Pruritus (itching) is a symptom that can cause significant discomfort and is one of the most common reasons for consultation with a clinician. It can occur with and without a primary skin eruption. Pruritus usually leads to scratching, which can cause inflammation, skin degradation, and possible secondary infection. Chronic skin changes can also occur as a result of scratching—the skin can become scaly, excoriated, or even lichenified—even in the absence of a primary skin disorder.
(See also Evaluation of the Dermatologic Patient.)
Pathophysiology of Pruritus
Pruritus can be prompted by diverse stimuli, including light touch, vibration, and wool fibers. There are a number of chemical mediators and different mechanisms by which the sensation of itch is transmitted. Specific peripheral sensory neurons mediate the itch sensation. These neurons are distinct from those that respond to light touch or pain and are composed primarily of C-nerve fibers and some specialized A-delta fibers that travel from the skin to the central nervous system and transmit the sensation. Such neurons also contain specialized itch receptors (eg, TRPV1, TRPA1), the stimulation of which causes the sensation of itch (1). Other key itch receptors include G protein–coupled receptors, such as protease-activated receptor 2 (PAR-2) and members of the Mas-related G protein–coupled receptor (MRGPR) family, which transduce itch signals when activated by pruritogens. These selective itch receptors (also called pruriceptors) detect itch stimuli and transmit signals through peripheral neurons that synapse with spinal neurons and interneurons, ultimately reaching multiple brain regions for processing.
Mediators
Histamine has traditionally been the mediator most well known for inducing acute pruritus. It is synthesized and stored in mast cells in the skin and is released via degranulation in response to various stimuli. Histamine typically works via histamine receptors H1 or H4 on C-nerve fibers and via TRPV1-gated cation influxes, causes action potentials, and, thereby, transmits the sensation of itch (2). Subsequent evidence has shown that other mediators may also be involved (3).
Th2 cytokines (particularly interleukins [IL]-4, IL-13, IL-31, and IL-33 as well as thymic stromal lymphopoietin) primarily work via JAK/STAT signaling pathways, causing either TRPA1 or TRPV1 sensitization, leading to cation influxes and subsequently to the formation of action potentials and transmission of the sensation of itch.
Other neurotransmitters (eg, substance P, gastrin-releasing peptide) and neurotrophins (eg, nerve growth factor) are also thought to play a central role in pruritus signal transmission (1); many of these mediators are thought to potentiate pruritus signal transmission via PAR and MRGPR (2).
Opioid signalling also modulates transmission of the sensation of itch centrally and peripherally through mu and kappa opioid receptors, contributing to both opioid-induced pruritus and chronic pruritus.
Mechanisms
There are 3 mechanisms of pruritus:
Dermatologic: This mechanism is typically caused by inflammatory or pathologic processes (eg, urticaria, atopic dermatitis,psoriasis).
Systemic: This mechanism is related to diseases of organs other than skin (eg, cholestasis, chronic kidney disease).
Neurogenic: This mechanism is related to disorders of the central or peripheral nervous system (eg, multiple sclerosis).
Intense pruritus stimulates vigorous scratching, which in turn can cause secondary skin conditions (eg, inflammation, excoriation, infection, lichenification), which can lead to more pruritus 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 pruritus at the level of the brain, exacerbating the itch–scratch cycle.
Pathophysiology references
1. Misery L, Pierre O, Le Gall-Ianotto C, et al. Basic mechanisms of itch. J Allergy Clin Immunol. 2023;152(1):11-23. doi:10.1016/j.jaci.2023.05.004
2. Coscarella G, Edwards E, Yosipovitch G. Basic mechanisms of itch and advances in clinical management. Ann Allergy Asthma Immunol. 2026;136(2):131-140. doi:10.1016/j.anai.2025.09.014
3. Szöllősi AG, Oláh A, Lisztes E, Griger Z, Tóth BI. Pruritus: A Sensory Symptom Generated in Cutaneous Immuno-Neuronal Crosstalk. Front Pharmacol. 2022;13:745658. Published 2022 Mar 7. doi:10.3389/fphar.2022.745658
Etiology of Pruritus
Pruritus can be a symptom of a primary skin disease or a systemic disease. Also, medications some and other substances can cause pruritus (see table ).
