management of rhinosinusitis in adults: clinical ... of rhinosinusitis in adults: clinical...

www.turner-white.com Vol. 9, No. 8 August 2002 JCOM 463

CASE-BASED REVIEW

Management of Rhinosinusitis in Adults: Clinical Applications of Recent Evidence and Treatment RecommendationsCase Study and Commentary, Rowena J. Dolor, MD, MHS, and John W. Williams Jr, MD, MHS

INSTRUCTIONSThe following article, “Management of Rhino-sinusitis in Adults: Clinical Applications of Re-

cent Evidence and Treatment Recommendations,” is acontinuing medical education (CME) article. To earncredit, read the article and complete the CME evaluationform on page 476.

OBJECTIVESAfter participating in the continuing educationactivity, primary care physicians should be able to:

1. Identify the common causes of sinonasal symptoms2. Understand symptoms and signs predictive of acute

rhinosinusitis3. Identify cost-effective strategies for the diagnosis and

treatment of rhinosinusitis4. Describe recent guidelines on the antimicrobial and

ancillary treatment of rhinosinusitis5. Understand indications for referral to allergy or oto-

laryngology specialist

CASE STUDY 1 Initial Presentation

A 30-year-old woman presents to her primary carephysician with a 5-day history of nasal congestion,

colored nasal discharge, cough, muscle aches, and sore throat.She has had temporary relief of her symptoms with over-the-counter cold medications but is concerned that she may needan antibiotic for a sinus infection.

History The patient reports that family members have had similar coldsymptoms that resolved after 3 or 4 days. She denies havingfever, facial pain, or toothache. She has a history of hay feversymptoms in the spring for which she takes over-the-counterdiphenhydramine as needed, but she has not required anymedication in the past 2 months. She is a nonsmoker.

Physical Examination On physical examination, the patient appears healthy. She has

a temperature of 37°C and blood pressure of 116/64 mm Hg.Eye and ear examinations are normal. She has no sinus ten-derness, and transillumination of the maxillary sinuses is nor-mal. Her nasal mucosa appears swollen and slightly erythe-matous with pale yellow discharge. Her oropharynx appearsmildly erythematous and is without discharge. She has no cer-vical, submandibular, or submental adenopathy.

• What are the most probable causes of this patient’ssymptoms?

Sinonasal complaints, such as nasal discharge, nasal con-gestion, and facial pain, are common in the primary care set-ting. An estimated 6% of annual office visits to primary carephysicians are due to inflammation of the paranasal sinus-es, with or without bacterial infections [1]. In a survey of arandom sample of the U.S. population, 16% of subjects gavea self-report of sinusitis [2]. However, not all sinus com-plaints represent sinusitis. The differential diagnosis forsinonasal symptoms can be grouped broadly into inflam-matory and noninflammatory causes and anatomic obstruc-tion (Table 1). The most common differential diagnoses fora patient with nasal or sinus symptoms presenting to a gen-eralist include acute viral upper respiratory infections, aller-gic rhinitis, vasomotor rhinitis (idiopathic or rhinitis med-icamentosa), nasal septal deviation, and bacterial sinusitis.Less common causes include nasal polyps, hormonal caus-es (pregnancy, hypothyroidism), and drug-induced vaso-motor rhinitis (eg, reserpine, guanethidine, prazosin,angiotensin-converting enzyme inhibitors, and cocaineabuse). Rare causes include sarcoidosis, Wegener’s granulo-matosis, tumor, and foreign body [3]. Establishing a proper

From the Division of General Internal Medicine, Department of Medicine,Duke University Medical Center, Durham, NC (Dr. Dolor) and the Center forHealth Services Research in Primary Care, Duke University, Durham, NC(Dr. Williams).

diagnosis is important in order to select appropriate thera-py and monitor response.

Sinusitis is broadly defined as inflammation of one ormore paranasal sinuses, but most use the term “sinusitis” torefer to infection of the sinuses. Sinusitis is often preceded byrhinitis and rarely occurs without concurrent rhinitis.Therefore, the term “rhinosinusitis” has been proposed bythe American Academy of Otolaryngology-Head and NeckSurgery Task Force to describe patients with a variety ofnasal and sinus symptoms, since both areas are often affect-ed simultaneously [4].

The majority (87%) of patients with sinusitis who seekmedical care go to primary care physicians [5]. Chronic rhi-nosinusitis is also frequently seen in primary care, but manyof these patients may receive concurrent medical care fromspecialists. In adults with acute rhinosinusitis, the maxillarysinuses are the most frequently involved, followed by thefrontal and ethmoidal sinuses. Isolated sphenoid rhinosi-nusitis is rare and constitutes a medical emergency [1].

• What clinical findings are used to establish the diagno-sis of rhinosinusitis?

Clinical FeaturesHistoryThe patient’s symptom history is essential for establishing adiagnosis of rhinosinusitis. Viral upper respiratory infections

often precede rhinosinusitis, with an estimated 0.5% of com-mon colds developing into acute rhinosinusitis [6]. Otherpredisposing factors include immunoglobulin deficiencies,disorders of mucociliary transport (eg, cystic fibrosis), andanatomic factors (such as septal deviation, hypertrophicturbinates, nasal polyps, or tumor). A history of allergicrhinitis is widely believed to be a predisposing factor for rhi-nosinusitis, but this association has not been proven. Ap-proximately 5% to 10% of patients with rhinosinusitis reporthaving had recent dental work or dental infections. In chil-dren, upper respiratory illness and nasal foreign body arethe most common antecedents to rhinosinusitis [7,8].

