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Mesalamine induced myocarditis following diagnosis of Crohn's disease

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RevPortCardiol.2013;32(9):717---720

Revista

Portuguesa

de

Cardiologia

Portuguese

Journal

of

Cardiology

www.revportcardiol.org

CASE

REPORT

Mesalamine-induced

myocarditis

following

diagnosis

of

Crohn’s

disease:

A

case

report

Carlos

Galvão

Braga

,

Juliana

Martins,

Carina

Arantes,

Vítor

Ramos,

Catarina

Vieira,

Alberto

Salgado,

Sónia

Magalhães,

Adelino

Correia

Servic¸odeCardiologia,HospitaldeBraga,Braga,Portugal

Received1December2012;accepted7December2012

Availableonline30August2013

KEYWORDS

Myocarditis; Mesalamine; Transthoracic echocardiography; Cardiacmagnetic resonanceimaging

Abstract MesalamineisacommontreatmentforCrohn’sdisease,andcanberarely associ-atedwithmyocarditisthroughamechanismofdrughypersensitivity.Wepresentthecaseof a19-year-oldmalewhodevelopedchestpaintwoweeksafterbeginningmesalaminetherapy. TheelectrocardiogramshowedslightST-segmentelevationwithupwardconcavityinthe infer-olateralleads;bloodtestsdemonstratedelevatedtroponinIandtheechocardiogramrevealed moderatelydepressedleftventricularsystolicfunctionwithglobalhypocontractility. Cardiac magneticresonanceimagingconfirmedthediagnosisofmyocarditis,revealingmultipleareas ofsubepicardialfibrosis.Theonsetofsymptomsaftermesalamine,andimprovementofchest pain, cardiacbiomarkersandleft ventricular systolicfunction afterdiscontinuing thedrug, suggestthatourpatientsufferedfromararedrug-hypersensitivityreactiontomesalamine. © 2012 SociedadePortuguesa de Cardiologia. Published by Elsevier España, S.L. All rights reserved.

PALAVRAS-CHAVE

Miocardite; Mesalamina; Ecocardiografia transtorácica; Ressonância magnéticacardíaca

Miocarditeinduzidapelamesalaminaapósodiagnósticodedoenc¸adeCrohn---relato deumcasoclínico

Resumo Amesalaminaéumtratamentocomumpara adoenc¸adeCrohn,associando-sede formararaàmiocarditeaguda,atravésdeumareac¸ãodehipersensibilidadeaofármaco.Os autores apresentamocasoclínicode umjovemde 19anoscomaparecimentodedor torá-cica duassemanas apóster iniciadotratamento commesalamina para adoenc¸a deCrohn. OeletrocardiogramamostrouumdiscretosupradesnivelamentodosegmentoST,de concavi-dadeascendente,nasderivac¸õesinfero-laterais;asanálisesrevelaramelevac¸ãodatroponinaI eoecocardiogramaexibiuumadepressãomoderadadafunc¸ãosistólicadoventrículoesquerdo, porhipocontractilidadeglobal.Aressonânciamagnéticacardíacaconfirmouodiagnósticode miocardite,evidenciandomúltiplasáreasdefibrosesubepicárdica.Oiníciodossintomasapóso comec¸odamesalaminaeamelhoriadadortorácica,biomarcadorescardíacosefunc¸ãosistólica

Correspondingauthor.

E-mailaddress:carlos.galvaobraga@gmail.com(C.GalvãoBraga).

0870-2551/$–seefrontmatter©2012SociedadePortuguesadeCardiologia.PublishedbyElsevierEspaña,S.L.Allrightsreserved. http://dx.doi.org/10.1016/j.repc.2012.12.018

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718 C.GalvãoBragaetal.

ventricularesquerdaapósasuspensãodomedicamento,sugeremqueonossopacienteteve umareac¸ãoraradehipersensibilidadeàmesalamina.

© 2012 SociedadePortuguesa de Cardiologia. Publicado por Elsevier España, S.L.Todos os direitosreservados.

Introduction

Mesalamine (5-aminosalicylicacid) is a well-known treat-ment for inflammatory bowel disease, often used as the first-line drug. Although rare, adverse cardiac reactions duetomesalaminehavebeen described intheliterature, and include pericarditis, myocarditis, coronary vasculitis and left ventricular dysfunction.1---4 We report a case of

mesalamine-inducedmyocarditisinapatientwitharecent diagnosisofCrohn’sdisease.

