What is the appropriate evaluation and management of nocturnal pruritus of the legs in a 68-year-old man?

Approach to Nocturnal Leg Pruritus in a 68-Year-Old Man

Begin with a focused laboratory workup including complete blood count with ferritin, liver function tests with bile acids, and renal panel, while immediately starting emollients twice daily and a non-sedating antihistamine, because systemic disease accounts for approximately 15-25% of cases and nocturnal worsening suggests cholestatic liver disease, uremia, or iron deficiency. 1, 2

Immediate Diagnostic Workup

Order the following tests without delay, as they identify the most common treatable causes:

• Complete blood count with differential and comprehensive iron studies (ferritin, serum iron, transferrin saturation) – Iron deficiency causes 25% of generalized pruritus cases and resolves completely within days of iron replacement 2, 3
• Liver function tests, total bilirubin, and serum bile acids – Cholestatic liver disease characteristically causes pruritus affecting palms/soles that worsens at night 1, 2, 4
• Renal panel (urea, creatinine, electrolytes) – Uremic pruritus from chronic kidney disease is common and severity correlates with disease stage 1, 2, 4
• Thyroid-stimulating hormone only if clinical features suggest thyroid dysfunction (weight changes, temperature intolerance, fatigue) 2, 4

Do not order routine chest X-rays, extensive cancer screening, or endocrine panels without specific systemic symptoms, as these have low yield and delay appropriate treatment 2, 4

Critical History Elements to Elicit

Focus your history on these specific red flags:

• Nocturnal worsening with palm/sole involvement strongly suggests cholestatic liver disease 1, 2
• Itching triggered by water contact (aquagenic pruritus) indicates polycythemia vera – order JAK2 V617F mutation analysis 1, 2
• Weight loss, fevers, night sweats, or lymphadenopathy suggests lymphoma – refer for lymph node biopsy 1
• Recent medication changes – Drug-induced pruritus accounts for 12.5% of cases and is reversible 2, 4
• Travel history or HIV risk factors – Order HIV and hepatitis A, B, C serologies if positive 2, 4

Immediate Symptomatic Treatment (Start Today)

While awaiting laboratory results, initiate:

• High-lipid content emollients applied at least twice daily – Universal first-line therapy for all pruritus, especially important in elderly patients with xerosis 1, 2, 4
• Non-sedating antihistamine (fexofenadine 180 mg daily or loratadine 10 mg daily) for symptomatic relief 2, 4
• Topical menthol 0.5% or pramoxine applied 2-3 times daily to legs for immediate relief 2, 5, 6

Avoid sedating antihistamines (hydroxyzine, diphenhydramine) except for short-term palliative use, as they increase dementia risk in elderly patients 1, 2, 4, 7

Cause-Specific Treatment Based on Laboratory Results

If Iron Deficiency Identified

• Oral iron replacement therapy leads to complete cessation of pruritus within days 2, 3

If Elevated Creatinine/Uremia

• Broadband UVB phototherapy is first-line with Level 1+ evidence 2, 4
• Gabapentin 300 mg at bedtime, titrate to 900-1200 mg daily in divided doses for refractory cases 1, 2, 5

If Elevated Liver Enzymes/Bile Acids

• Rifampin 150 mg twice daily as first-line systemic treatment 1, 2, 4
• Cholestyramine 9 g daily as second-line option 1, 2
• Refer to hepatology if significant hepatic impairment present 2, 4

If Elevated Hemoglobin/Hematocrit with Positive JAK2 Mutation (Polycythemia Vera)

• Aspirin 300 mg daily effectively relieves pruritus in many patients 1
• Consider cytoreductive therapy, interferon-alpha, SSRIs, or UVB phototherapy 1, 2

If Lymphoma Suspected

• Refer for lymph node excision or core biopsy 1
• Symptomatic management: cimetidine, gabapentin, carbamazepine, mirtazapine, or phototherapy 1, 2

Consider Neuropathic Pruritus if Workup Negative

If laboratory tests are unrevealing and pruritus has a "deep" or "internal" quality with burning/tingling:

• Gabapentin 300 mg at bedtime, titrate up to 900-3600 mg daily as primary treatment 2, 5
• Skin biopsy may show reduced intraepidermal nerve fiber density confirming small fiber neuropathy 2, 5
• Do not use gabapentin if hepatic disease present, as it worsens hepatic encephalopathy 5

Medication Review (Critical Step)

Perform comprehensive medication review including over-the-counter and herbal products, as drug-induced pruritus is common and reversible 2, 4. Consider trial discontinuation of potentially causative medications when risk-benefit analysis permits 4.

When to Refer

• Dermatology referral if pruritus persists >2-4 weeks despite first-line therapy or diagnosis remains uncertain 2, 4
• Hepatology referral for significant hepatic impairment or persistent liver enzyme elevation 2, 4
• Hematology referral for suspected polycythemia vera (elevated hemoglobin with positive JAK2 mutation) or lymphoma 2, 4

Common Pitfalls to Avoid

• Do not rely on ferritin alone – Order comprehensive iron studies to avoid missing iron deficiency 2
• Do not assume antihistamines will control systemic pruritus – They are generally ineffective for malignancy or organ-specific causes 2
• Do not delay medication review – Drug-induced pruritus is common and often reversible 2, 4
• Do not use long-term sedating antihistamines due to dementia risk in elderly patients 1, 2, 4
• Regular follow-up is essential when the underlying cause is not immediately evident, as systemic causes may not be apparent initially 1, 4

Refractory Cases (If No Improvement After 2-4 Weeks)

Consider escalation to:

• Antidepressants: paroxetine, fluvoxamine, or mirtazapine 2, 8
• Pregabalin as alternative to gabapentin 1, 5
• Opioid antagonists: naltrexone or butorphanol 2
• Anti-emetics: ondansetron or aprepitant 2