SymptomsNasal congestion, nasal obstruction, clear or purulent nasaldrainage, postnasal drip, sore throat, facial pain, anosmia,cough, fatigue, dental pain, ear fullness, headache, and hali-tosis are symptoms associated with rhinosinusitis. Mostadults will not have recorded an elevated temperature.Persistence of sinonasal symptoms for a duration longerthan 7 to 10 days usually indicates the development of acuterhinosinusitis [9]. Characteristic symptoms include mucopu-rulent nasal discharge, cough, and facial pain that increaseswhen bending over or that is unilateral. Pain in the upperteeth is an infrequent but highly specific symptom. Ethmoidrhinosinusitis may be associated with orbital symptoms (eg,edema of the eyelid, chemosis), while headache is frequent-ly the most prominent symptom of frontal or sphenoid rhi-nosinusitis.

ExaminationPhysical examination can also offer clues in establishing thediagnosis of rhinosinusitis; however, no one sign is pathog-nomonic for rhinosinusitis. Most primary care physicians arelimited to palpation and visualization of the nasopharyngealarea with an otoscope and transilluminator. Unless it is uni-lateral, tenderness to palpation along the frontal and maxil-lary sinuses is nonspecific. A limited examination of thenasal mucosa can be performed using a nasal speculummounted on a hand-held otoscope. The otoscope can visual-ize nasal edema, hyperemia, nasal deviation, and clear orpurulent nasal (or postnasal) discharge. Purulent secretion,particularly when seen coming from the middle meatus, ispredictive of acute rhinosinusitis. Pale and boggy mucosaoften indicates a chronic inflammatory (allergic) process.

Transillumination of the maxillary and frontal sinusesshould be performed in a darkened room by placing aWelch-Allyn Finnoff transilluminator or small flashlightover the infraorbital rim (for the maxillary sinuses) or belowthe supraorbital rim (for the frontal sinuses). For maxillarysinus evaluation, clinicians must allow their eyes to adjust to the completely darkened room before comparing light

464 JCOM August 2002 Vol. 9, No. 8 www.turner-white.com

RHINOSINUSITIS

Table 1. Diagnoses Presenting as Sinonasal Complaints

Inflammatory, infectiousViral upper respiratory infection (“common cold”)*Bacterial rhinosinusitis*Fungal rhinosinusitis

Inflammatory, noninfectiousAllergic rhinitis (seasonal or perennial)*SarcoidosisWegener’s granulomatosis

NoninflammatoryDrug-induced vasomotor rhinitis (reserpine, alpha blockers,

angiotensin-converting enzyme inhibitors, cocaine)Hormonally mediated conditions (pregnancy, hypothyroidism)Rhinitis medicamentosa (long-term use of topical decongestants)

ObstructionNasal septal deviation*Nasal polyposisForeign bodyTumors (benign or malignant)

*Most prevalent etiologies.

transmitted through the maxillary sinuses to the soft palate.A difference in brightness between the left and right sides ofthe soft palate is considered abnormal. Frontal sinuses canalso be transilluminated by placing a light against the floorof the frontal sinus at the superior medial edge of the orbit.A glow should be transmitted through the anterior wall ofthe sinus. The usefulness of transillumination is limited toruling out maxillary rhinosinusitis—a normal examinationefficiently rules out rhinosinusitis; however, absent or dimin-ished light transmission can be due to rhinosinusitis, sinuspolyps, or congenital absence of a sinus (present in 5% of thepopulation) [10].

Fiberoptic nasolaryngoscopy is not routinely performedin primary care practices, even though it would be an effec-tive means to diagnose a variety of sinonasal as well as pha-ryngeal complaints. A few primary care facilities are rou-tinely teaching and performing fiberoptic nasolaryngoscopyto establish nasopharyngeal diagnoses, determine therapy,and streamline appropriate referrals to otolaryngologists[11,12].

Predictors of SinusitisAlthough many symptoms and signs are interpreted bypatients and their physicians as indicative of rhinosinusitis,only a few of these are useful in diagnosis. Table 2 lists thesigns and symptoms that were found to be predictors ofacute maxillary sinusitis in studies comparing clinical find-ings to a diagnostic reference standard [13–18]. The differ-ences between studies can be attributed to the type of patientpopulation enrolled, the type of diagnostic reference stan-dard, and the specialty of the examining provider.

• Should empiric antibiotic therapy be used for acute rhi-nosinusitis?

Most patients with symptoms of acute rhinosinusitis have aviral infection. Of those who seek care, approximately 10%to 35% will have a bacterial infection [19]. Since a majorityof patients present to a primary care provider with an initialepisode of rhinosinusitis, empiric antibiotic treatment isoften given. Rhinosinusitis was the fifth leading cause forantibiotic prescriptions during ambulatory care visits be-tween 1985 and 1992. During this time period, the numberof prescriptions for acute and chronic rhinosinusitis dou-bled from 5.8 million prescriptions in 1985 to 13 million in1992 [20].

Treatment is aimed at alleviating symptoms, improvingsinus drainage, and eradicating pathogens. An evidence-basedguideline published by the American College of Physiciansrecommends symptomatic treatment for otherwise healthy

patients with mild symptoms [21,22]. Antibiotic therapy is rec-ommended for patients with a high probability of acute bacte-rial rhinosinusitis and moderately severe to severe symptoms.These recommendations are based on the observations thatacute rhinosinusitis resolves without antibiotics in most cases(> 60%) and that antibiotics give a relatively small (15%)absolute increase in treatment response. A cost-effectivenessanalysis compared no antibiotics, empiric antibiotic treat-ment, clinical criteria–guided treatment, and radiography-guided treatment; it showed that empiric antibiotics were cost-effective only for patients with severe or moderately severesymptoms and for patients with mild symptoms in clinicalsettings with extremely high prevalence rates [23]. Com-pared with other strategies, empiric antibiotic therapy result-ed in the shortest duration of illness and the highest curerate, but it also had the highest rate of adverse effects.

Diagnosis and Treatment Given the acute and mild nature of this patient’ssinonasal symptoms, the clinician suspects an acute

viral infection. He advises the patient to continue withhydration and over-the-counter medications (analgesicsand decongestants) to relieve her sinonasal symptoms, andto return to the clinic if her symptoms do not improve orresolve within 10 to 14 days.

