What are the causes, diagnosis, and management of pruritus?

Pruritus: Causes, Diagnosis, and Management

Generalized pruritus requires thorough investigation for underlying systemic causes, with initial management including emollients and nonsedating antihistamines, followed by targeted therapies based on the identified etiology. 1

Causes of Pruritus

Pruritus can be categorized based on etiology:

Dermatological Causes (60% of cases) 2

• Inflammatory skin conditions: eczema, psoriasis, seborrheic dermatitis
• Dry skin (xerosis), particularly common in the elderly
• Asteatotic eczema

Systemic Causes (15-30% of cases) 1, 3, 2

• Hematological disorders:

  • Iron deficiency (accounts for 25% of systemic pruritus cases) 3
  • Polycythemia vera (may present with aquagenic pruritus)
  • Lymphoma (particularly Hodgkin's)

• Metabolic and endocrine disorders:

  • Chronic kidney disease (uremic pruritus)
  • Liver disease (cholestatic pruritus)
  • Thyroid dysfunction
  • Diabetes mellitus

• Other systemic causes:

  • HIV and hepatitis infections
  • Parasitic infections
  • Small fiber neuropathy
  • Malignancy

Neuropathic Causes (25% of cases) 2

• Postherpetic neuralgia
• Notalgia paresthetica
• Nerve dysregulation (localized or generalized)

Drug-Induced Pruritus 3

• Opioids
• Antibiotics
• Biological therapies and immunotherapies

Generalized Pruritus of Unknown Origin (GPUO)

• Accounts for approximately 8% of all pruritus cases 3

Diagnostic Approach

Initial Assessment

1. Thorough history:

   • Duration and pattern of pruritus
   • Exacerbating and relieving factors
   • Associated symptoms (weight loss, night sweats, fever)
   • Medication review
   • Water-induced symptoms (suggestive of polycythemia vera)

2. Complete physical examination:

   • Examine for primary skin lesions
   • Check for lymphadenopathy or masses
   • Evaluate for signs of systemic disease

Laboratory Investigations 1, 3, 4

• First-line tests:

  • Complete blood count with differential
  • Blood film examination
  • Ferritin (to assess iron status)
  • Renal function tests
  • Liver function tests
  • Thyroid function tests
  • Lactate dehydrogenase and ESR

• Additional tests based on clinical suspicion:

  • Tissue transglutaminase antibodies (if iron deficiency present)
  • JAK2 V617F mutation (if polycythemia vera suspected)
  • HIV screening
  • Hepatitis serology
  • Chest radiography
  • Immunoglobulins and urinary paraproteins

Specialized Testing

• Skin biopsy: Consider in persistent unexplained pruritus to rule out skin lymphoma 1
• Indirect immunofluorescence: Consider in elderly patients to rule out bullous pemphigoid 1

Management

General Measures 1, 2

• Self-care advice:

  • Keep nails short to prevent excoriation
  • Avoid hot water and harsh soaps
  • Limit bathing time
  • Wear loose cotton clothing

• Topical treatments:

  • Emollients (moisturizers with high lipid content preferred in elderly)
  • Menthol, phenol, or pramoxine for symptomatic relief

First-Line Pharmacological Treatment 1, 2

• Nonsedating antihistamines: Short course for GPUO (avoid sedating antihistamines in elderly)
• Topical corticosteroids: For inflammatory causes and asteatotic eczema (2-week trial)

Treatment Based on Specific Etiology

Hematological Causes 1, 3

• Iron deficiency: Iron replacement therapy

• Polycythemia vera:

  • Aspirin 300 mg daily
  • Ruxolitinib (JAK1/JAK2 inhibitor)
  • Sodium bicarbonate baths
  • Consider interferon alpha therapy

• Lymphoma:

  • Curative treatment of the lymphoma
  • Symptomatic relief with cimetidine, gabapentin, carbamazepine, or mirtazapine
  • High-dose oral corticosteroids for palliation

Cholestatic Pruritus 5

• Cholestyramine resin: Forms insoluble complex with bile acids
• Other options: Rifampicin, naltrexone, sertraline

Uremic Pruritus 1

• UVB phototherapy
• Gabapentin
• Acupuncture (limited evidence)

Neuropathic Pruritus 2

• Topical agents: Menthol, pramoxine, lidocaine
• Systemic medications:
  • Gabapentin
  • Antidepressants (sertraline, doxepin)
  • Opioid receptor modulators (naltrexone, butorphanol)

Elderly Patients 1

• Emollients and topical steroids for 2 weeks initially
• Gabapentin if initial treatment fails
• Avoid sedating antihistamines

Refractory Cases

• Referral criteria 1:

  • Diagnostic uncertainty
  • Failure to respond to primary care management
  • Significant distress despite treatment

• Advanced therapies 2:

  • Systemic immunomodulators (methotrexate)
  • Biologics (dupilumab)
  • Consider dermatology referral

Common Pitfalls to Avoid

1. Failing to check iron status - Iron deficiency accounts for 25% of systemic pruritus 3
2. Overlooking medication review - Many drugs can cause or exacerbate pruritus 3
3. Performing unnecessary malignancy screening without specific symptoms 3
4. Using sedating antihistamines in elderly patients - Can cause confusion and falls 1
5. Not following up patients with GPUO - Underlying systemic cause may not be initially evident 1

By following this structured approach to diagnosis and management, pruritus can be effectively addressed to improve patient quality of life and reduce morbidity associated with chronic itching.