Vinod Doreswamy, M.D.Allergy, Asthma and Clinical Immunology

Northgate Office11011 Meridian Ave. NSuite 200Seattle, WA 98133Ph: 206-860-4454Fax: 206-860-4756

Madison Office904 7th Ave5th FloorSeattle, WA 98104Ph: 206-860-4454Fax: 206-860-4756

Ballard Office1801 Market StSuite 308Seattle, WA 98107Ph. 206-860-4454Fax: 206-860-4756

ANAPHYLAXIS FOR THE PRIMARY CARE PRACTITIONER

September 6th 2015

CME, Raleigh NC

Disclosures

None

Anaphylaxis - Summary

• What is Anaphylaxis?• Types, Epidemiology• Mechanisms• Causes• Risk Factors• Diagnosis• Treatment

Louis Pasteur, “In the fields of observation, chancefavors the prepared mind.”

Anaphylaxis - Discovery

Anaphylaxis is highly likely when any 1 of the following 3 criteria is fulfilled:1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (eg, generalized hives, pruritus or flushing, and swollen lips-tongue-uvula) AND at least 1 of the following:A. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)B. Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], syncope, incontinence)

Anaphylaxis - Criteria

2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to several hours):A. Involvement of the skin–mucosal tissue (eg, generalized hives, itch-flush, swollen lips-tongue-uvula)B. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)C. Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, incontinence)D. Persistent gastrointestinal symptoms (eg, cramping abdominal pain, vomiting)

Anaphylaxis - Criteria

3. Reduced BP after exposure to a known allergen for that patient (minutes to several hours):A. Infants and children: low systolic BP (age-specific) or greater than 30% decrease in systolic BP*B. Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s baseline

Anaphylaxis - Criteria

Anaphylaxis - Burden

• 0.05-2.0% lifetime prevalence• 1% of ED visits for Acute Allergic reactions given Dx• 40% of ED visits for food anaphylaxis given Dx• 30,000 anaphylaxis, 150 deaths 2/2 Food/year

Anaphylaxis - Epidemiology

• Age• Sex• Atopy• Route of administration• Gaps in administration• Time since reaction• Asthma• Socioeconomic Status• Geography• Diurnal• Race

Signs and symptoms Percentage of cases

Cutaneous >90

Urticaria/angioedema 85–90

Flush 45–55

Pruritus without rash 2–5

Respiratory 40–60

Dyspnea, wheeze 45–50

Upper airway angioedema 50–60

Rhinitis 15–20

Dizziness, syncope, hypotension 30–35

Nausea, vomiting, diarrhea, pain 25–30

Headache 5–8

Substernal pain 4–6

Seizure 1–2

Anaphylaxis – Signs/Symptoms

Anaphylaxis – Cardiovascular changes

At onset of reaction

Early stage (minutes) with no treatment

Prolonged shock

Blood pressure

Pulse

Cardiac output

Peripheral vascular resistance

Intravascular volume

Anaphylaxis - Types

IgG - II

Anaphylaxis - Causes

Immunologic mechanisms (IgE dependent)Foods - peanut, tree nut, shellfish, fish, milk, egg, sesame, food additivesFood dependent Exercise inducedMedications - b-lactam antibiotics and NSAIDs, biological agentsVenoms - stinging insects (Hymenoptera)Natural rubber latexOccupational allergensSeminal fluid (prostate-specific antigen)Inhalants - horse, hamster, other animal dander, grass pollen (rare)Radiocontrast mediaAllergy shots

Immunologic mechanisms (IgE independent, formerly classified as anaphylactoid reactions)

Dextran, such as high-molecular-weight iron dextranCytotoxicIgG Anti-IgA AA Metabolism disturbance – NSAIDsKallekrein-Kinin Contact system activation – Dialysis membranes, RCMMultimediator recruitment – Complement, Clotting, lysis, Kallekrein-contact

Anaphylaxis - Causes

Anaphylaxis - Causes

Non-immunologic mechanismsPhysical factors, such as exercise, cold, heat, and sunlight/UV radiationEthanolMedications - Opioids

Idiopathic anaphylaxisHidden or previously unrecognized allergensMastocytosis/clonal mast cell disorder

Figure 19-2 Polypeptide chain structure of the high-affinity IgE Fc receptor (FcεRI). IgE binds to the Ig-like domains of the α chain. The β chain and the γ chains mediate signal transduction. The boxes in the cytoplasmic region of the β and γ chains are ITAMs, similar to those found in the T cell

receptor complex (see Fig. 6-5). A model structure of FcεRI is shown in Chapter 14, Box 14-1.

