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DIAGNOSISANDTREATMENTOFCHRONICINFLAMMATORYRESPONSESYNDROME-CIRS

KarenD.JohnsonM.D.,ABOIM,IFMCP

www.karendjohnsonmd.com503-371-3232

Haveyoubeensickforalongtimewithoutanyimprovementinspiteofmultiplemedicalvisitstodifferentcliniciansandamultitudeoftestsandtreatments?YoumayhaveCIRS.CIRS,asthenameimplies,isachronicillness.Itisaclusterofsymptomsthataffectmultiplesystemsinthebody.ItwasfirstdescribedbyDr.RitchieShoemaker,whocontinuestodoextensiveresearchondiagnosing,treatingandunderstandingthesyndromedowntoagenomiclevel.(1)(5)CIRSiscausedbyexposuretoabiologicalagent(biotoxin)inyourenvironmentthatyourbodycannotclearinpartbecauseofyourgenetics.Thebiotoxincanbeexposureto:1.Moldfromawaterdamagedbuilding(CIRS-WDB).Upto50%ofbuildingsintheUShaveahistoryofwaterdamage,2.Lymeorco-infectionsfromatickbite(CIRS-LYME),resultingininabilitytoclearthebiotoxinafterantibiotictreatment3.ExposuretoadinoflagellatesuchasPfiesteriaorCiguatera.ThiscanoccuraftereatingtropicalreeffishcontaminatedwithCiguatoxinorexposuretoinfectedfishorwater,4.Exposuretoblue-greenalgae(CylindrospermopsisorMicrocystis)ininfectedwaterways,5.Bitefromreclusespider.ReturningtothegeneticsImentionedabove,youmayask,whyamIsickandnobodyelsethatlivesorworksintheWDBissick?WhydidInotgetbetterafterIwastreatedwithantibioticsforLymeandotherpeoplewhoweretreatedarenotstillsick?

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ThisisexplainedbyyourHLA(HumanLeukocyteAntigen)profile.Eachpersonhasanindividualprofilethatallowsourimmunesystemtorecognizeornotrecognizebiotoxins.Somepeoplecanbemoldsensitive,somecanbeLymesensitiveandsomecanhavemultiplesensitivities.Eachindividualprofileindicateswhetheryourbodycanefficientlyclearthatbiotoxinornotclearit.Approximatelyone-quarterofthepopulationissusceptibletomoldtoxins.AbloodtestcandetermineyourHLAprofile.Thereare2maincomponentstoourimmunesystem.Theinnateimmunesystemiswhatwewerebornwith.Itistheinitialdefenseagainstforeigninvaders.Whenconfrontedwithaninvader,theimmunesystemreleasessignalstothebodythatthereisdanger.Thebodyrespondsquicklyproducingchemicalsasthefirstlineofdefensetodestroytheinvader.Thisisnonspecificandcouldbecomparedtodumping“bleach”ontheinvader.Thesechemicals(notreallybleach)arewhatmakeusfeelsoillwhenweare“comingdownwithsomething”.Itisusuallynotthebugitselfthatmakesusfeelthiswaybutthehostresponsetotheillness.Thesecondpartoftheimmunesystemistheadaptiveimmunesystem.Thisisamuchmoreprecisesystemandratherthandumpingbleacheverywhere,producesantibodiestospecificallyremovetheinvader.Ittakestimeforourbodytomakeantibodiesspecifictotheinvaderandthereforewehavetheinnateimmunesystemasthefrontlineofdefense.Now,somepeoplelacktheabilitytomakeantibodiesagainstcertainbiotoxins.ThisiswhatIwasreferringtoabovewithHLAtypesthatcannotrecognizecertainbiotoxins.Ifthishappens,thetoxinscannotberemovedbytheadaptiveimmunesystemandpersistinourbody.Ourbodydoeshaveabackupplanwhichisnotveryefficient.Ourliversecretesthebiotoxinintothebilewhichisdumpedintothegut,howeverthesebiotoxinsareverytinyand95%ofthemarequicklyreabsorbedinthegut.Thisisfurthercompoundedifourproblemismoldtoxicityfromawaterdamagedbuilding(WDB)andwehaveongoingexposure.So,whathappens?Theinnateimmunesystemcontinuestodoitsjobintheonlywayitknowshowandkeepsdumping“bleach”ontheproblemandthepersonbecomesmoreandmoreillwithtime.

