Acute Rhino Sinusitis

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CLINICIANS CORNERCLINICAL CROSSROADS

CONFERENCES WITH PATIENTS AND DOCTORS

A 51-Year-Old Woman With Acute Onsetof Facial Pressure, Rhinorrhea, and Tooth PainReview of Acute RhinosinusitisPeter H. Hwang, MD, Discussant

DR REYNOLDS: Mrs D is a 51-year-old woman with a historyof seasonal allergies who presented with 5 days of upper res-piratory tract infection symptoms and facial pain.

Mrs D is in good health but has been spending time in alarge medical center recently, visiting her husband, whois un-dergoing chemotherapy. About 5 daysbefore presentation, shenoticed the onset of watery eyes, sneezing, chest congestion,nasal mucus production, and myalgias. She thought she hada cold. After a few days she began having pain in her left fore-head, under her eye, and near her left upper teeth (she doesnot have dental problems). She did not have a cough or fe-ver.Her nasal discharge,initially clear, becamegreen. She wasconcerned about transmitting a sinus infection to her immu-nocompromised husband. She did not take any over-the-counter medications for her symptoms.

Mrs D has a history of seasonal allergies. She previouslysaw an allergist who prescribed several years of injections;she then took prescription allergy medication but stopped2 years ago. She now uses nonprescription loratadine asneeded during the allergy season. She typically does not getallergy symptoms during the winter.

Mrs D has had a number of sinus infections diagnosedand treated with antibiotics over the years, the last occur-ring approximately 2 years ago. She has always been pre-scribedantibiotics when she has presented with these symp-toms in the past.

Mrs Ds medical history is significant for hypertension, os-teoarthritis, anda partial nephrectomy fora benigntumor. Hermedications include atenolol, hydrochlorothiazide, raniti-dine, and glucosamine and chondroitin. Mrs D moved to the

UnitedStatesin the1970sfrom Haiti.Shehas3 grown,healthychildren; she does not smoke tobacco, drink alcohol, or userecreational drugs. She has commercial medical insurance.

On physical examination, Mrs D had a blood pressure of138/78 mm Hg and a temperature of 96.0F (35.6C). Shelooked well and was in no acute distress. Her conjunctivae

This conference took place at the Medicine Grand Rounds at Beth Israel Deacon-

ess Medical Center, Boston, Massachusetts, on January 31, 2008.Author Affiliations:Dr Hwangis AssociateProfessor, Departmentof OtolaryngologyHead and Neck Surgery, Stanford University School of Medicine, Director, Stan-ford Sinus Center, and Director, Fellowship in Rhinology and Sinus Surgery, De-partment of OtolaryngologyHead andNeck Surgery,StanfordUniversity MedicalCenter, Stanford, California.Corresponding Author: Peter H. Hwang, MD, Department of Otolaryngology, 801Welch Rd, Stanford, CA 94305 ([email protected]).Clinical Crossroads at Beth Israel Deaconess Medical Centeris produced anded-ited by Risa B. Burns, MD,series editor; TomDelbanco,MD, HowardLibman,MD,Eileen E. Reynolds, MD, Amy N. Ship, MD, and Anjala V. Tess, MD.Clinical Crossroads Section Editor: Margaret A. Winker, MD, Deputy Editor.

Acute rhinosinusitisisa commonailmentaccountingformil-

lions of officevisits annually,including that of MrsD, a 51-

year-old woman presenting with 5 days of upper respira-

tory illness and facial pain. Her case is used to review the

diagnosis and treatment of acute rhinosinusitis. Acute vi-

ral rhinosinusitis can be difficult to distinguish from acute

bacterial rhinosinusitis, especially during the first 10 days

ofsymptoms.Evidence-basedclinical practiceguidelinesde-

velopedto guide diagnosis andtreatment of acute viral and

bacterialrhinosinusitisrecommendthat thediagnosisof acute

rhinosinusitis be based on thepresenceof cardinalsymp-

toms of purulent rhinorrhea and either facial pressure or

nasalobstruction of lessthan 4 weeks duration.Antibiotic

treatmentgenerally canbe withheld during thefirst 10 days

of symptoms for mild to moderate cases, given the likeli-

hoodofacuteviralrhinosinusitisorofspontaneouslyresolv-

ing acute bacterial rhinosinusitis. After 10 days, the likeli-

hood of acute bacterial rhinosinusitis increases, and initia-

tionof antibiotic therapyissupportedby practiceguidelines.

Complications of sinusitis, thoughrare, canbe serious and

require early recognition and treatment.

JAMA. 2009;301(17):1798-1807 www.jama.com

See also Patient Page.

CME available online at www.jamaarchivescme.comand questions on p 1833.

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were clear and without erythema. She had tenderness onpalpation over the left frontal and maxillary sinuses but nopain on palpation over her teeth and gums. She had mini-mal swelling below her left lower eyelid. Her nasal exami-nation showed white rhinorrhea. Her pharynx did not showerythema. Her lungs were clear and her cardiovascular ex-

amination results were normal.MRS D: HER VIEW

About a week ago, I was having a headache, felt very tired,and thought I was coming down with something, but I didntknow what it was. On Sunday I woke up with stuffy noseand watery eyes; headaches again. I felt like I had tooth-ache. And I thought, no, I know its not a toothache, I donthave anything wrong with my teeth. So I thought it mustbe a sinus infection that Im coming down with.

