Th54 - Pre-existing Cardiothoracic Comorbidity and Lung Disease in Still's

Background:  Still's disease is a rare, chronic inflammatory illness of unknown etiology. Parenchymal lung disease (LD) is not expected. In 2021, we reported a striking HLA association with severe delayed drug reaction, implicating inhibitors of interleukin (IL)-1 or IL-6. This reaction can include parenchymal LD. Five-year survival probability with co-occurring Still’s and LD, regardless of drug exposure, is reported as 42%.¹ Here, we associate risk of LD to certain pre-existing comorbidities. 



Methods: A retrospective analysis of 117 multi-center, international cases of parenchymal LD in Still’s patients, included regardless of IL-1 or IL-6 inhibitor exposure, was performed. Control data was the published population frequency for each co-morbidity, as available.

Results:   In the past two years, the annual rate of parenchymal LD in Still’s has increased to >20 fold above the rate prior to the introduction of IL-1 and IL-6 inhibitors. Evaluation of the 17 Still’s LD cases with no exposure to IL-1 or IL-6 inhibition revealed pre-existing comorbidity in 47% (8/17), specifically lung disease, congenital cardiopulmonary anomaly or Trisomy 21 (T21). A similar analysis of 100 cases with drug reaction-associated diffuse LD revealed enrichment above published frequencies for bronchopulmonary dysplasia of prematurity (4/100 vs 1.39/10,000), complex congenital heart disease (9/100 vs 12.9/10,000), or T21 (10/100 vs 1-2/1000 live births), including two T21 without another co-morbidity.

Conclusions:  Pre-existing cardiothoracic co-morbidities are associated with life-threatening parenchymal lung disease in the setting of Still’s disease, with or without inhibitor exposure.  Mechanisms are unknown.

¹Saper et al ARD 2019