Itching

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.

There are 3 mechanisms of itch:

• Dermatologic: This mechanism is typically caused by inflammatory or pathologic processes (eg, urticaria, eczema).

• Systemic: This mechanism is related to diseases of organs other than skin (eg, cholestasis).

• Neurogenic: This mechanism is related to disorders of the central or peripheral nervous system (eg, multiple sclerosis).

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.

Many skin disorders cause itching. The most common include

• Dry skin

• Atopic dermatitis (eczema)

• Contact dermatitis

• Fungal skin infections

In systemic disorders, itching may occur with or without skin lesions. However, when itching is prominent without any identifiable skin lesions, systemic disorders, medications, 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 and medications)

• Cholestasis

• Chronic kidney disease

Less common systemic causes of itching include hyperthyroidism, hypothyroidism, diabetes, iron deficiency, dermatitis herpetiformis, and polycythemia vera.

Medications

History of present illness

Review of systems should seek symptoms of causative disorders, including

• Irritability, sweating, weight loss, and palpitations (hyperthyroidism)

• Depression, dry skin, and weight gain (hypothyroidism)

• Headache, pica, hair thinning, and exercise intolerance (iron deficiency anemia)

• Constitutional symptoms of weight loss, fatigue, and night sweats (cancer)

• Intermittent weakness, numbness, tingling, and visual disturbances or loss (multiple sclerosis)

• Steatorrhea, jaundice, and right upper quadrant pain (cholestasis)

• Urinary frequency, excessive thirst, and weight loss (diabetes)

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 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).

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

Generalized itching that begins shortly after use of a medication or exposure to a substance (eg, IV contrast) is likely caused by that agent. 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 medications may be difficult. Sometimes the patient has been taking the offending medication 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).

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 kidney disease, cholestatic jaundice). Other systemic disorders that cause itching are suggested by findings (see table Some Causes of Itching). Rarely, itching is the first manifestation of significant systemic disorders (eg, polycythemia vera, certain cancers, hyperthyroidism).

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 complete blood count; liver, renal, and thyroid function measurements; and appropriate evaluation for underlying cancer.

Itching due to any cause benefits from use of cool or lukewarm (instead of 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.

Physical agents that may be effective for itching include ultraviolet phototherapy.