Importance: Familial chilblain lupus is a monogenic autosomal dominant form of cutaneous lupus erythematosus that in most cases is caused by mutations in the 3 prime repair exonuclease 1 (TREX1). Familial chilblain lupus presents in early childhood with cold-induced painful erythematous infiltrates leading to mutilation and is associated with systemic involvement illustrated by an elevated type I interferon (IFN) signature in the skin and blood. Effective treatment is currently not available. Objectives: To evaluate the clinical response to the Janus kinase inhibitor baricitinib in familial chilblain lupus and assess the effect of cold on patient fibroblasts. Design, Setting, and Participants: In this case series, 3 patients with familial chilblain lupus due to TREX1 mutation underwent treatment with baricitinib for 3 months. Interventions: Doses of baricitinib, 4 mg, were administered daily for 3 months. Main Outcomes and Measures: Reduction of cutaneous lupus lesions was measured by the revised cutaneous lupus area and severity index, pain due to skin and joint involvement was assessed by visual analog scale, type I IFN signature in blood was determined by polymerase chain reaction, and the in vitro response of fibroblasts to cold exposure was analyzed. Results: All 3 patients (2 women and 1 man; mean [SD] age, 51 [24] years) showed a significant improvement of cutaneous lupus lesions with suppression of systemic type I IFN activation. One patient had a complete remission regarding pain and, in 2 patients, pain associated with joint inflammation was partially reduced. No severe adverse reactions were reported. Exposure of patient fibroblasts to cold induced a stress response and enhanced senescence along with induction of IFN-stimulated gene in vitro. Conclusions and Relevance: These findings demonstrate the therapeutic efficacy of Janus kinase inhibition in a monogenic form of lupus among 3 patients and provide mechanistic insight into the process of disease exacerbation by cold in TREX1-deficient cells. This finding may be relevant to other type I IFN-mediated disorders and implicates Janus kinase inhibition as a potential therapeutic option also for multifactorial cutaneous lupus erythematosus.
Importance: Familial chilblain lupus is a monogenic autosomal dominant form of cutaneous lupus erythematosus that in most cases is caused by mutations in the 3 prime repair exonuclease 1 (TREX1). Familial chilblain lupus presents in early childhood with cold-induced painful erythematous infiltrates leading to mutilation and is associated with systemic involvement illustrated by an elevated type I interferon (IFN) signature in the skin and blood. Effective treatment is currently not available. Objectives: To evaluate the clinical response to the Janus kinase inhibitor baricitinib in familial chilblain lupus and assess the effect of cold on patient fibroblasts. Design, Setting, and Participants: In this case series, 3 patients with familial chilblain lupus due to TREX1 mutation underwent treatment with baricitinib for 3 months. Interventions: Doses of baricitinib, 4 mg, were administered daily for 3 months. Main Outcomes and Measures: Reduction of cutaneous lupus lesions was measured by the revised cutaneous lupus area and severity index, pain due to skin and joint involvement was assessed by visual analog scale, type I IFN signature in blood was determined by polymerase chain reaction, and the in vitro response of fibroblasts to cold exposure was analyzed. Results: All 3 patients (2 women and 1 man; mean [SD] age, 51 [24] years) showed a significant improvement of cutaneous lupus lesions with suppression of systemic type I IFN activation. One patient had a complete remission regarding pain and, in 2 patients, pain associated with joint inflammation was partially reduced. No severe adverse reactions were reported. Exposure of patient fibroblasts to cold induced a stress response and enhanced senescence along with induction of IFN-stimulated gene in vitro. Conclusions and Relevance: These findings demonstrate the therapeutic efficacy of Janus kinase inhibition in a monogenic form of lupus among 3 patients and provide mechanistic insight into the process of disease exacerbation by cold in TREX1-deficient cells. This finding may be relevant to other type I IFN-mediated disorders and implicates Janus kinase inhibition as a potential therapeutic option also for multifactorial cutaneous lupus erythematosus.
Authors: Kader Cetin Gedik; Lovro Lamot; Micol Romano; Erkan Demirkaya; David Piskin; Sofia Torreggiani; Laura A Adang; Thais Armangue; Kathe Barchus; Devon R Cordova; Yanick J Crow; Russell C Dale; Karen L Durrant; Despina Eleftheriou; Elisa M Fazzi; Marco Gattorno; Francesco Gavazzi; Eric P Hanson; Min Ae Lee-Kirsch; Gina A Montealegre Sanchez; Bénédicte Neven; Simona Orcesi; Seza Ozen; M Cecilia Poli; Elliot Schumacher; Davide Tonduti; Katsiaryna Uss; Daniel Aletaha; Brian M Feldman; Adeline Vanderver; Paul A Brogan; Raphaela Goldbach-Mansky Journal: Ann Rheum Dis Date: 2022-01-27 Impact factor: 27.973
Authors: Colton J Garelli; Maggi Ahmed Refat; Padma P Nanaware; Zaida G Ramirez-Ortiz; Mehdi Rashighi; Jillian M Richmond Journal: Front Immunol Date: 2020-07-02 Impact factor: 7.561