1. Michael DeGroote School of Medicine McMaster University
2. Dermatrials Research, Hamilton, ON, Canada
Pruritus, or itch, is a common sensation that causes a person to want to scratch. It is a complex process that may negatively impact quality of life and commonly occurs with skin disorders such as atopic dermatitis and urticaria. It could also be a symptom related to an underlying disease process such as cholestasis or hyperthyroidism, or simply be caused by dry skin, especially in the cold, winter months. Therapy is often aimed at eliminating the underlying cause first, followed by the management of the itchy sensation. Treatment may include prescription and over-the-counter (OTC) medications, herbal remedies, hydrotherapy, phototherapy, and ultraviolet therapy. This overview provides information regarding the various management and treatment options for pruritus.
pruritus, itch, urticaria
Pathophysiology of Pruritus
Pruritus is a complex process that involves the stimulation of free nerve endings found superficially in the skin. The sensation of pruritus is transmitted through the C-fibers in the skin to the dorsal horn of the spinal cord, and then, via the spinothalamic tract to the cerebral cortex for processing. Many chemicals have been found to be pruritogenic, therefore causing the itch sensation, including histamine, serotonin, cytokines, and opioids. There are six categories of pruritus: dermatologic, systemic, neurogenic, psychogenic, mixed, and other. Various treatment and management options exist depending on the category or cause.1
Treatment of pruritus can be categorized in several ways. A common method of grouping the various options is causative vs. symptomatic treatment. Causative treatment involves finding the underlying disorder and then correcting it, thereby eliminating the itch sensation. Symptomatic treatment involves substituting another sensation for the itch, using methods such as cooling, heating, or counter irritation (e.g., scratching). Symptomatic treatment can be used in addition to treating the underlying disease process in order to provide earlier relief. Most of the available treatment options are categorized under symptomatic therapy and management.
Prescription medications include topical and systemic antihistamines, corticosteroids, local anesthetics, and topical immunomodulators, among others. Some lower concentration preparations of these medications are available OTC.
Itching occurs when histamine is released, causing redness, swelling, warmth, and consequently itchiness. Antihistamines, or H1 antagonists, act by blocking the histamines, and are the most widely used medications for this condition. They take approximately 15–30 minutes to be effective and can be short- or long-acting.2
Topical antihistamines are available in prescription as well as nonprescription forms. Camphor (Caladryl®, Pfizer) is a common diphenhydramine preparation that has both antipruritic and anesthetic properties. This traditional therapy carries with it a small risk of contact dermatitis and allergic sensitization.3
Doxepin, a dibenzoxepin tricyclic compound, is a very active antihistamine that can be used for atopic dermatitis (AD) and also has a useful psychotherapeutic effect for pruritic patients. It acts by depressing cutaneous sensory receptors.4 The starting dose is 25–50mg, taken orally at bedtime. Doxepin cream 5% may be applied q.i.d. Some side-effects of this medication include drowsiness and localized burning or stinging, which are usually transient. Findings in a placebo-controlled, double-blind trial have confirmed the effectiveness of doxepin in the relief of pruritus caused by AD.5 In another study by Drake et al., topically applied doxepin was again found to be a safe and effective treatment for pruritus.5 Berberian et al. conducted a double-blind, controlled study that yielded similar results in which topical doxepin was added to topical hydrocortisone or topical triamcinolone resulting in a significantly faster and more substantial reduction in itching than corticosteroid alone, and a more prompt resolution of underlying AD.6
Hydroxyzine hydrochloride 25mg, po, t.i.d. or q.i.d., or diphenhydramine 25–50mg, po, may be given at bedtime when pruritus is usually at its worst.
Systemic antihistamines are effective in treating some, but not all causes of pruritus, for example, their role in treating AD is limited. They can provide some level of sedation, which may assist sleep, but may also carry with it the adverse effects of unwanted sedation and other anticholinergic properties such as dry mouth, gastrointestinal upset, stomach pain, nausea, and headache. This can be prevented by using nonsedating antihistamines such as fexofenadine (Allegra®, Aventis Pharmaceuticals).
