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Pruritus (PDQ®)

Health Professional Version

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.[1]

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%.[2]

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 [1] and may be an indicator of a less favorable prognosis when associated with significant fever or weight loss (“B” symptoms).[3] 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.[3]

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.[3]

Hypothesized mechanisms of pruritus have been inferred from studies of pain, since pain and itching share common molecular and neurophysiological mechanisms.[4] 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.[1,3-5]

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.[3] 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.[3]

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.

Cytotoxic Chemotherapy

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.[11]

Radiation Therapy

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,[12] 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.[12] 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.[13]

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]

Combination Therapy

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.[7] 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.[16]

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.[17-20] 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.[21] Reported skin changes include dryness and pruritic, erythematous, maculopapular rashes. Onset can be subtle or sudden; skin GVHD can progress to scleroderma and contracture.[22]

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).[3] Mechanisms of these reactions range from hypersensitivity to chemical interference with neural pathways.[4]

Infection

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.

References

  1. Abel EA, Farber EM: Malignant cutaneous tumors. In: Rubenstein E, Federman DD, eds.: Scientific American Medicine. New York: Scientific American, Inc, Chapter 2: Dermatology, Section XII, 1-20, 1992.
  2. Dangel RB: Pruritus and cancer. Oncol Nurs Forum 13 (1): 17-21, 1986 Jan-Feb. [PUBMED Abstract]
  3. Bernhard JD: Clinical aspects of pruritus. In: Fitzpatrick TB, Eisen AZ, Wolff K, et al., eds.: Dermatology in General Medicine. 3rd ed. New York, NY: McGraw-Hill, 1987, Chapter 7, pp 78-90.
  4. Greaves MW: Pathophysiology of pruritus. In: Fitzpatrick TB, Eisen AZ, Wolff K, et al., eds.: Dermatology in General Medicine. 3rd ed. New York, NY: McGraw-Hill, 1987, Chapter 7, pp 74-78.
  5. Duncan WC, Fenske NA: Cutaneous signs of internal disease in the elderly. Geriatrics 45 (8): 24-30, 1990. [PUBMED Abstract]
  6. Abel EA, Farber EM: Drug eruptions and urticaria. In: Rubenstein E, Federman DD, eds.: Scientific American Medicine. New York: Scientific American, Inc, Chapter 2: Dermatology, Section VI, 1-11, 1990.
  7. Dunagin WG: Clinical toxicity of chemotherapeutic agents: dermatologic toxicity. Semin Oncol 9 (1): 14-22, 1982. [PUBMED Abstract]
  8. Hood AF: Cutaneous side effects of cancer chemotherapy. Med Clin North Am 70 (1): 187-209, 1986. [PUBMED Abstract]
  9. Gullo SM: Adriamycin extravasation versus flare. Oncol Nurs Forum 7 (4): 7, 1980.
  10. Barlock AL, Howser DM, Hubbard SM: Nursing management of adriamycin extravasation. Am J Nurs 79 (1): 94-6, 1979. [PUBMED Abstract]
  11. Weiss RB: Hypersensitivity reactions to cancer chemotherapy. In: Perry MC, Yarbro JW, eds.: Clinical Oncology Monographs: Toxicity of Chemotherapy. Orlando, Fla: Grune and Stratton, Inc., 1984, pp 101-123.
  12. Hassey KM, Rose CM: Altered skin integrity in patients receiving radiation therapy. Oncol Nurs Forum 9 (4): 44-50, 1982 Fall. [PUBMED Abstract]
  13. Miaskowski C: Potential and actual impairments in skin integrity related to cancer and cancer treatment. Top Clin Nurs 5 (2): 64-71, 1983. [PUBMED Abstract]
  14. O'Rourke ME: Enhanced cutaneous effects in combined modality therapy. Oncol Nurs Forum 14 (6): 31-5, 1987 Nov-Dec. [PUBMED Abstract]
  15. Hassey KM: Skin care for patients receiving radiation therapy for rectal cancer. J Enterostomal Ther 14 (5): 197-200, 1987 Sep-Oct. [PUBMED Abstract]
  16. Phillips TL, Fu KK: Quantification of combined radiation therapy and chemotherapy effects on critical normal tissues. Cancer 37 (2 Suppl): 1186-1200, 1976. [PUBMED Abstract]
  17. Mayer DK, Smalley RV: Interferon: current status. Oncol Nurs Forum 10 (4): 14-9, 1983 Fall. [PUBMED Abstract]
  18. Krown SE: Interferons and interferon inducers in cancer treatment. Semin Oncol 13 (2): 207-17, 1986. [PUBMED Abstract]
  19. Spiegel RJ: Intron A (interferon alfa-2b): clinical overview and future directions. Semin Oncol 13 (3 Suppl 2): 89-101, 1986. [PUBMED Abstract]
  20. Irwin MM: Patients receiving biological response modifiers: overview of nursing care. Oncol Nurs Forum 14 (6 Suppl): 32-7, 1987 Nov-Dec. [PUBMED Abstract]
  21. Sullivan KM, Deeg HJ, Sanders JE, et al.: Late complications after marrow transplantation. Semin Hematol 21 (1): 53-63, 1984. [PUBMED Abstract]
  22. Nims JW, Strom S: Late complications of bone marrow transplant recipients: nursing care issues. Semin Oncol Nurs 4 (1): 47-54, 1988. [PUBMED Abstract]
  • Updated: June 30, 2011