10. Urticaria & Angioedema

Question 1

see paper cards for first half of questions (slides 1-55)

Answer 1

ok

Question 2

Which of the following has the pattern of low C4, normal C1INH antigen level, low C1INH function, and normal C1q?

A. Type I HAE
B. Type II HAE
C. HAE with normal C1INH
D. Acquired C1INH deficiency
E. ACE-I associated AE
F. non-histaminergic idiopathic AE

Answer 2

B. Type II HAE- mutations in SERPING1 gene causing functional C1 inhibitor deficiency

Question 3

C1 INH belongs to family of serine protease
inhibitors (serpins) and inhibits all but which of the following?
A. C1s and C1r (classical pathway)
B. Mannin binding lectin associated serine proteases
C. Platelet activating factor
D. FXIa (intrinsic pathway of coagulation)
E. FXIIa /f and kallikrein (contact system)
F. Weakly inhibits fibrinolytic pathway (Thrombin, plasmin, tissue type plasminogen activator)

Answer 3

C. Platelet activating factor

Question 4

C1 INH belongs to family of serine protease

inhibitors (serpins) and inhibits what pathways?

Answer 4

A. C1s and C1r (classical pathway)
B. Mannin binding lectin associated serine proteases
C. FXIa (intrinsic pathway of coagulation)
D. FXIIa /f and kallikrein (contact system)
E. Weakly inhibits fibrinolytic pathway (Thrombin, plasmin, tissue type plasminogen activator)

Question 5

What is the key mediator involved in Hereditary Angioedema Pathophysiology and how does it work?

Answer 5

Bradykinin.

Bradykinin increases vascular
permeability through B2 bradykinin
receptor on endothelial cells

Question 6

Which of the following is NOT one of the most common symptoms of an acute HAE attack?

A. extremity edema
B. vomiting
C. abdominal pain
D. laryngeal edema

Answer 6

B. vomiting

A. extremity edema 96%
C. abdominal pain 93%
D. laryngeal edema 50%

Question 7

A rash described as round, with a pale-pink center, surrounded by a slightly raised red outline spreading on the trunk and limbs can be a prodromal sign associated with what process?

Answer 7

Erythema marginatum

> 50% HAE patients have had
prodromal symptoms including EM, myalgias, fatigue

Question 8

A patient’s genetics reveals defective expression of 1 allele of C1 INH gene. What disease type would that be associated with?

A. Type I HAE
B. Type II HAE
C. HAE with normal C1INH
D. Acquired C1INH deficiency
E. ACE-I associated AE
F. non-histaminergic idiopathic AE

Answer 8

A. Type I HAE (~ 85% patients with C1 INH deficiency)

Type II HAE ~ 15 % patients with C1 INH deficiency due to Dysfunctional mutant protein

ACE-I associated AE 2/2 impaired bradykinin degradation

Question 9

Which of the following is NOT true about Acquired angioedema?

A. later onset than HAE
B. Facial angioedema is a more common presentation than laryngeal edema
C. almost all have C1q low
D. most commonly associated with MGUS and splenic marginal zone lymphoma
E. androgens are often effective for prophylaxis

Answer 9

E. Tranexamic acid often effective for prophylaxis (thromboembolic events a concern) but androgens with similar efficacy

A. 4th decade of life- Median onset age 62
B. Facial angioedema > abdominal pain > extremity > laryngeal
C. C1q low in 91%

Type I: paraneoplastic: consumption of C1-INH by neoplastic lymphatic tissue, low C1-INH level due to C1 activation

Type II: autoimmune: autoantibody to C1-INH, impairs enzyme function, normal C1-INH level

Question 10

Hereditary Angioedema with
normal C1INH is associated with mutations in all but which of the following in an autosomal dominant pattern?

A. SERPING1
B. FXII
C. angiopoietin
D. plasminogen

Answer 10

A. SERPING1 (Type I and II HAE)

• Normal C1 INH levels and function
• Predominantly female
• Facial > extremity swelling

Question 11

A 25 year old female presents with tongue and facial swelling. This happens every year or so, and does not happen to anyone else in her family. She has no symptoms preceding the onset of swelling, and no other swelling or pain in other areas. What is the most likely pattern of labs associated with this diagnosis?

