What are the possible causes of lower‑extremity pruritus in an otherwise healthy adult?

Causes of Lower Extremity Pruritus in Adults

Lower extremity pruritus in an otherwise healthy adult requires systematic evaluation for both localized dermatologic conditions and systemic diseases, with iron deficiency, chronic kidney disease, cholestatic liver disease, drug reactions, and neuropathic causes being the most important treatable etiologies to exclude.

Primary Dermatologic Causes

Localized skin conditions are the most common cause of lower extremity pruritus and should be evaluated first:

• Xerotic eczema (dry skin) is extremely common, particularly in elderly patients, and represents the most frequent cause of localized pruritus on the lower extremities 1, 2
• Atopic dermatitis can present with lower extremity involvement and is characterized by persistent pruritus 1, 3
• Contact dermatitis from clothing, topical products, or occupational exposures should be considered 1
• Prurigo nodularis characteristically occurs on the lower extremities and represents a chronic form of pruritic disease 4
• Stasis dermatitis associated with venous insufficiency commonly affects the lower legs 2

Systemic Causes Requiring Laboratory Investigation

Even without visible rash, systemic diseases must be excluded through targeted laboratory testing 5, 6:

Hematologic and Metabolic Disorders

• Iron deficiency accounts for approximately 25% of cases of generalized pruritus and can manifest with lower extremity predominance; iron replacement leads to complete cessation within days of treatment 6, 7
• Polycythemia vera characteristically presents with aquagenic pruritus (triggered by water contact) and requires JAK2 V617F mutation testing 6, 8
• Chronic kidney disease and uremia are well-established causes, with pruritus correlating with disease severity 5, 6, 9, 2
• Diabetes mellitus can cause pruritus through multiple mechanisms including neuropathy and xerosis 4
• Thyroid disorders (both hyperthyroidism and hypothyroidism) should be considered 1, 2

Hepatobiliary Disease

• Cholestatic liver disease is a major cause, with pruritus predominantly affecting palms and soles but can involve lower extremities, typically worsening at night 6, 8, 9, 2
• Hepatitis A, B, C, and E can all cause generalized pruritus 5, 8

Malignancy

• Hodgkin's lymphoma classically presents with severe pruritus that may precede other symptoms 6, 2
• Cutaneous T-cell lymphoma should be considered for persistent unexplained pruritus and requires skin biopsy 6, 8, 3
• Solid tumors can occasionally present with paraneoplastic pruritus 5

Medication-Induced Pruritus

Drug reactions account for 12.5% of pruritus cases without rash and require comprehensive medication review 6, 8:

• Opioids cause pruritus in 2-10% of oral users, 10-50% of intravenous users 8
• Statins can cause cholestatic hepatitis with pruritus as a cardinal symptom 8
• Over-the-counter pharmaceuticals and herbal remedies must be specifically queried 5, 8

Infectious and Parasitic Causes

Infections should be considered based on risk factors and exposure history 5:

• Scabies can present with severe pruritus and minimal skin signs, particularly in immunocompromised patients 5, 8
• HIV infection correlates with viral load and can present with pruritus as an early or late manifestation 5, 8, 2
• Parasitic infections including Strongyloides stercoralis and schistosomes (swimmer's itch) 5, 8

Neuropathic Causes

Nerve dysfunction can cause localized lower extremity pruritus 1:

• Small fiber neuropathy should be evaluated via skin biopsy for persistent unexplained pruritus 6, 8
• Postherpetic pruritus following varicella zoster infection 5, 8
• Notalgia paresthetica and other localized nerve dysregulation syndromes 1

Psychiatric and Psychogenic Factors

Psychological conditions are associated with chronic pruritus but require exclusion of physical causes first 5:

• Depression, anxiety disorder, obsessive-compulsive disorder are found commonly in patients with chronic pruritus 5
• Substance abuse should be considered in the differential 5
• Always look for a physical cause before labeling patients as 'psychogenic' 5

Essential Diagnostic Workup

The British Association of Dermatologists recommends the following initial panel for all patients with chronic pruritus 6:

• Complete blood count with differential 6, 1, 2
• Comprehensive iron studies (ferritin, serum iron, transferrin saturation) because iron deficiency accounts for 25% of cases 6, 7
• Liver function tests, total bilirubin, and serum bile acids 6, 8
• Renal panel (urea, electrolytes, creatinine) 6, 8, 1, 2
• Thyroid-stimulating hormone if clinical features suggest thyroid disease 6, 1, 2

History-Directed Additional Testing

• JAK2 V617F mutation if aquagenic pruritus suggests polycythemia vera 6, 8
• HIV and hepatitis serologies with appropriate risk or travel history 6, 8
• Skin biopsy for persistent unexplained pruritus to evaluate cutaneous lymphoma or small fiber neuropathy 6, 8

Critical Clinical Pitfalls

• Do not rely on ferritin alone; comprehensive iron studies are essential as ferritin is an acute-phase protein and may be falsely elevated despite true iron deficiency 7
• Always obtain complete medication history including over-the-counter and herbal products, as drug-induced pruritus is common and reversible 5, 8
• Consider scabies even with minimal visible signs, especially in immunocompromised or HIV-positive patients 5, 8
• Do not assume antihistamines will control systemic pruritus; they are generally ineffective for underlying malignancy or organ-specific causes 6