What are the management options for angioedema?

Management of Angioedema: OLDCARTS and Treatment Approach

For the management of angioedema, plasma-derived C1 inhibitor concentrates, bradykinin receptor antagonists (icatibant), or plasma kallikrein inhibitors (ecallantide) should be used as first-line treatments for acute attacks, while standard treatments like epinephrine, corticosteroids, and antihistamines are ineffective for hereditary angioedema. 1, 2

OLDCARTS for Angioedema Assessment

Onset

• Sudden onset is typical for all forms of angioedema
• HAE attacks typically progress over 24 hours, then slowly resolve over 48-72 hours 1
• ACE inhibitor-associated angioedema can occur within months of starting therapy or even after years of continuous use 1

Location

• Extremities (50% of attacks)
• Abdomen (50% of attacks)
• Face, oropharynx, larynx (less common but potentially life-threatening)
• Genitourinary tract
• Different HAE subtypes may have characteristic locations (e.g., HAE-PLG often affects the tongue) 1

Duration

• HAE attacks typically last 2-5 days without treatment
• With appropriate treatment, duration can be significantly shortened
• ACE inhibitor-associated angioedema may persist for days after drug discontinuation 1

Characteristics

• Non-pruritic, non-pitting angioedema
• No associated urticaria in HAE and ACE inhibitor-induced angioedema
• Possible prodromal symptoms in HAE: erythema marginatum (non-urticarial rash), localized tingling, skin tightness 1

Aggravating/Alleviating Factors

• Triggers: stress, trauma, estrogen exposure, ACE inhibitors 1
• HAE-FXII is particularly sensitive to estrogen 1
• Standard angioedema treatments (antihistamines, steroids, epinephrine) are ineffective for HAE 1

Radiation/Related Symptoms

• Abdominal attacks: severe pain, nausea, vomiting, fluid sequestration, hypotension 1
• Laryngeal attacks: voice changes, difficulty swallowing, breathing difficulty 1

Timing

• Episodic rather than continuous swelling
• Frequency varies greatly between patients and within the same patient over time 1

Severity

• Highly variable between patients and attacks
• Laryngeal attacks are most dangerous with potential for asphyxiation 1
• Abdominal attacks can mimic acute abdomen and lead to unnecessary surgery 1

Management of Acute Angioedema Attacks

First-Line Treatments for HAE

1. Plasma-derived C1 inhibitor concentrate

   • First-line for HAE attacks, especially in pregnancy and porphyria 1, 2
   • Most effective when administered early in an attack 1

2. Icatibant (bradykinin B2 receptor antagonist)

   • 30 mg subcutaneously in the abdomen
   • If inadequate response, additional injections may be given at ≥6-hour intervals
   • Maximum 3 injections in 24 hours 3
   • Patients can self-administer upon recognition of an attack 3

3. Ecallantide (plasma kallikrein inhibitor)

   • Effective for acute HAE attacks 1
   • Requires monitoring due to anaphylaxis risk 2

Alternative Options (when first-line treatments unavailable)

1. Fresh frozen plasma (FFP)

   • Contains approximately 1 unit/ml of C1-INH
   • Dosage: 10-15 ml/kg or 2 units 1, 2
   • Response typically occurs within 90 minutes to 12 hours 1
   • Caution: may occasionally worsen symptoms and carries risk of viral transmission 1, 2

2. Symptomatic treatment

   • For abdominal attacks: pain control, antiemetics, aggressive hydration 1
   • Caution with narcotic use: addiction risk, especially with frequent attacks 1

For ACE Inhibitor-Associated Angioedema

1. Discontinue the ACE inhibitor (or ARB) - cornerstone of therapy 1
2. Observe in controlled environment if airway involvement 1
3. Consider icatibant or FFP - case reports suggest efficacy but no controlled studies 1

Airway Management for Severe Angioedema

Critical Considerations

1. Close monitoring for signs of impending airway closure:

   • Change in voice
   • Loss of ability to swallow
   • Difficulty breathing 1

2. Early intubation or tracheotomy for upper airway angioedema, especially where first-line treatments are unavailable 1

3. Observation in medical facility capable of performing intubation or tracheostomy for all patients with oropharyngeal/laryngeal attacks 1

Prophylactic Treatment Options

Short-Term Prophylaxis (for predictable stressors like procedures)

1. Plasma-derived C1INH (1000-2000 U or 20 U/kg) 1-6 hours before procedure 2
2. Fresh frozen plasma (2 units) if C1INH unavailable 2
3. Short-term high-dose anabolic androgens 1

Long-Term Prophylaxis

1. Plasma-derived C1INH replacement - safe and effective 1
2. Lanadelumab - effective option 2
3. Attenuated androgens (e.g., danazol) - effective but with more side effects 1, 2
4. Antifibrinolytic agents - less effective than androgens but relatively safe 1
   • May be particularly effective for HAE-FXII 1

Common Pitfalls to Avoid

1. Misdiagnosis as allergic reaction, leading to inappropriate treatment 2
2. Delayed treatment of acute attacks, especially laryngeal attacks 2
3. Reliance on ineffective treatments (epinephrine, antihistamines, corticosteroids) for HAE 1, 2
4. Inappropriate use of narcotics for pain management in frequent abdominal attacks 1
5. Failure to discontinue ACE inhibitors in patients with angioedema 1
6. Unnecessary surgical interventions for abdominal attacks 1

Special Considerations

1. Pregnancy: Androgens contraindicated; plasma-derived C1INH preferred 2
2. Resource-limited settings: FFP may be the only available option 1
3. African Americans: Higher risk of ACE inhibitor-induced angioedema 1