P127 Lung disease in systemic JIA: an emerging problem linked with young age and anti-IL-1/IL-6
Authors: G Chen, V Saper, G Deutsch, RP Guillerman, K Jagadeesh, G Schulert, S Canna, Y Lu, J Birgmeier, A Leung, A Grom, G Bejerano, M Davis, P Khatri, E Mellins
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Post-doctoral fellow. <h3>Introduction</h3> The advent of anti-IL-1/IL-6 therapies transformed the management of systemic juvenile idiopathic arthritis (sJIA), a debilitating childhood inflammatory condition. However, concurrent with practice change, pediatric rheumatologists noted an increase in sporadic cases of types of lung disease in sJIA, that were rarely seen in previous decades. <h3>Objectives</h3> The study aims to provide an up-to-date characterization of lung disease and identify novel risk factors. <h3>Methods</h3> We organized a multi-center retrospective study and obtained information on 61 cases of lung disease in children with sJIA or sJIA-like disease. <h3>Results</h3> Clinical data from our cohort showed that lung disease in the setting of sJIA is associated with distinctive features, including acute clubbing (in 61%), atypical rash (in 56%) and an unusually high frequency of serious adverse reactions to tocilizumab (40%, OR=79 compared to the control). This lung disease has unique radiological findings and lung pathology similar to pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP, 64%) often with associated pulmonary vascular changes. Whole-exome sequencing on 18 patients ruled out a novel monogenic disorder or known causes of congenital PAP. Thus, the etiology of the disease is not clear, while its mortality is high (5 years survival: 42%, 25%–68%). When compared to a control cohort of children entered as sJIA in a patient registry, the lung disease cohort has similar overall anti-IL-1/IL-6 exposure level. However, in the anti-IL-1/IL-6 exposed subset, but not in the non-exposed, young sJIA onset age potently increased the risk of lung disease (age &lt;5 years, OR=7.3). The high-risk patients (early sJIA onset and exposed to anti-IL-1/IL-6) were highly enriched for PAP/ELP pathology (89%, 17/19 vs. low-risk: 35%, 6/17). In addition, children with Trisomy 21 (T21) and sJIA have dramatically elevated risk for lung disease (OR=50). Marked serum ferritin elevation and/or profound lymphopenia occur several months prior to lung disease detection and may be early indicators of lung disease. <h3>Conclusions</h3> Lung disease associated with anti-IL-1/anti-IL-6 therapies often presents as an alveolar and pulmonary vascular complication with high mortality in children with sJIA/sJIA-like disease. Risk is significantly increased in children with young age at sJIA onset or concurrent T21. In sJIA patients (including those with initial treatment response), emergence of atypical clinical features, rising ferritin and dropping absolute lymphocyte count should raise suspicion of this complication. <h3>Disclosure of Interest</h3> G. Chen: None declared, V. Saper: None declared, G. Deutsch: None declared, R. P. Guillerman: None declared, K. Jagadeesh: None declared, G. Schulert: None declared, S. Canna: None declared, Y. Lu: None declared, J. Birgmeier: None declared, A. Leung: None declared, A. Grom: None declared, G. Bejerano : None declared, M. Davis: None declared, P. Khatri: None declared, E. Mellins Grant/research support from: Novartis, GlaxoSmithKline, Codexis, Inc.