Itching is a symptom that can cause significant discomfort and is one of the most common reasons for consultation with a dermatologist. Itching leads to scratching, which can cause inflammation, skin degradation, and possible secondary infection. The skin can become lichenified, scaly, and excoriated.
(See also Evaluation of the Dermatologic Patient Evaluation of the Dermatologic Patient History and physical examination are adequate for diagnosing many skin lesions. Some require biopsy or other testing. Important information to obtain from history includes Personal or family... read more .)
Pathophysiology of Itching
Itch can be prompted by diverse stimuli, including light touch, vibration, and wool fibers. There are a number of chemical mediators as well as different mechanisms by which the sensation of itch occurs. Specific peripheral sensory neurons mediate the itch sensation. These neurons are distinct from those that respond to light touch or pain; they contain a receptor, MrgA3, the stimulation of which causes the sensation of itching.
Mediators
Histamine is the well-known mediator. It is synthesized and stored in mast cells in the skin and is released in response to various stimuli. Other mediators (eg, neuropeptides) can either cause the release of histamine or act as pruritogens themselves, thus explaining why antihistamines ameliorate some cases of itching and not others. Opioids have a central pruritic action as well as stimulating the peripherally mediated histamine itch.
Mechanisms
There are 4 mechanisms of itch:
Dermatologic: This mechanism is typically caused by inflammatory or pathologic processes (eg, urticaria Urticaria Urticaria consists of migratory, well-circumscribed, erythematous, pruritic plaques on the skin. Urticaria also may be accompanied by angioedema, which results from mast cell and basophil activation... read more
, eczema Atopic Dermatitis (Eczema) Atopic dermatitis is a chronic relapsing inflammatory skin disorder with a complex pathogenesis involving genetic susceptibility, immunologic and epidermal barrier dysfunction, and environmental... read more 
).Systemic: This mechanism is related to diseases of organs other than skin (eg, cholestasis).
Neuropathic: This mechanism is related to disorders of the CNS or peripheral nervous system (eg, multiple sclerosis Multiple Sclerosis (MS) Multiple sclerosis (MS) is characterized by disseminated patches of demyelination in the brain and spinal cord. Common symptoms include visual and oculomotor abnormalities, paresthesias, weakness... read more
).Psychogenic: This mechanism is related to psychiatric conditions.
Intense itching stimulates vigorous scratching, which in turn can cause secondary skin conditions (eg, inflammation, excoriation, infection), which can lead to more itching through disruption of the skin barrier. Although scratching can temporarily reduce the sensation of itch by activating inhibitory neuronal circuits, it also leads to amplification of itching at the level of the brain, exacerbating the itch–scratch cycle.
Etiology of Itching
Itching can be a symptom of a primary skin disease or, less commonly, a systemic disease. Also, drugs can cause itching (see see Table: Some Causes of Itching Some Causes of Itching Itching is a symptom that can cause significant discomfort and is one of the most common reasons for consultation with a dermatologist. Itching leads to scratching, which can cause inflammation... read more ).
Skin disorders
Many skin disorders cause itching. The most common include
Systemic disorders
In systemic disorders, itching may occur with or without skin lesions. However, when itching is prominent without any identifiable skin lesions, systemic disorders and drugs should be considered more strongly. Systemic disorders are less often a cause of itching than skin disorders, but some of the more common causes include
Allergic reaction (eg, to foods Food Allergy Food allergy is an exaggerated immune response to dietary components, usually proteins. Manifestations vary widely and can include atopic dermatitis, gastrointestinal or respiratory symptoms... read more , drugs Drug Eruptions and Reactions Drugs can cause multiple skin eruptions and reactions. The most serious of these are discussed elsewhere in THE MANUAL and include Stevens-Johnson syndrome and toxic epidermal necrolysis, hypersensitivity... read more
, and bites and stings)Cholestasis
Less common systemic causes of itching include hyperthyroidism Hyperthyroidism Hyperthyroidism is characterized by hypermetabolism and elevated serum levels of free thyroid hormones. Symptoms are many and include tachycardia, fatigue, weight loss, nervousness, and tremor... read more 
, hypothyroidism Hypothyroidism Hypothyroidism is thyroid hormone deficiency. It is diagnosed by clinical features such as a typical facial appearance, hoarse slow speech, and dry skin and by low levels of thyroid hormones... read more 
, diabetes Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more , iron deficiency, dermatitis herpetiformis Dermatitis Herpetiformis Dermatitis herpetiformis is an intensely pruritic, chronic, autoimmune, papulovesicular cutaneous eruption strongly associated with celiac disease. Typical findings are clusters of intensely... read more 
, and polycythemia vera Polycythemia Vera Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by an increase in morphologically normal red cells (its hallmark), but also white cells and platelets. Ten to 30%... read more .
