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CIA Review > Angioedema > Flashcards

Angioedema Flashcards

1
Q

Types of angioedema

1) What are the different types of HAE?
2) What are the findings on testing?
3) What are the underlying genetic mutations?

A

1) AAE (Acquired angioedema)
- Associated with B-cell lymphoproliferative disorders, including lymphoma, other B-cell malignancies, and monoclonal gammaopathies of undetermined significance (MGUS)
- multiple myeloma, systemic lupus erythematosus, eosinophilic granulomatosis with polyangitis (Churg-Strauss), and infections including HIV and Hepatitis B
- 2 AI, 2 infections, 3 cancers
2) HAE (see graphic)

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2
Q

What are the clinical features of HAE?

A
  • Recurrent attacks of non-pruritic, non-pitting, SC or submucosal angioedema
  • Circumscribed edema without urticaria
  • Abdominal attacks: bowel edema associated pain, vomiting, diarrhea
  • Angioedematous attacks can be preceded by prodromal symptoms like erythema marginatum
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3
Q

Diagnosis HAE: C1-INH testing

A
  • C1-INH level and/or function <50% of normal
  • Measurements should be performed twice, at an interval of at least 1 month
  • Testing under one year of age may not be reliable (unless genetic typing)
  • False elevation may occur during infection or other inflammatory state
  • False low level can or if sample not handled appropriately (outside lab)
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4
Q

Diagnosis HAE: C4 testing

A
  • C4 is normal between swelling events in 2%
  • If C4 is normal then question accuracy of C1 inhibitor results
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5
Q

Diagnosis of HAE

A
  • C4
  • C1-INH level
  • C1-INH function
  • Genetic testing
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6
Q

What are the genetics of HAE?

A
  • Autosomal dominant
  • Chromosome 11q12-q13.1
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7
Q

Anti-histamines, epinephrine and steroids in HAE

A
  • Most reports suggest that acute exacerbations of HAE or AAE typically do not respond to administration of antihistamines, glucocorticoids, or epinephrine.
  • However, some researchers have reported success in the acute management of AAE using these agents, probably owing to control of the mast cell degranulation and histamine release
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8
Q

Diagnosis of HAE with normal C1 inhibitor

A
  • Episodic angioedema affecting characteristic organs, without urticaria
  • FHx of angioedema and/or presence of a mutation to F12, ANGPT1, PLG, KNG1, myoferlin gene mutations associated with the disease
  • Failure to respond to chronic, high-dose antihistamine therapy (omalizumab, steroids)
  • Normal C4 and normal C1INH level and function
  • No medications that could cause angioedema, such ACE inhibitors or NSAIDs
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9
Q

Differential diagnosis of HAE with normal C1 inhibitor

A
  • Idiopathic bradykinin mediated angioedema (no family history)
  • Idiopathic histaminergic angioedema (needs adequate trial of high-dose antihistamine, omalizumab, oral corticosteroids)
  • Conditions mimicking angioedema (vocal cord dysfunction)
  • Factitious angioedema
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10
Q

Pathway in HAE and therapeutic targets

A
  • C1 inhibitor is produced in the liver
  • Androgens works by increasing C1 inhibitor from the good allele (can’t fix the bad allele)
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11
Q

Treatment options in HAE
(available options and their brand names)

A

OPTIONS AVAILABLE:

Icatibant (Firazyr)- bradykinin receptor blocker

Plasma dervived C1 inhibitor
- Berinert (IV)- plasma dervived C1 inhibitor
- Cinryze (IV) - long term plasma c1 inhibitor
- Haegarda (SC)- plasma-derived concentrate of C1 Esterase Inhibitor (Human)

Ecallantide - kallikrein inhibitor
Lanadelumab (Takhzyro)- human monoclonal antibody that targets plasma kallikrein

Ruconest- recombinant c1 inhibitor

ACUTE TREATMENT
- Intravenous plasma derived C1 inhibitor
- Icatibant

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12
Q

What are the recommended acute treatments for HAE (general)?

A

Effective treatments for acute attacks:
- IV plasma derived C1INH
- Icatibant
- Ecallantide
- IV recombinant human C1INH

Could be used for acute attacks if other therapies not available:
- Frozen plasma

Should not be used for acute attacks:
- Attenuated androgens
- Tranexamic acid

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13
Q

What are the recommended acute treatments for HAE (pregnant patients)?

A

Effective treatments for acute attacks:
- IV plasma derived C1INH

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14
Q

What are the recommended acute treatments for HAE (pediatric patients)?

A

Effective treatments for acute attacks in pediatric patients (moderate evidence):
- IV plasma derived C1INH

Effective treatments for acute attacks in pediatric patients (consensus):
- Icatibant
- IV recombinant human C1 INH

Effective treatments for acute attacks in adolescent patients:
- Ecallantide

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15
Q

What are the recommended acute treatments for HAE (with normal C1 INH)?

A

Effective treatments for acute attacks (moderate evidence):
- IV plasma derived C1INH

Effective treatments for acute attacks (consensus):
- Icatibant

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16
Q

What is recommended short-term prophylaxis for HAE?

A

IV plasma derived C1 INH

17
Q

What is recommended long-term prophylaxis for HAE (general)?

A

plasma derived C1 INH (?subcutaneous)
lanadelumab

(attenuated androgens in some patients)

18
Q

What is recommended long-term prophylaxis for HAE (pregnant patients)?

A

plasma derived C1 INH

(don’t use attenuated androgens)

19
Q

What is recommended long-term prophylaxis for HAE (pediatric patients)?