CASE STUDY 2 Initial Presentation

A 55-year-old man presents to the clinic with a per-sistent cold for the past 2 weeks. He complains of

nasal stuffiness, pain and pressure in his cheek area, inter-mittent upper tooth pain, and yellow-green dischargedespite use of over-the-counter nasal sprays and cold med-ication.

HistoryHis medical history is remarkable for hyperlipidemia andhypertension. He smokes 1 to 2 packs of cigarettes per day.His current medications include simvastatin and hydro-chlorothiazide.

Physical ExaminationOn examination, the patient appears mildly ill. His temper-ature is 37.5°C and his blood pressure is 144/88 mm Hg. Hehas right maxillary tenderness to palpation and normal lighttransmission through both sinuses. He has a slight rightnasal septal deviation, and his nasal mucosa is slightly ede-matous without erythema. Oropharyngeal examinationreveals discharge of the posterior pharyngeal wall withouttonsillar erythema or exudates. He has no lymphadenopa-thy and results of eye and ear examniations are within nor-mal limits.


CASE-BASED REVIEW

• Do radiologic studies play a role in diagnosing acuterhinosinusitis?

Need for Radiologic AssessmentRadiographic assessment is not necessary for most patientspresenting with an initial episode of acute rhinosinusitis.Acute rhinosinusitis is usually diagnosed clinically, an ap-proach that is more cost-effective than diagnostic testingwith radiographs [23]. Diagnostic testing is recommendedwhen the clinical history and examination make the diagno-

sis uncertain, or when a patient fails an initial course of ther-apy (Table 3). Compared with the gold standard of sinusaspiration and culture, plain film radiographs have a sensi-tivity of approximately 90% and a specificity of 61% for max-illary rhinosinusitis [24–27]. Plain film radiographs of themaxillary sinuses with a single Waters’ view correlates high-ly with the standard 4-view sinus series in diagnosing acutemaxillary rhinosinusitis [28,29]. Findings on plain film indicative of acute rhinosinusitis include opacification,air–fluid levels, or mucosal thickening greater than 6 mm.Plain films do not reliably assess the ethmoid sinuses. Whenclinicians decide to obtain sinus radiographs, they should


RHINOSINUSITIS

Table 2. Symptoms and Signs Predictive of Acute Maxillary Rhinosinusitis

Axelsson Berg Hansen Lindbaek van Duijn Williams(1976) [14] (1998) [15] (1995) [16] (1996) [17] (1992) [18] (1992) [13]

Patient population

Examiner

Diagnostic reference standard

SymptomsCoughDouble sickening

(2 phases in illness history)

Duration of symptoms

Facial pain while bendingAltered sense of smellMalaiseMaxillary facial pain,

unilateralMaxillary toothache

Poor response to OTC medications

Preceding URI or common cold

Purulent or colored rhinorrhea

Examination findingsAbnormal transilluminationPurulent nasal secretionSinus tenderness to

palpation

Note: √ = predictive. CT = computed tomography; ENT = ear, nose, and throat specialist; NA = not assessed; NS = not significant or not predictivein regression analyses; OTC = over the counter; PCP = primary care physician; URI = upper respiratory infection.

Otolaryngo-logy practice

ENT

Sinus radio-graph

√NA

NA

NS√√NS

√ (pain withmastication)

NA

√

√

NANSNA

Emergencyward

ENT

Sinus puncture

NANA

NA

NANSNS√

NA

NA

NA

√

NA√NS

Generalpractice

PCP

Sinus puncture

NSNA

NS(> 1 day)

NSNSNA√

√

NA

NS

√

NA√√

Generalpractice

PCP

CT

NS√

≥ 7 days(80% CTpositive)NSNSNSNS

NS

NA

NS

√

NA√NS

Generalpractice

PCP

Ultrasono-graphy

NSNA

NA

√NSNS√

√

NA

√

√

NANSNS

Generalpractice

PCP

Sinus radio-graph

NSNA

NS

NANSNSNS

√

√

NS

√

√√NS

evaluate and improve their own efficiency by comparingsystematically their physical examination results to the sinusradiograph results.

Computed tomography (CT) of the sinuses is a more sen-sitive test for rhinosinusitis (90% to 100% sensitive), but it haspoor specificity (approximately 60%). In patients with anuncomplicated viral upper respiratory infection, or “com-mon cold,” 95% had abnormalities on CT [30]. Rhinoviruswas isolated from 27% of subjects. The patients in this studywere not evaluated with sinus puncture to assess whetherthey had concomitant bacterial infection. For patients withpersistent sinonasal complaints despite 2 adequate antibiot-ic courses for rhinosinusitis, a CT may be helpful in estab-lishing anatomic abnormalities prior to referral to an oto-laryngologist. Magnetic resonance imaging (MRI) is notwidely used but may be helpful to the otolaryngologist indifferentiating soft-tissue tumors from inflammation and fordiagnosing fungal rhinosinusitis.

• Are cultures of nasal secretions helpful in distinguish-ing bacterial from viral rhinosinusitis?

The results of cultures of nasal secretions do not correlatewith the results of cultures of sinus antral aspirates (Table 4).Thus, nasal cultures are not useful in distinguishing the type

of rhinosinusitis. Although sinus aspiration and culture isthe research gold standard for establishing rhinosinusitis, itis recommended clinically only when sinus drainage isessential and for guiding antibiotic therapy in patients withcomplicated or refractory rhinosinusitis.

• What is the efficacy of antibiotic therapy for acute rhino-sinusitis?

• Which antimicrobial agents should be prescribed asinitial therapy for acute rhinosinusitis?