It was hurting on the whole side of my face, and then Icould see the puffiness under my eyes. Its like Im almostdeaf in one ear. Talking on the phone, I can hardly hear whatthe other person is saying. Thats how bad it can get.

What was coming out of my nose was clear at first, thenafter a few days it started to have a greenish color. Thatswhen I thought, definitely, its a sinus infection, and I needmedical attention.

In the past, when I had sinus infections, it usually hap-pened when I was at work. I couldnt concentrate at all, be-cause my head felt like it was going to explode any minute.But lately its been different symptoms. Basically, you canmistake it for a cold, or you might even think its allergiesbecause it starts with itchy eyes, itchy throat.

Allergies are usually temporary. I could go to bed withitchy eyes or an itchy throat, and by next morning its gone,so I know its allergies. A sinus infection lasts a long time.

Im used to having sinus infections and I know when Ihave one. I had one 2 years ago. So on my way to the doc-tor, I knew I was goingto ask for antibiotics, because theresno way I can treat this without having medication. With thattype of sinus infection, I dont think [pseudoephedrine hy-drochloride] or anythingover the counter would havehelpedme. Thats my own opinion, my situation.

I would like to knowwhatthe difference is between a com-mon cold and a sinus infection. Where does a sinus infec-tion come from? How do you get it? What triggers it?

QUESTIONS FOR DR HWANG

How can a physician diagnose acute rhinosinusitis based on

patient history and physical examination? What is the mi-crobiology of acute sinusitis? What are the indications, ifany, for imaging or endoscopy in patients with symptomsof acute sinusitis? How effective are antibiotics in the treat-ment of acute rhinosinusitis and what regimens, if any, doyou recommend for first-line treatment? What nonphar-macological treatments are effective? What complicationsof acute rhinosinusitis should primary care physicians lookfor? What do you recommend for Mrs D?

DR HWANG: Acute rhinosinusitis is defined as sympto-matic inflammation of the mucosa of the nasal cavity andparanasal sinuses lasting less than 4 weeks in duration. Be-cause the inflammatory condition almost always extends be-yond the sinus cavities to involve the nasal cavity as well,1,2

the term rhinosinusitis is preferred to sinusitis.

Each year, more than 20 million US adultsare diagnosedashavingacutebacterial rhinosinusitis.3 Thediagnosisandtreat-ment ofrhinosinusitis account foran estimated$5.8 billion peryearindirectmedicalexpenditures,$3billionofwhichisspenton acutebacterialrhinosinusitis.3,4 The socioeconomic impactofrhinosinusitisis evengreater whenconsideringindirectcostsfrom decreased work productivity and missed work days, inaddition to global impairment of quality of life.

The paranasal sinusesmaxillary, ethmoid, sphenoid, andfrontalare 4 paired air-filled spaceslocated between the or-bits and below the anterior cranial fossa. They are lined withciliated, secretory respiratory mucosa. The sinuses drainthrough narrow ostia several millimeters in diameter and areprone to obstruction when the mucosal lining swells in re-

sponseto viral infection or environmental irritation(FIGURE 1).

Diagnosis

The diagnosis of acute rhinosinusitis is based primarily onmedical history and is supported secondarily by confirma-tory physical findings. In 2007, an updated clinical prac-tice guideline was developed by a multidisciplinary expertpanel based on evidence from the literature.5 The guide-line proposes that a diagnosis of acute rhinosinusitis shouldbe based on presence of 2 cardinal symptoms: purulent rhi-norrhea andeither facial pressure or nasal obstruction. Othersuggestive signs and symptoms (though not required for thediagnosis) include headache, fever, fatigue, maxillary den-

tal pain, cough, hyposmia or anosmia, and ear pressure orfullness. Although the sensitivity and specificity of this al-gorithm for the diagnosisof acute sinusitis hasnot been stud-ied, earlier studies have determined the sensitivity and speci-ficity of the individual cardinal symptoms for a diagnosisof acute sinusitis: purulent rhinorrhea has a sensitivity of72% and a specificity of 52%; facial pressure has a sensitiv-ity of 52% and a specificity of 48%; and nasal obstructionhas a sensitivity of 41% and a specificity of 80%.6

Anterior rhinoscopy, performed with a handheld oto-scope or fiber-optic nasal endoscope, may reveal diffuse mu-cosal edema, inferior turbinate hypertrophy, and copiousrhinorrhea (FIGURE 2). Facial tenderness and oropharyn-

geal discharge may also be supportive of a diagnosis of acuterhinosinusitis. Notably, the aforementioned diagnostic cri-teria apply to both viral and bacterial rhinosinusitis and donot distinguish between them. The guidelines propose,basedon expert consensus, that the duration of acute rhinosinu-sitis is expected to be less than 4 weeks.1

