Hyperactivation of the JAK2/STAT5 Signaling Pathway and Evaluation of Baricitinib Treatment Among Patients With Eosinophilic Cellulitis.

Importance: The pathogenesis of eosinophilic cellulitis (EC) is poorly understood, limiting available treatment options. The current treatment paradigm focuses on delayed type 2 hypersensitivity reaction to various triggers. Objective: To gain further insight into the nature of EC inflammation and into the cellular signal transduction pathways that are activated in the context of EC. Design, Setting, and Participants: This case series was conducted in Lyon, France, from January 2018 to December 2021. Analysis of archival skin biopsy samples from patients with EC and from healthy control participants was performed using histology, Janus kinase (JAK)-signal transducer and activator of transcription (STAT) immunohistochemistry, and gene profiling. Data analysis was conducted between January 2020 and January 2022. Main Outcomes and Measures: Pruritus (visual analog score), percentage of body surface area with lesional skin, and RNA transcripts of inflammatory biomarkers from the skin (threshold cycle) were assessed in 1 index patient with refractory EC who received oral JAK1/JAK2 inhibitor baricitinib (4 mg/d). Results: This study included samples from 14 patients with EC (7 men and 7 women) and 8 healthy control participants (4 men and 4 women). The mean (SD) age of patients was 52 (20) years. Marked type 2 inflammation (chemokines CCL17, CCL18, and CCL26 and interleukin 13) with preferential activation of the JAK1/JAK2-STAT5 pathways in EC lesions was observed. In the 1 index patient with refractory EC, complete clinical remission of skin lesions was observed after 1 month of treatment with baricitinib. Conclusions and Relevance: These findings suggest that EC is a type 2 inflammatory disease with preferential activation of the JAK1/JAK2-STAT5 pathways. In addition, these results suggest the potential of treatment approaches targeting JAK1/JAK2 for patients with EC.

Contact dermatitis.

Contact dermatitis (CD) is among the most common inflammatory dermatological conditions and includes allergic CD, photoallergic CD, irritant CD, photoirritant CD (also called phototoxic CD) and protein CD. Occupational CD can be of any type and is the most prevalent occupational skin disease. Each CD type is characterized by different immunological mechanisms and/or requisite exposures. Clinical manifestations of CD vary widely and multiple subtypes may occur simultaneously. The diagnosis relies on clinical presentation, thorough exposure assessment and evaluation with techniques such as patch testing and skin-prick testing. Management is based on patient education, avoidance strategies of specific substances, and topical treatments; in severe or recalcitrant cases, which can negatively affect the quality of life of patients, systemic medications may be needed.