肥大細胞增多症的診斷和治療| Allergy & Autoimmune Disease

肥大細胞增多症(或肥大細胞活化症) 之疾病特徵為胃腸道(GI)、皮膚、骨髓、脾、肝和淋巴結中肥大細胞數量增加。

1 肥大細胞在發炎過程和如過敏性休克等嚴重反應中，扮演 ... Areyouahealthcareprofessional? Theinformationinthiswebsiteisintendedonlyforhealthcareprofessionals.Byenteringthissite,youareconfirmingthatyouareahealthcareprofessional. EnterSite ✕ Areyoualaboratoryprofessional? Theinformationinthiswebsiteisintendedonlyforlaboratoryprofessionals.Byenteringthissite,youareconfirmingthatyouarealaboratoryprofessional. EnterSite ✕ Allergy AllergyOverview RespiratoryAllergies RespiratoryAllergiesOverview AllergicRhinitis IndoorAllergies FoodAllergies FoodAllergiesOverview Cow'sMilkAllergy EggAllergy PeanutAllergy TreeNutAllergy FishAllergy ShellfishAllergy WheatAllergy SoyAllergy AtopicDermatitis Urticaria PetAllergy VenomAllergy DrugAllergy LatexAllergy ChronicOtitisMedia Mastocytosis Asthma AutoimmuneDisease AutoimmuneDiseaseOverview AntiphospholipidSyndrome ConnectiveTissueDiseases GastrointestinalDiseases RheumatoidArthritis AutoimmuneThyroidDisease Vasculitis HowtoTest HowtoTestOverview AllergyTestingOptions AutoimmunityTestingOptions ResourceCenter AllergenEncyclopedia ContactUs Home Allergy Mastocytosis   Mastocytosis:Overview,Diagnosis,andTreatment Symptoms Diagnosis Management PracticeParameters TestingInformation AboutMastocytosis Mastocytosis,ormastcellactivationdisorder,isadisorderthatischaracterizedbyanincreasednumberofmastcellsinthegastrointestinal(GI)tract,skin,bonemarrow,spleen,liver,andlymphnodes.1Mastcellsplayacentralroleininflammatoryprocessesandinseverereactionssuchasanaphylaxis.2Therearetwocommonformsofmastocytosis—systemicmastocytosisandcutaneousmastocytosis. Systemicmastocytosis(SM)isthemoresevereformofmastocytosisandismorecommoninadultsthanchildren.Thesymptomsvary,asdotheorgansaffected,andcanincludeskinlesions,painininnerorgans,bonepain,diarrheaandvomiting,weightloss,andcardiovascularsymptoms.TryptaselevelsareincreasedinthemajorityofvariouskindsofSM.3 Cutaneousmastocytosis(CM)isthemorebenignformofmastocytosis,affectingonlytheskin.Urticariapigmentosaisthemostcommonpresentationofcutaneousmastocytosisinchildrenandrepresents70to90percentofthecases.CMismorecommoninchildrenthanadults,andisoftenoutgrown.4,5 Itisnotknownhowmanypeoplearesufferingfrommastocytosis,buttheincidencehasbeenconservativelyproposedtobefromthreetosevennewpatientspermillionperyear.6Mostcasesofmastocytosishaveabenigncauseoveralifetime.Somecasesoccurduringinfancyandearlychildhoodandothersappearinadulthood.6Mastocytosisinchildhoodmayresolvespontaneouslyandusuallyonlyinvolvestheskin;whereasthecourseinpatientswithadult-onsetdiseaseisnormallychronicandincludesnotonlytheskinbutalsosystemicsymptomsfromotherorgansystems.6 3to7newpatientspermillionperyear6 Theincidenceofmastocytosishas beenconservativelyproposedtobe fromthreetosevennewpatients permillionperyear.6 Patientsthathavemastocytosismayalsohaveacutesystemicsymptoms,including:6 Flushing Shortnessofbreath Palpitations Nausea Diarrhea Hypotension Syncope Lethargy Fatiguelastingseveralhours Themostcommonphysicalsymptomsofmastocytosisinvolvetheskin,liver,spleen,andcardiovascularsystem.Inthecaseofsomechronicsystemicsymptoms,thegastrointestinaltractandnervoussystem mayalsobeinvolved.6 Mastocytosisdiagnosis:Testingfordifferentialdiagnosis    Themostcommonphysicalsymptomsofmastocytosisinvolvetheskin,liver,spleen,andcardiovascularsystem.Inthecaseofsomechronicsystemicsymptoms,thegastrointestinaltractandnervoussystemmayalsobeinvolved.6Mostpatientswiththisdiseasewillhaveitchylesionsontheirskin. TheWorldHealthOrganization(WHO)hasaconsensusondefinitionsofvariousformsofmastocytosisandondiagnosticcriteria.7 