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GLORIA ™ is supported by unrestricted educational grants from. GLORIA Module 3 Allergic Emergencies. WAO Expert Panel Authors: Richard F Lockey, USA Connie H Katelaris, Australia Michael Kaliner, USA Contributors: F.Estelle R. Simons, Canada Daniel Vervloet, France. Allergic Emergencies.

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GLORIA™ is supported by unrestricted educational grants from


Gloria module 3 allergic emergencies
GLORIA Module 3Allergic Emergencies


Allergic emergencies

WAO Expert PanelAuthors:Richard F Lockey, USAConnie H Katelaris, AustraliaMichael Kaliner, USAContributors:F.Estelle R. Simons, CanadaDaniel Vervloet, France

Allergic Emergencies


Allergic emergencies1

Allergic Emergencies

Section 1: Anaphylaxis

Section 2: Upper Airway Oedema

Section 3: Severe Asthma Exacerbations


Allergic emergencies2

Allergic Emergencies

Section 1: Anaphylaxis


Anaphylaxis lecture objectives
Anaphylaxis Lecture Objectives

After this lecture, participants will:

  • Have knowledge of the different mechanisms which cause anaphylaxis and the agents which are most likely to cause it;

  • Be able to recognize the signs and symptoms of anaphylaxis;

  • Understand how to treat anaphylaxis.


Definition of anaphylaxis
Definition of Anaphylaxis

  • Anaphylaxis – a syndrome with varied mechanisms,

    clinical presentations, and severity.

  • An acute life-threatening reaction.

  • Usually mediated by an immunologic mechanism, allergic anaphylaxis, but not always.

  • Includes non-allergic anaphylaxis (formerly

    referred to as an anaphylactoid reaction).

  • Results from the release of mast-basophil mediators.

    WAO Nomenclature Review Committee JACI2004


Gell and coombs hypersensitivity immunopathologic reactions
Gell and Coombs’ Hypersensitivity (immunopathologic reactions)

  • Type I Immediate

  • Type II Cytotoxic

  • Type III Immune Complex

  • Type IV Delayed Hypersensitivity

  • Types I, II and III can result in

    immunologically-induced or allergic anaphylaxis

    Kemp and Lockey JACI 2002


Biochemical mediators and chemotactic substances
Biochemical Mediators reactions)and Chemotactic Substances

  • Degranulation of mast cells and basophils.

  • Preformed granule-associated substances, e.g., histamine, tryptase, chymase, heparin, histamine-releasing factor, other cytokines.

  • Newly generated lipid-derived mediators, e.g., prostaglandin D2, leukotriene B4, PAF, LTC4, LTD4, and LTE4.

  • Eosinophils may play pro-inflammatory role (release of cytotoxic granule-associated proteins) or anti-inflammatory role (e.g., metabolism of vasoactive mediators).

    Kemp and Lockey JACI 2002


Shock organs in anaphylaxis
Shock Organs in Anaphylaxis reactions)

  • Guinea pig – bronchial smooth muscle constriction.

  • Rabbit– fatal pulmonary artery vasoconstriction with right ventricular failure.

  • Dog – venous system of liver contracts producing hepatic congestion.

  • Human – shock organs are the cardiovascular system, respiratory tract, skin, and gastrointestinal tract. Laryngeal oedema, respiratory failure, and circulatory collapse are common.

  • Asthma is an important risk factor for death from anaphylaxis.

    Kemp and Lockey JACI 2002

    Bock, Munoz-Furlong, Sampson JACI 2001


Incidence reactions)

  • Analysis of published studies of most common causes

  • 3.3 to 4 million Americans at risk.

  • 1,433 to 1,503 at risk for fatal reaction.

    Neugut, Ghatak, Miller Arch Int Med 2001

    Incidence Based on Epinephrine Rx for

    Out-of-Hospital Use

  • From Canada and Wales.

  • 0.95% of population in Manitoba, Canada.

  • 0.2 per 1000 in Wales.

  • Incidence increased in Wales between 1994 & 1999.

    Simons, Peterson, BlackJACI 2002

    Rangaraj, Tuthill, Burr, AlfahamJACI 2002


Incidence of anaphylaxis to specific agents 1
Incidence of Anaphylaxis to Specific Agents 1 reactions)

Antibiotics

  • Most common cause of drug induced anaphylaxis.

    Latex

  • Increased incidence last decade.

  • Population at risk includes multiple mucosal

    exposure to latex (catheterization & surgery) and

    healthcare workers.

    Radiocontrast agents

  • Introduction of lower osmolarity agents

    reduced reaction rate

    Lieberman In: Allergy: Principles and Practice. Mosby, 2003


Incidence of anaphylaxis to specific agents 2
Incidence of Anaphylaxis to Specific Agents 2 reactions)

Hymenoptera stings

  • Incidence ranges from 0.4% to 5%

  • Estimated fatalities 100 per year in U.S.A.

