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ANGIOEDEMA:ANGIOEDEMA:CASE & DISCUSSIONCASE & DISCUSSION
Pathophysiology and Pathophysiology and ManagementManagement
CaseCase GMGM 68 year old female68 year old female Presented to the casualty early hours of Presented to the casualty early hours of
morning on Saturday 6 April 2013morning on Saturday 6 April 2013 C/o swelling in mouth and face with C/o swelling in mouth and face with
increasing ‘tightening’ of throat, increasing ‘tightening’ of throat, progressively worsening over last 12hrsprogressively worsening over last 12hrs
No new medications, no medical or No new medications, no medical or food allergyfood allergy
PMHx:PMHx: HypertensionHypertension DMDM Current breast cancer patient on Current breast cancer patient on
chemotherapychemotherapy Had similar presentation one year ago, Had similar presentation one year ago,
treated at hospital treated at hospital No known allergiesNo known allergies
Social Hx:Social Hx: Nil of noteNil of noteSurgical historySurgical history: : Biopsy breast lump 3 years ago.Biopsy breast lump 3 years ago.
Meds:Meds: PerindoprilPerindopril HCTZHCTZ SimvastatinSimvastatin MetforminMetformin AspirinAspirin lasixlasix Chemotherapy (drug names unknown to Chemotherapy (drug names unknown to
patient’s daugther)patient’s daugther)
sats 97% R/A, BP 150/90 regular pulsesats 97% R/A, BP 150/90 regular pulse tachycardiactachycardiac No stridor No stridor Edema of lips and mainly of tongueEdema of lips and mainly of tongue Posterior pharyngeal wall not well Posterior pharyngeal wall not well
visualizedvisualized Flexible scope, larynx anatomically Flexible scope, larynx anatomically
normal no oedema or impending airway normal no oedema or impending airway obstructionobstruction
DDx:DDx: AngioedemaAngioedema Facial lymphedemaFacial lymphedema Autoimmune (Sjogren’s, SLE)Autoimmune (Sjogren’s, SLE) HypothyroidismHypothyroidism SVC syndromeSVC syndrome
Management:Management: Kept in casualty for initial treatmentKept in casualty for initial treatment Anti hypertensives given with omission of Anti hypertensives given with omission of
coversylcoversyl Lasix 20 mg iviLasix 20 mg ivi Decadron 8 mgDecadron 8 mg In 5 mins, the tongue almost halved in size and In 5 mins, the tongue almost halved in size and
patient was much more comfortable and not patient was much more comfortable and not distresseddistressed
Patient then admitted to ward for continuation Patient then admitted to ward for continuation of corticosteroids and monitering of vitalsof corticosteroids and monitering of vitals
Patient discharged after 24 hours of monitering Patient discharged after 24 hours of monitering and getting dexamethasone in the wardand getting dexamethasone in the ward
ANGIOEDEMAANGIOEDEMA
Definition:Definition: Rapid nonpitting edema of the dermis, Rapid nonpitting edema of the dermis,
subcutaneous tissue, mucosa and subcutaneous tissue, mucosa and submucosal tissuessubmucosal tissues
Areas of involvement:Areas of involvement: Face Face LipsLips LarynxLarynx ExtremitiesExtremities GenitalsGenitals IntestinesIntestines
If involvement of face/larynx = If involvement of face/larynx = potentially life-threateningpotentially life-threatening
94% of the time involves structures 94% of the time involves structures in the H&Nin the H&N
Epidemiology:Epidemiology: 10% of Americans have an episode 10% of Americans have an episode
once in their lifetime (20% in south once in their lifetime (20% in south africa)africa)
Higher in hypertensive patients that Higher in hypertensive patients that are on ACE inhibitorsare on ACE inhibitors
Usually in 3Usually in 3rdrd/4/4thth decades of life decades of life M=FM=F Attacks usually self-limiting and Attacks usually self-limiting and
resolve in 24-48 hours resolve in 24-48 hours Principal cause of mortality is airway Principal cause of mortality is airway
compromisecompromise
Basic Pathophysiology:Basic Pathophysiology: Increased vascular permeability in Increased vascular permeability in
the submucosal, subcutaneous, and the submucosal, subcutaneous, and deep dermal tissues.deep dermal tissues.
