A rare but potentially deadly inflammatory lung disease is emerging among children with systemic juvenile idiopathic arthritis (sJIA), a case series from 37 institutions shows.
Paediatric rheumatologist Dr Vivian Saper from Stanford University, California, and colleagues noted that pleuritis and pleural effusion were the usual lung complications seen in sJIA, however, in the last decade, increasing numbers of cases of high fatality, novel parenchymal lung disease (LD) had been detected worldwide.
In a retrospective study of 61 cases the research team found that the majority of cases were characterised by unusual clinical and radiological features, in association with a variant of pulmonary alveolar proteinosis/endogenous lipoid pneumonia.
“Strikingly, 61% of patients developed acute clubbing, sometimes as the first indicator of LD…. in over half of these, digital erythema occurred,” they wrote in their paper published in the Annals of the Rheumatic Diseases.
Another finding that preceded lung disease detection was significant lymphopaenia (absolute lymphocyte count <60% of age-adjusted, lower limit of normal).
Survival was drastically lower in the LD cohort (mortality: 159/1000 person-years) than in a UK cohort of patients with sJIA who required biologic agents (mortality: 3.9/1000 person-years).
Children with trisomy 21 and sJIA or earlier onset sJIA onset (>5 years) were particularly vulnerable to LD.
The most prevalent finding on chest CT was peripheral septal thickening ± ground glass opacities. Crazy-paving, consolidation and hyperenhancing lymph nodes were also observed.
Tissue diagnosis showed primarily PAP/ELP-like pathology which, compared to that found in other settings, was distinctive for its patchiness and associated vascular changes.
Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features and anaphylaxis to tocilizumab occurred in 38% of those exposed, the research team noted.
“The association between cytokine inhibition and sJIA-LD and related mechanistic hypotheses demand further investigation,” wrote the authors while acknowledging the limitations of the study which they said meant causality could not be claimed.
“Likewise, it is premature to make treatment recommendations solely on the basis of our findings,” they added.
“However, in children with risk factors, close attention to subtle pulmonary symptoms is advised, and approaches for early detection of altered pulmonary function, guided by a pulmonary specialist, should be considered,” they advised.
“In light of high fatality, efforts to determine LD prevalence, uncover molecular mechanism(s), and devise treatment and prevention approaches are urgently needed,” they added.