Dr. Kimura has received consultancy fees, speaking fees, and/or honoraria (less than $10,000 each) from Genentech and Novartis.
Pulmonary Hypertension and Other Potentially Fatal Pulmonary Complications in Systemic Juvenile Idiopathic Arthritis†
Article first published online: 23 APR 2013
Copyright © 2013 by the American College of Rheumatology
Arthritis Care & Research
Volume 65, Issue 5, pages 745–752, May 2013
How to Cite
Kimura, Y., Weiss, J. E., Haroldson, K. L., Lee, T., Punaro, M., Oliveira, S., Rabinovich, E., Riebschleger, M., Antón, J., Blier, P. R., Gerloni, V., Hazen, M. M., Kessler, E., Onel, K., Passo, M. H., Rennebohm, R. M., Wallace, C. A., Woo, P., Wulffraat, N. and The Childhood Arthritis Rheumatology Research Alliance Carra Net Investigators (2013), Pulmonary Hypertension and Other Potentially Fatal Pulmonary Complications in Systemic Juvenile Idiopathic Arthritis. Arthritis Care Res, 65: 745–752. doi: 10.1002/acr.21889
See Appendix A for a list of the contributing Childhood Arthritis and Rheumatology Research Alliance CARRAnet investigators.
- Issue published online: 23 APR 2013
- Article first published online: 23 APR 2013
- Accepted manuscript online: 8 NOV 2012 01:13PM EST
- Manuscript Accepted: 15 OCT 2012
- Manuscript Received: 29 JUN 2012
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.
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.
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.
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.