Several low-sedating antihistamines have become available in the last decade. These newer antihistamines, such as loratadine (Claritin®, Schering Canada), block histamine receptors and prevent the activation of cells by histamine, thus preventing an allergic response. Unlike the traditional antihistamines, loratadine, desloratidine (Clarinex®, Schering-Plough; Aerius®, Schering Canada), and cetirizine (Zyrtec®, Pfizer) do not cross the blood-brain barrier and, therefore, do not cause drowsiness. However, these medications have had limited success in the treatment of pruritus.4
Corticosteroid medications are derivatives of the natural hormones produced by the adrenal glands and have many functions including the control of inflammatory responses. Topical formulations are applied to the skin and typically used for localized pruritus such as dermatitis. Low potency preparations are available without a prescription. This class of medications has proven to be successful in the treatment of pruritus for many years by reducing skin inflammation, thus reducing the itching. Corticosteroids seldom alleviate generalized pruritus without dermatitis, but may rarely be helpful if used with lubricants in elderly patients with dry skin. Corticosteroid creams or ointments applied t.i.d. as maintenance therapy are most effective, especially for AD. Emollients, such as white petrolatum, hydrogenated vegetable oil, or hydrophilic petrolatum may be used as a supplement between corticosteroid applications to help hydrate the skin. Corticosteroids should not be used for prolonged periods because of the risk for skin atrophy.4
Oral corticosteroids, such as prednisone, should be considered a last resort, but if given, are best used in 1–2 week courses. Alternate-day use of this drug at 20–40mg every other morning may help to reduce side-effects.4
Topical anesthetics work by directly interfering with the transmission of impulses along the sensory nerve fibers or by depressing cutaneous sensory receptors. Those drugs that interfere with transmission include benzocaine, diperodon, and lidocaine.7 Hercogova suggested that caine-based anesthetics should be avoided due to risk of sensitization, but lotions or creams containing 0.25% – 0.5% menthol can be useful.4
Pramoxine, another topical anesthetic, has a documented antipruritic effect and is most useful for mild-to-moderate pruritus. It may be combined with coolants, such as menthol, to increase its effectiveness.8 One study demonstrated that both the magnitude and duration of histamine-induced itch were reduced by pramoxine.9
Capsaicin, the active ingredient in cayenne and red pepper, owes its antipruritic properties to the desensitization of nociceptive nerve endings responsible for transmitting the itch sensation. It is useful at concentrations of 0.025–0.075% in localized intractable pruritus,10 but may cause localized burning and stinging which can limit its use and reduce compliance in patients. This irritation will subside with repeated use of the medication if the patient chooses to overcome the initial irritations.
Topical calcineurin inhibitors pimecrolimus (Elidel® Cream 1%, Novartis) and tacrolimus (Protopic® Ointment, Astellas) possess anti-itch properties and, similar to corticosteroids, they reduce skin inflammation. However, they have a different mechanism of action and, thus, are not associated with the same adverse effects. Calcineurin inhibitors prevent T-cell activation, inhibit inflammatory cytokine release, and down-regulate high affinity immunoglobulin E receptor expression on the Langerhans’ cells.11 They are second-line therapies indicated for short-term and non-continuous chronic treatment of mild-to-moderate AD in non-immunocompromised people ages 2 and older who have failed to respond adequately to other topical prescription treatments or when those treatments are not advisable.
Pimecrolimus is an ascomycin macrolactam. It shows activity not only against T-cell activation, but also against mast cells and pruritus. In a study of real-life usage by Lubbe et al., incorporation of 1% pimecrolimus cream into patients’ standard treatment regimen was well tolerated and improved AD in approximately two-thirds of patients.12
Tacrolimus is a macrolide lactone isolated from Streptomyces tsukubaensis. The release of cytokines, such as interleukins 4 and 5, are inhibited by this drug.13 A study by Drake, et al. demonstrated that topical tacrolimus ointment was associated with significant quality of life benefits in adult and pediatric patients with AD.14
There is concern about continuous long-term use of calcineurin inhibitors, because of the risk of cancer development. This is based on the FDA’s public health advisory regarding information from animal studies, as well as case reports in a small number of patients. The FDA has received reports of lymphoma and skin cancer in children and adults treated with these drugs, however it has not been clearly established whether the reported cancers are associated with direct use of these products.15 Based on these findings, we suggest caution in prescribing these drugs for long-term use. Application should be limited to areas of the skin affected by AD.