Drugs
Drugs Drug Eruptions and Reactions Drugs can cause multiple skin eruptions and reactions. The most serious of these are discussed elsewhere in THE MANUAL and include Stevens-Johnson syndrome and toxic epidermal necrolysis, hypersensitivity... read more can cause itching as an allergic reaction or by directly triggering histamine release (most commonly morphine, some IV contrast agents).
Evaluation of Itching
History
History of present illness should determine onset of itching, initial location, course, duration, patterns of itching (eg, nocturnal or diurnal, intermittent or persistent, seasonal variation), and whether any rash is present. A careful drug history should be obtained including both prescription and over-the-counter medications with particular attention paid to recently started drugs. The patient's use of moisturizers and other topicals (eg, hydrocortisone, diphenhydramine) should be reviewed. History should include any factors that make the itching better or worse
Review of systems should seek symptoms of causative disorders, including
Headache, pica, hair thinning, and exercise intolerance (iron deficiency anemia Iron Deficiency Anemia Iron deficiency is the most common cause of anemia and usually results from blood loss; malabsorption, such as with celiac disease, is a much less common cause. Symptoms are usually nonspecific... read more
)Constitutional symptoms of weight loss, fatigue, and night sweats (cancer)
Intermittent weakness, numbness, tingling, and visual disturbances or loss (multiple sclerosis Multiple Sclerosis (MS) Multiple sclerosis (MS) is characterized by disseminated patches of demyelination in the brain and spinal cord. Common symptoms include visual and oculomotor abnormalities, paresthesias, weakness... read more
)Steatorrhea, jaundice Jaundice Jaundice is a yellowish discoloration of the skin and mucous membranes caused by hyperbilirubinemia. Jaundice becomes visible when the bilirubin level is about 2 to 3 mg/dL (34 to 51 micromol/L)... read more
, and right upper quadrant pain (cholestasis)
Past medical history should identify known causative disorders (eg, renal disease, cholestatic disorder, cancer being treated with chemotherapy) and the patient’s emotional state. Social history should focus on family members with similar itching and skin symptoms (eg, scabies, pediculosis); relationship of itching to occupation or exposures to plants, animals, or chemicals; and history of recent travel.
Physical examination
Physical examination begins with a review of clinical appearance for signs of jaundice, weight loss or gain, and fatigue. Close examination of the skin should be done, taking note of presence, morphology, extent, and distribution of lesions. Cutaneous examination also should make note of signs of secondary infection (eg, erythema, swelling, warmth, yellow or honey-colored crusting).
The examination should make note of significant adenopathy suggestive of cancer. Abdominal examination should focus on organomegaly, masses, and tenderness (cholestatic disorder or cancer). Neurologic examination should focus on weakness, spasticity, or numbness (multiple sclerosis).
Red flags
The following findings are of particular concern:
Constitutional symptoms of weight loss, fatigue, and night sweats
Extremity weakness, numbness, or tingling
Abdominal pain and jaundice
Urinary frequency, excessive thirst, and weight loss
Interpretation of findings
Generalized itching that begins shortly after use of a drug is likely caused by that drug. Localized itching (often with rash) that occurs in the area of contact with a substance is likely caused by that substance. However, many systemic allergies can be difficult to identify because patients typically have consumed multiple different foods and have been in contact with many substances before developing itching. Similarly, identifying a drug cause in a patient taking several drugs may be difficult. Sometimes the patient has been taking the offending drug for months or even years before developing a reaction.