Skin disorders
Many skin disorders cause pruritus. The most common include:
Systemic disorders
In systemic disorders, pruritus may occur with or without skin lesions. However, when pruritus is prominent without any identifiable skin lesions, systemic disorders, medications, and substances should be considered more strongly. Systemic disorders are less often a cause of pruritus than skin disorders, but some of the more common causes include:
Allergic reaction (eg, to foods and medications)
Cholestasis
Less common systemic causes of pruritus include hyperthyroidism, hypothyroidism, diabetes, iron deficiency, dermatitis herpetiformis, and polycythemia vera.
Medications
Medications and other substances can cause pruritus as an allergic reaction or by directly triggering histamine release (most commonly opioids (eg, morphine), some IV contrast agents).
Some Causes of Pruritus
Cause | Suggestive Findings | Diagnostic Approach |
|---|---|---|
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 | History and physical examination Sometimes skin biopsy | |
Dermatitis secondary to contact with allergen; erythema, vesicles | History and physical examination Sometimes patch testing | |
Dermatophytosis (eg, tinea capitis, tinea corporis, tinea cruris, tinea pedis) | Localized pruritus, 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 Wood lamp examination |
Areas of skin thickening secondary to repetitive scratching Lesions are discrete, erythematous, scaly plaques, well-circumscribed, rough, lichenified skin | History and physical examination Sometimes skin biopsy | |
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 Pruritus not necessarily limited to plaques Possibly small-joint arthritis manifesting as stiffness and pain | History and physical examination Sometimes skin biopsy | |
Small erythematous or dark papules at one end of a fine, wavy, slightly scaly line up to 1 cm long (also called burrows); 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 pruritus | History and physical examination Microscopic examination of skin scrapings from burrows | |
Evanescent, circumscribed, raised, erythematous lesions with central pallor Can be acute (< 6 weeks) or chronic (≥ 6 weeks) | History and physical examination Sometimes additional testing (eg, thyroid function tests, tests for autoimmune disorders, basophil activation tests) | |
Xerosis (dry skin) | Most common in the winter Pruritic, dry, scaly skin, mostly on lower extremities Exacerbated by dry heat | History and physical examination |
Systemic disorders | ||
Allergic reaction, internal (numerous ingested substances) | Generalized pruritus, rash with macules and papules or urticarial rash May or may not have known allergy | Trial of avoidance Sometimes allergy (skin-prick) testing |
Cancer (eg, Hodgkin lymphoma, polycythemia vera, mycosis fungoides) | Pruritus may precede any other symptoms Burning quality to pruritus, primarily in lower extremities (Hodgkin lymphoma) Pruritus after bathing (polycythemia vera) Heterogeneous cutaneous lesions—plaques, patches, tumors, erythroderma (mycosis fungoides) Intense oral erosions, crusting, and tense blisters (paraneoplastic pemphigus) Concentric erythematous lesions (erythema gyratum repens) | Complete blood count and bone marrow biopsy for polycythemia vera Lymph node or bone marrow biopsy for Hodgkin lymphoma Skin biopsy for mycosis fungoides |
Cholestasis | Findings suggestive of liver or gallbladder damage or dysfunction (eg, jaundice, steatorrhea, fatigue, right upper quadrant pain) Usually widespread pruritus without rash, developing sometimes in late pregnancy | |
Urinary frequency, thirst, weight loss, vision changes | Urine and blood glucose HbA1C | |
Fatigue, headache, irritability, exercise intolerance, pica, hair thinning | Hemoglobin, hematocrit, red cell indices, serum ferritin, iron, and iron-binding capacity | |
Intermittent intense pruritus, numbness, tingling in limbs, optic neuritis, vision loss, spasticity or weakness, vertigo | MRI Cerebrospinal fluid analysis Sometimes evoked potentials | |
Psychiatric illness† | Linear excoriations, presence of psychiatric condition (eg, clinical depression, delusions of parasitosis) | History and physical examination |
Renal disease | End-stage kidney disease Generalized pruritus, may be worse during dialysis, may be prominent on the back | |
Thyroid disorders* | Weight loss, heart palpitations, sweating, irritability (hyperthyroidism) Weight gain, depression, dry skin and hair (hypothyroidism) | TSH, T4, anti-thyroid antibodies (to thyroid peroxidase and thyroglobulin) |
