Pruritus (PDQ®): Supportive care - Health Professional Information [NCI]
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This PDQ cancer information summary provides comprehensive, peer-reviewed information for health professionals about the pathophysiology and treatment of pruritus. This summary is reviewed regularly and updated as necessary by the PDQ Supportive and Palliative Care Editorial Board.
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Pruritus (itching) is an unpleasant sensation that elicits the desire to scratch. It is a distressing symptom that can cause discomfort and threaten the effectiveness of the skin as a major protective barrier. Because of the subjective nature of pruritus, the lack of a precise definition, and the lack of suitable animal models, pruritus is a disorder that has not been researched adequately.
The skin accounts for 15% of the body's total weight and is the largest organ of the body. The skin has significant psychosocial and physical functions. Its function as a protective mechanism is the skin's most important role. But skin is also essential to self image and one's ability to touch and be touched, thereby providing an important component of communication.
Symptoms of generalized itching, without rash or skin lesions, may be related to anything from dry skin to an occult carcinoma, and the etiology of the symptoms should be explored. Common nonmalignant etiologic factors include drug reactions, xerosis, scabies, and primary skin diseases. Pruritus is one of the most common complaints of the elderly patient, but estimates of the significance of pruritic symptoms in the elderly population vary from 10% to 50%. The most common diagnosis related to pruritus in this population is simply dry skin.
Generalized pruritus is found in about 13% of all individuals with chronic renal disease and about 70% to 90% of those undergoing hemodialysis for its treatment. Cholestatic liver disease with intrahepatic or posthepatic obstruction, with or without increased serum levels of bile acids, is often associated with pruritus. Other etiologic factors include (but are not limited to) primary biliary cirrhosis, cholestasis related to phenothiazines or oral contraceptives, intrahepatic cholestasis in pregnancy, and posthepatic obstruction.
Etiology / Pathophysiology
Hematologic disorders that cause pruritus include polycythemia vera. Some conditions that cause iron deficiency, including exfoliative skin disorder, also cause pruritus. Diabetes and thyrotoxicosis are endocrine causes of pruritus.
Pruritus is a frequent clinical manifestation of people with AIDS, AIDS-related Kaposi sarcoma, and AIDS-related opportunistic infections. Pruritus with or without rash has been reported in approximately 84% of people with AIDS and 35.5% of those with AIDS-related Kaposi sarcoma. The incidence of pruritus associated with AIDS-related opportunistic infections approaches 100%.
Various malignant diseases are known to produce pruritus. Hodgkin lymphoma causes pruritus in 10% to 25% of patients. In some instances, pruritus precedes diagnosis of the lymphoma  and may be an indicator of a less favorable prognosis when associated with significant fever or weight loss ("B" symptoms). Pruritus associated with Hodgkin lymphoma is characterized by symptoms of burning and intense itching occurring on a localized skin area, frequently on the lower legs. Other lymphomas and leukemias have been associated with a less intense but more generalized pruritus. Adenocarcinomas and squamous cell carcinomas of various organs (i.e., stomach, pancreas, lung, colon, brain, breast, and prostate) sometimes produce generalized pruritus that is more pronounced on the legs, upper trunk, and extensor surfaces of the upper extremities.[1,3] Pruritus associated with malignant diseases has been observed to diminish or disappear with eradication of the tumor and reappear with recurrence of disease.
Drugs associated with secondary pruritus include opium derivatives (cocaine, morphine, butorphanol), phenothiazines, tolbutamide, erythromycin estolate, anabolic hormones, estrogens, progestins, testosterone and subsequent cholestasis, aspirin, quinidine and other antimalarials, biologics such as monoclonal antibodies, and vitamin B complex. Subclinical sensitivity to any drug may be related to pruritus.
Hypothesized mechanisms of pruritus have been inferred from studies of pain, since pain and itching share common molecular and neurophysiological mechanisms. Both itch and pain sensations result from the activation of a network of free nerve endings at the dermal-epidermal junction. Activation may be the result of internal or external thermal, mechanical, chemical, or electrical stimulation. The cutaneous nerve stimulation is activated or mediated by several substances including histamine, vasoactive peptides, enkephalins, substance P (a tachykinin that affects smooth muscle), and prostaglandins. It is believed that nonanatomic factors (such as psychological stress, tolerance, presence and intensity of other sensations and/or distractions) determine itch sensitivity in different regions of the body.
