Rev. Bras. Reumatol. vol.56 número6

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r e v b r a s r e u m a t o l . 2016;56(6):551–553

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

Childhood-onset

systemic

polyarteritis

nodosa

and

systemic

lupus

erythematosus:

an

overlap

syndrome?

Poliartrite

nodosa

sistêmica

e

lúpus

eritematoso

sistêmico

de

início

na

infância:

uma

síndrome

de

sobreposic¸ão?

Victor

L.S.

Marques

a

_,

_Andressa

_Guariento

a,b

,

Marlise

S.M.

Simões

a

,

Gabriela

Blay

a

,

Ana

Paola

N. Lotito

a

_,

_Clovis

_A.

_Silva

a,∗

a_Universidade_de_São_Paulo,_Faculdade_de_Medicina,_Unidade_de_Reumatologia_Pediátrica,_São_Paulo,_SP,_Brazil

b_Santa_Casa_de_{Misericórdia}_de_São_Paulo,_Departamento_de_Pediatria,_Unidade_de_Reumatologia_Pediátrica,_São_Paulo,_SP,_Brazil

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received7August2014 Accepted11January2015 Availableonline13July2015

Introduction

Childhood-onset systemic polyarteritis nodosa (c-PAN) is a rare necrotizing arteritis characterized by the pres-ence of aneurismal nodules, stenosis or occlusion of small and medium-sized vessels of the entire body.1–3

Recently, the European League Against Rheumatism (EULAR)/PaediatricRheumatology International Trials Orga-nisation(PRINTO)/PaediatricRheumatologyEuropeanSociety (PRES)proposed newvalidated criteriaforc-PAN diagnosis. Thisnewcriteriastudied150patientswithc-PANworldwide and demonstrated high sensitivity and specificity for the diagnosisofthissystemicvasculitis.3

∗ _{Corresponding}_author_.

E-mail:clovisaasilva@gmail.com(C.A.Silva).

Childhood-onset systemic lupus erythematosus (c-SLE) is an autoimmune and multisystemic disorder.4,5

Inflam-mation of the blood vessels is a common disease man-ifestation and may affect small, medium and large-sized vessels.4–7

Moreover, c-SLEand c-PAN may present similar clinical manifestations and laboratory alterations. However,to our knowledgetheoverlapsyndromeofthesetwodiseaseshas not previouslybeen described. Therefore, we reviewedour datafromJanuary1983toJuly2013andincluded5593patients followed atourPediatricRheumatology Unit.Weidentified 289(5.1%)c-SLEpatientsthatfulfilledtheAmericanCollege ofRheumatology(ACR)6_{classification}_criteria_and₁₅ _c-PAN

patientsthat fulfilledtheEULAR/PRINTO/PREScriteria.7 _We

http://dx.doi.org/10.1016/j.rbre.2015.01.004

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rev bras reumatol.2016;56(6):551–553

describedhereinapatient(0.34%)whopresentedapossible c-PANandc-SLEoverlap.

Case

report

A 9-year-old girl presented tender subcutaneous nodules on the feet, arterial hypertension, right hemiplegia and dysarthricspeech.Shewashospitalizedduetostroke, numb-nessinher extremitiesand left foot drop. Brain computer tomography showed ischemic stroke. Magnetic resonance angiography revealed stenosis in the middle cerebral and internalcarotidarteries.Electroneuromyographyidentifieda mononeuropathyoftheleftposteriortibialnerve.Therefore, C-PANwasdiagnosedaccordingtotheEULAR/PRINTO/PRES criteria.3 _Laboratory _tests _showed _hemoglobin ₁₂_g/dL,

white blood cell count (WBC) 5500/mm3 _(75% _neutrophils,

19% lymphocytes, 5% monocytes and 1% eosinophils), platelets264,000/mm3_,_erythrocyte_{sedimentation}_rate_(ESR)

45mm/1sthour,C-reactive protein(CRP) 0.9mg/dL (normal 0–0.3),aspartateaminotransferase22U/L(normal15–40), ala-nineaminotransferase21U/L(normal 10–35),urea26mg/dL (normal range 15–45mg/dL) and creatinine 0.7mg/dL (nor-mal range 0.6–0.9mg/dL). Urinalysis and 24-h proteinuria werenormal.Immunologicaltestsshowedantinuclear anti-bodies (ANA) 1:320 (fine speckled pattern), and negative anti-double-strandedDNA (anti-dsDNA),anti-Sm, anti-RNP, antineutrophil cytoplasmicautoantibodies(ANCA),IgG and IgM anticardiolipin antibodies, and lupus anticoagulant. She received three intravenous methylprednisolone pulse therapy, followed by prednisone (1.4mg/kg/day) that was progressively tapered, aspirin (150mg/day), six months of intravenouscyclophosphamide(500mg/m2_/month)_and_after

