How To Detect And Treat Pruritus

   Pruritus is a symptom complex rather than a dermatological condition. It is a very common manifestation of skin diseases described as an itch that makes a person want to scratch. It can be frustrating and cause some patients severe discomfort. Chronic itching can lead to sleeplessness, anxiety, depression and behavioral disorders (especially in young children). Symptoms of pruritus can be a result of skin conditions such as dry skin (xerosis), atopic dermatitis, eczema and contact dermatitis. Pruritus can also present with certain internal disorders or may be due to altered processing of the itch sensation within the nervous system.

   Pruritus is not fully understood and it is considered to be a complex process involving nerves that respond to certain chemicals such as histamine that are released into the skin. The treatment for nonspecific pruritus is directed mostly at preventing dry skin while treatment for disease-specific pruritus is focused on management of the systemic condition as well as the pruritus.

   In regard to pathophysiology, varied mechanical stimuli, such as soft touch, pressure, vibration and contact with irritants such as wool fibers, can produce pruritus. Heat and electrical stimuli may also generate itch sensations. Unspecified free nerve endings in the skin receive the itch sensation. Until recently, the same pathways were thought to transmit both itch and pain. The speculation was that low-intensity stimulation of unmyelinated C-fibers caused an itch and high intensity stimulation of these fibers caused pain. This concept has now been disputed because of the differences [3]in the features of pain and itch, namely that pain produces a withdrawal response and itch produces a desire to rub and scratch.

   Removal of the epidermis and upper dermis abolishes pruritus but not pain. Additionally, morphine relieves pain but makes itching much worse. Itch and pain can also be perceived separately at the same location simultaneously. It is now thought that pruritus and pain are different and independent sensory modalities. However, at this time, a morphologically separate end-organ for pruritus has not been positively recognized.

Understanding The Main Causes Of Pruritus

   Various authors have described several types of itch, including those related to dermatological conditions, systemic disease, direct damage to nerve fibers and psychological disorders. One may further classify pruritus by its three main causes:

   • the predisposing causes, such as genetic and allergic factors, in addition to endogenous and exogenous poisonings;
   • the chance causes due to emotional events and environmental factors such as temperature, humidity and wind; and
   • the determining causes like chemical agents, physical agents, infections and infestations.

   It is essential to differentiate the localized pruritus from the generalized pruritus. One can further separate these conditions into itch-due-to-skin [4] diseases, in which various mediators act on the free nerve endings; itch that is associated with internal diseases; and itch of unknown origin or “idiopathic pruritus.” Note that at any given time, patients may have pruritus caused by more than one of the causes or conditions discussed.

What Causes The Itch-Scratch Cycle?

   The itch-scratch cycle is well known but not well defined. A very simple model shows the process from a primary stimulus that causes the pruritus through the transition to scratching or rubbing, which in turn causes an irritation (inflammation) to the skin and continues the cycle. Understanding the diverse causes of pruritus is essential to managing the condition.

   Localized causes. Certain parts of the body can have a predilection for specific disease processes that may present as localized pruritus. Some of the important examples of localized pruritus are eczematous dermatitis, especially seborrheic and contact, neurodermatitis, psoriasis of the scalp; airborne irritants or allergens and allergic reactions to the makeup of the eyes; irritants and contaminants of the nose; eczema, contact dermatitis, scabies and mite infestation of the hands; gravitational and nummular eczema, asteatosis (winter’s itch), fungal infection and contact dermatitis of the legs and feet.

   General pruritus. Climate plays a key role in overall skin moisture and condition. Low humidity, whether it is due to cold weather or central heating, may make the skin dry and brittle. This allows minor irritants such as soap to penetrate, causing mild inflammation and pruritus. The dry skin (xerosis) of the elderly generally causes itchiness. Excessively dry skin associated with atopic eczema will also lead to pruritus. On the other hand, high humidity can also cause pruritus secondary to sweat retention in some individuals.