Antibiotic Therapy for Acute RhinosinusitisA meta-analysis of 6 trials comparing antibiotics to placebofor uncomplicated acute rhinosinusitis showed that antibi-otics were significantly more effective in reducing treatmentfailures by almost half (risk ratio, 0.54 [95% confidence inter-val {CI}, 0.37–0.79]). Interestingly, in the placebo group sinusi-tis symptoms were improved or disappeared in 69% (95% CI,57%–79%) of patients [31]. The variability in trial outcomesmay be due to differences in the diagnostic criteria each studyused, that is, whether the diagnosis of sinusitis was based onclinical symptoms or on stricter criteria, such as abnormalitieson examination, radiographs, or microbiology samples. Trialsthat enrolled sinusitis patients based on clinical criteria were


CASE-BASED REVIEW

Table 3. Performance and Cost of Radiologic Imaging

Imaging Sensitivity SpecificityTechnique Cost, $* (range or 95% CI) (range or 95% CI)

Waters’ view radiograph

Radiograph (3 views)

Ultrasonography

Computed tomography

Magnetic resonance imaging

CI = confidence interval. (Adapted from Conde MV, Williams JW,Witsell DL, Piccirillo JF. Management of a 35-year-old man with acutenasal and sinus complaints. J Clin Outcomes Manage 1998;5(3):63–76. Data for radiograph and ultrasonography are from Engels EA,Terrin N, Barza M, Lau J. Meta-analysis of diagnostic tests for acutesinusitis. J Clin Epi 2000;53:852–62.)

*Costs reports are national averages for Medicare-allowable chargesfrom 1 July 1999 to 30 June 2000 for procedure only; cost of inter-pretation not included.

Table 4. Microbial Causes of Acute Rhinosinusitis in Adults

Organism Detected on Culture, %

Sinus Aspiration* Nasal Swab†

Streptococcus 20–43 7.2 penicillin sensitivepneumoniae 4.0 pencillin interme-

diate or resistantHaemophilus 22–35 21.7

influenzaeMoraxella 2–10 28.9

catarrhalisStreptococcus 3–9 NR

speciesAnaerobes 0–9 NRStaphylococcus 0–8 17.9

aureusOther 4 NR

NR = not reported.

*Data are from Antimicrobial treatment guidelines for acute bacterialrhinosinusitis. Sinus and Allergy Health Partnership. Otolaryngol HeadNeck Surg 2000;123:S4–S31.†Data are from Sokol W. Epidemiology of sinusitis in the primary caresetting: results from the 1999–2000 respiratory surveillance program.Am J Med 2001;111:19S–24S.

39.17

58.87

137.58

268.89

412.19

85% (range,61%–93%)

90% (95% CI,68%–97%)

84% (95% CI,75%–90%)

Unknown butprobably ≥ 95%

Unknown butprobably ≥ 95%

80% (range,62%–94%)

61% (95% CI,20%–91%)

69% (95% CI,57%–79%)

61% (range,58%–84%)

Unknown

more likely to find no benefit from antibiotics; trials withtighter definitions for sinusitis were likely to find a greaterbenefit from antibiotics and to have a lower spontaneousimprovement rate in the placebo group [31,32].

In adults, the most common bacterial pathogens are S. pneu-moniae (35%) and H. influenzae (35%) [19] (Table 4). S. pyogenes,M. catarrhalis, and anaerobic bacteria each account for a smallpercentage of bacterial sinus infections. Fungal infectionsrarely occur in immunocompetent hosts. Since randomizedcontrolled trials have shown similar efficacy for many antibi-otics, selection is based on cost, dosing schedules, and side-effect profiles [32,33] (Table 5). In general, initial 10-day thera-py with amoxicillin 500 mg 3 times daily or trimethoprim-sulfamethoxazole 160/800 mg twice daily is appropriate.Antibiotics currently approved by the Food and Drug Administration for the treatment of rhinosinusitis includeamoxicillin-clavulanate, clarithromycin, cefprozil, cefuroximeaxetil, ciprofloxacin, loracarbef, levofloxacin, cefpodoxime

proxetil, cefdinir, gatifloxacin, and moxifloxacin. Physiciansshould stay attuned to the developing data on antibiotic-resistant organisms, which may make it necessary to revisethese recommendations.

The duration of therapy in acute maxillary rhinosinusitiswas evaluated in a study comparing 3-day versus 10-daytrimethoprim-sulfamethoxazole plus oxymetazoline nasalspray. Both groups showed equal improvement in clinicalsymptoms and radiograph scores at the 2-week follow-up;furthermore, symptomatic relapse and recurrence were sim-ilar [34].

β-Lactamase–producing strains of H. influenzae andM. catarrhalis are amoxicillin resistant but are not prevalent in previously untreated adults with acute rhinosinusitis(Table 4) [25,35,36]. β-Lactamase–producing strains vary byregion. Providers should ask the local microbiology laboratoryfor the percentage of strains that are β-lactamase positive. Theincrease of β-lactamase–producing strains means that patients


RHINOSINUSITIS

Table 5. Antibiotic and Adjuvant Therapy for Rhinosinusitis

Antibiotic Number of(Brand Name) Dose Frequency Duration Pills Cost, $*

First-line agentsAmoxicillin (generic) 500 mg TID 10 days 30 11.81Trimethoprim- 160 mg/ 800 mg BID 10 days 20 18.06

sulfamethoxazole(generic, Septra DS, or Bactrim)†

Second-line agentsAmoxicillin- 875/125 mg BID 10 days 20 112.260

clavulanate (Augmentin)Azithromycin (Zithromax)† 500 mg day 1, QD 05 days 06 43.09

250 mg days 2–5Cefaclor (Ceclor)† 250–500 mg TID 10 days 30 116.850Cefuroxime axetil (Ceftin) 250 mg BID 10 days 20 88.20Cefpodoxime proxetil (Vantin) 200 mg BID 10 days 20 103.990Cefprozil (Cefzil) 250–500 mg BID 10 days 20 84.17Cefdinir (Omnicef) 600 mg QD 10 days 10 85.63Clarithromycin (Biaxin) 250–500 mg BID 10 days 20 82.56Clindamycin 3 150 mg capsules QID Up to 6 weeks 6720 539.400Ciprofloxacin (Cipro) 500 mg BID 10 days 20 103.170Gatifloxacin (Tequin) 200–400 mg QD 10 days 10 89.55Levofloxacin (Levaquin) 500 mg QD 10 days 10 96.06Loracarbef (Lorabid) 400 mg BID 10 days 20 127.580Moxifloxacin (Avelox) 400 mg QD 10 days 10 94.23Metronidazole‡ 500 mg BID Up to 6 weeks 1120 35.84

BID = twice daily; QD = every day; TID = 3 times daily.

