The reader will come to appreciate that: • JAK inhibitors show promising efficacy across type I and II interferon-driven chILDs. • Disease-specific pathophysiology assessment enables precision targeting of inflammatory pathways. • Multicentre studies are needed to strengthen evidence beyond anecdotal reports. Childhood interstitial lung diseases (chILDs) associated with inflammatory diseases represent a heterogeneous group of rare conditions . To date, therapeutic approaches predominantly rely on broad-spectrum immunosuppressive agents , often independently of the underlying mechanism. During the l ast ten years, next generation sequencing techniques allowed the identification of monogenic auto-inflammatory diseases with the subsequent development of mechanism-based targeted immunomodulatory therapies. Among these emerging therapies, anti-cytokine agents occupy an increasingly prominent role in inflammatory chILDs. Janus kinase (JAK) inhibitors have emerged as a promising strategy, with initial efficacy demonstrated in monogenic type I interferonopathies involving the lung, such as STING-associated vasculopathy with onset in infancy (SAVI) and COPA syndrome. Their therapeutic scope has subsequently expanded to include disorders driven by type II interferon signalling, notably systemic juvenile idiopathic arthritis–associated lung disease and refractory pulmonary granulomatosis. In juvenile dermatomyositis with anti-melanoma differentiation-associated gene 5 (MDA5) antibodies, JAK inhibitors address refractory rapidly progressive interstitial lung disease. Further anti-cytokine therapies include tocilizumab (anti-interleukin-6) for juvenile systemic sclerosis-associated interstitial lung disease, anti-interleukin-1β/18 combinations (MAS-825), and anti-tumour necrosis factor-alpha. Whilst evidence remains predominantly limited to case reports and small series, these mechanism-based approaches represent a paradigm shift towards personalised medicine in chILDs. Understanding disease-specific pathophysiology—from interferon activity assessment to genomic sequencing—is essential for optimal therapeutic targeting. Multicentre collaborations are needed to evaluate long-term efficacy and safety of these targeted interventions.
Gonsard et al. (Sun,) studied this question.