Brazilian
Journal
of
OTORHINOLARYNGOLOGY
www.bjorl.org
SPECIAL
ARTICLE
Rhinosinusitis:
evidence
and
experience.
A
summary
夽
Rinossinusites:
evidências
e
experiências.
Um
resumo
Wilma
T.
Anselmo-Lima
a,∗,
Eulália
Sakano
b,
Edwin
Tamashiro
a,
André
Alencar
Araripe
Nunes
c,
Atílio
Maximino
Fernandes
d,
Elizabeth
Araújo
Pereira
e,
Érica
Ortiz
b,
Fábio
de
Rezende
Pinna
f,
Fabrizio
Ricci
Romano
f,
Francini
Grecco
de
Melo
Padua
g,
João
Ferreira
Mello
Junior
f,
João
Teles
Junior
h,
José
Eduardo
Lutaif
Dolci
i,
Leonardo
Lopes
Balsalobre
Filho
g,
Eduardo
Macoto
Kosugi
g,
Marcelo
Hamilton
Sampaio
b,
Márcio
Nakanishi
j,
Marco
César
Jorge
dos
Santos
k,
Nilvano
Alves
de
Andrade
l,
Olavo
de
Godoy
Mion
f,
Otávio
Bejzman
Piltcher
e,
Reginaldo
Raimundo
Fujita
g,
Renato
Roithmann
e,
Richard
Louis
Voegels
f,
Roberto
Eustaquio
Santos
Guimarães
m,
Roberto
Campos
Meireles
h,
Victor
Nakajima
n,
Fabiana
Cardoso
Pereira
Valera
a,
Shirley
Shizue
Nagata
Pignatari
haFaculdadedeMedicinadeRibeirãoPreto,UniversidadedeSãoPaulo(USP),SãoPaulo,SP,Brazil bUniversidadeEstadualdeCampinas(UNICAMP),Campinas,SP,Brazil
cUniversidadeFederaldoCeará(UFC),Fortaleza,CE,Brazil
dFaculdadedeMedicinadeSãoJosédoRioPreto(FAMERP),SãoJosédoRioPreto,SP,Brazil eUniversidadeFederaldoRioGrandedoSul(UFRGS),PortoAlegre,RS,Brazil
fHospitaldasClínicas,FaculdadedeMedicina,UniversidadedeSãoPaulo(USP),SãoPaulo,SP,Brazil gUniversidadeFederaldeSãoPaulo(UNIFESP),SãoPaulo,SP,Brazil
hFaculdadedeCiênciasMédicas,UniversidadedoEstadodoRiodeJaneiro(UERJ),RiodeJaneiro,RJ,Brazil iFaculdadedeCiênciasMédicas,SantaCasadeSãoPaulo(FCMSC-SP),SãoPaulo,SP,Brazil
jUniversidadedeBrasília(UnB),Brasília,DF,Brazil
kHospitalInstitutoParanaensedeOtorrinolaringologia,Curitiba,PR,Brazil lFaculdadedeMedicina,UniversidadeFederaldaBahia(UFBA),Salvador,BA,Brazil
mFaculdadedeMedicina,UniversidadeFederaldeMinasGerais(UFMG),BeloHorizonte,MG,Brazil nFaculdadedeMedicinadeBotucatu,UniversidadeEstadualPaulista(UNESP),SãoPaulo,SP,Brazil
Availableonline24November2014
夽
Pleasecitethisarticleas:Anselmo-LimaWT,SakanoE,TamashiroE,NunesAA,FernandesAM,PereiraEA,etal.Rhinosinusitis:evidence
andexperience.Asummary.BrazJOtorhinolaryngol.2015;81:8---18.
∗Correspondingauthor.
E-mail:[email protected](W.T.Anselmo-Lima).
http://dx.doi.org/10.1016/j.bjorl.2014.11.005
Introduction
Rhinosinusitis (RS)isan inflammatoryprocessof thenasal mucosa,anditisclassifiedasacute(<12weeks)orchronic (≥12weeks)accordingtothetimerequiredfortheevolution ofsignsandsymptoms,andaccordingtotheseverityofthe condition,asMild,ModerateorSevere.Diseaseseverityis classifiedthroughtheVisualAnalogScale(VAS)(Fig.1),from 0to10cm.Thepatientisaskedtoquantifyfrom0to10the degreeofdiscomfortcausedbythesymptoms;zeromeaning nodiscomfort,and10,thegreatestdiscomfort.Severityis thenclassifiedasfollows:Mild:0---3cm;moderate:>3---7cm; Severe:>7---10cm.1
Although VAS hasonly been validated for Chronic Rhi-nosinusitis(CRS)in adults,theEuropeanPositionPaperon Rhinosinusitis and Nasal Polyps (EPOS) 20121 also
recom-mends its use for Acute Rhinosinusitis (ARS). There are severalspecific questionnairesfor rhinosinusitis; however, in practice,most have limitedapplication, particularlyin acuteconditions.2---4
Acute
rhinosinusitis
Definition
Acuterhinosinusitis(ARS)isaninflammatoryprocessofthe nasalmucosaofsuddenonset,lastingupto12weeks.Itcan occuroneormoretimeswithinagivenperiod,butalways
with complete remission of signs and symptoms between
episodes.
Classification
There areseveral classifications for rhinosinusitis. Oneof themostoftenusedistheetiologicalclassification,which isbasedprimarilyonsymptomduration:1
- ViralorcommoncoldARS:agenerallyself-limited condi-tion,inwhichsymptomdurationislessthantendays; - Post-viralARS:whenthereisworseningofsymptomsfive
daysaftertheonsetofdisease,orwhensymptomspersist formorethantendays;
- Acutebacterialrhinosinusitis(ABRS):smallpercentageof patientswithpost-viralARScandevelopABRS.