Thefirst step inevaluationof MrsD isdetermining whethershehas acuterhinosinusitis, irrespective of either viral or bac-terial etiology. Mrs D describes symptomsof purulent rhinor-

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rhea, facial pressure, andnasal obstruction, satisfying the cri-teriafor cardinalsymptoms.Shealsoreportsmultiple second-ary criteria, including headache, fatigue,dental sensitivity,andearfullness.Thedurationofhersymptomsislessthan4weeks.Althoughshehasahistoryofnasalallergies,hercurrentsymp-toms ofpurulent rhinorrhea andfacial pain arenot consistent

with allergic rhinitis,which wouldbe expected to manifestasclearrhinorrhea,sneezing,and nasalpruritus.7 Physicalexami-nation findings such as facial tenderness to palpation or tym-panic membrane retraction may support a diagnosisof sinus-itis butare notrequired,althoughin hercase, earexaminationtoassessherreportsofearfullnesswouldbeappropriate.There-fore, on the basis of history it is reasonable to diagnose Mrs Das having acute rhinosinusitis.

Determining whether Mrs D has viral vs bacterial rhino-sinusitis is a more complex matter. The most common formofacute rhinosinusitis isacute viralrhinosinusitis (AVRS). Morethan 1 billion viral upper respiratory tract infections are esti-mated to occur each year in the United States, and an esti-mated 39% to 87% of upper respiratory tract infections are

estimated to result in acute viral rhinosinusitis.8,9 Acute viral

rhinosinusitis, a typically self-limited illness, may be clini-cally indistinguishable from upper respiratory tract infec-tions without sinusitis. Upper respiratory tract infection is aprimaryriskfactor forthedevelopment of acute bacterial rhino-sinusitis(ABRS), with approximately 0.5% to 2% of upper res-piratory tract infections progressing to bacterial infection.10

Acute bacterial rhinosinusitis is also largely a self-limited ill-ness, with a 40% to 60% rate of spontaneous resolution, basedon systematicreview of placebo-controlled clinical trials.5 How-ever, antibiotictherapy in patients with ABRS canshorten thedurationof symptoms; a meta-analysisof 16 randomized con-trolledtrials in ABRSshowedthatantibiotics conferreda higherrate of partial or complete resolution of acute rhinosinusitissymptoms compared with placebo, with an odds ratio of 1.64(95% confidence interval,1.35-2.00).11 The meta-analysis didnot detect a benefit from antibiotics in the prevention of sup-purative complications (orbital, intracranial extension), butgiven the rare incidence of complications, the meta-analysismay have been limited by sample size.

Sinceviral andbacterial rhinosinusitis canoverlap in clini-

cal presentation, it may be difficult to discern viral from bac-

Figure 1. Anatomy of Paranasal Sinuses and Nasal Passages

Ethmoid sinuses

Nasal septum

Sphenoid sinus

MAXILLARY

SINUS

Ethmoid sinus Frontal sinus

Middle turbinate

Inferior turbinate

Maxillary sinus

Frontal sinus

Sphenoid sinus

Normal Acute rhinosinusitis

Orifice ofeustachian tube

Middleturbinate

Inferiorturbinate

Frontal sinuses

O RBIT

Edematousmucosal lining

MUCUS

Middle meatus

Middle meatus

Patentostium

Blockedostium

VIEW

VIEW

PARASAGITTAL SECT IO N

CO RO NAL SECTIO N

LATERAL V IEW

Mitu

Mi

Superiorturbinate

The parasagittal view demonstrates mucociliary drainage patterns of the paranasal sinuses.

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terial etiologies. In the first 5 days of illness, AVRS and ABRSmaybeindistinguishable.Thediagnosticdistinctionisthusmadebasedondurationandprogressionofsymptoms.5 Theexpectedclinical course of AVRS is marked by resolution of symptomswithin10daysfollowingtheonsetofanupperrespiratorytractinfection, whereas ABRS is presumed when acute symptomspersist for 10 daysor more. Acutebacterial rhinosinusitismayalso bediagnosediftheacutesymptomcomplex existsfor lessthan 10 days but demonstrates clinical worsening after initialimprovement.5 The presence of double worsening carries alikelihood ratio of 2.1 for a diagnosis of ABRS, based on a ref-erencestandardofasinuscomputedtomography(CT)scan.12

Because Mrs Ds symptoms have been present for 5 days

and the temporal cut point for distinguishing viral from bac-terial sinusitis is 10 days, it cannot be determined with cer-tainty whether Mrs Ds symptoms represent true bacterialrhinosinusitis.

