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0.021592015400528908
] |
different\tfood\tallergen\tor\taeroallergen\t(i.e.,\ta\tpollen),\twhich\tmay\tthen\ttrigger\tan\tadverse\treaction\nsimilar\tto\tthat\ttriggered\tby\tthe\toriginal\tfood\tallergen;\tcross-reactivity\tis\tcommon,\n\tfor\texample,\namong\tdifferent\tshellfish\tand\tdifferent\ttree\tnuts,\tand\tin\tpollen-food\tallergy\tsyndrome\t(PFAS)\n•\t\nDesensitization:
|
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0.019362274557352066
] |
•\t\nDesensitization:\n\ta\tstate\tof\tclinical\tand\timmunologic\tnonresponsiveness\tto\ta\tfood\tallergen\tthat\ncan\tbe\tinduced\tby\tcareful,\tmedical-guided\tadministration\tof\tgradually\tincreasing\tamounts\tof\tthe\nallergen\tover\ta\tshort\tperiod\tof\ttime\t(hours\tto\tdays);\tthe\tmaintenance\tof\tsuch\tdesensitization\nusually\n\trequires\tcontinued\tregular\texposure\tto\tthe\tallergen
|
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reactivity:\n\tthe\tconcept\tthat\twhen\tthe\tbody’s\tnormal\ttolerance\nof\tfriendly\tantigenic\tsubstances\t(autoantigens\tproduced\tby\tan\tindividual’s\tbody)\tis\tdisrupted\nbecause\tof\tdisease,\tinjury,\tshock,\ttrauma,\tsurgery,\tdrugs,\tblood\ttransfusion,\tor\tenvironmental
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triggers,\tthe\tingestion\tof\tfoods\tcontaining\tantigenic\tsubstances\twith\ta\tcomposition\tsimilar\tto\nthose\tof\tthe\tbody’s\tautoantigens\tcan\tresult\tin\tthe\n\tproduction\tof\tantibodies\tthat\treact\tto\tthe\tfood\nantigens\tand\tthe\tbody’s\town\ttissues\t(Vojdani,\t2015)\n•\t\nFood\tintolerance:\n\tan\tadverse\treaction\tto\ta\tfood\tor\tfood\tcomponent\tthat\tlacks\tan\tidentified
|
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immunologic\tpathophysiology\n•\t\nFood\tsensitivity:\n\ta\tterm\toften\tused\tto\tdescribe\ta\treaction\twhen\tit\tis\tunclear\twhether\tit\tis\nimmunologically\tmediated\tor\tnot\n•\t\nOral\ttolerance:\n\tthe\tprocess\tthat\tallows\tan\tindividual\n\tto\teat\tfood\tthat\tis\t“foreign”\twithout\tany\till\neffects\tor\treactions\tto\tit\n•\t\nSensitivity-related\tillness:
|
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] |
effects\tor\treactions\tto\tit\n•\t\nSensitivity-related\tillness:\n\tthe\tconcept\tthat\tan\tindividual\twho\tis\texposed\tto\tsome\ttype\tof\ntoxicant\tor\tinsult\tmay\tthen,\tby\tas\tyet\tunclear\tmechanisms,\tbecome\tsensitive\tto\ta\tfood,\tinhalant,\nor\tchemical\t(Genuis,\t2010)
|
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] |
or\tchemical\t(Genuis,\t2010)\nSource:\tIOM\tGlobal\tReport:\tFinding\ta\tPath\tto\tSafety\tin\tFood\tAllergy:\tAssessment\tof\tthe\tGlobal\tBurden,\tCauses,\nPrevention,\tManagement\tand\tPublic\tPolicy.\nPrevalence\nThere\tis\tevidence\tthat\tadverse\tfood\treactions\tare\tmore\tprevalent\tthan\tin\tthe\tpast,\twith\ta\tdramatic
|
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] |
increase\tin\tfood\tallergies\tin\trecent\tdecades.\tIt\tis\testimated\tthat\t10.8%\tof\tU.S.\tadults\thave\tat\tleast\tone\nfood\tallergy,\tas\tevidenced\tfrom\tsymptoms\ttypical\tof\tan\tIgE-mediated\treaction.\tBut\tonly\tabout\thalf\tof\nthose\tfood\tallergic\tadults\n\thave\tbeen\tdiagnosed\tby\ta\tphysician.\tOf\teven\tmore\tinterest\tis\tthe\testimate\tthat
|
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0.08829127252101898,
0.05602414906024933,
0.03901868686079979,
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] |
19%\tbelieve\tthey\thave\ta\tfood\tallergy\t(\nGupta\tet\tal,\t2019\n).\tIn\tAustralia\tit\tmay\tbe\tas\thigh\tas\t10%\t(\nRenz\tet\nal,\t2018\n).\tThere\tare\talso\tdocumented\tworldwide\tincreases\tin\tfood\tallergy\tin\trapidly\temerging\tareas\tof\nAsia,\tsuch\tas\tChina.\tEstimates\tsuggest\tthat\t20%\tof\tthe\tpopulation\talter\ttheir\tdiet\tdue\tto\tperceived\nadverse\tfood\n\treactions\t(
|
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] |
adverse\tfood\n\treactions\t(\nTurnbull\tet\tal,\t2015\n).\nHowever,\tthere\tare\tgaps\tin\tthe\tprecise\tprevalence\tof\tadverse\tfood\treactions\tdue\tto\tmisuse\tof\tthe\tterms\n“food\tallergy”\tand\t“food\tintolerance,”\tvariations\tin\tstudy\tdesign\tand\tmethodologies,\tand\tinflated\tself-
|
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reporting.\tGeographic\tvariations;\tdiet\texposure\teffects;\tdifferences\tin\tage,\trace,\tand\tethnicity;\tand\tother\nfactors\talso\tcomplicate\tdata\treporting.\tDespite\n\tthe\tlack\tof\tprecise\tprevalence\tdata,\tthere\tis\tagreement\nthat\tchanges\tin\tdiet,\tlifestyle,\tand\tenvironmental\tinfluences,\tinteracting\twith\tgenetic\tpredisposition\tand
|
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microbiome\talterations,\tcan\tbe\timplicated\tin\tthe\tescalation\tof\tadverse\tfood\treactions\tand\tthe\tparallel\trise\nin\tother\tchronic\tdisorders\tsuch\tas\tasthma\tand\tautoimmune\tdiseases\t(\nSicherer\tand\tSampson,\t2018\n;\nNASEM,\t2017\n).\nEtiology\nAdverse\n\tfood\treactions\tillustrate\tthe\tcritical\timportance\tof\tappreciating\t“biochemical\tuniqueness”\tas\ta
