No abstract

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 coldinduced 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. 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 nextgeneration 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.

Ruxolitinib is a Janus kinase (JAK)1 and JAK2 inhibitor approved for the treatment of myelofibrosis and for polycythemia patients who are resistant or intolerant to hydroxyurea. We report a 72 year-old man patient with polycythemia vera who developed multiple cutaneous squamous cell carcinomas (cSCCs) with keratoacanthoma-like histological features while on treatment with ruxolitinib. Similar lesions have been reported in an isolated patient who also received ruxolitinib. Our case confirms that ruxolitinib may induce eruptive cSCCs with characteristic clinical and histological features that differentiate them from conventional non-drug induced lesions. Moreover, we performed a mutational panel analysis of the tumors. The lack of specific mutations in these tumors suggests an impairment of immunosurveillance in the origin of the cutaneous lesions. Frequent and thorough dermatological examinations in patients receiving ruxolitinib with a history of photodamage, skin cancer and/or previous hydroxyurea intake is thus recommended. (Ann Dermatol 31(2) 204∼208, 2019

No abstract