Pruritus

Pruritus is the medical term for itching of the skin. Pruritus may be generalized or localized, acute, or chronic. Localized pruritus is usually caused by dermatological conditions (e.g., allergic contact dermatitis), whereas generalized pruritus can also have systemic (e.g., uremia, hyperbilirubinemia), neurologic, psychogenic, or mixed causes. The evaluation of pruritus is based on a complete medical history and a detailed skin examination. Treatment of pruritus involves symptomatic relief and management of the underlying disease.

• Poorly understood
• Trigger; , i.e., mechanical, chemical, or thermal stimuli, as well as exposure to certain mediators (e.g., histamine, serotonin, prostaglandins, kinins) → activation of afferent C-fibers in the skin → interpreted by the CNS as pruritus
• Scratching and rubbing the skin → stimulation of inhibitory circuits and pain receptors → decreased pruritus in the short-term (however, in many patients, scratching increases irritation and ultimately worsens itching)
• Gate control theory: Painful input transmitted by A-fibers inhibits the transmission of pruritic input from the C-fibers.

Medical history

• Initiating factors (e.g., contact with specific substances, drug intake, insect bites)
• Location: generalized vs. localized (see below)
• Onset
  • Acute vs. chronic (> 6 weeks)
  • Time of day
  • Season
• Allergies
• Travel and environmental history
• Underlying disorders (e.g., polycythemia vera) and medications (e.g., chloroquine)
• Psychiatric history
• Substance abuse (e.g., opioids, cocaine, and amphetamines)

Physical examination

• Skin examination
  • Goal: Determine whether there are primary skin lesions, secondary skin lesions (e.g., excoriations, lichenification), or no skin lesions at all.
  • If skin lesions are visible, it is necessary to identify:
    • Location (e.g., flexor sides in atopic dermatitis, extensor sides of the joints in psoriasis, scalp in head lice infestation)
    • Type of lesion (e.g., exanthem, papules, pustules, scales, plaques)
    • Secondary changes as a result of scratching
  • Visible skin lesions are not always present.
• General physical examination: to determine the underlying disease (e.g., enlarged lymph nodes in Hodgkin disease, goiter in hyperthyroidism, jaundice in cholestasis)

Further diagnostics

Further evaluation depends on presentation and examination findings.

• Generalized pruritus
  • Primary skin lesions present (likely skin disease): consider skin biopsy (if indicated) or empirical treatment
  • Primary skin lesions absent (likely systemic disease: CBC with differential, liver function tests, renal function tests, TSH, chest radiograph
• Localized pruritus
  • Primary skin lesions present (likely dermatologic condition): further evaluation depends on specific site affected
  • Primary skin lesions absent (likely neuropathic or psychogenic pruritus): psychiatric/neurological evaluation

Pruritus without primary skin lesions should be further investigated, as it may be a sign of a serious underlying condition like malignancy.

• Skin disorders
  • Atopic dermatitis
  • Allergic contact dermatitis
  • Psoriasis vulgaris
  • Urticaria
  • Xerosis cutis
  • Dermatophyte infection
  • Lichen simplex chronicus
  • Scabies
  • Body lice infestation
  • Bullous pemphigoid
• Medical therapy
  • Opioids
  • Antihypertensives
  • Statins
  • NSAIDs
  • Antibiotics
  • Cytostatic agents
  • Chloroquine
• Systemic diseases
  • Chronic kidney disease with uremia (uremic pruritus)
  • HIV infection
  • Cholestasis
  • Hyperthyroidism or hypothyroidism
  • Diabetes mellitus
  • Connective tissue diseases
    • Systemic sclerosis
    • Dermatomyositis
    • Sjogren syndrome
    Hematologic disorders, malignancy
    • Polycythemia vera
    • Leukemias, multiple myeloma, mastocytosis
    • Hodgkin lymphoma
    • Skin cancers (e.g., mycosis fungoides)
    • Neuroendocrine tumor
    • Paraneoplastic syndromes
• Neurologic disorders
  • Polyneuropathy
  • Tabes dorsalis
  • Degeneration/compression of sensory nerve fibers
  • Shingles, postherpetic neuralgia
  • Multiple sclerosis
• Psychiatric disorders
  • Excoriation disorder
  • Substance use disorder
• Miscellaneous: advanced age

The differential diagnoses listed here are not exhaustive.

Secondary pruritus requires treatment of the underlying disease.

• General and symptomatic measures
  • Nonpharmacological: Moisturizers and/or calamine lotion (topical skin moisturizer)
  • Topical application of glucocorticoids, calcineurin inhibitors, capsaicin, antihistamines, and anesthetics
  • Systemic use of:
    • Second-generation H1-antihistamines (e.g., cetirizine, loratadine)
    • Naltrexone or naloxone
    • Antidepressants (e.g., mirtazapine, sertraline, doxepin for chronic pruritus)
    • Gabapentin
    • Thalidomide
  • Phototherapy
• Specific measures
  • Immunosuppressants (e.g., cyclosporine, mycophenolate) for patients with refractory atopic dermatitis
  • Biologic agents (e.g., IL-17A antibodies) for pruritus due to psoriasis