Itch is a poorly understood component of the nociceptive system that can be stimulated by systemic conditions as well as those of the skin. Like pain, itch is an unpleasant sensory experience that can impair quality of life. However, instead of eliciting the withdrawal reflex that pain does, itch elicits a scratch response. Two distinct responses to an itch stimulus have been described: a common localized itch that does not persist long after the stimulus is removed and a diffuse, poorly localized area around the stimulus site that responds to any subsequent stimulus, including light touch, with intense itching. Yosipovitch and colleagues reviewed the etiology, evaluation, and treatments for itch.

Itch is known to be transmitted by specific C neurons that have slow conduction velocities, lasting response to histamine, and extensive terminal branching. Nevertheless, no specific “itch center” appears to exist in the brain. Studies show that itch activates several areas of the forebrain, with significant overlap with the activation areas for pain. Pain is known to inhibit itch by central and peripheral mechanisms. Scratching and rubbing skin stimulates myelinated A neurons by mechanoreceptors that activate spinal suppression of itching. In addition to neuronal mechanisms, the proximity of mast cells to afferent C neuron terminals in the skin indicates a neurochemical mechanism for several aspects of itch. Stimulated mast cells could release tryptase, substance P, and other active compounds that could cause direct irritating effects or stimulate C neurons.

Four clinical forms of itch have been described; clinically significant itch may have elements of one or more types. Pruritoceptive itch results from skin inflammation, dryness, or damage; this is the familiar itch resulting from an insect bite or urticaria. Neuropathic itch occurs with any disease along the afferent neuronal pathway. Several neurologic diseases, such as postherpetic neuralgia, multiple sclerosis, and central nervous system neoplasms, can cause this form of itching. Neurogenic itch is a result of the central action of opioid neuropeptides and occurs in patients with cholestasis and renal failure. Psychogenic itch has no physiologic basis; it may be an independent behavior or associated with parasitophobia.

A detailed history and thorough physical examination may establish an underlying cause of itch. Two questionnaires assessing itch as a sensory disturbance and quantifying its effect on quality of life have been validated. Itch associated with renal failure or cholestasis is thought to be a result of a central action of opioid peptides. In these patients, itch can be debilitating, and treatment with opioid antagonists such as naloxone or naltrexone is recommended. For hepatic causes of itch, such as hepatitis C infection, cholestyramine also is useful. Itch can be an early primary symptom of human immunodeficiency virus (HIV) infection, or it may be secondary to HIV-associated skin conditions or systemic complications such as lymphoma or hepatic disease. When the CD4 count falls below 300 per mm³ (300 × 10⁶ per L), intensely pruritic eosinophilic folliculitis may occur. Central neuropathic itch that awakens the patient may be an early symptom of multiple sclerosis. Neuropathic itch also can occur with pain in herpes zoster. Central and peripheral mechanisms have been implicated in itching associated with atopic eczema. Treatment of dryness and infection may reduce itching, and sedating antihistamines are especially useful in preventing the characteristic nocturnal scratching. Severe itch may be reduced by modifying inflammation with topical steroids or by using phototherapy or photochemotherapy. Oral azathioprine, cyclosporine, and tacrolimus also have been used for treatment of severe atopic eczema.

While the treatment of itch should be directed at the underlying cause, the cause may not be apparent in pruritoceptive itch, and topical modalities may be effective. Capsaicin desensitizes nociceptive nerve endings; concentrations of 0.025 to 0.075 percent can be useful in the treatment of atopic eczema and other forms of itch. Local irritation can be reduced by use of topical anesthetic (EMLA). Topical doxepin can be an effective antipruritic agent, but even topical application can cause sedation. Topical aspirin also is a useful antipruritic agent, especially in patients with lichen simplex chronicus. Clinical trials of new antipruritic agents are in progress.