The Challenge of Treating PulmonaryVasculitis in Behçet Disease: TwoPediatric CasesSelcan Demir, MD,a Erdal Sag, MD,a Ummusen Kaya Akca, MD,a Tuncay Hazirolan, MD,b Yelda Bilginer, MD,a Seza Ozen, MDa

abstractBehçet disease (BD) is a multisystemic autoinflammatory disordercharacterized by recurrent mucocutaneous, ocular, musculoskeletal,gastrointestinal, central nervous system, and vascular manifestations.Pulmonary arterial involvement (PAI) of BD is probably the most severe formof vasculitis, at least in children. PAI has a high mortality, morbidity, andrecurrence rate. There are limited data regarding treatment and outcomes ofpediatric patients with BD with PAI. Herein, we report 2 pediatric patientswith BD presented with hemoptysis and support our data with a systematicreview. These patients were given immunosuppressive therapy, whichcovered pulse methylprednisolone followed by oral prednisolone, intravenouscyclophosphamide every 3 weeks for a total of 6 cycles, and interferon-a2aconcomitantly. These are the first reported cases in the literature successfullytreated with this treatment modality in a complication with 50% mortality.These patients have been followed up for a period of at least 4 years withoutany vascular recurrence. Pediatricians should be aware that patients with BDmay not present with full diagnostic criteria. They should consider BD ina child with PAI to avoid diagnostic delay and start life-saving accurateimmunosuppressive treatment.

Behçet disease (BD) is a multisystemicautoinflammatory disease of unknownetiology characterized by recurrent oraland genital ulcerations, uveitis, andskin lesions, first described by HulusiBehçet in 1937.1 Since the disease wasfirst identified, involvement of othersystems like the central nervoussystem, gastrointestinal system, and thecardiopulmonary system have beenreported. The vasculitis is 1 of the mainpathologic findings of BD and hasunique features. BD can affect botharteries and veins of any size, and thushas been classified as “variable vesselvasculitis” at the International ChapelHill Consensus Conference.2

The most severe complication of BD ispulmonary artery involvement (PAI)because of its high mortality rate.

Although PAI is the most frequentarterial involvement in BD, theprevalence is,5%.3 PAI occurs early inthe disease course, unlike other arterialinvolvements. Recent studies haveshown that PAI had strong associationswith peripheral venous thrombosis,central nervous system thrombosis, andcardiac thrombosis.3,4 Despite theincreasing awareness of this potentiallyfatal vasculitis, early diagnosis, andtreatment, its mortality is still high.Data regarding the treatment andoutcomes of pediatric patients with PAIare limited.

Herein, we report 2 pediatric patientswith BD presenting with PAI andtreated successfully with aggressiveimmunosuppressive treatment(Table 1).

aDivision of Rheumatology, Department of Pediatrics, Facultyof Medicine, Hacettepe University, Ankara, Turkey; andbDepartment of Radiology, Faculty of Medicine, HacettepeUniversity, Ankara, Turkey

Dr Demir managed the patient as primary doctor,performed the systematic review, drafted the initialmanuscript, and revised and finalized the finalmanuscript as submitted; Drs Sag and Kaya Akcamanaged the patient as primary doctor with DrDemir and revised and finalized the final manuscriptas submitted; Dr Hazirolan did the radiologic studies;Dr Bilginer managed the patient as primary doctorwith Dr Demir, coordinated and supervised datacollection, and revised and reviewed the manuscript;Dr Ozen diagnosed the patient with Behçet disease,coordinated and supervised data collection, andcritically reviewed the manuscript; and all authorsapproved the final manuscript as submitted.

DOI: https://doi.org/10.1542/peds.2019-0162

Accepted for publication May 10, 2019

Address correspondence to Seza Ozen, MD, Divisionof Rheumatology, Department of Pediatrics,Hacettepe University Faculty of Medicine, Ankara06100, Turkey. E-mail: sezaozen@hacettepe.edu.tr

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,1098-4275).

