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5SmellandTasteDisorders—DiagnosticandClinicalWork-Up
AntjeWelge-Luessen,DonaldA.Leopold,TakakiMiwa
Introduction
Smellandtastedisordersarecommoncomplaintspresentingtoear,nose,andthroat(ENT)physicians.
1–3
Approximatelyone-fifthofalladultshavesomeformofolfactorydysfunction,
2,4,5
increasingto30%or
moresufferingfromfunctionalanosmiaovertheageof70years.
2
Thesenumbersarereflectedby79,000
patients/yearincentralEurope(Austria,Germany,andSwitzerland),
6
andaround200,000patients/year
intheUSA,
7
consultingENTspecialistsaboutolfactorydisorders.
Tastedisordersseemtobelesscommon,affectingaround5%ofpeople
8
ifdiagnosedbytwodifferent
psychophysicaltests.If,however,onlyfourtastantsareappliedandtheincorrectidentificationofoneof
thesefourisdefinedastastedisorder,thentheprevalencerisestoalmost20%.
5
Otherepidemiological
studies,usingquestionnairestoevaluatethenumberofself-perceivedtastedisorders,reportnumbersin
therangeof0.6%
7
to0.93%.
9
Thesenumbersincreaseto8.7%inpatientsseekingmedicaladvice.
3
The
factthattherearethreedifferentnervesoneachside,alltransmittingtasteinformation,makesthissense
morerobustthanthesenseofsmell,andlesslikelytodecreasethroughlife.
Even thougholfactory receptor cells regeneratethroughoutlife, this regeneration seemstodecrease
withgrowingage.Patientssuffering fromage-relatedolfactory dysfunctionareoftennot evenaware of
the disorder,
10
which usually develops gradually and is most likely due to the reduced regenerative
capacityoftheolfactoryreceptorcell.Incontrasttohearingandvisuallosses,whichareoftennoticedby
spouses,familymembers,orfriends,smelllossesusuallyremainundetectedbyotherpersons.Thismight
explainwhy patients witholfactory disorders, particularlyolder people, are more likelyto encounter
hazardous events (e.g.,burningfood,ingesting spoiled food,fire) thana normosmiccontrol group.
11,12
Thesehazardshavetobeespeciallymentionedwhencounselingpatientswithsmellloss.Theincreased
riskofthesehazardscontributestothelossinqualityoflifeexperiencedbypatientssufferingfromsmell
loss.Boththeincreasedriskofhazardouseventsandthereductioninqualityoflifearelikelytoexplain
why patients with post-traumatic smell loss receive some financial reimbursement from insurance
providers(seeChapter18).Withgrowingage,thesenseoftastealsodecreases,butlessthanthedecline
seeninolfaction.
9,13,14
Makinganaccuratediagnosisofsmellortastedisorderisessentialinordertodetermineappropriate
treatmentandcounseling.The firststepistodeterminewhetherthedisorderisanolfactoryproblem,a
gustatoryproblem,orboth.Aspatientsdooftencomplainabouttasteproblemsorcomplainsimplythat,
“thefoodjustdoesnottastethesameanymore,”itisfirstnecessarytoevaluatethekindofchemosensory
deficitpresent.
Ithasbeenestablishedforsomeyearsnowthatself-assessmentofolfactory functionisunreliable.
15
Even in patients complaining of olfactory disorders, self-assessment correlates only moderately with
measured olfactory function.
16,17
The use of a validated test that actually measures olfactory ability,
gustatoryability,orbothis thereforemandatoryinall patientsseekingadvice (seeChapter6 forsmell
testing;Chapter14fortastetesting).
OlfactoryDisorders
Thevastmajorityofchemosensorycomplaintsareolfactory,andthepatient'shistorycanhelptoclassify
thedisorder.Smelldisordersareclassifiedassinonasal,postinfectious,post-traumatic,congenital,toxic
(includingdrug-induceddisorders),other(postoperative),andidiopathic.Thedetailedcharacteristicsof
eachofthesedisorders arediscussedinthefollowingchapters;however,inclinical consultationsitis
important to differentiate between sinonasal (sometimes called “conductive”) and nonsinonasal
(sometimescalled“neural”)disorderswithintheinitialwork-up.