Microbiology

The most common viruses implicated in AVRS, as deter-minedby maxillarysinus puncture and aspiration in an out-patient setting, are rhinovirus, adenovirus, influenza virus,and parainfluenza virus.13,14 Owing to a paucity of studies,the relative incidence of each virus in AVRS is not well char-acterized.Themost commonpathogensassociated with ABRSare Streptococcus pneumoniae (33%), Haemophilus influen-

zae (32%), Staphylococcus aureus (10%), and Moraxella ca-tarrhalis (9%).15 In approximately one-quarter of cases, 2distinct pathogens may be isolated.16 Since the introduc-tion of the 7-valent pneumococcal vaccine for children,thereappears to be a trend toward decreasing S pneumoniae iso-lates and increasing prevalence ofH influenzae isolates de-rived from adults with acute maxillary sinusitis.17

Inclinicalpractice,viralcultureofnasalsecretionsisnotrec-ommended for routine cases, given the self-limited nature of

AVRS.Bacterialcultureofpurulentsecretionsmaybeindicatedwhen there is concern regarding resistant pathogens, such asincasesthatarerefractorytoprimaryantibiotictherapy,orthoseinvolvingan immunocompromised host.18Whenculturesaredeemed necessary, a referral to an otolaryngologist is appro-priate,asculturemethodscansignificantlyaffecttheyield.Thegoldstandardforsinusculturetechniqueisantralpunctureandaspiration, which requires a large-bore trocar or needle to bepassedthroughthecaninefossaorinferiormeatus.Antralpunc-turemaynot bepractical for routineculturegiven themorbid-ityoftheprocedure,whichincludesdentalorfacialpain,bleeding,facial swelling, andfalse passageofthetrocar.19,20 An excellentalternativeto antral punctureis transnasal endoscopic culture,

which can be readily performed without significant morbid-ity in the otolaryngologists office using a topical anesthetic.20

Endoscopically guidedmiddle meatal cultureshavea satisfac-tory yield and show excellent correlation with antral aspi-ration.20-22 Inameta-analysisof126patients, 22 theyieldofendo-scopic middle meatal cultures was assessed against the goldstandardofmaxillarysinuspunctureandaspirationperformedinthesamepatient (131 culturepairs).Endoscopic culturehada sensitivity of80.9%, a specificityof 90.5%, a positivepredic-tive value of 82.6%, a negative predictive value of 89.4%, andan overall accuracy of 87.0%.

At the time of nasal endoscopy, the otolaryngologist canalso perform a more detailed examination of the nasal

anatomy to identify potential predisposing anatomic fac-tors such as nasal polyps, septal deviation, or nasal masses.Simple blind swabs of the nasal cavity are likely to be con-taminated by normal colonizing bacteria of the nasal vesti-bule and should not be performed.23,24

Since Mrs D has had uncomplicated symptoms for only 5days, there is no role for endoscopicculture in her case.How-ever, if her symptoms persisted for 10 days and she subse-quently failed a course of antibiotic therapy, referral for en-

Figure 2. Endoscopic Views of the Middle Meatus

Middleturbinate

Middle meatus

Nasal

septum

Nasal

septum

Lateral nasal wall

Middleturbinate

Angle and field of nasal endoscopic view

Lateralnasal wall

Middleturbinate

Middle meatus(filled with pus)

Lateral nasal wall

A Normal B Acute rhinosinusitis

Middle meatus

t

ateralasal wall

Middle meatus

See video at http://www.jama.com/cgi/content/full/301/17/1798/DC1.

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doscopic sinus cultures would potentially be indicated. Inaddition, if she were immunocompromised or if an extrasi-nus complication weresuspected, referral to an otolaryngolo-gist would also be indicated.23

Radiologic Studies

MrsD didnot have anyradiographicimaging during thisacuteepisode.Radiographicimaging isgenerallynotindicatedin theevaluation of routine uncomplicated acute rhinosinusitis.5 Ifpursued,plainsinus radiographymay providesatisfactory im-agesofthemaxillarysinus,andithasmoderatesensitivity(73%)and specificity (80%) for predicting positive antral punctureresults.25 Imagingoftheethmoid,frontal,andsphenoidsinusesoffers lower sensitivity and specificity owing to radiologic ar-tifact. Ultrasonography offers uneven diagnostic accuracy be-cause of operator-dependent factors and is therefore not rec-ommendedforroutineimaging. 25 Computedtomographyscansoffer improved bony and soft tissue detail, but in the contextof acute rhinosinusitis, CT scans may reveal sinus fluid levelsin patients with AVRS as well as those with ABRS (FIGURE 3).

Since CT scans cannot distinguish between viral and bacte-rial etiologies, their utility in evaluating acute rhinosinusi-tis is limited. In a study by Gwaltney et al,9 31 healthy par-ticipants who developed AVRS after controlled inoculationdemonstrated an 87% mucosal thickening or air-fluidlevelsof the maxillary sinuseson CT scan. Abnormalities werealsodocumented on CT in theethmoid, frontal, andsphenoid si-nusesin65%,32%, and39%,respectively.After 2 weeks, 79%oftheCTabnormalitieshadcleared.Otherstudieshaveshownthat radiologic evidenceof mucosal abnormality may be ob-served in as muchas 42%of asymptomatichealthyindividu-als26,27; thus, the significance of a positive CT result must beconsidered in the appropriate clinical context.

Imaging studies are indicated in the evaluation of pa-tients with a suspected complication of ABRS, such as thosepresenting with diminished visual acuity, diplopia, perior-bital edema, severe headache, or altered mental status.5 Com-puted tomography with contrast is the diagnostic study ofchoice for the evaluation of complicated acute sinusitis that

may be extending to the dura, brain, or orbits.