A

plasma derived C1 INH

(don’t use androgens)

20
Q

Considerations in management of HAE

A
  • consider acute treatment, short-term prophylaxis, long-term prophylaxis
  • consider self administration
  • inform regarding HAE patient associations
  • physicians should participate in an HAE registry and offer patients enrolment
21
Q

How do ACEi cause angioedema?

A
  • ACE inhibitors block the breakdown of bradykinin, causing levels of this protein to rise and blood vessels to widen (vasodilation).
22
Q

What is brand name of lanadelumab and approved for what age?

A

TAKHZYRO (lanadelumab-flyo) is a prescription medicine used to prevent attacks of hereditary angioedema (HAE) in people 2 years of age and older. It is not known if TAKHZYRO is safe and effective in children under 2 years of age.

23
Q

ACEi induced angioedema

A
  • Incidence of angioedema in patients on ACEi is 0.1-0.7% (up to 5x greater in people of African descent)
  • Usually affects lips, tongue, and face, although visceral edema presenting as acute abdominal pain possible
  • Symptoms typically begin during first week of treatment, but some develop after years of uneventful therapy
  • ARBs also associated with angioedema but only small % who develop ACEi-related angioedema continue to experience sx after switch to ARB, therefore ARBs do not have to be avoided
  • Impact of ACEi d/c may only be clear after several month, b/c some patients will have small # of recurrent episodes, particularly in first few months after ACEi d/c
24
Q

What is the M protein

A

Myeloma protein (aka monoclonal protein, M protein, M component, M spike, spike protein, or paraprotein)

  • An abnormal immunoglobulin or (more often) a fragment thereof, such as an immunoglobulin light chain, that is produced in excess by an abnormal monoclonal proliferation of plasma cells
  • Typically in multiple myeloma or MGUS
25
Q

What is MGUS?

A

Monoclonal gammopathy of undetermined significance
- Overproduction of one antibody but condition is benign
- Clinically asymptomatic premalignant clonal plasma cell or lymphoplasmacytic proliferative disorder
- Defined by presence of a serum monoclonal protein (M protein) at a concentration <3 g/dL, a bone marrow with <10 percent monoclonal plasma cells, and absence of end-organ damage (lytic bone lesions, anemia, hypercalcemia, kidney impairment, hyperviscosity) related to the proliferative process
- At a minimum, individuals suspected of having MGUS should be evaluated with the following studies: CBC, Serum Ca and Cr, Serum protein electrophoresis and immunofixation, Serum free light chain (FLC) assay, Quantitative immunoglobulins
- Over time, MGUS may develop into multiple myeloma

26
Q

Protein Electrophoresis, Immunofixation Electrophoresis

A

AKA
- Serum Protein Electrophoresis, Protein ELP, SPE, SPEP, Gel Electrophoresis, Capillary Electrophoresis, Immunosubtraction Electrophoresis, Urine Protein Electrophoresis, UPE, UPEP, IFE, CSF Protein Electrophoresis, Electrophoresis

When an abnormal protein (band or peak) is detected, additional tests are done to identify the type of protein (immunotyping). Immunofixation electrophoresis or immunosubtraction electrophoresis can be used to identify abnormal bands seen on protein electrophoresis, typically in the gamma region, in order to determine whether a type of antibody (immunoglobulin) is abnormally produced (e.g., IgG, IgA, IgM).

27
Q

Characteristics, lab findings and treatment/management of AAE?

A
  • AAE (Acquired angioedema)
  • Associated with B-cell lymphoproliferative disorders, including lymphoma, other B-cell malignancies, MGUS, multiple myeloma, SLE, EGPA, and infections (including HIV, Hep B)
  • Often later in life (typically 4th decade or later) vs. HAE
  • Low C4, normal or low C1-INH level, low C1-INH function (often <50%) and low C1q, but up to 30% of patients can have normal or near normal C1q levels.
  • If anti-C1-INH antibodies are present this can confirm AAE diagnosis, but this is not a required diagnostic test
  • When this dx is suspected, screening tests to consider include a CBC+diff, a serum protein electrophoresis and immunofixation, a CXR, and an abdominal ultrasound or CT.
  • Treatment: plasma derived C1-INH concentrate
  • Prophylaxis: tranexamic acid preferred therapy given concern of C1-INH resistance
  • If AAE and no associated medical disorder- closely follow for possible development of one (regularly scheduled cancer screenings, complete physical exam and screening tests listed above q1y)
28
Q

Prodromal rash before HAE episode+ other possible prodromal symptoms

A

Prodromal symptoms precede an angioedema attack by several hours or up to a day in up to 50% of patients with HAE. The most common prodromal symptoms include an erythematous nonurticarial rash (erythema marginatum), localized tingling, and a sense of skin tightness. 34 Other prodromal symptoms include fatigue, malaise, flulike symptoms, irritability, mood changes, hyperactivity, thirst, and nausea.

29
Q

Short term prophylaxis in HAE

A

2

Old exam answer:
Short-term Prophylactic Treatment (STP) (AACI 2018)
- No specific treatments are approved in Canada for STP
- C1-INH replacement is approved in Europe -> Cinryze (1000 units) is given w/in 24hrs of an anticipated
procedure while Berinert (1000 units) is given w/in 6hrs of a procedure

30
Q

On demand treatment in HAE

A

2

31
Q

Long term prophylaxis in HAE

A

4

CIA Review (28 decks)

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