Pruritus

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

Diagnosis

• 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

Treatment

• 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