Abstract Introduction Childhood interstitial lung disease (chILD) comprises a group of rare, chronic respiratory disorders that can be caused by systemic autoimmune genetic diseases. Interferonopathies represent an emerging class of genetic autoinflammatory diseases that can mimic more common conditions and require a high degree of clinical suspicion to diagnose. We present a 7-year-old female with rapidly progressive lung disease who was initially diagnosed with systemic lupus erythematosus (SLE) and was later diagnosed with USP18-related type 1 interferonopathy, a severe and potentially lethal disease. Case Report A 7-year-old female with history of KCNJ16-related channelopathy, hypothyroidism, a homozygous USP18 variant of unknown significance, SLE with class III lupus nephritis (on mycophenolate mofetil), non-alcoholic fatty liver disease, intracranial calcifications, and recurrent pneumonia presented to pulmonology clinic 2 months after completing treatment for community-acquired pneumonia. She had also completed 6 months of prednisone for SLE. Parents reported 2 months of chronic cough with associated epistaxis and fevers 2-3 times per week. Her exam demonstrated end-inspiratory crackles in the right upper lung field. A Computed Tomography (CT) chest demonstrated interstitial fibrosis and increased ground glass opacities in the lower lobes (Fig. 1a) which had not been seen on her CT scan 9 months prior. A flexible bronchoscopy, bronchoalveolar lavage (BAL), and transbronchial cryobiopsy were performed under general anesthesia. The Olympus BF-P190 flexible bronchoscope was used, and BAL was obtained from the right middle lobe (RML). The ERBE 1.1mm flexible cryoprobe was used with fluoroscopic guidance to obtain two transbronchial biopsies from the lateral segment of the RML. Histopathology demonstrated alveolar tissue with diffuse chronic interstitial inflammation, a single lymphoid aggregate, and peribronchiolar fibrosis (Fig. 1b), which are consistent with autoimmune-related ILD, likely secondary to her UPS18-related type 1 interferonopathy. A multidisciplinary discussion prompted reconsideration of her SLE diagnosis. Although her specific USP18 variant has not previously been described, other homozygous loss of function variants in USP18 are associated with type I interferonopathies. She was restarted on oral prednisone with symptomatic improvement while awaiting insurance approval for anifrolumab, an interferonopathy-directed treatment. One month after initiating anifrolumab, she has shown improvement in both clinical symptoms and pulmonary function tests. Discussion This case highlights the importance of considering genetic etiologies for chILD when standard autoimmune treatments are ineffective. Monogenic interferonopathies should be considered in children with severe, early-onset chILD, especially those with autoimmune features. Early genetic testing can lead to early diagnosis, targeted therapy, and improved outcomes with prevention of pulmonary fibrosis progression This abstract is funded by: None
Kenney et al. (Fri,) studied this question.