Eosinophilic cellulitis may benefit from treatment targeting Janus ... - Healio
June 30, 2023
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Disclosures: Morot reports no relevant financial disclosures. Please see the study for all other authors' relevant financial disclosures.
Key takeaways:
- Marked type 2 inflammation was present in eosinophilic cellulitis lesions.
- Preferential activation of the Janus kinase1/2-signal transducer and activator of transcription 5 pathways was also present.
Based on the pathogenesis of eosinophilic cellulitis, treatment targeting Janus kinase 1 and 2 should be developed to treat this disease, according to a study.
"Eosinophilic cellulitis (EC), also called Wells syndrome, is a rare eosinophilic dermatosis," Johanna Morot, MSc, of the Centre International de Recherche en Infectiologie, Université Claude Bernard in Lyon, France, and colleagues wrote. "Although clinical subtypes may exist within the EC spectrum, EC is typically characterized by fixed pruritic urticarial plaques, with blisters in the most severe cases."
The pathogenesis of EC remains poorly understood, which makes this condition difficult to treat. To gain further insight, Morot and colleagues conducted an analysis of skin biopsies from 14 patients with EC using histology, Janus kinase (JAK)-signal transducer and activator of transcription (STAT) immunohistochemistry and gene profiling.
The tests revealed that marked type 2 inflammation with preferential activation of the JAK1/JAK2-STAT5 pathways was present in EC lesions.
All the skin biopsies from patients with EC were positive for pSTAT5 expression (mean, 203 positive cells/mm²; P < .001), whereas the skin biopsies from the comparative eight healthy controls were not (mean, 1 positive cells/mm²; P < .001).
Compared with the gene profiling of healthy controls, the gene profiles of patients with EC showed upregulation of 64 messenger RNA transcripts. The top 20 overexpressed genes were comprised of markers that are linked with type 2 inflammation including chemokines CCL7, CCL17, CCL18 and CCL26, which are involved in the recruitment of type 2 helper T-cells (TH2). Interleukin-13 was also identified as a marker in these patients.
One of the patients had refractory EC; however, the patient achieved complete clinical remission and a normalization of the upregulated type 2 inflammation transcripts after 1 month of treatment with baricitinib, a JAK1/JAK2 inhibitor.
"The findings of this case series suggest that EC may be a TH2-related inflammatory disease with marked JAK2/pSTAT5 activation," Morot and colleagues concluded. "Together with the clinical response to baricitinib, our data advocate for the development of JAK1/JAK2 targeting treatment approaches in EC and other eosinophilic diseases."
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