Chronic itch, defined as an itching sensation that persists for more than 6 weeks, is a common complaint that is associated with a high burden of disease. Chronic itch can occur due to a variety of skin diseases, but can also feature as prominent symptom in various internal, neurologic, and psychiatric disorders. Importantly, chronic itch can be drug-related. Determining the underlying cause can be challenging, yet it is an essential step in the management of chronic itch. When generalized chronic itch presents with no primary skin lesions and/or secondary skin lesions, the diagnostic work-up should consist of a detailed history and physical examination with an initial limited screening of laboratory tests. Subsequent additional screening should be dictated by clinical suspicion. In 8% of patients, no underlying cause can be identified: pruritus of unknown origin. The management of chronic itch of unknown origin preferably follows a multimodal approach.
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