   Particulate matter, such as foreign bodies, hair, glass fiber and industrial exposure to powdered particles or fiberglass, can cause intense pruritus. Chemicals and some detergent (brighteners used in certain cleaning powders) may cause pruritic dermatoses. Parasite contact or infestations with scabies or mites of pets can cause marked pruritus.

   Aquagenic pruritus, which one may see with exposure to warm or hot water, may be a precursor symptom of polycythemia vera. Excessive bathing, in [5]contrast, may also cause the skin to become dry and lead to itching.

   Skin diseases. Pruritus is a feature of a wide variety of skin diseases. Generalized pruritus, such as pemphigoid and localized itch, can precede some skin diseases and may be a precursor to herpes infection. For a listing of common skin diseases that cause itching, see “A Guide To Common Skin Diseases That Can Cause Pruritus” below.

What You Should Know About Possible Systemic Causes

   A wide variety of systemic diseases can cause generalized pruritus without diagnostic skin lesions. The frequency of the association of generalized pruritus with significant internal disease is hard to assess but it has been estimated to range from as low as 10 percent to as high as 50 percent.

   Infectious causes (including tropical and intestinal parasites). These causes include rubella, varicella, trichinosis, onchocerciasis, schistosomiasis and fungal infection. Both localized and generalized pruritus have been associated with localized fungal infection.

   Endocrine disease. Diabetes may cause generalized itching but the pruritus is usually localized. Examples include itchiness of the genitalia or perianal area due to candidiasis, and pruritus of the scalp. Many patients with diabetes also complain of localized lower extremity pruritus. Other conditions that may be associated with pruritus include hyperthyroidism, hypothyroidism (due to skin dryness) as well as disorders of the parathyroid gland and carcinoid syndrome.

   Renal disease. Pruritus is common among patients with chronic renal failure. In patients on maintenance dialysis, over 80 percent are affected by itching skin.

   Hematological diseases (including lymphoproliferative disorders). Such diseases include polycythemia vera, in which pruritus may occur after contact with water or after a hot bath. The pruritus after a hot shower is neither sensitive nor specific for polycythemia. It can occur with Hodgkin’s disease, myeloid metaplasia or other disorders not to mention the fact that vasodilatation produced by heat [6]may enhance itchiness of almost any causes. Water induced itching may precede the development of polycythemia vera by many years.

   Iron deficiency has been repeatedly implicated as a cause of intractable pruritus in the absence of visible skin disease or even in the absence of anemia. About 30 percent of patients with Hodgkin’s disease complain of itching skin. Pruritus can be the early or presenting complaint. It can be severe, which may imply a worse prognosis. Excoriations, papules and prurigo nodules from continuous scratching may also be present. Mycosis fungoides, lymphosarcoma, chronic leukemia, myleomatosis, paraproteinemia and mast cell disease have all been reported to have pruritus as a presenting finding.

   Occult malignancy. Hematological and lymphoproliferative disorders show pruritus as an important but uncommon manifestation of carcinomas. Among the tumors reported to present with generalized pruritus, adenocarcinoma and squamous cell carcinoma are most common. Though generalized, the itching may be more marked on the legs and feet, upper trunk and the extensor surfaces of the upper limbs.

   Psychiatric/psychogenic causes. Emotional stress and psychological trauma intensifies all forms of pruritus and neurosis itself may be the cause for pruritus. Delusional parasitosis and hypochondrical psychosis can be causes for a patient’s complaint of pruritus. To make a diagnosis of pruritus, whether it is localized or generalized, as psychogenic or psychiatric in origin, one must exclude cutaneous and systemic causes.

   Drugs or therapy. Pruritus can be a side effect of a wide variety of medications and therapeutic agents. This includes the opium alkaloid, CNS stimulant/depressant, antibiotics (especially penicillin and erythromycin), niacinamide, cimetidine, aspirin, quinidine and chloroquine. Drugs can also cause pruritus via the mechanism of hepatic cholestasis. Subclinical sensitivity to any drug may cause pruritus.

