Use of tofacitinib in recalcitrant cases of chronic pruritus of unknown origin

Excerpt

Chronic pruritus of unknown origin (CPUO) is a distressing disorder which is characterised by a lack of obvious skin changes with concomitant intense itching with a predominant finding of marked eosinophilia (> 4% or > 0.30 K/mm³) [1]. Varied agents have been tried including antihistamines, mirtazapine [noradrenergic and specific serotonergic antidepressant (NaSSA)] and gabapentinoids (gabapentin and pregabalin) with no consistently effective treatment regimen. Published data has revealed that T helper 2 (Th2) immune pathways and the associated cytokines (IL-4, IL-10, IL-13 and IL-33) mediate itching [1, 2]. This is consistent with the concept of “immunosenescence” with loss of Th1 cell-driven protective immunity and skewing towards an allergic Th2 response [3]. Also, IL-4Rα & Janus Kinase 1 (JAK1) mediate sensory neuron activation, causing chronic itching which was abrogated in an experimental study by the use of tofacitinib (pan-JAKi), baricitinib (JAK1/2i), and upadacitinib (JAK1i) [4, 5]. …