(edited from the skintherapyletter.com article: Management and Treatment of Pruritus)



Pruritus, commonly known as “itch”, is a sensation that gives a person the desire or reflex to scratch. It’s estimated that one-fifth of the population is thought to suffer from some form of itch at any given moment.


Pruritus commonly occurs with skin disorders such as atopic dermatitis (eczema), contact dermatitis, psoriasis, dandruff and folliculitis. Chemicals in the body such as histamine and serotonin have been found to cause the itch sensation. It can also be caused by cold and dry weather, especially during the winter months.


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The intensity of pruritus ranges from mild to severe, and can have a significant impact on an individual, by interfering with their sleep and daily activities.


For most people, simply scratching will provide instant relief. However, some cases of pruritus may be more intense and long lasting. Treatment 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 article will review the vast array of management and treatment options for severe and chronic pruritus.


Treatment


Prevention

The most effective way to prevent pruritus is through good skin care. The following tips may help:


• Use gentle cleansers and moisturizers to hydrate the skin and prevent dryness.

• Avoid washing or bathing with hot water, as this can irritate and strip the skin of it’s natural oils. Take a bath with warm water

• Use soaps with a low ph and laundry detergents that are mild or formulated for sensitive skin.

• Avoid tight fitting clothing and fabrics such as wool and synthetics can help reduce skin irritation. Opt for softer garments made from cotton.

• Maintaining a cool environment can help the skin from drying out. The use of a humidifier at home is recommended.


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Antihistamines

Itching occurs when histamine in the body is released, causing redness, swelling, warmth, and consequently itchiness. Antihistamines act by blocking the histamines, and are the most widely used medications for this condition. On average, they take about 15–30 minutes to work 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 preparation that has both anti-itching and anesthetic properties. This traditional therapy carries with it a small risk of contact dermatitis and allergic sensitization.3


Doxepin is a very active antihistamine that can be used for eczema and also has a useful psychotherapeutic effect for individuals suffering from pruritus. It acts by hindering sensory receptors in the skin, which decreases the “itching sensation” that is felt.4 Some side-effects of this medication include drowsiness and localized burning or stinging, which are usually passing. Findings in a placebo-controlled, double-blind trial have confirmed the effectiveness of doxepin in the relief of pruritus caused by eczema.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 eczema.6


Systemic antihistamines are effective in treating some, but not all causes of pruritus, for example, their role in treating eczema is limited. They can provide some level of sedation, which may assist sleep, but may also carry with it the adverse effects of unwanted drowsiness and other effects 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


Corticosteroids

Corticosteroid medications are effective for 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 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 every other morning may help to reduce side-effects.4


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Local Anesthetics

Topical anesthetics work by directly interfering with the transmission of impulses along the sensory nerve fibers or by inhibiting sensory receptors. Those drugs that interfere with transmission include benzocaine, diperodon, and lidocaine.7


Pramoxine, another topical anesthetic, has a documented anti-itch 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 anti-itch properties to the desensitization of the nerve endings responsible for transmitting the itch sensation. However, it may cause localized burning and stinging which can limit its use. This irritation will subside with repeated use of the medication if the patient chooses to overcome the initial irritations.8


Calcineurin Inhibitors

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. They are second-line therapies indicated for short-term and non-continuous chronic treatment of mild-to-moderate eczema 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 medication typically used in the treatment of eczema. It works by suppressing the cells (T-cells, Mast cells) that cause itching. 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 eczema in approximately two-thirds of patients.12


Tacrolimus is in a class of medications called immunosupressants. It works by decreasing the activity of the immune system to prevent it from attacking the body’s own tissue. 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 eczema.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 eczema.


Rifampicin

Rifampicin is an antibiotic that has also been shown to improve pruritus. In one study, pruritus disappeared in 11 of 14 subjects receiving daily doses of rifampicin. 16


Naltrexone

Naltrexone 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. In this study, five of eight patients treated had considerably less itching.17 In another study, nine out of 20 patients receiving naltrexone had more than 50% improvement of pruritus. Side-effects in this study, including dizziness, nausea, vomiting, headache, drowsiness, dry mouth, and cramps, were passing symtpoms and did not require specific treatment.18


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Ultraviolet (UV) Light Therapy

UV phototherapy is used to treat various pruritic conditions including chronic renal failure; eczema; HIV; solar urticaria; Hodgkin’s lymphoma; and chronic liver disease amongst 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 are often a discouraging factor for patients. Erythema (skin disorder that causes redness and rash) is common in UVB, as is premature skin aging and the development of certain skin cancers with both UVA and UVB. Side-effects associated with PUVA include redness, burning, headache, and nausea.16,19


Cutaneous Field Stimulation (CFS)

CFS, which electrically stimulates thin nerve fibers, was reported to reduce 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


Over-the-Counter Treatments


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


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Alternative Therapies


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 include menthol, camphor, and phenol.7 Some other alternative therapies that have been suggested include herbal remedies, nutritional therapy, reflex therapy, and hydrotherapy.3


Herbal Remedies

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


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

Nutritional therapy 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

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


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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 some people, 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.


References:

1. Heymann WR. Itch. J Am Acad Dermatol 54(4):705-6 (2006 Apr).

2. DermNet NZ. Pruritus (itch). URL: http://www.dermnetnz.org/systemic/itch.html. Last accessed 2006 Dec 28.

3. Millikan LE. Alternative therapy in pruritus. Dermatol Ther 16(2):175-80 (2003).

4.  Hercogova J. Topical anti-itch therapy. Dermatol Ther 18(4):341-3 (2005 Jul-Aug).

5. 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).

6. 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).

7. Beers MH, Berkow R, editors. The Merck Manual of Diagnosis and Therapy, 17th Ed. New Jersey: John Wiley & Sons (1999).

8. Yosipovitch G, Hundley JL. Practical guidelines for relief of itch. Dermatology Nurs 16(4):325-8 (2004 Aug).

9. 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).

10. Yosipovitch G, Greaves MW, Schmelz M. Itch. Lancet 361(9358):690-4 (2003 Feb).

11. 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).

12. 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).

13. 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).

14. 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).

15.  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.

16. Khandelwal M, Malet PF. Pruritis associated with cholestasis: a review of pathogenesis and management. Dig Dis Sci 39(1):1-8 (1994 Jan).

17. 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).

18.  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).

19. Rivard J, Lim HW. Ultraviolet phototherapy for pruritus. Dermatol Ther 18(4):344-54 (2005 Jul-Aug).

20. Wallengren J, Sundler F. Cutaneous field stimulation in the treatment of severe itch. Arch Dermatol 137(10):1323-5 (2001 Oct).

21.  Vender R. The management of itchy skin. Skin Therapy Lett – Pharm Ed 1(2):1-3 (2006 Sep-Oct).

22.  Moses S. Pruritus. Am Fam Physician 68(6):1135-42 (2003 Sep).





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