Case

report

A19-year-oldmalewithnorelevantmedicalhistory,besides havingbeen diagnosed twoweekspreviously withCrohn’s diseaseforwhichhewasmedicatedwithmesalamine1500 mgtwice aday andbudesonide 9mg daily,wasadmitted tothelocalhospitalwithretrosternalchestpainradiating tothe left arm. He reported noaccompanying symptoms andnorelievingoraggravatingfactorswereidentified.The patient had no reported previous infection. The physical examination was unremarkable and there were no signs of hemodynamic instability or heart failure. The initial 12-leadelectrocardiogramrevealedsinusrhythmandslight ST-segmentelevationwithupwardconcavityinleadsI,II,III, aVFandV3---V6(Figure1).As laboratorytestsshowed ele-vatedcardiacnecrosisbiomarkers(troponinI9.1ng/ml),he wastransferredtoourhospitalforcardiologicalevaluation. Followingadmissiontothecardiaccareunit,hementioned some episodes of chest pain which improved after treat-ment with aspirin. Repeated blood tests demonstrated a furtherincreaseincardiacbiomarkers(peaktroponinI27.3 ng/mlandpeaktotalCK915IU/l)accompaniedbyelevation of NT-proBNP (6413 pg/ml) and inflammatory parameters (C-reactiveprotein130mg/l,15800leukocytes). Remodel-ingtherapywithACEinhibitorsandbeta-blockerswasalso introduced,duetothemoderatelydepressedleft ventricu-larsystolicfunction(ejectionfractionof38%)seen onthe transthoracicechocardiogram, withglobal hypocontractil-ity,althoughmorenoticeableintheposterior,inferiorand lateralwalls (Figure2).Cardiac magneticresonance imag-ing (MRI) withdelayed gadolinium enhancement revealed multipleareasofmyocardialfibrosis,mainlysubepicardial, suggestinganon-ischemicpattern(Figure3).Therewasno signofmyocardialinfarctionandthepatientwastherefore diagnosedwithacutemyocarditis.

In view of mesalamine’s cardiovascular toxicity as described in the literature, this drug was discontinued shortlyafteradmission.Thepatientremainedasymptomatic thereafterandlaboratorytestswerefavorable(NT-proBNP

905 pg/ml and troponin I 0.13ng/ml at discharge). Elec-trocardiogramsshowedprogressiveresolutionofST-segment elevationandtheechocardiogramwasrepeatedoneweek later,demonstratingimprovementinleftventricularsystolic function(ejectionfractionof45%).

Discussion

Classicmyocarditisreferstoinflammationoftheheart mus-cleasaresultofexposuretoeitherdiscreteexternalantigen triggers, such asviruses, bacteria, parasites or drugs, or tointernaltriggerssuchasautoimmuneactivationagainst self-antigens.Drugscanactasadirecttoxicagent (anthra-cyclinesandcocaine)orbyahypersensitivityreaction,asis thoughttobethecasewithmesalamineandother medica-tions (clozapine, sulfonamides, cephalosporins, penicillins andtricyclicantidepressants).5

Cardiac disease can be associated with Crohn’s dis-ease as an extraintestinal manifestation of inflammatory bowel disease or as a consequence of drug-induced side effects.1---4 Myocarditis associated with mesalamine is a

rarebutpotentially seriousphenomenon,generally occur-ring 2---4 weeks after the initial exposure to the drug, althoughpresentationmaybedelayedoveryears,especially if steroids are used concomitantly.6 Mesalamine’s

mech-anism of action is not fully understood, but it includes inhibitionofthecyclooxygenasepathway,inducingan anti-inflammatoryeffectinthecolon.Theexactmechanismfor mesalamine-inducedmyocardialinflammationisnotclearly identified,butitisthoughttobeahypersensitivityreaction ratherthanacytotoxiceffect.1,2Oneproposedmechanism

is humoral-mediated hypersensitivity, in which antibodies formed against mesalamine cross-react with cardiac tis-suecausinginflammation.6Thediagnosisofhypersensitivity

myocarditisis supportedbytwofacts:inflammation wors-ensifmesalamineisreintroducedduringtheacutephase,1

and resolution ofsymptoms occurswithinone week after drugdiscontinuation,ashasbeendescribedinallreported cases.1---4 Eosinophilic infiltration of the myocardium on

endomyocardial biopsy has also been described,7 which

seemstoconfirmthelinkbetweenmesalamineand hyper-sensitivitymyocarditis.