    Food

  • Estimated 2% of US population has food

    allergies with up to 100 deaths per year

  • Shellfish most common in adults; peanuts

    in children

    Lieberman In Allergy: Principles and Practice Mosby, 2003


Incidence of anaphylaxis to specific agents 3
Incidence of Anaphylaxis to Specific Agents 3 reactions)

Perioperative anaphylaxis

  • Incidence ranges from 1 in 4500 to 1 in 2500

    cases of general anaesthesia

  • Mortality rate can be as high as 3.4%

  • Most common agents responsible are

    muscle relaxants, which account for 50%

    to 75% of reactions.

    Lieberman In Allergy: Principles and Practice Mosby, 2003


Incidence of anaphylaxis to specific agents 4
Incidence of Anaphylaxis to Specific Agents 4 reactions)

Non Steroidal Anti-Inflammatory Drugs (NSAIDs)

  • Incidence varies depending on whether asthmatic subjects are included

  • NSAIDs probably second most common

    offending drug next to antibiotics.

    Lieberman In Allergy: Principles and Practice Mosby, 2003


Incidence of anaphylaxis to specific agents 5
Incidence of Anaphylaxis to Specific Agents 5 reactions)

Antisera

  • Heterologous antisera to treat snake bites (4.6% to 10%)

  • Immunosuppression, incidence for anti-lymphocyte globulin as high as 2%

    Idiopathic

  • Estimated to be between 20,592 and 47,024 cases in USA – deaths rare

    Lieberman in Allergy: Principles and Practice Mosby 2003


Allergen immunotherapy
Allergen Immunotherapy reactions)

  • Incidence of systemic reaction from 0.8% to

    46.7% depending on the dose of allergen and

    schedule used.

  • Deaths occur at a rate of 1 per 2,000,000

    injections.

    Stewart and Lockey JACI 1992

    Kemp et al In: Allergens and Allergen Immunotherapy

    Marcel Dekker, 2004


Signs and symptoms of anaphylaxis

Diffuse erythema reactions)

Diffuse pruritus

Diffuse urticaria

Angioedema

Bronchospasm

Laryngeal edema

Hyperperistalsis

Hypotension

Cardiac arrhythmias

Nausea

Vomiting

Lightheadedness

Headache

Feeling of impending doom

Unconsciousness

Flushing

Signs and Symptoms of Anaphylaxis

Kemp and Lockey JACI 2002


Differential diagnostic considerations in anaphylaxis
Differential Diagnostic reactions) Considerations in Anaphylaxis

  • Vasovagal reactions

  • Idiopathic flushing

  • Mastocytosis

  • Carcinoid syndrome

  • Anxiety-induced hyperventilation

  • Globus hystericus

  • Serum sickness

  • C-1 esterase inhibitor deficiency

  • Shock-associated with myocardial infarction, blood

    loss, septicemia

  • Scombroid poisoning

    Montanaro and Bardana JACI 2002


Comments about signs and symptoms of anaphylaxis
Comments About Signs and Symptoms reactions)of Anaphylaxis

  • Urticaria or angioedema and flush most common

    ( > 90%).

  • Cutaneous manifestations may be delayed or absent

  • Next most common manifestations are respiratory

    (40% to 60%).

  • Next are dizziness, unconsciousness (30% to 35%).

  • Gastrointestinal symptoms (20% to 30%).

  • More rapid onset, more likely serious.

  • Signs and symptoms within 5 to 30 minutes, but

    may not develop for hours.

    Lieberman In Allergy: Principles and Practice Mosby, 2003


Agents that cause anaphylaxis 1 anaphylactic ige dependent

Foods (peanut, tree nuts, and crustaceans) reactions)

Milk, egg and fish also important, especially in children

Medications (antibiotics)

Venoms

Latex

Allergen vaccines

Hormones

Animal or human proteins

Diagnostic allergens

Muscle relaxants

Colorants

(insect-derived, such as carmine)

Enzymes

Polysaccharides

Aspirin and other non-steroidal anti-inflammatory drugs (probably)

Exercise (possibly, in food and medication-dependent events)

Agents that Cause Anaphylaxis 1Anaphylactic (IgE-Dependent)

Kemp Immunol Allergy Clin N Am 2001


Agents that cause anaphylaxis 2 allergic but not ige mediated
Agents that Cause Anaphylaxis 2 (Allergic but not IgE Mediated)

Immune aggregates (Type II)

  • Intravenous immunoglobulin

  • Dextran (possibly)

    Cytotoxic (Type III)

  • Transfusion reactions to cellular elements (IgG, IgM)

    Kemp Immunol Allergy Clin N Am 2001


Agents that cause anaphylaxis 3 non allergic or ige independent
Agents that Cause Anaphylaxis 3 Mediated) (Non-allergic or IgE-independent)

Multimediator complement

activation/activation of contact system:

  • Radiocontrast media

  • Ethylene oxide gas on dialysis tubing

  • Protamine (possibly)

  • ACE-inhibitor administered during renal dialysis with sulfonated polyacrylonitrile, cuprophane, or polymethylmethacrylate dialysis membranes

    Kemp Immunol Allergy Clin N Am 2001


Agents that cause anaphylaxis 4 non allergic or ige independent
Agents that Cause Anaphylaxis 4 Mediated) (Non-allergic or IgE Independent)

Nonspecific degranulation of mast cells

and basophils

  • Opiates

  • Idiopathic

  • Physical factors:

    • Exercise

    • Temperature (cold, heat)

      Kemp Immunol Allergy Clin N Am 2001


Adrenergic blockade
-Adrenergic Blockade Mediated)

  • By mouth or topically.