Assessment of a patient depends on the situation. In general, one has to distinguish between an
asymptomatic patient who has to be evaluated because of a medicolegal reason (e.g., preoperatively
[before anyendonasal operation]or inthecontext ofa thoroughENTexamination [e.g.,for anexpert
opinion]) anda patient presenting withanolfactory complaint. In asymptomatic patients, the use ofa
validatedscreeningtestisrecommended(seeChapter6).Itisimportanttobearinmindthatthetesthas
beenadaptedtoculturalfactors
18,19
(fordetails,seeChapter6).Onlyifthistestrevealsanypathological
resultsisfurthertestingrequired.InJapan,aself-administeredodorquestionnaireissometimesusedas
aninstantindex.
17
However,patients seeking medical advice forolfactory disorders have different expectations.They
expectnotonlyadiagnosis,butalsoinformationconcerningprognosisandtreatment(or,atleast,coping
strategiesincasesinwhichtherapeutictools arelacking).To meet theseexpectations,classificationof
thedisorderismandatory.
GustatoryDisorders
Likeolfactorydisorders,gustatory disorders should be classified andmeasured using a validatedtest.
Unlikepreoperativesmelltestingbeforeendonasaloperations,thereiscurrentlynoconsensusaboutthe
need for preoperative taste testing in asymptomatic patients undergoing enoral operations such as
tonsillectomyorteethextraction.Whetherthisapproachwillchangeinthefutureremainstobeseen,and
is likely to depend onthe number ofcomplaints about postoperative taste problemsobserved in such
patients(fordetails,seeChapter15).
Nevertheless we do recommend performing a screening taste test in every patient receiving an
extensiveolfactorytest,andviceversa.
ExaminationofthePatient
History:Olfaction
Theimportanceofadetailedhistorycannotbeoveremphasized.Ofspecialimportanceisthetimecourse
ofthecomplaint.
Hasthedisorderstartedsuddenlyorhasitdevelopedoveralongerperiodoftime?Inthiscontext,itis
important to remember that the patient should recall a temporal connectionto, for example, accidents,
intakeofmedication,oracuteinfectionsuchasrhinitisorrhinosinusitis.However,theexaminershould
becautiousnottooverinterpretpossiblecausativecorrelationssometimesofferedbypatients.
Hasthepatienteverexperiencedsomethinglikethisbefore?Arethereanyadditionalnasalsymptoms
(discharge, rhinorrhea, postnasal drip, nasal breathing) or concomitant diseases (e.g., thyroid,
cardiopulmonary,hepatic,orrenaldisease,orallergies)?Ahistoryofmovementdisorders(tremor,etc.)
or disturbances in memory should also be taken. Afamily historyof Parkinson or Alzheimer disease
shouldbeevaluatedandconsidered.
The existence ofadditional qualitativedisturbances, ifnot mentionedspontaneously,shouldalsobe
evaluated(see below). Theuseofasimplehistoryquestionnaire asdepictedinFig. 5.1(adaptedfrom
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ref.20)canbeofgreathelpinclinicalpracticeandisrecommended.Animportantquestioniswhether
thedisorderiscontinuouslypresentorwhetherisitfluctuating.Fluctuatingdisorderspointtoasinonasal
(conductive)problem.Olfactorydistortionsmostoftenpresentinfemalesinthesecondtofifthdecadesof
life.Ifadistortionisnotedintheteensortwenties,ametabolicdisordershouldbesuspected.
21
Itshould
alsobenotedwhetherthedistortionisexperiencedduringinhalationorexhalationandwhetherblocking
oneorbothnostrilscaneliminateit.
History:Gustation
Once again, a meticulous history is of great importance. The onset of the disorder—suddenly versus
gradually—andanypossiblecausativefactorshavetobeevaluated.Concomitantdiseases(renal,liver,
other systemic diseases such as autoimmune diseases, etc.) should also be assessed, and a thorough
medicationhistorytaken.Localfactorssuchastheuseofmouthirrigationsorsalivaproblemsshouldbe
assessed. If possible, the examiner should try to evaluate whether a quantitative or a predominantly
qualitativedisorderispresent;however,qualitativedisordersmightalsobeaccompaniedbyquantitative
disorders, so a quantitative assessment should always be made. For more details aboutthe history of
gustatorydisorders,seeChapter15.