Copyright © 2019 by the American Academy ofPediatrics

FINANCIAL DISCLOSURE: The authors have indicatedthey have no financial relationships relevant to thisarticle to disclose.

FUNDING: No external funding.

POTENTIAL CONFLICT OF INTEREST: The authors haveindicated they have no potential conflicts of interestto disclose.

To cite: Demir S, Sag E, Kaya Akca U, et al. TheChallenge of Treating Pulmonary Vasculitis inBehçet Disease: Two Pediatric Cases. Pediatrics.2019;144(2):e20190162

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CASE 1

In December 2012, a 15-year-oldboy was referred to our hospital forthe evaluation and treatment ofthrombosis. Three months beforereferral, he was admitted to a localhospital with abdominal pain, fever,and fatigue. An abdominal Dopplerultrasonography was performed andrevealed stenosis of the vena cavainferior (VCI) with a thrombus.Transthoracic echocardiography(TTE) detected that the thrombusextended from the VCI to the rightatrium (RA). Ventilation-perfusionscintigraphy results were consistentwith pulmonary thromboembolism.Fibrinolytic therapy andanticoagulant therapy wereinitiated. The patient’sthrombophilia mutations werescreened, and a heterozygote

mutation in factor V Leiden anda homozygous mutation inmethylenetetrahydrofolatereductase (MTHFR) 1298 andplasminogen activator inhibitor-1(PAI-1) were detected. When hestarted to have hemoptysis, he wasreferred to our hospital for furtherevaluation. His body temperaturewas 37.5°C, pulse was 76 beats perminute, respiratory rate was 18breaths per minute, and arterialblood pressure was 110/55 mmHg.The physical examination revealeda parasternal 4/6 systolic ejectionmurmur, a genital ulcer (10 3 10mm), and hepatomegaly. The lungfields were clear to auscultation.The laboratory findings were asfollows: white blood cells (WBCs)were 7900 cells per mm3 with 60%neutrophil, hemoglobin (Hb) was

13.1 g/dL, platelets were 230.000/mm3, C-reactive protein (CRP) was8.5 mg/dL, and erythrocytesedimentation rate (ESR) was90 mm/hour.

TTE revealed a left ventricleejection fraction of ∼60% anda mobile mass seen in the RA apex,which was well circumscribed. Thechest and abdominal computedtomography angiography (CTA)revealed bilateral aneurysmaticdilatation with thrombi in thepulmonary arteries and thickeningof the pulmonary artery walls,thrombosis in the VCI at thesuprahepatic level, and thrombi inthe vena hepatica (Fig 1A).Anticoagulant treatment wasimmediately stopped because hehad pulmonary artery aneurysm

TABLE 1 Clinical Characteristics of the Patients

Characteristics Patient 1 Patient 2

Age at diagnosis of BD, y 15 15The initial symptoms of BD Abdominal pain, fever, and hemoptysis Cough, intermittent hemoptysis, fever, wt loss,

and fatigueAge at PAI At the time of diagnosis At the time of diagnosisType of PAI PAA and PAT PAATime between BD diagnosis and PAI, mo 3 4Follow-up duration 6 y 4 yOral ulcer 2 1Genital ulcer 1 2Pathergy Negative result Negative resultHLA B5 Negative result Positive resultOcular lesions 2 2Skin involvement 2 1Other vascular involvement Suprahepatic VCI, vena hepatica (BCS), and RA RAImmunosuppression Pulse methylprednisolone (intravenous),

prednisolone (po), cyclophosphamide(intravenous), IFN-a2a (subcutaneous),adalimumab (subcutaneous)

Pulse methylprednisolone (intravenous),prednisolone (po),cyclophosphamide(intravenous), IFN-a2a (subcutaneous),azathioprine (po)

Anticoagulation Received anticoagulation before referral to ourcenter

2

ThrombophiliaFactor V Leiden 1/2 2/2MTHFR 677 2/2 1/1MTHFR 1298 1/1 2/2PAI-1 4g/4G 1/1 4g/4G 1/1Antiphospholipid antibodies Negative Negative

Laboratory tests at the time of PAIWBC, cells per mm3 7900 9300Hb, g/dL 13.1 9.4Platelets, per mm3 230.000 332.000CRP, g/dL 8.5 4.7ESR, mm/h 58 90

po, per oral; 2, negative; 1, positive.