  • Paradoxical bradycardia, profound hypotension,

    and severe bronchospasm.

  • Can exacerbate disease and may impede treatment.

  • Selective β-blockers do not produce clinically significant adverse respiratory effects in mild-moderate asthma (including COPD). Not studied in anaphylaxis.

    Toogood CMAJ 1987

    Kivity and Yarchovsky JACI 1990

    Salpeter, Ormiston, Salpeter Annals Int Med 2002


Recurrent and persistent anaphylaxis
Recurrent and Persistent Anaphylaxis Mediated)

  • Recurrent or biphasic anaphylaxis occurs 8 to 12

    hours in up to 20%.

  • Subjects with biphasic do not differ clinically but

    more epinephrine may be necessary for initial

    symptoms.

  • Persistent anaphylaxis may last from 5 to 32 hours.

    Lee and Greenes Pediatrics, 2000

    Kemp and deShazo In: Allergens and Allergen

    Immunotherapy to Treat Allergic Diseases. Marcel Dekker, 2004


Physician supervised management of anaphylaxis 1
Physician-Supervised Management of Anaphylaxis 1 Mediated)

I. Immediate Intervention

a) Assessment of airway, breathing, circulation, and mentation.

b) Administer EPI, 1:1000 dilution, 0.3 - 0.5 ml

(0.01 mg/kg in children, max 0.3 mg dosage) IM, to control SX and BP. Repeat, as necessary.

Kemp and Lockey JACI 2002

Simons et al JACI 1998

Simons, Gu, Simons JACI 2001


Physician supervised management of anaphylaxis 2
Physician-Supervised Management of Anaphylaxis 2 Mediated)

I. Immediate Intervention continued

c) IM into the anterolateral thigh (vastus lateralis) produces higher & more rapid peak plasma level versus SQ & IM in arm. Therefore, with moderate, severe, or progressive ANA, EPI IM into anterolateral thigh. Alternatively, an EPI autoinjector given through clothing in same manner. Repeat, as necessary.

Kemp and Lockey JACI 2002

Simons et al JACI 1998

Simons, Gu, Simons JACI 2001


Physician supervised management of anaphylaxis 3
Physician-Supervised Management of Anaphylaxis 3 Mediated)

I. Immediate Intervention - continued

d) Aqueous EPI 1:1000, 0.1- 0.3ml in 10ml NS (1:100,000

to 1:33,000 dilution), IV over several minutes prn.

e) For potentially moribund subjects, tubercular syringe, EPI 1:1000, 0.1 ml, insert into vein (IV), aspirate 0.9 ml of blood (1:10,000 dilution). Give as necessary for response.

Kemp and Lockey JACI 2002


Physician supervised management of anaphylaxis 4
Physician-Supervised Management of Anaphylaxis 4 Mediated)

II. General measures

a) Place in recumbent position and elevate lower

extremities.

b) Maintain airway (endotracheal tube or

cricothyrotomy).

c) O2, 6 - 8 liters/minute.

d) NS, IV. If severe hypotension, give volume

expanders (colloid solution).

e) Venous tourniquet above reaction site.

Question if decreases absorption of allergen.

Kemp and Lockey JACI 2002


Physician supervised management of anaphylaxis 41
Physician-Supervised Management of Anaphylaxis 4 Mediated)

III. Specific Measures that Depend on

Clinical Scenario

a) Aqueous EPI 1:1,000, ½ dose (0.1- 0.2 mg) at reaction site.

b) Diphenhydramine, 50 mg or more in divided

doses orally or IV, maximum daily dose 200 mg

(5 mg/kg) for children and 400 mg for adults.

c) Ranitidine, 50 mg in adults and 12.5 - 50 mg

(1 mg/kg) in children, dilute in 5% G/W, total 20 ml,

inject IV, over 5 minutes. (Cimetidine 4 mg/kg OK

for adults, not established for pediatrics).

Kemp and Lockey JACI 2002


Physician supervised management of anaphylaxis 5
Physician-Supervised Management of Anaphylaxis 5 Mediated)

III. Specific Measures that Depend on

Clinical Scenario

d) Bronchospasm, nebulized albuterol 2.5 - 5 mg in 3 ml NS or levalbuterol 0.63 - 1.25 mg

as needed.

e) Aminophylline, 5mg/kg over 30 min IV may be helpful. Adjust dose based on age, medications, disease, current use.

f) Refractory hypotension, give dopamine,

400 mg in 500 ml G/W IV 2 - 20 μg/kg/min

more or less.

Kemp and Lockey JACI 2002


Physician supervised management of anaphylaxis 6
Physician-Supervised Management of Anaphylaxis 6 Mediated)

III. Specific Measures that Depend on

Clinical Scenario

g) Glucagon, 1- 5 mg (20 - 30 μg/kg [max

1 mg] in children), administered IV

over 5 minutes followed with IV infusion

5-15 μg/min.

h) Methylprednisolone, 1- 2 mg/kg per

24 hr; prevents prolonged reactions

and relapses.

