Dyshidrotic eczema associated with Upadacitinib use: a paradoxical adverse event or serendipity?

We report the case of a 39-year-old man with long-standing ileocolonic Crohn's disease, with a history of prior ileocecal resection and secondary loss of response to infliximab and ustekinumab, who initiated treatment with upadacitinib (UPA) 45 mg/day due to severe clinical, biochemical, and endoscopic recurrence. The patient achieved a rapid clinical response with normalization of inflammatory biomarkers. Two weeks after UPA initiation, he developed pruritic vesicular lesions on the palms and fingers, which were diagnosed as de novo dyshidrotic eczema by an expert dermatologist. The cutaneous manifestation was mild to moderate and resolved rapidly with topical corticosteroids, without the need to discontinue UPA. Crohn's disease remained in clinical and biochemical remission after 9 months of follow-up. Possible immunological mechanisms underlying this paradoxical reaction are discussed, including selective JAK1 inhibition-related immune imbalance, with disruption of the Th1/Th2 axis, altered IL-4 and IL-13 signaling, and a potential predominance of Th1/Th17 responses. Although UPA has been exceptionally used as a therapeutic option for refractory dyshidrotic eczema, and this condition has been reported as an infrequent adverse event in pivotal ulcerative colitis trials, this case likely represents the first report of upadacitinib-induced dyshidrotic eczema in Crohn's disease.