What is the best approach to assess and treat lower‑leg pruritus without rash and to interpret the recent chest X‑ray and echocardiogram?

Assessment and Management of Lower-Leg Pruritus Without Rash

Order a comprehensive laboratory panel immediately—including complete blood count with differential, ferritin, liver function tests, total bilirubin, serum bile acids, and renal function (urea, creatinine, electrolytes)—because approximately 25% of generalized pruritus without rash is caused by iron deficiency and an additional 15% by other treatable systemic disorders such as renal, hepatic, or hematologic disease. 1

Immediate Diagnostic Workup

The British Association of Dermatologists recommends the following initial panel for all patients with chronic generalized pruritus without rash: 1

• Complete blood count with differential to screen for polycythemia vera, lymphoma, and anemia 1
• Comprehensive iron studies (serum iron, ferritin, transferrin saturation) because iron deficiency accounts for one-quarter of cases and responds completely to iron replacement 1
• Liver function tests, total bilirubin, and serum bile acids to identify cholestatic liver disease, which often presents with lower-extremity involvement and nocturnal worsening 1
• Renal panel (urea, electrolytes, creatinine) because chronic kidney disease and uremia are well-established causes of generalized pruritus 1
• Thyroid-stimulating hormone only if clinical features suggest thyroid dysfunction 1

Do not perform routine chest radiographs or extensive malignancy screens unless specific systemic symptoms are present. 1

Critical History Elements to Obtain

Focus your history on these specific features that guide diagnosis: 1

• Medication review: Perform a comprehensive review of all medications, including over-the-counter and herbal products, because drug-induced pruritus occurs in approximately 12.5% of drug reactions and is often reversible 1, 2
• Timing and triggers: Ask specifically about worsening with water exposure (suggests polycythemia vera), nocturnal worsening (suggests cholestasis), or salt intake (suggests fluid retention from kidney/liver/heart disease) 1
• Distribution pattern: Lower-leg pruritus can indicate neuropathic causes if localized, or systemic disease if part of generalized pruritus 3
• Travel and risk factors: Obtain HIV and hepatitis serology if appropriate travel or risk history exists 1

Immediate Symptomatic Treatment (While Awaiting Results)

Begin symptomatic relief immediately without waiting for diagnostic results: 1, 2

• Emollients applied liberally at least twice daily as universal first-line therapy for all pruritus 1, 2
• Non-sedating antihistamines: Fexofenadine 180 mg daily or loratadine 10 mg daily for symptomatic relief 1, 4
• Avoid sedating antihistamines (e.g., hydroxyzine) for long-term use due to dementia risk in older adults; reserve only for short-term sleep-disrupting pruritus 4, 2

Cause-Specific Treatment Algorithm

If Iron Deficiency Is Identified

• Oral iron replacement leads to complete cessation of pruritus shortly after therapy initiation 1

If Uremic Pruritus (Elevated Creatinine/Uremia)

• Broadband UVB phototherapy is first-line treatment with Level 1+ evidence 1
• Gabapentin 300-1200 mg daily in divided doses for refractory cases 1, 5
• Refer to nephrology for dialysis optimization if on dialysis 1

If Hepatic/Cholestatic Pruritus (Elevated Bile Acids/Bilirubin)

• Rifampin 150 mg twice daily as first-line systemic treatment 1
• Cholestyramine 9 g daily as second-line option 1, 6
• Refer to hepatology if significant hepatic impairment or persistent elevation is present 1

If Polycythemia Vera (Aquagenic Pruritus, Elevated Hemoglobin)

• Order JAK2 V617F mutation analysis for confirmation 1
• Management includes cytoreductive therapy, low-dose aspirin, or narrow-band UVB phototherapy 1

Integration with Chest X-Ray and Echocardiogram Review

When reviewing the chest X-ray and echocardiogram today: 1, 7

• Assess for heart failure: Heart failure is a recognized cause of pruritus, likely related to fluid retention and systemic inflammation 1
• Screen for lymphoma: Chest X-ray may reveal mediastinal lymphadenopathy suggesting Hodgkin's lymphoma, a known cause of severe pruritus 1, 7
• Evaluate for solid tumors: Malignancy can present with paraneoplastic pruritus before other manifestations 1, 7

If the echocardiogram shows heart failure, address volume status and consider that pruritus may improve with diuretic optimization. 1

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

If first-line measures fail, consider these second-line systemic agents: 1, 5

• Antidepressants: Paroxetine, fluvoxamine, or mirtazapine 1, 5
• Neuropathic agents: Gabapentin or pregabalin (avoid in hepatic disease) 1, 5
• Opioid antagonists: Naltrexone or butorphanol 1, 8
• Anti-emetics: Ondansetron or aprepitant 1

When to Refer

• Dermatology: Persistent pruritus >2-4 weeks despite first-line therapy, or if diagnosis remains uncertain 1
• Hepatology: Significant hepatic impairment or persistent elevation of liver enzymes 1
• Hematology: Suspected polycythemia vera (elevated hemoglobin/hematocrit with positive JAK2 mutation) 1
• Consider skin biopsy: For persistent unexplained pruritus to evaluate for cutaneous lymphoma or small-fiber neuropathy 1

Critical Pitfalls to Avoid

• Do not rely on ferritin alone: Comprehensive iron studies are essential to avoid missed iron-deficiency cases 1
• Do not assume antihistamines alone will control systemic pruritus: They are generally ineffective for underlying malignancy or organ-specific causes 1, 4
• Do not delay medication review: Drug-induced pruritus is common and often reversible 1, 2
• Do not assume pruritus is psychogenic: Systematically evaluate for dermatologic, systemic (renal, hepatic, thyroid), and medication-induced causes before attributing to psychiatric factors 4
• Consider scabies: Even with minimal skin findings, especially if immunocompromised or HIV-positive 1