Behrens, Edward M.

Objective Systemic juvenile idiopathic arthritis–associated lung disease (SJIA‐LD) is a life‐threatening disease complication. Key questions remain regarding clinical course and optimal treatment approaches. The objectives of the study were to detail management strategies after SJIA‐LD detection, characterize overall disease courses, and measure long‐term outcomes. Methods This was a prospective cohort study. Clinical data were abstracted from the electronic medical record, including current clinical status and changes since diagnosis. Serum biomarkers were determined and correlated with presence of LD. Results We enrolled 41 patients with SJIA‐LD, 85% with at least one episode of macrophage activation syndrome and 41% with adverse reactions to a biologic. Although 93% of patients were alive at last follow‐up (median 2.9 years), 37% progressed to requiring chronic oxygen or other ventilator support, and 65% of patients had abnormal overnight oximetry studies, which changed over time. Eighty‐four percent of patients carried the HLA‐DRB1*15 haplotype, significantly more than patients without LD. Patients with SJIA‐LD also showed markedly elevated serum interleukin‐18 (IL‐18), variable C‐X‐C motif chemokine ligand 9 (CXCL9), and significantly elevated matrix metalloproteinase 7. Treatment strategies showed variable use of anti–IL‐1/6 biologics and addition of other immunomodulatory treatments and lung‐directed therapies. We found a broad range of current clinical status independent of time from diagnosis or continued biologic treatment. Multidomain measures of change showed imaging features were the least likely to improve with time. Conclusion Patients with SJIA‐LD had highly varied courses, with lower mortality than previously reported but frequent hypoxia and requirement for respiratory support. Treatment strategies were highly varied, highlighting an urgent need for focused clinical trials.

Sweat out the fat with TSLP! Thymic stromal lymphopoietin (TSLP) is a cytokine that can promote immune responses that characterize allergic diseases. Choa et al . found that mice engineered to produce elevated TSLP displayed selective white adipose tissue loss that protected them from obesity, insulin resistance, and steatohepatitis (see the Perspective by Schneider). Protection was not mediated by eosinophils, regulatory T cells, or innate lymphoid cells. Rather, TLSP induced the migration of conventional T cells to sebaceous glands in the skin. Once there, these T cells promoted white adipose tissue loss by the hypersecretion of sebum, a lipid-rich substance that augments the skin’s barrier function. This mechanism, which likely evolved to enhance cutaneous antimicrobial defenses, could be possibly targeted in future treatments for obesity. —STS