What is the diagnosis and treatment for intermittent red burning palms with associated body pruritis and hives?

Differential Diagnosis and Management of Intermittent Red Burning Palms with Pruritus and Hives

Most Likely Diagnosis: Polycythemia Vera

The combination of red burning palms (erythromelalgia) with generalized pruritus and urticaria strongly suggests polycythemia vera (PV), a myeloproliferative disorder that requires urgent hematologic evaluation. 1

Key Diagnostic Features

• Red burning palms are characteristic of erythromelalgia, which occurs in up to 40% of PV patients and represents a paraneoplastic manifestation 2
• Generalized pruritus affects 30-50% of PV patients, often triggered by water exposure (aquagenic pruritus) and can be severe enough to significantly impact quality of life 1
• Urticaria/hives can occur as part of the systemic inflammatory response in myeloproliferative disorders 2

Immediate Diagnostic Workup

First-Line Laboratory Tests (Order Immediately)

• Complete blood count with differential - look for elevated hemoglobin (>16.5 g/dL in men, >16 g/dL in women) or elevated hematocrit, often with microcytosis suggesting secondary iron deficiency 1
• JAK2 V617F mutation analysis - present in up to 97% of PV cases and confirms diagnosis 1
• Platelet count and white cell count - frequently elevated in PV 1
• ESR - characteristically low in PV 1

Additional Testing if JAK2 Negative

If JAK2 mutation is absent, investigate secondary causes of polycythemia: 1

• Renal and liver function tests
• Serum erythropoietin level (low in PV)
• Oxygen saturation measurement
• Chest X-ray
• Abdominal ultrasound

Alternative Diagnoses to Consider

If Patient is Pregnant

Intrahepatic cholestasis of pregnancy (ICP) presents with pruritus predominantly affecting palms and soles, worse at night, without primary rash (though excoriations may develop from scratching) 1

• Check serum bile acid levels using mass spectrometry assays 1
• ICP poses minimal maternal risk but significant fetal risk including stillbirth 1

Other Systemic Causes to Exclude

Based on clinical context, consider: 1

• Hepatic disease: Check liver function tests and bile acids; pruritus from cholestasis can be severe 1
• Renal failure: Check urea and electrolytes 1
• Lymphoma: Particularly if constitutional symptoms present; may require skin biopsy from trunk even if skin appears normal 1
• HIV and viral hepatitis: Obtain travel history, sexual history, and IV drug use history; check HIV and hepatitis A, B, C serology 1
• Drug-induced: Review all medications including over-the-counter and herbal remedies; trial cessation if risk-benefit acceptable 1

Treatment Algorithm

If Polycythemia Vera Confirmed

First-line therapy for PV-associated symptoms: 1

1. Aspirin 300 mg daily - effective for erythromelalgia and pruritus in PV patients 1, 2
2. Cytoreductive therapy - phlebotomy or hydroxyurea to normalize blood counts 1
3. Ruxolitinib (JAK1/JAK2 inhibitor) - produces rapid reductions in pruritus scores in recent RCT 1

Additional symptomatic options if pruritus persists despite normalized counts: 1

• SSRIs (selective serotonin reuptake inhibitors)
• Interferon-alpha (dual benefit as cytoreductive agent, though poorly tolerated)
• UVB phototherapy (NB-UVB, BB-UVB) or PUVA
• Cimetidine or atenolol

If Hepatic Cholestasis Confirmed

Stepwise treatment approach: 1

1. First-line: Rifampicin (Strength of recommendation A)
2. Second-line: Cholestyramine
3. Third-line: Sertraline
4. Fourth-line: Naltrexone or nalmefene
5. Fifth-line options: Dronabinol, phenobarbitone, topical tacrolimus, or bile acid transport blockers

Symptomatic Management (All Causes)

Universal measures while awaiting diagnosis: 1, 3

• Emollients liberally - particularly urea-containing moisturizers (5-10%) for skin barrier restoration 4, 5
• Avoid triggers: Limit hot water exposure, frequent bathing, skin irritants 4, 3
• Oral antihistamines - provide nonspecific relief for urticaria, though sedating antihistamines should be avoided long-term (dementia risk) 1, 6
• Short-term low-potency topical corticosteroids for urticarial lesions 6, 3

Critical Pitfalls to Avoid

• Do not dismiss burning palms as simple dermatitis - this symptom pattern with systemic pruritus demands hematologic evaluation for PV, which can be fatal if untreated 1, 2
• Do not use gabapentin for hepatic pruritus - it is contraindicated 1
• Do not delay bile acid testing in pregnant patients - ICP carries significant fetal mortality risk 1
• Do not perform routine endocrine testing unless additional clinical features suggest endocrinopathy 1
• Consider skin biopsy from trunk if pruritus persists without explanation, as cutaneous lymphoma can present with normal-appearing skin 1

Urgent Referral Indications

• Hematology referral: If JAK2 mutation positive or PV suspected based on elevated hemoglobin/hematocrit 1
• Hepatology referral: If significant hepatic impairment detected 1
• Maternal-fetal medicine: If pregnant with suspected ICP 1