If an etiology is not immediately obvious, the appearance and location of skin lesions can suggest a diagnosis (see Table: Some Causes of Itching Some Causes of Itching Itching is a symptom that can cause significant discomfort and is one of the most common reasons for consultation with a dermatologist. Itching leads to scratching, which can cause inflammation... read more ).
In the minority of patients in whom no skin lesions are evident, a systemic disorder should be considered. Some disorders that cause itching are readily apparent on evaluation (eg, chronic renal failure, cholestatic jaundice). Other systemic disorders that cause itching are suggested by findings (see Table: Some Causes of Itching Some Causes of Itching Itching is a symptom that can cause significant discomfort and is one of the most common reasons for consultation with a dermatologist. Itching leads to scratching, which can cause inflammation... read more ). Rarely, itching is the first manifestation of significant systemic disorders (eg, polycythemia vera, certain cancers, hyperthyroidism).
Testing
Many dermatologic disorders are diagnosed clinically. However, when itching is accompanied by discrete skin lesions of uncertain etiology, biopsy can be appropriate. When an allergic reaction is suspected but the substance is unknown, skin testing (either prick or patch testing depending on suspected etiology) is often done. When a systemic disorder is suspected, testing is directed by the suspected cause and usually involves CBC; liver, renal, and thyroid function measurements; and appropriate evaluation for underlying cancer.
Treatment of Itching
Any underlying disorder is treated. Supportive treatment involves the following (see also table Some Therapeutic Approaches to Itching Some Therapeutic Approaches to Itching Itching is a symptom that can cause significant discomfort and is one of the most common reasons for consultation with a dermatologist. Itching leads to scratching, which can cause inflammation... read more ):
Local skin care
Topical treatment
Systemic treatment
Skin care
Itching due to any cause benefits from use of cool or lukewarm (but not hot) water when bathing, mild or moisturizing soap, limited bathing duration and frequency, frequent lubrication, humidification of dry air, and avoidance of irritating clothing. Avoidance of contact irritants (eg, wool clothing) also may be helpful.
Topical drugs
Topical drugs may help localized itching. Options include lotions or creams that contain camphor and/or menthol, pramoxine, capsaicin, or corticosteroids. Corticosteroids are effective in relieving itch caused by inflammation but should be avoided for conditions that have no evidence of inflammation. Topical benzocaine, diphenhydramine, and doxepin should be avoided because they may sensitize the skin.
Systemic drugs
Systemic drugs are indicated for generalized itching or local itching resistant to topical agents. Antihistamines, most notably hydroxyzine, are effective, especially for nocturnal itch, and are most commonly used. Sedating antihistamines must be used cautiously in elderly patients during the day because they can lead to falls; newer nonsedating antihistamines such as loratadine, fexofenadine, and cetirizine can be useful for daytime itching. Other drugs include doxepin (typically taken at night due to high level of sedation), cholestyramine (for renal failure, cholestasis, and polycythemia vera), opioid antagonists such as naltrexone (for biliary pruritus), and possibly gabapentin (for uremic pruritus).
Physical agents that may be effective for itching include ultraviolet phototherapy.
Geriatrics Essentials
Age-related changes in the immune system and in nerve fibers may contribute to the high prevalence of itch in older adults.
Xerotic eczema is very common among elderly patients. It is especially likely if itching is primarily on the lower extremities.
Severe, diffuse itching in the elderly should raise concern for cancer, especially if another etiology is not immediately apparent.
When treating the elderly, sedation can be a significant problem with antihistamines. Use of nonsedating antihistamines during the day and sedating antihistamines at night, liberal use of topical ointments and corticosteroids (when appropriate), and consideration of ultraviolet phototherapy can help avoid the complications of sedation.
Key Points
Itching is usually a symptom of a skin disorder or systemic allergic reaction but can result from a systemic disorder.
If skin lesions are not evident, systemic causes should be investigated.
Skin care (eg, limiting bathing, avoiding irritants, moisturizing regularly, humidifying environment) should be observed.
Symptoms can be relieved by topical or systemic drugs.