The viralARS or commoncoldhas asymptom duration thatistraditionallylessthan10days.Whenthereis symp-tomworseningaroundthefifthday,or persistencebeyond tendays(andlessthan12weeks),itcouldbeclassifiedas apost-viral RS.It isestimated thatasmallpercentageof post-viralARSdevelopsintoABRS,around0.5---2%.
Regardlessoftimeofduration,thepresenceofatleast threeof thesigns/symptoms belowmay suggest bacterial ARS:
1cm|__|__|__|__|__|__|__|__|__|__|10cm
Figure1 VisualAnalogScale(VAS).
- Nasalsecretion(withunilateralpredominance)and pres-enceofpusinthenasalcavity;
- Intenselocalpain(withunilateralpredominance); - Fever>38◦C;
- Elevated erythrocyte sedimentation rate (ESR) and C-reactiveprotein(CRP)levels;
- ‘‘Doubleworsening’’:acuterelapseordeteriorationafter theinitialperiodofmildsymptoms.
Clinicaldiagnosis
Signsandsymptoms
Atthelevelofprimaryhealthcareandforepidemiological purposes,ARScanbediagnosedbasedonsymptomsalone, withoutdetailedotorhinolaryngologicalexaminationand/or imaging studies. In these cases, the distinction between types of ARS is mainly by means of medical history and physicalexaminationperformedbymedicalgeneralistsand specialists,eitherotorhinolaryngologistsornot.Itisworth mentioning that, at the time of the medical assessment, patientsmayfailtoreport‘‘worsening’’ifnotasked specif-ically.Thehistoryofadurationofsymptomslastingafew daysfollowedbyarelapseisfrequent.Itisuptothe assis-tantphysiciantorecognizethat,andinmostcases,itcould representthe evolutionof the samedisease, fromaviral ARStoapost-viralone,ratherthantwodistinctinfections. SubjectiveevaluationofpatientswithARSanditsdiagnosis arebasedonthepresenceoftwoormoreofthefollowing cardinalsymptoms:1
• Nasalobstruction/congestion;
• Anterior or posterior nasal discharge/rhinorrhea (most often,butnotalways,purulent);
• Facialpain/pressure/headache;
• Olfactorydisorder.
Inadditiontotheabovesymptoms,odynophagia, dyspho-nia,cough,earfullnessandpressureandsystemicsymptoms suchasasthenia,malaiseandfevermayalsooccur.Thefew studiesonthefrequencyof thesesymptomsinARS inthe communityhaveshown greatvariability.5---7 The possibility
ofABRSisgreaterinthepresenceofthreeormoreofthe followingsignsandsymptoms:1
• Nasalsecretion/presenceofpus inthenasalcavitywith unilateralpredominance;
• Localpainwithunilateralpredominance;
• Fever>38◦C;
• Symptom worsening/deterioration after the initial dis-easeperiod;
• Elevated erythrocyte sedimentation rate (ESR) and C-reactiveprotein(CRP)levels.
ARS symptoms have a characteristically sudden onset, withoutarecenthistoryofrhinosinusitissymptoms.Inthe acuteexacerbationofchronicrhinosinusitis(CRS), diagnos-tic criteriaand treatments similar tothose used for ARS should be used.1 Cough, although considered an
oneof thefour cardinal symptoms, ratherthan olfactory disorders.1,8
Nasal obstruction isone of theimportant symptomsof ARS andshould be evaluatedtogether withother patient complaints. Although methods of objective evaluation of nasalobstructionsuchasrhinomanometry,nasalpeak inspi-ratoryflow andacoustic rhinometryare rarely applied in dailypracticeinpatientswithARS,studieshaveshowngood correlationbetweenthesymptomsreportedbypatientsand objectivemeasurementsobtainedbythesemethods.1
Purulent rhinorrhea is often interpreted in clinical practiceasanindicatorofbacterialinfectionrequiringthe useofantibiotics.9,10 However,theevidence forthis
asso-ciationis limited.Despitebeingasymptom thatseemsto increasethechancesofpositivebacterialculture,purulent rhinorrheaalonedoesnotcharacterizeABRS.11Purulent
rhi-norrheawithunilateral predominanceandthepresenceof pusinthe nasalcavityhave apositivepredictive valueof only50%and17%,respectively,forpositivebacterialculture obtainedbymaxillarysinusaspirate.12Therefore,the
pres-enceofpurulentrhinorrheadoesnotnecessarilyindicatethe existenceof bacterialinfectionand shouldnotbe consid-eredasanisolatedcriterionforantibioticprescription.11---13
Reduction in the sense of smell is one of the most
difficult symptoms to quantify in clinical practice and is usuallyevaluatedonlysubjectively.Hyposmiaandanosmia arecomplaintscommonly associatedwith ARS,which can beassessed byvalidated objectivetests andwith subjec-tivescalesthatexhibitgoodcorrelation.14,15Itisimportant
thattheseolfactory functiontestsgothroughtheprocess oftranslation,culturalandsocioeconomicadaptationtobe usedindifferentpopulations.16
Facialpainandpressurecommonlyoccurin ARS.When unilateral,facialor evendentalpainhasbeen considered apredictor of acute maxillarysinusitis.5,17 The complaint
of dental pain in the upper teeth on the topography of themaxillary sinus showed astatistically significant asso-ciation with the presence of positive bacterial culture,
with a predominance of Streptococcus pneumoniae and
Haemophilusinfluenzae,obtainedbysinusaspirate.18
How-ever,inanotherstudy,thepositivepredictivevalueofthe unilateralfacepainsymptomforbacterialinfectionwasonly 41%.17
Severalstudiesandguidelineshavesoughttodefinethe combination of symptoms that bestdetermine thehigher probabilityofbacterialinfectionandantibioticresponse.1
Inthe study by Bergand Carenfelt,7 the presence of two
or more findings (purulent rhinorrhea andlocal pain with unilateralpredominance,pusinthenasalcavityand bilat-eralpurulent rhinorrhea) showed 95% sensitivity and 77% specificityforthediagnosisofABRS.