The itch impulse is transmitted along the same neural pathway as pain impulses, i.e., traveling from peripheral nerves to the dorsal horn of the spinal cord, across the cord via the anterior commissure, and ascending along the spinothalamic tract to the laminar nuclei of the contralateral thalamus. Thalamocortical tracts of tertiary neurons are believed to relay the impulse through the integrating reticular activating system of the thalamus to several areas of the cerebral cortex. Factors that are believed to enhance the sensation of itch include dryness of the epidermis and dermis, anoxia of tissues, dilation of the capillaries, irritating stimuli, and psychological responses.[1,3,4,5]
The motor response of scratching follows the perception of itch. Scratching is modulated at the corticothalamic center and is a spinal reflex. After scratching, itching may be relieved for 15 to 25 minutes. The mechanism through which the itch is relieved by scratching is unknown. It is hypothesized that scratching generates sensory impulses that break circuits in the relay areas of the spinal cord. Scratching may actually enhance the sensation of itching, creating a characteristic itch-scratch-itch cycle. Other physical stimuli such as vibration, heat, cold, and ultraviolet radiation diminish itching and increase the release of proteolytic enzymes, potentially eliciting the itch-scratch-itch cycle.
A pinprick near or in the same dermatome as an itchy point will abolish the itch sensation. It is known that hard scratching may substitute pain for the itch, and in some instances, the patient might find pain the more tolerable sensation. It is thought that spinal modulation of afferent stimuli (Gate theory) and central mechanisms may play a role in the relief of itch.
Hypothesized pathogenesis of pruritus associated with underlying disease states are varied. Biliary, hepatic, renal, and malignant diseases are thought to produce pruritus through circulating toxic substances. Histamine released from circulating basophils and the release of leukopeptidase from white blood cells may trigger pruritus associated with lymphomas and leukemias. Elevated blood levels of kininogen in Hodgkin lymphoma, release of histamine or bradykinin precursors from solid tumors, and release of serotonin in carcinoid may all be related to pruritus.[1,6]
People receiving cytotoxic chemotherapy, irradiation, and/or biologic response modifiers for treatment of malignancy are likely to experience pruritus. This same population is quite likely to be exposed to many of the other etiologic factors relating to pruritus ranging from nutritionally related xerosis (dry skin) to radiation desquamation, chemotherapy and biologic agent–induced side effects, antibiotic reactions, and other drug sensitivities.
Each of the major classes of antineoplastic agents (alkylating agents, antimetabolites, antibiotics, plant alkaloids, nitrosoureas, and enzymes) include drugs capable of producing cutaneous reactions including pruritus. Patients receiving antineoplastic drugs frequently report dry skin and scaling, thought to be related to effects on sebaceous and sweat glands.[7,8] Many problems are self-limiting and require no active intervention. Other problems warrant anticipation and implementation of preventive measures.
Hypersensitivity to cytotoxic agents can be manifested by pruritus, edema, urticaria, and erythema. Hypersensitivity reactions vary in symptomatology and depend on the drug, the dosage, and the allergy history of the patient. The agents most associated with hypersensitivities include doxorubicin, daunorubicin, cytarabine, L-asparaginase, paclitaxel, and cisplatin. In most reports, these reactions have been localized to the area of the vascular access and dissipate within 30 to 90 minutes.[9,10] More dramatic and even life-threatening reactions can occur, and the development of pruritus may represent an early stage of serious hypersensitivity reactions.
Radiation therapy–related pruritus is usually associated with dry desquamation of skin within the treatment field. Dryness and pruritus may occur at an accumulated dose of 20 Gy to 28 Gy, and is caused by obliteration of sebaceous glands within the field. This is an acute phenomenon that correlates with the depletion of actively proliferating basal cells in the epidermal layer of the skin, a fixed percentage of which die with each dose fraction of irradiation. Remaining basal cells undergo cornification and shed at an increased rate, while nonproliferating basal cells are stimulated and their cell cycle shortened. Subsequent peeling of the skin is defined as dry desquamation. The skin becomes dry, and the patient may notice itching and burning sensations. Dry skin is susceptible to further injury through scratching and/or formation of fissures, augmenting the risk of infection and tissue necrosis.
