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For further information, see CMDT Part 6-43: Pruritus (Itching)

Key Features

  • Causes of generalized pruritus

    • Dry skin

    • Scabies

    • Atopic dermatitis

    • Insect bites, pediculosis

    • Contact dermatitis, fiberglass dermatitis

    • Drug reactions

    • Urticaria

    • Psoriasis

    • Lichen planus, lichen simplex chronicus

  • Persistent pruritus not explained by cutaneous disease or associated with a primary skin eruption should prompt a staged workup for systemic causes

  • Other causes

    • Endocrine disorders, such as hypothyroidism, hyperthyroidism, or hyperparathyroidism

    • Psychiatric disturbances

    • Lymphoma

    • Leukemia

    • Iron deficiency anemia

    • Certain neurologic disorders

  • Pruritus accompanying a specific skin disease will subside when the skin disease is controlled

  • Pruritus accompanying serious internal disease may not respond to any type of therapy

Clinical Findings

  • Severity of the liver disease may not correlate with the degree of itching

  • Burning or itching involving the face, scalp, and genitalia may be manifestations of primary depression and is treatable with antidepressant drugs


  • Clinical

  • Role of interleukins

    • Increased interleukin-31 (IL-31) signaling through the IL-31 receptor on epithelial cells and keratinocytes is associated with itch, especially in allergic skin disease

    • IL-4 and IL-13 (via binding to the IL-4R) likely lower the itch threshold of sensory neurons

    • Janus kinase signaling (which occurs downstream from the IL-4R) also seems important in the pathophysiology of itch


  • Emollients for dry skin (see Table 6–2)

    • Creams are preferred over lotions

    • Should be generously applied from neck to toe immediately after towel drying and again one more time per day

  • In neuropathic disease, especially in diabetic patients, neurally acting agents may be beneficial

    • Gabapentin (starting at 300 mg orally at around 4 PM and a second dose of 600 mg orally at bedtime)

    • Pregabalin (150 mg orally daily)

  • In refractory cases, the following can be tried:

    • Combinations of antihistamines

    • Sinequan

    • Gabapentin

    • Pregabalin

    • Mirtazapine

    • Opioid antagonists

  • In cancer-associated and other forms of pruritus, aprepitant (Emend) 80 mg orally daily for several days can be dramatically effective

  • Phototherapy with ultraviolet B or PUVA may help the pruritus of uremia in conjunction with hemodialysis and to a lesser degree the pruritus of liver disease

  • In pruritus associated with liver disease, naltrexone and nalmefene have been shown to provide relief

  • In advanced chronic kidney disease, gabapentin or mirtazapine may be effective

  • Crisaborole (a topical phosphodiesterase 4 inhibitor) and dupilumab (an interleukin 4 inhibitor)

    • Approved for the treatment of atopic dermatitis

    • Demonstrate some efficacy in the treatment of itch

  • IL-31 blockade (nemolizumab), IL-4 blockade (dupilumab), and inhibition of the Janus kinase pathway (tofacitinib) appear efficacious in the treatment of chronic pruritus

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