Kemp and Lockey JACI 2002


Vasodepressor vaso vagal
Vasodepressor (Vaso-Vagal) Mediated)

Definition

  • Non-allergic reaction characterized by slow pulse

    nausea, pallor, sweating, clammy skin, and/or

    hypotension.

    Kemp and Lockey JACI 2002


Vasodepressor vaso vagal1
Vasodepressor (Vaso-Vagal) Mediated)

Management

a) Place patient in supine position with elevated lower extremities.

b) For severe vasodepressor reaction ONLY (i.e., bradycardia, nausea, pallor, sweating, cool clammy skin, hypotension), atropine 0.3 - 0.5 mg (0.02 mg/kg) SQ every 10 minutes (max 2 mg/adult and 1 mg/child).

c) If hypotension persists, give IV fluids.

Kemp and Lockey JACI 2002


Measures to reduce the incidence of drug induced anaphylaxis and anaphylactic deaths 1
Measures to Reduce the Incidence of Drug- Induced Anaphylaxis and Anaphylactic Deaths 1

General Measures

  • Obtain thorough history for drug allergy.

  • Avoid drugs with immunological or biochemical cross-reactivity with any agents to which the patient is sensitive.

  • Administer drugs orally rather than parenterally when possible.

  • Check all drugs for proper labeling

  • Keep patients in clinic for 20 to 30 minutes after injections.

    Lieberman In: Allergy: Principles and Practice Mosby, 2003


Measures to reduce the incidence of anaphylaxis and anaphylactic deaths 2
Measures to Reduce the Incidence of Anaphylaxis and Anaphylactic Deaths 2

Measures for Patients at Risk

  • Avoid causative factor/s.

  • Have patient wear and carry warning identification.

  • Teach self-injection of epinephrine and caution patient

    to keep epinephrine kit with them.

  • Discontinue -adrenergic blocking agents, ACE

    inhibitors (controversial), monoamine oxidase

    inhibitors, and tricyclic antidepressants, where

    possible.

    Lieberman In: Allergy: Principles and Practice. Mosby, 2003


Measures to reduce the incidence of anaphylaxis and anaphylactic deaths 3
Measures to Reduce the Incidence of Anaphylaxis and Anaphylactic Deaths 3

Measures for Patients at Risk

  • Use preventive techniques when patient is required to

    undergo a procedure or take an agent which places

    them at risk. Such techniques include:

    Pretreatment

    Provocative challenge

    Desensitization

    Lieberman In: Allergy: Principles and Practice. Mosby, 2003


Summary
Summary Anaphylactic Deaths 3

Prognosis

FactorPoorGood

Dose of antigen (allergen) Large Small

Onset of symptoms Early Late

Initiation of treatment Late Early

Route of exposure Parenteral Oral*

β-adrenergic blocker use Yes No

Presence of underlying disease Yes No

* True for drugs, not foods


Allergic emergencies3

Allergic Emergencies Anaphylactic Deaths 3

Section 2: Upper Airway Oedema


Upper airway oedema lecture objectives
Upper Airway Oedema Anaphylactic Deaths 3 Lecture Objectives

  • To understand the causes of angioedema;

  • To review the spectrum and management of hereditary angioedema;

  • To review Angiotensin Converting Enzyme (ACE) inhibitor related angioedema.


Outline of lecture
Outline of Lecture Anaphylactic Deaths 3

  • Clinical description

  • Classification

  • Examples of life-threatening oedema:

    • Hereditary angioedema

    • Acquired oedema

    • Angiotensin enzyme inhibitor-induced oedema

      • Clinical description

      • Pathophysiology

      • Management


Angioedema
Angioedema Anaphylactic Deaths 3

  • First described by Quincke in 1882

  • Well-demarcated non-pitting oedema

  • Caused by same pathological factors that cause urticaria

  • Reaction occurs deeper in dermis and subcutaneous tissues

  • Face, tongue, lips, eyelids most commonly affected

  • May cause life-threatening respiratory distress if larynx involved


Classification of angioedema 1
Classification of Angioedema 1 Anaphylactic Deaths 3

Hereditary

  • Type 1: C1 esterase inhibitor deficiency

  • Type 2: functional abnormality of C1 esterase inhibitor

    Acquired

  • Idiopathic

  • IgE-mediated

  • Non-IgE-mediated

  • Systemic disease

  • Physical causes

  • Other


Classification of angioedema 2
Classification of Angioedema 2 Anaphylactic Deaths 3

IgE-mediated

  • Drugs

  • Foods

  • Stings

  • Infections (eg viral, helminthic)

    Non-IgE-mediated

  • Cyclooxygenase inhibition (ASA and other NSAIDS)

  • Angiotensin converting enzyme inhibition


Classification of angioedema 3

Systemic diseases Anaphylactic Deaths 3

Systemic lupus erythematosis

Hypereosinophilia

Lymphoma:

abnormal antibodies activate complement system

Classification of Angioedema 3


Classification of angioedema 4

Physical causes Anaphylactic Deaths 3

Cold

Cholinergic

Solar

Vibratory

Other

Some contact reactions

Autoantibodies to C1-esterase inhibitor

Unopposed complement activation

Classification of Angioedema 4


Incidence
Incidence Anaphylactic Deaths 3

  • Chronic idiopathic urticaria/angioedema occurs in 0.1% population

  • 65% remit within 3 years

    85% remit within 5 years

    95% remit within 10 years

  • Angioedema occurs most commonly with

    urticaria (40% cases)

