简介：Nonceliacglutensensitivity(NCGS)isasyndromecharacterizedbyacohortofsymptomsrelatedtotheingestionofgluten-containingfoodinsubjectswhoarenotaffectedbyceliacdisease(CD)orwheatallergy.Thepossibilityofsystemicmanifestationsinthisconditionhasbeensuggestedbysomereports.Inmostcasestheyarecharacterizedbyvaguesymptomssuchas‘foggymind’,headache,fatigue,jointandmusclepain,legorarmnumbnessevenifmorespecificcomplaintshavebeendescribed.NCGShasanimmune-relatedbackground.IndeedthereisastrongevidencethataselectiveactivationofinnateimmunitymaybethetriggerforNCGSinflammatoryresponse.ThemostcommonlyautoimmunedisordersassociatedtoNCGSareHashimotothyroiditis,dermatitisherpetiformis,psoriasisandrheumatologicdiseases.ThepredominanceofHashimotothyroiditisrepresentsaninterestingfinding,sinceithasbeenindirectlyconfirmedbyanItalianstudy,showingthatautoimmunethyroiddiseaseisariskfactorfortheevolutiontowardsNCGSinagroupofpatientswithminimalduodenalinflammation.Onthesebases,anautoimmunestigmainNCGSisstronglysupported;itcouldbeacharacteristicfeaturethatcouldhelpthediagnosisandbesimultaneouslymanaged.ApossibleneurologicalinvolvementhasbeenunderlinedbyNCGSassociationwithglutenataxia,glutenneuropathyandglutenencephalopathy.NCGSpatientsmayshowevenpsychiatricdiseasessuchasdepression,anxietyandpsychosis.Finally,alinkwithfunctionaldisorders(irritablebowelsyndromeandfibromyalgia)isatopicunderdiscussion.Inconclusion,thenoveltyofthismatterhasgeneratedanexpansionofliteraturedatawiththeunavoidableconsequencethatsomereportsareoftenbasedonlowlevelsofevidence.Therefore,onlystudiesperformedonlargesampleswiththeinclusionofcontrolgroupswillbeabletoclearlyestablishwhetherthelargeinformationfromtheliteratureregardingextra-intestinalNCGSmanifestationscouldbesupportedbyevidence-basedagreements.