Medications | ||
Opioids Antibiotics (eg, penicillin) ACE inhibitors (eg, enalapril, ramipril) Antimalarials (eg, hydroxychloroquine) Statins (eg, atorvastatin) Interleukin-2 agents (eg, aldesleukin) Chemotherapeutic agents (eg, epidermal growth factor receptor inhibitors such as erlotinib, BRAF inhibitors such as vemurafenib) Immune checkpoint inhibitors (eg, ipilimumab, pembrolizumab) | History of use | Typically history alone |
* Pruritus as the patient’s presenting symptom is unusual. | ||
† Diagnosis of exclusion. | ||
ACE = angiotensin-converting enzyme; HbA1C = glycosylated hemoglobin; KOH = potassium hydroxide; T4 = thyroxine; TSH = thyroid-stimulating hormone. | ||
Evaluation of Pruritus
History
History of present illness should determine onset of pruritus, initial location, progression, duration, patterns of pruritus (eg, nocturnal or diurnal, intermittent or persistent, seasonal variation), and whether any rash is present (1, 2). A careful medication history should be obtained including both prescription and over-the-counter medications with particular attention paid to recently started medications. The patient's use of moisturizers and other topicals (eg, hydrocortisone, diphenhydramine) should be reviewed. History should include any precipitating or relieving factors for pruritus.
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, kidney disease, cholestatic disorder, cancer being treated with chemotherapy) and the patient’s emotional state. Social history should focus on family members with similar pruritus and skin symptoms (eg, scabies, pediculosis); relationship of pruritus 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 any lesions. Cutaneous examination also should make note of signs of secondary infection (eg, inflammatory color change, swelling, warmth, yellow or honey-colored crusting), excoriations, or lichenification.
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 pruritus that begins shortly after use of a medication or exposure to a substance (eg, IV contrast, vancomycin) is likely caused by that agent. Localized pruritus (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 pruritus. Similarly, identifying the causative medication 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 ).
In the minority of patients in whom no skin lesions are evident, a systemic disorder should be considered. Some disorders that cause pruritus are readily apparent on evaluation (eg, chronic kidney disease, cholestatic jaundice). Other systemic disorders that cause pruritus are suggested by findings (see table ). Rarely, pruritus is the first manifestation of a significant systemic disorder (eg, polycythemia vera, certain cancers, hyperthyroidism).
Testing
Many dermatologic disorders can be diagnosed clinically (1, 2). However, when pruritus is accompanied by discrete skin lesions of uncertain etiology, biopsy can be appropriate.
When an allergic reaction is suspected but the substance is unknown, cutaneous allergy testing (either skin-prick or patch testing depending on suspected etiology) is often done.
When a systemic disorder is suspected, specific 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.
Evaluation references
1. Steinhoff M, Cevikbas F, Yeh I, Chong K, Buddenkotte J, Ikoma A. Evaluation and management of a patient with chronic pruritus. J Allergy Clin Immunol. 2012;130(4):1015-6.e7. doi:10.1016/j.jaci.2012.08.006
2. Rupert J, Honeycutt JD. Pruritus: Diagnosis and Management. Am Fam Physician. 2022;105(1):55-64.
Treatment of Pruritus
Any underlying disorder is treated. Supportive treatment involves the following (see also table ):
Local skin care
Topical treatment
Systemic treatment
Skin care
Pruritus due to any cause benefits from using cool or lukewarm (instead of hot) water and mild or moisturizing soap when bathing, and limiting the duration and frequency of bathing. Additionally, frequent emollient use, humidification of dry air, and avoidance of irritating clothing (eg, wool) are recommended. Avoidance of contact irritants (eg, products with fragrance) also may be helpful.
Topical treatment
Topical medications may help localized pruritus. Options include lotions or creams that contain camphor and/or menthol, pramoxine, capsaicin, or glucocorticoids. Topical glucocorticoids, particularly in ointments (eg, hydrocortisone 2.5%, triamcinolone 0.1%) effectively relieve pruritus caused by inflammation (1). Topical calcineurin inhibitors (eg, tacrolimus 0.1%) may also be effective.
