What is the treatment for C1 esterase inhibitor deficiency?

Treatment of C1 Esterase Inhibitor Deficiency

For acquired C1 inhibitor deficiency, treat acute attacks with C1 inhibitor concentrate (though patients with high autoantibody levels may be resistant), ecallantide, or icatibant, and prioritize antifibrinolytic drugs over androgens for long-term prophylaxis while aggressively treating any underlying B-cell proliferative disorder. 1

Distinguishing Acquired from Hereditary C1 Inhibitor Deficiency

The treatment approach differs significantly between acquired and hereditary forms:

• Acquired C1 inhibitor deficiency is associated with underlying B-cell proliferation (lymphoma or monoclonal gammopathy) and often involves autoantibodies against C1 inhibitor 1
• Hereditary angioedema (HAE) is an autosomal dominant genetic condition with absent or dysfunctional C1 inhibitor 2, 3

Acute Attack Management

For Acquired C1 Inhibitor Deficiency

Acute attacks do not respond to antihistamines, corticosteroids, or epinephrine—these should never be used as first-line treatment. 1

Effective acute treatments include:

• C1 inhibitor replacement therapy may be effective, but patients with high levels of C1 inhibitor autoantibodies can be resistant to this therapy 1
• Ecallantide (kallikrein inhibitor) has demonstrated efficacy 1
• Icatibant (bradykinin B2 receptor antagonist) has demonstrated efficacy 1, 4

For Hereditary Angioedema (HAE)

Plasma-derived C1 inhibitor concentrate (1000-2000 U IV or 20 U/kg for children) is the most effective first-line treatment and should be administered as early as possible during an attack. 5

Alternative acute treatments:

• Icatibant 30 mg subcutaneously (can repeat at 6-hour intervals, maximum 3 injections in 24 hours) 5, 4
• Ecallantide (must be administered by healthcare professional due to anaphylaxis risk) 5
• Recombinant human C1 inhibitor 5, 3
• Fresh frozen plasma (10-15 mL/kg) only in resource-limited settings where first-line treatments are unavailable 5

Critical airway management: Laryngeal attacks require observation in a facility capable of intubation or tracheostomy, with close monitoring for voice changes, inability to swallow, or breathing difficulty 5

Long-Term Prophylaxis

For Acquired C1 Inhibitor Deficiency

Antifibrinolytic drugs (tranexamic acid) are MORE effective than androgens in acquired C1 inhibitor deficiency—this is the opposite of hereditary angioedema. 1

Prophylaxis options in order of preference:

1. Antifibrinolytic drugs (tranexamic acid) - first-line for acquired form 1
2. 17α-alkylated androgens (danazol) - less effective than in HAE 1
3. Treat the underlying disease - essential and may lead to remission 1

For autoantibody-positive patients, consider:

• Rituximab - sustained remission reported in 3 patients 1
• Plasmapheresis 1
• Cyclophosphamide 1
• High-dose intravenous immunoglobulin 1

For Hereditary Angioedema (HAE)

First-line options for long-term prophylaxis:

• Plasma-derived C1 inhibitor concentrate 5, 3
• Lanadelumab 5, 3

Second-line options:

• Attenuated androgens (danazol): initiate at high or low dose, titrate slowly to lowest effective dose, adjust no more frequently than once per week 5, 6
• Tranexamic acid 5, 3

Danazol dosing considerations: The drug exhibits non-linear pharmacokinetics—a 4-fold increase in dose produces only a 1.6-2.5 fold increase in drug exposure 6

Short-Term (Preprocedure) Prophylaxis

For HAE patients undergoing dental work, surgery, or invasive procedures, administer plasma-derived C1 inhibitor concentrate (1000-2000 U or 20 U/kg for children) before the procedure. 5

• For cesarean section, use epidural anesthesia (not general) to avoid endotracheal trauma and administer prophylactic C1 inhibitor 1
• For vaginal delivery with forceps or vacuum extraction, administer C1 inhibitor 1

Special Populations

Pregnancy

Plasma-derived C1 inhibitor concentrate is the first-line therapy for both acute attacks and prophylaxis during pregnancy. 1, 5

• Discontinue danazol at least 2 months before attempting conception due to risk of fetal masculinization 1, 5
• Discontinue tranexamic acid several days before attempting conception (half-life 2-8 hours) 1
• Antifibrinolytics can be used for mild attacks if C1 inhibitor is unavailable 1, 5
• No data available for icatibant, ecallantide, or recombinant C1 inhibitor in pregnancy—avoid these agents 1
• Fresh frozen plasma carries risk of anaphylaxis and may paradoxically worsen symptoms by supplying bradykinin substrates 1

Postpartum monitoring: Close follow-up for at least 72 hours after delivery is essential due to increased attack risk 1

Pediatric Patients

Danazol should generally be avoided in children before Tanner Stage V of puberty due to effects on growth and development. 5

Common Pitfalls to Avoid

• Never use antihistamines, corticosteroids, or epinephrine as first-line treatment—they are ineffective for C1 inhibitor deficiency 1, 5
• Do not delay treatment of acute attacks, especially laryngeal involvement—historical mortality from laryngeal attacks is approximately 30% 5
• In acquired C1 inhibitor deficiency, do not assume androgens will be as effective as in HAE—antifibrinolytics work better 1
• Always investigate and treat underlying B-cell disorders in acquired C1 inhibitor deficiency—this may lead to disease remission 1
• Do not use attenuated androgens during pregnancy or within 2 months of attempting conception 1, 5

Self-Administration and Home Treatment

All HAE patients should be trained for self-administration of acute treatments at home, except ecallantide which requires healthcare professional administration due to anaphylaxis risk. 5, 3

• Home therapy improves compliance (71.2% of attacks treated at home vs. 21.6% in hospital) 7
• Self-administration is particularly valuable for patients with high attack frequency 7
• Home treatment with icatibant results in average savings of €121.30 per acute attack compared to hospital administration 8