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HowdoyouknowifyouhaveCIRS?Dr.ShoemakerhasspecificcasecriteriaforCIRSdiagnosisandtheseinclude:1. Exposurehistorythatincludesoneofthefollowing:livingorworkingina

WDB,historyofatickbite,onsetofsymptomsafterbecomingillfromeatingreeffishorexposuretobluealgaeordinoflagellates.ExposuretoWDBcanbeverifiedbypresenceofvisiblemoldgrowth,mustysmellsorapositiveERMI(EnvironmentalRelativeMoldinessIndex).ERMIisatestdoneonthebuildinginquestionbyobtainingdustsamplesthatarethenevaluatedforthepresenceofmoldfragmentsorsporesthatwereintheairandsettledinthedust.ERMItestingcanbeorderedfromhttps://www.mycometrics.com.

2. Yoursymptomscannotbeexplainedastheresultofanyotherillness.Thisincludestakingacompletehealthhistoryanddoingathoroughphysicalexam.

3. YouneedtohavemultiplesymptomsinmultiplesystemsofyourbodytobediagnosedwithCIRS.Dr.Shoemakerhasdevelopedasymptomcharttoevaluatepatientsformultisystem,multi-symptomillness:

Youneedatleast1symptominatleast6ofthe13symptomclusterstobeconsideredforCIRS.8of13symptomclustersindicatesahighprobabilityofCIRS.

Ifthesecriteriaaremet,additionaltestingwillbedone.AsimpleadditionaltestincludesVisualContrastSensitivitytesting.Thistestisdoneinmyofficeandisnotthesameasavisiontesttoassessyournearandfarvision,butisatestthatmeasuresyourabilitytodiscerncontrast.Visualcontrastperceptionisimpairedinasignificantnumberof

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peoplewithCIRSasaresultoftheeffectthebiotoxinhasonreducingtheflowofbloodinthebloodvesselsaroundtheopticnerve.Labtestsarethenordered.Mostpeoplehavehadextensivelabtestsdonealready,howevertestsforCIRSspecificallylookathowyourimmunesystemisrespondingtoabiotoxin.Thetestscanindicateifyourinnateimmunesystemisbeingoverstimulated.StandardlabtestsdonearetypicallynormalinCIRSandifabnormalusuallyaretheresultofsomeotherproblem.FiveofthefollowinglabtestsorderedneedtobeabnormaltodiagnoseCIRS:1. HLAhaplotypedetermination(asdiscussedabove).24%ofthe

populationhaveanHLAtypethatmakesthemsusceptibletoCIRS-WDB.However,havingthehaplotypedoesnotmeanyouwillgetCIRS.Youstillneedtheexposure.95%ofpeoplewithCIRShaveasusceptiblehaplotype.

2. MSH(alphamelanocytestimulatinghormone)level.Thisisaprotein

releasedfromthehypothalamusandpituitaryglandinthebrain.Itcontrolsmelatoninandhormonelevelsincludingsexhormonesandcortisol.MSHaffectsmucusmembraneintegrity(thinkleakygut),regulatesourimmunesystemandcontrolsinflammation.IfMSHislow,manysymptomswillbeexperiencedincludingheadache,brainfog,chronicfatigue,sleepdisruptionandchronicpain.ChronicpaincanbeamajorsymptomwithCIRSandresultsfromreductioninournaturalendorphinproductioninadditiontotheinflammatoryeffectsofcytokines(signalingmoleculesthatresultfromstimulationoftheinnateimmunesystem).NormalMSHrange:35-81pg/ml

3. MMP-9(MatrixMetalloproteinase-9).Itsreleaseistriggeredbytheinnateimmunesystem.MMP-9contributestoincreasedpermeability(leakymembranes)bydissolvingaproteinintissuetoallowmoleculestopassmorereadilyoutofbloodvessels,intojoints,thelung,nervesandthebrain(2).Thisisneededinanacuteinjurytogetthefighting

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powertothesiteofinjury,butisverydangerouslongtermastherewillbeongoingdeliveryofinflammatorycompoundsintotheabovetissues.NormalMMP-9range:85-332ng/ml

