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Pruritus is usually an unpleasant sensation that elicits a desire to scratch, subjectively quantified by intensity, severity, location, and intractability. It may be proposed that itch is akin to pain, as both are thought to be transmitted from skin to central nervous system (CNS) through nociceptive small-caliber C nerve fibers. Perception of pruritus, much like pain, is greatly altered by psychological and CNS factors, thereby accounting for the great subjective variability between individuals in perceived pruritus from the same pruritogen. 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.
For the purpose of this discussion, a focus will be placed on pruritus in the absence of a primary dermatosis, as is often encountered in patients receiving cancer treatment. However, there may still be significant secondary skin change noted in the form of lichen simplex chronicus, prurigo nodules, linear excoriations, linear petechiae, or superficial erosions in places the patient can reach to scratch (either with fingernails, back scratchers, or makeshift tools).
It is estimated that pruritus is a manifestation of an underlying systemic disease in approximately 10% to 25% of affected individuals. Nondermatologic conditions that can lead to generalized pruritus include the following:
Despite the wide array of diseases that may present with pruritus, a systematic evaluation of the differential using a good history, review of systems, and appropriate blood work will lead to a rational and finite group of etiologies. Then correction of the underlying cause (if possible) and treatment of the pruritus with currently available therapies may ensue.
In this summary, unless otherwise stated, evidence and practice issues as they relate to adults are discussed. The evidence and application to practice related to children may differ significantly from information related to adults. When specific information about the care of children is available, it is summarized under its own heading.
When a primary dermatitis is present, the differential may be narrowed by the history and physical findings, such as with stigmata of atopic dermatitis, psoriasis, scabies, allergic contact dermatitis, or primary cutaneous lymphoma. Biopsy of skin dermatitis may be extraordinarily helpful in this scenario if the etiology is not readily evident from history and physical exam alone. In contrast, Table 1 provides a list of differential diagnoses for when there is little or no primary dermatitis identifiable. Where available, the incidence of pruritus in that condition is given.
As evident from the differential, a solid history and physical are essential for sorting through the possibilities. To corroborate the clinical impression, it is also possible to use a limited number of laboratory and radiological examinations to rule in or rule out many of the possibilities. Refer to the Assessment section of this summary for more information.
Hypothesized mechanisms of pruritus have been inferred from studies of pain because 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 the following:
It is believed that nonanatomic factors (such as psychological stress, tolerance, and 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.[9,10,11,12]
The motor response of scratching follows the perception of itch. Scratching is modulated at the corticothalamic center and is a spinal reflex. Itching may be relieved for 15 to 25 minutes after scratching. 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 carcinoids may all be related to pruritus.[10,13]
People receiving cytotoxic chemotherapy, radiation therapy, 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-induced and biologic agent-induced side effects, antibiotic reactions, and other drug sensitivities. Because many of these therapies lead to decreased cell turnover, skin can become thin, atrophic, and dehydrated. Long-term xerosis may also occur with poor recovery of sweat, sebaceous, and apocrine gland function after a course of cytotoxic therapy.
Pruritus is a symptom, not a diagnosis or disease. Generalized pruritus should be investigated because of its strong medical significance, as outlined above (refer to the Etiology/Pathophysiology section of this summary for more information), particularly if it is interfering with daily activities or sleep, and/or is intractable. Assessment of pruritus must incorporate an accurate and thorough history and physical examination.
The history includes the following data:
Physical examination will provide data from assessment of the following:
First-line studies should include the following:
Second-line laboratory studies guided by review of systems and physical exam may include the following:
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ Editorial Boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
If an underlying cause of pruritus is identified, treatment of the primary disease or correction of the underlying abnormality is primary therapy, when feasible. For example, iron supplementation in the setting of iron-deficiency anemia or thyroid supplementation for hypothyroidism should be initiated first. However, gentle skin techniques as outlined below are indicated, even if they are not expected to completely alleviate the symptoms-they should be considered helpful adjuvant therapies.