© 2005 Elsevier

FcεRI

Mast Cell Activation

Figure 19-3 Mast cell activation. Antigen binding to IgE cross-links FcεRI molecules on mast cells, which induces the release of mediators that cause the hypersensitivity reaction (A, B). Other stimuli, including the complement fragment C5a, can also activate mast cells. A light photomicrograph of a resting mast cell with

abundant purple-staining cytoplasmic granules is shown in C. These granules are also seen in the electron micrograph of a resting mast cell shown in E. In contrast, the depleted granules of an activated mast cell are shown in the light photomicrograph (D) and electron micrograph (F). (Courtesy of Dr. Daniel Friend, Department of

Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.)

Downloaded from: StudentConsult (on 11 May 2010 09:13 PM)

© 2005 Elsevier

Mast cell activation

ANAPHYLAXIS - MEDIATORS

© 2005 Elsevier

Effects of Mediators

GENETIC SUSCEPTIBILITY

Risk factors for severe anaphylaxis and fatality

Age•Infants•Adolescents/young adults•Pregnancy•ElderlyComorbidities•Asthma/respiratory diseases•CVDs•Mastocytosis/clonal mast cell disorders•Allergic rhinitis/eczema•Depression/psychiatric diseases•Thyroid diseaseMedication/chemical use•Sedatives/hypnotics/antidepressants/ethanol/recreational drugs•B-Blockers and ACE inhibitors

Anaphylaxis – Differential Diagnosis

Flush Syndromes

Carcinoid

Medullary Ca Thyroid

Perimenopause

Autonomic Epilepsy

Restaurant Syndromes

Scrombroidosis

MSG

Sulfite

Shock

Excess endogenous HistamineMastocytosisBasophilic LeukemiaAcute PML

MiscellaneousHereditary AngioedemaProgesterone AnaphylaxisPanic attacksVCDRedman SyndromeUrticarial VasculitisMunchausen Syndrome

Anaphylaxis - Diagnosis

• History• Histamine, Tryptase, Other mediators• IgE tests – Skin, Blood• Allergen challenge – food, drug• Work up for DDx

Schwartz DA, Immunol Allergy Clin N Am 26 (2006) 451–463

1. Immediate intervention:a. Assessment of airway, breathing, circulation, and adequacy of mentationb. Administer IM epinephrine every 5 to 15 minutes, as necessary, to control anaphylaxis signs and symptoms and prevent progression to more severe symptoms (eg, respiratory distress, hypotension, and unconsciousness)c. Place patient in recumbent position and elevate lower extremities, as tolerated

The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol 2010;126:480, e32.

Management of Anaphylaxis

2. Subsequent measures depending on response to IM epinephrine:a. Consider call for assistance and transportation to an emergency department or an intensive care facilityb. Establish and maintain airwayc. Administer oxygend. Establish venous accesse. Use IV (IO) crystalloid (eg, 0.9% saline or Ringer’s lactate) for fluid replacement

Management of Anaphylaxis

3. Specific measures to consider after epinephrine injections, where appropriate:a. Consider dilute epinephrine infusionb. Consider H1 and H2 antihistaminesc. Consider nebulized beta2-agonist (eg, albuterol) for bronchospasm resistant to epinephrined. Consider systemic glucocorticoidse. Consider vasopressor (eg, dopamine)f. Consider glucagon for patient taking b-blocker

Management of Anaphylaxis

4. Observation and subsequent outpatient follow-up:a. Observation periods after apparent resolution must be individualizedb. After recovery from the acute episode, every patient should receive epinephrine autoinjectors and be instructed in proper techniquec. Every patient after anaphylaxis requires a careful diagnostic evaluation in consultation with an allergist-immunologist

Management of Anaphylaxis

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Anaphylaxis in the Community

QUESTIONS?