What are the causes of bilateral hand swelling?

Bilateral Hand Swelling: Causes and Diagnostic Approach

Bilateral hand swelling indicates systemic disease processes rather than local obstruction, requiring evaluation for inflammatory, rheumatologic, drug-induced, endocrine, and vascular causes. 1, 2

Critical Distinction: Bilateral vs. Unilateral Presentation

• Bilateral swelling suggests systemic causes including inflammatory arthritis, drug toxicity, endocrine disorders, or systemic vascular processes 1, 2
• Unilateral swelling indicates local obstruction (DVT, infection, trauma) requiring urgent evaluation—this is NOT your clinical scenario 1, 3

Primary Systemic Causes of Bilateral Hand Swelling

Rheumatologic and Inflammatory Conditions

• Erosive hand osteoarthritis targets interphalangeal joints with inflammatory symptoms including soft tissue swelling, erythema, paresthesias, and mildly elevated CRP levels 2
• Psoriatic arthritis causes painful, swollen joints with characteristic dactylitis ("sausage digits") affecting hands and feet 2
• Scleroderma (systemic sclerosis) presents with hand swelling, Raynaud's phenomenon, and may be associated with pulmonary hypertension; notably, persistent bilateral hand swelling after carpal tunnel release can be an early clue to underlying scleroderma 2, 4
• Thyroid eye disease (Graves' disease, Hashimoto's thyroiditis) causes bilateral but potentially asymmetric edema and erythema of periorbital tissues and can be associated with peripheral edema 5

Drug-Induced Causes

• Chemotherapy-induced hand-foot syndrome (HFS/PPES) causes redness, marked discomfort, swelling, and tingling in palms and soles, occurring with 5-fluorouracil (6%-34%), capecitabine (50%-60%), doxorubicin (22%-29%), and PEGylated liposomal doxorubicin (40%-50%) 5
• Targeted therapy-induced hand-foot skin reaction (HFSR) from BRAF inhibitors (vemurafenib, dabrafenib) and multikinase VEGFR inhibitors (sorafenib 10%-62%, cabozantinib 40%-60%, sunitinib 10%-50%) causes well-defined painful hyperkeratosis on pressure areas 5
• Intravenous drug abuse causes "puffy hand syndrome" or "red puffy hand syndrome"—bilateral, painless, non-pitting erythema and edema of dorsal hands from lymphatic blockage due to direct drug toxicity, impurities, or infection complications; commonly associated with hepatitis C infection 6, 7

Vascular and Systemic Causes

• Increased capillary hydrostatic pressure from superior vena cava syndrome, bilateral DVT, or reflex sympathetic dystrophy 2
• Increased capillary permeability from systemic allergic reactions, widespread infection, or systemic inflammatory states 2
• Venous hypertension from central venous stenosis (particularly in dialysis patients with AV access) forces blood flow through collaterals, producing chronic venostasis that can progress to skin ulceration 3

Vasculitis and Systemic Inflammatory Disorders

• Kawasaki disease (primarily pediatric) presents with fever ≥5 days, swollen red palms and soles, polymorphous rash, strawberry tongue, and cervical lymphadenopathy; coronary artery aneurysm is a lethal complication 5
• Sarcoidosis and other systemic vasculitides can cause bilateral hand involvement with conjunctival nodules, restrictive myopathy, and multi-organ involvement 5

Diagnostic Algorithm

Initial Assessment

1. Determine medication history: Specifically ask about chemotherapy agents (5-FU, capecitabine, doxorubicin, targeted kinase inhibitors), as drug-induced causes are common and treatment-modifiable 5
2. Assess for injection drug use history: Even remote history (years prior) can manifest as puffy hand syndrome; screen for hepatitis C 6, 7
3. Evaluate for rheumatologic symptoms: Morning stiffness, joint pain pattern, Raynaud's phenomenon, skin tightening, rashes 2, 4
4. Screen for thyroid disease: Family history, symptoms of hyper/hypothyroidism, smoking history 5

Laboratory Evaluation

• Rheumatoid factor, anti-CCP antibodies, ANA, ESR/CRP for inflammatory arthritis 2
• Thyroid function tests (TSH, free T4) if thyroid disease suspected 5
• Hepatitis C serology if injection drug use history 6, 7
• Caution: Elevated rheumatoid factor may be falsely attributed to rheumatoid arthritis when actually due to untreated hepatitis C in puffy hand syndrome 7

Imaging When Indicated

• Plain radiographs in two planes are mandatory first investigation for any musculoskeletal pathology with swelling 1
• Duplex ultrasound to exclude bilateral upper extremity DVT if vascular obstruction suspected (though less likely with bilateral presentation) 1, 3
• MRI for suspected malignancy or detailed soft tissue evaluation 1

Management Approach by Etiology

Drug-Induced HFS/HFSR (Chemotherapy)

• Grade 1-2: Continue drug at current dose; initiate oral tetracycline (doxycycline 100 mg twice daily OR minocycline 50 mg twice daily for 6 weeks) AND topical low/moderate steroid; reassess after 2 weeks 5
• Grade ≥3 or intolerable Grade 2: Interrupt drug until Grade 0-1; continue oral antibiotic and topical steroid; add systemic corticosteroids (prednisone 0.5-1 mg/kg for 7 days); consider low-dose isotretinoin (20-30 mg/day) with dermatology consultation 5

Puffy Hand Syndrome (Drug Abuse-Related)

• Discontinue systemic immunosuppressive therapy (methotrexate, prednisone) if mistakenly prescribed for presumed inflammatory arthritis 7
• Daily compression bandaging with compression stockings for persistent swelling 3, 6
• Lymphedema decongestion therapy and occupational therapy 7
• Treat hepatitis C if present 6, 7

Inflammatory Arthritis

• Refer to rheumatology for disease-modifying therapy based on specific diagnosis 2
• NSAIDs (topical preferred for safety profile) for mild-moderate pain 3

Scleroderma

• Recognize that persistent bilateral hand swelling after carpal tunnel surgery is a red flag for underlying systemic sclerosis 4
• Refer to rheumatology for systemic evaluation and management 2

Common Pitfalls to Avoid

• Do not assume bilateral swelling is benign edema—it requires systematic evaluation for underlying systemic disease 1, 2
• Do not empirically treat as cellulitis without considering drug-induced causes, especially in patients on chemotherapy or with injection drug history 5, 6, 7
• Do not mistake puffy hand syndrome for inflammatory arthritis based solely on elevated rheumatoid factor, which may be secondary to hepatitis C 7
• Recognize that chemotherapy-induced HFS can develop days to 6 months after therapy initiation, depending on pharmacokinetics 5
• Do not overlook scleroderma when bilateral hand swelling persists after carpal tunnel release 4

Follow-Up Protocol

• Reassess within 48-72 hours to evaluate response to initial management and ensure no progression 3, 2
• Schedule formal evaluation at 6 weeks if edema persists to detect delayed complications or underlying pathology 1, 3, 2