28,29

Mag-netic resonance imaging is not indicated for routine evalu-ation of ABRS but may provide complementary soft tissuedetail to CT for the evaluation of complications of acuterhinosinusitis.28,29

Treatment

To minimize the inappropriate use of antibiotics for viralinfections, antibiotic treatmentshould be initiated only whena higher likelihood of ABRS exists.30 The 10th day of symp-toms represents the recommended cut point for initiatingantibiotic therapy because most cases of AVRS would be ex-pected to resolve within 10 days.5 Furthermore, since 40%to 60% of ABRS resolves spontaneously, a significant pro-

portion of patients who have true bacterial sinusitis showevidence of symptom abatement or resolution by day 10 anddo not require antibiotics. For patients with fewer than 10days of symptoms, observation without antibiotics is there-fore recommended if the symptoms are mild and if clinicalseverity is either stable or improving. Antibiotic treatmentis recommended within the first 10 days if patients have se-vere symptoms or symptoms of double worsening. Addi-tional consideration for earlier initiation of antibiotic treat-ment should be given in immunocompromised hosts.5 MrsD was only 5 days into her course when she was evaluated;because she is an otherwise healthy host, she did not re-quire antibiotic therapy at this stage. She expressed con-

Figure 3. Radiologic Features of Acute Rhinosinusitis (Coronal Noncontrast Computed Tomography)

A B

A, Image demonstrates an air-fluid level in the right maxillary sinus (arrowhead) as well as partial opacification of the ethmoid sinuses bilaterally. B, Image showsmucosal thickening of the left sphenoid sinus (arrowhead). Radiologic imaging is not routinely indicated for the diagnosis of acute rhinosinusitis.

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cern over her infection given her husbands immunocom-promised state, but since her infection is most likely viral,antibiotics still would not be indicated. She should prac-tice careful hygiene, washing her hands frequently with soap.

For patients with 10 or more days of symptoms, clini-cians have the option of initiating antibiotics or continuing

with watchful waiting (TABLE

). If a patient has symptomsthat are mild or improving and a temperature less than38.1C, clinical guidelines support the option of continuedobservation without antibiotics for an additional 7 days.5 Thepatient may be treated with supportive care forrelief of symp-toms in lieu of antibiotics. Observation is supported as a vi-able option by randomized controlled trials (RCTs) of an-timicrobials vs placebo; spontaneous improvement ofcommunity-acquired, uncomplicated rhinosinusitis may beas high as 73% after 7 to 12 days (vs 87% with antibioticsin the same period).31 The watchful waiting option re-quires a reliable patient who will notify the clinician promptlyof any worsening of symptoms, at which point antibioticsshould be given. The clinician should also consider factors

such as age, immune status, and comorbidities when choos-ing to observe patients with ABRS.

For patients with 10 or more days of persistent symp-toms of rhinosinusitis, antibiotic therapy is equally accept-able as is watchful waiting. Antibiotics are administered tocontrol infection and to secondarily reduce mucosal edemaand restore ostial patency.35 The literature regarding the ef-ficacy of antibiotic treatment for acute rhinosinusitis is dif-ficult to interpret because of wide variations in diagnosticinclusion criteria. For example, an RCT by Williamson etal36 concludedthat antibiotics (alone or in combination with

nasal steroids) showed no benefit vs placebo in the treat-ment of acute maxillary sinusitis. Participants were olderthan 15 years of age and met Berg and Carenfelt diagnosticcriteria for acute maxillary sinusitis.37 However, patients hada range of 1 to 28 days of symptoms, with a median of 7days, and based on other studies it is likely that the RCT

included significant numbers of patients with viral rhino-sinusitis. The subgroup of patients with a longer durationof symptoms may have benefited from antibiotics.

Systematic reviews offer grade B evidence to support theuse of antibiotics in ABRS.11,38-43 For mild cases of ABRS, theincremental benefit is somewhat modest. Antibiotics ap-pear to shorten the duration of illness and may increase therate of cure by 15% (95% confidence interval,4%-25%) com-pared with placebo (35% cure for placebo at 7-12 days vs50% for antibiotics).31 The authors calculated that 7 pa-tients would need to be treated to achieve 1 additional posi-tive outcome, while diarrhea and adverse events were 80%more common in those treated with antibiotics. For mod-erate cases, no RCTs have been published, but treatment of

moderate ABRS offers the implied benefit of reducing po-tential complications.

When antibiotic therapy is initiated, choosing an antimi-crobial with the narrowest spectrum against the most prob-able pathogen is prudent to minimize the risk of cultivatingresistance. Amoxicillin (500 mg every 8 hours) is recom-mended as first-line therapy, given its narrow spectrum, lowcost, and favorable adverse effect profile.5 Increased rates ofpenicillin resistance due to penicillin-binding proteinproducing S pneumoniae have led to the use of higher dosingregimens of amoxicillin (penicillin-binding proteins can be

Table. Summary of Best Available Evidence for Medical Therapy for Acute Rhinosinusitisa

Source Treatment Study DesignSample

Size Outcome

Falagas et al,11 2008 Antibiotics Meta-analysisof placebo-controlled RCTs

1813

2648

1963

Antibiotics were associated with a higher rate of cure (OR,1.82; 95% CI, 1.34-2.46).

