Chilblain lupus is considered a dermatological subtype of systemic lupus erythematosus (SLE), and is typically characterized by tender, bluish red swellings and nodules on the hands, feet, ears, and nose, with histological changes of lupus [Crowson and Magro, 1997]. The phenotype is induced by cold so that patients frequently report a worsening of lesions in the winter months. A cold dependency likely explains the peripheral distribution of the cutaneous lesions seen.

Chilblain lupus usually occurs sporadically in middle-aged women, and the pathology of the disorder remains poorly understood. However, a familial form of the disease, inherited as an autosomal dominant trait, has been described in two families segregating distinct mutations in TREX1 [Lee-Kirsch et al., 2007a; Rice et al., 2007a]. TREX1 mutations also cause some cases of the genetic encephalopathy Aicardi–Goutieres syndrome (AGS)[Crow et al., 2006]. Interestingly, approximately 40% of patients with AGS experience chilblains, so that familial chilblain lupus (FCL) might usefully be considered as a forme fruste of AGS [Rice et al., 2007b]. Of further note, heterozygous mutations in TREX1 represent the single most common cause of SLE identified to date [Lee-Kirsch et al., 2007b]. In 2009, we reported biallelic SAMHD1 mutations in patients with AGS [Rice et al., 2009]. More recently, we have described mutations in SAMHD1 to cause a relatively nonspecific inflammatory phenotype including a progressive arthropathy with distal joint contractures, painful mouth ulcers, and chilblains [Dale et al., 2010]. Here, we present a mother and son with typical features of FCL, segregating a heterozygous mutation in SAMHD1. The proposita is a 46-year-old white woman who was initially seen at the age of 13 years because of chilblains. Since the age of 4 years she experienced recurrent lesions, particularly prominent over the winter months, affecting her hands, feet, buttocks, and thighs (Fig. 1). Additionally, she complained of sensitivity to the