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core\tclinical\tconcept\tin\tnutrition\tassessment.\tNumerous\tfactors\thave\tbeen\tidentified\tthat\tplay\ta\trole\tin\ninfluencing\timmune-\tand\tnonimmune-mediated\tresponses\tto\tfood\tor\tfood\tcomponents\tand\ttheir\tultimate\ninterpretation\tby\tthe\tbody\tas\teither\t“friend”\tor\t“foe,”\tincluding:\nIndividual\tFactors\nAge\nGenetics\tand\tepigenetics
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] |
Individual\tFactors\nAge\nGenetics\tand\tepigenetics\nEarly\tlife\tfactors\t(maternal\tnutrition,\tbirth\tdelivery\tmethod,\tbreast\tor\tformula\tfeeding)\nImmunocompetence\tand\tpersonal\tdifferences\tin\timmune\tfunction\nIntestinal\tand\tskin\tbarrier\tdefects\nMicrobiome\nIncreased\thygiene\nUse\tof\tmedications\t(e.g.,\tantacids,\tnonsteroidal\tantiinflammatory\tmedications)
|
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0.001961486181244254
] |
Underlying\tdisease\nPresence\tof\tchronic\tstress\nEnvironmental\tinfluences\n\t(toxin\tand\tchemical\texposures\tsometimes\treferred\tto\tas\tthe\texposome)\nFood-related\tfactors\nModern\twesternized\tdiet\nPrenatal\tperinatal,\tand\tmaternal\tnutrition\nAllergen\ttype,\tdose,\tand\troute\tof\texposure\nMicrobial\tproducts\tand\tcontamination\twith\tmicroorganisms
|
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] |
Microbial\tproducts\tand\tcontamination\twith\tmicroorganisms\nFood\tmatrix\t(proteins,\tlipids,\tand\tglycosylated\tsugars)\nCooking\ttemperature\nEpithelial\tbarrier\tinsulting\tagent\t(alcohol,\tadditives,\n\ttoxins,\tunknown\tingredients)\t(\nSampson\tet\tal,\n2018\n).\nGenetics\tand\tepigenetics
|
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Sampson\tet\tal,\n2018\n).\nGenetics\tand\tepigenetics\nIt\thas\tbeen\trecognized\tfor\tmore\tthan\ta\tcentury\tthat\tgenetics\tplays\ta\trole\tin\tallergies\tand\tasthma.\tFamilial\naggregations\tand\theritability\testimates\tfrom\ttwin\tstudies\tprovide\tinitial\tevidence\tfor\tgenetic
|
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predisposition\tfor\tfood\tallergy,\talthough\tamong\tsiblings,\tan\tincreased\trate\tof\tsensitization\tdoes\tnot\nequate\tto\n\tclinical\treactivity.\tA\tnumber\tof\tmonogenic\tdisorders\tassociated\twith\tatopy\tand\tfood\tallergy\nhave\tbeen\tidentified;\thowever,\tthe\tgenetics\tof\tfood\tallergy\thave\tshifted\tfrom\tidentifying\ta\tsingle\tchange
|
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of\tfood\tallergy\tare\tmultifactorial\tand\tcomplex.\tThe\nexpression\tof\tfood\tallergy\tis\tinfluenced\tby\tthe\tenvironment,\tgene-environment\tinteractions,\tand\nepigenetic\n\tmodification\tof\tthe\tgenome\t(“epigenome”).\tThe\tepigenome\tis\tlargely\testablished\tin\tutero\tand\nis\trelevant\tto\tearly\tlife\torigins\tof\tallergic\tdisease\t(\nNASEM,\t2017\n;
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NASEM,\t2017\n;\t\nCarter\tand\tFrischmeyer-Guerrerio,
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] |
2018\n).\nMore\trecently,\tgenome\twide\tassociation\n\tstudies\t(GWASs)\tidentified\tgenes\tassociated\twith\tfood\nallergies.\tOne\tGWAS\tstudy\texamined\t1500\tchildren\twith\tfood\tallergies\tin\tGermany\tand\tthe\tUnited\tStates.\nThis\tstudy\texamined\tmore\tthan\tfive\tmillion\tgenetic\tvariations\tor\tsingle\tnucleotide\tpolymorphisms\t(SNPs)
|
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] |
in\teach\tchild\tin\tthe\tstudy\tand\tcompared\tthe\tfrequency\tof\tthese\tSNPs\twith\tthe\tcontrol\tsubjects.\tIn\naddition\tto\tthe\tlarge\tnumber\tof\tsubjects,\n\tunlike\tother\tstudies,\tthe\tresearchers\talso\tincluded\tan\toral\tfood\nchallenge\tto\tconfirm\tthe\tallergy\tdiagnosis.\tThe\tstudy\tidentified\tfive\tgenetic\trisk\tloci\tfor\tfood\tallergies,
|
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and\tfour\tof\tthem\tshowed\ta\tstrong\tassociation\twith\tloci\tfor\t\natopic\tdermatitis\n\t(hereditary\teczematous\nrash),\tasthma,\tand\tother\tchronic\tinflammatory\tand\tautoimmune\tdiseases.\tThe\t\nSERPINB\n\tgene\tcluster\ton\nchromosome\t18\twas\tpinpointed\n\tas\ta\tspecific\tgenetic\trisk\tlocus\tfor\tfood\tallergies.\tThe\tgenes\tin\tthis
|
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] |
particular\tcluster\tare\texpressed\tin\tthe\tskin\tand\tmucous\tmembrane\tof\tthe\tesophagus,\twhich\tare\tinvolved\nin\tmaintaining\tepithelial\tbarrier\tintegrity\t(\nMarenholz\tet\tal,\t2017\n).\nAnother\tGWAS\tstudy\tincluded\ta\tmeta-analysis\tof\ttwo\tphenotypes,\tpeanut\tallergy\tand\tfood\tallergy,\tand\nexamined\tseven\tstudies\tfrom\tCanadian,\tAmerican,\tAustralian,
|
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] |
examined\tseven\tstudies\tfrom\tCanadian,\tAmerican,\tAustralian,\n\tGerman,\tand\tDutch\tpopulations.\tMultiple\ngenes\twere\tidentified\tas\trisk\tfactors\tfor\tpeanut\tallergy\tand\tfood\tallergy\tand\tare\tinvolved\tin\tepigenetic\nregulation\tof\tgene\texpression\t(\nAsai\tet\tal,\t2018\n).