Clinical examination of the patient with ARS should involve,initially,themeasurementofvitalsignsand physi-calexaminationoftheheadandneck,withspecialattention to the presence of localized or diffuse facial edema. At theoroscopy, posterior purulentsecretion inthe orophar-ynxisanimportantfinding.8Anteriorrhinoscopyisapartof
thephysical examinationthat shouldbeperformed inthe primaryevaluation of patients withnasal symptoms, and althoughitofferslimitedinformation,itmaydisclose impor-tant aspects of the nasal mucosa and secretions.1 Fever
maybepresentinsomepatientswithARSinthefirstdays
ofinfection,19 andwhenhigherthan38◦Citisconsidered
indicative of more severe disease and may indicate the needformoreaggressivetreatment,especiallywhen associ-atedwithotherseveresymptoms.Feverisalsosignificantly associatedwithpositivebacterialcultureobtainedbynasal aspirateespeciallyS.pneumoniaeandH.influenzae.
Despite the limited data in the literature, in patients withARS,thepresenceofedemaandpainonpalpationof themaxillofacialregionmaybeindicative ofmore severe disease,requiringantibiotics.9
At the primary health care levels, nasal endoscopy is generally not routinely available and is not considered a
compulsory examination for the diagnosis of ARS. When
available, it allows the specialist better visualization of thenasalanatomyandtopographicdiagnosis,aswellasan opportunitytoobtainmaterialformicrobiologicalanalysis.1
At the assessment and clinical examination of patients, possible variations between geographicalregions and dif-ferentpopulations shouldbeconsidered. Climatic, social, economicandculturaldifferences,aswellasdiverse oppor-tunity of health care access, among other factors, may changethesubjectiveperceptionofthedisease,aswellas potentially generatepeculiarclinical features.The impor-tanceofthisvariabilityisunknownfromthepointofview ofscientificevidence;morestudiesarenecessarytodetect them.
Treatment
Thereisworldwideconcernwiththeindiscriminateuseof antibioticsandwiththedevelopmentofbacterialresistance existsworldwide.Itisestimatedthatapproximately50 mil-lionantibioticprescriptionsforrhinosinusitisintheUSAare unnecessary,beingprescribedforviralinfections.Whenthe patient follows a more selective algorithm for antibiotic treatment,thebenefitisgreater,anditisonlynecessaryto treatthreepatientsforonetoreachtheexpectedresult.20
Thus,thereisaworldwidetrendtotreatARSaccordingto diseaseseverityandduration.
Antibiotics
Meta-analyses with placebo-controlled, randomized,
double-blindclinical trialsshowtheefficacyofantibiotics inimprovingsymptomsofpatientswithABRS,especiallyif administeredcarefully. They arenotindicated incases of viralrhinosinusitis,astheydonotalterthediseasecourse,21
andshouldneverbeprescribedassymptomatictreatment, thus avoiding indiscriminate use that may contribute to increasedbacterialresistance.22
Clinicalstudies have demonstratedthat approximately 65%ofthepatientsdiagnosedwithABRShavespontaneous clinicalresolution,23andinsomecasesmildABRScanresolve
spontaneously within the first ten days;21 therefore, the
initial adjuvant treatment, without antibiotics, may be a viable option for mild and/or post-viral RS.The introduc-tion of antibiotics shouldbe considered when thereis no improvementaftertreatmentwithadjuvantmeasuresorif thesymptomsareincreasinginseverity.Antibioticsare indi-catedincasesofmoderatetosevereABRS,inpatientswith severesymptoms(fever>37.8◦
duration,andincasesofmildoruncomplicatedABRSthat do not improve with initial treatment with topical nasal corticosteroids.24,25
There arenostudies todefine theoptimal durationof treatmentwithantibiotics.Ingeneral,treatment duration is7---10daysfor mostantimicrobialagentsand14daysfor clarithromycin. Amoxicillin is considered the first choice antibioticinprimaryhealthcarecenters,duetoits effec-tivenessandlowcost.Macrolideshavecomparableefficacy to amoxicillin and are indicated for patients allergic to
-lactam antibiotics.22,25,26 In cases of suspectedS.
pneu-moniae resistant to penicillin, severe cases and/or cases associated withcomorbidities, broad-spectrum antimicro-bialsareindicated.
Intranasaltopicalcorticosteroids
Patientsolderthan12yearswithpost-viralRS,or uncompli-catedABRSpatientswithmildormoderatesymptoms,24and
withoutfeverorintensefacialpain,25 benefitfromtopical
nasalcorticosteroidsasmonotherapy.Inadditionto reliev-ing the symptoms of rhinorrhea, nasal congestion, sinus pain,andfacialpain/pressure,24topicalcorticosteroids
min-imizetheindiscriminateuseofantibiotics,reducingtherisk ofbacterialresistance.25
Studieshavesuggestedthattopicalnasalcorticosteroids associated with appropriate antibiotic therapy result in
more rapid relief of general and specific symptoms of
RS,especiallycongestionandfacialpain,27---32 accelerating
patientrecovery,evenwhenthereisnosignificant improve-ment in radiographic images.30,31,33 However,the optimal
doseandtimeoftreatmentareyet tobeestablished.28---31
Althoughtherearenostudiesthatcomparethe effective-nessofdifferenttypesofnasalcorticoidsinARS,manyof
them, such as budesonide, mometasone furoate and
flu-ticasone propionate have shown benefits.33 Their use is
recommended for at least 14 days for symptom
improve-ment.
Oralcorticosteroids
The use of oral corticosteroids is recommended for adult patientswithABRSwhohaveintensefacialpain,aslongas theyhave no contraindications totheir use.34,35 Oral
cor-ticosteroids shouldbeused forthreeto fivedays,onlyin the first few days of the acute event, and always asso-ciatedwith antibiotictherapy, shortening the durationof facial pain34 and decreasing the consumption of
conven-tional analgesics.35 The evaluation after 10---14 days of
treatment shows that there arenosignificant differences insymptom resolution or treatmentfailurewhen compar-ing isolatedantibiotic therapy withoral corticosteroids.35
Thefewstudies intheliteratureusingoralcorticosteroids inthetreatmentofABRShaveshownfavorableresultswith methylprednisoloneandprednisone.
