may be considered in patients with aspirin- sensitive rhinosinusitis7 (acetylsalicylic acid sensitivity),6 asthma7 and nasal polyposis.1,7 They may be useful in patients with refractory postnasal drainage and nasal congestion.4 Table VI: Available antibiotic therapies1 Antibiotic therapy Dosage (mg) Daily frequency Duration Non-macrolide antibiotics Amoxicillin or clavulanate 875 Twice 10-14 days Cefuroxime 250 Twice 10-14 days Cefaclor 250-500 Three 10-14 days Cefprozil 250-500 Twice 10-14 days Cefpodoxime 200 Twice 10-14 days Trimethoprim-sulphamethoxazole 160/800 Twice 10-14 days Levofloxacin 500 Once 10-14 days Moxifloxacin 400 Once 10 days Macrolides Clarithromycin 500 Short-course: Twice daily 14 days Long-term course:*,** Once daily 12 weeks Azithromycin 500 Once 3 days Erythromycin 250-800 Four times 10 days Roxithromycin 150 Short-course: Once daily 10 days Long-term course:*,** Once daily 12 weeks * Long-term macrolide therapy is not recommended in patients with nasal polyps1 ** Potential adverse effects, as well as possible interactions with other medication, should be considered with prolonged macrolide therapy1 Table VII: The duration of treatment of oral antibiotics Short-term Two weeks’ treatment may be used for the acute exacerbation of rhinosinusitis7 Non-macrolide treatment for < 3 weeks may be considered for CRSsNP when purulence is present1 Doxycycline may be considered for nasal polyposis1 Doxycycline 200 mg once, then 100 mg daily for 20 days, may be considered for CRSwNP1,2,4 Long-term (≥ 12 weeks) Macrolides may be considered1,2 for CRSsNP CRSsNP: chronic rhinosinusitis without nasal polyps, CRSwNP: chronic rhinosinusitis with nasal polyps S Afr Fam Pract 2015;57(5):20-2524 The page number in the footer is not for bibliographic referencingwww.tandfonline.com/ojfp 24 CRS: chronic rhinosinusitis , CRSsNP: chronic rhinosinusitis without nasal polyps, CRSwNP: chronic rhinosinusitis with nasal polyps, CT computed tomography, INCS: intranasal corticosteroids Figure 1: Medical therapy for chronic rhinosinusitis The following diagnosis may be considered for individuals who did not respond to medical therapy: • Allergic conditions, such as fungal rhinosinusitis and allergic rhinitis • Non-allergic rhinitis • Vasomotor rhinitis • Trigeminal neuralgia • Deformation of the nasal septum • Other headaches, atypical facial pain and migraines • Invasive fungal rhinosinusitis • Temporomandibular joint dysfunction Urgent referral: • In case of severe pain or swelling of the sinus areas • Immunocompromised individuals • If invasive fungal sinusistis is suspected Early referral: • No response to ≥ 1 course of maximal medical therapy • ≥ 4 sinus infections per annum Consider: • Antihistamine (systemic) • Antileukotriene agents • Allergy immunotherapy Continue treatment Does the patient have concurrent allergic rhinitis? Persistent symptoms? Yes Yes Yes Yes No No No No Daily use of INCS and saline irrigation CRSwNP treatment Mild or resolved symptoms Treatment may be continued Acute exacerbation or when symptoms are persistent CRSsNP treatment If results are negetive for CRS: • Assume recurrent sinusitis and treat with INCS • Consider alternative diagnoses Long-term antibiotic, i.e. a macrolide for 3 months: • Clarithromycin 250-500 mg daily, or • Roxithromycin 150 mg daily Consider short course • Oral corticosteroid • Culture-directed antibiotic if mucopurulent discharge is present on examination Short course (14-21 days) Oral corticosteroid (taper when indicated): • Prednisone 30-50 mg daily, or • Prednisolone 20-60 mg daily Consider • Doxycycline (a short course of 200 mg once, followed by 100 mg daily for 21 days), or • Culture-directed antibiotic when mucopurulent discharge is present on examination Endoscopy or CT Are polyps present Use a short-course antibiotic when indicated: • Culture directed, or • Broad spectrum Chronic sinusitis as per diagnosis (see text) Resolved or mild symptoms Endoscopic sinus surgery may be considered Reassess in 1-3 months Is active mucopurulence present? Chronic rhinosinusitis 25 The page number in the footer is not for bibliographic referencingwww.tandfonline.com/ojfp 25 Antihistamines Antihistamine treatment may be helpful in patients with CRS and concomitant allergic rhinitis.1,4 It is uncertain whether or not antihistamines provide any additional benefit in patients who are already using topical glucocorticoids. However, it may be worthwhile in patients who have persistent nasal symptoms despite the use of INCS.4 Decongestants Currently, there is no evidence to support the use of decongestants for CRSwNP or CRSsNP.2 The chronic use of oral decongestants, such as pseudoephedrine, is generally avoided for the maintenance treatment of CRSsNP.4 Nasal drops or sprays containing sympathomimetic agents, i.e. ephedrine