Fig. 5.1 History questionnaire. CT, computed tomography; rad.-sinuses, x-rays of the nasal sinuses; MRI, magnetic resonance imaging.
(Adapted from Hummel T, Welge-Lüssen A. Riech- und Schmeckstorungen: Physiologie, Pathophysiologie und Therapeutische Ansatze.
Stuttgart:Thieme;2005.)
ClinicalExamination:OlfactionandGustation
ThemainfocusoftheclinicalexaminationisexaminationoftheheadandathoroughENTexamination.
An anteriorrhinoscopy shouldbefollowedbyanendonasalendoscopy(withorwithoutdecongestion)
withanarrow2.7-mmendoscopetoevaluate theregionoftheolfactory cleft.Isitvisible?Arepolyps
present? Is it not completely visible because of high septal deviation? Signs of acute (Fig. 5.2) and
chronic(Fig.5.3)rhinosinusitisshouldbeevaluated.
After takinga historyandperforminganendonasalendoscopicexamination,the examinershould be
abletoconfirmorexcludeanacuteorchronicsinonasaletiology.Incasesofacutesinonasaldiseaseand
concomitant olfactory complaints, the acute infection should be treated appropriately and the patient
shouldbeseenagainseveralweekslater.Iftheolfactorydisorderpersistsafterrecoveryfromtheacute
infection,anolfactorytestusingavalidatedtoolshouldbeperformed.Ifsignsofacuterhinosinusitisare
lacking,olfactorytestingshouldalsobeperformed,asdepictedinFig.5.4.
Incasesofassumedtastedisorder,acarefulexaminationoftheoralcavityhastobeperformed.For
detailsoftastedisorderclassification,examination,work-up,andtherapy,seeChapter15.
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Fig.5.2Acutesinusitis,pusinsidemiddleandsuperiornasalduct.
Fig.5.3a,bChronicrhinosinusitis.
aPolypswithpusandcrusts.
bPolypsonly.
QuantificationofSmellDisorder
The patient'ssymptomsshould be verifiedusing a validatedsmell test(seeChapter6).Additionally, a
suprathreshold taste test should be included. The results of these tests can be used to classify smell
function as normosmic, hyposmic (diminished), or anosmic (completely missing). However, it is
important toremember that, for example, the Sniffin’ Stickstest uses normative data from a groupof
healthyindividualsagedbetween16and35yearsinordertodefineabsolutenormosmiaorhyposmia.
22,23
Theageofthepatienthastobekeptinmindwheninterpretingthetestresults.
Incontrasttothesequantitativedisorders,qualitativedisordersaredifficulttomeasure.Nevertheless,
thepresenceorabsenceofthese,aswellastheirtimecourse,shouldbeaskedwhentakingthehistory.
Accordingtotheexistingdefinitions,qualitativedisordersareclassifiedas:
Fig.5.4Work-upofolfactorydisorder.
•Parosmia:Disturbedodorantperceptioninpresenceofanodorant.
•Phantosmia:Perceptionofanodorantintheabsenceofanodorant.
•Pseudosmia:Imaginativereinterpretationofanodorantwithinthecontextofstrongfeelings.Canbeof
significancewithinthepresenceofpsychiatricdisorders.
•Olfactoryintolerance:Exaggeratedsubjectivesensitivitytowardodorants.
AdditionalWork-up
Incasesinwhicholfactorydysfunctionduetoasuspectedsinonasaldisorderisconfirmedbyolfactory
testing, further analysis is required. In general, sinonasal olfactory disorders are those in which the
etiology lies within the nose or the paranasal sinuses. This can be either inflammatory (chronic
rhinosinusitis) or noninflammatory (intranasal tumors, stenosis, scarring). Inflammatory disorders can
furtherbeclassifiedasinfectiousornoninfectious(Fig.5.5).ThesearediscussedindetailinChapter7.
If the history suggests a sinonasal disorder but the endonasal findings do not correspond with this,
computedtomographycanbe helpful, especiallyindetecting slight opacificationofthe olfactory cleft,
whichsometimescannotbevisualizedendoscopically.Incasesofsuspectedsinonasaldisorderwithout
clear or distinct signs, it is controversial whether or not to prescribe a short course of decreasing
systemicsteroids
24
withoutpriorimaging.Inthesecasesinparticular,anycontraindicationsforperoral
steroidsmustberuledoutbeforeprescribingthemedication.