4. TGF-beta-1(TransformingGrowthFactorbeta-1)isaconductorofourimmunesystem(3).IfTGF-betaisinthenormalrangeitkeepsbalancebetweenthesideofourimmunesystemthatneedstobealerttofightanintruder(pathogenicTcells),butyetnotbesoactivethatourimmunesystemattacksourowntissue.ThiscontrolismanagedbybeneficialTregulatorycells(T-reg)andThelpercells.WhenthereisimbalanceanddeficiencyofT-regcells,auto-immunediseasecandevelop.ElevatedTGF-betanotonlysignalsourbodytokeepmakingcellstofighttheintruderbutthesesamecellshaveapositivefeedbackandstimulatetheproductionofmoreTGF-beta.HighlevelsofTGF-betacanleadtoremodelingoftissueinlungleadingtoshortnessofbreathandasthmalikesymptoms.Otherorgansinthebodysuchasliver,heartandkidneycanalsobeaffected.NormallevelTGF-beta-1isunder2380pg/ml

5. ADH(AntiDiureticHormone)andosmolality-ADHassistsincontrollingthesaltandwaterbalanceinourbody.Inanormalsituation,ifwearedehydrated,ADHoutputincreasestopreventdiuresis(urination),andthiswillthereforeconservefluid.ADHisproducedinthebrainandstoredinthepituitarygland.ItsreleaseiscontrolledbyMSH.ThedysregulationinnormalproductionofMSHaffectsADHlevels.Thisresultsinsymptomsofheadaches,increasedthirst,frequenturinationandifsevereenough,ourbodytriestosweatouttheexcesssaltresultinginincreasedsusceptibilitytostaticshocksfromthesodiumpresentontheskin.NormalrangeADH:1-13.3pg/ml;Osmolality:280-300mosmol

6. VEGF(VascularEndothelialGrowthFactor).VEGFisproducedbythebodytostimulatethegrowthofnewbloodvessels.InitiallyVEGFlevelsriseasaresultofdecreasedbloodflowtothetissueastheresultofcytokinesattractingstickysubstancestotheliningofbloodvesselscausingwhitebloodcellstobecometrapped,blockingthebloodvessel.

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Thereishowever,asubsequentdeclineinVEGFasaresultofprolongedelevationofTGF-beta-1.Unfortunately,theblockageinthebloodvesselspersists,worseninganalreadycompromisedbloodflowtothetissue.NormalrangeVEGF:31-86pg/ml

7. C4aandC3a.Thesearesplitproductsofthecomplementsystem.Theybothareanaphylatoxins(causeallergicreaction).Biotoxinsstimulatetheinnateimmunesystemtoproducethesesubstances.Complementsplitproductscanresultinswelling,histaminerelease,contractionofsmoothmuscles…essentiallyallthesymptomsofanallergicreaction.Highlevelsresultinincreasedsymptoms.InordertoproduceC3a,youneedamicrobialcellmembranepresent.Thisthenrequireslookingforaninfectiveagent.LymeisoneinfectionthatneedstobeconsideredwithelevationofC3aNormalrangeC4a:lessthan2830ng/ml;NormalrangeC3a:lessthan940ng/ml

8. VIP(VasoactiveIntestinalPeptide)ismadeinthegut,pancreasandbrain.Itisinvolvedinreducingtheinflammatoryresponsebyregulatingtheimmuneresponse(4).TreatmentwiththissubstancecanrestoremanyoftheimbalancesandsymptomsseenwithCIRS.NormalrangeVIP:23-63pg/ml

9. CortisolandACTHlevels.MSHcontrolsreleaseofACTHfromthepituitarygland.ACTHisreleasedinresponsetostressandstimulatestheadrenaltoproducecortisol.ThereisaninitialriseincortisolinCIRS,howeverasthestressoftheillnesspersists,dysregulationisseeninbothlevelsofACTHandcortisol.Normalrange:ACTH:8-37pg/ml;AMCortisol:4.3-21ug/dl

10. MARCoNS(MultipleAntibioticResistantCoagulaseNegativeStaphylococcus).MARCoNSisfrequentlyculturedfromthebackofthenoseinpeoplewithCIRS.ItdoesnotusuallycausesymptomsandisnottobeconfusedwithMRSA.Itisnotaninfectioninthetruesenseoftheword,howeveritturnsonfurtherdamagingcytokines.LowMSH

