Assessment of Clinical Response to Janus Kinase Inhibition in Patients With Familial Chilblain Lupus and TREX1 Mutation.

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.