title: Pulmonary hypertension and other potentially fatal pulmonary complications in systemic juvenile idiopathic arthritis.
abstract: OBJECTIVE
  Systemic juvenile idiopathic arthritis (JIA) is characterized by fevers, rash, and arthritis, for which interleukin-1 (IL-1) and IL-6 inhibitors appear to be effective treatments. Pulmonary arterial hypertension (PAH), interstitial lung disease (ILD), and alveolar proteinosis (AP) have recently been reported with increased frequency in systemic JIA patients. Our aim was to characterize and compare systemic JIA patients with these complications to a larger cohort of systemic JIA patients.
  
  
  METHODS
  Systemic JIA patients who developed PAH, ILD, and/or AP were identified through an electronic Listserv and their demographic, systemic JIA, and pulmonary disease characteristics as well as their medication exposure information were collected. Patients with these features were compared to a cohort of systemic JIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry.
  
  
  RESULTS
  The patients (n = 25) were significantly (P < 0.05) more likely than the CARRA registry cohort (n = 389) to be female; have more systemic features; and have been exposed to an IL-1 inhibitor, tocilizumab, corticosteroids, intravenous immunoglobulin, cyclosporine, and cyclophosphamide. Twenty patients (80%) were diagnosed with pulmonary disease after 2004. Twenty patients (80%) had macrophage activation syndrome (MAS) during their disease course and 15 patients (60%) had MAS at pulmonary diagnosis. Sixteen patients had PAH, 5 had AP, and 7 had ILD. Seventeen patients (68%) were taking or recently discontinued (<1 month) a biologic agent at pulmonary symptom onset; 12 patients (48%) were taking anti-IL-1 therapy (primarily anakinra). Seventeen patients (68%) died at a mean of 10.2 months from the diagnosis of pulmonary complications.
  
  
  CONCLUSIONS
  PAH, AP, and ILD are underrecognized complications of systemic JIA that are frequently fatal. These complications may be the result of severe uncontrolled systemic disease activity and may be influenced by medication exposure.
authors.affiliation: Division of Pediatric Rheumatology, Joseph M. Sanzari Children’s Hospital, Hackensack University Medical Center, 30 Prospect Avenue, Hackensack, NJ 07601, USA. YKimura@HackensackUMC.org
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kimura
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Weiss
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Haroldson
authors.forename: Tzielan
authors.initials: T
authors.lastname: Lee
authors.forename: Marilynn
authors.initials: M
authors.lastname: Punaro
authors.forename: Sheila
authors.initials: S
authors.lastname: Oliveira
authors.forename: Egla
authors.initials: E
authors.lastname: Rabinovich
authors.forename: Meredith
authors.initials: M
authors.lastname: Riebschleger
authors.forename: Jordi
authors.initials: J
authors.lastname: Antón
authors.forename: Peter R
authors.initials: PR
authors.lastname: Blier
authors.forename: Valeria
authors.initials: V
authors.lastname: Gerloni
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Hazen
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kessler
authors.forename: Karen
authors.initials: K
authors.lastname: Onel
authors.forename: Murray H
authors.initials: MH
authors.lastname: Passo
authors.forename: Robert M
authors.initials: RM
authors.lastname: Rennebohm
authors.forename: Carol A
authors.initials: CA
authors.lastname: Wallace
authors.forename: Patricia
authors.initials: P
authors.lastname: Woo
authors.forename: Nico
authors.initials: N
authors.lastname: Wulffraat
mesh_terms: D000293:Adolescent; D001171:Arthritis, Juvenile / Q000150:complications / Q000175:diagnosis* / Q000401:mortality*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality*; D007223:Infant; D008297:Male; D012042:Registries; D012189:Retrospective Studies; D011795:Surveys and Questionnaires