First Aid, Chapter 8, Immunologic Disorders, Hereditary and Acquired Angioedema Flashcards
What is the dominance of hereditary angioedema?
Autosomal dominant
Where is the C1 inhibitor gene located?
chromosome 11
What do C1 esterase inhibitor mutations cause?
C1esterase inhibitor mutations cause decreased protein (type I) or dysfunctional protein (type II).
What does C1 inh deficiency cause an overproduction of?
Bradykinin is the major mediator of swelling, and the lack of C1-INH leads to bradykinin overproduction.
What percentage of HAE have new mutations?
15%
What type of rash might precede HAE swelling episodes?
Nonpruritic rash, erythema marginatum.
What triggers HAE swelling episodes?
spontaneous or triggered by trauma or stress
How long do HAE episodes last?
2-4 days
What percentage of HAE type 1 patients experience laryngeal edema?
50%
What does swelling of the GI system cause in HAE?
Severe abdominal pain and third spacing.
What is HAE type 1 and what percentage of HAE patients does it constitute?
HAE type I: A mutation of one of the C1-INH gene alleles, leading to low or absent protein; 85% of patients present with HAE
What is HAE type 2 and what percentage of HAE patients does it constitute?
HAE type II: A mutation of one of the two gene alleles, leading to normal or high levels of a nonfunctioning C1 inhibitor protein; 15% of patients with HAE
What is HAE type 3? Who does it affect? What is it’s inheritance? What mutation might it be due to?
HAE type III: Normal C1-INH. Estrogen-dependent, seen primarily in women, and often triggered by pregnancy or exogenous estrogen administration. Inheritance is dominant, which may be due to a mutation in factor XII that augments its activity as an initiator of bradykinin formation.
What lab tests are decreased in HAE type 1? What are normal?
Decreased: C4 (often undetectable during an attack), decreased C1-inh level and function, normal C1q, normal C3
C2 decreased during an attack, normal when asymptomatic
What lab tests are decreased in HAE type 2? What are normal?
Increased: C1-inh normal or increased
C1 inh function: decreased
C4 level: decreased
Normal: C1q, C3
C2 decreased during an attack, normal when asymptomatic
What lab tests are decreased in HAE type 3? What are normal?
All complements are normal: C1 inh level and function, C1q, C4, and C3.
What lab tests are decreased in AAE type 1? What are normal?
decreased: c1 inh level and function, c1q, C4
Normal or decreased C3
What lab tests are decreased in AAE type 2? What are normal?
Decreased: C1 inh level (or may be normal), C1 inh function, C1q (or may be normal), C4, C3 (or may be normal)
What is the treatment for acute attacks in HAE?
- Airway management
- Hydration
- Pain control
- HAE-specific therapies: C1-INH concentrate, kallikrein inhibitor (ecallantide), bradykinin receptor antagonist (icatibant)
- Fresh frozen plasma has been historically used, but may lead to paradoxical worsening
How do androgen derivatives work in HAE? What are adverse effects?
Attenuated androgens: Androgen derivatives, such as danazol and stanozolol, help prevent attacks by inducing hepatic synthesis of C1-INH. Common adverse effects of this type of long-term therapy include hepatotoxicity, dyslipidemia, masculinization, and headaches.
What is the indication of Cinryze? What is it? What is the dose? What is the potential adverse effects?
Indication: long-term prophylaxis
Plasma-derived C1-inh
Dose: 1000 U IV q3-4 days
Adverse effect: Thrombotic events (rare)
What is the indication of Berinert? What is it? What is the dose? What is the potential adverse effects?
Indication: acute attacks
Plasma-derived C1-inh
Dose: 20 units/kg IV
Adverse effect: Thrombotic events (rare)
What is the indication of Kalbitor? What kind of drug is it? What is the dose? What is the potential adverse effects?
Indication: acute attacks
Kallikrein inhibitor ecallantide
Dose: 30 mg subq
Adverse effect: Anaphylaxis (~3-4% risk; black box warning)
What is the indication of Firazyr? What kind of drug is it? What is the dose? What is the potential adverse effects?
Indication: acute attacks
Bradykinin receptor antagonist
Dose: 30 mg subq, may repeat q6h (max 3 doses/24 hours)
Adverse effect: Injection site reactions
Which complement component is decreased in acquired, but not hereditary, angioedema?
c1q
Which medication approved for treatment of acute attacks of HAE carries a black box warning for anaphylaxis?
Ecallantide (Kalbitor)
What are the indications for short-term prophylaxis in HAE?
Indicated prior to oral or general surgical procedures. Angioedema episodes typically happen within 48 hours of trauma or surgery.
What medications are used for short-term prophylaxis in HAE?
Androgens: High dose, 3–5 days prior to planned procedure
C1 esterase inhibitor, infused 1–2 hours prior to procedure
What contraception should be used if it is used in HAE?
Estrogens should be avoided. Progestins can be used
What is the treatment of HAE during pregnancy? What is contraindicated?
Pregnancy:
o Attenuated androgens are contraindicated
o Plasma-derived C1-INH is preferred for acute treatment, short-term and long-term prophylaxis
Are HAE complications common for women during delivery? Is prophylaxis recommended?
o Complications during vaginal delivery are rare
o Plasma-derived C1-INH prophylaxis is advised before caesarian section, and forceps or vacuum extraction
What are the two types of acquired angioedema? What conditions are they associated with? What are the C1-inh levels in each?
Classification
-Type I (paraneoplastic)
o Associated with B-cell lymphoproliferative diseases
o Monoclonal gammopathy of uncertain significance (MGUS)
o Consumption of C1-INH by neoplastic lymphatic tissue
-Type II (autoimmune)
o Autoantibody to C1-INH always present. Impairs enzyme function
o C1-INH levels are normal
When does acquired angioedema present? What causes it? What complement level distingues it from hereditary? Why is the C1-inh level low?
- Late onset, after fourth decade
- Overproduction of bradykinin
- The low C1q level distinguishes this condition from the hereditary disorder
- C4, C2, and C3 may also be depleted
- Low C1-INH level caused by C1 activation.
What are causes of recurrent angioedema? How often is urticaria and pruritus present?
Recurrent angioedema may be due to medications, allergen-induced, or physically induced. In about 50% of cases, urticaria and pruritus are associated.
What is the most common cause of acute angioedema in the ED? What is the mechanism? What is being investigated as a potential treatment?
- ACE I use
- The mechanism is thought to involve impaired bradykinin degradation. Icatibant, which is a bradykinin receptor antagonist, is being investigated for potential use in ACEI-induced angioedema.