MAJORCRITERIA Histological/immunohistochemicalalterations:Mastcellaggregatescontainingmorethan15mastcellsinbonemarrowsections MINORCRITERIA Cytologicalalterations:>25%ofmorphologicallyabnormalmastcells Detectionofc-kitmutationsoncodon816 Immunophenotypicalterations:ExpressionofCD25(±CD2)inmastcellsfrombonemarrow,peripheralblood,orotherorgan Totalserumtryptaselevelspersistently>20ng/mL(notapplicableifthereisacomorbidblooddisorderorevidenceofacutemastcellrelease) DIAGNOSISOFSYSTEMICMASTOCYTOSIS Atleastonemajorcriterionplusoneminorcriterion Atleastthreeminorcriteria Mastocytosisandanaphylaxis Tryptasetestingcanmeasurethetotalleveloftryptasereleasedbymastcellsintothecirculation.Thisenablesahealthcareprovidertoevaluateaperson’sbaselinetryptaseleveloranytransientincreasesintheleveloftryptaseafterasuspectedallergicreaction.Inhealthyindividuals,thetryptasebaselinelevelshavebeenreportedtorangeapproximatelybetween1–15μg/l.3,8Eachindividualhasitsownuniquebaselinelevel,whichusuallyisstableovertime.8 Theprevalenceofanaphylaxisinadultswiththediagnosisofmastocytosisisreportedlyashighas49percent,significantlyhigherthanexpectedinthegeneralpopulation.6Inchildren,therisktodevelopanaphylaxisisrestrictedtothosewithextensiveskinsymptomsandalsoahighbaselineserumleveloftryptase.6Therobustnessoftryptasemakesitausefultoolforconfirmingmastcellinvolvement.6  COLLECTINGASAMPLE Themeasuringrangeis1–200μg/landtheamountofserumorplasmaneededpertestis40μl.Bothserumandplasmasamplesfromvenousbloodcanbeused.Thereisnoneedforspecialprocedureswhencollectingbloodorpreparingthesamples. Sample1(peaklevel):Assoonaspossibleafterthereaction(15minutesto3hours).12-14 Sample2(baselinelevel): Aftercompleteresolutionofallclinicalsymptoms(approximately24to48hours,orlater).10,15-17 TIMING Tryptaselevelspeakbetween15and120minutesafterananaphylacticreaction.Usuallytheelevatedlevelsoftryptasecanbedetectedforuptothreetosixhoursaftertheanaphylacticreaction,anditreturnstobaselinenormallevelwithin12to14hours. Iflevelsarestillabovenormalrangeafter24hours,anothersampleshouldbetakenafter1to2weekstoestablishbaselinelevels. Sequentialmeasurementduringanaphylaxisandcomparisontoindividualbaselinelevelshasalsobeensuggested. Tomeasurebaselinelevel: Bloodsamplescanbecollectedanytime(beforeorafter)outsidetheperiodofanacutereaction.10,15-17 Toconfirmmastcellactivation: Bloodsamplesshouldbecollectedasclosetothereactionaspossible,between15minutesandthreehoursaftertheonsetofanaphylacticsymptoms.Elevatedtryptaselevelscanusuallybedetecteduptosixhoursfollowingananaphylacticreactionandreturntobaselinelevelsapproximately24to48hoursaftercompleteresolutionofallclinicalsymptoms.12-14 Mastcellactivationisconfirmedif: ∆-tryptase(peak–baseline)is≥20%oftheindividual’sownbaselinetryptase+2μg/l.11 TestingConfidence TestingIncreasesDiagnosticConfidence Addingdiagnostictestingtoaidinadifferentialdiagnosishasbeenshowntoincreaseconfidenceindiagnosisto90percent.i,ii Conventionally,adiagnosisofallergicorautoimmunediseasereliesonthecasehistoryandaphysicalexamination.However,addingdiagnostictestingtoaidinadifferentialdiagnosishasbeenshowntoincreaseconfidenceindiagnosis.i,ii Diagnostictestingcanalsohelptoimprovethepatient’squalityoflifeandproductivity,reducecostsassociatedwithabsenteeism,andoptimizeuseofmedication,inadditiontodecreasingunscheduledhealthcarevisits.iii,iv  i.Duran-TauleriaE,VignatiG,GuedanMJ,etal.TheutilityofspecificimmunoglobulinEmeasurementsinprimarycare.Allergy.2004;59(Suppl78):35-41. ii.NiggemannB,NilssonM,FriedrichsF.PaediatricallergydiagnosisinprimarycareisimprovedbyinvitroallergenspecificIgEtesting.PediatrAllergyImmunol.2008;19:325-331 iii.WelshN,etal.TheBenefitsofSpecificImmunoglobulinETestinginthePrimaryCareSetting.JAmPharmAssoc.2006;46:627. iv.SzeinbachSL,WilliamsB,MuntendamP,etal.Identificationofallergicdiseaseamongusersofantihistamines.JManagCarePharm.2004;10(3):234-238 Getscientificinformationonmorethan550allergens. AllergenEncyclopedia Learnmoreabouttesting.   