Antibiotics were associated with a higher rate of cure orimprovement (OR, 1.64; 95% CI, 1.35-2.00).

Antibiotics were associated with a higher rate of adverseevents (OR, 1.87; 95% CI, 1.21-2.90).

Rosenfeld et al,31 2007 Antibiotics Meta-analysisof placebo-controlled RCTs

3108 Antibiotics were associated with incrementally higher cureat 7-12 d (absolute RD, 0.15; 95% CI, 0.04-0.25).Antibiotics were not associated with a higher rate ofcure at 3-5 d (RD, 0.01; 95% CI, 0.02 to 0.05).Antibiotics were not associated with a higher rate ofcure at 14-15 d (RD, 0.04; 95% CI, 0.02 to 0.11)

Zalmanovici and Yaphe,32

2007Topical nasal

corticosteroidsMeta-analysis

of placebo-controlled RCTs

1943 Topical nasal steroids were associated with a higher rate ofimprovement or cure (relative risk, 1.11; 95% CI,1.04-1.18) (RD, 0.07; 95% CI, 0.03-0.11).

Braun et al,33 1997 Antihistamines Placebo-controlled RCTs

139 In atopic patients with acute rhinosinusitis, loratadinesignificantly reduced sneezing (P = .003) after 14 d andnasal obstruction (P = .002) after 28 d. No nonatopicpatients studied.

Rabago et al,34 2002 Saline irrigations RCT withnontreatment arm

76 Daily irrigation with hypertonic saline improved disease-specific quality-of-life measure at 3 mo (P .001) and 6mo (P .001) in a mixed population of patients withrecurrent acute sinusitis and chronic sinusitis.

Abbreviations: CI, confidence interval; OR, odds ratio; RCT, randomized controlled trial; RD, rate difference.a Based on systematic review. No RCTs are available studying decongestants for treatment of acute bacterial rhinosinusitis.

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overcomeby theuseof amoxicillininstead of penicillin).How-ever, -lactamaseproducing M catarrhalis and H influenzaecannot be overcome by higher dosing and may require com-bination therapy with clavulanic acid or a change in class ofantimicrobial. Resistance rates varyregionally and range from12% to 31% for intermediate or highly resistant S pneumo-

niae; 30% to40% for H influenzae; and

90% for M catarrha-lis.3,44,45 The increasing incidence of methicillin-resistantS au-reus is also of concern (69% incidence among S aureus isolatesin data from 2004-2006).46 In addition, identification of-lactamasenegative ampicillin-resistant strains ofH influen-zae have been reported from Japan and Spain47,48; the mecha-nism of resistance appears to be a mutation in penicillin-binding proteins.49 Locoregional histograms of bacterialresistance should be referenced to understand resistance trendsin the localcommunity.Trimethoprim-sulfamethoxazole, mac-rolides, and second- and third-generation oral cephalospor-ins have also been validated by RCTs and are cost-effective,acceptable alternative first-line therapies in penicillin-allergic patients.3,50-55

The recommendedduration of antimicrobial therapy basedon clinical guidelines is 10 days,5 based mostly on the typicalduration of therapy used in RCTs.5 However, according to ameta-analysis of 12 RCTs,11 no statistical difference in effi-cacy existed between short-course (3-7 days) vs long-course(6-10 days) treatment (odds ratio, 0.95; 95% confidence in-terval, 0.81-1.12). Adverse events were fewer in the 5- vs 10-day course (odds ratio, 0.79; 95% confidence interval, 0.63-0.98). This meta-analysis was limited by heterogeneity in theentry criterion of symptom duration (any patient with symp-toms30 days with positive radiological findings). Further-more,there was overlap in thetreatmentduration of thecom-parison groups, with the long-course group including 6- and

7-day treatments and the short-course group also including7-day treatments. The optimal duration of therapy remainsto be definitively validated by clinical trials.

Treatment failure is defined as progression of symptomsat any time during treatment or failure to improve after 7days of therapy.5 Patients in whom first-line therapy withamoxicillin fails or who relapse within 6 weeks require analternative antibiotic with a broader spectrum. Fluoroqui-nolones (250 mg/d) or high-dose amoxicillin-clavulanate(4 g/d) may be considered.3 If an odontogenic source is iden-tified, enhanced coverage of anaerobes and gram-negativebacteria is indicated.56 For refractory cases, specialty refer-ral to an otolaryngologist may be beneficial for obtaining

endoscopic cultures to guide therapy.Adjunctive Therapies

A wide variety of over-the-counter remedies have been of-fered for symptomatic relief of acute rhinosinusitis. On thewhole, no adjunctive therapy has been proven to shortenthe duration of illness. However, these treatments are gen-erally well tolerated and may be beneficial for patients who,like Mrs D, can be managed with watchful waiting.