If the desquamation process continues, the dermis will eventually be exposed, resulting in moist desquamation. This side effect increases the risk of infection, discomfort, and pain, possibly necessitating interruption of a treatment plan to allow for healing. This interruption can compromise the final outcome of cancer therapy. For this reason, it is desirable to anticipate and prevent the progression of skin reactions to this stage.
External beam therapy with electrons may elicit more skin reactions than photon therapy since the depth of penetration and linear energy transfer is closer to the skin surface with electrons. Radiation delivery techniques (bolus doses and tangential fields) also influence the degree of reaction. Fields that include skin folds (i.e., the axilla, breast, perineum, and gluteus) are anticipated to have increased reactions because of friction, higher moisture content, and low aeration.[14,15]
Therapy combining radiation and chemotherapy plays a significant role in state-of-the-art cancer therapy. The synergism of these cytotoxic modalities enhances normal tissue reaction and can be expected to precipitate higher complication rates. The total combined effects of the drugs and irradiation exceed the individual effects of either modality. Significant cutaneous reactions are thought to occur more frequently when chemotherapy and irradiation are administered concurrently.
Biologic Response Modifiers
Biologic response modifiers used in the treatment of malignant disease are associated with a wide variety of side effects and toxic effects. Pruritus has been a side effect associated with several biologics but has been most reported in patients receiving interferons.[17,18,19,20] Reports of pruritus as a side effect of biologics are primarily anecdotal and have not been a focus of attention.
Bone Marrow Transplantation
Graft-versus-host disease (GVHD) affects 25% to 50% of patients who live longer than 100 days after bone marrow transplantation. The incidence of skin GVHD is reported to be 80% to 90%, and symptoms vary in severity and type. Reported skin changes include dryness and pruritic, erythematous, maculopapular rashes. Onset can be subtle or sudden; skin GVHD can progress to scleroderma and contracture.
Other Pharmacologic Support During Cancer Treatment
Many pharmacologic agents employed at any point during the cancer course, whether in a primary treatment plan or incorporated into a symptom control or supportive care program, are capable of eliciting a pruritic reaction. These drugs include morphine, other opium derivatives, and aspirin used in pain management; corticosteroids; antibiotics; phenothiazines; and, to a lesser degree, hormonal agents (estrogen, progestins, and testosterone). Mechanisms of these reactions range from hypersensitivity to chemical interference with neural pathways.
Pruritus can be a symptom of infection. Pruritus involving anal or vulvar areas might be caused by infections with Trichomonas or fungi, local tumors, hemorrhoids, anal fissures, fistula discharge, wound effluent, or surgical wound drainage.
Pruritus is a symptom, not a diagnosis or disease. Generalized pruritus is a "cardinal symptom of medical significance" and should be taken seriously.
- Location, onset, duration, and intensity of itching.
- Previous history of pruritus.
- Previous history of malignant disease.
- Current malignant disease and treatment.
- Nonmalignant systemic diseases.
- Use of analgesics.
- Use of antibiotics.
- Use of other prescription and nonprescription drugs.
- Presence of infection.
- Nutritional and fluid level status.
- Current skin care practices.
- Existence of other pruritic risk factors.
- Review of relevant laboratory values (complete blood cell chemistry).
- Factors that relieve and aggravate itching.
- Patient's emotional state.
Physical examination will provide data from assessment of the following:
- All skin surfaces for signs of infection.
- All skin surfaces for signs of drug reaction.
- Environmental factors (temperature, humidity).
- Physical factors (tight, constrictive clothing).
- Evidence of scratching (erythema, dryness, excoriation).
- Skin turgor, texture, color, temperature, and lesions.
Management of pruritus associated with neoplastic disease is directed toward effective management of the underlying malignancy, elimination of actual or potential alterations in skin integrity, and promotion of comfort. Given the subjective nature of itching, the extent to which any therapy is effective may be modified by psychological factors. Multiple approaches and combined efforts may be needed to promote comfort and prevent alterations in the integrity of the skin.
|1.||Patient education and minimizing or eliminating provocative factors.|
|2.||Application of topical preparations.|
|4.||Physical treatment modalities.|
Patient Education and Elimination of Provocative Factors
Patients and caregivers must be included in planning care and providing care to the extent possible. Education is an important aspect of symptom control. Skin care regimens incorporate protection from the environment, good cleansing practices, and internal and external hydration. The intensity of the regimen and the techniques employed will vary according to etiologic factors and the degree of distress associated with the pruritus.