Mediated by vasoactive substances:Mediated by vasoactive substances:• HistamineHistamine• BradykininBradykinin• Products of complement cascade: C3a, Products of complement cascade: C3a,
C5aC5a
5 Main Causes:5 Main Causes:1.1. Hereditary C1INH deficiencyHereditary C1INH deficiency2.2. Acquired C1INH deficiencyAcquired C1INH deficiency3.3. ACE inhibitorsACE inhibitors4.4. Allergic reactionsAllergic reactions5.5. IdiopathicIdiopathic
Can sub-divide the causes of angioedema by Can sub-divide the causes of angioedema by mediators involved:mediators involved:
BradykininBradykinin – Induced: – Induced: Hereditary or acquired C1 inhibitor Hereditary or acquired C1 inhibitor
deficiencydeficiency ACE inhibitorsACE inhibitorsHistamineHistamine – Induced: – Induced: Allergic angioedemaAllergic angioedemaUnknownUnknown IdiopathicIdiopathic
BradykininBradykininBradykininBradykinin Peptide in blood coagulation subsystem Peptide in blood coagulation subsystem
• ‘‘contact system’contact system’ Release regulated by C1-INHRelease regulated by C1-INH
Stimulus for production:Stimulus for production: ToxinsToxins Injury/inflammationInjury/inflammation IschemiaIschemia Viral infectionsViral infections
Kinin-Kallikrein SystemKinin-Kallikrein System High molecular weight kininogen is High molecular weight kininogen is
combined with prekallikreincombined with prekallikrein Prekallikrein broken down by factor Prekallikrein broken down by factor
XIIa to kallikreinXIIa to kallikrein Kallikrein then breaks high molecular Kallikrein then breaks high molecular
weight Aminogen to bradykininweight Aminogen to bradykinin Bradkinin is main mediator of Bradkinin is main mediator of
vasopermeabilityvasopermeability
Kinin-Kallikrein SystemKinin-Kallikrein SystemC1-INH inhibits the reaction cascade at two C1-INH inhibits the reaction cascade at two
points:points: Prevents self-activation of factor XII (PreKPrevents self-activation of factor XII (PreKK)K) Inhibits release of bradykinin from HMW kininogenInhibits release of bradykinin from HMW kininogen
BradykininBradykinin
BradykininBradykininSupport for Bradykinin as mediator:Support for Bradykinin as mediator:
Cicardi (2003)Cicardi (2003) : showed increased : showed increased levels of bradykinin in affected arms of levels of bradykinin in affected arms of patientspatients
BUT increased bradykinin levels in BUT increased bradykinin levels in normal patients taking ACEIs (prolongs normal patients taking ACEIs (prolongs survival of bradykinin)survival of bradykinin)
ACEi AngioedemaACEi Angioedema Recently become the leading cause Recently become the leading cause
of acquired angioedemaof acquired angioedema Corresponds with increasingly Corresponds with increasingly
widespread use of ACEi to manage widespread use of ACEi to manage hypertension and CHFhypertension and CHF
Renin-Angiotensin-Renin-Angiotensin-Aldosterone System (RAAS)Aldosterone System (RAAS)
ACEi AngioedemaACEi Angioedema
Mechanism:Mechanism:ACE inhibition:ACE inhibition: reduces the catabolism of bradykininreduces the catabolism of bradykinin increase the availability of bradykininincrease the availability of bradykinin
*BUT bradykinin elevated in ALL *BUT bradykinin elevated in ALL patients on ACEi’s and <1% develop patients on ACEi’s and <1% develop angioedemaangioedema
ACEi AngioedemaACEi AngioedemaIncidence:Incidence: Can occur at ANY time during Can occur at ANY time during
treatment.treatment. Most severe episodes occur within Most severe episodes occur within
the first week of treatment.the first week of treatment. Some reports of incidence AFTER Some reports of incidence AFTER
discontinuation of therapy therefore discontinuation of therapy therefore may have latent effect.may have latent effect.
ACEi AngioedemaACEi AngioedemaLarge Trial - Determine Incidence:Large Trial - Determine Incidence:
Omapatrilat Cardiovascular Treatment Omapatrilat Cardiovascular Treatment versus Enalipril (versus Enalipril (O.C.T.A.V.E.O.C.T.A.V.E.) trial Kostis ) trial Kostis et al (2004)et al (2004)
• Double-blinded RCTDouble-blinded RCT• N = 24,302N = 24,302• Primary outcome: drug efficacy in Primary outcome: drug efficacy in
cardiac settingcardiac setting• Secondary outcome – incidence of Secondary outcome – incidence of
angioedemaangioedema• 2.17% vs 0.68%2.17% vs 0.68%
ACEi AngioedemaACEi AngioedemaEpidemiology:Epidemiology: More common in Black populations More common in Black populations
than Caucasian 3:1than Caucasian 3:1 Increased risk unrelated to dose, Increased risk unrelated to dose,
type of ACEi or concomitant type of ACEi or concomitant medicationsmedications
Increased sensitivity to elevated Increased sensitivity to elevated bradykinin levelsbradykinin levels
ACEi AngioedemaACEi AngioedemaOther Risk Factors:Other Risk Factors: ImmunocompromisedImmunocompromised Prior history of idiopathic Prior history of idiopathic
angioedemaangioedema Seafood allergySeafood allergy
ACEi AngioedemaACEi AngioedemaClinical presentation:Clinical presentation: Wide range of symptoms Wide range of symptoms
• Life-threatening to minor swelling (may Life-threatening to minor swelling (may not report to health-care provider)not report to health-care provider)
• Can resolve spontaneouslyCan resolve spontaneously In severe cases:In severe cases:
• Swelling of lips, tongue, post pharynx, Swelling of lips, tongue, post pharynx, eyeseyes
• Dyspnea, dysphagia, dysphonia in up to Dyspnea, dysphagia, dysphonia in up to 20% patients 20% patients a/w obstruction a/w obstruction
ACEi AngioedemaACEi AngioedemaTreatment: Treatment:
*Difficult to tailor Rx as difficult to *Difficult to tailor Rx as difficult to determine etiology in acute scenariodetermine etiology in acute scenario
ABCs always firstABCs always first• establish a/westablish a/w• Tongue edema is NON pitting therefore Tongue edema is NON pitting therefore
difficult orotracheal intubationdifficult orotracheal intubation• May require nasotracheal intubation or trachMay require nasotracheal intubation or trach
Secondary goal = prevent further edemaSecondary goal = prevent further edema
ACEi AngioedemaACEi AngioedemaTreatment:Treatment: Antihistamines often used, but ~ no Antihistamines often used, but ~ no
effecteffect Corticosteroids – minimal/no benefitCorticosteroids – minimal/no benefit Epinephrine – works in non-specific Epinephrine – works in non-specific
manner (vasoconstriction of leaky blood manner (vasoconstriction of leaky blood vessels)vessels)
FFP (likely the effect of functional FFP (likely the effect of functional kininase II – breaks down bradykinin)kininase II – breaks down bradykinin)
ACEi AngioedemaACEi Angioedema Currently NO diagnostic test to Currently NO diagnostic test to
determine who is at riskdetermine who is at risk
ARB AngioedemaARB Angioedema Links have been made with ARBs and Links have been made with ARBs and
angioedemaangioedema Highly variable results depending on the Highly variable results depending on the
studystudy Controversial evidence for triggering Controversial evidence for triggering
angioedemaangioedema ARBs not supposed to be involved in kinin ARBs not supposed to be involved in kinin
metabolismmetabolism Seen in patients who previously developed Seen in patients who previously developed
angioedema with ACEiangioedema with ACEi
ARB AngioedemaARB Angioedema Also present in patients who never Also present in patients who never
received ACEi’sreceived ACEi’s Unknown mechanism Unknown mechanism Unknown incidenceUnknown incidence
ARB AngioedemaARB AngioedemaCicardi et al (2004):Cicardi et al (2004): 2 of 26 patients with ACEi induced 2 of 26 patients with ACEi induced
angioedema also had angioedema angioedema also had angioedema when placed on an ARBwhen placed on an ARB
Effect disappeared upon w/drawl of the Effect disappeared upon w/drawl of the ARBARB
Recommendations: use ARBs Recommendations: use ARBs cautiously in patients w/ history of cautiously in patients w/ history of ACEi angioedemaACEi angioedema
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Rare (1:50 000-1:150 000)Rare (1:50 000-1:150 000) Autosomal dominantAutosomal dominant No ethnic or sexual prediliction No ethnic or sexual prediliction Individuals affected = commonly Individuals affected = commonly
heterozygous heterozygous Disorder of C1 inhibitor (C1INH)Disorder of C1 inhibitor (C1INH)
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Genetics - C1INH:Genetics - C1INH: C1 inhibitor – heavily glycosylated C1 inhibitor – heavily glycosylated
serine protease inhibitorserine protease inhibitor Chromosome 11q11-13.2Chromosome 11q11-13.2 Single dysfunctional allele results in Single dysfunctional allele results in
diseasedisease
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
C1INH:C1INH: Only regulator of classical Only regulator of classical
complement pathway activationcomplement pathway activationInvolved in:Involved in:
Contact system (XII and kallikrein)Contact system (XII and kallikrein) Complement cascade (C1r,C1s, MASP 2)Complement cascade (C1r,C1s, MASP 2) Intrinsic coagulation cascade (XI, plasmin, Intrinsic coagulation cascade (XI, plasmin,
tPA)tPA) Low levels C1INH OR dysfunctional Low levels C1INH OR dysfunctional
C1INH = HAEC1INH = HAE
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
2 types of HAE:2 types of HAE: Type IType I (85%) (85%)
low levels of C1INH and functional low levels of C1INH and functional deficiencydeficiency
Type IIType II (15%) (15%) Normal protein concentration but Normal protein concentration but
functional defectfunctional defect
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Diagnosis – Type I or II:Diagnosis – Type I or II: Measure C1INH antigen and Measure C1INH antigen and
functional levelsfunctional levels Type I – values <50% normalType I – values <50% normal Not specific asNot specific as::
absolute C1INH level is NOT correlated absolute C1INH level is NOT correlated with freq or degree of symptomswith freq or degree of symptoms
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Epidemiology:Epidemiology: Onset of attacks usually w/in 2Onset of attacks usually w/in 2ndnd
decade of lifedecade of life Time of onset to diagnosis 3-8 yearsTime of onset to diagnosis 3-8 years
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Clinical Presentation:Clinical Presentation: Repeated episodes of edema (NON Repeated episodes of edema (NON
pruritic and NON pitting):pruritic and NON pitting): FaceFace Extremities Extremities Genitals Genitals Intestines (w/ pain, N/V/D)Intestines (w/ pain, N/V/D) Larynx (less common) Larynx (less common) **Combination and migratory attacks **Combination and migratory attacks
commoncommon
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Clinical Presentation:Clinical Presentation: Laryngeal edemaLaryngeal edema
Usually in 3Usually in 3rdrd decade of life decade of life Lifetime incidence of 70% Lifetime incidence of 70% Retrospective review (Bork, 2000): Retrospective review (Bork, 2000):
40% pt’s lost family member to 40% pt’s lost family member to asphyxiationasphyxiation
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Clinical Presentation:Clinical Presentation: Erythema marginatum and macular rash Erythema marginatum and macular rash
in SOME patientsin SOME patients ***NO urticaria***NO urticaria Swelling increases over 24 hours then Swelling increases over 24 hours then
subsides over next 24-72 hourssubsides over next 24-72 hours Frequency, duration and severity of Frequency, duration and severity of
symptoms VARIABLE even w/in same symptoms VARIABLE even w/in same familyfamily
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Clinical Presentation:Clinical Presentation: Recognized triggers:Recognized triggers:
OCP (Estrogen – containing)OCP (Estrogen – containing) MensesMenses TraumaTrauma InfectionInfection Stress Stress Dental surgery(trigger for laryngeal Dental surgery(trigger for laryngeal
attack)attack)
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Labs:Labs: 1) C1INH - low levels, or elevated 1) C1INH - low levels, or elevated
levels of dysfunctional C1 esterase levels of dysfunctional C1 esterase inhibitor (detected by an immune inhibitor (detected by an immune assay).assay).
2) Between attacks, low levels of C4 2) Between attacks, low levels of C4 are noted.are noted.
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Economic/Burden:Economic/Burden: Untreated patients lose up to 100-Untreated patients lose up to 100-
150 work days/year150 work days/year Morbidity ~50%Morbidity ~50%
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Diagnostic Criteria:Diagnostic Criteria:A) A) Clinical:Clinical: Self-limited, angioedema without Self-limited, angioedema without
urticaria, recurrent and >12 hoursurticaria, recurrent and >12 hours Self-remitting abdo pain without Self-remitting abdo pain without
clear organic etiology, recurrent and clear organic etiology, recurrent and >6hrs>6hrs
Recurrent laryngeal edemaRecurrent laryngeal edema
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Diagnostic Criteria:Diagnostic Criteria:B) B) Laboratory:Laboratory: C1INH<50% at 2 sep determinations C1INH<50% at 2 sep determinations
with patient at basal conditionwith patient at basal condition C1INH function <50% C1INH function <50% Mutation in C1INH gene altering Mutation in C1INH gene altering
protein syn/functionprotein syn/function*low C4 not mentioned in criteria *low C4 not mentioned in criteria
although part of initial w/ualthough part of initial w/u
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Supportive treatment:Supportive treatment:Laryngeal edema:Laryngeal edema: Prudent use ETT intubationPrudent use ETT intubation Monitored setting until resolution of Monitored setting until resolution of
attackattack Steroids/antihistamines NOT usefulSteroids/antihistamines NOT useful Adrenaline nebs may decrease the Adrenaline nebs may decrease the
vascular component of edema but vascular component of edema but doesn’t change the underlying processdoesn’t change the underlying process
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Supportive treatment:Supportive treatment:Intestinal edema:Intestinal edema: Aggressive replacement fluid losses (3Aggressive replacement fluid losses (3rdrd
spacing and V/D)spacing and V/D) Pain managementPain management Non-sedating anti-emeticsNon-sedating anti-emetics Avoid interventional procedures unless Avoid interventional procedures unless
unusual s/s (hematemesis, hematochezia)unusual s/s (hematemesis, hematochezia)
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Established Pharmacologic Treatments:Established Pharmacologic Treatments:ProphalaxisProphalaxis::1)1) Androgen derivativesAndrogen derivatives2)2) Antifibrinolytic agentsAntifibrinolytic agents
Acute attacks:Acute attacks:3) FFP (replacement)3) FFP (replacement)4) Purified C1INH (not available in SA)4) Purified C1INH (not available in SA)
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Mechanism of action:Mechanism of action:1) Androgens (Danazol)1) Androgens (Danazol) Stimulate hepatocytes and other Stimulate hepatocytes and other
cells to secrete more C1INHcells to secrete more C1INH
2) Antifibrinolytics (2) Antifibrinolytics (Transexamic acid)Transexamic acid) Inhibits fibrinolysis and reduces Inhibits fibrinolysis and reduces
consumption of C1INHconsumption of C1INH
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Mechanism of action:Mechanism of action:3) FFP3) FFP Replaces C1INH Replaces C1INH
missing/dysfunctional in recipientmissing/dysfunctional in recipient
4)4) Purified C1INHPurified C1INH Replaces C1INHReplaces C1INH
