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Inflammatory stimuli activate Th2 cells (though these antigens are not well characterized) which make IL4/5/13 to activate mast cells, IgE & B cells, Basophils, ILC2s Kim et al STM 2013 Kim et al J Immunol 2014 https://stm.sciencemag.org/content/5/170/170ra16.short?casa_token=rwrE2EX0LcwAAAAA:NLP28WUUyOqDv5Uwjs8weZ2VUPeaJKD2pkYpDtgPw337XhU7SYEgYG7dDb4r3cAU0iWZ4o0jq9RNHQ
How does the skin sense itch? The somatosensory neurons in the skin are complex & interact w the immune system https://www.sciencedirect.com/science/article/pii/S1074761320301667
15% of sensory neurons respond to #histamine & #capsaicin to meditate #itch
But anti-histamines have been unsuccessful in several puritic conditions.
5% of sensory neurons can also react to itch stimuli via IL31 & IL4 https://www.sciencedirect.com/science/article/pii/S0092867417309315
But anti-histamines have been unsuccessful in several puritic conditions.
5% of sensory neurons can also react to itch stimuli via IL31 & IL4 https://www.sciencedirect.com/science/article/pii/S0092867417309315
Targeting IL31 has efficacy in #atopicdermatitis https://www.nejm.org/doi/full/10.1056/NEJMoa1606490
Knocking IL4Ra out of neurons prevents itch in mice, and dupilumab (anti-IL4Ra) works to treat patients w AD!
https://www.sciencedirect.com/science/article/pii/S0092867417309315 https://www.nejm.org/doi/full/10.1056/NEJMoa1610020
https://www.sciencedirect.com/science/article/pii/S0092867417309315 https://www.nejm.org/doi/full/10.1056/NEJMoa1610020
JAKi to block downstream cytokine signaling also works! https://jamanetwork.com/journals/jamadermatology/article-abstract/2751371?casa_token=Q0Ufj8qLWO0AAAAA:boO9LL3DJX79_VKQkqFjx7CHW6oYJMEuQV21otG_FiijP6TLZSEBwXFFUmm_3CuuAZ8d70T5Pw
Daily #itch scores (NRS) in patients seem to average out, w some exhibiting wide variations in scores. So, acute itch in #AD may use different pathways, and different patients have different flare patterns (Fang Wang in @itchdoctor lab)
20% of patients have this acute itch flare pattern, and many had serum allergen-specific #IgE (moreso than patients without acute itch). MC903 sensitization in mice induces acute itch partially dependent on IgE. Re-exposure to antigen induces itch bouts 
@itchdoctor
@itchdoctor
In human blood, circulating #basophils are primed in #AD & have higher expression of IgE receptor than healthy controls.
Knocking in the receptor for CNO into basophils in plus administration of CNO mediates acute itch!
Knocking in the receptor for CNO into basophils in
plus administration of CNO mediates acute itch!
Genetic basophil deletion prevents acute itch in mice. Leukotriene C4 produced by basophils helps to meditate this, as it is capable of activating TRPV1 & TRPA1 neurons!
Chronic itch appears to be more dependent on lymphocytes, whereas acute itch appears more dependent on basophils. @itchdoctor hypothesizes "barrier inflammation may override typical immune pathways" as mast cells appear not as central in #AD pathogenesis
