Pruritus

Pruritus, or itching, is a common symptom that can arise from a broad spectrum of dermatologic and systemic conditions. Pruritus may be localized or generalized and can occur with or without primary skin lesions. Evaluation is guided by a focused history and physical examination, with laboratory testing used to assess for potential systemic etiologies. Management focuses on identifying and treating the underlying cause while providing symptomatic relief. The therapeutic approach is guided by clinical findings, with topical therapies commonly used for inflammatory or localized neuropathic causes, and systemic agents (such as gabapentinoids or immunosuppressants) considered for generalized or unclear etiologies.

The cause of pruritus is often multifactorial.

Dermatologic causes ^[1][2]

• Inflammatory ^[3]
  • Atopic dermatitis
  • Allergic contact dermatitis
  • Urticaria
  • Xerosis cutis ^[3]
  • Bullous pemphigoid
  • Lichen simplex chronicus
  • Psoriasis
  • Dermatitis herpetiformis
  • Sunburn
• Infectious
  • Scabies
  • Dermatophytoses
  • Pediculosis
  • Folliculitis
• Neoplastic (e.g., cutaneous T-cell lymphoma)

Nondermatologic causes ^[1][2]

Systemic

• Endocrine
  • Diabetes mellitus
  • Thyroid disorders
• Hepatic
  • Cholestasis
  • Primary biliary cholangitis
  • Viral hepatitis (e.g., hepatitis C)
• Hematologic
  • Polycythemia vera
  • Mastocytosis
  • Iron deficiency anemia
  • Hemochromatosis
• Renal: chronic kidney disease-associated pruritus
• Rheumatic
  • Dermatomyositis
  • Sjogren syndrome
• Neoplastic
  • Leukemia
  • Lymphoma
  • Multiple myeloma
  • Paraneoplastic syndromes due to solid tumors (e.g., prostate cancer, colorectal cancer)
• Infections
  • HIV infection
  • Herpes zoster
  • Parasitic infection (e.g., ascariasis, giardiasis, schistosomiasis, helminthiasis)
• Pregnancy-related
  • Pruritus gravidarum
  • Intrahepatic cholestasis of pregnancy
  • Pemphigoid gestationis
  • Polymorphic eruption of pregnancy
• Medication-induced
  • Opioids
  • Antihypertensives (e.g., ACE inhibitors, hydrochlorothiazide)
  • Statins (simvastatin)
  • Nonsteroidal anti-inflammatory drugs
  • Antibiotics (e.g., penicillins, trimethoprim/sulfamethoxazole)
  • Cytostatic agents (e.g., paclitaxel, tamoxifen)
  • Antimalarial drugs (chloroquine)
  • Amiodarone
  • Allopurinol
  • Granulocyte-macrophage colony-stimulating factor
  • Interleukin-2 agonists (aldesleukin)
  • Hydroxyethyl starch
  • Exogenous estrogens (e.g., hormone replacement therapy, transgender hormone treatment)

Neurologic

• Multiple sclerosis
• Polyneuropathy
• Brain abscess
• Stroke
• Postherpetic neuralgia
• Notalgia paresthetica

Psychiatric

• Mood disorders (e.g., depression, anxiety)
• Obsessive-compulsive disorder
• Excoriation disorder
• Substance use disorder
• Psychogenic pruritus

• 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.

Focused history ^[2]

• Duration
  • Acute (e.g., sunburn, allergic contact dermatitis)
  • Chronic (> 6 weeks), e.g., psoriasis, atopic dermatitis
• Onset
  • Time of day: Pruritus associated with scabies is more severe at night. ^[4]
  • Season: Xerosis is often worse during the winter.
• Location
  • Generalized distribution suggests a systemic cause.
  • Localized distribution suggests a dermatologic or neuropathic cause.
• Presence or absence of skin lesions: Absence of lesions suggests a systemic rather than dermatologic cause.
• Triggers: : initiating factors such as contact allergens, insect bites, new medications, water exposure in polycythemia vera
• Symptoms suggestive of systemic cause, e.g.:
  • Symptoms of CKD
  • Constitutional symptoms in lymphoma
• Psychiatric history (including substance use)
• Travel and environmental history: may suggest infestation (e.g., scabies, lice).
• Family history of skin disorders (e.g., atopy)

