HemophagocyticLymphohistiocytosis

吞噬血細(xì)胞性淋巴組織細(xì)胞增多癥ContentsDefinition/DiagnosisPathophysiologyClinicalFeaturesLabTestsDiagnosisTreatmentPrognosisIntroduction1952“familialhemophagocyticreticulosis”Familial/SporadicwithVariableTriggers

1999perforinmutationdiscovered

FeaturesPathologicImmuneActivationPancytopeniaSymptoms/SignsofExtremeinflammationDefinition

asyndromicdisorder,definedanddiagnosedbyauniquepatternofclinicalfindings

theHLH-1994clinicaltrialDiagnosisCriteria

theHLH-2004clinicaltrialDiagnosisCriteriaDiagnosisCriteriaofHLHMoleculardiagnosisconsistentwithHLH:pathologicmutationsof

PRF1,

UNC13D,

Munc18-2,

Rab27a,

STX11,

SH2D1A,orBIRC4ORB.Fiveofthe8criterialistedbelowarefulfilled:????1.Fever≥38.5°C????2.Splenomegaly????3.Cytopenias(affectingatleast2of3lineagesintheperipheralblood)

Hemoglobin<90g/L(ininfants<4weeks:hemoglobin<100g/L)；Platelets<100×109/L；Neutrophils<1×109/L????4.TG↑

(fasting,>2.9mmol/L)and/orFBG↓

(<1.5g/L)????5.Hemophagocytosisinbonemarrow,spleen,lymphnodes,orliver????6.LoworabsentNK-cellactivity????7.Ferritin>500ng/mL?????8.ElevatedsCD25(α-chainofsIL-2receptor)§DetailsabouttheCriteria

ModifiedCriteria

Blood2011;118:4041ImmunologicTest(sCD25,NKactivity)shouldnotdelaydiagnosisandtreatment.OtherConditionsforTreatment

Ferratin>3000ng/mLor

FerratinincreaserapidlyorsCD25↑CNSsymptoms+Cytopenia+FeverCNSsymptoms+Hepatitis+CoagulopathyHypotension+Fever+FailureofextendedspectrumantibioticsPathophysiologyCategory1:predisposingimmunodeficiencyCategory2:significantimmuneactivationCategory3:abnormalimmunopathologyLoworabsentNK-cellfunction*Fever*Cytopenias*Geneticdefectofcytotoxicity*Splenomegaly*/hepatomegalyDecreasedfibrinogenorincreasedtriglycerides*FamilyhistoryofHLHElevatedferritin*(>3000ng/mL)Hemophagocytosis*Priorepisode(s)ofHLHorunexplainedcytopeniasElevatedsCD25*HepatitisMarkersofimpairedcytotoxicity:decreasedexpressionofperforin,SAP,XIAP,ormobilizationofCD107aElevatedsCD16393CNSinvolvementApathophysiologicviewofHLHpatternsSAPindicatesSLAM-associatedprotein;andXIAP,X-linkedinhibitorofapoptosisprotein.*TheHLH-2004diagnosticcriteria.HemophagocytosisClinicalManifestationSx&SnRatioProlongedFever97%Splenomegaly97%Hepatomegaly95%Lymphadenopathy33%Neurologicsymptoms33%Rash31%AdditionalClinicalFeaturesProlongedFever

LiverDisease

Coagulopathy

BoneMarrowFailure

SkinManifestations(>50%)

PulmonaryDysfunction

Brain,ophthalmic,andneuromuscularsymptomsHLHSkinLesionsOtherimportantmarkersLiverALT/AST↑>3×ULN(50-90%)LDH↑(85%)Bil↑(>80%)GGT↑

TG↑↑

coagulationLiverProduction↓

DIC

Fbg↓↓MAS:HLHinrheumaticdisease

CM:fever,hepatosplenomegaly,hepatitis,lymphadenopathy,DICCytopeniaisalatemanifestation.AssociatedDiseases:Systemic-onset