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

Abstract

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.

• Authors: Johanna Morot, Ester Del Duca, Marine Chastagner, Marie Fernandes, Yeriel Estrada, Marine-Alexia Lefevre, Jean Kanitakis, Olivier Harou, Denis Jullien, Jean-Francois Nicolas, James G Krueger, Marc Vocanson, Emma Guttman-Yassky, Axel P Villani
• Journal: JAMA dermatology (JAMA Dermatol) Vol. 159 Issue 8 Pg. 820-829 (08 01 2023) ISSN: 2168-6084 [Electronic] United States
• PMID: 37342057 (Publication Type: Journal Article)

Chemical References

• baricitinib
• JAK2 protein, human
• Janus Kinase 1
• Janus Kinase 2
• STAT5 Transcription Factor

Topics

• Female
• Humans
• Middle Aged
• Inflammation
• Janus Kinase 1 (metabolism)
• Janus Kinase 2 (genetics, metabolism)
• Signal Transduction
• STAT5 Transcription Factor (metabolism)
• Male
• Adult
• Aged