Nasallavage
Despite the frequent use of isotonic or hypertonic saline solutioninthenasallavageofpatientswithrhinitisandRS, littleisknownaboutitsrealbenefitinARS.
Randomized trials36 comparing nasal lavagewith
phys-iological saline solution and hypertonic solution showed greater patient intolerance to the hypertonic solution.
A meta-analysis of placebo-controlled, randomized and
double-blindtrialsshowedlimitedbenefitofnasalirrigation withnasalsalinesolutioninadults,ingeneral,not
demon-strating, any difference between patients and control
groups. Only one study showed a mean difference of
improvementinthetimeofsymptomresolutionof0.3days, withoutstatisticalsignificance.37
In another meta-analysis in patients younger than 18 yearswithARS,therewasnoclear evidence that antihis-tamines,decongestantsandnasallavagewereeffectivein childrenwithARS.38
Despitelittleevidenceofclinicalbenefit,theuseofnasal saline lavage is generally recommended in patients with ARS.Itresultsinimprovedciliaryfunction,reducesmucosal edemaandinflammatory mediators,thus helpingtoclean thenasalcavityofthesecretionsoftheinfectiousprocesses, andhasnoreportedsideeffects.39
Chronic
rhinosinusitis
Definition
CRS is an inflammatory disease of the nasal mucosa that persistsforatleast12weeks.Inspecificcases,anisolated sinusinvolvementcanbeobserved,asoccursinodontogenic sinusitisor infungalball. Itcanbedividedphenotypically intotwomainentities:CRSwithnasalpolyposis(CRSwNP) andCRSwithoutnasalpolyposis(CRSsNP).Currently,there isevidencetosuggestthatthesetwoentitieshavedistinct physiopathogenicmechanisms.
CRSisacommondiseaseinthepopulationandstudieson itsepidemiologicaldataareimportanttoevaluateits distri-bution,analyze itsriskfactors andpromote publichealth policies.However,such data arescarce in the literature. Additionally,differentdefinitionsandtheheterogeneityof methodologiesusedinthe studies---and,consequently,in theresultsobtained---makeitdifficulttocomparedata.
Clinicaldiagnosis
Severalclinicaltestshave been developedfor theclinical diagnosis ofCRS, but in most patients itis based only on thepresenceofsinonasalsignsandsymptoms,witha dura-tionofgreaterthan12weeks.40---42Sinonasalendoscopyand
computed tomography (CT) are complementary
examina-tionsandhelpindiseaseclassification.InboththeCRSwNP andCRSsNPforms,themainsymptomsare:
• Nasalobstruction41,42:Extremelysubjectivesymptom.It
isoneofthemostfrequentcomplaintsinclinicalpractice, affecting approximately 83.7% of the patients,43 being
evenmoreimportantinpatientswithnasalpolyposis.Itis causedbythecongestionofsinusoidalvessels, resulting in local edema, followed by tissuefibrosis, and it sub-sequentlyonlyresolveswiththeuseofvasoconstrictors. Althoughitisasubjectivesymptom,severalarticlesinthe literaturehavevalidated nasalobstructionasan impor-tantsymptomofCRS,usingacousticrhinomanometryand peaknasalinspiratoryflow.44
63.6% of the patients with CRS. It may also be associ-atedwithcacosmia,coughandhoarseness.Itisadifficult symptomtovalidateorquantify.43
• Olfactory disorders: Hyposmia or even anosmia is fre-quent,especially inCRSwNP, found inup to46% ofthe patients.42,43 Itcanbecausedbyan obstructiveprocess
(polyps), mucosal edema and/or degeneration caused
by the chronic inflammatory process, with or without the presence of nasalpolyps,45 or due tolocal surgical
procedures.40Thereareseveraltestswithexcellent
lev-els of evidence in the literature, which show olfactory disordersinpatientswithCRS.15
• Facial pain or pressure:Symptom withvariable preva-lence (18---80%).1 It is more often found in CRSwNP, in
patientswithallergicrhinitisof difficultcontrol or dur-ingexacerbation processes.1 Rhinogenic headacheis an
diagnosis of exclusion, according to the International HeadacheSociety(IHS).1
• Cough: It is a frequent symptom in childhood, often unproductive,andmaybetheonlymanifestationpresent
in CRS. In addition to the usual symptoms, such as
phlegm,pharyngeal-laryngeal irritation, dysphonia, hal-itosis,earfullness,adynamiaandsleepdisordersshould bequestioned.40---42 Duringtheinterview,itisimportant,
in additionto the classic symptoms already described, toincludequestionsaboutsystemicdiseasesand predis-posing factorsthat may favorthe developmentof CRS. Personal habitssuch assmoking, cocaineuse, exposure totoxic inhalants,type of climate in the regionwhere the patient resides and environmental pollutionshould beinvestigated.