Inourcase,theonsetandresolutionofsymptomswere similar to those reported in the literature. Soon after discontinuing mesalamine,our patient evolvedwell, with progressive falls in cardiac biomarkers and improvement in left ventricular systolic function. Considering this evo-lution and the fact that there wasno previous infection, mesalamine-inducedmyocarditiswasconsidered tobethe mostlikelydiagnosis.

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Mesalamine-inducedmyocarditisfollowingdiagnosisofCrohn’sdisease 719

Figure1 Electrocardiogramondayofchestpainonset:sinusrhythmandslightST-segmentelevationwithupwardconcavityin leadsI,II,III,aVFandV3---V6.

Figure2 Echocardiograminparasternalshort-axisviewshowingmoderatelydepressedleftventricularsystolicfunction(ejection fractionof38%),withglobalhypocontractility,althoughmoreobviousintheposterior,inferiorandlateralwalls(A---diastole;B ---systole).

Figure3 Cardiacmagneticresonanceimagingwithmyocardialsuppressionaftercontrast.Lategadoliniumenhancementreveals multipleareasofsubepicardialmyocardialfibrosis,mainlyintheinferiorandlateralwalls,inshort-axis(A)and4-chamberviews(B).

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720 C.GalvãoBragaetal.

Conclusion

Thiscaseillustratestheimportanceofelicitingathorough medicalhistory andbeing awareof the timing when new medicationsarestarted.Itisimperativethatanynewonset ofchestpaininthesettingofinflammatoryboweldisease treated withmesalamineshould be evaluatedvia cardiac enzymes,electrocardiogram,echocardiogram andpossibly cardiacMRItorapidlydiagnoseanycomplicationcausedby eithertheinflammatoryboweldiseaseitselfor anadverse drugreaction.

Ethical

disclosures

Protection of human and animal subjects.The authors declarethatnoexperimentswereperformedonhumansor animalsforthisinvestigation.

Confidentiality of data.The authors declare that they have followed the protocols of their work center on the publication of patient data and that all the patients included in the study received sufficient informationand gavetheir written informedconsent toparticipatein the study.

Righttoprivacyandinformedconsent.Theauthorshave obtainedthe written informed consentof the patients or

subjectsmentionedinthearticle.Thecorrespondingauthor isinpossessionofthisdocument.

Conflict

of

interests

Theauthorshavenoconflictofintereststodeclare.

References

1.Perez-ColonE,DadlaniGH,WilmotI,etal.Mesalamine-induced myocarditisandcoronaryvasculitisinapediatriculcerative col-itispatient:acasereport.CaseRepPediatr.2011,524364. 2.Merceron O, Bailly C, Khalil A, et al. Mesalamine-induced

myocarditis.CardiolResPract.2010,930190.

3.Garcia-FerrerL,EstornellJ,PalancaV.Myocarditisbymesalazine withcardiac magneticresonance imaging. EurHeart J.2009; 30:1015.

4.AtayO,RadhakrishnanK,ArrudaJ,etal.Severechestpainin apediatriculcerativecolitispatientafter5-aminosalicylicacid therapy.WorldJGastroenterol.2008;14:4400---2.

5.BonowR,MannD,ZipesD,etal.Myocarditis.In:LiuP,Baughman K,editors.Braunwald’sheartdisease:atextbookof cardiovascu-larmedicine.Philadelphia:ElsevierScience;2012.pp.1596---9. 6.Waite R, Malinowski J. Possible mesalamine-induced

peri-carditis: case reportand literaturereview. Pharmacotherapy. 2002;22:391---4.

7.SteltsM,TaylorH,NappiJ,etal.Mesalamine-associated hyper-sensitivitymyocarditisinulcerativecolitis.AnnPharmacother. 2008;42:904---5.

Imagem

Figure 2 Echocardiogram in parasternal short-axis view showing moderately depressed left ventricular systolic function (ejection fraction of 38%), with global hypocontractility, although more obvious in the posterior, inferior and lateral walls (A --- dias

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