Researchers at Hackensack University Medical Center in Hackensack, N.J., performed a retrospective review of systemic juvenile idiopathic arthritis (sJIA) patients who developed pulmonary artery hypertension (PAH), interstitial lung disease (ILD), and alveolar proteinosis (AP). Their purpose was to identify and characterize the cases and compare them to a larger cohort of sJIA patients. Consequently, they were compared with such a cohort enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) pediatric rheumatic diseases registry.
The cases (N=25) were significantly more likely (P
<0.05) than the CARRA registry cohort (N=389), to be female and have more systemic features. They were also significantly more likely to have been exposed to an IL-1 inhibitor, tocilizumab, infliximab, corticosteroids, intravenous immunoglobulin, cyclosporine, and cyclophosphamide. Twenty (80%) patients had macrophage activation syndrome (MAS) during their disease course and 16 (64%) had suspected/confirmed MAS at pulmonary diagnosis. Sixteen patients had PAH, 7 AP, and 8 ILD. Dyspnea on exertion and shortness of breath were the most common symptoms. One patient was diagnosed at autopsy and did not have any known prior pulmonary symptoms. Seventeen (68%) patients were taking or recently (<1 month) discontinued a biologic agent at pulmonary symptom onset, and 12 (48%) were taking anti-IL1 therapy (primarily anakinra). Seventeen (68%) patients died at a mean of 10.2 months from pulmonary diagnosis.
"This is the first time that a large cohort of sJIA patients who developed PAH, AP, and ILD has been described," the investigators noted. "These are important, largely fatal, and under-recognized complications of sJIA which are likely to be the result of severe uncontrolled systemic disease activity and inflammation, but may be influenced by exposure to certain medications."