• Physical examination: Anterior rhinoscopy (with and without vasoconstrictor): it is of limited usefulness, except in cases of polyposis, when polyps can be visu-alized by the simple inspection of the nasal vestibule. However,itisimportanttodescribesignssuchas hyper-trophicinferiorandmiddleturbinates,septaldeviations or mucosal degeneration. It is worth mentioning that therearenopathognomonicsignsofCRS.1,41
• Oropharyngoscopy:The presenceofretropalatal muco-catarrhal secretion explains the symptom of postnasal discharge,regardlessofthecolor.1,41,42
Complementaryexaminations
Nasalendoscopy
Nasalendoscopyallowsthesystematicvisualizationofthe nasal cavity (inferior, middle and upper turbinate), nasal septum,inadditiontothenasopharynxanddrainage path-ways,anditcanbeperformedwithandwithouttopicalnasal decongestants.The presence ofpolyps, mucosal degener-ation, secretion, crusts, structural alterations, scars and nasal tumorsmay also be observed. It can be performed at baseline or at regular intervals (e.g., 3, 6, 9, and 12 months)toaiddiagnosis,tosupervisediseasefollow-upand postoperativeperiods,aswellastocollectmaterialfor sup-plementarytests.46,47
It is important to perform a systematic assessment of thenasal cavities,suchas: examination of the nasal sep-tum,turbinates,visualizationofthemiddlemeatus,ofthe sphenoethmoidalrecess andofthenasopharynx. Itis also
necessarytoverifythepresenceofcrusts,ulcerations, sep-talperforation,signsofnasalbleedingaswellassecretions, and toexcludethe possibilityof associated polyposisand expansivelesions.Itisveryimportanttoperformthe endo-scopic assessmentofpatients whoareundergoingorhave previouslyhadsurgery.Theevidenceofmucosaldiseasesix monthsaftersurgeryshouldbeconsideredasCRS.Another factor to betaken into accountin patients withprevious surgery isthe recirculationof mucus bynot includingthe natural ostium of the maxillary sinus in the antrostomy. Nasal endoscopy is an examination of the utmost impor-tancetoaid diagnosis, tosupervisediseasefollow-up and inthe postoperativeperiod,aswellastocollectmaterial forsupplementarytests.
Imagingassessment
CTisthemethodofchoiceforCRS; however,itisnotthe firststeptoattaindiagnosis,exceptin casesofunilateral signsandsymptomsandsuspectedcomplication.
Bacterioscopy/sinussecretionculture
Indicated in cases refractorytotreatment, andwhen the materialcollectedisnotcontaminated.Itisperformed by punctureofthemaxillarysinusthroughthecaninefossaand usinganendoscope,withthecollectionbeingperformedin themiddlemeatus.48
Biopsy
Itisimportantforthestudyandclassificationofthe
inflam-matory state of the CRS and nasal polyposis and it is
indicatedforthedifferentialdiagnosisofautoimmune, gran-ulomatousdiseasesandtoruleoutneoplasms(especiallyin unilateralcases).
Comments
ThediagnosticinvestigationofCRSisbasedonthepatient’s natural history, signsand symptoms,endoscopic examina-tionandCT.The latter is considereda mainfactor in the analysisofdiseaseevolutionandinthedecisionforsurgical intervention.Themultiple causesofCRScanonlyprovoke manifestations in the sinonasal region, but one should rememberthatthenasalcavityandparanasalsinusesmay reflecttheonsetofsystemicdiseases.Theidentificationof predisposingfactorsanddiseasesassociatedwithRSareof theutmostimportanceforadequatepatientmanagement.
Clinicaltreatment
Treatmentwithsystemicandtopicalantimicrobials
TheincreasingperceptionofCRSasamultifactorial inflam-matory process has been expressed clearly in the latest consensus,i.e.,itisnotapersistentbacterialinfection.49
Thisfacthasledtoamandatorytheoreticalreassessmentof antimicrobialuseforthetreatmentofthisentity.However inpractice,unfortunately,itisnotsurprisingthat,thisgroup ofdrugsremainsasaconstantpartofthedrugarsenalused intheeverydaylifeofthesepatients,aswellaspersistently identified amongthe different proposals for the manage-mentofthisdisease.50 This ispossiblyduetolackofboth
and/orbiofilm.Thismaintheoreticalbasisforthechoiceof antibioticsalsosuffersfromtoolsthatallowthe differentia-tionoftheactualroleofthebacteriafoundintheparanasal sinuses,astheiridentificationalonedoesnotmeanthe pres-enceofaninfectiousorinflammatoryconditioninresponse totheirpresence.51 However,theidentificationofbacteria
such as Staphylococcus and Pseudomonas at higher per-centagesinpatientswithrecurrentevents(postoperative) continuestoperpetuatethebeliefthattheyarepartofthe CRSpathogenesis.Forthepurposeofillustrationand ques-tioning,in spite of the statistically significant analysis,it isnoteworthy thatinterms ofpercentage,thenumberof positive culturesin this study washigh both in the group withpooroutcomeandinthegroupwithfavorableoutcome (87%vs.73%),andforthesespecificbacteriatheabsolute differencewasof14%(39%vs.25%).52
Recent studies have investigatedbacteria asnecessary andaccountable elements,dependingontheirinteraction withthehost,tomaintainthebalanceoftheinflammatory response.The topicaluseofprobioticsand bacteriainan attempttoestablishfloraandbiofilminductorsofsinonasal homeostasisisanexample.53
Overthepastfiveyears,therehasbeennonewdramatic evidence for the use of antimicrobials in CRS. Neverthe-less, thereis a recommendation for macrolide use in the longterm,for instance,inthe absenceof elevatedserum IgE.1,54---58 Meltzer et al.,59 in a review article, concluded
thereis lack of publications capable of defining aproven effective proposal for the treatment of CRS, and empha-sizedthat,foraslongasthedifferentpresentationsofthe diseasearenotwelldefined,severaltreatmentswillfollow withlimitationsinresultinterpretationandextrapolation. Theyalsostressedthat therearesignsof increased inter-est in the developmentof research; however, the simple comparisonofcurrentrecordsofrandomizedcontrolled tri-als (RCTs) versus placebo, i.e.,designsthat areadequate for the searchof such responses at the National Institute ofHealth(NIH---ClinicalTrial.gov)doesnotallowthe verifi-cationofthiseffort.(http://clinicaltrials.gov/ct2/results). Thus, more specific inclusion and exclusion criteria, ran-domization,prospectivedesign,andstudycontrolarmsare requiredforthestudyofantibiotictreatmentinCRS.
