Rev. Bras. Reumatol. vol.55 número2

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rev bras reumatol.2015;55(2):174–176

w w w . r e u m a t o l o g i a . c o m . b r

REVISTA

BRASILEIRA

DE

REUMATOLOGIA

Case

report

Relapsing

polychondritis

with

severe

hearing

loss

Francisco

Vileimar

Andrade

de

Azevedo

∗

_,

_Juliana

_de

_Deus

_e

_Albuquerque,

Deborah

Pereira

Gonc¸alves

HospitalGeralDr.WaldemarAlcântara,Fortaleza,CE,Brazil

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Articlehistory:

Received3October2013 Accepted20March2014 Availableonline5January2015

Keywords:

Policondritis Auditiveloss Vasculitis

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Relapsingpolychondritisisanuncommon,immune-mediatedconditioncharacterizedby episodesofinflammationofcartilaginousstructures,especiallytheears,nose,jointsand respiratorytract.RPalsoaffectsproteoglycan-richstructuressuchastheeyes,heart,blood vesselsandinnerear.Aroundonethirdofcasesareassociatedwithotherdiseasessuchas vasculitides,connectivetissuediseasesormyelodysplasticsyndrome.Disordersoftheinner earoccurin40–50%ofpatients.Profoundhearinglossisrare.Theaimofthisstudywasto describethecaseofapatientwithrelapsingpolychondritisassociatedwithseverebilateral hearinglossandclinicalmanifestationsofsystemicvasculitis.Thisstudyreinforcesthe importanceofanearlydiagnosisandimmediatetreatmentincaseofseveremanifestations ofthedisease.

Policondrite

recidivante

com

perda

auditiva

severa

Palavras-chave:

Policondrite Perdaauditiva Vasculite

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Policondriterecidivanteéumacondiçãorara,imunomediada,caracterizadaporepisódios deinflamaçãodeestruturascartilaginosas,principalmenteorelhas,nariz,articulaçõese sistemarespiratório.Acometetambém estruturas ricasem proteoglicanoscomo olhos, coração, vasos sanguíneos e ouvido interno. Em torno de 1/3 dos casos apresentam associaçãocomoutrasdoençascomovasculitessistêmicas,doençasdotecidoconectivoou síndromemielodisplásica.Desordensdoouvidointernoocorremem40%-50%dospacientes. Perdaauditivaprofundaérara.Oobjetivodoestudofoidescreverocasodeumapaciente comdiagnósticodepolicondriterecidivanteassociadoàperdaauditivaseverabilaterale manifestaçõesclínicasdevasculitesistêmica.Estetrabalhoreforçaaimportânciado diag-nósticoprecoceedotratamentoimediatoemcasodemanifestaçõesseverasdadoença.

∗ _{Corresponding}_author_.

E-mail:vileimar@yahoo.com.br(F.V.A.deAzevedo). http://dx.doi.org/10.1016/j.rbre.2014.03.029

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175 Introduction

Relapsing polychondritis (RP) is a rare, immune-mediated conditioncharacterizedbyepisodesofinflammationof car-tilaginous structures, especially the ears, nose, joints and respiratorysystem.Italsoaffectsproteoglycan-richstructures suchastheeyes,heart,bloodvesselsandinnerear.The dis-easewasfirstdescribedin1923byJaksch-Wartenhorst,who namedthediseasepolicondropathy.Pearsonetal.introduced thetermpolychondritisin1960.1_The_condition_affects_men

and womenequally and can beseen inall races. Itspeak incidenceisbetween40and60years.2

TheetiologyofRPisunknown.Thegeneticpredisposition issuggestedbytheassociationwithleukocyteantigen HLA-DR4.3_There_is_evidence_for_the_emergence_of_{autoimmunity,}

bothhumoralandcellular, againstcartilagematrix compo-nentssuchascollagentypesII,IX,XIandmatriline-1.2

WereportthecaseofRPassociatedwithseverehearing lossandvasculiticskinlesions.

Case

report

DMD, 31 years old, female, with an everyday fever for twomonths, associated withchills, asthenia,polyarthritis, progressivebilateral hearing loss, tinnitus and episodes of dizziness.Amonthago,hercaseevolvedwiththeappearance ofskinlesionsonthehandsandlowerlimbs,bilateraledema intheeyelidsand ears,andacontinuouspaininthedistal regionof2ndrightfinger.