Topical glucocorticoids should be avoided when treating conditions that have no evidence of inflammation, especially if a concomitant infection is present. Topical benzocaine, diphenhydramine, and doxepin should be avoided because they may cause allergic contact dermatitis via sensitization on contact.
Systemic treatment
Systemic medications are indicated for generalized or local pruritus resistant to topical agents. First-generation antihistamines, most notably hydroxyzine and doxepin, are effective, especially for nocturnal pruritus. First-generation antihistamines are sedating and must be used cautiously in older adults during the day because of the risk of falls. Second-generation antihistamines such as loratadine, fexofenadine, levocetirizine, and cetirizine are less sedating and can be useful for daytime pruritus (2).
For chronic pruritus that is recalcitrant to antihistamines, biologics (eg, dupilumab, nemolizumab, lebrikizumab) can be considered depending on the underlying cause (eg, atopic dermatitis, prurigo nodularis) (2).
Other medications include cholestyramine (for renal failure, cholestasis, and polycythemia vera), opioid antagonists such as naltrexone (for biliary pruritus), and possibly gabapentin (for uremic pruritus). Difelikefalin is a kappa opioid receptor agonist that may be used for moderate-to-severe chronic kidney disease–associated pruritus in adults who are undergoing hemodialysis.
Physical agents that may be effective for pruritus include ultraviolet phototherapy.
Some Therapeutic Approaches to Pruritus
Medication/Agent | Comments |
|---|---|
Topical therapy | |
Capsaicin cream | May require ≥ 2 weeks for effect Vegetable oil can help with removal Initial burning sensation dissipates with time |
Glucocorticoid creams or ointments (eg, hydrocortisone, triamcinolone) | Avoid face, moist intertriginous areas Should not be used for prolonged periods of time (> 2 weeks) |
Menthol-containing and/or camphor-containing creams | These preparations have strong odors |
Pramoxine cream | Can cause dryness or irritation at application site |
Calcineurin inhibitors (tacrolimus ointment or pimecrolimus cream) | Should not be used for long periods of time or on children < 2 years |
Ultraviolet B therapy | Sunburn-like adverse effects can occur Long-term risk of skin cancer, including melanoma |
Systemic therapy | |
Cetirizine* | Rarely can have a sedating effect in older adults |
Cholestyramine (cholestatic pruritus) | Adherence can be poor Constipating, unpalatable Can interfere with absorption of other medications |
Cyproheptadine† | Sedating, also helpful when given before bedtime |
Diphenhydramine† | Sedating, also helpful when given before bedtime |
Doxepin | Helpful in severe and chronic pruritus Very sedating so taken at bedtime; reduce dose for older adults |
Fexofenadine* | Headache can be an adverse effect |
Gabapentin (uremic pruritus) | Given after hemodialysis Sedation can be a problem Low doses to start and titrated up to clinical effect |
Hydroxyzine† | Sedating, also helpful when given before bedtime |
Loratadine* | Rarely can have a sedating effect in older adults |
Naltrexone (cholestatic pruritus) | Can lead to withdrawal symptoms in patients with tolerance to opioids |
* Nonsedating antihistamine. | |
† Sedating antihistamine. | |
Treatment references
1. Butler DC, Berger T, Elmariah S, et al. Chronic Pruritus: A Review. JAMA. 2024;331(24):2114-2124. doi:10.1001/jama.2024.4899
2. Coscarella G, Edwards E, Yosipovitch G. Basic mechanisms of itch and advances in clinical management. Ann Allergy Asthma Immunol. 2026;136(2):131-140. doi:10.1016/j.anai.2025.09.014
Geriatrics Essentials: Pruritus
Age-related changes in the immune system and in nerve fibers may contribute to the high prevalence of pruritus in older adults.
Xerotic eczema is very common among older adults. It is especially likely if pruritus is primarily on the lower extremities.
Severe, diffuse pruritus in older adults should raise concern for cancer, especially if another etiology is not immediately apparent.
When treating older adults, sedation can be a significant problem with antihistamines, so dose reduction may be appropriate. Use of nonsedating antihistamines during the day and sedating antihistamines at night, liberal use of topical ointments and glucocorticoids (when appropriate), and consideration of ultraviolet phototherapy can help avoid the complications of sedation.
Key Points
Pruritus (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 medications.
Drug Information for the Topic