|
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] |
regulation\tof\tgene\texpression\t(\nAsai\tet\tal,\t2018\n).\nUnlike\tother\tdiseases,\tthe\tnumber\tof\tidentified\tloci\tfor\tfood\tallergies\tis\trelatively\tsmall.\tMost\tof\tthe\nidentified\tcandidate\tgenes\tencode\tfor\tproducts\tinfluencing\timmune\tmechanisms\ttoward\ta\tTh2\ninflammatory
|
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0.061103709042072296,
0.10668684542179108,
0.12551447749137878,
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] |
inflammatory\n\tshift.\tIt\tis\thypothesized\tthat\tgenetic\tpredispositions\tin\tthe\tcontext\tof\tcertain\tenvironmental\ninfluences\tsuch\tas\tintestinal\tviral\tinfection\tmay\tresult\tin\timmune\tsystem\tdysfunction\tand\tresult\tin\tfood\nallergy\t(\nNASEM,\t2017\n).\t(See\t\nChapters\t6\n\tand\t\n7\n).\nPathophysiology\tof\tfood\tallergy
|
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] |
).\t(See\t\nChapters\t6\n\tand\t\n7\n).\nPathophysiology\tof\tfood\tallergy\nMajor\tadvances\tin\tresearch\tare\tproviding\tfurther\tinsights\tinto\tthe\tmechanisms\tleading\tto\tfood\tallergies.\nA\tbasic\n\tunderstanding\tof\tthe\timmune\tsystem\tis\tessential\tsince\tthe\tmechanisms\tentail\tmultiple\tmolecules\ninvolved\tin\timmune\tregulation.\nImmune\tsystem\tbasics\nAntibodies
|
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] |
involved\tin\timmune\tregulation.\nImmune\tsystem\tbasics\nAntibodies\n\tare\tspecialized\timmune\tproteins\tthat\tare\tproduced\tin\tresponse\tto\tthe\tintroduction\tof\tan\nantigen\n\t(an\t\nallergen\n,\ttoxin,\tor\tforeign\tsubstance)\tinto\tthe\tbody.\tBecause\tof\ttheir\tassociation\twith\tthe\nimmune\tsystem,\tantibodies\tare\treferred\tto\n\tas\t\nimmunoglobulins\t(Ig)
|
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] |
immune\tsystem,\tantibodies\tare\treferred\tto\n\tas\t\nimmunoglobulins\t(Ig)\n.\tFive\tdistinct\tclasses\tof\tantibodies\nhave\tbeen\tidentified:\tIgA,\tIgD,\tIgE,\tIgG,\tand\tIgM.\tEach\tIg\thas\ta\tspecific\tfunction\tin\timmune-mediated\nreactions\t(\nBox\t25.2\n).\nBOX\t25.2\nThe\tImmunoglobulins\nIgA
|
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reactions\t(\nBox\t25.2\n).\nBOX\t25.2\nThe\tImmunoglobulins\nIgA\nFound\tin\ttwo\tforms—serum\tIgA\tand\tsecretory\tIgA\t(sIgA).\tThe\tlatter\tis\tpresent\tin\tmucus\tsecretions\tin\nthe\tmouth,\trespiratory\tand\tgastrointestinal\ttracts,\tvagina,\tand\tcolostrum\n\tin\tmammalian\tmilk.\tIt
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in\tmammalian\tmilk.\tIt\nincludes\ta\t“secretory\tpiece”\tin\tits\tstructure\tthat\tprotects\tit\tfrom\tprotein-destroying\tenzymes\tin\tthe\ndigestive\ttract\tso\tthat\tit\tsurvives\tin\tan\tactive\tform\tas\ta\t“first-line”\tdefense\tagainst\tantigens\tentering\nfrom\tthe\texternal\tenvironment.\tSerum\tIgA,\twhich\tdoes\tnot\thave\tthe\tsecretory\tpiece,\tis\tin\tthe\tsecond
|
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highest\tamount\tin\tcirculation,\texceeded\tonly\tby\tIgG.\nIgD\nFound\tin\n\tsmall\tamounts\tin\tthe\ttissues\tthat\tline\tthe\tbelly\tand\tchest;\tinvolved\tin\timmunoglobulin\tclass\nswitching.\tSignals\tB\tcells\tto\tbe\tactivated.\tSuggestion\tthat\tIgD-producing\tB\tcells\tare\tauto\treactive
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lymphocytes\tand\tmay\tbe\tinvolved\tin\tautoimmune\tdisease.\tIts\trole\tin\tallergy\tis\tprobably\tminimal.\nIgE\nThe\tclassic\tallergy\tantibody\tof\thay\tfever,\tasthma,\teczema,\tfood-induced\tallergy,\tfood-induced\nanaphylaxis,\n\tpollen-food\tallergy\tsyndrome\t(PFAS),\tand\tlatex-fruit\tallergy.\tImmediate\tallergic\treactions
|
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0.06496410071849823,
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0.016240477561950684,
0.08038261532783508,
0.09541565924882889,
0.022481022402644157
] |
usually\tinvolve\tIgE\tand\tare\tthe\tmost\tclearly\tunderstood\tmechanisms.\nIgG\nThe\tonly\tantibody\tthat\tcrosses\tthe\tplacenta\tfrom\tmother\tto\tbaby\tand\tis\tthe\tmost\tcommon\tantibody\nin\tthe\tblood.\tDefends\tagainst\tpathogens\tand\tpersists\tlong\tafter\tthe\tthreat\tis\tover.\tFour\tsubtypes\ninclude\tIgG1,\tIgG2,\tIgG3,\tand\tIgG4.\tFood
|
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0.003989288117736578,
0.05008804053068161,
0.07595489919185638,
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] |
include\tIgG1,\tIgG2,\tIgG3,\tand\tIgG4.\tFood\n\tprotein–specific\tIgG\tantibodies\ttend\tto\trise\tin\tthe\tfirst\tfew\nmonths\tafter\tthe\tintroduction\tof\ta\tfood\tand\tthen\tdecreases\teven\tthough\tthe\tfood\tmay\tcontinue\tto\tbe\nconsumed.\tIt\tappears\tto\tbe\tpart\tof\tthe\tprocess\tof\tdevelopment\tof\ttolerance\tto\tfood.\tA\trise\tin\tantigen-
|
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] |
