What is the probable diagnosis for a patient presenting with a puffy face and swelling of hands?

Probable Diagnosis: Systemic Sclerosis (Scleroderma) or Nephrotic Syndrome

The combination of puffy face and hand swelling most strongly suggests systemic sclerosis (scleroderma) in the "prescleroderma" phase, particularly if accompanied by Raynaud phenomenon, or nephrotic syndrome if associated with significant proteinuria and hypoalbuminemia. 1, 2

Critical Initial Assessment

Immediate Life-Threatening Considerations

• Rule out heart failure first: Assess for jugular venous distension, pulmonary rales/crackles, S3 gallop, and peripheral edema extending beyond hands to determine if this represents volume overload from cardiac dysfunction 1
• Evaluate for nephrotic syndrome: Check for severe proteinuria (>3.5g/24hr), hypoalbuminemia (<3g/dL), and hyperlipidemia, as this can lead to acute renal failure, thrombosis, and infections 2, 3
• Consider superior vena cava syndrome: Bilateral upper extremity swelling with facial edema suggests central venous obstruction requiring urgent imaging 4

Key Distinguishing Features by Volume Status

Hypervolemic (with edema):

• Heart failure presents with dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and objective signs including elevated jugular venous pressure, pulmonary rales, and S3 gallop 1
• Nephrotic syndrome shows peripheral edema, hypoalbuminemia, severe proteinuria, and hyperlipidemia without signs of cardiac or hepatic failure 2, 3

Euvolemic (no obvious volume overload):

• Systemic sclerosis "prescleroderma" phase presents with puffy fingers, Raynaud phenomenon, and specific autoantibodies before definite skin thickening develops 1
• Dermatomyositis causes periorbital edema (heliotrope rash), facial erythema, and proximal muscle weakness with elevated muscle enzymes 1

Hypovolemic (with dehydration):

• Hyponatremia with syndrome of inappropriate antidiuresis can cause facial puffiness despite relative hypovolemia 5, 6

Systematic Diagnostic Algorithm

Step 1: Assess Distribution Pattern

• Bilateral hand and face involvement suggests systemic process: scleroderma, nephrotic syndrome, heart failure, or superior vena cava syndrome 1, 4, 2
• Unilateral hand swelling only requires urgent duplex ultrasound to exclude upper extremity deep vein thrombosis (10% of all DVTs) 4, 7

Step 2: Identify Associated Features

For Systemic Sclerosis:

• Raynaud phenomenon occurs in nearly all patients with scleroderma and is a critical diagnostic clue 1
• Puffy fingers in the "prescleroderma" phase, with specific antibodies (anti-centromere, anti-Scl-70, anti-RNA polymerase III) and abnormal nailfold capillaroscopy 1
• Screen for interstitial lung disease (40-75% prevalence) and pulmonary arterial hypertension with pulmonary function tests and echocardiography 1

For Nephrotic Syndrome:

• Fatigue and swelling without signs of severe liver damage or cardiac failure 2
• Hypoalbuminemia (<3g/dL), severe proteinuria (>3.5g/24hr), hyperlipidemia, and peripheral edema 2, 3
• Risk of venous thrombosis, acute renal failure, and infections as major complications 2, 3

For Heart Failure:

• At least ONE symptom: dyspnea (exertional, at rest, orthopnea, paroxysmal nocturnal dyspnea), decreased exercise tolerance, fatigue, or worsened end-organ perfusion 1
• At least TWO physical findings OR one physical finding plus one laboratory criterion: peripheral edema, pulmonary rales, increased jugular venous pressure, S3 gallop, or significant weight gain (>3-4 lbs in 3-4 days) 1

For Dermatomyositis:

• Periorbital edema with heliotrope rash (violaceous discoloration), Gottron papules on hands, and proximal muscle weakness 1
• Elevated creatine kinase levels and abnormal electromyography findings 1