   Other causes include hepatic disease, pregnancy with intrahepatic cholestasis, obstructive jaundice, primary biliary cirrhosis, drug-induced cholestasis such as intrahepatic biliary obstruction due to chlorpromazine, contraceptive pills and [7]testosterone.

Which Topical Treatments Are Effective?

   A topical approach to relieving itch is particularly helpful for pruritus resulting from skin damage or rashes, inflammation, insect bites or dryness. The medications can come in many different forms. The most common are creams, lotions, ointments and gels. The choice often depends on the location of the pruritus and patient preferences.

   Commonly used topical treatments include emollients, low pH cleansers and moisturizers, which restore and preserve the barrier function of skin. There are several additional topical applications that include cooling agents, topical anesthetics, topical antihistamines, capsaicin, topical corticosteroids and topical immunomodulators.

   Topical creams are semisolid emulsions suspended in a water base. They are often white and non-greasy. One should store them in cool places and close containers tightly to prevent evaporation.

   Topical ointments are emulsions of water droplets suspended in oil that do not absorb. They are oil-based and appear greasy and clear. Although they are messy, they provide an occlusive dressing and allow for maximum penetration of the medicine.

   Topical lotions are suspensions of powder in water. They may require shaking before application. After the patient applies the lotion, the water evaporates and leaves a fine powder on the skin. Immediate itch relief occurs as the water evaporates and the skin cools.

   Topical gels are semisolid emulsions, clear and often sticky. Some gels are alcohol-based and may cause dryness.

   Emollients are the first line of therapy for patients with chronic itch. While emollients are generally not considered antipruritics, they can help reduce itch, particularly in patients with xerosis. Xerosis is the most common cause of pruritus without an associated rash and it can be connected to inflammatory skin diseases one sees with normal aging, systemic diseases such as hypothyroidism, as well as with atopic dermatitis. Changes in the barrier function of dry skin, such as stratum corneum abnormalities in surface lipid content, keratinization and water content, may add to the sensation of itchiness. Emollients help return this altered acid mantle function. Water normally evaporates from the skin surface rapidly but emollients contain lipids and other substances that seal in the moisture. Patients should apply emollients right after bathing to promote hydration of the skin by preventing transepidermal water loss.

Pointers On Using Topical Anesthetics, Antihistamines And Corticosteroids

   Topical anesthetics, including pramoxine 1% cream and a eutectic mixture of lidocaine and prilocaine 2.5% cream (EMLA^®, AstraZeneca Pharmaceuticals), have a documented antipruritic effect as does lidocaine 3% (LidaMantle^®, Doak Dermatologics) in an acid mantle cream and lotion. These topical anesthetics are most useful for mild to moderate localized pruritus and one may combine them with coolants to heighten effectiveness.

   Topical antihistamines, which block H1-receptors, are successful as antipruritics, particularly when one utilizes them for localized urticaria and insect bites. Doxepin, a tricyclic antidepressant, is perhaps the most effective topical antihistamine and is available as a 5% cream (Zonalon^®, Doak Dermatologics). It is of benefit in many patients with atopic dermatitis, lichen simplex chronicus and chronic localized pruritus. However, the topical antihistamine is not generally suitable for use in children.

   The patient would apply doxepin three or four times a day to no more than 10 percent of the body surface and would never cover the treated area. On average, the intensity of the itch reduces by about half. Sometimes, the initial benefit is apparent after 15 minutes and typically, there is an increasing benefit during the first week.

   About 15 percent of patients complain initially of localized stinging or burning on application. These symptoms generally decrease in time. Dry mouth can occur in some patients. As with all tricyclic antidepressants, one should discontinue monoamine oxidase inhibitors at least two weeks before starting treatment with topical doxepin. Patients using prescribed doxepin should also avoid the concurrent use of drugs that inhibit cytochrome P450. These drugs include cimetidine, imidazoles, antifungals and macrolide antibiotics.

