TABLE 2.

Overview of the potential pathogenesis of itch in selected pruritic diseases and pathological conditions.

Disease	Factors potentially involved in the pathogenesis of pruritus
Irritant contact dermatitis (ICD)	Keratinocyte injury and barrier damage → inflammatory response, Th1 cytokines
Allergic contact dermatitis (ACD)	Allergen specific, T cell mediated inflammatory responses, typically Th2 type → 5-HT↑, ET-1↑, TSLP↑, CXCL10↑, IL-33↑
Urticaria	IgE, degranulation of mast cells, dysregulation of basophils and eosinophils → histamine↑, other pruritic mediators
Atopic dermatitis (AD)	Barrier disturbances, vicious itch-scratch cycle → irritant and allergen permeation↑
	Type 2 inflammation: IL-4↑, IL-13↑, IL-31↑, TSLP↑
	Dysregulation of cutaneous signaling pathways: opioid, cannabinoid, neuropepitide (SP→NKR1) signaling
	Innervation density↑
	Inflammatory lipid mediators↑
	Periostin synthesis↑ (linked to type 2 inflammation)
Psoriasis	Th17↑ → IL-17↑, IL22↑
	IL31↑, TSLP↑, SP↑, NPY↓
	NGF↑ → innervation density↑
Prurigo nodularis	Innervation density↑ → SP↑, CGRP↑
	Eosinophils↑, mast cells↑, T cells↑ → IL4↑, VIP↑, histamine↑ prostaglandins↑
Cutaneous T-cell lymphoma	IL-31↑, IL-31RA↑, OSMRβ↑
	IL-4?, IL-13?, SP?
Dermatomyositis	CD4+ cells↑ → IL-31↑, IL-31RA↑
Systemic sclerosis	Neuropathic component: Destruction of sensory fibers by accumulating collagen, and later regeneration by the inflammatory milieu
	Mast cells↑, histamine↑
Chronic renal failure	Eosinophils↑, mast cells↑, histamine↑, tryptase↑, inflammation↑
	Peripheral neuropathy
	Imbalance of μ- and κ -opioid receptor activity
Cholestatic liver diseases	Endogenous opioids↑, histamine↑, serotonin↑, lysophosphatidic acid↑ (→TRPV1), bilirubin↑, bile acids↑
	Lysophosphatidylcholine → TRPV4 (epidermis) → miR-146a↑ → neural TRPV1 activation↑
	Bile acids↑ → TGR5 → TRPA1 (mouse)
	Bile acids↑ → MRGPRX4 (human)
	BAM8-22↑ → MRGPRX1/MRGPRC11↑ → TRPA1