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(PAA). The results of the pathergytest, human leucocyte antigen (HLA)B5, and HLA B51 were negative.Although he did not have enoughrevised International Criteria ofBehçet Disease (ICBD) criteria, wediagnosed him with BD because hehad thrombi in PAA, which is almostpathognomonic. He was givenimmunosuppressive therapy, withpulse methylprednisolone at a doseof 500 mg for 3 days along with andfollowed by oral prednisolone at1 mg/kg per day, intravenouscyclophosphamide at a dose of500 mg (15 mg/kg) every 3 weeksfor a total of 6 cycles, andinterferon-a2a (IFN-a2a) 3 timesa week. Within 1 month, thehemoptysis and fever disappearedand his CRP and ESR valuesnormalized. After a 3-monthtreatment, TTE and CTA revealedthat thrombi shrank significantly.The dosage of prednisolone wastapered gradually and stopped2 years later. After 6 doses ofcyclophosphamide and 6 months ofIFN-a2a, immunosuppressivetreatment was continued withadalimumab. The patient has beenmanaged in remission withadalimumab for nearly 6 yearsto date.

CASE 2

A 15-year-old boy was referred toour hospital in July 2014 for theevaluation of fever for .4 monthsand a thrombus in his RA. He hada 3-month medical history of cough,dyspnea, fever, intermittenthemoptysis, and significant weightloss (14 kg). He had severaladmissions to different hospitalsand had been prescribed antibioticswith the diagnosis of pneumonia. InJune 2014, a TTE was performedand detected a mass 20 3 30 mm insize in the right ventricle (RV). Withthe suspicion of infectiveendocarditis, broad-spectrumantibiotics were initiated. Later on,he had undergone thrombectomyfollowed by anticoagulant therapy.The blood and urine cultures (3times) were sterile. High feverpersisted for 3 weeks despiteantibiotics together with elevatedacute phase reactants. A control TTErevealed a recurrent mass (20 3 20mm) in the RV. He was referred toour hospital for further evaluation.His body temperature was 38.5°C,blood pressure was 120/85 mmHg,and heart rate was 104 beats permin. Physical examination revealedacnelike rashes over the face and

back, multiple ulcers on the buccalmucosa, bilaterally inspiratory andexpiratory wheezing, and a 3/6systolic ejection murmur at the leftupper parasternal area. A CTAconfirmed the thrombus in the RAand revealed bilateral multipleaneurysms along the pulmonaryartery and its branches andthickening of the pulmonary arterywalls (Fig 1B). Laboratory testsrevealed 9300 WBCs per mm3 with80% neutrophils, Hb of 9.4 g/dL,platelets at 332.000/mm3, CRP at4.7 mg/dL, and ESR at 90 mm/hour.HLA-B51 was positive but thepathergy test was negative.Thrombophilia tests revealeda homozygous mutation in MTHFR677 and in PAI-1. According torevised ICBD, the patient wasdiagnosed with BD because ofhaving aphthous ulcers,pseudofolliculitis, and vascularinvolvement. Intravenousmethylprednisolone (500 mg/day)for 3 days was followed by oralprednisolone at a dose of 1 mg/kgper day, which was subsequentlytapered. Intravenouscyclophosphamide at a dose of500 mg (15 mg/kg) was also givenevery 3 weeks for a total of 6 cycles,followed by oral azathioprine.Concomitant subcutaneous IFN-a2awas given 2 times per week for 6months. Within 2 weeks, the coughand fever disappeared and CRP andESR values normalized. After 1 year,the pulmonary artery aneurysmdisappeared and cardiac thrombosisresolved and returned nearlynormal. We have been managing thepatient with azathioprine for4 years without recurrence.