*Average wholesale prices are from 2002 Drug Topic Red Book. Montvale (NJ): Thomson Medical Economics; 2002.†Not approved by the Food and Drug Administration for the treatment of acute sinusitis.‡Use with macrolide antibiotic for treatment of chronic rhinosinusitis.

who do not respond to therapy with amoxicillin should beswitched to an antibiotic with β-lactamase activity.

• Which ancillary therapies should be offered?

Adjunctive or nonantibiotic therapy for the treatment of rhi-nosinusitis has not been widely studied (Table 6). Nasalhumidification with saline nasal spray or a humidifier isoften recommended to moisturize the nasal mucosa andreduce crusting. Humidifiers should be cleaned regularly

because they can cause exacerbation of symptoms in somepatients with mold allergy.

Oral or topical decongestants are frequently prescribed toreduce mucosal swelling. Many trials of antimicrobial treat-ment of rhinosinusitis are confounded by use of deconges-tants [9]. One study compared a nasal decongestant alone,decongestant plus sinus irrigation, and decongestant plus an8- to 10-day course of antibiotics in patients with acute max-illary rhinosinusitis. Antibiotics and sinus irrigation resultedin greater radiographic improvement, but the clinicalresponse was not statistically significant compared withdecongestant alone [37]. Topical decongestants have an


CASE-BASED REVIEW

Table 6. Nonantibiotic Therapy for Rhinosinusitis

Treatment Number of(Brand Name) Dose Frequency Bottles/Pills Cost, $*

HumidificationNasal saline spray 2 or 3 sprays As required 1 2.73Humidifier 1 22.00

DecongestantsTopical

Oxymetazoline (Afrin) 2 or 3 sprays BID 1 4.68Xylometazoline (Otrivin) 2 or 3 sprays BID 1 5.86Phenylephrine (Neo-Synephrine) 1 or 2 sprays Every 4 hr 1 3.59

OralPseudoephedrine 30 to 60 mg Every 4–6 hr 30 0.96–1.50Pseudoephedrine XR 120 mg BID 20 6.64

Mucolytic agentGuaifenesin 600 mg BID 60 24.22

Antihistamines, nonsedatingDesloratadine (Clarinex) 5 mg QD 30 65.75Fexofenadine (Allegra) 180 mg QD 30 70.55Loratadine (Claritin) 10 mg QD 30 94.07

Corticosteroids, topicalBeclomethasone (Beconase, 2 sprays BID 1 47.15

Vancenase)Beclomethasone Aqueous 2 sprays BID 1 58.56

(Beconase AQ, Vancenase AQ)Beclomethasone Aqueous 2 sprays BID 1 53.33

(Vancenase AQ)Flunisolide (Nasalide) 2 sprays BID–TID 1 52.24Flunisolide (Nasarel) 2 sprays BID–TID 1 48.95Fluticasone propionate (Flonase) 2 sprays QD 1 61.91Mometasone (Nasonex) 2 sprays QD 1 66.13Budesonide (Rhinocort) 2 sprays BID 1 46.15Budesonide Aqueous (Rhinocort Aqua) 2 sprays BID 1 64.39Triamcinolone (Tri-Nasal) 2–4 sprays QD 1 55.68Triamcinolone (Nasocort, Nasocort AQ) 2–4 sprays QD 1 61.59

BID = twice daily; QD = every day; TID = 3 times daily.

*Average wholesale prices are from 2002 Drug Topic Red Book. Montvale (NJ): Thomson Medical Economics; 2002.

advantage over systemic decongestants since they are lesslikely to cause systemic effects in patients with hypertension,hyperthyroidism, ischemic heart disease, or diabetes or inthose on monoamine oxidase inhibitors. However, prolongeduse of topical decongestants can cause rebound edema orvasomotor rhinitis. No controlled trials have been done com-paring the benefit of topical or systemic vasoconstrictors inrhinosinusitis.

Antihistamines are not usually recommended because oftheir anticholinergic effects, which can potentially dry outsecretions. However, the newer second-generation antihista-mines may be prescribed in patients with rhinosinusitis anda history of allergic rhinitis.

Mucoevacuants such as guaifenesin have been promot-ed for the prevention and treatment of rhinosinusitisbecause they thin mucus, which promotes clearing. Oneplacebo-controlled, double-blind study of patients withHIV infection and either acute or chronic rhinosinusitisfound that guaifenesin reduced nasal congestion and post-nasal drainage [38].

Diagnosis and Initial TreatmentThe patient’s history and examination reveal a highlikelihood of rhinosinusitis. The physician prescribes

a 10-day course of amoxicillin and a decongestant anddecides not to order sinus radiographs. The patient noticesimprovement of his symptoms within 5 days of starting treat-ment.

• What changes should be made to therapy if symptomsworsen on initial treatment?

• Does a longer duration of symptoms change the choiceof antimicrobial agent or the length of treatment?

In most cases the initial therapeutic intervention shouldresult in clinical cure, and no specific follow-up will be need-ed. However, patients who do not improve or who developrecurrent disease need further evaluation and therapy. Ifresponse to therapy is partial or incomplete, a second courseof antibiotics with activity against β-lactamase–producingstrains is recommended. Most studies show that patients’recognition of their own improvement precedes radiologicimprovement. Further radiologic tests (plain film or CT) areoften encouraged in a patient with persistent sinonasalsymptoms. Completely normal radiographs make bacterialrhinosinusitis very unlikely. Sinus radiographs are useful toevaluate persistent symptoms; normal sinus radiographsmake acute or chronic rhinosinusitis unlikely. In patientswith consistent symptoms and an abnormal radiograph, a

14- to-21-day course of a broad spectrum antibiotic effectiveagainst β-lactamase–producing organisms should be pre-scribed.

