Pruritus
DEFINITION AND ETIOLOGY
Pruritus or itch is defined as an unpleasant sensation of the skin that provokes the urge to scratch. It is a characteristic feature of many skin diseases and an unusual sign of some systemic diseases.1,2 Pruritus may be localized or generalized and can occur as an acute or chronic condition. Itching lasting more than 6 weeks is termed chronic pruritus.2 Itching can be intractable and incapacitating, as well as a diagnostic and therapeutic challenge.
PATHOPHYSIOLOGY
Peripheral Mechanisms
Physical Stimuli and Neural Pathways
Itch can be produced by mechanical (gentle touch, pressure, vibration, and wool), thermal and electrical stimuli such as transcutaneous or direct nerve stimulation. The sensation is received by free nerve endings in the skin and transmitted via unmyelinated C fibers and myelinated Aδ fibers to the central spinothalamic tracts.1,2 Microneurography studies have demonstrated that itch and pain are transmitted by separate neural pathways.3,4
Chemical Mediators
Histamine is one of the most important mediators of itch, although other chemical substances have also been implicated.3 Some, such as neuropeptides, act by releasing histamine from mast cells, and itching caused by them responds to antihistamines. Others act independently; therefore antihistamines are not effective in some forms of pruritus. Opioids have a central pruritic action and also act peripherally by augmenting histamine itch.
Central Mechanism
Patients with tumors and lesions of the central nervous system have been reported to have intractable pruritus.1,5–7 Administration of opioids in epidural anesthesia can also lead to pruritus.
Etiology
Itching is associated with dermatologic and systemic causes, and it is important to determine whether there is an associated skin eruption. A characteristic rash usually establishes the diagnosis of a primary dermatologic disorder. Several skin diseases are associated with pruritus; some are listed in Box 1. Itching is an important component of some disorders (atopic eczema, dermatitis herpetiformis, lichen simplex chronicus, and nodular prurigo) and these conditions are rarely diagnosed in its absence. In conditions such as mild urticaria or aquagenic pruritus, the levels of histamine are sufficient for a sensory but not a vascular response, and there may be no skin findings. Bullous pemphigoid can manifest with a prebullous pruritic phase for several months before the characteristic blisters appear.8 An invisible form of mycosis fungoides can occur as pruritus without a rash and is diagnosed on biopsy.9
Box 1 Select Dermatologic Disorders Associated with Chronic Pruritus*
Adapted from Pujol RM, Gallardo F, Llistosella E, et al: Invisible mycosis fungoides: A diagnostic challenge. J Am Acad Dermatol 2002;47:S167-S171; and Ständer S, Weisshaar E, Mettang T, et al: Clinical Classification of itch: A position paper of the International Forum for the Study of Itch. Acta Derm Venereol 2007:87 291-294.
Select systemic conditions associated with itching are listed in Box 2. Several are potentially serious, and it can be dangerous to label a case of generalized pruritus “nonspecific eczema” until these conditions are excluded. Pruritus of systemic disease is usually generalized, it may be the only manifesting symptom, and a specific rash is not present. Neurologic and psychiatric conditions associated with chronic pruritus are included in Box 2.
Box 2 Select Systemic Causes of Chronic Pruritus
Adapted from Pujol RM, Gallardo F, Llistosella E, et al: Invisible mycosis fungoides: A diagnostic challenge. J Am Acad Dermatol 2002;47:S167-S171; and Ständer S, Weisshaar E, Mettang T, et al: Clinical Classification of itch: A position paper of the International Forum for the Study of Itch. Acta Derm Venereol 2007:87 291-294.