SYSTEMATIC REVIEW OF THELITERATURE

We performed a review of theliterature using PubMed, combiningthe main keywords “Behçet’sdisease AND Pulmonaryinvolvement; OR BD ANDpulmonary artery aneurysm; OR BD

FIGURE 1Chest CTA of a patient with BD with PAI. A, Bilateral aneurysmatic dilatation in the pulmonaryarteries (arrows). B, Bilateral multiple aneurysms along the pulmonary artery and its branches(arrows).

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AND Pulmonary artery thrombus.’’The searches were limited toEnglish language and pediatricpatients. Randomized andnonrandomized controlled trials,observational studies (case-control,cohort studies, and case series), andsingle case reports involving thepediatric patients with BD withpulmonary involvement wereincluded. The references for thesestudies and review articles foradditional publications were alsoreviewed (Table 2). The author S.D.searched the literature andmanually evaluated the titles andabstracts for relevance.Inconsistencies were resolved bydiscussion with the authors S.O. andY.B. (Fig 2).

DISCUSSION

We presented 2 pediatric patientswith pulmonary involvement of BDand treated the disease successfullywith aggressive immunosuppressivetreatment.

BD is a multisystemic inflammatorydisorder and usually diagnosed inyoung men; however, it can occur inchildhood as well. Previously,International Study Group (ISG) andlater on ICBD criteria have been usedto diagnose BD; however, bothcriteria sets were developed for adultpatients. Because there are differentdisease characteristics in adult andpediatric patients with BD, in 2015,an international expert consensusgroup suggested new classificationcriteria for pediatric Behçet disease(PEDBD).12 According to this novelPEDBD criteria, all symptomcategories have the same weight, andoral aphthosis is not a mandatorycriterion anymore. The patient shouldhave 3 or more of the followingcriteria to be classified as having BD:oral aphthosis ($3 attacks per year),genital aphthosis (typical with scars),skin involvement (necrotic folliculitis,acneiform lesions, erythemanodosum), neurologic involvement

(except isolated headaches), ocularmanifestations (anterior uveitis,posterior uveitis, retinal vasculitis),and vascular signs (venousthrombosis, arterial thrombosis,arterial aneurysms).12

Although the patient in case 1 did nothave enough PEDBD criteria, thepatient in case 2 fulfilled PEDBDcriteria with recurrent oral aphthosis,skin involvement, and vascularinvolvement. The first symptoms ofBD may present at early ages;however, all of the criteria for BDdiagnosis may not be fulfilled before16 years of age in more than 80% ofpatients.13 Koné-Paut et al14 reported86 children diagnosed with BD and21 of them failed to fulfill the ISGcriteria of BD. Children who arestrongly suspected of having BD (eg,who have the pathognomonic findingof PAA with thrombi) and do notfulfill the diagnostic criteria can stillbe diagnosed as having BD. It isimportant to include BD in thedifferential of pulmonary thrombi andaneurysms because early diagnosisand prompt treatment will be life-saving. Thus, the pediatricians mustbe aware that patients may notalways fulfill the criteria.

BD may involve any size of vessel inboth the arterial and venous systemsleading to the formation ofthrombosis, stenosis, andaneurysms.15 In a multicenter studyof 86 children with BD, arterial andvenous involvement (except cerebralvenous sinus thrombosis) werepresent in 7% and 12% of thepatients, respectively.14 Togetherwith PAI, the patient in case 1 hadgenital ulcer, cardiac thrombosis, andBudd-Chiari syndrome (BCS), and thepatient in case 2 had oral ulcers,pseudofolliculitis, and cardiacthrombosis at the same time. Similarto that, the diagnosis of BD and PAIhad been done concomitantly in 5patients reviewed from theliterature.6,7,9,10 When their medicalhistories were evaluatedretrospectively, other features

supporting BD were identified exceptin 1.6 Cohle and Colby6 presenteda 10-year-old African American boywho presented with massivehemoptysis and died in a short timeperiod at the hospital. At autopsy, thispatient had bilateral inflammatoryaneurysms of the lower lobe branchesof the pulmonary arteries.6