Interventions for pruritus can be categorized into four distinct groups:
Prevention and Elimination of Provocative Factors
Patients and caregivers must be included in planning 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.[Level of evidence: IV] The intensity of the regimen and the techniques employed will vary according to etiologic factors and the degree of distress associated with the pruritus.
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 mL is suggested as a guideline but may not be possible for some individuals.[2,3]
Aggravating factors should be avoided, including the following:
Alleviating factors should be promoted, as follows:
Heat increases cutaneous blood flow and may enhance itching. Heat also lowers humidity, and skin loses moisture when the relative humidity falls below 40%. A cool, humid environment may reverse these processes. Extensive bathing aggravates dry skin, and hot baths exacerbate fluid loss by causing vasodilation. The vasodilation results in increased blood flow, which enhances itching. Tepid baths have an antipruritic effect, possibly resulting from capillary vasoconstriction.
The goal of skin cleansing is to remove dirt and prevent odor, but actual hygienic practices are influenced by skin type, lifestyle, and culture. Bathing should be limited to 30 minutes every day or every 2 days.
Many soaps are salts of fatty acids with an alkali base, leading to excessive defatting of the skin lipids and altered skin pH, thus irritating the skin. Older adults or individuals with dry skin should limit use of soaps to areas with apocrine glands. Plain water should suffice for cleaning other skin surfaces. Mild soaps have less soap or detergent content. Soap is a degreaser and can also irritate skin. 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.
Residue left by detergents after bathing or used in laundering clothes and linens, as well as fabric softeners and antistatic products, may aggravate pruritus. Clothing 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 also may offer a solution.
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.
Some topical agents-including cornstarch, talcum powder, perfumed powders, and bubble baths-can irritate the skin and cause pruritus. Cornstarch has been an acceptable intervention for pruritus associated with dry desquamation related to radiation therapy; however, it should not be applied to moist skin surfaces, areas with hair, sebaceous glands, skin folds (intertriginous zones), or areas close to mucosal surfaces, such as the vagina and rectum.[5,6] 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. Talcum-based agents are otherwise preferred over cornstarch-based modalities when needed, particularly for intertriginous zones. Other common ingredients in over-the-counter lotions and creams that may enhance skin reactions include alcohol, topical antibiotics, and topical anesthetics.
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 using emollients. Emollients reduce evaporation by forming occlusive and semi-occlusive films over the skin surface, encouraging the production of moisture in the layer of epidermis beneath the film (hence the term moisturizer).[Level of evidence: IV]
Knowledge about the ingredients in skin care products is essential because many ingredients may enhance skin reactions. The three main ingredients of emollients are as follows:
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 variables such as the individual's skin, the desired effect, the consistency and texture of the preparation, and its cost and acceptability to the patient.[Level of evidence: IV] Emollient creams or lotions should be applied at least two or three times daily and after bathing. Gels with a local anesthetic (0.5%-5% lidocaine) can be used on some small areas (with the caveat that gels are composed of mostly alcohol-based vehicles), as often as every 2 hours if necessary.[Level of evidence: IV]
Over-the-counter products containing menthol, camphor, pramoxine, or capsaicin can be used for certain areas of worst pruritus. These substances soothe, cool, or inhibit itch sensations, thereby raising the threshold for itch perception. Capsaicin-based therapies are more likely to be beneficial in pruritus of neuropathic origin.
If significant skin breakdown from scratching has occurred or there is evidence of impetiginization, the use of dilute bleach baths, as is done for the atopic dermatitis population, may be helpful. A half-cup of plain unscented sodium hypochlorite (bleach) is added to half a tub of tap water for soaking at the beginning of the bath period. If sponge bathing is required, this is equivalent to approximately 5 mL of bleach to 1 gal of water.