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predisposestodevelopmentofMARCoNSbyimpairingmucosalimmunefunction.MARCoNScantheninterferewithproductionofMSH,compoundingtheproblem.MARCoNScanresideinbiofilmwhichprotectsitfromourownnaturaldefensesandfromantibiotics.MARCoNScanalsoaffectgeneticsbycontrollingwhichgenesareturnedofforon.CultureforMARCoNSisobtainedbytakinga2-3inchDEEPnasalcultureandsendingitforAPIStaphculture.Normalresult:Negativeculture

AdditionallabteststhatalsocanbeabnormalinCIRSinclude:1. Leptinisahormoneproducedbythefatcells.Leptincontrolsourappetite

andalsoallowsourfatcellstobeburnedforenergy.LeptinattachestotheleptinreceptorinthehypothalamusofthebrainandisresponsibleforcontrollingtheproductionofMSHandbetaendorphin(asubstancethatisournaturalpainreliever).Cytokinescrossthebloodbrainbarrierandbindtoreceptorspreventingleptinfrombinding.Thebodytriestocompensatebyproducingmoreleptin.Thiscyclecanresultinweightgainandinabilitytolosebodyfatinspiteofdietingandexercise.Normalrange:Women:1.1-27.5ng/ml;Men:0.5-13.8ng/ml

2. VonWillebrand’sPanel.vonWillebrand’sdiseasecanbeacquiredasaresultofelevatedC4alevelinCIRS.Itresultsineasybleeding,inparticularnosebleeds.Thiscomplicationisrare.TestinginvolvesavonWillebrand’spanelandnormalresultsindicateabsenceofthedisease.

3. Screeningforpresenceofauto-immuneantibodies.ThereareseveralthatcanbeabnormalasaresultofelevationofTGF-beta-1.Twoexamplesareanti-gliadinantibodieswhich,ifpresent,resultinglutensensitivityandanti-cardiolipinantibodieswhichcancauseclottingdisorders.

4. CD4+CD25++T-regs.Theseareimmunecellswiththesespecificmarkers

onthecellsurface.ThesecellsincreaseasMSHlevelsriseandindicateanimprovingimmunesystem(3).LowlevelsofT-regsincreasethechanceofallergyandautoimmunity.Thelevelsofthesecellscanmonitorprogressoftreatment.

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CD4+CD25++levelsshouldbegreaterthan18%

5. Hormonetesting.TestosteronelevelsmaybelowasaresultofdecreasedproductionofLH(LuteinizingHormone)andFSH(FollicleStimulatingHormone)fromthepituitary.TestosteronelevelfallsevenfurtherasaresultofincreasedaromataselevelsinCIRS.Aromataseisanenzymethatconvertstestosteronetoestrogen.Testosteronelevelsmaybelowandestrogenlevelselevatedwithsymptomsoftestosteronedeficiencyandestrogenexcessinbothmenandwomen.TestingincludesDHEA-S,testosteroneandestradiollevels.Normallevelsvaryforsexandage.6.PAXGenetestingisbeingdevelopedbyDr.Shoemakertofurtherunderstandtheeffectofthebiotoxinonourgenesandtheresponsetotreatmentatageneticleveltofurtherassistindiagnosisandtreatment(5).ADDITIONALSCREENING-NEUROQUANTCRANIALMRIAnMRIofthebrainthatisadditionallyinterpretedwithasoftwareprogramcalledNeuroQuant.NeuroQuantmeasuresthevolumeofdifferentareasofthebrain(6).ThiscanbeverydiagnosticbecausetheabnormalitiesseenwithCIRS-WDBaredifferentfromCIRS-LYME.PeoplewithCIRS-WDBwillhaveshrinkage(atrophy)ofanareacalledthecaudatenucleusaccompaniedbyswellinginotherareas.CIRS-LYME,howeverresultsinatrophyoftheputamen.Thistestcanalsomonitorprogressoftreatment.NeuroQuantisalsobeingusedintheBredesenprotocoltomonitorpatientswithcognitiveimpairment.