Microscopic examination in bothpulmonary arteries revealednecrotizing lymphocytic vasculitis.There were organized andrecanalized thromboembolisms insegmental pulmonary arterybranches. He did not have oral orgenital ulcerations or eye and skinlesions. Although he did not fulfill theISG, ICBD, or PEDBD criteria, he wasdiagnosed with BD on the basis of theautopsy findings.6

The most important type of vascularinvolvement in BD is the PAI,especially, PAAs, because of its highmortality rate and poor prognosis.16

Koné-Paut et al14 reported that 3 of86 children with BD had PAI. Unlikeother arterial involvements of BD,PAI usually occurs early in thedisease course with a malepredominance.4,17–19 Consistent withthese, our 2 patients and all of thereviewed patients from the literatureexcept 1 were male.11 The mostcommon initial symptom of PAI ishemoptysis and is followed by cough,fever, dyspnea, and chest pain.10 Bothof our patients and 6 cases from theliterature presented withhemoptysis.5–7,9,10 It has been shownthat the mortality ratio for the 14- to24 year-old age group with BD is10 times higher than that of thegeneral population. Most of thismortality is related to vascularthrombosis and especially PAA.20 PAIhas a poor prognosis. In a previousretrospective study of adult patientswith BD, the mortality was 50%among 24 patients with PAA within1 year after the onset ofhemoptysis.18 Seyahi et al10 reportedthat in 47 adult patients with BD withPAI after a mean follow-up of 7 years,

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TABLE2Summaryof

Reported

PatientsWho

HadPAIAssociated

With

JuvenileBD

Ozen

etal52010

Cohleand

Colby6

2002

Vivanteet

al72009

AlkaabiandPathare8

2011

Uzun

etal92008

Uzun

etal92008

Seyahi

etal102012

Bahabri

etal111996

Sex

Male

Male

Male

Male

Male

Male

Male

NAAgeat

BDdiagnosis,y

1410

1410

1717

12,16

Initial

symptom

ofPAI

Hemoptysis

Hemoptysis

Fever,wtloss,oralulcers,

andhemoptysis

NAHemoptysis,chest

pain,fever,and

fatigue

Hemoptysis,chest

pain,cough,

sputum

,wtloss,

andabdominal

pain

Hemoptysis

NA

ISGcriteria

Yes

NoYes

NANA

NANo

Yes

ICBD

(revised)

Yes

NoYes

NANA

NAYes

Yes

PEDB

Dcriteria

Yes

NoYes

NANA

NAYes

Yes

Ageat

PAI,y

1710

1415

1717

12NA

Timefram

ebetweenBD

diagnosisandPAI,

mo

480

060

00

0NA

Type

ofpulmonary

involvem

ent

PAA

PAA

PAA

PAA

PAA

PAT

PAA

PAA

Othervascular

involvem

ent

22

Cardiacthrombus

Cardiacthrombus

DVT

2Hepatic

vein

thrombosis-

BCS

NA

Pathergy

NANA

1NA

NANA

22

Oral

ulcer

12

11

NANA

11

Genitalulcer

12

2NA

NANA

21

Eyelesion

22

2NA

NANA

21

Skin

lesions

Erythemanodosum

2Papulopustular

lesions

NANA

NAErythemanodosum

Erythema

nodosum

HLA-B5

Positive

NANA

NANA

NANA

NAImmunosuppressive

treatm

ent

Pulsemethylprednisolone

(intravenous),

prednisolone

(po),

cyclophosphamide

(intravenous)

2Colchicine,pulse

methylprednisolone

(intravenous),

prednisolone

(po),

cyclophosphamide

(intravenous)

cyclophosphamide

Corticosteroid,

colchicum

Corticosteroid

Prednisolone,

cyclophosphamide

(intravenous),

infliximab

(subcutaneous)