Calcineurin inhibitors are not indicated for use in children 4
Pruritus is a common and sometimes disabling manifestation of cholestasis. Cholestyramine is a nonabsorbable, basic polystyrene that serves as an anion exchange resin binding bile salts in the gut lumen. It is effective in a large proportion of cases of cholestasis-related pruritus. The resin depletes the serum bile salt pool, and has a greater affinity for dihydroxy bile salts than for trihydroxy bile salts. Cholestyramine also has complex effects on absorption of a variety of compounds other than bile salts, and it has been reported to improve pruritus in polycythemia rubra vera and uremia. Side-effects are mild, but common, and include constipation, fat malabsorption, and an unpleasant taste. These side-effects may make compliance an issue.16
Rifampicin is an antibiotic that has also been shown to lower hepatocyte bile salt concentrations by competing for the uptake of these salts into the hepatocyte. In one study, pruritus disappeared in 11 of 14 subjects receiving rifampicin 600mg/day and three experienced partial improvement. 16
Naltrexone, an opiate receptor antagonist, was studied in a randomized, double-blind, placebo-controlled trial to assess the antipruritic effects in patients with chronic cholestatic liver disease. The investigators found that oral naltrexone may be an effective and well-tolerated alternative for pruritus, refractory to regular antipruritic therapy. In this study, five of eight patients treated had considerably less itching.17 In another study, nine out of 20 patients receiving naltrexone had >50% improvement of pruritus. Side-effects in this study, including dizziness, nausea, vomiting, headache, drowsiness, dry mouth, and cramps, were transient and did not require specific treatment.18
Ultraviolet (UV) Light Therapy
UV phototherapy is used to treat various pruritic conditions including chronic renal failure; AD; HIV; aquagenic pruritus; solar, chronic, and idiopathic urticaria; urticaria pigmentosa; polycythemia vera; pruritic folliculitis of pregnancy; breast carcinoma skin infiltration; Hodgkin’s lymphoma; chronic liver disease; and acquired perforating dermatoses, among others. It is often undertaken after multiple attempts to treat stubborn itch, and can offer relief without many of the side-effects and risks of systemic medications. UV-based therapy utilizes UVB and UVA in both broadband and narrowband, as well as PUVA (psoralen UVA). Cost and side-effects can be a prohibitive factor for patients. Erythema is common in UVB, as is premature aging and photocarcinogenesis with both UVA and UVB. Side-effects associated with PUVA include redness, burning, headache, and nausea.16,19
UVA, UVB, and PUVA light therapies have been especially useful in the treatment of pruritus in HIV patients, as well as in those patients with systemic mastocytosis and cutaneous T-cell lymphoma. It localizes the effect on the superficial nerve endings, sparing the remaining helper cells, and relieving the pruritus. Because of its more superficial penetration, UVB is believed to be safer than UVA. UVB also spares the remaining helper cells in HIV patients and may localize the effect on the superficial nerve endings, thus relieving pruritus. Systemic mastocytosis and cutaneous T-cell lymphoma also respond to UV therapy and because destruction of the proliferating CD4 clone is desirable, UVA is usually the preferred modality over UVB, although Millikan suggests that the relief of pruritus is more predictable with UVB than with UVA.3
Cutaneous Field Stimulation (CFS)
CFS, which electrically stimulates thin afferent fibers, including nocireceptive C-fibers, was reported to inhibit histamine-induced itching. The reduction in itching is accompanied by degeneration of the epidermal nerve fibers. In one open trial, localized itching responded to CFS treatment, and pruritus was reduced by 49% at the end of 5 weeks. Itch relapsed gradually after the discontinuation of CFS, which led the researchers to conclude that nerve fibers regenerated into the epidermis.20
In addition to the nonprescription medications mentioned above, there are other OTC treatments that can be helpful for treating and managing pruritus. Moisturizing after a bath is extremely important, and emollients such as white petrolatum, or petrolatum depositing moisturizing body washes, and in-shower moisturizers (e.g., Olay® Ribbons®, Procter & Gamble; emulsifying ointment USP) can be helpful when applied while the skin is still wet.21
There is new evidence to show that moisturizers containing niacinamide and glycerin (e.g., Olay® Quench®, Procter & Gamble) not only hydrate the skin, but improve the skin’s resistance to external factors and improve the barrier function. Glycerin is required for moisturizers to work quickly and add moisture to the skin, but the niacinamide helps to sustain that benefit over a longer period of time.21
