Itching: A Merck Manual of Patient Symptoms podcast

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 Table 1: Approach to the Dermatologic Patient: 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).

Table 1
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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 HbA1C 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, T4 *Itching as the patient's presenting complaint is unusual. HbA1C = glycosylated Hb; KOH = potassium hydroxide; T4 = thyroxine; TSH = thyroid-stimulating hormone. 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 HbA1C 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, T4 *Itching as the patient's presenting complaint is unusual. HbA1C = glycosylated Hb; KOH = potassium hydroxide; T4 = 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 Table 1: Approach to the Dermatologic Patient: 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 1: Approach to the Dermatologic Patient: 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 Table 2: Approach to the Dermatologic Patient: 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.

Table 2
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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. 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.

Last full review/revision March 2013 by Robert J. MacNeal, MD