Familial chilblain lupus (FCL) is an autosomal dominant form of cutaneous lupus erythematosus caused by mutations in the 3 prime repair exonuclease 1 (TREX1 [OMIM 606609]). Familial chilblain lupus presents in early childhood with cold-induced bluish-red infiltrates on acral locations that tend to ulcerate and may be associated with signs of systemic lupus erythematosus.^1-4TREX1 is a cytosolic DNase anchored in the outer nuclear membrane that safeguards the cell against innate immune activation by degrading short DNA metabolites derived from the nucleus that leak into the cytosol.¹ In TREX1-deficient cells, self-DNA accumulates in the cytosol and stimulates the cyclic guanosine monophosphate (cGAS)–adenosine monophosphate synthase–stimulator of interferon (STING) pathway, leading to induction of type I interferons (IFNs).^1,2,5 Inappropriate activation of chronic type I IFN can break immune tolerance and promote autoimmunity. In keeping with this finding, patients with FCL exhibit constitutive upregulation of IFN-stimulated genes and proteins in blood and skin.⁴

Chilblain lupus erythematosus is a rare form of cutaneous lupus erythematosus characterized by bluish red infiltrates in acral locations of the body mostly affecting middle-aged women. We recently described a familial form of chilblain lupus manifesting in early childhood caused by a heterozygous mutation in the TREX1 gene, which encodes a 3′-5′ DNA exonuclease. Thus, familial chilblain lupus represents the first monogenic form of cutaneous lupus erythematosus. Here we describe the unusual clinical course of this newly defined genodermatosis in an 18-year-old female member of the family in which familial chilblain lupus was originally described.

Summary: Eosinophils contribute to the pathogenesis of bullous pemphigoid (BP) by secretion of proinflammatory cytokines and proteases. Trafficking of eosinophils into tissue in animal models and asthma depends on interleukin-5 and a family of chemokines named eotaxins, comprising CCL11, CCL24 and CCL26. Up-regulation of CCL11 has been described in BP, but the expression of the other two members of the eotaxin-family, CCL24 and CCL26, has not been investigated. In addition to these chemokines, expression of adhesion molecules associated with eosinophil migration to the skin should be analysed. We demonstrate that similar to CCL11, the concentration of CCL26 was up-regulated in serum and blister fluid of BP patients. In contrast, the concentration of CCL24 was not elevated in sera and blister fluid of the same BP patients. In lesional skin, CCL11 and CCL26 were detected in epidermis and dermis by immunohistochemistry. In contrast to CCL11, CCL26 was expressed strongly by endothelial cells. In line with these findings, eosinophils represented the dominating cell population in BP lesional skin outnumbering other leucocytes. The percentage of eosinophils expressing very late antigen (VLA): VLA-4 (CD49d) and CD11c correlated with their quantity in tissue. Macrophage antigen (MAC)-1 (CD11b/CD18) was expressed constitutively by tissue eosinophils. In conclusion, these data link the up-regulation of the eosinophil chemotactic factor CCL26 in BP to the lesional accumulation of activated eosinophils in the skin. Thereby they broaden the understanding of BP pathogenesis and might indicate new options for therapeutic intervention.