What systemic diseases can cause pruritus?

Systemic Diseases That Cause Pruritus

The most common systemic causes of pruritus are iron deficiency (accounting for 25% of systemic pruritus cases), chronic kidney disease, cholestatic liver disease, and polycythemia vera, which should be investigated first in any patient presenting with generalized itching without a primary skin condition. 1, 2

Primary Systemic Causes to Investigate

Hematologic Disorders

• Iron deficiency is the single most common systemic cause, representing 25% of all systemic pruritus cases 2
• Polycythemia vera presents characteristically with aquagenic pruritus (itching triggered by water contact) and accounts for approximately 2% of cases 2
• Hodgkin's lymphoma and other hematological malignancies can cause severe generalized pruritus 1, 3
• Iron overload (hemochromatosis) can also trigger pruritus 1

Renal Disease

• Chronic kidney disease and uremia are well-established causes of generalized pruritus 1, 2, 4
• Urea and electrolytes should be part of the initial investigation in all patients with unexplained pruritus 5, 2

Hepatobiliary Disease

• Cholestatic liver disease, particularly primary biliary cholangitis, is a major cause of generalized pruritus 1, 2, 4
• Liver function tests should be performed in all cases of generalized pruritus without rash 5, 2

Endocrine Disorders

• Thyroid disorders (both hyperthyroidism and hypothyroidism) can cause pruritus 1, 3
• Diabetes mellitus may be associated with pruritus 1
• However, routine endocrine testing is not recommended unless clinical features specifically suggest endocrinopathy 5, 2

Malignancy

• Solid tumors can cause paraneoplastic pruritus 1
• Pruritus with systemic symptoms of malignancy requires tailored investigations to rule out specific cancers 5

Infectious Causes

• HIV infection can present with generalized pruritus 1, 3
• Hepatitis A, B, and C should be considered 5
• Parasitic infections including malaria, strongyloidiasis, and schistosomiasis (particularly with travel history) 5

Other Systemic Causes

• Heart failure can be associated with pruritus 1
• Neurological disorders including small fiber neuropathy 5, 1
• Drug-induced pruritus, particularly from opioids 1
• Pregnancy-related pruritus 1
• Psychological and emotional factors can trigger or worsen pruritus 1

Essential Diagnostic Workup

The British Association of Dermatologists recommends the following initial investigations for all patients with chronic generalized pruritus without rash 5, 2:

• Full blood count and ferritin levels (checking for anemia, polycythemia, or hematologic malignancy) 5, 2
• Liver function tests (assessing for cholestasis) 5, 2
• Urea and electrolytes (evaluating renal function) 5, 2
• Consider bile acids and antimitochondrial antibodies if liver disease suspected 5

Critical Diagnostic Pitfall

Ferritin is an acute-phase protein and may be falsely elevated despite true iron deficiency; if iron deficiency is suspected clinically, check serum iron and total iron binding capacity even if ferritin appears normal. 2

Additional Investigations Based on Clinical Suspicion

• JAK2 V617F mutation analysis if polycythemia vera suspected (raised hemoglobin or hematocrit) 5
• HIV and hepatitis serology with appropriate travel or risk history 5
• Thyroid function tests only if clinical features suggest thyroid disease 5
• Lactate dehydrogenase and erythrocyte sedimentation rate if hematological malignancy suspected 5
• Skin biopsy for persistent unexplained pruritus to evaluate for cutaneous lymphoma or small fiber neuropathy 5