What are the differential diagnoses and treatment options for facial puffiness?

Differential Diagnosis of Facial Puffiness

Immediate Life-Threatening Causes to Exclude First

Angioedema without urticaria must be ruled out immediately, requiring measurement of serum C4 to screen for hereditary or acquired C1 inhibitor deficiency, which can be fatal if involving the airway. 1

• If C4 is low (<30% mean normal), confirm with quantitative and functional C1 inhibitor assays 1
• ACE inhibitor-induced angioedema results from inhibition of kinin breakdown and requires immediate drug cessation 1
• Look for lip, tongue, or periorbital swelling that develops over hours without pruritus or urticaria 1

Cardiac and Vascular Causes

Superior vena cava syndrome from mediastinal masses presents with facial puffiness, distended neck veins, and requires urgent chest imaging. 2

• A 12-year-old with mediastinal lymphoma presented with facial puffiness for 1 month and cardiac tamponade 2
• Uhl's anomaly (right ventricular dysplasia) causes facial puffiness with lower limb edema from right heart failure 3
• Examine for jugular venous distension, muffled heart sounds, and peripheral edema 3, 2
• Obtain chest X-ray and echocardiography if cardiac cause suspected 3, 2

Endocrine Causes

Primary hypothyroidism causes facial puffiness with coarse facial features, hoarseness, and easy fatigability, diagnosed by elevated TSH and low free T4. 4

• A 22-year-old presented with 6 months of facial puffiness, coarseness of features, and hoarseness from pituitary hyperplasia secondary to hypothyroidism 4
• Check thyroid function tests (TSH, free T4) in all patients with facial puffiness 4
• Thyroid hormone replacement resolves symptoms completely 4
• Cushing's syndrome causes moon facies with central obesity, striae, and proximal muscle weakness

Renal Causes

Nephrotic syndrome presents with periorbital edema worse in the morning, requiring urinalysis for proteinuria and serum albumin measurement.

• Morning facial puffiness that improves throughout the day suggests fluid redistribution from lying supine
• Check urinalysis, serum creatinine, and albumin levels
• Acute glomerulonephritis causes hypertension and hematuria in addition to facial edema

Infectious and Inflammatory Causes

Pott's puffy tumor from frontal sinusitis causes forehead swelling with headache and requires urgent CT/MRI to detect osteomyelitis and intracranial extension. 5

• A 27-year-old presented with intermittent forehead swelling over months with epidural abscess formation 5
• Maxillary sinusitis can cause facial pain and swelling, most commonly from viral or bacterial infection 1
• Salivary gland disorders (stones, tumors, infections) cause intermittent swelling before eating with tender glands 1
• Perform bimanual palpation of submandibular glands and check for slow salivary flow 1

Allergic Causes

Acute urticaria with angioedema presents with pruritic wheals and facial swelling developing within minutes to hours of allergen exposure. 1

• IgE-mediated reactions to foods (nuts, fish), drugs, or latex can be confirmed by skin-prick testing 1
• Chronic ordinary urticaria requires full blood count, ESR, and thyroid autoantibodies if not responding to H1 antihistamines 1
• Thyroid autoimmunity occurs in 14% of chronic urticaria patients versus 6% of controls 1

Physiologic and Benign Causes

Self-perceived facial puffiness from mild fluid retention shows objectively increased water content and skin thickness, particularly in the lower eyelid region in women over 40. 6

• Water content and skin thickness are significantly higher during perceived puffiness episodes 6
• Skin elasticity changes significantly when facial puffiness subsides 6
• This is most common in women aged 20-68 years and does not pose health risks 6
• Dietary sodium intake, premenstrual fluid retention, and sleep position contribute to morning puffiness 6

Diagnostic Algorithm

Begin with focused history on timing (morning vs. constant), associated symptoms (dyspnea, hoarseness, urticaria), medication use (ACE inhibitors, NSAIDs), and systemic symptoms (fatigue, weight changes). 1

Essential Physical Examination Elements:

• Visual inspection for color changes, distribution (periorbital, generalized, unilateral), and skin lesions 1
• Palpation of salivary glands, lymph nodes, and thyroid 1
• Cardiovascular exam for jugular venous distension, heart sounds, and peripheral edema 3, 2
• Cranial nerve examination to exclude neurologic causes 1

Initial Laboratory Investigations:

• Serum C4 if angioedema suspected (low C4 has high sensitivity for C1 inhibitor deficiency) 1
• TSH and free T4 for all patients with facial puffiness 4
• Urinalysis with protein quantification and serum albumin if morning periorbital edema 1
• Complete blood count and ESR if chronic or associated with systemic symptoms 1
• Ferritin if chronic pruritus accompanies puffiness 1

Imaging When Indicated:

• Chest X-ray or CT if dyspnea, distended neck veins, or suspected mediastinal mass 2, 5
• Echocardiography if cardiac symptoms or signs present 3, 2
• CT/MRI of sinuses if forehead swelling with headache to exclude Pott's puffy tumor 5
• Ultrasound of salivary glands if intermittent swelling before eating 1

Common Pitfalls to Avoid

• Missing ACE inhibitor-induced angioedema by not obtaining complete medication history, which can progress to airway compromise 1
• Failing to check C4 levels in patients with isolated facial swelling without urticaria, delaying diagnosis of potentially fatal hereditary angioedema 1
• Overlooking hypothyroidism in patients with gradual onset facial puffiness and nonspecific symptoms like fatigue 4
• Dismissing morning periorbital edema as benign without checking urinalysis, missing nephrotic syndrome 6
• Not obtaining chest imaging in patients with facial puffiness and dyspnea, missing superior vena cava syndrome from mediastinal masses 2
• Attributing chronic facial swelling to allergies without proper workup, missing cardiac, renal, or endocrine causes 1, 4, 3