or xylometazoline, can increase nasal vasoconstriction.7 Short-term intranasal decongestants, in combination with topical corticosteroids, may be helpful in exacerbations of rhinosinusitis with nasal blockage.7 Aspirin desensitisation and therapy Anti-IgE monoclonal antibody treatment with omalizumab may be considered in patients with the combination of CRSwNP, asthma and aspirin intolerance.4 Anti-IgE monoclonal antibody treatment Anti-IgE monoclonal antibody treatment (omalizumab) can be considered in patients with chronic sinusitis with polyposis and asthma.1,4 Summary of the recommendations for the treatment of chronic rhinosinusitis Figure 1 contains a summary of the approach to medical therapies for CRS.1,5,6 Depending on the response to treatment, a patient’s chronic sinusitis-specific symptoms may be classified as persistent, mild or resolved. Persistent symptoms have a negative effect, while mild symptoms do not have a negative effect on daily productivity, functioning or quality of life.1 Chronic rhinosinusitis without nasal polyps CRSsNP accounts for approximately two thirds of CRS cases.4 Initial treatment involves the use of INCS, in conjunction with saline irrigation.1 Intensive medical management of patients with CRSsNP who have not received treatment in the immediate past includes either long-term macrolide treatment, or a short course of oral glucocorticoids combined with a prolonged course of oral antibiotics for 3-4 weeks, which may be extended for up to six weeks (or for an additional seven days after the symptoms have cleared),4 with one or more adjunctive therapies, i.e. intranasal saline or INCS.4 Patients without polyps may benefit from a prolonged course of macrolide therapy.1,2 There is no consistent evidence supporting the routine use of short-course systemic corticosteroids in CRSsNP.1A short course of oral steroids may be considered in patients with persistent or severe symptoms.1,6 Short-course antibiotics are generally considered when the symptoms indicate infection, i.e. pain or purulence.1,6 Chronic rhinosinusitis with nasal polyps In the absence of facial pain, pressure or purulent drainage, and when bacterial infection is unlikely, the initial treatment of CRSwNP focuses on establishing a regimen which reduces or controls the mucosal inflammation, and reduces the size and/or extent of nasal polyps.4 Initial therapy includes INCS, in conjunction with saline irrigation.1 Short-course oral corticosteroids6 are followed by maintenance INCS.1 Antileukotriene agents may be considered in patients with acetylsalicylic acid sensitivity.1,6 A short or long course of doxycycline may also be considered.1,2 Systemic antibiotics are generally not indicated in the absence of infection when managing CRSwNP.1 A broad-spectrum or a culture- directed oral antibiotic may be necessary during periods of acute exacerbation with superimposed infection.1 Allergic fungal rhinosinusitis Surgery is usually required for patients with AFRS in order to maximise sinus ventilation and drainage via the removal of inspissated mucus, which should be cultured for fungus.4 Treatment after surgery usually involves the use of oral and topical corticosteroids. The use of oral and topical antifungal agents is not recommended.4 Conclusion The aim of medical therapies is not only to minimise the risk of acute inflammatory exacerbation, but also to optimise patients’ quality of life and daily functioning.1 The development of appropriate treatment strategies, as well as advances in the understanding of the pathophysiology of CRS, have improved outcomes for patients with CRS.5 References • Rudmik L, Soler ZM. Medical therapies for adult chronic sinusitis: a systematic review. JAMA. 2015;314(9):926-939. • Ah-See KL, MacKenzie JM, As-See KW. Management of chronic rhinosinusitis. BMJ. 2012;345:e7054. • Brook I. Microbiology and antibiotic management of chronic rhinosinusitis. UpToDate [homepage on the Internet]. 2015. c 2 0 1 5 . Av a i l a b l e f r o m : h t t p : / / w w w. u p t o d a t e. c o m / c o n t e n t s / microbiology-and-antibiotic-management-of-chronic-rhinosinusitis • Hamilos DL. Chronic rhinosinusitis: management. UpToDate [homepage on the Internet]. 2015. c2015. Available from: http://www.uptodate.com/ contents/chronic-rhinosinusitis-management • Desrosiers M, Evans GA Keith PK, et al. Canadian clinical practice guidelines for acute and chronic rhinosinusitis. Allerg Asthma Clin Immunol. 2011;7(1):2. • Kaplan A. Canadian guidelines for chronic rhinosinusitis: clinical summary. Can Fam Physician. 2013:59(12):1275-1281. • Scadding GK, Durham SR, Mirakian R, et al. BSACI guidelines for the management of rhinosinusitis and nasal polyposis. Clin Exp Allergy. 2007;38(2):260-275. • Brook I. Microbiology of sinusitis. Proc Am Thorac Soc. 2011;8(1):90-100.