A. low C4, normal C1INH antigen level, low C1INH function, and normal C1q
B. low C4, low C1INH antigen level, low C1INH function, and normal C1q
C. low C4, low/normal C1INH antigen level, low C1INH function, and low/normal C1q
D. normal C4, normal C1INH antigen level, normal C1INH function, and normal C1q

Answer 11

D. Hereditary Angioedema with
normal C1INH

A. Type II HAE
B. Type I HAE
C. Acquired AE

Question 12

Which of the following is not a preferred therapy for acute treatment for C1
INH Deficiencies?
A. FFP
B. C1 INH concentrate
C. kallikrein inhibitor
D. bradykinin B2 receptor antagonist
E. recombinant C1 INH

Answer 12

A. FFP (May worsen acute attack in small percentage)

Question 13

What is the preferred short term

prophylaxis for C1INH Deficiencies with anticipated procedures?

Answer 13

1. C1 INH concentrate 20
   u/kg <1 hr before
   procedure
2. Androgens 5 10 days
   prior and 2 days after
3. FFP (3 rd line)

Question 14

List the long term prophylaxis options for patients with for C1INH Deficiencies?

Answer 14

• C1 INH concentrate
• Landelumab (anti kallikrein mab
• Attenuated Androgens (danazol , stanozolol, oxandrolone)
• Antifibrinolytics (aminocaproic acid (Amicar tranexamic acid ( Lysteda)

Question 15

What routine evaluation should be performed in patients receiving attenuated androgens for HAE prophylaxis?

Answer 15

Annual ultrasounds and liver function tests every 6-12 mos (usually dose related AE of hepatotoxicity (rarely liver carcinoma))

Question 16

Which of the following is NOT a contraindication to receiving attenuated androgens for HAE prophylaxis?

A. Pregnancy
B. headaches
C. Lactation
D. childhood
E. prostate CA

Answer 16

B. headaches

Question 17

Which HAE specific therapy is associated with a pseudoallergic reaction due to MRGPRX2 stimulation?

Answer 17

Bradykinin-B2 receptor
antagonist - Icatibant- Firazyr

Injection site reactions (97%)

Question 18

Which HAE specific therapy is associated with a black box warning for anaphylaxis?

Answer 18

Kallikrein inhibitor

Ecallantide (Kalbitor)

Question 19

Which HAE specific therapy is contraindicated in a patient with a known or
suspected rabbit allergy?

Answer 19

Recombinant C1-INH
(Ruconest ®)
- Made in transgenic rabbits

Question 20

see chart for mechanisms of acute and long term treatments

Answer 20

(see additional slide in notes p 34)

see page 43 for kinin activation pathway

Question 21

Which acute treatment for HAE is effective in 100% of patients?

Answer 21

Bradykinin-B2 receptor
antagonist - Icatibant- Firazyr

• C1INH 20u/kg effective in 91%
• Tranexamic acid least effective

Question 22

What are the 3 subtypes of urticarial vasculitis?

Answer 22

Normocomplementemic (NUV)
Hypocomplementemic UV (HUV)
Hypocomplementemic UV syndrome (HUVS)

Question 23

Which type of urticarial vasculitis is most commonly associated with SLE?

Answer 23

SLE: 54% HUV (3% NUV)

see additional slide in notes p 34

Question 24

Which type of urticarial vasculitis is more severe and most commonly associated with COPD in 50%?

Answer 24

HUVS (McDuffie syndrome)

Patients with UV and low complement not fulfilling criteria considered to have HUV

(see additional slide in notes p 34)

Question 25

Which of the following lab abnormalities that can be seen in urticarial vasculitis is only associated with the hypocomplementemic form of UV?

A. elevated ESR
B. ANA positive
C. low complement levels (C3, C4, CH50)
D. very low C1q levels
E. anti-C1q antibodies

Answer 25

E. Anti C1q antibodies present in 100% of HUV

see additional slide in notes p 34

Question 26

Which should be avoided in pregnant patients with HAE, progestins or estrogens?

Answer 26

estrogens

• androgens are contraindicate
• preferred tx is plasma derived C1-INH