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ThisisanexcellentflowchartDr.ShoemakerdevelopedtounderstandthecourseofCIRS:

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TREATMENT-YESTHEREISHOPE!Treatmentisstepwise,startingatthebottomofthepyramidandmovingup.Jumpingstepswillnotassistinmorerapidrecoveryandmayactuallyinterferewithrecovery.Dr.ShoemakerusesthistreatmentpyramidincorrectingabnormalitiesinCIRS:

AteachstepretestingofVCSandinnateimmunemarkerssuchasMMP-9,C4a,TGF-beta-1,CD4+CD25++T-regsandanypreviousabnormalitiescanbemonitoredtoassessprogress.1. Thefirststepisremovalfromexposureandthisprimarilyappliesto

CIRS-WDB.Thisisthemostdifficultforpatientsformultiplereasonsincludingcostandattachmenttopersonalitems.ERMItestingis

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indicatedtodeterminewhereexposureisoccurring.Theworkplacemayneedtoalsobetested.Symptomaticimprovementwillnotoccurifongoingexposuretothebiotoxincontinues.TheprofessionalassistanceofanIndoorEnvironmentalProfessional(IEP)isstronglyrecommendedtoassistinevaluationandremediation(7).Theaffectedpersonshouldnotoccupytheaffectedbuildingduringremediation.Repeattesting,eitherwithERMIorHERTSMI-2whichstandsforHealthEffectsRosterofTypeSpecificFormersofMycotoxinsandInflammagens(seehttps://www.mycometrics.com)isrequiredbeforere-enteringtheaffectedbuilding.Inflammagensarechemicalsthattriggeraninflammatoryresponseinthebody.

2. Removalofbiotoxins.ItisimportanttounderstandifyouhaveCIRS-

WDBthatyouDONOThavemoldgrowinginyourbody.Instead,youhavetoxinsfrommoldexposure.YouDONOTtakeanti-fungalmedicationstotreatthisillness.

Cholestyramine(CSM)isadrugthatisapprovedforcholesterolloweringandisbeingusedofflabelinthistreatmentapplication(thatmeansitdoesnothaveFDAapprovaltotreatthiscondition).CSMhasapositivechargeandstructurethatattractsthenegativelychargedbiotoxinsthatarepresentinthebile.Thebiotoxinsareirreversiblyboundandeliminatedinthestool.CSMisnotabsorbedhoweverdoeshavesideeffectsofconstipation,gasandbloating.Thedoseis4gramsin6ozofwaterfollowedbyanother6ozofwater,4timesdaily30minutesbeforemeals.Itcanbindtoprescriptionmedsandsupplementsandtheseshouldbetaken1hourpriortoCSMor2hoursafter.Constipationmustbeavoided.Dietaryfiber,magnesiumandotherbowelstimulantsmayberequiredtopreventconstipation.Analternativetreatmentisaprescriptiondrug,Welchol625mgandisdosed2tabletsthreetimesdailywithmeals.ThisdrugisalsoFDAapprovedtotreatelevatedcholesterol.Welcholisonly25%aseffectiveasCSMasabinder,howeveritcausesfewerGIsideeffects.Itisalsomuchmoreexpensive.Somepeoplebecomeillwithbindersandthisislikelytheresultoftheirmobilizationofmorecytokines,especiallyMMP-9.Sideeffectscanbereducedwithhighdose(3-4grams)omega-3supplementationdailystarting1weekbeforestartingCSM.

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TreatmentwithbindersiscontinueduntilVCStestresultsarenormal,symptomsarethesameascontrolsandlabresultshavenormalized.Alowamylosedietisveryhelpfulinreducinginsulinlevels,reducinginflammationandassistinginweightloss.(8)ThisdietisrecommendedalongwithCSM.

3. EradicationofMARCoNS.IfMARCoNStestingbyAPIStaphswabispositiveitneedstobetreatedafteronemonthoftreatmentwithCSM.ThetreatmentforMARCoNSiswithBEGnasalspraythatismadebyacompoundingpharmacy.ItcontainsBactroban0.2%,EDTA1%andGentamicin0.5%inabasethatimprovesadherencetomucousmembranes.Dosingis2sprayseachnostril3timesdailyfor1month.Thesprayisirritatingandcanresultinnasalburning,congestionandnosebleeds.Thiswillallresolveaftercompletingtreatment.Repeatcultureneedstobedoneposttreatment.Ifthecultureremainspositive,otherfamilymembersordogsmaybethesourceofre-infection.Catsareoffthehookhere!

4. Glutenfreedietshouldbefollowedifglutenantibodiesarepresent.

Thisdietshouldbefollowedforaminimumof3months.Retestingshouldbedoneandifantibodiesarestillpositive,thelikelihoodofceliacdiseaseneedstobeconsidered.Eliminatingglutenalsoreducesamyloseinyourdiet.Manypeopleareglutensensitiveasaresultofleakygutandmostfeelbettereliminatinggluteneveniftestingisnegative.Itisworthatrialwithnorisk.

