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Itching

(Pruritus)

by Robert J. MacNeal, MD

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

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.

Mediators

Histamine is one of the most significant mediators. 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—typically caused by inflammatory or pathologic processes (eg, urticaria, eczema)

  • Systemic—related to diseases of organs other than skin (eg, cholestasis)

  • Neuropathic—related to disorders of the CNS or peripheral nervous system (eg, multiple sclerosis)

  • Psychogenic—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. However, scratch can temporarily reduce the sensation of itch by activating inhibitory neuronal circuits.


Etiology

Itching can be a symptom of a primary skin disease or, less commonly, a systemic disease (see Some Causes of Itching).

Skin disorders

Many skin disorders cause itching. The most common include

  • Dry skin

  • Atopic dermatitis (eczema)

  • Contact dermatitis

  • Fungal skin infections


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, drugs, and bites and stings)

  • Cholestasis

  • Chronic renal failure

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


Drugs

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

Cause

Suggestive Findings

Diagnostic Approach

Primary skin disorders

Atopic dermatitis

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

Contact dermatitis

Dermatitis secondary to contact with allergen; erythema, vesicles

Clinical evaluation

Dermatophytosis (eg, tinea capitis, tinea corporis, tinea cruris, tinea pedis)

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

Lichen simplex chronicus

Areas of skin thickening secondary to repetitive scratching

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

Clinical evaluation

Pediculosis

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

Psoriasis

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

Scabies

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

Urticaria

Evanescent, circumscribed, raised, erythematous lesions with central pallor

Can be acute or chronic ( 6 wk)

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

Cancer (eg, Hodgkin lymphoma, polycythemia vera, mycosis fungoides)

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)

CBC

Peripheral smear

Chest x-ray

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

Cholestasis

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

Diabetes*

Urinary frequency, thirst, weight loss, vision changes

Urine and blood glucose

HbA 1C

Drugs (eg, aspirin, barbiturates, morphine, cocaine, penicillin, some antifungal drugs, chemotherapeutic agents)

History of ingestion

Clinical evaluation

Iron deficiency anemia

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

Hb, Hct, red cell indices, serum ferritin, iron, and iron-binding capacity

Multiple sclerosis

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

MRI

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)

TSH, T 4

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

HbA 1C = glycosylated Hb; KOH = potassium hydroxide; T 4 = thyroxine; TSH = thyroid-stimulating hormone.


Evaluation

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; both oral (eg, opioids, cocaine, aspirin, prescription and OTC) and topical (eg, hydrocortisone, benadryl, moisturizers) drugs are included. History also should include any factors that make the itching better or worse.

Review of systems should seek symptoms of causative disorders, including steatorrhea and right upper quadrant pain (cholestasis); constitutional symptoms of fever, weight loss, and night sweats (cancer); intermittent weakness, numbness, tingling, and visual disturbances or loss (multiple sclerosis); irritability, sweating, weight loss, and palpitations (hyperthyroidism) or depression, dry skin, and weight gain (hypothyroidism); urinary frequency, excessive thirst, and weight loss (diabetes); and headache, pica, hair thinning, and exercise intolerance (iron deficiency anemia).

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 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 Some Causes of Itching). 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

Any underlying disorder is treated. Supportive treatment involves the following (see also 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 or tight 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, 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

Drug/Agent

Usual Regimen

Comments

Topical therapy

Capsaicin cream

Apply regularly for required period of time

May require 2 wk 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 wk)

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 yr

Ultraviolet B therapy

1–3 times/wk until itching lessens

Treatment often continued for months

Sunburn-like adverse effects can occur

Long-term risk of skin cancer, including melanoma

Systemic therapy

Cetirizine*

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

Cyproheptadine

4 mg po tid

Sedating, also helpful when given before bedtime

Diphenhydramine

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

Sedating, also helpful when given before bedtime

Doxepin

25 mg po once/day

Helpful in severe and chronic itching

Very sedating so taken at bedtime

Fexofenadine*

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

Hydroxyzine

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

Sedating, also helpful when given before bedtime

Loratadine*

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

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.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • No US brand name
  • DURAMORPH PF, MS CONTIN
  • ANBESOL
  • EPIFOAM
  • ZONALON
  • No US trade name
  • NEURONTIN
  • PROGRAF
  • QUTENZA
  • REVIA
  • ALLEGRA
  • ALAVERT, CLARITIN
  • VISTARIL
  • ZYRTEC
  • ELIDEL

* This is a professional Version *