Children with systemic juvenile idiopathic arthritis and severe, chronic lung disease have distinctive clinical and immunological changes that are not yet fully characterized, researchers have found.

The study, “Systemic Juvenile Idiopathic Arthritis-Lung Disease: Characterization and Risk Factors,” was published in Arthritis and Rheumatology.

Systemic juvenile idiopathic arthritis (SJIA) has been shown to be associated with pulmonary complications, which are often fatal. About 10–15% of those with systemic juvenile idiopathic arthritis also develop life-threatening macrophage activation syndrome (MAS), a condition characterized by severe inflammation of the immune system.

In the last few years, the number of patients with rheumatic disease-related pulmonary complications has increased, and children with SJIA have been reported to have more severe and life-threatening lung disease; however, the latter remains poorly characterized.

Researchers at the Cincinnati Children’s Hospital Medical Center (CCHMC) set up to describe the clinical characteristics, risk factors, and cellular/tissue features of SJIA-associated lung disease.

In this prospective cohort study, “patients were identified upon lung disease detection or referral to CCHMC for consultation or second opinion,” the researchers said.

The team searched the medical records for relevant clinical data and had the patients undergo cellular, biochemical, and genomic analysis.

Since 2010, researchers have evaluated 18 children (nine girls and nine boys) with SJIA-associated lung disease. Radiological examination revealed pulmonary changes and swollen lymph nodes, indicative of an infection. High levels of plasma cells — i.e. infection-fighting cells — surfactant (a mixture of lipids and proteins released by certain cells in the lungs) accumulation, and lipid buildup were found in the patients’ lung tissue.

Compared to those without pulmonary complications, children with SJIA-associated lung disease were younger at the time of rheumatic disease diagnosis, had had prior episodes of macrophage activation syndrome and reacted badly to biologic therapy.

Those with lung disease were also found to have higher levels of serum interleukin 18 (IL-18), a cytokine that has been used to monitor both SJIA and MAS activity. In addition, some patients had elevated concentrations of two chemokines: CXCL9 and CXCL10. Chemokines are small signaling proteins secreted by immune cells that play key roles in the regulation of the immune system.

When looking into the children’s genetics, scientists found increased activation of the molecular pathways involved in the regulation of inflammatory and immune responses. “This signature was also present in SJIA-LD lung tissue sections lacking substantial histopathological findings, suggesting it may precede and drive lung [disease manifestations],” the researchers noted.

Although the results indicate several risk factors for developing pulmonary complications in SJIA,  the team believes that larger studies including different geographic areas and medication regimens are necessary.