What is the treatment and workup for a pediatric patient presenting with angioedema?

Treatment and Workup for Pediatric Angioedema

Immediate Assessment and Stabilization

Immediately assess for life-threatening airway involvement by checking for oropharyngeal or laryngeal edema, respiratory distress, voice changes, difficulty swallowing, or signs of shock. 1, 2

• Monitor the child in a facility capable of performing intubation or tracheostomy if oropharyngeal or laryngeal involvement is present 1, 2
• Consider elective intubation if signs of impending airway closure develop (voice changes, inability to swallow, breathing difficulty) 2
• Have backup tracheostomy equipment immediately available 3
• Administer high-flow oxygen via face mask for severe laryngeal edema 1
• Avoid direct visualization of the airway unless absolutely necessary, as trauma can worsen angioedema 3

Determine Angioedema Type

The critical first step after securing the airway is differentiating between histamine-mediated (allergic) and bradykinin-mediated angioedema, as treatments differ completely. 2, 3

Key Clinical Distinctions:

• Histamine-mediated: Accompanied by urticaria (hives), pruritus, responds to antihistamines and epinephrine 4, 2
• Bradykinin-mediated (HAE): No urticaria, no pruritus, does NOT respond to standard allergy treatments 2, 3

Initial Laboratory Workup

For angioedema without urticaria, immediately order serum C4 level as the screening test for hereditary or acquired C1 inhibitor deficiency. 4

• If C4 is low (<30% mean normal), confirm with quantitative and functional C1 inhibitor assays 4
• C1q level helps distinguish hereditary (normal C1q) from acquired C1 inhibitor deficiency (low C1q) 4
• For angioedema with urticaria, laboratory workup is generally not needed acutely unless recurrent 4

Treatment Based on Type

For Histamine-Mediated Angioedema (with urticaria):

Administer intramuscular epinephrine immediately for significant symptoms or any airway involvement, with weight-based dosing for children. 1, 2

• Give IV diphenhydramine 50 mg (or weight-appropriate pediatric dose) 2, 3
• Administer IV methylprednisolone 125 mg (or 1-2 mg/kg for children) as adjunctive therapy 1, 2
• Add H2 blockers: ranitidine 50 mg IV or famotidine 20 mg IV (weight-adjusted for children) 2, 3

For Bradykinin-Mediated Angioedema (HAE):

Administer C1 inhibitor replacement therapy (20 IU/kg) as the preferred treatment for hereditary angioedema with laryngeal involvement. 1, 5

• Critical: Standard allergy treatments (epinephrine, antihistamines, corticosteroids) are completely ineffective for HAE and should not delay specific therapy 2, 3
• If C1-INH concentrate unavailable, use fresh frozen plasma 10-15 mL/kg as an alternative 1, 2
• Icatibant (0.4 mg/kg subcutaneously, maximum 30 mg) is effective in pediatric patients aged 2-18 years, with median time to symptom relief of 1 hour 6
• Administer C1-INH within 8 hours of reconstitution at approximately 4 mL per minute 5

Supportive Care

• Provide aggressive IV hydration for abdominal attacks 1, 3
• Administer antiemetics for nausea/vomiting 1, 3
• Give appropriate analgesia for pain control, but avoid creating narcotic dependence in patients with frequent attacks 3
• Avoid sedatives in patients with respiratory compromise 1

Observation and Disposition

• Observe until symptoms have significantly improved before discharge 1
• For laryngeal attacks, extended observation is mandatory as historical mortality rates approach 30% without treatment 2
• Following self-administration of treatment for laryngeal HAE attacks, patients must immediately seek medical attention 5

Long-Term Management for HAE Patients

Tranexamic acid (30-50 mg/kg/day) is the preferred long-term prophylaxis in children where first-line C1-INH replacement is unavailable. 2, 7

• Attenuated androgens (danazol) may be considered but carry high side effect burden in children, including delayed menarche 2, 7
• For short-term prophylaxis before dental or surgical procedures, administer C1-INH concentrate 1000-2000 U or 20 IU/kg 4, 2
• Educate families on trigger avoidance: trauma (even minor), emotional stress, estrogen-containing medications 4
• Refer to allergist/immunologist for ongoing management and family screening 1

Critical Pitfalls to Avoid

• Never delay epinephrine in histamine-mediated angioedema with airway involvement 2, 3
• Never use standard allergy treatments for confirmed or suspected HAE—they are ineffective and waste critical time 2, 3
• Never discharge patients with oropharyngeal or laryngeal involvement without adequate observation 2, 3
• Never prescribe ACE inhibitors to patients with any form of angioedema, especially HAE 4
• Avoid estrogen-containing contraceptives in female HAE patients as they increase attack frequency 4