Management and Treatment of Pruritus

P. Lovell, RN, BScN; R. B. Vender, MD, FRCPC


Skin Therapy Letter. 2007;12(1) 

In This Article

Prescription Medications

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.[8]

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 <2 years of age, and for tacrolimus, only 0.03% b.i.d. should be used in 2-15 year olds. In adults, tacrolimus ointment should be applied to the skin as a 0.03% or 0.1% ointment b.i.d., and discontinued following resolution of symptoms. If symptoms persist beyond 6 weeks, the patient should be re-examined and the diagnosis confirmed.[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]


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