Focused physical examination ^[2]

• Skin examination: examination of scalp, nails, and anogenital area to assess
  • Primary skin lesion
  • Location: flexor surfaces in atopic dermatitis, extensor surfaces in psoriasis, interdigital spaces in scabies
  • Changes as a result of scratching (secondary skin lesions)
• General examination: for signs of systemic disease (e.g., goiter in hyperthyroidism, jaundice in cholestasis)
• Neurological examination: focused examination of sensation for signs of peripheral neuropathy

Approach ^[2][3]

Diagnostic evaluation depends on presentation and examination findings (e.g., presence or absence of primary skin lesions).

• If primary lesions are present and suggest an underlying diagnosis, proceed to empiric treatment.
• If primary lesions are absent, perform initial studies such as blood tests or imaging to help identify a systemic cause.
• Obtain additional studies (e.g., skin biopsy) if initial studies are inconclusive.
• If diagnosis remains unclear, consider specialist referral (e.g., dermatology or other specialist based on the suspected cause).

Generalized pruritus without primary skin lesions strongly suggests a systemic cause and warrants prompt evaluation for underlying medical conditions, including malignancy. ^[2]

Initial studies ^[2][3]

• Blood tests
  • CBC with differential: abnormal in hematologic or malignant disease, e.g., polycythemia vera, hemochromatosis, lymphoma
  • Liver chemistries: elevated in cholestatic pruritus
  • BMP: elevated in CKD-associated pruritus
  • TSH levels can be elevated or decreased, as pruritus is associated with both hyperthyroidism and hypothyroidism.
  • Diagnostic studies for iron deficiency anemia
  • HbA1c: to identify pruritus associated with dermatophyte infections or diabetic neuropathy
  • HIV serology ^[5]
  • ESR may be elevated in systemic inflammatory conditions or malignancy.
• Imaging: chest x-ray to evaluate for malignancy

Additional studies ^[2]

If the diagnosis remains unclear after initial evaluation, further testing may be considered, often in consultation with a dermatologist.

• Skin biopsy: to evaluate for inflammatory, autoimmune, or neoplastic conditions
• Skin scrapings (e.g., KOH test): to evaluate for superficial fungal infections
• Culture: to identify bacterial, fungal, or atypical infections

Dermatological causes of pruritus

Systemic causes of pruritus

Management involves treating the underlying cause and tailoring systemic or local therapies to clinical findings. ^[3]

• General measures ^[2]
  • Dry skin regimens (e.g., moisturizing ointments or emollients)
  • Cool temperatures or wraps
  • Brief, lukewarm showers and baths
• Rash present and cause identified
  • Inflammatory pruritus (e.g., atopic dermatitis, allergic contact dermatitis)
    • Topical glucocorticoids (e.g., hydrocortisone, triamcinolone)
    • Topical calcineurin inhibitors (e.g., tacrolimus, pimecrolimus)
    • Topical biologics: ruxolitinib
  • Infective pruritus: anti-infective medications (e.g., scabicidal agents for scabies)
• Rash absent and systemic cause identified: Treat the systemic cause.
• Rash absent and no systemic cause identified
  • Neuropathic pruritus
    • Localized: topical agents (e.g., capsaicin, topical anesthetics)
    • Generalized: gabapentinoids, antidepressants (e.g., sertraline), opioid receptor antagonists (e.g., naltrexone)
  • Inflammatory or mixed etiology pruritus
    • Localized: topical agents (e.g., topical glucocorticoids)
    • Generalized: biologic agents, phototherapy, systemic immunosuppressants (e.g., oral corticosteroids)