  • May occur in isolation (10% cases)


Hereditary angioedema hae
Hereditary Angioedema (HAE) Anaphylactic Deaths 3

  • 1888 - family described by William Osler

  • 1963 - Donaldson and Evans described the biochemical defect responsible - absence of C1 inhibitor


Hereditary angioedema hae1
Hereditary Angioedema (HAE) Anaphylactic Deaths 3

Subtypes

Type 1*

  • Autosomal dominant

  • Markedly suppressed C1 esterase

    inhibitor protein levels

    * Accounts for 85% cases


Hereditary angioedema hae2
Hereditary Angioedema (HAE) Anaphylactic Deaths 3

Subtypes

Type 2*

  • Autosomal dominant, with a point mutation leading to synthesis of a dysfunctional protein

  • Functional assay required for diagnosis as level may be normal

    * Accounts for 15% cases


Hereditary angioedema hae3
Hereditary Angioedema (HAE) Anaphylactic Deaths 3

Epidemiology

  • 1:10,000 - 1:150,000 with no racial or gender

    predilection

    Clinical manifestations

  • Usually manifests in 2nd decade

  • May be seen in young children

  • Oedema may develop in one or several organs

  • Presentation depends upon site of swelling

  • Attacks last 2- 5 days before spontaneous resolution

Nzeako Arch Intern Med, 2001


Clinical manifestations 1
Clinical Manifestations 1 Anaphylactic Deaths 3

  • Angioedema may develop in subcutaneous tissues of extremities, genitalia, face, trunk.


Clinical manifestations 2
Clinical Manifestations 2 Anaphylactic Deaths 3

  • Oedema of wall of intestine may present as an acute abdominal emergency.

  • Submucosal oedema of larynx or pharynx may cause asphyxiation – this may occur on first presentation.

    Bork Mayo Clin Proc 2000


Clinical manifestations 3
Clinical Manifestations 3 Anaphylactic Deaths 3

Laryngeal oedema

Commonest cause of mortality in HAE

  • Time from onset of swelling to death 1- 14 hours (mean 7 hours)

  • May be presenting feature

  • Death may occur in those with no previous laryngeal oedema episodes

  • Increased risk within certain families

  • Early symptoms - lump in throat, tightness in throat

  • Hoarseness, dysphagia, progressive dyspnoea

Bork Mayo Clin Proc 2000


Hereditary angioedema hae4
Hereditary Angioedema (HAE) Anaphylactic Deaths 3

Diagnosis

  • Clinical presentation

  • For screening - quantitative and functional assays of C1 inhibitor

  • C4 and C2 levels reduced in acute attack

  • C4 persistently low in most patients

Nzeako Arch Intern Med 2001


Hereditary angioedema hae pathophysiology 1
Hereditary Angioedema (HAE) Anaphylactic Deaths 3 Pathophysiology 1

C1 inhibitor

  • Single chain glycoprotein; molecular weight 104,000; serine protease family

  • Important regulatory protein of complement cascade

  • Inactivates C1 esterase complex

  • Regulates coagulation, fibrinolytic, kinin, complement systems

Nielson Immunopharmacology 1996


Hereditary angioedema hae pathophysiology 2
Hereditary Angioedema (HAE) Pathophysiology 2 Anaphylactic Deaths 3

  • Lack of C1 inhibitor leads to abnormal activation of complement pathway, reduced C2 and C4 levels

  • Hageman factor induces formation of kallikrein from prekallikrein

  • Bradykinin is released from high molecular weight kininogen

  • All these mediators increase capillary permeability and are responsible for attacks of angioedema

Kaplan JACI 2002


Genetics
Genetics Anaphylactic Deaths 3

  • Autosomal dominant; all patients heterozygous

  • 25% no prior family history - spontaneous mutations

  • More than 100 different mutations reported

  • Varied clinical pattern may be explained by variable effect of mutations on C1 inhibitor synthesis

Agostini Medicine (Baltimore) 1992


Hereditary angioedema hae management
Hereditary Angioedema (HAE) Anaphylactic Deaths 3 Management

Principles

  • Action plan for acute episodes

  • Strategy for long term prophylaxis

  • Short term prophylaxis for high risk procedures

  • Regular follow up for education and monitoring side effects of therapy


Management 1
Management 1 Anaphylactic Deaths 3

Acute attacks

  • Treatment of choice is C1 inhibitor concentrate,

    500 - 1,000U intravenous infusion

  • Safe and effective - no long term side effects reported

  • Excellent and prompt response in most patients

  • Not available in USA, but in clinical trials

Bork Arch Intern Med 2001


Management 2
Management 2 Anaphylactic Deaths 3

Acute attacks when C1 inhibitor concentrate not

available

  • Intubation and respiratory support may be necessary when laryngeal oedema present

  • Fresh frozen plasma (FFP) has been used successfully for acute attacks. Exacerbation of symptoms by supplying more kallikrein substrate is a theoretical consideration but is rarely seen

