What are the causes of generalized pruritus?

Causes of Generalized Pruritus

Generalized pruritus has multiple systemic causes including iron metabolism disorders, renal disease, liver disease (especially cholestasis), hematological disorders, malignancies, infections, endocrine disorders, neurological conditions, psychological factors, and medication side effects. 1, 2

Classification of Pruritus

Pruritus can be broadly classified into:

1. Pruritus with associated underlying dermatosis
2. Pruritus without underlying dermatosis
   • Secondary pruritus due to underlying systemic disorder
   • Generalized pruritus of unknown origin (GPUO)

Systemic Causes of Generalized Pruritus

Iron Metabolism Disorders

• Iron deficiency: A common and treatable cause of generalized pruritus
  • Accounts for 25% of all patients with pruritus with systemic disease 1
  • May respond rapidly to iron replacement therapy
• Iron overload: Can occur with hemochromatosis or hyperferritinemia 1

Renal Disease

• Uremic pruritus: Associated with chronic kidney disease
• Affects a significant proportion of hemodialysis patients 3

Hepatic Disease

• Cholestasis: Primary mechanism is accumulation of bile acids in tissues 1
• Cholestyramine can be effective by binding bile acids in the intestine, preventing their reabsorption 4

Hematological Disorders

• Polycythemia vera: Often presents with characteristic aquagenic pruritus (triggered by water contact) 1
• Hodgkin lymphoma: May present with pruritus, especially with night sweats, weight loss, and fevers 1
• Other: Non-Hodgkin lymphoma (less common), myeloma (rare) 1

Malignancies

• Solid tumors: Can cause paraneoplastic pruritus
• Lymphoma: Especially Hodgkin lymphoma
• Cancer treatments: Biological therapies and targeted agents can cause pruritus 1

Infections

• HIV
• Hepatitis viruses
• Parasitic infections

Endocrine Disorders

• Thyroid dysfunction: Both hypothyroidism and hyperthyroidism
• Diabetes mellitus

Neurological Disorders

• Small fiber neuropathy
• Central nervous system disorders

Psychological and Emotional Factors

• Depression
• Anxiety
• Functional itch disorder (psychogenic itch) 5

Medication-Induced Pruritus

• Opioids: Common cause in palliative care settings 6
• Antibiotics
• Biological therapies and immunotherapies 1

Other Causes

• Heart failure
• Pregnancy
• Pruritus of elderly skin
• Pruritus of unknown origin (GPUO): Accounts for approximately 8% of all pruritus cases 2

Diagnostic Approach

Essential Investigations

• Complete blood count and ferritin: To evaluate for iron deficiency or hematological disorders 1
• Renal function tests: BUN, creatinine
• Liver function tests: Especially for cholestatic parameters
• Thyroid function tests
• Blood glucose

Additional Investigations Based on Clinical Suspicion

• Blood film, lactate dehydrogenase, ESR: If hematological disorders are suspected 1
• Tissue transglutaminase antibodies: In patients with iron deficiency 1
• Chest X-ray or CT scan: If lymphoma or solid tumors are suspected
• Skin biopsy: In persistent unexplained pruritus to rule out skin lymphoma 1

Common Pitfalls to Avoid

1. Failing to check iron status: Iron deficiency is a common, treatable cause of generalized pruritus 1, 2
2. Overlooking medication review: Many medications can cause pruritus as a side effect 2
3. Missing hematological disorders: Especially polycythemia vera with its characteristic aquagenic pruritus 1, 2
4. Neglecting psychological factors: These can either cause or exacerbate pruritus 3
5. Performing unnecessary malignancy screening: Should be guided by specific symptoms rather than done routinely 2

Generalized pruritus significantly impacts quality of life, with effects comparable to chronic pain 1. A systematic approach to diagnosis is essential to identify treatable underlying causes and provide appropriate symptomatic relief.