Baricitinib Ameliorates Cutaneous Leukocytoclastic Angiitis in Rats

Cutaneous leukocytoclastic angiitis (CLA) is a skin-limited, small-vessel vasculitis characterized by neutrophil infiltration with leukocytoclastosis. Inflammatory cytokines released from activated neutrophils play crucial roles in the pathogenesis. Glucocorticoids and immunosuppressive drugs are used for treatment. However, susceptibility to infections occurs due to the long-term administration of these drugs. Therefore, the development of new drugs is desired. A recent study suggested that Janus kinase (JAK)1 and JAK2 are involved in CLA pathogenesis. This pilot study aimed to demonstrate the efficacy of baricitinib that can inhibit both JAK1 and JAK2 on CLA using an animal model. CLA was induced in Wistar Kyoto rats (n = 7) on Day 0, and these rats were divided randomly into two groups: baricitinib group (n = 4) and vehicle group (n = 3). The baricitinib group received baricitinib (10 mg/kg) once daily orally from Days 0 to 6. Skin tissues (four sites/rat) were harvested on Day 7, and histopathological examinations were conducted. The phosphorylation of JAK1 and JAK2 in the inflammatory cells and the amount of IL-6 secreted in the skin lesion was suppressed by baricitinib. Correspondingly, baricitinib decreased histological scores of CLA represented by a sum of the inflammatory cell infiltration score (0-3) and the leukocytoclastosis score (0, 1) (Vehicle: 2.1 ± 0.4; Baricitinib: 1.5 ± 0.3; p < 0.05). Interestingly, baricitinib suppressed leukocytoclastosis particularly, suggesting that JAK1 or JAK2 might be implicated in the mechanism underlying leukocytoclastosis. This study could serve as a motivation to advance baricitinib to the next stage to examine its efficacy on CLA using a larger number of rats.