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Julia Benedetti

, MD, Harvard Medical School

Last full review/revision Feb 2019| Content last modified Feb 2019
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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.

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.


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 4 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).

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

  • 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).

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

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


Drugs can cause itching as an allergic reaction or by directly triggering histamine release (most commonly morphine, some IV contrast agents).


Some Causes of Itching


Suggestive Findings

Diagnostic Approach

Primary skin disorders

Presence of erythema, possible lichenification, keratosis pilaris, xerosis, Dennie-Morgan lines, hyperlinear palms

Usually a family history of atopy or chronic recurring dermatitis

Clinical evaluation

Dermatitis secondary to contact with allergen; erythema, vesicles

Clinical evaluation

Localized itching, circular lesions with raised scaly borders, areas of alopecia

Common sites are genital area and feet in adults; scalp and body in children

Sometimes, predisposing factors (eg, moisture, obesity)

KOH examination of lesion scrapings

Areas of skin thickening secondary to repetitive scratching

Lesions are discrete, erythematous, scaly plaques, well-circumscribed, rough, lichenified skin

Clinical evaluation

Common sites are scalp, axillae, waist, and pubic area

Areas of excoriation, possible punctate lesions from fresh bites, possible bilateral blepharitis

Visualization of eggs (nits), and sometimes lice

Plaques with silvery scale typically on extensor surfaces of elbow, knees, scalp, and trunk

Itching not necessarily limited to plaques

Possibly small-joint arthritis manifesting as stiffness and pain

Clinical evaluation

Small erythematous or dark papules at one end of a fine, wavy, slightly scaly line up to 1 cm long (burrow); possibly on web spaces, belt line, flexor surfaces, and areolas of women and genitals of men

Family or close community members with similar symptoms

Intense nocturnal itching

Clinical evaluation

Microscopic examination of skin scrapings from burrows

Evanescent, circumscribed, raised, erythematous lesions with central pallor

Can be acute or chronic ( 6 weeks)

Clinical evaluation

Xerosis(dry skin)

Most common in the winter

Itchy, dry, scaly skin, mostly on lower extremities

Exacerbated by dry heat

Clinical evaluation

Systemic disorders

Allergic reaction, internal (numerous ingested substances)

Generalized itching, rash with macules and papules or urticarial rash

May or may not have known allergy

Trial of avoidance

Sometimes skin-prick testing

Itching may precede any other symptoms

Burning quality to itching, primarily in lower extremities (Hodgkin lymphoma)

Itching after bathing (polycythemia vera)

Heterogeneous cutaneous lesions—plaques, patches, tumors, erythroderma (mycosis fungoides)


Peripheral smear

Chest x-ray

Biopsy (bone marrow for polycythemia vera, lymph node for Hodgkin lymphoma, skin lesion for mycosis fungoides)


Findings suggestive of liver or gallbladder damage or dysfunction (eg, jaundice, steatorrhea, fatigue, right upper quadrant pain)

Usually widespread itching without rash, developing sometimes in late pregnancy

Liver function tests and evaluation for cause of jaundice

Urinary frequency, thirst, weight loss, vision changes

Urine and blood glucose


Fatigue, headache, irritability, exercise intolerance, pica, hair thinning

Hemoglobin, hematocrit, red cell indices, serum ferritin, iron, and iron-binding capacity

Intermittent intense itching, numbness, tingling in limbs, optic neuritis, vision loss, spasticity or weakness, vertigo


CSF analysis

Evoked potentials

Psychiatric illness

Linear excoriations, presence of psychiatric condition (eg, clinical depression, delusions of parasitosis)

Clinical evaluation

Diagnosis of exclusion

Renal disease

End-stage renal disease

Generalized itching, may be worse during dialysis, may be prominent on the back

Diagnosis of exclusion

Thyroid disorders*

Weight loss, heart palpitations, sweating, irritability (hyperthyroidism)

Weight gain, depression, dry skin and hair (hypothyroidism)



Drugs (eg, opioids, penicillin, ACE inhibitors, statins, antimalarials, epidermal growth factor inhibitors, interleukin 2, vemurafenib, ipilimumab, other anti-neoplastic agents)

History of ingestion

Clinical evaluation

*Itching as the patient’s presenting complaint is unusual.

HbA1C = glycosylated Hb; KOH = potassium hydroxide; T4 = thyroxine; TSH = thyroid-stimulating hormone.

Evaluation of Itching


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

  • 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

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).

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). 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 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):

  • 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.


Some Therapeutic Approaches to Itching


Usual Regimen


Topical therapy

Capsaicin cream

Apply regularly for required period of time to a localized area of neuropathic itch

May require 2 weeks for effect

Vegetable oil can help with removal

Initial burning sensation dissipates with time

Corticosteroid creams or ointments

Apply to affected area twice daily for 5–7 days

Avoid face, moist skinfolds

Should not be used for prolonged periods of time (> 2 weeks)

Menthol-containing and/or camphor-containing creams

Apply to affected areas as needed for relief

These preparations have strong odors

Pramoxine cream

Apply as needed, 4–6 times/day

Can cause dryness or irritation at application site

Tacrolimus ointment or pimecrolimus cream

Apply to affected area twice daily for 10 days

Should not be used for long periods of time or on children < 2 years

Ultraviolet B therapy

1–3 times/week until itching lessens

Treatment often continued for months

Sunburn-like adverse effects can occur

Long-term risk of skin cancer, including melanoma

Systemic therapy


5–10 mg po once/day

Rarely can have a sedating effect in elderly patients

Cholestyramine (cholestatic pruritus)

4–16 g po once/day

Adherence can be poor

Constipating, unpalatable

Can interfere with absorption of other drugs


4 mg po tid

Sedating, also helpful when given before bedtime


25–50 mg po q 4–6 hours (no more than 6 doses in 24 hours)

Sedating, also helpful when given before bedtime


25 mg po once/day

Helpful in severe and chronic itching

Very sedating so taken at bedtime


60 mg po bid

Headache can be an adverse effect

Gabapentin (uremic pruritus)

100 mg po after hemodialysis

Sedation can be a problem

Low doses to start and titrated up to clinical effect


25–50 mg po q 4–6 hours (no more than 6 doses in 24 hours)

Sedating, also helpful when given before bedtime


10 mg po once/day

Rarely can have a sedating effect in elderly patients

Naltrexone (cholestatic pruritus)

12.5–50 mg po once/day

Can lead to withdrawal symptoms in patients with tolerance to opioids

*Nonsedating antihistamine.

Sedating antihistamine.

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.

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