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*
Autoimmune
Dermatitis herpetiformis
Dermatomyositis
Pemphigoid
Sjögren's syndrome
Genetic
Darier's disease
Hailey-Hailey disease
Ichthyoses
Sjögren-Larsson syndrome
Infections and Infestations
Arthropod reactions
Dermatophytosis
Folliculitis
Impetigo and other bacterial infections
Insect bites
Pediculosis
Scabies
Viral
Inflammatory
Asteatosis (dry skin), including aging and senile pruritus
Atopic eczema
Contact dermatitis (irritant, allergic)
Drug reactions
“Invisible dermatoses”
Lichen planus
Lichen simplex chronicus
Mastocytosis (urticaria pigmentosa)
Miliaria
Psoriasis
Scars
Urticaria
Neoplastic
Cutaneous T-cell lymphoma or mycosis fungoides (especially Sézary syndrome)
Cutaneous B-cell lymphoma
Leukemia cutis
Pregnancy
Pemphigoid gestationis
Polymorphic eruption of pregnancy
Prurigo gestationis
*Generalized or localized depending on extent of disease
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.
It is important to establish if pruritus preceded the appearance of a skin eruption. Severe itching leads to scratching that causes secondary skin changes of excoriation, lichenification, dryness, eczematization, and infection. Excessive bathing and contact allergy to topical therapies can lead to dermatitis. These findings should not be interpreted as the primary skin disorder.
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
Endocrine and Metabolic Diseases
Chronic renal failure
Diabetes mellitus (questionable; may be localized to scalp)
Hyperthyroidism
Hypothyroidism
Liver disease (with or without cholestasis)
Malabsorption
Perimenopausal pruritus
Infectious Diseases
Helminthosis
HIV infection
Parasitosis
Neoplastic and hematological
Hodgkin's disease
Iron deficiency
Leukemia
Non-Hodgkin's lymphoma
Multiple myeloma
Plasmacytoma
Polycythemia rubra vera
Visceral Neoplasms
Carcinoid syndrome
Solid tumors of the cervix, prostate, or colon
Pregnancy
Pruritus gravidarum (with or without cholestasis)
Drugs
Allopurinol
Amiodarone
Angiotensin-converting enzyme inhibitors
Estrogen
Hydrochlorothiazide
Hydroxyethyl cellulose
Opioids
Simvastatin
Other
Neurologic disease
Abscess
Infarcts
Multiple sclerosis
Notalgia Paresthetica
Tumors
Psychiatric disease
Anxiety disorders
Depression
Obsessive-compulsive disorder
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.