brazjinfectdis2019;23(4):278–280
w w w . e l s e v ie r . c o m / l o c a t e / b j i d
The
Brazilian
Journal
of
INFECTIOUS
DISEASES
Letter
to
the
editor
Rhabdomyolysis
following
fish
consumption:
a
contained
outbreak
of
Haff
Disease
in
São
Paulo
DearEditor:
Haffdisease ischaracterizedbymyalgia and rhabdomyoly-sisfollowingfishconsumption,symptomsstartingwithin24h aftereatingcontaminatedfish.1Thediseasewasfirstreported
in1924 inPrussia and Sweden and other caseswere later describedinBrazil,China,Japan,andUS.1–4Nevertheless,Haff
diseaseremainsarareconditionandlackofawareness con-tributestodelayeddiagnosis.
A 38-year-old male (patient 1) and his 39-year-old wife (patient 2) presented to an emergency department in São Paulo(Brazil)complainingofintensediffusemyalgiathathad startedthatsameday.Thesymptomswererecurring:bothhad complainedofmildtomoderatemusclepainfourdaysbefore whichhadresolvedwithanalgesics.Theyalsonoteda dark-eningurinebeforeadmission(patient1presentedwithdark yellowandpatient2hadredbrownishurine).Theyhadno substantialpastmedicalhistoryanddeniedfever,headache, upperairwaysymptoms,orskinchanges.Theyalsodenied usingnewmedicationsordrugsandhavinganytraumaor per-formedhigh-intensityexercise.Thecouplehadreturnedfrom atriptoNortheastofBrazil10daysbeforeonsetofsymptoms. Physical examination of patient 1 was remarkable for severeanddisablingmuscularpainintheback,thighs,legs, arms,thorax,andabdomen.Patient2wasunabletowalkand presentedwithmoreweaknessanddisablingpaininherlower limbs.Vitalsignswerestable,andtherestoftheirphysical examinationwasotherwiseunremarkable.
Diagnosis of rhabdomyolysis was suspected and con-firmedbylaboratorytestsshowinghighlyelevatedcreatinine phosphokinase (CPK) (Patient 1: CPK=11,286U/L; Patient 2: CPK=2921U/L; Reference: 55–170). Aspartate aminotrans-ferase (AST) and alanine aminotransferase (ALT) were also elevated (Patient1: AST=108U/L and ALT=111U/L; Patient 2:AST=80U/Land ALT=75U/L;Reference: AST=17–59and ALT=21–72).Atadmission, bothpatientshad normal com-pletebloodcellcountandserumcreatinine,buturinedipstick waspositiveforbloodandprotein.
Atthispoint,thecouplewasenquiredabouttheirrecent foodintake.Theyrecalledhavingeatencookedfish,aspecies called‘Olho-de-boi’ (Seriolaspp)(Fig.1), afewhours before
bothepisodesofmyalgia.Thefishhadbeenboughtintheir vacation to theNortheast ofBrazil,packedin astyrofoam duringtheflight,manually washedbypatient1andstored in the refrigerator.It was later discoveredthat patient 1’s mother, who had also eaten the fish, developed mild dif-fusemyalgiaaswell.AdiagnosisofHaffdiseasewasmade andconfirmedbyexcludingotherpotentialinfectiouscauses of rhabdomyolysis (CMV, HIV, Epstein–Barr, dengue, yellow fever, zika virus, parechovirus, enterovirus, and hepatitis). The patients were initially managed with aggressive fluid therapy and opioidsforpain. They alsoreceived bicarbon-ate solutionin ordertopreventacute kidney failure. Their CPKcontinuedtoincreaseandpeaked24–36hlater(Patient1: CPK=28,571U/L;Patient2:CPK=73,391U/Lat36and24hafter admission,respectively).Similarly,AST/ALTlevelsroseupto 1134/375U/L(patient1)and1128/546UL/L(patient2)twodays afteradmission.Althoughtheirrenalfunctionremained sta-ble,bothdevelopedbilateralparenchymalnephropathywith normalcorticomedullaryratioonultrasound.Afterthethird dayofhospitaladmission,bothpatientsshowedmarked clin-icalandlaboratoryimprovementandwereasymptomaticat discharge,sevendaysafteradmission.
Haffdiseasehasbeendescribedfollowingtheingestionof cookedoruncookedcrayfish,freshwaterandmarinefish.2
Pre-viouslyreportedspeciesassociatedwithHaffdiseaseinclude crayfishProcambarusclarkii,Badejo(Mycteropercaspp.),Atlantic salmon (Salmo salar), and Buffalo fish (Ictiobus cyprinellus),
amongothers.2–4
Thediseaseisbelievedtobecausedbyanunknown ther-mostabletoxin,whichisnotdestroyed bycookingthefish; howeverinaprevious outbreakofHaffdisease(2016–2017) inSalvador,Brazil,samplesofrawfishweresenttotheFood andDrugAdministrationfortoxinanalysisandnoconclusion wasdrawnontheetiologyofthedisease.3Therefore,Haff
dis-ease remainsa clinicaldiagnosis that shouldbesuspected when other frequentcauses of rhabdomyolysis(infections, drugs, electrolyte imbalance, trauma or heatstroke) have been excluded.Inthis situation,enquiring afterrecent fish consumption and investigating whether other people have developedsimilarsymptomsisessentialnotonlyforaprecise diagnosis,butalsobecausediseaseoutbreaksmayoccur.3
brazj infect dis.2019;23(4):278–280
279
Fig.1–(A)GlobalincidenceofHaffDisease(1942–2019).(B)Fishboughtbythepatients.Theyhadeatenthegrayonebelow (‘Olho-de-boi’–Seriolaspp)beforedevelopingthesymptomsofHaffdisease.
