William J. Freeman, Eileen C. Rife, Randy Q. Cron
Hofstra Northwell School of Medicine and Steven and Alexandra Cohen Children’s Medical Center of New York. University of Alabama at Birmingham Heersink School of Medicine and Children’s of Alabama.
United States
Frontiers in Immunology
Front Immunol 2026;
DOI: 10.3389/fimmu.2026.1798455
Abstract
Introduction: Systemic juvenile idiopathic arthritis-associated lung disease (sJIA-LD) is a rare, potentially fatal complication of sJIA, often accompanied by pulmonary hypertension (PHTN) and macrophage activation syndrome (MAS). The underlying pathophysiology remains poorly understood and optimal management strategies have yet to be established. Recent retrospective data suggest that combination therapy with cyclophosphamide (CYC) and rituximab (RTX) may be effective in children with severe or life-threatening manifestations of rheumatic disease. Yet, literature on combination therapy in sJIA-LD is lacking.
Methods: We describe two pediatric cases of sJIA-LD complicated by PHTN and recurrent episodes of MAS. Both patients remained refractory to conventional sJIA therapies, necessitating escalation with combination CYC-RTX.
Results: Following combination CYC-RTX therapy, both patients demonstrated marked clinical improvement, including resolution of hyperferritinemia, normalization of acute phase reactants, and recovery of hepatic function profiles. Patient 1 experienced a reduction in supplemental oxygen requirement from 4 liters per minute (LPM) to 0.5 LPM nocturnally as well as improved PHTN measures: mean pulmonary arterial pressure decreased from 47 to 25 mmHg, and pulmonary vascular resistance decreased from 11.1 to 4.3 Wood units. Patient 2 experienced improved height velocity from <3rd percentile to >10th percentile and weaned off all therapies. Daily prednisone requirement for patient 1 decreased from 1 to <0.2 mg/kg/day. Chest computed tomography showed notable improvements in ground-glass opacities and septal and pleural thickening in both patients.
Conclusion: Combination therapy with CYC and RTX may represent a valuable therapeutic approach in refractory sJIA complicated by lung disease, particularly in patients with concomitant MAS or PHTN.
Category
Class I. Pulmonary Hypertension Associated with Connective Tissue Disease
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes