Gustavo Deza, Anna Mensa-Vilaró, Alvaro March-Rodriguez, Silvia Sánchez, Ramon M. Pujol, Juan I. Aróstegui, Ana M. Giménez-Arnau
DOI: 10.2340/00015555-3292

Acquired cold urticaria (ACU) is characterized by the development of itchy wheals after cold exposure. Generalized urticarial skin rashes triggered by cold exposure characterize certain monogenic autoinflammatory diseases (AIDs). The objective of this study is to investigate the presence of variants in genes causing AIDs that present with cold-induced urticarial skin rashes in patients clinically diagnosed with ACU, in order to look for susceptibility factors for the disease. Fifty patients with primary ACU were studied. Germline and post-zygotic variants on the NLRP3, NLRP12, NLRC4 and PLCG2 genes were investigated using next-generation sequencing technology. Seven patients (14%) carried 8 heterozygous germline variants in the following genes: NLRP3 (n = 1), NLRP12 (n = 3), NLRC4 (n = 1), PLCG2 (n = 3). No pathogenic or likely pathogenic variants were detected, and deep analyses of the sequences obtained did not identify any post-zygotic variant. In conclusion, ACU is not related to post-zygotic or germline pathogenic variants in the NLRP3, NLRP12, NLRC4 and PLCG2 genes.

Acquired cold urticaria represents a subtype of inducible urticaria characterized by the development of itchy wheals after cold exposure. Generalized cold-induced urticarial rashes are also seen in certain monogenic autoinflammatory diseases. In the present study, we demonstrated that acquired cold urticaria is not related to the presence of germline and post-zygotic pathogenic variants on genes causing autoinflammatory diseases that present with cold-induced urticarial skin rashes (i.e. NLRP3, NLRP12, NLRC4 and PLCG2 genes). However, the presence of cold urticaria in addition to systemic manifestations, family history and/or laboratory abnormalities should alert physicians to the potential diagnosis of a monogenic autoinflammatory disease.