NA

Anticoagulation

22

1(afterresolutionof

hemoptysis)

NA2

Enoxaparin

1coum

adin

2NA

Follow-upandoutcom

e18-mofollow-upwith

novascular

relapse

Dead

before

diagnosis

becauseof

massive

hemoptysis

7-mofollow-upwith

novascular

relapse

Dead

after2yof

diagnosisbecause

ofmassive

hemoptysis

Dead

at16

mo

becauseof

massive

hemoptysis

Aliveat

7mo

Dead

at12

mobecause

ofhepatic

failure

NA

DVT,deep

venous

thrombosis;po,per

oral;N

A,notavailable.

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the mortality rate was 26% and therecurrence rate was 20%. Dataregarding treatment and outcomes ofpediatric patients with pulmonaryartery involvement are limited, andonly a few pediatric cases have beenreported with this pathology in theliterature.

The other main type of pulmonaryartery involvement is pulmonaryartery thrombus (PAT). PAT could

occur with or without PAA.Hemoptysis is also the mainpresenting symptom in PAT; however,it is less likely to be severe than PAA.Other clinical features are similar inboth conditions.3,10 Uzun et al9

showed that the prognosis of patientswith BD with PAI presenting asisolated PAT was better than theprognosis presenting with PAA.However, Seyahi et al10 demonstratedthat the mortality rate was similar for

patients with PAA (26%) and forpatients with isolated PAT (23%).

PAT is strongly associated withother venous involvements, such aslower-extremity deep venousthrombosis, cerebral venous sinusthrombosis, and intracardiacthrombosis.4 Cardiac thrombosis ismostly located on the right side ofthe heart and adhered to theendocardium or myocardium.21

Both of our patients hadconcomitant cardiac thrombosis inthe RA. Similar to our patients,Vivante et al7 presented a 14 year-old Arab boy who had bilateral PAAand right ventricular thrombus atthe diagnosis of BD. Alkaabi andPathare8 reported a 15-year-old boywho had PAA and intracardiacthrombosis who was uncompliant tothe treatment and died at 24 monthsbecause of massive hemoptysis.

It is important to make a fastdifferential diagnosis in PAI toprovide an early and accuratetherapy. More than half of the PAAsare due to congenital cardiac (such asatrial septal defects, ventricularseptal defects, patent ductusarteriosus, and other structural heartdefects) and vessel anomalies (suchas Ehler-Danlos syndrome, Marfansyndrome, cystic medial necrosis).However, there are also acquiredcases, including infections(tuberculosis, syphilis, endocarditis,septic embolism), pulmonary arterialhypertension, inflammatory lungdiseases (bronchiectasis, pulmonaryfibrosis, interstitial lung disease),iatrogenic causes (cardiothoracicsurgery, pulmonary arteryangiography), trauma, and vasculitis(BD, Hughes-Stovin syndrome).22

PAT can be either due tothromboembolic causes (infections,central venous catheters, positivity inthrombophilia mutations,immobilization, surgery, trauma,cancer, inflammatory conditions suchas BD, systemic lupus erythematosus,and inflammatory bowel disease) or

FIGURE 2Systematic review flowchart.

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due to in situ PAT (local causes suchas congenital heart disease,pulmonary artery anomalies, lungtransplant).22,23 However, thrombiinside the aneurysmatic dilatation ofthe pulmonary arteries are almostpathognomonic for BD.