Bork Arch Intern Med 2001


Management 3
Management 3 Anaphylactic Deaths 3

Long term – adults

  • Attenuated androgens (stanozolol, danazol, oxandrin) can prevent attacks

  • Increase levels of C1 inhibitor, C4 and C2

  • Titrate to lowest effective dose to control attacks - for danazol may be able to reduce to 200 mg/d every second day

  • Regular monitoring necessary

Nzeako Arch Intern Med 2001


Management 4
Management 4 Anaphylactic Deaths 3

Long term – children

  • Antifibrinolytic agents have been used as first line prophylaxis

  • Low dose danazol

Nzeako Arch Intern Med 2001


Management 5
Management 5 Anaphylactic Deaths 3

Short term prophylaxis

  • Necessary for high risk interventions,

    eg, dental procedures, tonsillectomy

  • C1 inhibitor concentrate, where available, given before procedure

  • Increasing dose of attenuated androgen for a few days beforehand

  • Fresh frozen plasma


Management 6
Management 6 Anaphylactic Deaths 3

Other

  • Avoid oral contraceptive pill, ACE inhibitor medication

  • Premedicate before procedures requiring radiocontrast media or streptokinase as they may decrease C1 inhibitor levels

  • Reassurance; address issues such as ongoing stress

  • Treat infections promptly

  • Genetic counseling and screening


Acquired angioedema aae 1
Acquired Angioedema (AAE) 1 Anaphylactic Deaths 3

Type 1

  • Associated with rheumatologic diseases, B cell lymphoproliferative disorders

  • Activation of complement by complexes of anti-idiotypic antibodies and surface immunoglobulins consumes C1 inhibitor so levels decline

    Type 2

  • Development of autoantibodies against C1 inhibitor

  • Autoantibodies bind at active site on molecule leading to inactivation

Markovic Ann Int Med 2000


Acquired angioedema aae 2
Acquired Angioedema (AAE) 2 Anaphylactic Deaths 3

  • Decreased C1q levels distinguish AAE from HAE where C1q is usually normal

  • Treatment of underlying condition may result in resolution

  • For acute attacks, C1 inhibitor concentrate, where available should be used

  • Attenuated androgen may be useful in Type 1

  • Immunosuppressive therapy for Type 2

Laurent Clin Rev Allergy Immunol 1999


Angiotensin converting enzyme ace inhibitors and angioedema 1
Angiotensin Converting Enzyme (ACE) Inhibitors and Angioedema 1

  • Angioedema develops in 0.1% to 0.5% of those receiving the drug

  • Onset from 1st week of use to 2 - 3 years of use

  • Symptoms resolve within 24 - 48 hours of cessation of drug

  • Most commonly seen with captopril and enalopril but described with all in class

  • Genetic factors may be important

  • Subjects with a history of angioedema from other causes are more susceptible to ACE-induced angioedema

Slater JAMA 1988


Angiotensin converting enzyme ace inhibitors and angioedema 2
Angiotensin Converting Enzyme (ACE) Inhibitors and Angioedema 2

  • Face and lips most commonly involvedbut laryngeal oedema reported

  • Risk factors include obesity, prior endotracheal intubation and face and neck surgery

  • ACE inhibitors will trigger attacks in those with HAE so avoid in these patients

Jain Chest 1992


Angiotensin converting enzyme ace inhibitors and angioedema 3
Angiotensin Converting Enzyme (ACE) Inhibitors and Angioedema 3

Pathophysiology

  • ACE inhibitors may cause bradykinin accumulation resulting in vasodilatation, capillary leakage and angioedema

  • Patients may have a congenital or acquired impairment of kininase 1 which degrades bradykinin leading to bradykinin accumulation once ACE is blocked


Angiotensin converting enzyme ace inhibitors and angioedema 4
Angiotensin Converting Enzyme (ACE) Inhibitors and Angioedema 4

Management

  • Stop drug and use other classes of antihypertensive agents

  • ALL ACE inhibitors are to be avoided

  • Management of angioedema depends on site of involvement - securing the airway by intubation may be necessary

  • ACE receptor antagonists are generally considered to be safe


Angioedema conclusions
Angioedema - Conclusions Angioedema 4

  • Most often occurs in association with urticaria

  • When angioedema occurs alone, consider HAE, AAE

  • HAE is a rare disease but must be identified as it can be life-threatening

  • Refer to appropriate specialist for ongoing management

  • ACE-inhibitor induced angioedema is an important cause in older people


Allergic emergencies4

Allergic Emergencies Angioedema 4

Section 3: Severe Asthma Exacerbations


Lecture objectives
Lecture Objectives Angioedema 4

At the end of this lecture participants will be able to:

  • Understand the risk factors for asthma exacerbations;

  • Identify the signs and symptoms of acute asthma;

  • Outline appropriate treatment strategies.