Several alternatives to traditional treatment of pruritus have been proposed. Often these therapies can be used in conjunction with prescribed or OTC medications to relieve symptoms quickly. Compounds that have been found to be effective for pruritus by depressing cutaneous sensory receptors include menthol, camphor, and phenol.7 Some other alternative therapies that have been suggested include herbal remedies, nutritional therapy, reflex therapy, and hydrotherapy.3
Potential Causes of Itch
|Eyes, eyelids||• Allergic blepharitis
• Allergic conjunctivitis
• Atopic dermatitis
• Allergic contact dermatitis
|Nose||• Allergic rhinitis|
|Arm||• Brachioradial pruritus (lateral)
• Xerotic eczema
• Eczematous dermatitis (antecubital)
• Allergic contact dermatitis
|Hands||• Dyshidrotic eczema (pompholyx)
• Allergic contact dermatitis
• Scabies (web spaces)
|Groin||• Tinea cruris
• Allergic contact dermatitis
|Feet||• Tinea pedis
• Eczematous dermatitis
• Allergic contact dermatitis
|Legs||• Xerotic eczema (shin)
• Stasis dermatitis
• Atopic dermatitis (popliteal fossa)
• Lichen simplex (lateral malleolus)
• Dermatitis herpetiformis (knee)
• Seborrheic dermatitis
• Allergic contact dermatitis
|Ear Canal||• Otomycosis
• Otitis externa (early)
• Allergic contact dermatitis
• Seborrheic dermatitis
|Back||• Notalgia paresthetica
|Anus||• Pruritus ani
• Anal fissure
• Condyloma acuminatum
|Table 1: Causes and Location of Pruritus 22|
Several herbs have been proposed as corticosteroid-sparing agents and may provide a viable alternative to topical steroids and their side-effects. Oatmeal baths appear to be most useful because of its colloidal protein and high mucilaginous content. Other herbs have been suggested because of their high mucilage content as well, including flax, fenugreek, English plantain, hearts ease, marshmallow, mulberry, mullein, and slippery elm.3 More extensive research needs to be conducted regarding their possible use and effectiveness for the treatment of pruritus.
Tannins, also derived from herbs, may be helpful as well. The exact mechanism of action is unclear, but may perhaps be related to the coagulation of proteins in the skin. The most common tannin-containing herb is witch hazel, but others include oak bar, English walnut leaf, goldenrod, Labrador tea, lady’s mantel, lavender, and St. John’s wort.
Other possible herbs that may be advantageous include chamomile, which has shown to be equivalent to low concentrations of hydrocortisone, aloe vera, and capsaicin.3 Some side-effects may include irritant or allergic contact dermatitis. Some herbals can be toxic if ingested as well. Some of the oldest group of medications used to soothe and cool pruritic skin is menthol and camphor, which are both considered low risk and safe to use topically. 3,4
Nutritional therapy, despite not being sufficiently researched as a monotherapy for pruritus, may be helpful in combination with other anti-itch treatments. Vitamins D and E, and linolenic acid have shown some efficacy in the treatment of psoriasis and atopic eczema.3
Reflex Therapy, Acupuncture, and Hydrotherapy
While they are not traditionally used, reflex therapy, acupuncture, and hydrotherapy are three treatments that may be beneficial as adjunctive therapy, however further research is needed. There is little research available regarding the effectiveness of reflex therapy and hydrotherapy. These options may be considered in difficult-to-treat patients where traditional approaches have been unsuccessful. Acupuncture is based on the gate theory of neurotransmission, however it is infrequently used in the Western world, and therefore has insufficient evidence to fully support its use. 3
The management of symptoms is paramount in the treatment of pruritus. Patients should be educated regarding the self-care aspects of this condition. Eliminating the use of irritating or tight clothing is recommended, as well as maintaining a cool environment. Patients should avoid the frequent use of soap, topical irritants in clothing, dry environments, and vasodilators such as caffeine, alcohol, and hot water. Patients should be advised to take brief, tepid or lukewarm baths using mild cleansers with a low pH. Soap film should be rinsed off completely and skin should be patted lightly, followed by the generous application of a moisturizing lotion or cream.4,7,22
Pruritus is a common complaint, but one that can often be a challenge to treat. It can be a major quality of life issue for patients, so it is important that both the underlying disease and associated symptoms are treated as quickly and effectively as possible. Health teaching regarding the prevention and management of pruritus should be included in the overall treatment of the cause and symptoms.