BCS is another severe complication ofBD and seems to be rare in children.14

BCS usually presents concomitantlywith lower-extremity deep venousthrombosis, iliac vein thrombosis, andintrahepatic VCI thrombosis.3 It hasbeen shown that the prognosis isbetter if the patient with BD with BCSpresented without ascites.24 Thepatient in case 1 presented with PAIand BCS concomitantly. Similar to thispatient, Seyahi et al10 reported a 12-year-old patient who was diagnosedwith BD having pulmonary arterialaneurysms and BCS. He haddeveloped hepatic encephalopathyand died of hepatic failure under thetreatment prednisolone andcyclophosphamide.10

There are no randomized controlledstudies evaluating treatmentoptions in pulmonary involvementof BD. The main goal of treatment isto control the inflammationcompletely; thus,immunosuppressive therapy isessential. PAI is a life-threateningcondition and should be managedwith more aggressive medicaltherapy. In 2018, an internationalgroup of experts published theEuropean League AgainstRheumatism (EULAR)–endorsedrecommendations for themanagement of BD.25 According tothese recommendations, treatmentshould be personalized according toage, sex, and type and severity oforgan involvement.25 Colchicine issuggested for ulcers in BD, althoughit is probably not effective in theprevention or treatment ofvasculitis. Again, theaforementioned recommendationssuggest for the primarymanagement of PAA and PAT ashigh-dose glucocorticoids and

cyclophosphamide.25

Cyclophosphamide may be givenmonthly for 6 or 12 months, andglucocorticoids are usually given as3 intravenous methylprednisolonepulses followed by oralprednisolone at a dose of 1 mg/kgper day.17,26 There is no consensusand evidence for the benefit ofanticoagulation treatment in thevasculitis of BD. Although it is clearthat the only contraindication ofanticoagulation is the presence ofPAA because of the risk of rupture,they can still be used for otherthrombotic involvement in BD.25

In accordance with the literature andEULAR recommendations, ourpatients had been given pulsemethylprednisolone at a dose of500 mg for 3 days along with andfollowed by oral prednisone at a doseof 1 mg/kg per day, and intravenouscyclophosphamide at a dose of500 mg every 3 weeks for a total of 6cycles. We strengthened ourimmunosuppressive treatment withIFN-a2a.

IFN-a2a is successfully used to treatBS-related uveitis.27,28 In addition, italso has been shown beneficial inmucocutaneous and articularmanifestations.29,30 There is no datain the literature regarding the use ofIFN-a2a in PAI treatment along withlow-dose cyclophosphamide. Ourpatients were treated successfullywith this treatment modality, and theclinical response was good. Therewere no mortality or recurrenceswithin the 6- and 4-year follow-upperiods.

CONCLUSIONS

Because of its high mortality rate andthe need to establish a promptdiagnosis and initiate appropriatetreatment, pediatricians shouldinclude BD in the differential ofadolescents who present witha combination of hemoptysis andoral or genital ulcers. Early andaggressive immunosuppressivetherapy may improve prognosis.

REFERENCES

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2. Jennette JC, Falk RJ, Bacon PA, et al.2012 Revised International Chapel HillConsensus Conference Nomenclature ofVasculitides. Arthritis Rheum. 2013;65(1):1–11

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ABBREVIATIONS

BCS: Budd-Chiari syndromeBD: Behçet DiseaseCRP: C-reactive proteinCTA: computed tomography

angiographyESR: erythrocyte sedimentation rateEULAR: European League Against

RheumatismHb: hemoglobinHLA: human leucocyte antigenICBD: International Criteria of

Behçet DiseaseIFN-a2a: interferon-a2aISG: International Study GroupMTHFR: methylenetetrahydrofolate

reductasePAA: pulmonary artery aneurysmPAI: pulmonary arterial

involvementPAI-1: plasminogen activator

inhibitor-1PAT: pulmonary artery thrombosisPEDBD: pediatric Behçet diseaseRA: right atriumTTE: transthoracic

echocardiographyVCI: vena cava inferiorWBC: white blood cell

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DOI: 10.1542/peds.2019-0162 originally published online July 18, 2019; 2019;144;Pediatrics 

and Seza OzenSelcan Demir, Erdal Sag, Ummusen Kaya Akca, Tuncay Hazirolan, Yelda Bilginer

Pediatric CasesThe Challenge of Treating Pulmonary Vasculitis in Behçet Disease: Two

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Pediatric CasesThe Challenge of Treating Pulmonary Vasculitis in Behçet Disease: Two

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