specific\tIgG4\taccompanied\tby\ta\tdrop\tin\tIgE\toften\tindicates\ttolerance\tof\tthe\tfood.\tPeople\twith\ninflammatory\tbowel\tdisorders\tsuch\tas\tuntreated\n\tceliac\tdisease\tor\tulcerative\tcolitis\toften\thave\thigh\nlevels\tof\tIgG\tand\tIgM\t(Stapel\tet\tal,\t2008),\tpossibly\tindicating\tthe\tpassage\tof\tfood\tmolecules\tas\n“foreign\tinvaders”\tinto\tcirculation.\nIgM
|
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] |
“foreign\tinvaders”\tinto\tcirculation.\nIgM\nThe\tlargest\tantibody,\ta\tfirst-line\tdefender\tthat\tcan\tmop\tup\tmany\tantigens\tat\tone\ttime.\tIt\tis\tproduced\nby\tthe\tfetus\tin\tutero\tand\tits\tlevel\trises\tin\tthe\tpresence\tof\tan\tin\tutero\tinfection.\nStapel\tSO,\tAsero\n\tR,\tBallmer-Weber\tBK,\tet\tal:\tTesting\tfor\tIgG4\tagainst\tfoods\tis\tnot\trecommended\tas\ta
|
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diagnostic\ttool:\tEAACI\tTask\tForce\tReport,\t\nAllergy\n\t63:793–796,\t2008.\nThe\tproduction\tof\tantibodies\tis\ta\tmajor\tfunction\tof\tthe\timmune\tsystem\tand\tis\tcarried\tout\tby\ta\nparticular\ttype\tof\t\nlymphocyte\n\t(white\tblood\tcell).\tThere\tare\ttwo\timportant\tgroups\tof\tlymphocytes:\t\nB-
|
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cells\n\tarising\tfrom\tstem\tcells\tin\tthe\tbone\tmarrow,\n\tand\t\nT-cells\n,\talso\toriginated\tfrom\tstem\tcells\tbut\tlater\ntransported\tto\tthe\tthymus\tgland\twhere\tthey\tmature,\thence\tthe\tname\tT-cells.\tMonocytes\tand\nmacrophages\tare\tprimarily\tphagocytes\tthat\tengulf\tforeign\tmaterial,\tbreak\tit\tapart,\tand\tdisplay\tspecific
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] |
different\tcircumstances,\tand\tthey\tsecrete\tdifferent\tsets\tof\t\ncytokines\n\t(chemical\tmessengers).\t\nTh\tcells\nare\thelper\tcells\tthat\tadjust\tthe\tsystem.\t\nTh1\tcells\n\tregulate\tthe\tactivities\tof\tthe\tB-cells\tto\tproduce\nantibodies\tand\tdirect\tdamage\tto\ttarget\tcells,\tresulting\tin\tthe\n\tdestruction\tof\tantigens.\tThis\tfunction\tis
|
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] |
destruction\tof\tantigens.\tThis\tfunction\tis\nuseful\tin\tdefending\tagainst\tbacteria,\tviruses,\tand\tother\tpathogenic\tcells.\t\nTh2\tcells\n\tmediate\tthe\tallergic\nresponse\tby\tregulating\tthe\tproduction\tby\tB-cells\tof\tIgE\tsensitized\tto\tfood\tor\tother\tallergens.\tOther\tT-cells\nare\t\nT-regulatory\tcells\t(T-reg\tcells)\n\tand\t\nT-suppressor\tcells
|
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] |
are\t\nT-regulatory\tcells\t(T-reg\tcells)\n\tand\t\nT-suppressor\tcells\n\tthat\tregulate\tthe\timmune\tresponse\tso\tthat\nthere\tis\ttolerance\tof\tthe\tforeign\tbut\n\tsafe\tmolecule.\nAlso\tinvolved\tin\tallergic\treactions\tare\t\ngranulocytes\n,\tcells\tthat\tcontain\tintracellular\tgranules,\twhich\tact
|
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granulocytes\n,\tcells\tthat\tcontain\tintracellular\tgranules,\twhich\tact\nas\tstorage\tdepots\tfor\tdefense\tchemicals\tor\tinflammatory\tmediators\tthat,\twhen\treleased,\tnot\tonly\tprotect\nthe\tbody\tfrom\tinvading\tpathogens\tbut\talso\tcan\tproduce\tallergic\tsymptoms.\tGranulocytes\tcalled\t\nmast\ncells\n\tare\tlocated\tin\tthe\tlungs,\tskin,\ttongue,\tand\tlinings\tof\tthe\tnose\tand
|
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] |
are\tlocated\tin\tthe\tlungs,\tskin,\ttongue,\tand\tlinings\tof\tthe\tnose\tand\n\tintestinal\ttract,\tand\tthose\tcalled\nbasophils\n\tare\tin\tthe\tcirculation.\tOf\timportance\tin\tnon-IgE\tmediated\tallergy\tare\t\neosinophils\n,\tanother\nform\tof\tgranulocytes\tthat\tare\tin\tblood\tand\ttissues\tand,\twhen\tstimulated\tby\tcytokines\tproduced\tby\tTh2
|
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cells,\tmigrate\tto\tthe\tsite\tof\tan\tallergic\treaction.\nWhen\tgranulocytes\tdegranulate\tthey\trelease\t\ninflammatory\tmediators\n,\tsuch\tas\thistamine,\tchymase,\nand\ttryptase\n\tand,\tin\tthe\tcase\tof\tmast\tcells,\tthere\tis\tde\tnovo\tsynthesis\tof\tlipid\tmetabolites\tof\tarachidonic
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] |
acid—prostaglandins,\tleukotrienes,\tand\tplasma\tactivating\tfactor\t(PAF).\tEach\tof\tthese\tmediators\thas\ta\nspecific\teffect\ton\tlocal\ttissues\tand\tat\tother\tsites,\tresulting\tin\tthe\tsymptoms\tof\tan\tallergic\treaction—\nvasodilation,\tincreased\tvascular\tpermeability\tleading\tto\tangioedema,\tnociceptive\t(painful)\tnerve\nactivation
|
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] |
activation\n\tcausing\titchiness,\tsmooth\tmuscle\tconstriction,\tmucous\tsecretion,\tand\tacute\tdiarrhea.\nAllergic\tresponse\nThe\tpathophysiology\tof\tthe\tallergic\tresponse\tcan\tbe\tdescribed\tin\tthree\tphases:\tthe\tbreakdown\tof\toral\ntolerance,\tallergen\tsensitization,\tand\treactivity\tto\tallergens\tleading\tto\tallergy\tsymptoms.\nBreakdown\tof\toral\ttolerance.