Inordertohaveabetterunderstandingofthe epidemiol-ogyofthedisease,wesearchedPubMedandLILACSdatabases from inception to March 2019. Sinceits discovery in1924, 1768cases ofHaff disease have been reported around the world1–5 (Fig. 1), mostof which occurred in Northern and
EasternEurope(56.56%).There were also638casesinAsia (36%)and35 intheUS(1.94%). InBrazil,95patients(5.4%) havebeendiagnosedwithHaffdisease,mostlydueto out-breaksinthe North and Northeast.3 Althoughno previous
caseshadbeenreportedinSoutheastofBrazil,itisnoteworthy thatbothdescribedpatientsingestedafishbroughtfromthe Northeast.
Because the distribution of the disease is clearly het-erogenousthroughouttheworldandevenwithinindividual countries,lackofphysicianawarenessmightdelaythe diagno-sis,withnegativeimpactsonpatientoutcomesandincreased risk of outbreaks. As an example, in 2013, a 66-year-old ChinesepatientwithHaffdiseasewasmisdiagnosedas hav-ing lumbar disk disease and was discharged home with analgesics.Onedaylaterhewasreadmittedwithsevere rhab-domyolysisanddiedafterdevelopingmultipleorganfailure.5
Havingsaidthat,promptidentificationofthediseaseis neces-sarytorapidlyinitiatetreatment,whichismainlysupportive andfocusedonpreventionorreversionofacuteorganfailure. Aggressivefluidtherapyandcorrectionofelectrolyte imbal-ancesarethemainstay,alongwithavoidingdrugswhichcould potentiallyworsenrhabdomyolysis,suchasnon-steroid anti-inflammatorymedications.
Inaddition,onceadiagnosisofHaffdiseaseismade,health careprovidersshoulddotheirbesttoidentifythesourceof contaminatedfishandreportthecasetohealthauthorities,so
thatoutbreakscanbecontainedandat-riskpopulationscould bealertedabouttheneedtoseekhelpincasetheydevelop similarsymptoms.
Inconclusion,giventheglobalizedworldwehavetoday, it is important to reinforce the need to investigate a his-tory of recent fish consumption when assessing causes of rhabdomyolysis,even in regions wherethe disease has not been reported. Consequently, reporting new cases is essentialtoimprovetheknowledgeonthedisease epidemi-ologyand increasephysicianawareness,hopefullyallowing patients to be diagnosed earlier and containing outbreaks sooner.
Disclaimers
Theopinionsexpressedbyauthorscontributingtothisjournal donotnecessarilyreflecttheopinionsoftheBrazilian Soci-etyofInfectiousDiseasesortheinstitutionswithwhichthe authorsareaffiliated.Theauthorshavenocompeting inter-eststodeclare.
Author
declaration
Allauthorshaveseenandapprovedthefinalversionofthe manuscriptbeingsubmitted.Wewarrantthatthearticlehas notbeenpreviouslypublishedandisnotunderconsideration forpublicationelsewhere.
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braz j infect dis.2019;23(4):278–280Financial
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Thisreportwasapprovedbytheinstitutionalresearchreview board.Thisresearchdidnotreceiveanyspecificgrantfrom fundingagenciesinthepublic,commercial,ornot-for-profit sectors.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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1.BuchholzU,MouzinE,DickeyR,etal.Haffdisease:fromthe BalticSeatotheU.S.shore.EmergInfectDis.2000;6:192–5.
2.DiazJH.Globalincidenceofrhabdomyolysisaftercooked seafoodconsumption(Haffdisease).ClinToxicol(Phila). 2015;53:421–6.
3.BandeiraAC,CamposGS,RibeiroGS,etal.Clinicaland laboratoryevidenceofHaffdisease–caseseriesfroman outbreakinSalvador,Brazil,December2016toApril2017.Euro Surveill.2017;22.
4.GuoB,XieG,LiX,etal.OutbreakofHaffdiseasecausedby consumptionofcrayfish(Procambarusclarkii)inNanjing,China. ClinToxicol(Phila).2018;17:1–7.
5.FengG,LuoQ,ZhuangP,GuoE,YaoY,GaoZ.Haffdisease complicatedbymultipleorganfailureaftercrayfish consumption:acasestudy.RevBrasTerIntensiva. 2014;26:407–9.
LynaK.R.Almeida ,FernandaGushken , DarioR.Abregu-Diaz ,RobertoMunizJr. ∗, LuizaH.Degani-Costa
HospitalIsraelitaAlbertEinstein–AvenidaAlbertEinstein,627/701 –Morumbi,SãoPaulo,SPCEP:05652-900,Brazil
∗Correspondingauthor.
E-mailaddresses:rmunizjr@gmail.com,
roberto.muniz@einstein.br(R.MunizJr.). Received22May2019
Accepted21June2019 Availableonline24July2019 1413-8670/
©2019SociedadeBrasileiradeInfectologia.Publishedby ElsevierEspa ˜na,S.L.U.Thisisanopenaccessarticleunder theCCBY-NC-NDlicense(http://creativecommons.org/ licenses/by-nc-nd/4.0/).