Incasesinwhichneitherhistorynorclinicalexaminationsuggestasinonasalolfactorydisorder,one
hastosuspectanolfactorydisorderthatisnonsinonasal.ThiscanbecharacterizedaccordingtoFig.5.6.
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Fig.5.5Differentiationofsinonasaldisorders.
Postinfectiousandpost-traumaticdisorderscan,inmostcases,easilybe diagnosedfromthehistory.
However,patientswithsevereheadtraumamaypresentmuchlaterthanthosewithminortraumabecause
theyarenotawareoftheirsmelldeficitinitially.Postinfectiousdisordersarealsodiagnosedaccordingto
thehistory,whichistypicalinsuchcases.However,sometimesthedifferentiationofasinonasaldisorder
canbedifficult(fordetailsseeChapter9).
Toxic disorders are difficulttodiagnose,especiallyasmost patientsare exposed tomore thanone
potentially toxic agent. A systematic evaluation of potentially toxic drugs, including all medications,
shouldbeincludedwithinthehistory.
Sentencesinthehistorysuchas,“Icannotrecalltohaveeversmelled”suggestacongenitaldisorder.
Mostofthesepatientspresentaschildrenorteenagersbuttheymaysometimespresentasadults.Inthese
uncommon cases, magnetic resonance tomography (MRT) can reveal aplasia of the olfactory bulb to
confirm the diagnosis.
25,26
If the olfactory disorder is not classifiable based on the history and
examination, a neurological examinationshould be performed torule outearlyParkinson disease.
27–30
MRT imaging can also help exclude any intracranial tumors; moreover, MRT can also visualize the
olfactorybulbanditsvolume(fordetailsseeChapter17).
Diseases such as diabetes mellitus,
31
hypothyroidism, lupus erythematodes, renal disease, liver
disease, vitaminAorB
12
deficits, or Wegener granulomatosis
32
canalso be associatedwith olfactory
disorders.Inmostofthesecases, adecreaseinolfactoryfunctionisapparent,
33,34
ratherthancomplete
anosmia.
If all the previously mentioned causes of olfactory disorder have been ruled out and any
contraindication to the use of systemic steroids has been excluded, one might try a short course of
systemicsteroidsusingadecreasingregimen(e.g.,startingwithprednisone60mg/d)overaperiodof14
days,accordingtotheguidanceoftheWorkingGroupofOlfactionandGustation.
24
Ifolfactoryfunction
improves,asinonasaldisorderseemslikelyanditshouldbeinvestigatedfurther;if,however,olfactory
abilityremainsunchanged,anidiopathicdisorderisthemostlikelydiagnosis.
Bearinginmindthatonlyalimitednumberoftherapeuticmeasuresexists,adequatecounselingofthese
patients is very important. Patients should be accurately informed about prognosis and spontaneous
recoveryrates,especiallyincasesofpostinfectiousandpost-traumaticdisorders(seeChapter9).Coping
mechanisms(e.g.,consideringdinnerasa“socialevent”ratherthanconcentratingontheexperienceofthe
food;checkingtheexpirydateoffood;appropriateuseofperfume;regularventilationofhomes;regular
washing days for clothes; and the purchase of fire/gas detectors) and working conditions should be
discussed. While inmostcases loss ofsmell doesnot affectabilitytowork, some patients (e.g.,food
industryworkersorgastechnicians)mightnotbeabletocontinuetheiroriginalworkandneedspecial
advice.
Fig.5.6Differentiationofnon-sinonasalolfactorydisorders.
Summary
Agrowingnumberofpatientscomplainaboutsmelland tastedisorders.Todetermineappropriate
treatment and provide adequate counseling regarding prognosis, the disorder must be accurately
classified. A thorough history—including exact time course of the observed disorder—and
standardized olfactory or gustatory testing is mandatory. Additional investigations might be
necessary before the disorder can be classified. Only then can therapy be chosen and adequate
counselingbeprovided.
References
1.LandisBN,KonnerthCG,HummelT.Astudyonthefrequencyofolfactorydysfunction.Laryngoscope2004;114(10):1764–1769
2. Brämerson A, Johansson L, Ek L, Nordin S, Bende M. Prevalence of olfactory dysfunction: the Skövde population-based study.
