What are the causes of itching in the lower limbs?

Causes of Itching in the Lower Limbs

Itching in the lower limbs can arise from primary skin diseases, systemic disorders affecting iron metabolism, renal or hepatic function, hematological malignancies, neurological conditions, infections, or psychological factors—with iron deficiency being the most common systemic cause when no rash is present. 1

Primary Classification Framework

Lower limb pruritus falls into two major categories that guide diagnostic approach 1:

• Pruritus with underlying dermatosis - visible skin disease causing the itch 1
• Pruritus without underlying dermatosis - either secondary to systemic disease or of unknown origin 1

Dermatological Causes (With Visible Skin Changes)

When a rash or skin lesion is present on the lower limbs, consider 1, 2:

• Atopic dermatitis/eczema - particularly in the popliteal fossae (behind knees), with characteristic eczematous changes 1, 2
• Contact dermatitis - from clothing, topical products, or environmental exposures 3
• Fungal infections - tinea pedis with extension, often with macerated toe webs that can serve as entry points for secondary bacterial infection 1
• Venous stasis dermatitis - associated with chronic venous insufficiency and leg edema 1
• Cellulitis/erysipelas - bacterial skin infection with redness, warmth, and edema, though itching is not the primary symptom 1

Systemic Causes (Without Primary Rash)

Iron Metabolism Disorders

Iron deficiency is the most common systemic cause of generalized pruritus, including lower limb involvement 1:

• Iron deficiency causes pruritus that can resolve completely shortly after starting iron replacement therapy 1
• Check ferritin levels in all patients with chronic pruritus without rash; ferritin below 15-25 μg/L warrants iron replacement 1
• Iron overload (hemochromatosis or hyperferritinemia) can also cause pruritus 1

Renal Disease

• Uremia from chronic kidney disease causes pruritus through mixed neurogenic and neuropathic mechanisms 1, 4, 5
• Pruritus affects up to 40% of dialysis patients 5

Hepatic Disease

• Cholestatic liver disease is a major cause of generalized pruritus, including the lower extremities 1, 4, 5
• Intrahepatic cholestasis presents with pruritus predominantly on palms and soles, worse at night 1

Hematological Disorders

• Polycythemia vera - characterized by aquagenic pruritus (triggered by water contact), often affecting the legs 1, 4
• Hodgkin lymphoma - pruritus can be a presenting symptom with night sweats and weight loss 1
• Other lymphoproliferative disorders less commonly cause pruritus 1, 5

Endocrine and Metabolic Conditions

• Diabetes mellitus - can cause diabetic neuropathy leading to regional pruritus affecting the trunk and limbs 1, 6
• Thyroid disorders (hypo- or hyperthyroidism) 1, 6

Neurological Causes

Neuropathic pruritus results from nerve dysfunction anywhere along sensory pathways 1, 7:

• Small fiber neuropathy - can occur in diabetes, HIV, sarcoidosis, causing localized or generalized pruritus 1, 7
• Nerve compression - causes pruritus in the corresponding dermatome 1
• Central nervous system lesions - multiple sclerosis, spinal cord tumors can cause neuropathic itch 1, 7
• Sensory symptoms like burning, tingling, and stinging often accompany neuropathic pruritus 1

Infectious Causes

• Parasitic infections - particularly in travelers, including onchocerciasis (causing pruritic dermatitis over legs and buttocks), strongyloidiasis (larva currens on legs), and schistosomiasis 1
• HIV infection - can cause generalized pruritus and small fiber neuropathy 1, 6

Medication-Related

• Adverse drug reactions - particularly opioids, hydrochlorothiazide, and others 1, 6

Psychological Factors

• Stress and emotional factors - can trigger or worsen pruritus through neural circuit activation 1, 6
• Psychogenic pruritus requires exclusion of physical causes first 1

Critical Diagnostic Pitfalls

Do not assume dry skin without checking ferritin - iron deficiency is frequently missed as it can present with normal hemoglobin 1

Do not overlook medication review - drug-induced pruritus can occur without visible changes 6, 8

Do not dismiss localized lower limb itch as purely dermatological - it may represent early neuropathy or systemic disease 1, 7

Check for tinea pedis and toe web maceration - these serve as reservoirs for streptococcal cellulitis and can perpetuate pruritus 1

Initial Workup for Lower Limb Pruritus Without Rash

Based on British Association of Dermatologists guidelines 1, 6:

• Full blood count and ferritin - to assess for iron deficiency/overload and hematological disorders
• Liver function tests - to evaluate for cholestatic disease
• Renal function (urea and electrolytes) - to assess for uremia
• Fasting glucose or HbA1c - if diabetic neuropathy suspected
• Thyroid function - if clinical features suggest endocrinopathy
• Consider HIV and hepatitis serology with appropriate risk history 6