Features of a severe asthma exacerbation
Features of a Severe Asthma Exacerbation Angioedema 4

One or more present:

  • Use of accessory muscles of respiration

  • Pulsus paradoxicus >25 mm Hg

  • Pulse > 110 BPM

  • Inability to speak sentences

  • Respiratory rate >25 - 30 breaths/min

  • PEFR or FEV1 < 50% predicted

  • SaO2 <91- 92%

McFadden Am J Respir Crit Care Med 2003


Risk factors for fatal or near fatal asthma attacks
Risk Factors for Fatal or Near-Fatal Angioedema 4Asthma Attacks

  • Previous episode of near-fatal asthma

  • Multiple prior ER visits or hospitalizations

  • Poor compliance with medical treatments

  • Adolescents or inner city asthmatics

  • (USA) African-Americans>Hispanics>Caucasians

  • Allergy to Alternaria

  • Recent use of oral CCS

  • Inadequate therapy:

    • Excessive use of β-agonists

    • No inhaled CCS

    • Concomitant β-blockers

Ramirez and Lockey In: Asthma, American College of Physicians, 2002


Physical findings in severe asthma exacerbations
Physical Findings in Severe Asthma Exacerbations Angioedema 4

  • Tachypnea

  • Tachycardia

  • Wheeze

  • Hyperinflation

  • Accessory muscle use

  • Pulsus paradoxicus

  • Diaphoresis

  • Cyanosis

  • Sweating

  • Obtundation

Brenner, Tyndall and Crain In: Emergency Asthma. Marcel Dekker 1999


Causes of asthma exacerbations
Causes of Asthma Exacerbations Angioedema 4

  • Lower or upper respiratory infections

  • Cessation or reduction of medication

  • Concomitant medication, e.g. β-blocker

  • Allergen or pollutant exposure


Differential diagnosis
Differential Diagnosis Angioedema 4

  • COPD

  • Bronchitis

  • Bronchiectasis

  • Endobronchial diseases

  • Foreign bodies

  • Extra- or intra-thoracic tracheal obstruction

  • Cardiogenic pulmonary edema

  • Non-cardiogenic pulmonary edema

  • Pneumonia

  • Pulmonary emboli

  • Chemical pneumonitis

  • Hyperventilation syndrome

  • Pulmonary embolus

  • Carcinoid syndrome

Brenner, Tyndall, Crain In: Emergency Asthma. Marcel Dekker, 1999


Peak flow meters
Peak Flow Meters Angioedema 4

Use peak flow meters to monitor asthma and prevent exacerbations:

  • Inexpensive

  • Easy to use

  • Accurate

  • Provide “real life” measurements at worst and

    best times of the day

  • Provide objective measurement of pulmonary

    function

  • Detect early changes of asthma worsening


Patient self management
Patient “Self Management” Angioedema 4

If personal best peak flow measurements:

  • Fall 10+%, double dose of inhaled CCS

  • Fall 20+%, use short-acting bronchodilator Q4 -6 hour, plus 2 x inhaled CCS

  • Call office, try to determine if infection is present

  • Fall 40 - 50%, add oral CCS

  • Fall greater than 50%, urgent visit to either

    • Outpatient office

    • Emergency room

Kaliner In: Current Review of Asthma. Curent Medicine, 2003


Stages of asthma exacerbations stage 1
Stages of Asthma Exacerbations Angioedema 4Stage 1:

Symptoms

  • Somewhat short of breath

  • Can lie down and sleep through the night

  • Cannot perform full physical activities without shortness of breath

    Signs

  • Some wheezes on examination

  • Respiratory rate, 15 (normal <12)

  • Pulse 100

  • Peak flows and spirometry reduced by 10%


Stages of asthma exacerbations stage 2
Stages of Asthma Exacerbations Angioedema 4Stage 2:

Symptoms

  • Less able to do physical activity due to shortness of breath

  • Dyspnea on walking stairs

  • May wake up at night short of breath

  • Uncomfortable on lying down

  • Some use of accessory muscles of respiration

    Signs

  • Wheezing

  • Respiratory rate 18

  • Pulse 111

  • Peak flows and spirometry reduced by 20+%


Stages of asthma exacerbations stage 3
Stages of Asthma Exacerbations Angioedema 4Stage 3:

Symptoms

  • Unable to perform physical activity without shortness of breath

  • Cannot lie down without dyspnea

  • Speaks in short sentences

  • Using accessory muscles

    Signs

  • Wheezing

  • Respiratory rate 19 - 20

  • Pulse 120

  • Peak flows and spirometry reduced by30+%


Stages of asthma exacerbations stage 4
Stages of Asthma Exacerbations Angioedema 4Stage 4:

Symptoms

  • Sitting bent forward

  • Unable to ambulate without shortness of breath

  • Single word sentences

  • Mentally-oriented and alert

  • Use of accessory muscles

    Signs

  • Wheezing less pronounced than anticipated

  • Respiratory rate 20 - 25

  • Pulse 125+

  • Peak flows and spirometry reduced by 40+%

  • SaO2 91- 92%


Stages of asthma exacerbations stage 5
Stages of Asthma Exacerbations Angioedema 4Stage 5:

Symptoms

  • Reduced consciousness

  • Dyspnea

  • Silent chest – no wheezing

    Signs

  • Fast, superficial respiration

  • Respiratory rate >25

  • Unable to perform peak flows or spirometry

  • Pulse 130 - 150+

  • SAO2 <90


Severity of asthma as graded by predicted fev1
Severity of Asthma as Graded by % Predicted FEV1 Angioedema 4