Laryngoscope2004;114(4):733–737
3.DeemsDA,DotyRL,SettleRG,etal.Smellandtastedisorders,a studyof750patientsfromtheUniversityofPennsylvaniaSmelland
TasteCenter.ArchOtolaryngolHeadNeckSurg1991;117(5):519–528
4.MurphyC,SchubertCR,Cruickshanks KJ,KleinBE,KleinR,NondahlDM.Prevalenceofolfactoryimpairmentinolderadults.JAMA
2002;288(18):2307–2312
5.Vennemann MM,HummelT,BergerK.The associationbetweensmokingandsmelland tasteimpairmentin thegeneralpopulation. J
Neurol2008;255(8):1121–1126
6.DammM,Temmel A,Welge-LüssenA,etal.Olfactorydysfunctions.Epidemiologyandtherapy in Germany,AustriaandSwitzerland.
[ArticleinGerman]HNO2004;52(2):112–120
7. Hoffman HJ, Ishii EK, MacTurk RH. Age-relatedchanges in the prevalence of smell/taste problems among the United States adult
population.Resultsofthe1994disabilitysupplementtotheNationalHealthInterviewSurvey(NHIS).AnnNYAcadSci1998;855:716–
722
8. Welge-Lüssen A, Dörig P, Wolfensberger M, Krone F, Hummel T. A study about the frequency of taste disorders. J Neurol
2011;258(3):386–392
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NYAcadSci2009;1170:514–530
10.NordinS,MonschAU,MurphyC.UnawarenessofsmelllossinnormalagingandAlzheimer'sdisease:discrepancybetweenself-reported
anddiagnosedsmellsensitivity.JGerontolBPsycholSciSocSci1995;50(4):187–192
11.SantosDV,ReiterER,DiNardoLJ,CostanzoRM.Hazardouseventsassociatedwithimpairedolfactoryfunction.ArchOtolaryngolHead
NeckSurg2004;130(3):317–319
12.MiwaT,FurukawaM,TsukataniT,CostanzoRM,DiNardoLJ,ReiterER.Impactofolfactoryimpairmentonqualityoflifeanddisability.
ArchOtolaryngolHeadNeckSurg2001;127(5):497–503
13.SchiffmanSS.Tasteandsmelllossesinnormalaginganddisease.JAMA1997;278(16):1357–1362
14.WeiffenbachJM,CowartBJ,BaumBJ.Tasteintensityperceptioninaging.JGerontol1986;41(4):460–468
15.LandisBN,HummelT,HugentoblerM,GigerR,LacroixJS.Ratingsofoverallolfactoryfunction.ChemSenses2003;28(8):691–694
16.Welge-LuessenA,HummelT,StojanT,WolfensbergerM.Whatisthecorrelationbetweenratingsandmeasuresofolfactoryfunctionin
patientswitholfactoryloss?AmJRhinol2005;19(6):567–571
17.TakebayashiH,TsuzukiK,OkaH,FukazawaK,DaimonT,SakagamiM.Clinicalavailabilityofaself-administeredodorquestionnairefor
patientswitholfactorydisorders.AurisNasusLarynx2011;38(1):65–72
18.SaitoS,Ayabe-KanamuraS,TakashimaY,etal.Developmentofasmellidentificationtestusinganovelstick-typeodorpresentationkit.
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ChemSenses2006;31(4):379–391
19.ShigaH,TodaH,KobayakawaT,etal.UsefulnessofcurryodorantofodorstickidentificationtestforJapaneseinolfactoryimpairment
screening.ActaOtolaryngolSuppl2009;(562):91–94
20.CorneliaH,LandisBN,FrasnelliJ,HummelT.Computerizedhistoryofolfactorydysfunction.ChemSenses2005;30:265–278
21. LeopoldDA, Preti G, MozellMM, Youngentob SL,Wright HN. Fish-odor syndromepresenting as dysosmia. Arch Otolaryngol Head
NeckSurg1990;116(3):354–355
22.KobalG,KlimekL,WolfensbergerM,etal.Multicenterinvestigationof1,036subjectsusingastandardizedmethodfortheassessmentof
olfactory function combining tests of odor identification, odor discrimination, and olfactory thresholds. Eur Arch Otorhinolaryngol
2000;257(4):205–211
23.DotyRL,ShamanP,DannM.DevelopmentoftheUniversityofPennsylvaniaSmellIdentificationTest:astandardizedmicroencapsulated