Rhinosinusitis is often categorized into 4 types based onsymptom duration: acute, subacute, recurrent, and chronic.Acute rhinosinusitis is defined as the presence of sinonasalsymptoms for 4 weeks or less. Subacute rhinosinusitis isdefined as symptoms lasting 4 to 12 weeks. These patientsmay or may not have been treated for acute rhinosinusitis;however, the symptoms usually resolve with effective thera-py. The microbiology of subacute rhinosinusitis is similar tothat of acute rhinosinusitis in the early phase and chronic rhi-nosinusitis when symptom duration approaches that ofchronic rhinosinusitis. Therefore, empiric treatment can con-sist of first-line antibiotics for a slightly longer duration (eg,14 to 21 days). Patients who fail to improve after 5 to 7 daysof therapy can be switched to second-line antibiotics.Radiologic examination of the sinuses is not warrantedexcept for treatment failures.

Patient Course Over Next Year The patient improves after treatment with antimi-crobial therapy. He presents to his primary care

provider 3 more times over the following year with moder-ately severe sinus symptoms similar to his last presentation.All episodes respond to antibiotic therapy. He has had a coldfor the past month, and he presents today because he mayneed another course of antibiotics. He continues to smokecigarettes. Upon further questioning, he complains of nasalcongestion that is worse at night and after awakening andthat improves during the daytime. On examination, he againhas right maxillary tenderness, purulent nasal discharge,right septal deviation, and mucosal edema.

• Does the patient have recurrent or chronic rhinosinusitis?

Recurrent rhinosinusitis consists of 4 or more episodes ofacute rhinosinusitis per year, with complete resolution aftereffective medical therapy, and usually a symptom-free periodof at least 8 weeks between attacks. The microbiology of recur-rent rhinosinusitis is similar to that of acute rhinosinusitis.

Chronic rhinosinusitis is defined as symptoms lastinglonger than 12 weeks. It affects 5% to 15% of the urban pop-ulation, or more than 31 million individuals [39]. Acute exac-erbations of chronic rhinosinusitis are defined as worseningof rhinosinusitis symptoms with return to baseline symp-toms after treatment [4]. The most common symptoms ofchronic rhinosinusitis are nasal congestion and nasalobstruction; less frequent symptoms are facial pressure andpostnasal discharge. Environmental, systemic, and local host


RHINOSINUSITIS

issues may predispose individuals to develop chronic rhi-nosinusitis. Indoor and outdoor environmental pollution is asignificant factor in the development of chronic rhinosinusi-tis and asthma. Smoking causes both ciliary loss and cyto-logic changes in nasal mucosa [40]. A definitive link betweensmoking and chronic rhinosinusitis has not been established;however, smoking increases the risk of recurrent infections,especially following sinus surgery, thus increasing the like-lihood of requiring subsequent reoperation [41]. Allergyexposure may be a predisposing factor for chronic rhinosi-nusitis since it causes nasal edema, which can result in sec-ondary obstruction of the osteomeatal complex and affectthe maxillary, anterior ethmoid, and frontal sinuses.

Local host factors include congenital or acquired immun-odeficiency. For example, selective IgA deficiency or hypo-gammaglobulinemia, cystic fibrosis, AIDS, sarcoidosis, andprimary ciliary dyskinesia significantly increase develop-ment of rhinosinusitis [42–44]. The incidence of rhinosinusi-tis in persons with asthma has been estimated to range from40% to 75%. The direct causal factor is unknown, but studieshave shown that medical and surgical treatment of rhinosi-nusitis results in improvement, subjective and objective, ofasthma [45]. Finally, some patients with asthma and nasalpolyposis have a sensitivity to aspirin; this disorder, calledSamter’s triad, is frequently associated with both severe rhi-nosinusitis and asthma and has a familial tendency [46].Therefore, some physicians advise patients with nasal poly-posis and asthma to avoid ingestion of aspirin and non-steroid anti-inflammatory drugs.

• Do radiologic studies play a role in diagnosing recur-rent or chronic rhinosinusitis?

For patients with recurrent or chronic sinonasal symptoms(eg, after 2 adequate antibiotic courses for rhinosinusitis), CTmay help confirm the diagnosis of rhinosinusitis and establishwhether anatomic abnormalities are present. The decision toobtain CT before referral should be made with input from theotolaryngologist because some will be able to use only naso-laryngoscopy to complete their consultation. If CT is used toaid in the diagnosis of rhinosinusitis, it is best to perform thetest 2 weeks after a viral upper respiratory infection or 6 weeksafter an episode of acute bacterial rhinosinusitis since acutechanges on CT persist during those time periods.

• Which antimicrobial agents should be prescribed astherapy for recurrent or chronic rhinosinusitis?

Antimicrobial Therapy for Chronic RhinosinusitisBecause recurrent rhinosinusitis often responds similarly toantibiotics for acute rhinosinusitis, it is unclear whetherrecurrent rhinosinusitis differs from isolated episodes ofacute rhinosinusitis (thus warranting a separate classifica-tion) or merely represents the chance occurrence of severaldiscrete episodes of acute rhinosinusitis. Empiric therapywith first-line antibiotics for 7 to 10 days can be initiated, butoften second-line antibiotics are prescribed when recur-rences are frequent or symptom duration becomes chronic.

