Janus kinase (JAK) inhibitors represent a novel class of small molecule inhibitors that alters the JAK/signal transducer and activate the transcription (STAT) signaling pathway.

The US Food and Drug Administration has approved selected JAK inhibitors for managing atopic dermatitis (AD) and their successful use in the management of AD, providing optimism that these medications also may have potential application in allergic contact dermatitis (ACD). Recent literature indicates that the two conditions may be more robustly linked mechanistically than previously understood. Hence, AD and ACD often are managed with the same therapeutic agents. 

Although the exact etiology of ACD still remains unclear, activation of T cells and cytokines plays a crucial role. More than 40 cytokines are known to exert their effects via the JAK/STAT signaling pathway, including IL-2, IL-6, IL-17, IL-22 and IFN-γ.

Skin inflammation and chronic pruritus, which are significant components of ACD, may also be mediated by JAK signaling.

Early clinical studies and case reports have highlighted the effective use of JAK inhibitors in managing ACD in humans. A 37-year-old male with occupational airborne ACD to Compositae demonstrated full dermatitis clearance with daily oral abrocitinib after the failure of topical corticosteroids and dupilumab. Yet another patient, a 57-year-old woman, demonstrated near-complete resolution of chronic Parthenium-induced airborne ACD after starting twice-daily oral tofacitinib; however, she had previously experienced treatment failure with allergen avoidance and multiple drugs, including topical and oral corticosteroids, topical calcineurin inhibitors and azathioprine.

Furthermore, a phase 2 study on patients with irritant and nonirritant chronic hand eczema demonstrated that most patients achieved treatment success with topical delgocitinib vs. vehicle. Hence, these studies highlight the potential role of JAK inhibitors in managing refractory ACD. However, following the potential for treatment-related adverse effects, regular follow-up and laboratory monitoring in these patients are recommended.

Source: Johnson H, Guenther J, Adler BL, et al. Janus kinase inhibitors: a promising therapeutic option for allergic contact dermatitis. Cutis. 2023;111(2):92-95,105.