Genes affected:
(1) TREX1 (exonuclease) at 3p21.31
(2) SAMHD1 (exonuclease), at 20pter-q12
(3) STING (signaling molecule in the cytosolic DNA sensing pathway)
Clinical features:
(1) family members are affected (autosomal dominant with TREX1)
(2) exposure to cold temperatures or cold water results in painful bluish-red papules, nodules and/or plaques on exposed skin
(3) arthralgias affecting major joints
(4) no evidence of damage to internal organs
(5) negative for photosensitivity
(6) negative for antibodies to Ro/SSA and/or La/SSB
(7) negative for cold agglutinins
A biopsy of a skin lesion resembles cutaneous lupus erythematosus. Direct immunofluorescence shows granular depositis of IgM, IgA and C3.
Therapy with a JAK1/2 inhibitor can result in significant improvement.