Anaerobes, coagulase-negative and coagulase-positivestaphylococci, and gram-negative organisms are more com-mon in chronic rhinosinusitis [35]. Patients with chronic rhi-nosinusitis are often prescribed a 3-week to 6-week course ofantibiotic therapy with activity against Staphylococcus,Streptococcus, anaerobes, M. catarrhalis, Pseudomonas aeruginosa,and Klebsiella pneumoniae. Therapy is prolonged in chronic rhi-nosinusitis because of poor mucociliary clearance, mucosalhypertrophy, or bony involvement. In the absence of trial data,experts recommend continued treatment until the patient feelswell plus 7 days. Broad-spectrum antibiotics, such as cefurox-ime axetil, amoxicillin-clavulanate, clarithromycin, and lev-ofloxacin, are often prescribed. Topical or oral corticosteroidsmay be useful to reduce mucosal edema and improve mucocil-iary clearance. Treatment failures or recurrences after a briefasymptomatic phase can be treated with a second course ofantibiotics, either the same antibiotic or one with a differentspectrum of activity. Failure to respond may indicate the pres-ence of an anaerobic infection. Several species are often isolat-ed, including those of the Peptostreptococcus, Bacteroides, Fuso-bacterium, and Corynebacterium genera. Metronidazole andclindamycin are appropriate for these types of infections.Allergic fungal rhinosinusitis accounts for 2% to 7% of chronicrhinosinusitis, most commonly in severe atopic or asthmaticindividuals [47]. Treatment consists of a combination of surgi-cal intervention for aeration of the sinus with use of anti-inflammatory therapies, including oral and topical cortico-steroids [9].

• Which ancillary therapies should be offered for chron-ic rhinosinusitis?

• What advice can patients be given for preventing orrelieving chronic sinus symptoms?

The use of corticosteroids in patients with rhinosinusitis iscontroversial. Corticosteroids may be useful because of theirability to reduce mucosal swelling, thereby facilitatingdrainage of the sinuses. Because topical corticosteroids have


CASE-BASED REVIEW

been proved effective in shrinking nasal polyps and treatingallergic and nonallergic rhinitis, many clinicians postulatethat corticosteroids are essential in the treatment of all typesof rhinosinusitis; however, few controlled trials support this.One trial using flunisolide versus placebo as an adjunct toantibiotic therapy (amoxicillin/clavulanate) for acute rhino-sinusitis showed improvement of symptoms and a trendtoward greater regression of radiologic abnormalities in thecorticosteroid group compared with placebo spray [48]. Theaddition of a 21-day treatment of intranasal corticosteroidsto 10-day antimicrobial therapy and a 3-day course of a top-ical decongestant has been shown to improve the clinicalsuccess rate and accelerate recovery of patients with historyof chronic rhinitis or recurrent rhinosinusitis who present fortreatment of acute rhinosinusitis [49].

Patients on immunotherapy who develop recurrent orchronic sinus disease should continue with treatment. Pro-fessional organizations’ recommendations for the treatmentof rhinosinusitis are summarized in Table 7.

The following comfort measures may be helpful in reliev-ing the symptoms of rhinosinusitis, and can be recommend-ed to patients with chronic symptoms: get adequate rest,increase hydration, humidify the home and work environ-

ments, use analgesics and/or warm facial packs for pain,and sleep with the head of the bed elevated. Prevention mea-sures include treatment of allergies and upper respiratoryinfections and avoidance of cigarette smoke, pollution, baro-trauma, and diving/swimming. Instruct patients to phone ifsymptoms worsen (eg, severe headache or high fever) or donot begin to resolve within 5 to 7 days of treatment [45].

• When is it appropriate to refer the patient to a specialist?

Indications for ReferralComplications from rhinosinusitis are extremely rare. Whetherthe low complication rate is due to a benign natural history orthe widespread use of antibiotics is unknown. Direct spread ofinfection from the sinus to skin, bone, or cranial sites can occur.Precise incidence rates are unavailable, but at one center suchcomplications occurred in 5.4% of patients hospitalized foremergent rhinosinusitis [50]. Patients with acute febrile illness,toxic appearance, change in mental status, cranial nerve defi-ciencies, or seizures should be suspected of having complica-tions. These include orbital cellulitis, intracranial abscess, subperiosteal abscess, meningitis, and cavernous sinus throm-bosis. Osteomyelitis of the frontal bone, also known as Pott’spuffy tumor, is associated with chronic rhinosinusitis. Presenceof skin erythema or severe facial pain requires urgent consul-tation within 24 hours. Suspicion of intracranial or orbitalspread indicates an emergency referral. Emergent CT and oph-thalmic examination aid in diagnosis.

Referral is indicated for those who fail 2 adequate trials ofantibiotic therapy, those with recurrent acute rhinosinusitis,and those who have chronic persistent sinonasal symptomsdespite at least 8 weeks of nasal corticosteroids, deconges-tants, or antihistamines. In addition, referral is appropriatefor complications of rhinosinusitis, including otitis media,nasal polyps, asthma, bronchiectasis, or bronchitis (Table 8).

• Should the patient see an allergist, otolaryngologist, orboth?

A detailed evaluation for allergic rhinitis or immunodefi-ciencies by an allergist/immunologist may identify impor-tant predisposing causes. Allergic rhinitis can be confirmedwith skin testing with dust and tree and weed pollens. Anatopic individual who fails environmental control and phar-macotherapy may need immunotherapy. However, there areno controlled trials demonstrating the efficacy of allergenimmunotherapy in preventing rhinosinusitis. The workupof immunodeficiency entails measurement of quantitative


RHINOSINUSITIS

Table 7. Guideline Summary of Medical Treatment Options inAcute Rhinosinusitis

American College of Physicians–American Society of InternalMedicine [21,22]

Mild symptoms: symptomatic treatment with antipyretics, analgesics,and decongestants; patient reassurance and education of chosenmanagement strategy

Moderately severe symptoms (defined as symptoms for fewer than7 days with maxillary facial pain or maxillary tooth pain and purulent nasal discharge): narrow-spectrum antimicrobial agent forStreptococcus pneumoniae and Haemophilus influenzae (eg, amoxi-cillin, trimethoprim-sulfamethoxazole, doxycycline)