Itisimportanttoallowhealingtooccuronmanylevelsandthefoodweeatprovidesinformationtoourcellsthatcanbegoodorbaddependingonourchoices.Avoidingtoxicexposuretothebestofone’sabilityreducestheoveralltoxicburdeninthebody.Eatorganicwheneverpossible.Payattentiontowhatyoueat,theairyoubreatheandwhatyouputonyourskin.

5. Correctionofhormonelevels.ThisisdonecarefullywiththeadditionofDHEA.EstrogenandDHEA-SlevelsneedtobemonitoredwhileontreatmentandDHEAwillbediscontinuedwhenlevelsreturntonormal.

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DHEAisahormonethatisconvertedtotestosterone.LessconversiontoestrogenoccurswithDHEAthanwithtestosteronesupplementation.Iftestosteroneisgivendirectly,itwillbeconvertedtoestrogen,worseningtheimbalanceinbothmenandwomen.Thisimbalancewillresolveoncetheunderlyingoverstimulationoftheinnateimmunesystemiscorrected.

6. CorrectADH/osmolality.DDAVPisaprescriptionformofADHandcan

beusedcautiously0.2mgeveryothernightfor2weeks.This,again,isofflabeluse.Dailyweights,monitoringbloodpressureandforedemaneedstobedonewhileontreatment.ADH/osmolalityandelectrolytelevelsneedtoberetestedin2weeksafterstartingtreatment.

7. CorrectelevatedMMP-9.Thisinvolvesreducinginflammationwitha

lowamylosedietand3-4gramsofomega-3dailyforonemonth.IfthereisnoimprovementActos45mgdailyfor10dayscanbeused.Actosworksbyreducinginsulinresistanceandinflammation.ItsusehaslostfavorbecauseofablackboxwarningbytheFDAofdevelopingbladdercancerwithlongtermuseofover1year.

8. CorrectVEGF.Treatmentwithlowamylosedietandhighdoseomega-3

supplementationshouldbecontinuedifVEGFabnormalitiespersist.ThefinalstepintreatmentwithVIPnasalspraywillalsoaddressthis.

9. CorrectelevatedC3a.Theunderlyingcauseneedstofirstbeaddressed.

IfitisduetoLyme,thisneedstobetreated.Auto-immunediseasessuchaslupusalsoresultinelevationofC3a.Aftertheunderlyingcausehasbeenaddressed,inflammationandC3alevelsarereducedwithhighdose(80mg)statins.Pre-treatmentwithCo-Q10200mgdailystarting10daysbeforethestatinreducestheriskofsideeffects.Musclepain,fatigueandelevationofliverenzymescanoccurwithhighdosestatins.

10. CorrectelevatedC4awithVIPnasalspray50mcg/0.1ml,1sprayin

alternatingnostrils4timesdailyforminimumdurationof4months.Whensymptomsimproveandlabvaluesnormalize,dosagecanbereducedto50mcgtwicedailyfor1month.BeforeVIPcanbeused,thefollowingrequirementsmustbemet:VCStestingmustbenormal,

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MARCoNStestingisnegative,lipaselevelisnormalandERMIislessthan2orHERTSMI-2lessthanorequalto10.Thefirstdoseshouldbeadministeredintheofficeandpatientmonitoredwithpreandpostlabs.Ifnoadversereaction,lipase,C4a,TGF-beta-1,MMP-9andanyabnormallabsshouldbecheckedin1month.VIPneedstobediscontinuediflipaseelevatesorabdominalpainorrashdevelops.

11. CorrectelevatedTGF-beta-1.Losartan(adrugtolowerbloodpressure)

producesadegradationproductthatlowersTGF-beta.Dosageis12.5mgdailyandincreasedto25mgtwiceadayiftolerated.Ifapersonalreadyhaslowbloodpressure,itmaynotbetoleratedandVIPnasalspray,withtheabovedirectionsandguidelinescanbesubstituted.NotethatotherbloodpressuremedicationsdonothavethesameeffectasLosartan.