Decongestants. Topical decongestantssuch as oxymetazo-line are more effective than oral decongestants such as pseu-doephedrine,although both forms arelikelyto alleviatesymp-toms.57,58 There is grade C evidence but no RCT to supporttheir use.5 Patients using topical decongestants should becautioned against prolonged use of medication (5 days)

to avoid the risk of rebound rhinitis.

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Corticosteroids.Topical nasal corticosteroids reduce in-flammation of the nasal mucosa and may have possible ef-ficacy in treating acute rhinosinusitis. A 2007 Cochrane re-view supported the use of topical nasal corticosteroids asmonotherapy or adjuvant therapy to antibiotics32 based ona meta-analysis of 4 double-blind, placebo-controlled trials.Currently, there is no US Food and Drug Administrationapproved indication for the use of topical corticosteroids inacute rhinosinusitis. As with the studies of antibiotics inABRS, published reports investigating topical corticoste-roids should be interpreted carefully because they are oftenbasedon heterogeneous patient populations (acute, chronic,and/or viral rhinosinusitis) and treatment regimens (con-

comitant decongestant, saline irrigation, antibiotic). Morewell-designed clinical trials are needed to definitively vali-date the routine use of topical nasal steroids in acute rhino-sinusitis. There is no evidence to support the routine use oforal corticosteroids for acute rhinosinusitis.

Antihistamines. Studies evaluating the role of antihista-mines in acute rhinosinusitis comprise only grade D evi-dence.5 Antihistaminesmay have a minorroleintreating atopicpatientswith acute rhinosinusitisandarenotindicated in nona-topicpatients.33,60 InMrs Ds case, her symptomsare moresug-gestive of an infectious etiology thanan atopic etiology; there-fore, antihistamines are not indicated.

Saline Irrigations. Buffered isotonic saline may be deliv-

ered to the nasal cavity by active (squeeze bottle) or pas-sive (Neti pot) means. The mechanical cleansing of the na-sal cavity has been shown to be beneficial in patients withrecurrent acute sinusitis, chronic rhinosinusitis, and aller-gic rhinitis,34,61,62 but no studies have been done in patientswith ABRS alone. Clinical guidelines neither advocate nordiscount the use of irrigations.5 Given its low adverse effectprofile, saline irrigation may be beneficial for patients seek-ing self-care options to supplement pharmacotherapy.

Complications

Complications of AVRS areuncommon, but specific rates aredifficultto quantifybecausemany cases of AVRS do not come

to medical attention. While transient hyposmia is commonin AVRS, permanent anosmia mayalso occur rarely.63Womenmay be disproportionatelyaffected by viral-inducedsmell dis-turbances compared with men; women represented 67% ofpatients presenting with viral-induced olfactory loss to a ma-jor smell and taste clinic.64 The most common complicationof AVRS is secondary bacterial infection resulting in ABRS.10

Although the incidence of complications in ABRS is rare,estimated at 1 in 1000,38 all patients with ABRS should be

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screenedfor the possibility of an underlying infectious com-plication. Complications of ABRS may be associated withsignificant morbidity or even mortality. The primary sitesinvolved in complicated ABRS are the orbits and central ner-vous system, typically by direct extension (FIGURE 4). Or-bital infections may range from preseptal cellulitis to sub-

periosteal abscess to orbital abscess, typically transmittedfrom the ethmoid sinus across the medial orbital wall.65 Or-bital extension may lead to cavernous sinus thrombosis.Acute sphenoid sinusitis or frontal sinusitis may be associ-ated with CNScomplicationsranging from meningitis to epi-dural abscess or frank brain abscess.66 Physical findings sug-gestive of a complication may include periorbital edema,disconjugate gaze, disorientation, or prostration. Any pa-tient with ABRS who presents with visual symptoms, se-vere headache, somnolence, or high fever should be evalu-ated radiologically with an emergent sinus CT scan withcontrast.29 While there is no indication for surgery in pa-tients with uncomplicated ABRS, surgery may be emer-gently indicated in patients experiencing extrasinus com-

plications of ABRS.

RECOMMENDATIONS FOR MRS D

Mrs D presents with a 5-day history of symptoms that is con-sistent with acute rhinosinusitis. The possibility of ABRS ex-ists, but given the relatively early stage of presentation, it isnot possible to readily distinguish between AVRS and ABRS.

Given that her symptoms appear to be mild to moderate inseverity, I would favor treating for 5 more days with symp-tomatic measures, such as topical decongestant sprays, oraldecongestants, over-the-counter analgesics, and saline ir-rigations. If she improves, the presumptive diagnosis wouldbe AVRS or spontaneously resolving ABRS. She should be

instructed to contact her physician in the meantime if shedevelops a fever or her symptoms otherwise worsen. Par-ticularly in light of her husbands immunocompromised state,she should wash her hands frequently to avoid transmit-ting infection.

