What causes itching all over the body?

Generalized Pruritus (Itching All Over): Causes and Diagnostic Approach

Itching all over the body without a visible rash requires systematic investigation for underlying systemic disease, with iron deficiency being the single most common treatable cause, followed by chronic kidney disease, liver disease, hematological disorders, and malignancy. 1

Most Common Systemic Causes

Iron Deficiency (Most Common Treatable Cause)

• Iron deficiency anemia accounts for 25% of all generalized pruritus cases with underlying systemic disease and responds rapidly to iron replacement therapy 1
• Iron replacement can lead to complete cessation of pruritus very shortly after starting treatment 1
• Check full blood count and ferritin levels in ALL patients with chronic generalized pruritus 1, 2
• Note that ferritin is an acute-phase protein and may appear falsely normal despite iron deficiency; if suspected, also check serum iron and total iron binding capacity 1
• Consider celiac disease screening (tissue transglutaminase antibodies) in unexplained iron deficiency 1

Chronic Kidney Disease/Uremia

• Affects 42-60% of patients with end-stage renal disease 3
• Check urea and electrolytes in all patients with unexplained generalized pruritus 2
• Secondary hyperparathyroidism commonly accompanies renal failure and may contribute to pruritus 1, 3
• Uremic pruritus typically worsens at night and during summer months 3

Hepatobiliary Disease

• Cholestatic liver disease is a major cause of generalized pruritus 2
• Perform liver function tests in all cases of generalized pruritus without rash 2
• Consider hepatitis A, B, C serology with appropriate risk history 2

Hematological Disorders (2% of cases)

• Polycythemia vera presents characteristically with aquagenic pruritus (intense itching triggered by water contact without skin lesions) 1, 2
• Hodgkin lymphoma causes pruritus with night sweats, fever, weight loss, and lymphadenopathy 1
• Non-Hodgkin lymphoma and myeloma rarely cause pruritus 1
• Check full blood count, blood film, lactate dehydrogenase, and ESR 1, 2
• Consider JAK2 V617F mutation analysis if polycythemia vera suspected 2

Less Common Systemic Causes

Malignancy

• Solid tumors are relatively rare causes of pruritus 1
• Heightened concern for malignancy in patients >60 years with diffuse itch <12 months duration and liver disease history 4
• Pruritus can be paraneoplastic, related to cancer treatment (especially biological therapies), or multifactorial 1
• Investigation should be guided by thorough history and physical examination for specific cancer symptoms (see Table 3 in guidelines) 1

Endocrine/Metabolic Disease

• Thyroid disease association with pruritus is uncommon (only 27% of thyroid patients have pruritus) 1
• Thyroid function tests should only be performed if clinical features suggest thyroid disease 2
• Diabetes may contribute through small fiber neuropathy mechanisms 3

Infectious Causes

• HIV infection can cause generalized pruritus 2
• Consider HIV and hepatitis serology with appropriate travel or risk history 2

Drug-Induced Pruritus

• 12.5% of cutaneous drug reactions present as pruritus without visible rash 5
• Medication review is essential in all cases 5
• Opioids commonly cause pruritus 1

Initial Diagnostic Workup

All patients with chronic generalized pruritus without rash should receive the following screening tests: 2

• Full blood count with differential (screens for anemia, eosinophilia, polycythemia, lymphoma) 1, 2
• Ferritin level (iron deficiency is the most common treatable cause) 1, 2
• Liver function tests (cholestatic disease) 2
• Urea and electrolytes (chronic kidney disease) 2
• Blood film examination (hematologic abnormalities) 5

Additional targeted investigations based on clinical suspicion: 2

• Thyroid function tests (only if clinical features suggest thyroid disease) 2
• Lactate dehydrogenase and ESR (if lymphoma suspected) 1, 5
• JAK2 V617F mutation (if aquagenic pruritus suggests polycythemia vera) 2
• HIV and hepatitis serology (with appropriate risk history) 2
• Calcium, phosphorus, intact PTH (in chronic kidney disease patients) 3

Critical Diagnostic Pitfalls

• Do not perform routine full malignancy screening in the absence of specific clinical indicators; investigation should be guided by history and examination 1
• Ferritin can be falsely elevated as an acute-phase reactant despite true iron deficiency; check serum iron and total iron binding capacity if iron deficiency suspected clinically 1
• Skin biopsy should be considered for persistent unexplained pruritus to rule out early cutaneous lymphoma or small fiber neuropathy, even when skin appears normal 1, 2
• Antihistamines are generally ineffective for systemic causes of pruritus (except urticaria); do not rely on antihistamine response to rule out systemic disease 1, 3

Pruritus of Unknown Origin (GPUO)

• After comprehensive evaluation, approximately 8% of generalized pruritus cases remain unexplained 1, 2
• This diagnosis can only be made after thorough investigation excludes systemic causes 6
• Psychogenic causes should be considered but only after organic causes are ruled out 7