12. CorrectlowVIP.Ifrecoveryhasnotyetoccurred,VIPnasalsprayisto

becontinuedwiththeaboveguidelinesanddosage.VIPnasalsprayhasmanybeneficialeffects.VIPdownregulatescytokines,raisesVEGF,CD4+CD25++T-regs,restorescircadianrhythm(sleep),regulatesauto-immunity,restoresnormalhormonelevelsbydownregulatingaromatase,increasesendorphins,improvesexercisetoleranceandhasbeenshowntonormalizegenomics.VIPcanalsohelppeoplewithmultiplechemicalsensitivitiesbydownregulatingolfactorydrivenneurons.Avoidingre-exposureiscritical,howeversometimesunavoidable.Peopledonotwanttoliveinterroroftravellingoutsideoftheir“safebubble”.Ifre-exposureoccurs,identifyingthesourceisbeneficialtopreventrepeatexposure.RetestVCSandlabmarkersandifabnormal,retreatwithCSM/Welchol.Continueupthepyramiduntilsymptomsresolveandmarkersarebackinthenormalrange.PeoplewhohavehadCIRShaveatendencytobecome“sicker,quicker”uponre-exposure.Preventionisbest.CIRSisaverymisunderstooddiseaseatbestanddeniedbymanyatworst.ThankstotheresearchanddedicationofDr.Shoemaker,who

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followedtheevidence,thereisnowclinicalvalidationsupportedbythousandsofcasesforthediagnosisandtreatmentofCIRS.Itisimportanttounderstandthepathwaythebiotoxintakesinourbodywhichresultsinacascadeofsymptoms.Thisunderstandingprovidestheknowledgeofthehowandwhythesetreatmentstepsaretakeninordertoreversethedisease.Thisdiagnosisisnotmadeeasily.Asoutlinedabove,multiplecriteriamustbemet.Thediagnosisisthenvalidatedwithnumeroustestswhichanalyzetheeffectofthebiotoxinonmultiplesystemsofthebody.TestsrangefromVCStesting,multiplelabtestsincludingdetermininggeneticsusceptibility,MRIvolumetricimaging,andnowDr.Shoemakerisonthecuttingedgewithhisgenomicresearch.Thiswill“personalize”diagnosisandtreatmentbyunderstandingwhatthebiotoxinisdoinginyourbodyatacellular/geneticlevel.Thisisanexcitingfrontiertobepartof.Forme,itprovidesaveryimportantpiecetoapuzzleofchronicillness.

References:

1. Shoemaker:“Survivingmold-WhatisCIRS”December2014.http://www.survivingmold.com/news/2014/12/what-is-cirs/

2. Al-Sadi,Rawat,Ma:InflammatoryBowelDiseases:February2017.MMP-9

ModulationofIntestinalEpithelialJunctionPermeability.http://journals.lww.com/ibdjournal/Abstract/2017/02001/P_272_MMP_9_Modulation_of_Intestinal_Epithelial.275.aspx

3. Noack,Miossec:AutoimmunityReviews,June2014.Th17andT-regcell

balanceinautoimmuneandinflammatorydisease.http://www.sciencedirect.com/science/article/pii/S1568997214000081

4. Ganea,Hooper,Kong:ActaPhysiologica,December2014.The

neuropeptidevasoactiveintestinalpeptide:directeffectsonimmunecells

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andinvolvementininflammatoryandautoimmunediseases.http://onlinelibrary.wiley.com/doi/10.1111/apha.12427/full

5. Ryan,Wu,Shoemaker:BMCMedicalGenomics,April2015.Transcriptomics

inCIRS/Ciguatoxinhttps://www.ncbi.nlm.nih.gov/pubmed/25889530

6. Shoemaker,House,Ryan:NeurotoxicologySeptember2014,Structural

brainabnormalitiesinpatientswithinflammatoryillnessacquiredfollowingexposuretowaterdamagedbuildings:AvolumetricMRIstudyusingNeuroQuant.

https://www.ncbi.nlm.nih.gov/pubmed/24946038

7. Berndtson,McMahon,Ackerly,Rapaport,Gupta,Shoemaker:MedicallysoundremediationofwaterdamagedbuildingsincasesofCIRS.January2016.

https://www.survivingmold.com/docs/MEDICAL_CONSENSUS_1_19_2016_INDOOR_AIR_KB_FINAL.pdf

8. Maier:TheNo-Amylosediet.August2013http://www.livestrong.com/article/335261-the-no-amylose-diet/#ixzz18n8hXyTi