Topical steroids can reduce itching, but they reduce blood flow to the skin, resulting in thinning of the skin and increased susceptibility to injury.[Level of evidence: IV] They should therefore be reserved for pruritic skin with associated primary dermatitis or inflammatory etiologies. Some practitioners may formulate their own mixture of dilute steroid-containing moisturizer to serve this purpose by compounding menthol 0.5% and fluocinonide 0.0125% into a Vanicream base (fluocinonide 0.05% 60 g, menthol 480 mg, and Vanicream QSAD 240 g). Topical steroids should not be applied to skin surfaces inside a radiation field during treatment but may be used successfully for postradiation-induced dermatitis after the treatment course has concluded.
For more-severe xerosis or keratoderma, humectants may be indicated. These not only provide an occlusive or semi-occlusive barrier for water, but also chemically exfoliate an excessively cornified layer while drawing dermal fluid into the epidermal compartment. Choices include salicylic acid 6% cream, ammonium lactate 12% cream, or creams and ointments containing urea 10% to 50%.[Level of evidence: IV] These can significantly improve skin pliability and reduce fissuring, but care must be taken that they do not get into fissures because they can cause stinging sensations on open erosions.
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; however, they are not considered useful in pruritus of neuropathic origin. It is believed that the sedative effect of antihistamines adds to their antipruritic efficacy; therefore, a higher dose of antihistamine at bedtime may produce desirable potentiation of the antipruritic effect by also providing this sedative effect. If one antihistamine is ineffective, one from another class may provide relief (see Table 2).
Second-generation antihistamines have several advantages over first-generation antihistamines. Decreased activity on nonhistamine receptors results in fewer adverse effects. Second-generation antihistamines dissociate slowly from histamine receptors, allowing for once-daily dosing. Compared with first-generation antihistamines, second-generation antihistamines produce less central nervous system penetration and therefore less sedation. Given these advantages, using doses of levocetirizine and desloratadine higher than those approved by the U.S. Food and Drug Administration has been suggested to provide relief for some patients with chronic urticarial conditions. However, studies have produced conflicting results with cetirizine.[16,17]
Several alternative medications can be used to alleviate pruritus (see Table 3). Antidepressants can have strong antihistamine and antipruritic effects.[Level of evidence: IV] Tricyclic antidepressants (TCAs) such as doxepin, amitriptyline, nortriptyline, and trimipramine have additional antihistaminic effects, making them of additional benefit in dermatological conditions such as urticaria. However, the generally more-favorable side-effect profile of selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs) has made them the first-line agents in the management of psychogenic pruritus.[Level of evidence: II]
Aspirin seems to have reduced pruritus in some individuals with polycythemia vera, 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.[Level of evidence: III]
Novel agents that may be tried in recalcitrant cases may include gabapentin, pregabalin, and botulinum toxin injection, particularly for neurogenic itch such as post-herpetic neuralgia.[27,28] Aprepitant has been used successfully in the treatment of pruritus by blocking the neurokinin-1 receptor (NKR-1), which is activated by substance P.[Level of evidence: III]
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. Choices include ursodeoxycholic acid and cholestyramine; however, cholestyramine is not always effective and produces gastric side effects. Because of the association of pruritus with opioid receptor agonism, increased catabolism of endogenous opioids using rifampin in uremia may be beneficial. Opioid antagonists such as naloxone, naltrexone, nalmefene, butorphanol, and nalbuphine may also have some benefit, particularly in uremic pruritus.[25,39][Level of evidence: III]
Alternatives to scratching for the relief of pruritus can help the patient interrupt the itch-scratch-itch cycle. Substituting scratching with application of emollients may help reduce skin breakdown. 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.[Level of evidence: IV]; 
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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Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the pathophysiology and treatment of pruritus. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
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PDQ® Supportive and Palliative Care Editorial Board. PDQ Pruritus. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/treatment/side-effects/skin-nail-changes/pruritus-hp-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389231]
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