   Capsaicin is useful in relieving itch associated with many conditions, particularly intractable pruritus at a localized site. It has the potent component of cayenne or red peppers, and acts by desensitizing nerve endings responsible for itch and pain. It may cause localized burning and stinging, which limits its use as an antipruritic. This irritation subsides with repeated use of capsaicin but patients may have [8]difficulty maintaining compliance. If patients initially use capsaicin four times per day to overcome the irritation, then the number of daily applications may decrease. One may use the topical anesthetic, EMLA cream, in conjunction with capsaicin to reduce the initial irritation.

   Topical corticosteroids may indirectly provide relief of itching associated with inflammatory skin diseases such as localized contact dermatitis and atopic dermatitis. However, one should not use these modalities to treat generalized itch. These antiinflammatory agents come in different strengths from mild to potent. As one moves up in the strength of the agent, there is a greater chance the agent will work but there is also a greater risk of side effects.

   When it comes to corticosteroids, it is best to use them to bring an acute condition such as poison ivy or contact dermatitis under control or to treat minor local dermatoses like nummular or localized eczema. The side effects of long-term steroid use include atrophy of the skin, which may lead to skin fragility, telangiectasia, easy bruising and stretch marks.

   Lidocaine 3% and hydrocortisone 0.5% (LidaMantle-HC^®, Doak Dermatologics) in an acid mantle cream or lotion, provide a combination of a local anesthetic and a mild corticosteroid. This mixture is highly effective in treating the pruritus of localized conditions.

   Topical immunomodulators inhibit T-lymphocyte activation. Accordingly, they reduce inflammation and ultimately decrease pruritus. Pimecrolimus cream (Elidel^®, Novartis) and tacrolimus ointment (Protopic^®, Astellas Pharma) preparations significantly reduce inflammation and pruritus in patients with moderate to severe atopic dermatitis with little resultant toxicity. Keep in mind that use of these agents over a wide area commonly causes a burning or stinging sensation on the first one or two applications. The role of these topical immunomodulators as an antipruritic for other pruritic conditions is not clear. One should reserve these for treatment of mild localized pruritus.

Other Topical Options That May Have An Impact

   Low pH cleansers and moisturizers are useful in restoring and maintaining the acidic pH of the skin, which helps to preserve barrier function. The acidic skin surface is important in reducing skin irritation, which ultimately helps to reduce pruritus. Elevated skin surface pH has been noted in xerosis, atopic dermatitis and uremia.

   Cooling agents are traditional, topical antipruritic over-the-counter preparations, which usually contain menthol, camphor or phenol. These substances stimulate the nerve fibers that transmit the sensation of cold, thereby masking the itching sensation. One can add these agents to aqueous cream to make a 1 to 2% compound cream, and the patient can apply the cream topically several times a day. All of the cooling agents are reasonably safe. However, applying large amounts of alcohol-containing preparations can cause stinging and can also irritate the skin.

   Using wet wrap dressings for patients with refractory atopic dermatitis and localized eczema can reduce itching and promote healing. One may apply emollients or corticosteroid dilutions to the affected skin and then cover them with cool, occlusive, wet dressings. Patients may use ice to massage the area of intense pruritus to help bring it under control. The side effects are minimal and this treatment provides one more option for managing this disorder.

   Bathing agents such as rice bran broth, hot water for psoriasis, miscible bath oils or vegetable oils, colloidal oatmeal baths, tar baths and sodium bicarbonate baths can also assist in soothing the sensation of itch. Mild and/or low pH [9]cleansers and moisturizers are recommended. Clinicians should caution patients to avoid cleansers that contain alcohol and apply moisturizers immediately after bathing to keep the moisture from evaporating.

What Oral Options Are Available?