If Mrs D reached the day 10 cut point without improve-ment in her symptoms, I would prescribe oral amoxicillinfor 10 days for presumed ABRS. I would expect near-complete resolution by the end of the 10-day course of an-tibiotics. If she were to have lingering or worsening symp-toms after 10 days of amoxicillin, I would extend therapyfor an additional 10 days using amoxicillin/clavulanate ora respiratory fluoroquinolone. At that point, I would con-sider obtaining endoscopic cultures as well to guide therapy.

QUESTIONS AND DISCUSSION

QUESTION: A lot of patients present like this patient and saythat theyve had multiple episodes of sinusitis and they getbetter only after antibiotics. What do you tell them?

DR HWANG: Its certainly possible that such a patient mayhave true recurrent ABRS, but this diagnosis can be diffi-

Figure 4. Anatomy of the Orbital Apex and Parasellar Region

Ethmoidsinuses

Sphenoid sinus

E YE

B R A I N

Internalcarotid artery

Internalcarotid artery

Pituitary gland

Pituitary glandNasal septum

Medial wallof orbit

Medial rectusmuscle

Orbital fat

Cavernoussinus

Cavernoussinus

Optic nerve

Optic nerve Internalcarotid artery

CN III

CN VI

CN V1

CN V2

CN IV

Cranial nerves (CN)

Sphenoidsinuses

Dura

Dura

VIEW

AX I AL SE C T I ON C OR ON AL S EC T I ONVIEW

Complications of acute sinusitis may include extrasinus spread of infection resulting in orbital cellulitis or cavernous sinus thrombosis.

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cult to distinguish from recurrent viral rhinitis or viral si-nusitis. If a patient with recurrent viral sinusitis has re-ceived antibiotics on the fifth day of symptoms every timetheyve presented to their physician, then that patient mightassociate the receiving of antibiotic to the resolution of theirdisease. In actuality, the natural course of this patients dis-

ease process dictates that symptoms would have resolvedon their own regardless of antibiotic intervention.In my practice, I would perform a nasal endoscopy to

evaluate for purulent discharge or anatomic abnormalitiesthat might be predisposing the patient to recurrent infec-tions. If the endoscopy results were normal, I would en-courage the patient to forgo antibiotics at the time of thenext exacerbation, under my close supervision. As we edu-cate our patients about thedifferences between viral andbac-terial infections, they become comfortable with the notionof not receiving antibiotics. And while some patients willmanifest true recurrent ABRS, many patients will find thattheir disease process resolves without antibiotics.

QUESTION: Are there normal bacterial flora in the si-

nuses? What are the defenses that prevent either the nor-mal flora or other organisms from turning into a sinusitis?Are there defensins or other local products that are se-creted? And is there more mechanistic information aboutwhat gets disrupted when there is a viral infection?

DR HWANG: Thats a great question. Colonizing bacteriahave been isolated from the sinuses, but we do not expectto encounter the pathogens typically associated with ABRS,such as S pneumoniae, H influenzae, or M catarrhalis.67 Inaddition, the nasal vestibule is heavily colonized with bac-teria. A simple nasal swab taken for the purpose of sinusculture will likely be contaminated by vestibular flora with-out yielding true pathogens. In contrast, an endoscopically

derived culture specifically targeting deeper areas of the nosewill have much greater yield. Thus, I recommend that allsinus cultures be obtained endoscopically.

In terms of local defenses against infection, mucociliaryclearance is the primary macroscopic defense against par-ticulate penetration of the sinus cavities. At a microscopiclevel, the sinonasal mucosa also demonstrates innate im-mune functions that maintain the protective barrier of theintact epithelium. Endogenous agents such as toll-like re-ceptors, defensins, and nitric oxide may have important lo-cal immune functions. A viral insult may disrupt local im-munity by overwhelming the milieu with toxic cytokinesand degranulation products of white blood cells.55 Injury

to the epithelial barrier may disrupt both ciliary functionand local immune surveillance, thereby predisposing to bac-terial superinfection.56

QUESTION: Could you comment further about the guide-line recommendations for amoxicillin as first-line therapy?Would that change if the person were immunocompro-mised or had other comorbid conditions that could com-plicate the potential flora? There are certainly some limita-tions to the spectrum of coverage of amoxicillin.

DR HWANG: Absolutely. The recommendations discussedtoday apply to immunocompetent individuals with mild tomoderate sinusitis. If you are treating a transplant patient ora patient with diabetes with a more severe clinical presenta-tion of acute sinusitis, it is likely that your threshold for in-tervention will be lower. If the patient has severe symptoms,

youmay notchoose to wait 10 days to beginantibiotic therapy,and I think it would be very reasonable to broaden your cov-erage beyond amoxicillin. One may see a higher incidenceof amoxicillin-resistant organisms such as -lactamaseproducing H influenzae, methicillin-resistantS aureus, or evenPseudomonas. If you do not see a clinical response after thefirst few days of therapy, you may wish to consult an otolar-yngologist for endoscopy and culture for precise identifica-tion of the pathogen and its antibiotic sensitivities.

Financial Disclosures: None reported.Additional Information: Online video is available at http://www.jama.com/cgi/content/full/301/17/1798/DC1.Additional Contributions: We thank thepatient forsharing herstory andfor pro-viding permission to publish it.

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