|
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] |
Breakdown\tof\toral\ttolerance.\nHumans\tare\texposed\tto\tthousands\tof\tforeign\tmolecules\tdaily\tfrom\n\tfood\tand\tthe\tenvironment.\tExposure\tto\nthese\tforeign\tmolecules\tin\tthe\tdigestive\ttract\tthrough\tingested\tsubstances\tis\tusually\tfollowed\tby\timmune\nregulation\tor\tsuppression,\tsuch\tthat\tthe\tsubstance\tor\tfood\tis\trecognized\tas\t“foreign\tbut\tsafe,”\twhich\tis\ta
|
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prerequisite\tfor\tthe\tdevelopment\tof\ttolerance\tto\ta\tfood\tor\tfood\tcomponent.\t\nOral\ttolerance\n\tis\tthe\nmechanism\tby\twhich\tpotentially\tantigenic\tsubstances\n\tdo\tnot\ttrigger\tan\timmune\tresponse\tand\tis\tthe\nnormal\tphysiologic\tresponse\tto\tingested\tantigens\t(\nTordesillas\tand\tBerin,\t2018\n).\tThe\tdevelopment\tof
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Tordesillas\tand\tBerin,\t2018\n).\tThe\tdevelopment\tof\nimmunologic\tand\tclinical\ttolerance\tis\tthus\tcritical\tto\tpreventing\tfood\tallergies\tand\tother\tchronic\ninflammatory\tdiseases.\tOral\ttolerance\tis\tmediated\tby\tseveral\timmune\tcells,\tincluding\tAPCs\tsuch\tas\ndendritic\tcells\t(DCs)\n\tand\tmacrophages,\tand\tregulatory\tT-cells\n\t(T\nreg\n\tcells)\t(\nBauer\tet\tal,\t2015
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] |
(T\nreg\n\tcells)\t(\nBauer\tet\tal,\t2015\n).\tTolerance\nis\tacquired\twith\tinnate\tand\tadaptive\timmune\tresponses\tacting\tin\ta\tcoordinated\tmanner\tto\tmount\ta\nresponse\tto\tantigen\texposure.\tIt\tis\ta\tprocess\tthat\tstarts\tin\tutero\tand\tpersists\tthroughout\tlife\t(\nRenz\tet\tal,\n2018\n).
|
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] |
Renz\tet\tal,\n2018\n).\nThe\tgut\tmicroenvironment\tsupports\tand\tpromotes\texpansion\tof\tthe\tregulating\tactivity\tof\tT-reg\tcells\nthrough\tmultiple\tprocesses\tincluding\tthe\n\tpresence\tof\tretinoic\tacid\t(from\tvitamin\tA)\tand\tmicrobial\nmetabolites,\tsuch\tas\tshort-chain\tfatty\tacids.\tB-cells\talso\tinhibit\thostile\timmune\treactivity.\t\nB-regulatory\n(B-reg)\tcells
|
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B-regulatory\n(B-reg)\tcells\n\tact\tmainly\tthrough\tinterleukin-10\t(IL-10),\tan\tantiinflammatory\tcytokine\tto\treduce\tinfection\nand\tallergic\tinflammation\tand\tto\tpromote\ttolerance.\tA\tbreakdown\tin\tthe\ttolerogenic\tprocess\tleads\tto\ta\nshift\taway\tfrom\tT-reg\tcell\n\tinduction\tto\tthe\tgeneration\tof\tproallergic\tTh2\tcells\tand\tresults\tin\tsensitization
|
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] |
to\tfood\tallergens\t(\nRenz\tet\tal,\t2018\n;\t\nSampson\tet\tal,\t2018\n).\nSensitization.\nSensitization\n\tto\tfood\tantigens\tcan\ttake\tplace\tin\tthe\tgastrointestinal\ttract,\toral\tcavity,\tskin,\tand\noccasionally\tin\tthe\trespiratory\ttract\t(\nSampson\tet\tal,\t2018\n).\tGastrointestinal\t(GI)\tfunction\tis\tkey\tto\tthe\nmaintenance\tof\toral\ttolerance,
|
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] |
maintenance\tof\toral\ttolerance,\n\tand\tavoidance\tof\tallergic\tsensitization\tand\tallergic\tresponse,\tsince\tthe\nvast\tmajority\tof\tfood\tproteins\tare\tbroken\tdown\tby\tgastric\tacid\tand\tdigestive\tenzymes\tin\tthe\tstomach\tand\nintestine.\nRecognized\tas\tbeing\tincreasingly\tessential\tto\tthis\tfunction\tof\tthe\tGI\ttract\tis\tthe\tpresence\tof\tthe\tgut\nmicrobiome
|
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] |
microbiome\n,\tthe\tcollection\tof\tdifferent\ttypes\tof\tmicrobes\t(bacteria,\tbacteriophage,\tfungi,\tprotozoa,\tand\nviruses)\tthat\tlive\tinside\tthe\tgut.\tThe\tintestinal\tmicrobiome\tis\tresponsible\tfor\tregulating\tthe\texpansion\tof\nT-reg\tcells\tand\tTh1\tand\tTh2\ttype\tcells\tto\tpromote\timmune\tbalance.\t(\nRussler-Germain\tet\tal,\t2017\n).\nDysbiosis
|
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Russler-Germain\tet\tal,\t2017\n).\nDysbiosis\n\toccurs\twhen\tthere\tis\tan\timbalance\tin\tthe\tmicrobial\tecosystem,\twhich\tcan\tcontribute\tto\nincreased\tintestinal\tpermeability\tor\t“leaky\tgut,”\n\tand\tthe\tincreased\tlikelihood\tthat\tintact\tfood\nproteins\tand\tpeptides\twill\tpass\tthrough\tthe\tintestinal\tlumen\tand\treach\tthe\tlymphoid\ttissue,\tleading\tto
|
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immune\tsensitization\tand\tpossibly\treactivity\t(\nPlunkett\tand\tNagler,\t2017\n).\tThe\t\ngut-associated\tlymphoid\ntissue\t(GALT)\n\tis\tthe\tlargest\tmass\tof\tlymphoid\ttissue\tin\tthe\tbody\tand\tantigen\tpenetration\tand\npresentation\tto\tthe\tGALT\tdrives\tfood\tsensitization\t(\nFritscher-Ravens\tet\tal,\t2014\n).\tOther\tconditions\n\tsuch
|
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] |
Fritscher-Ravens\tet\tal,\t2014\n).\tOther\tconditions\n\tsuch\nas\tGI\tdisease,\tmalnutrition,\tfetal\tprematurity,\tand\timmunodeficiency\talso\tmay\tbe\tassociated\twith\nincreased\tgut\tpermeability\tand\trisk\tof\tdevelopment\tof\tfood\tallergy.\tDisruptions\tin\tthe\tmicrobiome\tand
|
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] |
the\tintestinal\twall\tbarrier\tare\tthe\tresult\tof\tvarious\tfactors,\tincluding\tcesarean\tdelivery,\tformula\tfeeding,\nantibiotics,\tchronic\tstress,\tinfections,\tand\talterations\tin\tthe\tmicrobiome\tdue\tto\tdisease\n\t(see\t\nChapters\t1\nand\t\n27\n\tfor\tfurther\tdiscussion\tof\tthe\tmicrobiome).