thatshewastreatedwithazathioprine(1.6mg/kg/day)for19 months.At13yearsand10months,shepresentedmultiple erythematous scalyplaques over the malararea, earsand chest. The skin biopsy from the left ear evidenced focal psoriasiform hyperplasia with perivascular mononuclear infiltrate and direct immunofluorescence showed granular immunoglobulin G (IgG), IgA, IgM and C3 deposits at the dermoepidermal junction. She was treated with topical hydrocortisone1% with improvementof skin lesions after 3months. At the age of 14 years and 9 months, she pre-sented malar rash, photosensitivity, edema inlower limbs andarterialhypertension.Atthatmoment,hemoglobinwas 11.61g/dL,WBCwas 3500/mm3 _(80%_neutrophils, _15%

lym-phocytesand5%monocytes),platelets391,000/mm3_,_ESR_was

54mm/1sthour,CRP7.0mg/dL,urea20mg/dLandcreatinine 0.4mg/dL. Urinalysis showed leukocyturia and hematuria. Theproteinuriawas1.7g/day.ANAwas1/1280(homogeneous nuclear pattern) and anti-dsDNA antibodies were posi-tive.Anti-Sm, anti-RNP, ANCA, IgG and IgManticardiolipin antibodies and lupusanticoagulant were negative.C3 was 41mg/dL(range79–152)andC4was4.5mg/dL(range16–38). Renal biopsy showed focal proliferative and membranous glomerulonephritiswithimmunedepositsofC1q,C3,IgG,IgM andIgA.ShefulfilledtheAmericanCollegeofRheumatology classificationcriteria forSLE8 _and _the_SLE _Disease_Activity

Index 2000 (SLEDAI-2K)9 _was _18. _She _was _treated _with

prednisone (0.6mg/kg/day), hydroxychloroquine (6.0mg/kg/day)andmycophenolatemofetil(2.0g/day).

Discussion

Wereportedhereinauniquecaseofapossiblec-PANandc-SLE overlapoveraperiodof30yearsatourtertiaryhospital.

Itwasobservedthatourpatienthadstenosisinthemiddle cerebralandinternalcarotidarteriescompatiblewithc-PAN5 yearsbeforethec-SLEdiagnosis,thussuggestingthepresence oftwodifferentautoimmunediseasesoveralongperiodof time.

Primaryvasculitishasbeenrarelyreportedinassociation withSLE.6,7 _Of_note,_Kawasaki_disease_is_an_acute_childhood

systemicvasculitisthatmainlyaffectsthemediumvessels, particularlycoronaryarteries,andmayoverlapwithc-SLE.6

Moreover,subacutecutaneouslupuserythematosusoccurs in 7–27% of adultswith SLE and has been rarely reported in pediatriclupus population. Thelesionsare papulosqua-mous, affectingareas exposed tosunlight,asevidenced in ourpatient.10_{Interestingly,}_the_subacute_cutaneous_lupus_is_a

newtopicoftherecentSystemicLupusInternational Collab-oratingClinics(SLICC)criteria,validatedforadultandc-SLE populations.11,12

Ourcasefulfilledthec-PAN diagnosiscriteria.According tothenewpediatricEULAR/PRINTO/PREScriteria,3_a_patient

is classified with c-PAN if presents necrotizing vasculitis involvingmediumorsmallarteriesoranangiographic abnor-malityshowinganeurysm,stenosis,orocclusionofamedium or small-sized artery, plus one of these following criteria: skininvolvement(livedoreticularis,skinnodulesorinfarcts), peripheral neuropathy, arterial hypertension, myalgia or muscletendernessandrenalinvolvement.Remarkably, sensi-tivityandspecificityofthesenewcriteriaforc-PANdiagnosis were89.6%and99.6%,respectively.3

Since the two diseases coexisted over a long period time, the association between them may suggest an over-lap syndrome. Indeed, the subsequent change of clinical andlaboratorialabnormalitieswiththe presenceofspecific autoantibodies,decreasedcomplementlevels,13_and_skin_and

kidneybiopsiesconfirmedthec-SLEdiagnosis.Furthermore, the presenceofANCAwasreported insixout of47 tested c-PANpatientsinamulticenterstudy2_and_ANA_is_generally

negativeinc-PAN.1

However,allofc-PANmanifestationsofourpatientmay beevidencedinc-SLEandwecannotexcludethepossibility that thefirstsigns andsymptomsmay beattributedsolely tolupus.Therefore,thispatientmaybesufferingfromc-SLE withvisceralmanifestationsofvascultismimickingc-PAN.

Inconclusion,wedescribedhereinapossibleoverlap syn-dromeoftwoautoimmunediseases,wherec-PAN occurred fiveyearsbeforethec-SLEdiagnosis.

Funding

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rev bras reumatol.2016;56(6):551–553

553

doDesenvolvimento CientíficoeTecnológico(CNPQ–grant 302724/2011-7toC.A.S.),byFedericoFoundationtoC.A.S.and byNúcleodeApoioàPesquisa“SaúdedaCrianc¸aedo Adoles-cente”daUSP(NAP-CriAd).

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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