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Recent Study (CSL Behring):Recent Study (CSL Behring):The The I.M.P.A.C.TI.M.P.A.C.T. trial (International Multi-. trial (International Multi-centre Prospective Angioedema C1-inhibitor centre Prospective Angioedema C1-inhibitor TrialsTrials
Phase III study conducted in N America and Phase III study conducted in N America and EuropeEurope
Comparing human pasteurized C1-INH vs Comparing human pasteurized C1-INH vs placebo for speed of relief of symptomsplacebo for speed of relief of symptoms
Studying patients with acute abdominal or Studying patients with acute abdominal or facial HAEfacial HAE
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Future Therapies:Future Therapies:2 Treatments Under Investigation:2 Treatments Under Investigation:• DX-88DX-88• Bradykinin Antagonist – IcatibantBradykinin Antagonist – Icatibant
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
DX-88DX-88 binds and inhibits proteolytic binds and inhibits proteolytic
activity of kallikrein activity of kallikrein 300x more specific than C1INH300x more specific than C1INH Lumry et al (2006) showed Lumry et al (2006) showed
successful resolution symptoms in successful resolution symptoms in all 215 attacks treated with DX-88all 215 attacks treated with DX-88
Kinin-Kallikrein SystemKinin-Kallikrein System
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Bradykinin antagonist – IcatibantBradykinin antagonist – Icatibant potent, selective bradykinin potent, selective bradykinin
receptor antagonistreceptor antagonist Bork et al (2007) showed treatment Bork et al (2007) showed treatment
considerably shortened duration of considerably shortened duration of attacks compared with untreated attacks compared with untreated attacks (1.0 hr vs several hrs)attacks (1.0 hr vs several hrs)
Hereditary Angioedema Hereditary Angioedema (HAE)(HAE)
Resolution after attack - not well Resolution after attack - not well understoodunderstood
Theories:Theories:1)1) Consumption of available Consumption of available
substrates for kallikreinsubstrates for kallikrein2)2) Removal of triggerRemoval of trigger
Acquired Angioedema Acquired Angioedema (AAE)(AAE)
2 Types:2 Types:1)1) Type I (AAE-I)Type I (AAE-I)
• associated with other diseases, most associated with other diseases, most commonly B-cell lymphoproliferative commonly B-cell lymphoproliferative disordersdisorders
2)2) Type II (AAE-II)Type II (AAE-II)• an autoimmune process (autoantibody an autoimmune process (autoantibody
directed against the C1 inhibitor directed against the C1 inhibitor molecule (C1-INH). molecule (C1-INH).
Acquired Angioedema Acquired Angioedema (AAE)(AAE)
Pathophysiology:Pathophysiology:1)1) AAE-IAAE-I
• assoc disorders (usually assoc disorders (usually lymphoproliferative malignancies, most lymphoproliferative malignancies, most common – B cell lymphoma) common – B cell lymphoma)
• produce complement-activating factors, produce complement-activating factors, antibodies, or other immune complexesantibodies, or other immune complexes
• destroy C1-INH functiondestroy C1-INH function
Acquired Angioedema Acquired Angioedema (AAE)(AAE)
PathophysiologyPathophysiology2)2) AAE-IIAAE-II
• normal C1-INH molecule is normal C1-INH molecule is synthesized in adequate amountssynthesized in adequate amounts
• subpopulation of B cells secretes subpopulation of B cells secretes autoantibodies to the C1-INH moleculeautoantibodies to the C1-INH molecule
• autoantibody binds to the reactive autoantibody binds to the reactive center of C1-INH and its regulatory center of C1-INH and its regulatory capacity is diminished/destroyed.capacity is diminished/destroyed.