|
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] |
(see\t\nChapters\t1\nand\t\n27\n\tfor\tfurther\tdiscussion\tof\tthe\tmicrobiome).\nAdditional\tforces\tdriving\ttolerance\tbreakdown\tand\tpotential\tsensitization\tmight\tarise\toutside\tthe\nintestine,\tas\tthere\tis\tevidence\tthat\tfood\tallergen\tentry\tcan\toccur\tthrough\tscratched,\tbroken,\tand\ninflamed\tskin\t(\nRenz\tet\tal,\t2018
|
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] |
inflamed\tskin\t(\nRenz\tet\tal,\t2018\n).\tLike\tthe\tgut,\tthe\tskin\tmicrobiome\tconsists\tof\tthousands\tof\tmicrobial\norganisms\tand\ttheir\tbyproducts\n\tthat\tinhabit\tthe\tskin.\tA\tharmonious\tbalance\tof\tthe\tgut-skin-microbiota\tis\nnow\tthought\tto\tbe\tvital\tto\ta\twell-functioning\timmune\tsystem.
|
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] |
Reaction.\nThe\tthird\tphase\tof\tthe\tallergic\tresponse\tis\treactivity\twhenever\tan\tallergen\tto\twhich\tthe\timmune\tsystem\tis\nnow\tsensitized\tenters\tthe\tbody\tagain.\tBecause\tindividuals\tcan\tdevelop\timmunologic\tsensitization\tas\nevidenced\tby\tthe\tproduction\tof\tallergen-specific\n\tIgE\t(sIgE)\tor\tother\timmune\tcell\tsensitization\twithout
|
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IgE\t(sIgE)\tor\tother\timmune\tcell\tsensitization\twithout\nhaving\tallergic\tsymptoms\tupon\tsubsequent\texposure\tto\tthose\tfoods,\tan\tIgE-mediated\tor\tnon–IgE-\nmediated\tfood\tallergy\trequires\tthe\tpresence\tof\tnot\tonly\tloss\tof\ttolerance\tand\tsensitization\tbut\talso\tthe\npresence\tof\tclinical\tsymptoms\tdue\tto\tthe\trelease\tof\tinflammatory\tmediators\talready\tdiscussed\t(
|
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] |
NASEM,\n2017\n)\t(\nFig.\t25.2\n).\nFIG.\t25.2\nSensitization\tprocess\tand\tIgE-mediated\tallergic\treaction.\nIgE-mediated\treactions\n\toccur\twhen\tsIgE\tproduced\tin\tresponse\tto\tthe\tpresence\tof\tthe\tallergen\nattaches\tto\tmatching\tsIgE\tantibodies\ton\tthe\tmast\tcell\tor\tbasophil,\tforming\ta\t“bridge”\tbetween\tthem.\tThis
|
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bridging\tactivates\tthe\tmast\tcell\tor\tbasophil\tby\ta\tseries\tof\tenergy-requiring\tprocesses\tresulting\tin\tthe\ncell’s\tdegranulation\tand\n\trelease\tof\tthe\tinflammatory\tmediators,\tand\tthe\tappearance\tof\tallergic\tsymptoms.\nIgE-mediated\tfood\tallergic\treactions\tare\trapid\tin\tonset,\toccurring\twithin\tminutes\tto\ta\tfew\thours\tof
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] |
exposure\tthrough\teither\tinhalation,\tskin\tcontact,\tor\tingestion.\tA\twide\trange\tof\tsymptoms\tare\tattributed\nto\tthis\ttype\tof\treaction,\tand\tusually\tinvolve\tthe\tGI,\tdermatologic,\tor\trespiratory\tsystems\tand\tcan\trange\nfrom\tmild\n\thives\tto\tlife-threatening\tmultiple\torgan\tanaphylaxis\t(\nFig.\t25.3\n).
|
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] |
FIG.\t25.3\nA\n\tand\t\nB\n,\tAtopic\teczema:\tAn\tIgE-mediated\tskin\treaction\tto\ta\tfood\tallergen,\tcommonly\tseen\ton\tthe\thands,\nback\tof\tknees,\tand\tthe\tinside\tof\telbows.\n\t\nSource:\n\tA,\tFrom\t\t\nwww.istockphoto.com\n.\nNon–IgE-mediated\treactions\n\tare\tbased\ton\tthe\tactivation\tof\tcells\tother\tthan\tIgE,\tsuch\tas\teosinophils,
|
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] |
and\ttheir\tdegranulation\tand\trelease\tof\tmediators.\tNon–IgE-mediated\treactions\tare\tpresent\tin\tdelayed\n\tor\nchronic\treactions\tto\tfood\tallergen\tingestion.\tSee\t\nTable\t25.2\n\tfor\ta\tcomparison\tof\tIgE-\tand\tnon–IgE-\nmediated\tallergic\treactions.
