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.)
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. 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:
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Systemic: This mechanism is related to diseases of organs other than skin (eg, cholestasis).
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Neuropathic: This mechanism is related to disorders of the CNS or peripheral nervous system (eg, multiple sclerosis).
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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
Itching can be a symptom of a primary skin disease or, less commonly, a systemic disease. Also, drugs can cause itching (see {blank} Some Causes of Itching).
Skin disorders
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
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 |
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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 |
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Dermatitis secondary to contact with allergen; erythema, vesicles |
Clinical evaluation |
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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 |
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Areas of skin thickening secondary to repetitive scratching Lesions are discrete, erythematous, scaly plaques, well-circumscribed, rough, lichenified skin |
Clinical evaluation |
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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 |
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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 |
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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 |
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Evanescent, circumscribed, raised, erythematous lesions with central pallor Can be acute or chronic (≥ 6 weeks) |
Clinical evaluation |
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Xerosis(dry skin) |
Most common in the winter Itchy, dry, scaly skin, mostly on lower extremities Exacerbated by dry heat |
Clinical evaluation |
Systemic disorders |
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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 |
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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) |
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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 |
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Urinary frequency, thirst, weight loss, vision changes |
Urine and blood glucose HbA1C |
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Fatigue, headache, irritability, exercise intolerance, pica, hair thinning |
Hemoglobin, hematocrit, red cell indices, serum ferritin, iron, and iron-binding capacity |
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Intermittent intense itching, numbness, tingling in limbs, optic neuritis, vision loss, spasticity or weakness, vertigo |
MRI CSF analysis Evoked potentials |
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Psychiatric illness |
Linear excoriations, presence of psychiatric condition (eg, clinical depression, delusions of parasitosis) |
Clinical evaluation Diagnosis of exclusion |
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Renal disease |
End-stage renal disease Generalized itching, may be worse during dialysis, may be prominent on the back |
Diagnosis of exclusion |
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Thyroid disorders* |
Weight loss, heart palpitations, sweating, irritability (hyperthyroidism) Weight gain, depression, dry skin and hair (hypothyroidism) |
TSH, T4 |
Drugs |
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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 |
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*Itching as the patient’s presenting complaint is unusual. HbA1C = glycosylated Hb; KOH = potassium hydroxide; T4 = thyroxine; TSH = thyroid-stimulating hormone. |
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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 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
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Irritability, sweating, weight loss, and palpitations (hyperthyroidism)
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Depression, dry skin, and weight gain (hypothyroidism)
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Headache, pica, hair thinning, and exercise intolerance (iron deficiency anemia)
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Constitutional symptoms of weight loss, fatigue, and night sweats (cancer)
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Intermittent weakness, numbness, tingling, and visual disturbances or loss (multiple sclerosis)
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Steatorrhea, jaundice, and right upper quadrant pain (cholestasis)
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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
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).
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 Some Therapeutic Approaches to Itching):
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, 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
Drug/Agent |
Usual Regimen |
Comments |
Topical therapy |
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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 |
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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) |
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Menthol-containing and/or camphor-containing creams |
Apply to affected areas as needed for relief |
These preparations have strong odors |
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Pramoxine cream |
Apply as needed, 4–6 times/day |
Can cause dryness or irritation at application site |
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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 |
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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 |
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Cetirizine* |
5–10 mg po once/day |
Rarely can have a sedating effect in elderly patients |
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Cholestyramine (cholestatic pruritus) |
4–16 g po once/day |
Adherence can be poor Constipating, unpalatable Can interfere with absorption of other drugs |
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Cyproheptadine† |
4 mg po tid |
Sedating, also helpful when given before bedtime |
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Diphenhydramine† |
25–50 mg po q 4–6 hours (no more than 6 doses in 24 hours) |
Sedating, also helpful when given before bedtime |
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Doxepin |
25 mg po once/day |
Helpful in severe and chronic itching Very sedating so taken at bedtime |
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Fexofenadine* |
60 mg po bid |
Headache can be an adverse effect |
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Gabapentin (uremic pruritus) |
100 mg po after hemodialysis |
Sedation can be a problem Low doses to start and titrated up to clinical effect |
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Hydroxyzine† |
25–50 mg po q 4–6 hours (no more than 6 doses in 24 hours) |
Sedating, also helpful when given before bedtime |
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Loratadine* |
10 mg po once/day |
Rarely can have a sedating effect in elderly patients |
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Naltrexone (cholestatic pruritus) |
12.5–50 mg po once/day |
Can lead to withdrawal symptoms in patients with tolerance to opioids |
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*Nonsedating antihistamine. †Sedating antihistamine. |
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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
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Itching is usually a symptom of a skin disorder or systemic allergic reaction but can result from a systemic disorder.
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If skin lesions are not evident, systemic causes should be investigated.
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Skin care (eg, limiting bathing, avoiding irritants, moisturizing regularly, humidifying environment) should be observed.
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Symptoms can be relieved by topical or systemic drugs.