Affected individuals (either patients or caregivers) should have a good understanding of factors that promote or aggravate itching. Knowledge of factors that alleviate symptoms provides rationale for the development and implementation of effective and reasonable self-care interventions.
Adequate nutrition is essential to the maintenance of healthy skin. An optimal diet should include a balance of proteins, carbohydrates, fats, vitamins, minerals, and fluids. Daily fluid intake of at least 3,000 cc is suggested as a guideline but may not be possible for some individuals.[4,5]
Aggravating factors should be avoided, including the following:
- Fluid loss secondary to fever, diarrhea, nausea and vomiting, or decreased fluid intake.
- Use of ointments (e.g., petroleum, mineral oil).
- Bathing with hot water.
- Use of soaps that contain detergents.
- Frequent bathing or bathing for longer than ½ hour.
- Adding oil early to a bath.
- Genital deodorants or bubble baths.
- Dry environment.
- Sheets and clothing laundered with detergent.
- Tight restrictive clothing or clothing made of wool, synthetics, or other harsh fabric.
- Emotional stress.
- Use of opium alkaloids, morphine, and antibiotics.
- Underarm deodorants or antiperspirants.
Alleviating factors should be promoted, as follows:
- Basic skin care.
- Application of emollient creams or lotions.
- Use of mild soaps or soaps made for sensitive skin.
- Limiting bathing to ½ hour daily or every other day.
- Adding oil at the end of a bath or adding a colloidal oatmeal treatment early to the bath.
- Use of cornstarch to areas of irradiated skin following bathing.
- Maintenance of a humid environment (e.g., humidifier).
- Use of cotton flannel blankets if needed.
- Washing of sheets, clothing, and undergarments in mild soaps for infant clothing (e.g., Dreft).
- Wearing of loose-fitting clothing and clothing made of cotton or other soft fabrics.
- Use of distraction, relaxation, positive imagery, or cutaneous stimulation.
- Use of antibiotics if pruritus is secondary to infection.
- Use of oral antihistamines, with increased doses at bedtime.
- Use of topical mild corticosteroids (except for pruritus secondary to radiation therapy).
Topical Skin Care
If pruritus is thought to be primarily related to dry skin, interventions to improve skin hydration can be employed. The main source of hydration for skin is moisture from the vasculature of underlying tissues. Water, not lipid, regulates the pliability of the epidermis, providing the rationale for use of emollients. Emollients reduce evaporation by forming occlusive and semiocclusive films over the skin surface, encouraging the production of moisture in the layer of epidermis beneath the film (hence, the term moisturizer).
Knowledge of the ingredients of skin care products is essential, since many ingredients may enhance skin reactions. Three main ingredients of emollients are petrolatum, lanolin, and mineral oil. Both petrolatum and lanolin may cause allergic sensitization in some individuals.
Petrolatum is poorly absorbed by irradiated skin and is not easily removed. A thick layer could produce an undesired bolus effect when applied within a radiation treatment field. Mineral oil is used in combination with petrolatum and lanolin to create creams and lotions and may be an active ingredient in bath oils. Other ingredients added to these products, such as thickeners, opacifiers, preservatives, fragrances, and colorings, may cause allergic skin reactions.
Product selection and recommendations must be made in consideration of each patient's unique needs and should incorporate such variables as the individual's skin, the desired effect, the consistency and texture of the preparation, its cost, and acceptability to the patient. Emollient creams or lotions should be applied at least two or three times daily and after bathing. Recommended emollient creams include Eucerin or Nivea or lotions such as Lubriderm, Alpha Keri, or Nivea. Gels with a local anesthetic (0.5%–2% lidocaine) can be used on some areas, as often as every 2 hours if necessary.
Some topical agents including talcum powders, perfumed powders, bubble baths, and cornstarch can irritate the skin and cause pruritus. Cornstarch has been an acceptable intervention for pruritus associated with dry desquamation related to radiation therapy, but it should not be applied to moist skin surfaces, areas with hair, sebaceous glands, skin folds or areas close to mucosal surfaces, such as the vagina and rectum.[9,10] Glucose is formed when cornstarch is moistened, providing an excellent medium for fungal growth. Agents with metal ions (i.e., talcum and aluminum used in antiperspirants) enhance skin reactions during external beam radiation therapy and should be avoided throughout the course of radiation therapy. Other common ingredients in over-the-counter lotions and creams that may enhance skin reactions include alcohol and menthol. Topical steroids can reduce itching, but they reduce blood flow to the skin, resulting in thinning of the skin and increased susceptibility to injury.