|
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0.08247535675764084,
0.01990027353167534,
0.11775307357311249,
0.003288437845185399
] |
TABLE\t25.2\nComparison\tof\tIgE-\tand\tNon–IgE-Mediated\tAllergic\tReactions\nCharacteristics/Target\nOrgan\nIgE\tMediated\nNon–IgE-Mediated\nMixed\tIgE-\tand\nNon–IgE-\nMediated\nMechanism\nTh2\tactivation\tstimulates\nproduction\tof\tIgE\tby\tactivated\tB-\ncell\tlymphocytes.\tAllergen\tbinds\nwith\tthe\treceptors\ton\tsensitized\nIgE\tantibodies\ton\tmast\tcells\tor
|
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0.09828244894742966,
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] |
with\tthe\treceptors\ton\tsensitized\nIgE\tantibodies\ton\tmast\tcells\tor\nbasophils.\tUpon\tbinding,\tchemical\ninflammatory\tmediators\tare\nreleased.\nT-cells\tand\nsometimes\neosinophils\tare\nassociated\twith\ntriggering\n\trelease\nof\tinflammatory\nmediators\tand\ndevelopment\tof\nsymptoms.\nA\ncombination\nof\tIgE\tand\nnon-IgE\nmechanisms\nTiming\nQuick\tonset
|
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] |
A\ncombination\nof\tIgE\tand\nnon-IgE\nmechanisms\nTiming\nQuick\tonset\nFirst\tphase:\timmediate\treaction—\nminutes\tto\t1\thour\n*\nLate\tbiphasic\tphase:\tmay\toccur\nseveral\thours\t(4\tto\t6)\tafter\tinitial\nreaction\t(e.g.,\talpha\tgal)\nDelayed\tonset:\t>2\nhours;\toften\t4\tto\t6\nhours;\trelapsing\nDelayed\nonset:\t>2\nhours;\toften\n4\tto\t6\thours\nVolume\tRequired\n\tfor\nReaction\nSmall
|
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] |
hours;\toften\n4\tto\t6\thours\nVolume\tRequired\n\tfor\nReaction\nSmall\nSometimes\tlarger\nSometimes\nlarger\nSystemic\nAnaphylaxis\nFood-associated\texercise\tinduced\nanaphylaxis\t(FEIA)\nNSAID-associated,\taspirin-\nassociated,\tor\talcohol-associated\nfood-induced\tanaphylaxis\nNA\nNA\nSkin\nGeneralized\turticaria\nAcute\tcontact\turticaria\nAngioedema\nRash\nItching\nFlushing
|
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] |
Acute\tcontact\turticaria\nAngioedema\nRash\nItching\nFlushing\nContact\tdermatitis\nDermatitis\nherpetiformis\nAtopic\ndermatitis\n(eczema)\t(see\nFig.\t25.3\n)\nGastrointestinal\tTract\nImmediate\tgastrointestinal\t(GI)\nhypersensitivity\tor\tspasm\nOral\tallergy\tsyndrome\t(OAS)\tor\npollen-food\tallergy\tsyndrome\n(PFAS)\nAbdominal\tpain\nNausea\nVomiting\nBelching\nBloating
|
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] |
(PFAS)\nAbdominal\tpain\nNausea\nVomiting\nBelching\nBloating\nDiarrhea\nConstipation\nFood\tprotein–\ninduced\nenteropathy\nsyndromes\t(FPIES)\nFood\tprotein–\ninduced\nproctocolitis\t(FPIP)\nCeliac\tdisease\nEosinophilic\nesophagitis\t(EoE)\nEosinophilic\tgastritis\nEosinophilic\ngastroenteritis\n(EGE)\nNA\nRespiratory\nAcute\trhinitis\t(stuffy\tnose)\nRhinorrhea\t(runny\tnose)
|
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] |
NA\nRespiratory\nAcute\trhinitis\t(stuffy\tnose)\nRhinorrhea\t(runny\tnose)\nAsthma\nBronchospasm\nLaryngeal\tedema\nNA\nAsthma\nCardiovascular\nHypotension\nDizziness\tor\tfainting\nNA\nNA\n*\t\nIn\tcontrast\tto\ttypical\tfood\tanaphylaxis\tthat\toccurs\twithin\tminutes\tto\t2\thours\tfollowing\tingestion\tof\tthe\ttrigger\tfood,\tIgE-mediated\talpha-gal-related
|
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reactions\tto\tmammalian\tmeat,\n\twith\tthe\tsame\tanaphylaxis\tsymptoms\tare\tdelayed,\toccurring\t3\tto\t8\thours\tafter\tingestion.\nNA\n,\tNot\tapplicable.\nSources:\tNational\tAcademies\tof\tSciences,\tEngineering,\tand\tMedicine\t(NASEM),\tInstitute\tof\tMedicine\t(IOM)\t\nFinding\ta\tpath\tto\tsafety\tin\tfood\tallergy:
|
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] |
Finding\ta\tpath\tto\tsafety\tin\tfood\tallergy:\nAssessment\tof\tthe\tglobal\tburden,\tcauses,\tprevention,\tmanagement,\tand\tpublic\tpolicy\n.\tWashington,\tDC:\tThe\tNational\tAcademies\tPress,\t2017\tp.\t40.\nRenz\tH,\tAllen\tKJ,\tSicherer\tSH,\tet\tal:\tFood\tallergy,\tNature\tReviews-Disease\tPrimers,\tvol\t4:\tArticle\tnumber\t17098,\tpublished\tonline\tJan\t4,\t2018.\nJoneja\tJV:
|
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] |
Joneja\tJV:\t\nThe\thealth\tprofessional’s\tguide\tto\tfood\tallergies\tand\tintolerances\n,\tChicago,\tIL,\t2013,\tAcademy\tof\tNutrition\tand\tDietetics.\nIgE-mediated\tfood\tallergies\nAlthough\tany\tfood\tcan\tcause\tan\tallergic\treaction,\ta\tsmall\tnumber\tof\tfoods\tcause\tthe\n\tvast\tmajority\tof\tIgE-
|
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] |
vast\tmajority\tof\tIgE-\nmediated\tfood\tallergies.\tFoods\tthat\tare\tmore\tlikely\tto\tinduce\tan\tallergic\tresponse\tvary\tby\tcountry\tand\nregion\tof\tthe\tworld\taccording\tto\ta\tpopulation’s\teating\thabits.\tIn\tthe\tUnited\tStates\tthe\tcommon\tallergenic\nfoods\tare\tcow’s\tmilk,\teggs,\tpeanuts,\ttree\tnuts,\tfish,\tshellfish,\twheat,\tand\tsoy\t(\nNASEM,\t2017\n).\tAmong\tU.S.