Acquired Angioedema Acquired Angioedema (AAE)(AAE)
EpidemiologyEpidemiology Rare (150 cases reported in the Rare (150 cases reported in the
literature)literature) ?M=F??M=F? Race?Race? Onset most common after 4Onset most common after 4thth decade decade
of lifeof life
Acquired Angioedema Acquired Angioedema (AAE)(AAE)
Clinical presentation:Clinical presentation: *no family history (distinguish from *no family history (distinguish from
HAE)HAE) PainlessPainless Non-pruritic Non-pruritic Non-pitting Non-pitting Usually not assoc with urticariaUsually not assoc with urticariaEdema of the skin and subcutaneous Edema of the skin and subcutaneous
tissuestissues
Acquired Angioedema Acquired Angioedema (AAE)(AAE)
Labs:Labs: AAE-I and AAE-II AAE-I and AAE-II
Low C1-INH levels Low C1-INH levels Low C1q levels (except 1 reported case) Low C1q levels (except 1 reported case) Low C4 levels Low C4 levels Low C2 levels Low C2 levels
AAE-II - Positive immunoblot assay AAE-II - Positive immunoblot assay findings for 95-kd C1-INH cleavage findings for 95-kd C1-INH cleavage product product
Acquired Angioedema Acquired Angioedema (AAE)(AAE)
Management:Management: Supportive (airway)Supportive (airway) Androgens Androgens
may be beneficial in AAE-I but are of no may be beneficial in AAE-I but are of no value in AAE-IIvalue in AAE-II
AntifibrinolyticsAntifibrinolytics more effective for long-term prophylaxis more effective for long-term prophylaxis
in those with AAE.in those with AAE.
Acquired Angioedema Acquired Angioedema (AAE)(AAE)
Management:Management: Immunosuppressive therapyImmunosuppressive therapy
Direct toward decreasing autoantibody Direct toward decreasing autoantibody production may be of value in patients production may be of value in patients with AAE-IIwith AAE-II
Allergic Allergic Angioedema/UrticariaAngioedema/Urticaria
Allergic Allergic Angioedema/UrticariaAngioedema/Urticaria
Reactions are induced by histamine Reactions are induced by histamine and mediated by IgEand mediated by IgE
IgE mediated hypersensitivity IgE mediated hypersensitivity reactionreaction
Reaction with allergen induces the Reaction with allergen induces the release of histamine and other release of histamine and other mediatorsmediators
Result: vasodilatation and edemaResult: vasodilatation and edema
Allergic Allergic Angioedema/UrticariaAngioedema/Urticaria
Allergic Allergic Angioedema/UrticariaAngioedema/Urticaria
Biochemistry:Biochemistry: Dependent on presence IgE molec Dependent on presence IgE molec
sp to proteins in causative agentsp to proteins in causative agent IgE molec bind to patients mast cellsIgE molec bind to patients mast cells Trigger rxn upon re-exposure to Trigger rxn upon re-exposure to
antigenantigen
Allergic Allergic Angioedema/UrticariaAngioedema/Urticaria
Inciting Agents:Inciting Agents: MedicationsMedications FoodsFoods Latex Latex Environmental (includes insect Environmental (includes insect
bites)bites)
Allergic Allergic Angioedema/UrticariaAngioedema/Urticaria
Clinical Presentation:Clinical Presentation: Highly variableHighly variable Depends on:Depends on:
prev sensitizationprev sensitization type of allergentype of allergen
+/- urticaria+/- urticaria(pruritic)(pruritic)
Allergic Allergic Angioedema/UrticariaAngioedema/Urticaria
Clinical Presentation:Clinical Presentation: Often seen in patients with other Often seen in patients with other
allergic conditions:allergic conditions: Atopic dermatitisAtopic dermatitis Allergic rhinitis Allergic rhinitis Asthma Asthma
Allergic Allergic Angioedema/UrticariaAngioedema/Urticaria
Management:Management: As always, airway firstAs always, airway first AAE does respond to:AAE does respond to:
SteroidsSteroids H1 and H2 blockersH1 and H2 blockers subcutaneous epinephrinesubcutaneous epinephrine antihistamines. antihistamines.
Management Management AngioedemaAngioedema