What are the causes of palmar erythema?

Causes of Palmar Erythema

Palmar erythema results from either physiologic states (pregnancy, hereditary, idiopathic) or secondary systemic diseases, most importantly chronic liver disease, rheumatoid arthritis, thyroid disorders, and certain medications including chemotherapy agents. 1

Physiologic/Primary Causes

• Pregnancy: Occurs in at least 30% of pregnant women due to the hyperestrogenic state and hyperdynamic circulation, with palmar erythema and spider angiomas developing as normal physiologic changes 2, 1
• Hereditary palmar erythema (Lane's disease): Autosomal dominant transmission, present from birth, asymptomatic, affecting thenar and hypothenar eminences 3
• Idiopathic: Diagnosis of exclusion when no underlying cause is identified 1
• Aging: Normal physiologic finding in elderly patients 4

Secondary/Pathologic Causes

Hepatic Disease

• Chronic liver disease/cirrhosis: Present in 23% of patients with cirrhosis, caused by abnormal serum estradiol levels 1
• Wilson disease and hereditary hemochromatosis: Rare neonatal liver diseases manifesting with palmar erythema alongside other systemic features 1

Rheumatologic Conditions

• Rheumatoid arthritis: Occurs in over 60% of patients and is associated with a favorable prognosis; patients with palmar erythema have higher hemoglobin levels and less ulnar deviation 1, 5

Endocrine Disorders

• Thyrotoxicosis: Present in up to 18% of patients 1
• Diabetes mellitus: Occurs in 4.1% of diabetic patients, more frequently than classic manifestations like necrobiosis lipoidica diabeticorum (0.6%) 1

Medication-Induced

• Chemotherapy agents: Multiple cytotoxic agents cause palmar-plantar erythrodysesthesia syndrome (PPES), including 5-fluorouracil (6%-34%), capecitabine (50%-60%), doxorubicin (22%-29%), PEGylated liposomal doxorubicin (40%-50%), docetaxel (6%-58%), and cytarabine (14%-33%) 2
• BRAF and MEK inhibitors: Vemurafenib, dabrafenib, encorafenib, sorafenib (10%-62%), cabozantinib (40%-60%), sunitinib (10%-50%), and regorafenib (47%) cause hand-foot skin reaction (HFSR) with palmoplantar involvement 2
• Other medications with hepatic damage: Amiodarone, gemfibrozil, cholestyramine 1
• Medications without hepatic damage: Topiramate and albuterol 1

Infectious Causes

• Early gestational syphilis 1
• HTLV-1-associated myelopathy 1

Neoplastic Disease

• Brain tumors: Present in 15% of patients with both metastatic and primary brain neoplasms, postulated to be caused by increased angiogenic factors and estrogens from solid tumors 1

Dermatologic Conditions

• Atopic dermatitis: Patients with atopic diathesis are more likely to have palmar erythema than matched controls 1
• Contact dermatitis: Caused by frequent hand sanitizer use, particularly relevant during COVID-19 pandemic 6
• Erythema ab igne: Can mimic palmar erythema 1

Environmental/Toxicologic

• Smoking 1
• Chronic mercury poisoning 1

Clinical Pitfall

The chemotherapy-induced palmar erythema (PPES/HFSR) differs from other causes by progressing from dysesthesia and tingling to burning pain, swelling, erythema, and potentially blisters, desquamation, erosions, and ulcerations, typically developing within days to weeks (occasionally up to 6 months) after treatment initiation 2. This requires specific management with behavioral modifications, topical steroids, and potential dose interruption, unlike the benign physiologic forms that require no treatment 2, 1.