Aphysicalexaminationrevealedarthritisinwrists,elbows, ankles and proximal interphalangeal joints bilaterally. Her skin lesions were characterized by papules, pustules and purplish plaques on the hands, feet and anterior legs. In heroropharynx,aphthousulcerswereobserved.Itwasalso noticedalobe-sparingswellingandpainonpalpationinher pinnae,andbilateralconjunctivaledemaanderythema.The distal region of 2nd right finger exhibited a fixed painful cyanosis,associatedwithlowertemperatures(Fig.1).

Complementary tests showed normocytic and

nor-mochromic anemia (hemoglobin 7.9g/dL), leukocytosis of 16,000mm3 _without _shift, _and _elevation _of _inflammatory markers: C-reactive protein (CRP 196mg/L), erythrocyte

Fig.1–Left,vasculiticinjuryin2ndrightchirodactyl.Right, edemainthepinna,sparingtheearlobe.

Fig.2–Hyalinecartilage(pinna)containingnumerous inflammatorycellswithmatrixdegeneration.

(Hematoxylin–eosin–100×).Inset:evidenceofinfiltrate

withnumerousneutrophils,inassociationwith lymphocytesandhistiocytes(400×).

sedimentation rate (ESR, 45mm within 1h). Serology for hepatitisBand CandHIVwerenegative,andthepresence ofautoantibodies(antinuclearantibody,antineutrophil cyto-plasmicantibody,rheumatoidfactor)andcryoglobulinswere negative,aswellasforAFBinlymph.DirectCoombs,dosage ofcomplements,urinalysisandliverandrenalfunctionswere within normal standards. High digestive endoscopy, chest radiography, abdominal ultrasound, and Doppler forlimbs werenormal.Theechocardiogramshowednochanges.Blood and urine cultures showed no growth of microorganisms. Biopsiesofskinlesionswereperformedinthe2ndrightfinger andpinna.

The diagnosis ofrelapsing polychondritis was proposed based on the clinical manifestationsfound and on results of complementary tests. In the light of these findings, a treatment with prednisone 1mg/kg/day was initiated. The condition progressed to resolution of fever, conjunctival lesionsandjointconditions,butwithnoimprovementofthe deafnessandofischemiainthe2ndchirodactylafteraweek oftreatment.Atthatmoment,itwasdecidedtostartpulse therapywithmethylprednisolone1g/dayforthreedays.

The histopathology of the pinna showed the cartilage withlymphocyticandneutrophilicinfiltrateassociatedwith degenerationofhyalinematrix(Fig.2).Thehistopathologyof cutaneous lesionsoftheright hand revealednecrosiswith extensiveinfiltrationofneutrophilsandlymphocytes.

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176 Discussion

Patientswithrelapsingpolychondritisexhibitabroad spec-trumofclinicalsignsandsymptomsthatoftenincreasethe diagnosticchallenge.Thediagnostic criteriahavebeen pro-posedbyMacAdam,andrequirethreeormoreofthefollowing clinicalfeatures: bilateralauricular chondritis,seronegative non-erosive polyarthritis, nasal chondritis, ocular inflam-mation, respiratory tract chondritis and vestibulocochlear dysfunction.4_A_recent_modification_of_these_criteria_suggests

thatthediagnosis canbemadebythe presenceofatleast oneoftheMacAdamcriteria,inassociationwithhistological confirmation ofcartilage damage or chondritisin two dis-tinctanatomicalregions,withresponsetocorticosteroidsor dapsone.5

Thepatientdescribedhadbilateralchondritisofthepinna, bilateralconjunctivitis,seronegativenon-erosive polyarthri-tis,sensorineuralhearinglossandcompatible histopatholog-icalfindings,incompliancewithcriteriaforthediagnosisof RP.Apinnabiopsywasperformed,butthehistopathologyis notalwaysnecessarytoconfirmthediagnosis.

