What is the cause and red flag for a 60-year-old female presenting with a red, puffy face without a clear cause or recent changes in intake or trauma?

Red, Puffy Face in a 60-Year-Old Female Without Clear Trigger

This presentation requires urgent evaluation for angioedema, particularly hereditary angioedema (HAE), superior vena cava syndrome, or allergic reaction, as facial swelling without trauma or obvious cause can represent a life-threatening condition requiring immediate intervention.

Immediate Red Flags and Life-Threatening Causes

Angioedema - Highest Priority

• Airway compromise is the critical red flag - assess for tongue swelling, difficulty swallowing, voice changes, or stridor, as upper airway edema can result in death from asphyxia 1
• Hereditary angioedema (HAE-C1-INH) presents with transient, well-circumscribed, nonpruritic swellings of the deep cutaneous, subcutaneous, or submucous tissue, commonly affecting the face 1
• Unlike allergic angioedema, HAE does not respond to antihistamines, corticosteroids, or epinephrine 1
• If airway involvement is suspected, plasma-derived human C1 inhibitor concentrate should be immediately available 1

Superior Vena Cava Syndrome

• Facial swelling with puffy appearance, particularly if bilateral and associated with neck vein distension, suggests venous obstruction 2
• This represents a medical emergency requiring urgent imaging and oncologic evaluation

Allergic Reaction

• Even without reported new exposures, occult allergen exposure remains possible
• Presence of urticaria, pruritus, or respiratory symptoms would support this diagnosis 1

Systematic Evaluation Approach

Critical Assessment Points

Immediate examination must include:

• Airway patency - inspect oropharynx, listen for stridor, assess voice quality 1
• Vital signs - blood pressure, pulse, oxygen saturation 1
• Distribution of swelling - localized vs. generalized, presence of lip/tongue involvement 1
• Skin characteristics - presence or absence of urticaria, erythema, warmth 1
• Associated symptoms - difficulty breathing, chest tightness, abdominal pain 1

Key Distinguishing Features

Angioedema (HAE or acquired):

• Nonpruritic, well-demarcated swelling 1
• May have history of recurrent episodes 1
• Family history of similar episodes suggests HAE 1
• Absence of urticaria favors HAE over allergic angioedema 1

Allergic reaction:

• Often accompanied by urticaria, pruritus 1
• Responds to antihistamines and epinephrine 1
• May have identifiable trigger upon careful history 1

Medication-related:

• ACE inhibitors can cause angioedema even after years of use 1
• Dupilumab is associated with facial swelling and blepharitis in 32-55% of patients 1
• Immune checkpoint inhibitors can cause facial edema 1

Diagnostic Workup

Laboratory Evaluation

If HAE is suspected:

• C4 level (screening test - low in HAE) 1
• C1-INH level and functional assay 1
• C1q level (helps distinguish HAE from acquired angioedema) 1

General workup:

• Complete blood count 3
• Erythrocyte sedimentation rate 3
• Serum albumin and calcium 3
• Thyroid function tests (thyroid dysfunction can cause facial puffiness) 4

Imaging Considerations

• Chest X-ray if superior vena cava syndrome suspected 3
• CT chest/neck with contrast if venous obstruction or mass suspected

Management Algorithm

If Airway Compromise Present or Imminent:

1. Call for emergency airway support immediately 1
2. Administer plasma-derived C1-INH concentrate (20 U/kg) if HAE suspected 1
3. For allergic angioedema: epinephrine 0.3-0.5mg IM, antihistamines, corticosteroids 1
4. Prepare for potential intubation - have equipment ready 1

If No Immediate Airway Threat:

1. Observe closely for progression - re-examine frequently 1
2. Discontinue potential causative medications (ACE inhibitors, NSAIDs) 1
3. Initiate treatment based on suspected etiology:
   • For suspected allergic reaction: antihistamines (cetirizine, fexofenadine) 1
   • For HAE: arrange for C1-INH concentrate availability 1
   • For blepharitis component: warm compresses and ophthalmology referral if eyelid involvement 1

Special Considerations in 60-Year-Old Female

Age-Related Factors

• Facial tissue changes with aging include loss of subcutaneous fat and decreased blood flow, but these do not cause acute swelling 1
• New-onset angioedema at age 60 more likely represents acquired angioedema (medication-related or associated with lymphoproliferative disorder) rather than HAE 1

Systemic Disease Associations

• Oro-facial granulomatosis can present with facial swelling and should be considered if swelling persists 3
• Rheumatoid arthritis and other autoimmune conditions may be associated with facial mucinosis 4
• Sarcoidosis should be considered with persistent facial swelling 3

Critical Pitfalls to Avoid

• Never delay airway management while awaiting diagnostic confirmation 1
• Do not assume allergic angioedema and treat with antihistamines/steroids alone if HAE is possible, as these are ineffective 1
• Do not start corticosteroids before ophthalmologic examination if eye involvement present, as this may worsen infectious causes or mask diagnosis 1
• Do not discharge without clear follow-up plan and emergency action plan, as biphasic reactions can occur up to 6 hours later 1

Disposition

• Admit for observation if any airway symptoms, severe swelling, or diagnostic uncertainty 1
• Discharge with emergency medications (epinephrine auto-injector if allergic etiology suspected) and clear return precautions 1
• Arrange urgent follow-up within 24-48 hours for diagnostic workup completion 3