- Heymann WR. Itch. J Am Acad Dermatol 54(4):705-6 (2006 Apr).
- DermNet NZ. Pruritus (itch). URL: http://www.dermnetnz.org/systemic/itch.html. Last accessed 2006 Dec 28.
- Millikan LE. Alternative therapy in pruritus. Dermatol Ther 16(2):175-80 (2003).
- Hercogova J. Topical anti-itch therapy. Dermatol Ther 18(4):341-3 (2005 Jul-Aug).
- Drake L, Cohen L, Gillies R, et al. Pharmakinetics of doxepin in subjects with pruritic atopic dermatitis. J Am Acad Dermatol 41(2):209-14 (1999 Aug).
- Berberian BJ, Breneman DL, Drake LA, et al. The addition of topical doxepin to corticosteroid therapy: an improved treatment regimen for atopic dermatitis. Int J Dermatol 38(2):145-8 (1999 Feb).
- Beers MH, Berkow R, editors. The Merck Manual of Diagnosis and Therapy, 17th Ed. New Jersey: John Wiley & Sons (1999).
- Yosipovitch G, Hundley JL. Practical guidelines for relief of itch. Dermatology Nurs 16(4):325-8 (2004 Aug).
- Yosipovitch G, Maibach HI. Effect of topical pramoxine on experimentally induced pruritus in humans. J Am Acad Dermatol 37(2 Pt 1):278-80 (1997 Aug).
- Yosipovitch G, Greaves MW, Schmelz M. Itch. Lancet 361(9358):690-4 (2003 Feb).
- Hanifin JM, Pallor AS, Eichenfield L, et al. Efficacy and safety of tacrolimus ointment treatment for up to 4 years in patients with atopic dermatitis. J Am Acad Dermatol 53(2 Suppl 2):S186-94 (2005 Aug).
- Lubbe J, Friedlander SF, Cribier B, et al. Safety, efficacy, and dosage of 1% pimecrolimus cream for the treatment of atopic dermatitis in daily practice. Am J Clin Dermatol 7(2):121-31 (2006).
- Kawashima M, QOL Research Forum for Patients with Atopic Dermatitis. Quality of life in patients with atopic dermatitis: impact of tacrolimus ointment. Int J Dermatol 45(6):731-6 (2006 Jun).
- Drake L, Prendergast M, Maher R, et al. The impact of tacrolimus ointment on health-related quality of life of adult and pediatric patients with atopic dermatitis. J Am Acad Dermatol 44(1 Suppl):S65-72 (2001 Jan).
- FDA Public Health Advisory: Elidel (pimecrolimus) cream and Protopic (tacrolimus) ointment. URL: http://www.fda.gov/cder/drug/advisory/elidel_protopic.htm. Last accessed 2006 Jan 1.
- Khandelwal M, Malet PF. Pruritis associated with cholestasis: a review of pathogenesis and management. Dig Dis Sci 39(1):1-8 (1994 Jan).
- Wolfhagen, FH, Sternieri E, Hop WC, Vitale G, Bertolotti M, Van Buuren HR. Oral naltrexone treatment for cholestatic pruritus: a double-blind, placebo-controlled study. Gastroenterology 113(4):1264-9 (1997 Oct).
- Terg R, Coronel E, Sorda J, Munoz AE, Findor J. Efficacy and safety of oral naltrexone treatment for pruritus of cholestasis: a crossover, double-blind, placebo-controlled study. J Hepatol 37(6):717-22 (2002 Dec).
- Rivard J, Lim HW. Ultraviolet phototherapy for pruritus. Dermatol Ther 18(4):344-54 (2005 Jul-Aug).
- Wallengren J, Sundler F. Cutaneous field stimulation in the treatment of severe itch. Arch Dermatol 137(10):1323-5 (2001 Oct).
- Vender R. The management of itchy skin. Skin Therapy Lett – Pharm Ed 1(2):1-3 (2006 Sep-Oct).
- Moses S. Pruritus. Am Fam Physician 68(6):1135-42 (2003 Sep).