AllergyTestingOptions Managementandcareofpatientswithmastocytosis Unfortunatelyforhealthcareprovidersandpatients,thereisnoonesingletreatmentthatcanbeusedtoaddressmastocytosis.Themainstrategyisavoidanceofidentifiedtriggersandallergens,suchasinsectstings,temperatureextremes,irritation,alcohol,ormedications(e.g.,aspirin,radiocontrastagents,certainanestheticagents).9 Thetreatmentofmastocytosisincludestheuseofthreedifferenttypesofinterventiontominimizetheriskofallergenexposure. 1.Dietaryandenvironmentalallergenavoidance 2.Pharmacologicalmanagement 3.Immunotherapy Clinicalguidelineshavebeendevelopedtohelpguidethemanagementandtreatmentofpatientswithmastocytosis.Acrosspracticeparametersandguidelines,re-evaluationisrecommendedformastocytosis,especiallyinyoungchildren.11Practiceparametersfortheusageofallergenimmunotherapymayalsobearelevantresource. Evenwithaspecificmanagementplaninplace,symptomsmayrecur.Patientswithahistoryofanaphylaxisrequirethemostvigilantmaintenance.Ifanaphylaxisisinitiatedbyaknownallergen,especiallythatofHymenopteravenom,youwilllikelywanttoconsiderimmunotherapyanddiscussthepossibilitywithyourpatientsduringsubsequentfollow-upvisits.10Ifsymptomspersist,orifyoususpectadditionalallergieshavedeveloped,itmaybehelpfultoconductfurthertesting. Practiceparametersandguidelines formastocytosis: Mastocytosis:2016updatedWHOclassificationandnovelemergingtreatmentconcepts Stinginginsecthypersensitivity-Apracticeparameterupdate(2016) Stinginginsecthypersensitivity(2011) AllergenImmunotherapy SublingualImmunotherapy ReadPatientCaseStudies References ValentP,etal.Standardsandstandardizationinmastocytosis:consensusstatementsondiagnostics,treatmentrecommendationsandresponsecriteria.EurJClinInvest.2007;37.435-53.  ValentP,etal.Definitions,criteriaandglobalclassificationofmastcelldisorderswithspecialreferencetomastcellactivationsyndromes:aconsensusproposal. IntArchAllergyImmunol.2012;157(3):215-225. Schwartz,LB.Diagnosticvalueoftryptaseinanaphylaxisandmastocytosis. ImmunolAllergyClinNAm.2006;26(3):451-463.  HartmannK,etal.Cutaneousmanifestationsinpatientswithmastocytosis:ConsensusreportoftheEuropeanCompetenceNetworkonMastocytosis;theAmericanAcademyofAllergy,Asthma&Immunology;andtheEuropeanAcademyofAllergologyandClinicalImmunology. JAllergyClinImmunol. 2016Jan;137(1):35-45  CastellsMetal.Diagnosisandtreatmentofcutaneousmastocytosisinchildren:practicalrecommendations. AmJClinDermatol.2011Aug1;12(4):259–270.  BrockowK,MetcalfeDD.Mastocytosis. ChemImmunolAllergy.2010;95:110–24.  ValentP,AkinC,MetcalffeDD.Mastocytosis:2016updatedWHOclassificationandnovelemergingtreatmentconcepts. Blood.2017Mar16;129(11):1420-1427   Komarowetal.Serumtryptaselevelsinatopicandnonatopicchildren. JAllergyClinImmunol. 2009(124):845-47.   MolderingsGJ,BrettnerS,HomannJ,etal.Mastcellactivationdisease:aconcisepracticalguidefordiagnosticworkupandtherapeuticoptions.JHematolOncol.2011;4:10. GonzálezdeOlanoD,Alvarez-TwoseI,Esteban-LópezMI,etal.SafetyandeffectivenessofimmunotherapyinpatientswithindolentsystemicmastocytosispresentingwithHymenopteravenomanaphylaxis.JAllergyClinImmunol.2008;121(2):519-526. Castells,M,MetcalfeDD,andEscribanoL.GuidelinesfortheDiagnosisandTreatmentofCutaneousMastocytosisinChildren.AmJClinDermatol.2011;12(4):259-270.