The goal of skin cleansing is to remove dirt and prevent odor, but actual hygienic practices are influenced by skin type, lifestyle, and culture. Extensive bathing aggravates dry skin, and hot baths cause vasodilation, which further promotes itching. Many soaps are salts of fatty acids with an alkali base. Soap is a degreaser and can also irritate skin. Older adults or individuals with dry skin should limit use of soaps to those areas with apocrine glands. Plain water should suffice for other skin surfaces. Mild soaps have less soap or detergent content. Superfatted soaps deposit a film of oil on the skin surface, but there is no proof that they are less drying than other soaps and they may be more expensive.
Tepid baths have an antipruritic effect, possibly resulting from capillary vasoconstriction. The bath should be limited to a half hour every day or every two days. Examples of mild soaps that can be recommended include Dove, Neutrogena, and Basis. Oil can be added to the water at the end of the bath or applied to the skin before towel drying.
Heat increases cutaneous blood flow and may enhance itching. Heat also lowers humidity, and skin loses moisture when the relative humidity is less than 40%. A cool, humid environment may reverse these processes.
Residue left by detergents used in laundering clothes and linens, as well as fabric softeners and antistatic products, may aggravate pruritus. Detergent residue can be neutralized by the addition of vinegar (1 teaspoon per quart of water) to rinse water. Mild laundry soaps marketed for infant items may offer a solution as well.
Loose-fitting, lightweight cotton clothes and cotton bed sheets are suggested. The elimination of heavy bedcovers may alleviate itching by decreasing body heat. Wool and some synthetic fabrics may be irritating. Distraction, music therapy, relaxation, and imagery may be useful to relieve symptoms.
If treatment of the underlying disease and/or control of other aggravating factors provides inadequate relief of pruritus, topical and oral medications may be useful. Topical steroids may provide relief when symptoms are related to a steroid-responsive dermatosis, but anticipated benefits must be weighed against the vasoconstrictive side effects. Topical steroids have no role in the management of pruritus of unknown origin. Topical steroids should not be applied to skin surfaces inside a radiation treatment field.
Systemic medications useful in the management of pruritus include those directed toward the underlying disease or control of symptoms. Antibiotics can reduce symptoms associated with infection. Oral antihistamines may provide symptomatic relief in histamine-related itching. A higher dose of antihistamines at bedtime may produce antipruritic and sedative effects. Diphenhydramine hydrochloride, 25 mg to 50 mg every 6 hours, has demonstrated effectiveness. Hydroxyzine hydrochloride, 25 mg to 50 mg every 6 to 8 hours, or cyproheptadine hydrochloride, 4 mg every 6 to 8 hours, may provide symptomatic relief. Oral chlorpheniramine (4 mg) or hydroxyzine (10 mg or 25 mg) orally every 4 to 6 hours has been used with good results. If one antihistamine is ineffective, one of another class may provide relief.
Sedative or tranquilizing agents may be indicated, especially if relief is not provided by other agents. Antidepressants can have strong antihistamine and antipruritic effects. Diazepam may be useful in some situations to alleviate anxiety and promote rest.
Sequestrant agents may be effective in relieving pruritus associated with renal or hepatic disease through binding and removing pruritogenic substances in the gut and reducing bile salt concentration. Cholestyramine is not always effective and produces gastric side effects.
Aspirin seems to have reduced pruritus in some individuals while increasing pruritus in others. Thrombocytopenic cancer patients should be cautioned against using aspirin. Cimetidine alone or in combination with aspirin has been used with some effectiveness for pruritus associated with Hodgkin lymphoma and polycythemia vera.
Alternatives to scratching for the relief of pruritus can help the patient interrupt the itch-scratch-itch cycle. Application of a cool washcloth or ice over the site may be useful. Firm pressure at the site of itching, at a site contralateral to the site of itching, and at acupressure points may break the neural pathway. Rubbing, pressure, and vibration can be used to relieve itching.[2,12]
There are anecdotal reports of the use of transcutaneous electronic nerve stimulators (TENS) and acupuncture in the management of pruritus. Ultraviolet phototherapy has been used with limited success for pruritus related to uremia.
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Changes to This Summary (08 / 14 / 2008)
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Date Last Modified: 2008-08-14