FEV% predicted Severity

  • 70 - 100 Mild

  • 60 - 69 Moderate

  • 50 - 59 Moderately severe

  • 35 - 49 Severe

  • < 35 Very severe

    (life-threatening)


Treatment of asthma exacerbations 1
Treatment of Asthma Exacerbations 1 Angioedema 4

Preferred treatment choices

  • β2-agonists

    • Inhaled by MDI or nebulizer

    • Injected

  • Anticholinergics

    • Inhaled by MDI or nebulizer

  • Corticosteroids

    • Parenteral, oral or inhaled


Treatment of asthma exacerbations 2
Treatment of Asthma Exacerbations 2 Angioedema 4

Secondary treatment choices

  • Aminophylline or theophylline (oral, parenteral)

  • Leukotriene receptor antagonists (oral)

  • Oxygen

  • Magnesium sulfate


Treatment of asthma exacerbations 3 beta agonists
Treatment of Asthma Exacerbations 3 Angioedema 4Beta Agonists

Inhaled is preferred route

  • MDI plus spacer, 4 - 8 puffs Q 20 min x 3

  • Nebulizer, 2.5 - 5 mg albuterol Q 20 min x 3

  • Epinephrine SQ, 0.3 - 0.5ml (0.01 ml/kg children)

  • Levalbuterol, 0.63 - 1.25 mg Q 4 - 8 hours (if available)


Treatment of asthma exacerbations 4 anticholinergics
Treatment of Asthma Exacerbations 4 Angioedema 4Anticholinergics

Ipratropium

  • Preferred use: combined with beta agonist

  • MDI plus spacer, 2 - 4 puffs Q 20 min x 3

  • Nebulizer, 500 μg Q 20 min x 3


Treatment of asthma exacerbations 5 corticosteroids
Treatment of Asthma Exacerbations 5 Angioedema 4Corticosteroids

  • No immediate effect

  • Earliest effects 6 hours after high dose

  • Oral is as effective as parenteral

  • Prednisone (equivalent), 45 - 60 mg

  • Higher doses have increased side effects and no appreciable increased therapeutic benefit

  • Methylprednisolone, 1 – 2 mg/kg/24 hours

  • No substantial data for usefulness in acute setting


Treatment of asthma exacerbations 6 aminophylline and theophylline
Treatment of Asthma Exacerbations 6 Aminophylline and Theophylline

  • Controversial:

    • Added no benefit to inhaled beta agonists

    • Increased complications

  • Loading dose for aminophylline: 5 – 6 mg/kg over 20 - 30 min

  • Maintenance dose: 0.4 mg/kg/hr (adjust for heart and liver disease)

  • Try to achieve 5 - 15 μg/ml, monitor plasma levels to adjust dose

  • Doses for theophylline similar but slightly less


Treatment of asthma exacerbations 7 leukotriene modifiers
Treatment of Asthma Exacerbations 7 Leukotriene Modifiers Theophylline

  • Few studies

  • Suggest usefulness in reducing hospitalizations

  • Montelukast, 10 mg orally

  • Zafirlukast, 20 mg orally


Treatment of asthma exacerbations 8 magnesium sulfate
Treatment of Asthma Exacerbations 8 Magnesium Sulfate Theophylline

  • Controversial:

    • Inconsistent data

  • Used in very severe asthma in emergency settings:

    • FEV1 < 25% predicted

    • Other signs of severe disease

  • 1.2 - 2 gm IV over 10 - 20 min in 50 ml saline

  • Minor side effects


Preventing exacerbations 1 oral corticosteroids
Preventing Exacerbations 1 TheophyllineOral Corticosteroids

  • Oral corticosteroids are the most powerful medications available to reduce airway inflammation

  • Use until attack completely abated:

    • PEFR and FEV1 at baseline levels

    • Symptoms gone

  • Taper to QOD and determine if patient can remain well if corticosteroids are withdrawn completely


Preventing exacerbations 2 inhaled corticosteroids
Preventing Exacerbations 2 TheophyllineInhaled Corticosteroids

  • Place patient on high dose inhaled corticosteroids

    • Fluticasone, 880 - 1760 μg

    • Budesonide, 800 - 1600 μg

  • Once oral corticosteroids are withdrawn, reduce the inhaled dose incrementally, while maintaining PEFR at personal best level

  • Consider combination of long acting β2-agonist and inhaled corticosteroid in order to achieve the lowest dose of corticosteroid possible


Preventing exacerbations 3 underlying causes and patient education
Preventing Exacerbations 3 TheophyllineUnderlying Causes and Patient Education

Evaluate patient for:

  • Allergy

  • Infection

  • Compliance

  • Inappropriate concomitant medications

  • Social factors

  • Tobacco, drugs, irritants, fumes

  • Psychiatric disorders

    Patient education  www.anafylaxis.nl


World allergy organization wao
World Allergy Organization (WAO) Theophylline

For more information on the World Allergy Organization (WAO), please visit www.worldallery.org or contact the:

WAO Secretariat

555 East Wells Street, Suite 1100

Milwaukee, WI 53202

United States

Tel: +1 414 276 1791

Fax: +1 414 276 3349

Email: [email protected]


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