Severe symptoms (regardless of duration): antibiotic therapy as out-lined above; also consider risk factors that may predispose toantibiotic-resistant bacteria (eg, recent antibiotics, day care)

American Academy of Otolaryngology-Head and Neck Surgery [8]Beneficial in all cases: humidification, saline nasal sprays, mucolytic

agents, decongestants, antibiotics (choice should be based on dos-ing schedule, side effects, history of drug allergy, history of previousantibiotic therapy, and local resistance patterns of pathogenicorganisms)

Beneficial in some cases: antihistamines, ipratropium bromide nasalspray, steroid nasal sprays

Joint Council of Allergy, Asthma, and Immunology [45]Acute rhinosinusitis: humidification, decongestants, antibiotic therapy

(amoxicillin, trimethoprim-sulfamethoxazole), and possibly mucolyticagents

Underlying allergic rhinitis or bronchial hyperresponsiveness: antihist-amines and steroid nasal sprays

serum IgG, IgA, and IgM and assessment of specific anti-body responses to protein and polysaccharide antigens (eg,tetanus toxoid or pneumovax). For the referring physician,consultants can clarify the allergic, immunologic, or nonal-lergic etiologic basis for chronic rhinosinusitis; identify spe-cific allergens or other triggers for chronic sinus symptoms;assist in developing an effective treatment plan, includingpatient education, allergy avoidance, pharmacotherapy,antimicrobial therapy, and immunotherapy as appropriate;and provide preparation of extracts for immunotherapy [45].

Referral to an otolaryngologist is useful for assessinganatomic factors that may contribute to chronic rhinosinusi-tis symptoms, biopsy, and surgical management. Sinus end-oscopy performed as an outpatient allows complete visual-ization of the nasopharynx and attainment of material forbacteriologic culture. Anatomic details that may be missedon CT scan can be seen on nasal endoscopy. Since CT exam-ination can be normal in some symptomatic patients andabnormal in asymptomatic patients, many physicians con-sider endoscopic examination essential for diagnosis andtreatment of sinus disease. As a result, they refer patients forCT scan only when endoscopy fails to explain symptoms orfor staging purposes prior to sinus surgery [51]. Biopsy ofnasal mucosa is helpful for assessing granulomatous dis-ease, neoplasms, ciliary dyskinesia, or fungal infections.Maxillary antral puncture for culture and relief of pain maybe useful prior to surgical interventions.

Absolute indications for surgery for rhinosinusitis includeacute complicated rhinosinusitis (subperiosteal or orbitalabscess, Pott’s puffy tumor, brain abscess or meningitis), mas-sive nasal polyposis, mucocele or mucopyocele, invasive orallergic fungal sinusitis, tumors causing sinonasal obstruction,and cerebrospinal fluid rhinorrhea [52]. Surgery is also indi-cated and efficacious for patients with chronic rhinosinusitiswho do not respond to medical therapy. Traditional open sur-gical approaches (eg, Caldwell Luc procedure) involved strip-ping of the mucosal lining; however, current techniques con-sist of limited transnasal endoscopic approaches. Functionalendoscopic sinus surgery (FESS) aims to restore mucociliaryclearance by removing bony sinus partitions and polypoidmucosa. Usually this entails endoscopic widening of the max-illary and ethmoid ostia, plus reduction of the middle turb-inate. Early postoperative follow-up involves endoscopicdebridement at weekly intervals and prolonged medical ther-apy is important in reducing inflammation and restenosis[53,54]. Surgical complications are infrequent, affecting 0.5% ofpatients; these include hemorrhage, permanent damage tovision, and cerebrospinal fluid leak [9].

For the referring physician, otolaryngologists can assessthe need for surgical revision of abnormal anatomy and thelikelihood that surgery will improve chronic sinus disease,determine whether an adequate trial of medical, allergic, or

immunologic therapy has been provided prior to surgery,recommend the specific procedure(s) for individual patientsand alternative approaches, and counsel patients on the risksof the proposed procedure [45].

Additional Treatment and ReferralThe clinician conducts a thorough history and physi-cal examination to assess for factors that would pre-

dispose the patient to recurrent rhinosinusitis episodes. Aplainfilm sinus radiograph reveals findings consistent with acuterhinosinusitis. Given the previous antibiotic treatments, theclinician prescribes a 10-day course of a second-line antibiotic,a 3-day course of a topical nasal decongestant, and a 21-daycourse of a topical corticosteroid. They discuss his use of tobac-co products, and after counseling the patient elects to enroll ina smoking cessation program. In addition, since the patient hashad multiple recurrences within the past year, the physicianrecommends further evaluation by an otolarynologist.

Corresponding author: Rowena J. Dolor, MD, MHS, Duke UniversityMedical Center, 2400 Pratt St., Durham, NC 27705; [email protected].

Financial support: None.

Author contributions: conception and design, RJD; drafting of thearticle, RJD, JWW; critical revision of the article for important intel-lectual content, JWW; final approval of the article, RJD, JWW.

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CASE-BASED REVIEW

Table 8. Rhinosinusitis Referral Indications

Allergy/immunologyDifferentiation of allergic, immunologic, or nonallergic etiology for

recurrent or chronic symptomsIdentification of allergens or other triggers for persistent sinonasal

complaintsAssistance in developing treatment plan (patient education, aller-

gen avoidance, medications, and if needed, immunotherapy)Otolaryngology

EmergentSuspected orbital or intracranial spread

UrgentSkin erythema or severe facial painFrontal or sphenoid rhinosinusitis

NonurgentSymptoms despite 2 adequate trials of antibiotic therapyRecurrent acute rhinosinusitisChronic sinonasal symptoms despite ≥ 8 weeks of deconges-

tants, antihistamines, or topical corticosteroids

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CASE-BASED REVIEW

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EVALUATION FORM: Management of Rhinosinusitis in Adults: Clinical Applications of Recent Evidenceand Treatment Recommendations

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