|
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] |
NASEM,\t2017\n).\tAmong\tU.S.\nadults\twith\tfood\tallergies\tthe\tfive\tmost\tcommon\tfood\tallergies\n\tare\tshellfish\t(2.9%),\tpeanut\t(1.8%),\tmilk\n(1.9%),\ttree\tnuts\t(1.2%),\tand\tfin\tfish\t(0.9%)\t(\nGupta\tet\tal,\t2019\n).\tIn\tother\tcountries,\tfor\texample,\tJapan,\negg,\tcow’s\tmilk,\twheat,\tshellfish,\tfruit,\tand\tbuckwheat\taccount\tfor\tapproximately\t75%\tof\tfood\tallergies\n(
|
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] |
(\nMatsuo\tet\tal,\t2015\n).\nThe\tmain\tIgE-mediated\tallergic\treactions\tare\tfood-induced\tanaphylaxis;\tfood-dependent,\texercise-\ninduced\tanaphylaxis\t(FDEIA);\n\t\ncow’s\tmilk\tprotein\tallergy\t(CMPA)\n;\toral\tallergy\tsyndrome\t(OAS),\twhich
|
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recently\tis\trecognized\tas\tbeing\ttwo\tsyndromes,\tpollen-food\tallergy\tsyndrome\t(PFAS)\tand\tlipid\ttransfer\nprotein\tsyndrome\t(LTPS);\tlatex-fruit\tor\tlatex-food\tsyndrome;\tand\tsystemic\tnickel\tallergy\tsyndrome\n(SNAS).\nFood-induced\tanaphylaxis\nFood-induced\t\nanaphylaxis\n\tis\tan\tacute,\tsystemic,\toften\tsevere,\tand\tsometimes\tfatal\timmune\n\tresponse
|
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] |
response\nthat\tusually\toccurs\twithin\ta\tlimited\tperiod\tfollowing\texposure\tto\ta\tfood\tantigen.\tMultiple\torgan\tsystems\nare\taffected.\tSymptoms\tinclude\trespiratory\tdistress,\tabdominal\tpain,\tnausea,\tvomiting,\tcyanosis,\narrhythmia,\thypotension,\tangioedema,\turticaria,\tdiarrhea,\tshock,\tcardiac\tarrest,\tand\tdeath.
|
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] |
The\tvast\tmajority\tof\tanaphylactic\treactions\tto\tfoods\tin\tadults\tin\tNorth\tAmerica\tinvolve\tpeanuts,\n\ttree\nnuts,\tfish,\tand\tshellfish.\tIn\tchildren,\tpeanuts\tand\ttree\tnuts\tare\tthe\tmost\tcommon\tcauses\tof\tanaphylactic\nreactions,\tbut\tanaphylactic\treactions\tto\tcow’s\tmilk\tand\teggs\thave\tbeen\treported.\tPeanuts\tare\tthe\tmost
|
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common\tfood\tallergen\tin\tfatal\tanaphylactic\treactions\t(\nTurnbull\tet\tal,\t2015\n).\nPeople\twith\tknown\tanaphylactic\treactions\tto\tfood\tallergens\tshould\tcarry\tand\tbe\tprepared\tto\tuse\nepinephrine\n\tvia\ta\tportable\tinjectable\tdevice\t(often\tcalled\tan\tEpiPen)\tat\tall\ttimes.\tEpinephrine\tis\tthe\tdrug
|
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of\tchoice\tto\treverse\tan\tallergic\tanaphylactic\treaction.\tDelayed\tuse\tof\tepinephrine\thas\tbeen\tassociated\nwith\tan\tincreased\trisk\tof\tbiphasic\treactions,\tin\twhich\ta\trecurrence\tof\tsymptoms\t4\tto\t12\thours\tafter\tthe\ninitial\tanaphylactic\treaction\tmay\tbe\tfatal.\tSee\tSimons\t(2014)\tfor\tmanagement\tof\tan\tanaphylactic\n\treaction
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] |
reaction\nand\tthe\twebsite\tfor\tFood\tAllergy\tResearch\tand\tEducation\t(FARE).\tImmediate\tcoordination\tof\tcare\tand\nreferral\tto\ta\tphysician\tspecializing\tin\tallergy\tmedicine\tis\tessential\tfor\tpatient\tsafety.\tIf\tyou\twitness\ta\nsevere\tallergic\tresponse\tor\tanaphylaxis,\tcall\t911\timmediately\tand\tbe\tprepared\tto\tadminister
|
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cardiopulmonary\tresuscitation\t(CPR)\tif\tnecessary.\nFood-dependent,\texercise-induced\tanaphylaxis\n\t(FDEIA)\nFood-dependent,\texercise-induced\tanaphylaxis\t(FDEIA)\n\tis\ta\trare\tdistinct\tform\tof\tallergy\tin\twhich\tan\noffending\tfood\ttriggers\tan\tIgE-mediated\tanaphylactic\treaction\tonly\twhen\tthe\tsensitized\tindividual
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] |
exercises\twithin\t2\tto\t4\thours\tafter\teating,\tor\toccasionally,\tbefore\teating\tthe\tfood.\tSigns\tof\tdeveloping\nanaphylaxis\tare\turticaria\t(hives),\tpruritus\t(itching),\tand\terythema\t(reddening)\tfollowed\n\tby\tbreathing\ndifficulty\tand\tGI\tsymptoms.\tThe\tingestion\tof\tthe\tfood\tis\tnot\tproblematic\tin\tthe\tabsence\tof\texercise,\tand
|
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exercise\tis\tnot\tproblematic\tin\tthe\tabsence\tof\tconsumption\tof\tthe\tfood.\tFDEIA\tappears\tto\tbe\tmore\ncommon\tin\tadolescents\tand\tyoung\tadults,\tand\tin\tthose\twith\tknown\tfood\tallergy\tor\ta\thistory\tof\nanaphylaxis.\tShellfish,\tseafood,\tcertain\tfruits,\tcow’s\tmilk,\tcelery,\ta\tgliadin\tcomponent\n\tin\twheat,\tand\tother\nfoods\thave\tbeen\treported\tas\toffending\tagents\t(
|
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0.014836077578365803,
0.12607020139694214,
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] |
in\twheat,\tand\tother\nfoods\thave\tbeen\treported\tas\toffending\tagents\t(\nAsaumi\tand\tEbisawa,\t2018\n).\nIn\tFDEIA,\tthe\tcombination\tof\ta\tsensitizing\tfood\tand\texercise\tprecipitates\tsymptoms,\tpossibly\trelated\tto\nincreased\tGI\tpermeability\tand\tabsorption,\tblood-flow\tredistribution,\tand\tincreased\tosmolality.\tAdditional
|
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] |
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