Comments
Thisis awarningregardingthefrequentuse of antimicro-bialsandtheimportanceofbeingabletodifferentiatethem amongthetherapeuticoptionsfortheCRS.Moreover,there isnotenoughinformationinorderfortheirusetobe com-pletely discarded. It is necessary to findways to identify theexactpatientwhocouldbenefitfromtheuseof antimi-crobialsincasesofunequivocalclinicalflare-upandbetter identifytheinvolvedagentsthroughcultureandsensitivity testing.ThechoiceofextendedantimicrobialuseinCRSwNP cases, in which there is persistence of severe symptoms that havenot improved withmultiple treatments, includ-ingsurgery,andevenso,withoutserumIgEelevation,still lacksproofofbenefitanditspossiblebiologicaleffectsmust becarefullyconsideredwhenrestrictingitsuse.Thereisnot enoughevidence,inquantitativeandqualitativeterms,to recommendtheuseoftopicalantibioticsforCRS withand withoutnasalpolyposis.
Corticosteroidsinchronicrhinosinusitis
Therapywithtopicaland/orsystemiccorticosteroids(CS)is avaluableresourceinthetreatmentofCRS.Thiseffecthas beenmore decisivelydemonstrated inpatients with poly-posis.Althoughmoreevidence-basedproofandstudiesare necessary,theseagents areconsidered an adjuvantinthe fightagainstCRSingeneral,especiallywhenusedtopically. TheirsystemicadministrationissuggestedforCRScaseswith uncontrolled symptoms, in which the aim is todecrease, eventemporarily,thediseaseimpactonthepatient’slife. In these situations, it is recommended touse the lowest effective dose for theshortest possible time tominimize thepotentiallyseveresideeffects.
Preoperativeuseinpatientswithsurgicalindication
Although there are differences of opinion, patients with purulentCRSsNPcanreceiveamoxicillinclavulanate875mg every12 hours or cefuroxime 500mg every 12 hours pre-operatively for 7---10 days, and maintain the treatment postoperatively for 7---21 days. In some cases, fluoro-quinolonesandmacrolidesmaybeprescribed.
InpatientswithCRSwNP,theuseoforalcorticosteroids forthreetofivedaysis suggested,maintaining the treat-mentpostoperatively,dependingontheextentofdisease. Example: prednisolone 0.50mg/kg/day. Irrigation of the nasalmucosawithsaline(isotonic)andhypertonicsolutions, withandwithoutpreservatives,isaclassicandsafemeasure inthetreatmentofCRS andveryuseful inmobilizing sec-retionsandhydratingthemucosapre-andpostoperatively. Thereisnoevidencefortheiractionasisolatedtreatment.49
Surgicaltreatment:techniques
Severalsurgicaltechniqueshavebeendescribedforpatients withCRSwNPandCRSsNP,refractorytomedicaltreatment. Itisworthmentioningthatthereisnogoldstandard tech-nique that can be applied to all cases. Due to the lack ofrandomizedcontrolledtrials,severalaspectsofsurgical managementremaincontroversial. Themost importantof themistheextent ofsurgical dissection.Asaresult, cur-rentguidelines,primarilybasedoncase-seriesstudiesand expertopinion, indicate thatsurgical managementshould beindividualized.The currenttrendinCRSwithand with-outnasalpolyposis(NP)issurgicaldissection,extendingas farastheextentofthedisease.1
The most frequent surgical approach is the endonasal access.However,somecasesmayrequireexternalora com-binedaccess.Examplesarelateralmaxillaryorfrontalsinus lesions,orevenincaseswithalackofreliableanatomical landmarksfor an exclusivelyendonasal approach. Regard-less of the technique and instrumentation used, there is clearlyalearningcurveinendoscopicsinonasalsurgery.It is essential that the surgeon has deep knowledge of the surgicalanatomy andundergoes previous training through specificcoursestolearndissectionofthenoseandparanasal sinuses.
The surgical treatment of CRS has expanded greatly
because of the use of nasal endoscopy. The image accu-racyprovidedbyendoscopes(Optical0degreewideangle),
as well as their angulations (30, 45 and 70 degrees),
other specific equipment and instruments for intranasal andsinusapproach(e.g.,dilationballoons,neuronavigator andmicrodebrider) allowsperformingsurgical procedures rangingfromsimple dilationofthedrainageostiato com-plete marsupializationof paranasal sinuses into thenasal cavity.60---62
Postoperativetreatment---topical
Severalproducts havebecome available forpostoperative topical treatment. They can be used at high or low vol-umes withhigh, low or negative pressure.63 The capacity
of the drug to reach the appropriate anatomical region in the paranasal sinuses has been the subject of exten-siveresearchoverthepastfiveyears.Theeffectivetopical therapydependsonseveralfactorssuchasapplication tech-nique,postoperativesinonasalanatomyandfluiddynamics (volume,pressure,position).Thesecombinedfactorsseem tohave significant impact onthe effectiveness of topical therapyinpatients’sinonasalmucosa.64---67
The mechanicalremovalofmucus,antigen,pollutants, inflammatoryproductsand bacteria/biofilmsisthe aimof topicaltreatment.Thisinterventionveryoftendependson high-volumepositive-pressuresolutions tosupply shearing forcesthatcanchange thesurfacetensionbetweenliquid andair.However,thesameapproachmaynotbeappropriate fortheuse ofpharmaceuticalsolutionsthatrequire prop-ertiespromotingcompletedistributionwithintheparanasal sinus,longtimeofcontactwiththemucosaforlocal absorp-tionandminimalwastage.63
Itisconsideredveryimportanttocontinuemedical treat-mentpostoperativelyinalmostallformsofCRS.Currently, it is recommended to use nasal saline wash and topical nasalcorticosteroidsaftersinonasalendoscopicsurgeryfor CRS.63,68 The drug use directly at the disease site has
the advantage of allowing high local doses and minimiz-ingside effects.64 The distribution of thetopical solution
to the non-operated sinuses seems to be limited. Thus, sinonasalendoscopicsurgeryisessentialtoalloweffective topicaldistributiontotheparanasalsinuses.1Postoperative
distributionis superiorwithhigh-volumepositive-pressure devices.65---67Low-volumespraysanddropshavepoor
distri-butionandshouldbeconsideredastreatmentonlyforthe nasalcavity,especiallybeforesinonasalendoscopicsurgery.
