Familial Chilblain Lupus L93.2

Very rare, autosomal dominantly inherited, monogenic form of cutaneous lupus erythematosus. Familial chilblain's lupus belongs to the group of type 1 interferonopathies and is characterized mainly by typical skin manifestations and ischemia of the acras.

Various mutations that can lead to this disease have been detected. Most frequently, mutations in the TREX1 gene can be detected. Less common are mutations in the SAMHD1 and STING1 (Stimulator of Interferon Genes) genes.

These gene defects have in common that they are all involved in the process of recognition of intracellular free DNA, which subsequently leads to increased production of type 1 interferons and the induced gene products. This then leads to autoinflammation and autoimmunity characteristic of the disease.

As early as infancy or childhood, cold-related, painful, red-livid, cushion-like papules or plaques occur predominantly on the fingers, toes, nose, cheeks, and ears. In addition, there are recurrent lesional ulcerations. Raynaud's attacks are common.

Activation of interferon-induced genes is controlled by the JAK-STAT system; therefore, JAK inhibitors can be successfully used to treat type 1 interferonopathies (Fiehn C 2017; Zimmermann N et al. 2019).

Yi C et al (2020) performed a genetic study in a large, non-blood-related Chinese family with 13 members over 4 generations affected by Chilblain lupus. Whole-exome sequencing was performed in the index patient. Detection of significant variants was subsequently validated by resequencing using Sanger sequencing in the index patient and other family members. Detection was a novel pathogenic mutation in TREX1 p.Asp18His. The mutation was present only in the affected individuals. This mutation was previously detected in a patient with Aicardi-Goutière syndrome.

1. Fiehn C (2017) Familial chilblain lupus: type I interferonopathy with model character. Z Rheumatol 76: 322-327
2. Günther C et al (2015) Familial chilblain lupus due to a novel mutation in the exonuclease III domain of 3' repair exonuclease 1 (TREX1). JAMA Dermatol 151:426-431.
3. Yi C et al (2020) Familial chilblain lupus due to a novel mutation in TREX1 associated with Aicardi-Goutie'res syndrome. Pediatr Rheumatol Online J 18:32.
4. Zimmermann N et al (2019) Assessment of Clinical Response to Janus Kinase Inhibition in Patients With Familial Chilblain Lupus and TREX1 Mutation. JAMA Dermatol155: 342-346.