   Antihistamines. The three classes of antihistamines are H1, H2 and H3. Antihistamines of the H1 type can treat urticaria and some types of allergic diseases such as hay fever and allergic rhinitis. The H1 antihistamines fall into three categories including: first-generation (classic, marked sedative and anticholinergic actions; second-generation (low sedation); and third-generation (minimal or no sedation) antihistamines.

   Sedating antihistamines, such as hydroxyzine (Vistaril^®, Pfizer) 25 to 50 mg PO and diphenhydramine (Benadryl^®, Warner Lambert) 25 mg PO, are helpful in breaking the itch-scratch cycle. Patients preferably should take them at bedtime. These medications are helpful for patients whose itching prevents sleep or among patients who scratch during the night due to conditions such as atopic dermatitis and lichen simplex chronicus. Several newer minimally sedating antihistamines have become available including loratadine (Claritin^®, Schering-Plough) 10-mg tablet and cetirizine (Zyrtec^®, Pfizer) 5- to 10-mg tablet. Patients may take both of these during the day or just at night.

   Corticosteroids. Systemic corticosteroids are strong antiinflammatory drugs clinicians may employ to treat acute forms of contact dermatitis, phototoxic/photoallergic dermatitis and atopic dermatitis. On occasion, one may utilize corticosteroids to treat eczema, prescribing them for a short-term period of less than four weeks. The patient would normally take an oral agent such as prednisone with an intermediate duration of action in a single daily dose. In regard to severe dermatoses, one may divide the dose into two to four doses per day for better initial control. The daily dose of prednisone depends on the severity of the disease, the intensity of pruritus and the body weight of the patient. The daily dose may initially range between 40 to 60 mg. If there is a need to reduce corticosteroid effects, methylprednisolone (Medrol®, Pfizer) 2 to 4 mg twice a day may be preferable.

   Intramuscular administration of corticosteroids is also possible for very severe forms of eczema. One should not give long-acting intramuscular agents such as triamcinolone acetonide more often than about four to six times a year. Intravenous administration is usually not necessary in treating pruritus in eczema patients and its use is limited for very severe forms only. Most commonly, oral administration of corticosteroids continues on a maintenance basis after intravenous application.

   Side effects are usually not common in short-term therapy. When they occur, patients may demonstrate gastrointestinal intolerance, weakness, muscle effects, increased appetite, weight gain, mood changes, nervousness, acneform eruptions, increased infections, derailed diabetes and impaired wound healing. Systemic corticosteroid use is contraindicated in patients with active peptic ulcers, active tuberculosis, severe depression or psychosis and known hypersensitivity to an ingredient.

   Tricyclic antidepressants. Tricyclic antidepressants such as doxepin have antihistamine activity in addition to central effects and are useful for chronic, severe pruritic states. It appears that low-dose doxepin (10 to 25 mg PO at bedtime) is a potentially effective and well-tolerated alternative in patients who do not respond to conventional antihistamines. This success may be in part due to the more potent H1- and H2-blocking properties associated with doxepin.

   Sometimes, clinicians successfully prescribe amitriptyline for pruritus, especially when it is of neuropathic origin. Amitriptyline has some antihistamine H1 blocking activity and it may be useful in the treatment of urticaria even when conventional antihistamines have failed. Patients would take a 5- to 10-mg dose at bedtime.

Other Treatments One May Consider For Pruritus

   Dietary lipid supplementation. Diet supplements [10] such as primrose oil (linoleic and alpha-linolenic acids) and fish oil (eicosapentaenoic acid or omega-3 fatty acid) may be helpful in some patients with pruritus secondary to xerosis. However, this supplementation has failed to show any advantage in the treatment of atopic dermatitis.

   Phototherapy. Some conditions may benefit from natural sunlight. These conditions may include atopic dermatitis, nummular eczema, dyshidrotic eczema and hyperkeratotic fissured eczema. However, other conditions such as acute contact dermatitis and seborrhoeic eczema may get worse with exposure to natural sunlight.