There are limited data on the exact amount necessary
toallowcomplete distribution.Nasal lavagewithisotonic salinesolutionmaybeusedintheimmediateCRS postopera-tiveperiod,aswellastopicalnasalcorticosteroids,which maybestartedtwotothreeweeksaftersurgery, orafter crustdisappearance.Therearenorelevantdatainthe liter-aturetosupportthepostoperativeuseofothernasaltopical agentsinCRS.
Postoperativetreatment---systemic
Corticosteroids(CS). AfterthesurgicaltreatmentofCRS, systemiccorticosteroids (CS) canbeused inbasically two ways:inshortdoses,of betweensevenand 14days,with dose maintenancefor the entire treatment, or for longer periods,usingtapering doses.69,70 The primaryroleofthe
CSinthistypeofdiseaseistoreducemucosalinflammation, thusprovidingbettersurgicaloutcomes.However,useofthis
medication is stillavoided bymany surgeons due totheir potentialsideeffects.
Antibiotics. Thepurposeofantibioticusepostoperatively is to prevent infection of the secretions retained in the paranasalsinusesimmediatelyaftersurgery.Ifthereis puru-lent secretion during the surgical procedure, antibiotics shouldbeprescribed, basedontheculture andsensitivity testing. Otherwise, antibiotics effective against the most commonpathogensshouldbeemployed.70
Despitethescarcityofliteraturedataonantibiotic effec-tivenessinthepostoperativeperiodofendoscopicsinonasal surgery,itisbelievedthattheycanimprovesymptomsand endoscopicappearance,ifusedforalongerperiod(atleast 14days),buttherearenoconclusivedataabouttheduration ofthesebenefits.Ingeneral,penicillinderivatives, particu-larlyamoxicillin+clavulanicacidandcefuroximeaxetilare theagentsmostoftenused.
Special
aspects
of
rhinosinusitis
in
children
Diagnosis
TheclinicaldiagnosisofARSinchildrenisnoteasytoattain.
Many symptoms are common to other childhood diseases
such ascolds, flu and allergicrhinitis. Additionally, there arelimitationsanddifficultiesrelatedtotheclinical exam-inationinthepediatricpopulation.
Mostcommonsignsandsymptoms
Studiesinchildren withARSshowthattheclinical picture oftenincludesfever (50---60%),rhinorrhea(71---80%),cough (50---80%)andpain(29---33%),71plusretronasalsecretionand
nasalobstruction.72Inchildrenuptopreschoolage,thepain
symptomhasalowprevalence,beingreplacedbycoughing. As for schoolchildrenand adolescents,painasasymptom
becomesmorecommon.
Althoughtherearenotmanystudies,mostmedical pro-fessionalsandguidelinesrecommendthatthediagnosis of bacterial ARS be clinical, based on the timeof evolution (URTIsymptomsformorethan10days),theabruptonsetof high-intensitysymptoms(asearlyasinthefirst4days),or symptomworseningafteraninitialperiodofimprovement
during a URTI, known as double worsening. The
follow-ing may be part of the signs and symptoms: high fever, profuse nasal purulent discharge, periorbital edema and facialpain.1,72---76
Clinicalexamination
In addition to the abovementioned signs and symptoms,
Imagingstudy
Thereisanearconsensusinallthemostrecentguidelines thatthediagnosisofARSshouldnotbebasedonradiological studies,particularlyonplainradiographs.1,73,76
Viralprocessesinchildrenofteninvolvethesinuses. Chil-dren exhibiting symptoms of URTI with at least six days durationoftheclinicalpictureusuallyshowsignsof abnor-malityinallsinuses:maxillaryandethmoid,sphenoidand frontal,inorderoffrequency.The opacificationis nonspe-cificandmayoccurinviral,bacterialandallergicprocesses, aswellasintumors,orevenduetosinusnonformationin particular.
CTstudiesinchildren withaclinicalpicturesuggestive ofARSshowedthateventhemostimportantfindingsshow significantregressionofalterationsaftertwoweeks.77
Indi-cationsforCTinacutesinusconditionsshouldthereforebe reservedforpatientswhodonotimproveandwhose symp-tomspersistafterappropriatetherapy,aswellasthosewith suspectedcomplications.74
DrugtreatmentofARSinchildren
Mostareself-limited,resolvingspontaneously.1
Antibiotictherapy
Resultsof meta-analysissuggest thattherateof
improve-ment and resolution in ARS between 7 and 15 days is
slightly higher when antibiotic therapy is used.78 For this
reason,itisbelievedthatantibioticsshouldbereservedfor moreseverecasesorwhenthereareconcomitantdiseases presentthatcouldbeexacerbatedbyARS,suchasasthma and chronic bronchitis.1,73,75 However,there is no
univer-sal consensus regarding antibiotic use in ARS. In general, amoxicillin(40mg/kg/dayor80mg/kg/day)isstillindicated asa reasonable initial treatment in most studies. Amoxi-cillin/clavulanate andcephalosporins areconsidered good optionsagainstbetalactamaseproducers1andareindicated
incasesoffirsttreatmentfailure.
