Pathophysiology, diagnosis, and management of chronic pruritus

"Itch" is an unpleasant sensation that elicits a desire to scratch. It is a common complaint among many patients and is associated with a markedly reduced quality of life. The pathogenesis of itch begins with various pruritogens stimulating free nerve endings in the skin, which causes an itch signal to travel through the spinothalamic tract to the brain where the sensation is processed. Scratching an itch initially activates the reward systems in the midbrain and striatum, and this positive reinforcement leads to the repetitive scratching behavior that damages the skin barrier. Mediators such as histamine, serotonin and cytokines are released from the damaged skin, which further aggravates the itch and initiates a vicious "itch-scratch cycle". Such processes may eventually lead to neural sensitization, where weaker stimuli can cause a more severe pruritic sensation. Chronic itch is one that lasts beyond 6 weeks. Pathologic pruritus can be classified into four different categories based on its cause: dermatologic, systemic, neuropathic, and psychogenic itch. Regardless of the cause, antihistamines are often prescribed as a first-line treatment of chronic itch, but more often than not they prove to be ineffective in bringing symptom relief. Both topical and systemic therapies are used to treat itch, and adequate treatment selection is considered according to symptom severity and chronicity. As the pathogenesis of itch becomes elucidated, more exciting new therapeutic options targeting pruritogenic mediators are becoming increasingly available. This review provides an overview of the pathophysiology, causes and the treatment of chronic itch.