Step 3: Laboratory Evaluation Priority

1. Serum albumin and 24-hour urine protein to diagnose nephrotic syndrome 2, 3
2. BNP or NT-proBNP if heart failure suspected (though serial measurements for therapy guidance not well established) 1
3. Autoantibody panel (ANA, anti-Scl-70, anti-centromere, anti-RNA polymerase III) if scleroderma suspected 1
4. Serum sodium and osmolality to exclude hyponatremia with inappropriate antidiuresis 5, 6
5. Creatine kinase and aldolase if dermatomyositis suspected 1

Step 4: Imaging Studies

• Echocardiography to assess cardiac function, estimate pulmonary artery pressure, and screen for pulmonary arterial hypertension 1
• Duplex ultrasound of upper extremities if unilateral swelling or asymmetric involvement to exclude deep vein thrombosis (sensitivity and specificity >80%) 4, 7
• High-resolution chest CT if interstitial lung disease suspected in scleroderma patients 1
• Nailfold capillaroscopy to detect microvascular changes characteristic of scleroderma 1

Common Pitfalls to Avoid

• Do not dismiss puffy fingers as benign edema: This may represent the "prescleroderma" phase, and up to half of these patients develop defined connective tissue disease during long-term follow-up 1
• Do not attribute all facial and hand swelling to heart failure: Carefully assess for other systemic features like Raynaud phenomenon, skin changes, or proteinuria that suggest alternative diagnoses 1, 2
• Do not overlook nephrotic syndrome complications: Even without obvious symptoms, patients are at high risk for venous thrombosis (including renal vein thrombosis), acute renal failure, and infections requiring prophylactic measures 2, 3
• Do not wait for skin thickening to diagnose scleroderma: The "prescleroderma" phase with puffy fingers, Raynaud phenomenon, and specific antibodies warrants early screening for organ involvement 1
• Do not ignore unilateral hand swelling: This indicates obstruction requiring urgent evaluation for upper extremity DVT, unlike bilateral swelling which suggests systemic causes 4, 7

Management Approach Based on Diagnosis

If Systemic Sclerosis Confirmed:

• Organ-based screening: Pulmonary function tests, echocardiography, and blood pressure monitoring (especially with anti-RNA polymerase III antibodies for scleroderma renal crisis risk) 1
• Raynaud phenomenon treatment: Calcium channel blockers first-line, then phosphodiesterase 5 inhibitors or intravenous iloprost 1
• Early diffuse cutaneous disease: Consider autologous hematopoietic stem cell transplantation for high-risk patients with very high modified Rodnan skin scores or moderate skin involvement with worsening interstitial lung disease 1
• Interstitial lung disease: Mycophenolate mofetil as initial therapy; add nintedanib if fibrotic and progressing 1

If Nephrotic Syndrome Confirmed:

• Corticosteroids as first-line treatment for most primary nephrotic syndrome cases 2
• Alternative immunosuppression: Calcineurin inhibitors, mycophenolate mofetil, or rituximab for steroid-resistant cases 2
• Thromboprophylaxis consideration given high venous thrombosis risk 2, 3
• Monitor for complications: Acute renal failure, infections, and severe hyperlipidemia 2, 3

If Heart Failure Confirmed:

• Initiate or intensify treatment specifically for heart failure: This requires more than just oral diuretic changes 1
• Assess volume status and weight at each visit to guide diuretic therapy 1
• Repeat measurement of ejection fraction after clinical change or treatment that might significantly affect cardiac function 1

If Dermatomyositis Confirmed:

• High-dose corticosteroids (prednisone 1mg/kg/day up to 60-80mg/day) concurrent with steroid-sparing agent (methotrexate, azathioprine, or mycophenolate mofetil) 1
• For severe disease: High-dose methylprednisolone plus intravenous immunoglobulin, cyclophosphamide, rituximab, or cyclosporine 1
• Screen for malignancy as dermatomyositis can be paraneoplastic 1