PA24 Abnormal interferon signature in a patient with chilblain lupus

Abstract

Abstract A 5-year-old girl of Sri Lankan ancestry with no history of parental relatedness presented with the clinical features of chilblain lupus. This was particularly florid over her dorsal fingers, toes and the soles of her feet with areas in keeping with panniculitis on her calves and an epidermal naevus on the right side of her trunk. There was no ulceration or necrosis. Her parent reported occasional fevers and palpable lymph nodes in her neck. She also has bilateral astigmatism and mild valvular and supravalvular pulmonary stenosis. Blood tests showed a persisting mild transaminitis, an antinuclear antibody of 1 in 160 and a negative double-stranded DNA. She had a skin biopsy that showed supporting features for chilblain lupus. A lymph node biopsy showed nonspecific changes. The clinical suspicion was of a mild form of Aicardi–Goutières syndrome (AGS), and a genetic panel was performed that included TREX1, RNASEH2B, TMEM173 and SAMHD1 (all negative). The common mechanism behind these conditions is a type I interferonopathy. We sent blood on a research basis for RNA extraction and testing of her interferon (IFN) gene signature (IGS), which came back as abnormal (11.895; cutoff score of 2.758); she had normal expression of neutrophil-associated genes. This IFN score is on par with patients who have confirmed AGS or STING-associated vasculopathy with onset in infancy. An IGS is derived from the expression of IFN-regulated genes. A raised IGS has not only been reported to be useful as a biomarker in many rheumatic diseases, but is also used to help identify type I interferonopathies where genetic testing has not identified any clear pathogenic mutations (Crow YJ, Stetson DB. The type I interferonopathies: 10 years on. Nat Rev Immunol 2022; 22:471–83). National Institute for Health and Care Excellence guidelines allow for treatment of interferonopathies with baricitinib in patients with two documented high IFN gene signatures, which is our current plan for this patient.