Similartotherecommendations foracuteotitismedia, inARS thereis alsotheoption ofasingledose of ceftria-xone 50mg/kg IV (intravenous) or IM (intramuscular) for childrenwhoarevomitingandthusunabletotolerateoral medication.11---13 If there is clinical improvement in 24h,
treatmentiscompletedwithoralantibiotics.75
For penicillin-allergic patients, there is some
contro-versy among the latest international guidelines. Some
consider trimethoprim/sulfamethoxazole, macrolides and clindamycingoodfirstchoices1inthesesituations.Othersdo
notrecommendtheuseoftrimethoprim/sulfamethoxazole andmacrolidesduetotheincreasingresistanceof Pneumo-cocci and H. influenzae to these drugs, and suggest a quinolone,suchaslevofloxacin,asanalternative,especially in older children, even in view of toxicity, high cost and emergingresistance.79,80Therearenoreviewsonthe
opti-maltreatmentduration.Recommendationsbasedonclinical observationshaveshownvariedresults,from10to28days oftreatment.Onesuggestionhasbeentomaintaintherapy forsevendaysaftersymptomresolution.81
Intranasalcorticosteroids
IntranasalCS for three weeks associated withthe antibi-oticseemstohaveadvantageswhencomparedtotreatment of ARS in children and adolescents withantibiotic alone, especiallyin relation tocough and nasal discharge.28,35,38
Thereisalsosomeevidence,basedonasingledouble-blind, randomizedtrial, that in patients older than 12 years, a doubledoseofintranasalCSasasingledrugmaybemore effectiveincontrollingtheARSthantheantibiotictherapy alone.28
RecurrentARS(RARS)
MostauthorsagreethatRARSisdefinedbyacuteepisodes lastinglessthan30days,withintervalsofatleast10days withacompletelyasymptomaticpatient.Accordingtosome authors,thepatientshouldhaveatleastfourepisodesayear tomeetthecriteriaforrecurrence.75
As in chronic conditions, one should seek to rule out some causes of systemic origin. The investigation should include allergic processes, by performing specific tests; immunoglobulin deficiencies, with quantitative research, particularly IgA and IgG;cystic fibrosis; gastroesophageal reflux, and ciliary diseases.82 Pharyngeal tonsil
hypertro-phy,evenmild,shouldalsobeconsidered,sinceitcanact asareservoir forpathogens.Anatomicalfactors,although usuallynot relevant in children, should alsobe ruled out (conchabullosa,septaldeviation,etc.).Inthesecases,CT, nasalendoscopyand/ormagnetic resonanceimaging(MRI) mayaid inthediagnosis oftheobstructiveprocessandof malformation.
The bacteriology is the same as for ARS and, there-fore,thetreatment ofthe acutephase shouldfollow the sameprinciples.83 Unfortunately, it is necessary to
recog-nizethat thefrequentuseof antibioticsatshortintervals can contribute to bacterial resistance. Prophylaxis with antimicrobials should be reserved for exceptional cases, usuallythosewithconfirmed underlying diseases, particu-larlyimmunodeficiencies.
Thefollowingoverallprophylacticmeasuresare recom-mended:annualvaccinationforinfluenzaandpneumococcal vaccine.Incaseswhereallergicrhinitisorgastroesophageal
reflux are associated, the frequency of acute events
decreaseswhenthe associateddiseaseis treated.Several studieshave demonstrated thatimmunostimulatory medi-cationssuchasbacteriallysateshelpcontrolrecurrentviral andbacterialRTIs, andmaybean adjunct therapy inthe controlofRARS.84
Particularities
of
chronic
rhinosinusitis
in
children
Clinicalanddiagnosticpicture
Theclinicaldiagnosisofchronicrhinosinusitisinchildrenis stillconsidered a challenge,as it often overlaps thoseof othercommonchildhooddiseases, suchasviralinfections oftheupperrespiratorytract,hypertrophy,withorwithout infectionofthepharyngealtonsilsandadenoidsandallergic rhinitis. The most important signs and symptoms include nasal blockage/obstruction/congestion, rhinorrhea (ante-rior/posterior),±facial pain/pressure, cough±and/or endoscopicsignsofdisease.CTcanshowrelevantchanges intheparanasalsinuses.1
Imagingstudies
Studiesthat have assessedthe incidenceof abnormalities intheparanasalsinusesonCT,obtainedforclinicalreasons unrelatedtotheCRSinchildrenhaveshownapercentageof sinusradiographicabnormalitiesrangingfrom18%2,3to45%,
percentagesthataresimilartothosefoundinchildrenwith CRSsymptoms. Thisdemonstrates thatthe significanceof animagingstudyisrelativeandmustalwaysbeconsidered togetherwiththeclinicalpicture.
Bacteriology
TherearefewstudiesonthebacteriologyofCRSinchildren. Microorganismsthat have alreadybeen found in aspirates orintraoperativelyinclude:S.alphahemolyticand Staphy-lococcus aureus, S. pneumoniae, H. influenzae and M. catarrhalis, as well as anaerobic organisms such as bac-teroidesandBrookIfusobacterium.85---87
Treatment
Drugtreatment
Currentstudiesdemonstrate thatthetreatment ofCRS in childrenwith antibiotics for a shortperiodof timeis not justifiable.1 On the other hand, both nasal CSand saline
solutionhaveshown benefits,andareconsideredfirst-line treatmentsforthisdisease,withorwithoutthepresenceof polyps.88,89
Surgicaltreatment
Thesurgicalapproachshouldalwaysbereservedforspecial cases,i.e.,childrenwhohavenotrespondedtoappropriate medicaltreatment.Studieshaveshownsignificant improve-mentintheclinical pictureandin qualityof life,without negative repercussions in relation to facial osteoskeletal sequelae.90 Unfortunately, the majority of studies
sup-porting this recommendation do not have a prospective, randomizeddesign.Ingeneral,thesurgicalapproach,when indicated,mayconsistinitiallyofanadenoidectomy,90with
maxillarysinuslavage.91 Surgerycanbeperformedwithor
without balloon dilation,92,93 followed by paranasal sinus
endoscopic surgery in case of symptom recurrence.94 In
casesofchildrenwithcysticfibrosis,NP,antrochoanalpolyps orallergicfungalRS,endoscopicsurgeryisthefirstoption. Perhaps future studies comparing the different methods
of treatment with standardized symptom questionnaire,
pre- and postoperatively, can guide the best therapeutic approachinpediatricpatientswithCRS.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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