   Existing phototherapy is comprised of UVB, UVA, combined UVA/UVB, long-wavelength UVA-1, narrow-band UVB and photochemotherapy with psoralens (PUVA) applied systemically, topically or as a bath. Phototherapy is beneficial in appropriate patients in addition to topical treatment. Therapeutic success depends upon proper selection of the phototherapy for adequate indications.

   Psychological approaches. It has become increasingly clear that psychological factors can affect the course of any physical disease process. Group psychotherapy, support groups and biofeedback help to improve quality of life in different forms of skin diseases such as atopic dermatitis, psoriasis and chronic pruritus.

   Synthetic opioid antagonists. Naloxone (Narcan^®, DuPont) is a specific antipruritic drug that may be useful in treating intractable pruritus. Generally speaking, it is difficult for controlled studies to evaluate therapy for pruritus because of the subjective nature of this complaint. Even though naloxone may be effective in reducing pruritus, there are three major restrictions for long-term use. Naloxone has a short half-life and therefore requires frequent dosing. Naloxone also has a significant first-pass metabolism and patients must take it parenterally as it is not orally bioavailable. Potential tachyphylaxis is possible with long-term treatment.

   How Can Patients Minimize Pruritus?
   • Restrict time in the shower or bathtub.
   • Bathe in cool or lukewarm water rather than hot water, which can be drying.
   • Use mild cleansers.
   • Use low pH cleansers and moisturizers.
   • Avoid cleansers containing alcohol.
   • Rinse soap film off completely and pat the skin lightly to dry.
   • Apply moisturizer immediately after bathing to help retain moisture from the shower/bath.
   • Use a humidifier at home, especially in winter.
   • Wear light and loose clothing.
   • Avoid wearing wool or tight clothing.
   • Keep the home cool.
   • Apply cool moist wraps or ice as needed.
   • Avoid rapid changes in environmental humidity.
   • Avoid hot or spicy foods.
   • Minimize caffeine and alcoholic beverages.

In Conclusion

   Pruritus is a symptom complex rather than a dermatological condition and it can be caused by anything from dry skin to malignancy. Consequently, it is important to look for the underlying problem and treat this condition whenever possible. Maintaining healthy skin may relieve pruritus and good skin care includes adequate nutrition and daily fluid intake, protection from the environment, and cleansing practices that do not dry the skin.

   In addition to the skin care factors, the use of topical or oral medications may be necessary to treat pruritus. Antibiotics or antifungals may relieve itching caused by infection. Antihistamines, sedatives, tranquilizers and antidepressants may be useful in some cases of pruritus. Aspirin seems to facilitate reduced itching in a few patients but increases itching for others. Combining aspirin with cimetidine may be effective for patients with Hodgkin’s disease or polycythemia vera.

   Interrupting the itch-scratch-itch cycle at any point along the cycle may also help to alleviate pruritus. The cycle may break when one applies a cool washcloth or ice over the affected area. Rubbing the skin gently and applying acupressure or electrical vibration to the skin may also help. Other methods that may be useful in relieving symptoms include distraction, music therapy, relaxation and imagery techniques. As with other conditions, it may take a combination of several different techniques to control pruritus effectively in some patients.

Dr. Dockery is a Fellow of the American College of Foot and Ankle Surgeons. He is a Fellow of the American Society of Podiatric Dermatology and a Fellow of the American College of Foot and Ankle Pediatrics. He is board certified by the American Board of Podiatric Surgery. Dr. Dockery is the author of Cutaneous Disorders of the Lower Extremity (Saunders, 1997). He is the Chairman of the Board and Director of Scientific Affairs of Northwest Podiatric Foundation for Education and Research, USA in Seattle.

Editor’s note: For related articles, see “How To Identify And Treat Pruritic Conditions In Athletes” in the April 2005 issue of Podiatry Today or check out the archives at www.podiatrytoday.com [11].

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