Earlydiagnosisisadifficulttask.TrenthamandLereported thatthe average timeto its establishmentisof2.9years.6

Themostfrequentclinicalmanifestationisanunilateralor bilateralinflammationoftheearcartilage,withanincidence rangingfrom43to83%.Arthritisisthesecondmostcommon manifestation.Aroundonethirdofcasesoccurinassociation withother diseases suchas systemicvasculitides, connec-tivetissuediseasesormyelodysplasticsyndrome.2_In_the_case

reported, besidesauricular chondritis and polyarthritisthe patienthadseveresensorineuralhearinglossand vasculitis-compatiblecutaneousmanifestations.

Disordersoftheinnerearoccurin40–50%ofpatients. Pro-foundhearinglossisrare.3,7_It_was_reported_an_association_of

cutaneousvasculitisandseverehearingloss,butthe patho-genesisofthissensorineural injuryisstilluncertain.There isapossibilityofanobliterativevasculitisintheinner audi-toryartery,causing otologicalinjury.8,9 _Another_hypothesis,

raisedbyIssingetal.,wouldbethepresenceofantilabyrinth antibodies in the serum of patients with audiovestibular dysfunction.10

Mucocutaneousmanifestationsoccurinmorethan50%of cases;aphthousulcersarethemostcommonchange.2_A

his-tologicalevaluationofskinlesionshasshownleukocytoclastic vasculitis,neutrophilicinfiltratesandthrombosisofskin ves-selsmoreoften.11

Vasculitisishistologicallyobservedin14–25%ofcasesand canbeindolentorfulminant; additionally,itandcanoccur simultaneouslyorindependentlyofothermanifestations.12

Drug treatment in patients with chondritis or arthritis shouldbestartedwithnonsteroidalanti-inflammatorydrugs, dapsoneorcorticosteroids.Inthosepatientswithsevere man-ifestations,systemicvasculitisorsensorineuralhearingloss, prednisone1mg/kg/day orpulse therapywith methylpred-nisolone is the treatment ofchoice. In casesof resistance tosteroids,otherimmunosuppressiveagents,including aza-thioprine,methotrexateandcyclophosphamide,arereported asbeinguseful.Isolatedcasereportswerepublished show-ing potentiallybeneficial resultswithantagonists oftumor

necrosisfactor.2_In_the_case_reported,_prednisone₁_mg/kg/day

wasstartedinapatientwithaclinicalpicturecompatiblewith cutaneousvasculitisandsevereinjuryinherinnerear.Asthe conditionhasnotevolvedwiththeexpectedimprovementof itsmostseveremanifestations,wedecidedinfavorofpulse therapywithmethylprednisoloneandcyclophosphamide.

Itisestimatedthatthefive-yearsurvivalis74%.Patients youngerthan51yearsoldandwithsystemicvasculitishavea worseprognosis.13

Relapsing polychondritis is a multisystem disease with variable presentation, which,inits spectrumof manifesta-tions,canleadtoseriousand irreversibledamagetotarget organs.Itislikely,thatinthecasereported,thepermanence ofa severehearing sequel,evenwiththe institutionofan aggressive therapy, is explained by the long time elapsed fromtheonsetofclinicalmanifestationstothediagnosisand institutionoftherapy.Anearlydiagnosis,combinedwithan aggressivetherapyincasesofseveremanifestations,can pro-ducebeneficialeffectsinthepreventionofserioussequelae.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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3.ZeunerM,StraubRH,RauhG,AlbertED,SchölmerichJ,Lang B.Relapsingpolychondritis:clinicalandimmunogenetic analysisof62patients.JRheumatol.1997;24:96–101. 4.McAdamLP,O’HanlanAM,BluestoneR,RearsonCM.

Relapsingpolychondritis:prospectivestudyof23patients andareviewoftheliterature.Medicine(Baltimore). 1976;55:193–215.

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Otorhinolaryngol.1990;256:163–6.

11.FrancesC,elRassiR,LaporteJL,RybojadM,PapoT,PietteJC. Dermatologicmanifestationsofrelapsingpolychondritis.A studyof200casesatasinglecenter.Medicine(Baltimore). 2001;80:173–9.

12.BarzegarC,VrtovsnikF,DevarsJF,MignonF,PradalierA. VasculitiswithmesangialIgAdepositscomplicatingrelapsing polychondritis.ClinExpRheumatol.2002;20:89–91.