testofolfactoryfunction.PhysiolBehav1984;32(3):489–502
24. Riechstörungen—Leitlinie zur Epidemiologie, Pathophysiologie, Klassifikation, Diagnose und Therapie.
http://www.awmf.org/leitlinien/detail/ll/017-050.html
25.YousemDM,GeckleRJ,BilkerWB,McKeownDA,DotyRL.MREvaluationofpatientswithcongenital hyposmiaoranosmia. AmJ
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26.AbolmaaliND,HietscholdV,VoglTJ,HüttenbrinkKB,Hummel T.MRevaluationinpatientswithisolatedanosmiasincebirthorearly
childhood.AJNRAmJNeuroradiol2002;23(1):157–164
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6AssessmentofOlfactionandGustation
ThomasHummel,CorneliaHummel,AntjeWelge-Luessen
Summary
Smelldisordersoccurfrequently.Ingeneral,5to6%ofthepopulationexhibitfunctionalanosmia.
Typically, interviewsare insufficient toproperlyassess patients’ symptoms.Structureddiagnostic
procedures are required to quantify olfactory function. Among diagnostic measures, simple
psychophysical instruments are most important, but electrophysiological procedures are widely
establishedaswell.Inaddition,bothimagingmethods—e.g.,volumetricassessmentoftheolfactory
bulb or functional magnetic resonance imaging with gustatory or olfactory stimulation—and
immunohistochemicalevaluationofbiopsymaterialareavailable.
WhyAssesstheChemicalSenses?
Approximately5%ofthepopulationareunabletosmellandroughly20%abovetheageof50yearsare
sufferingfromsignificantsmellloss,
1
withthemaincausesbeingsinonasaldisorders
2
oragedependent
impairmentofolfaction.
3,4
To evaluate smell disorders, they need first to be quantified. A patient history is important but
insufficient becauseofthe discrepancy betweenself-described and quantified olfactory functionin the
majorityofpatients.
5
Asimilar situationexistswith respecttogustatory function.
6
Interestingly, it has
beenshownthatself-descriptionofolfactoryperformancedoesnotreflectolfactoryfunctionperse,but
rathernasalairflow!Onlyifthepatient'sfocusis directedtowardtheiractual olfactoryacuity (e.g., by
meansofasmell test)doesrating oftheir own olfactorysensibilitybecome moreaccurate.
5
Therefore,
assessmentofchemosensoryperformanceisindispensable.
Note
Self-ratingsofolfactionandgustationcorrelatepoorlywithquantifiedtestresults.Smellandtaste
functionneedtobeassessedproperly;subjectiveestimatesareoflimitedvalue.
Psychophysical methods to evaluate the sense of smell are widely used. Approximately 200
psychophysicaltestingmethodsareavailablebutonlythemostimportantwillbeintroducedhere:First,
becausemanytestsarebasicallyverysimilarand,second,becausemostofthemareunvalidated(seeref.
7). Themajoritycurrentlyassess orthonasal olfaction(withodors entering the nose bysniffing)rather
thanretronasalolfaction(inwhichodorsreachthenoseduringeatinganddrinking).However,significant
differencesbetweenprocessingolfactorystimulifromthetwopathwayshavebeenestablished,
8,9
which
arealsopresentonaclinicallevel.
10
Psychophysicaltestsarebaseduponinterviewingpatientsandrelyupontheircooperation.Incasesof
insufficient ability to cooperate (e.g., in children or patients with cognitive impairment) or lack of
motivation to accomplish the test (e.g., if the aim of the test is to yield an expert medical opinion),
findingsmaybedifficulttoevaluate.Here,differentproceduresmaybehelpful,particularlyonesbased
upon electrophysiological methods,suchasrecordingofolfactoryevent-relatedpotentials(seebelow).
These procedures, granting a higher degree of objectivity, are technically more demanding than
psychophysicaltests,andrequiretheinvestigator'sexpertise.Owingtotheirexpense,theyareprimarily
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