What are the diagnostic criteria, treatment, and types of hypersensitivity reactions for anaphylaxis, including the drug of choice for anaphylactic shock?

Anaphylaxis: Diagnostic Criteria, Treatment, and Hypersensitivity Classification

Diagnostic Criteria for Anaphylaxis

Anaphylaxis is diagnosed when any ONE of three clinical criteria is fulfilled, as established by the NIAID/FAAN consensus and validated in emergency department settings. 1, 2

The Three Diagnostic Criteria:

Criterion 1: Acute onset (minutes to hours) of skin/mucosal involvement (hives, pruritus, flushing, swollen lips/tongue/uvula) PLUS at least one of the following: 1

• Respiratory compromise (dyspnea, wheeze/bronchospasm, stridor, reduced peak expiratory flow, hypoxemia)
• Reduced blood pressure or end-organ dysfunction (hypotonia/collapse, syncope, incontinence)

Criterion 2: Two or more of the following occurring rapidly after exposure to a likely allergen: 1

• Skin/mucosal tissue involvement (generalized hives, itch/flush, swollen lips/tongue/uvula)
• Respiratory compromise (dyspnea, wheeze/bronchospasm, stridor, reduced peak expiratory flow, hypoxemia)
• Reduced blood pressure or associated symptoms (hypotonia/collapse, syncope, incontinence)
• Persistent gastrointestinal symptoms (crampy abdominal pain, vomiting)

Criterion 3: Reduced blood pressure alone after exposure to a known allergen for that specific patient (minutes to hours): 1

• Adults: systolic BP <90 mmHg or >30% decrease from baseline
• Infants (1 month to 1 year): systolic BP <70 mmHg 3

Critical Diagnostic Considerations:

• Skin findings are absent in 10-20% of anaphylaxis cases, so do not wait for cutaneous manifestations before diagnosing and treating. 1, 4
• The NIAID/FAAN criteria demonstrated a positive likelihood ratio of 3.26 and negative likelihood ratio of 0.07 in prospective validation studies. 2
• Clinical judgment supersedes formal criteria—epinephrine should be administered when anaphylaxis is suspected, even if all criteria are not yet met. 2

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Drug of Choice and Administration for Anaphylactic Shock

Intramuscular epinephrine administered into the anterolateral thigh (vastus lateralis) is the first-line, life-saving treatment for anaphylaxis and must be given immediately. 1, 3, 5

Dosing and Administration:

Adults and children ≥30 kg (66 lbs): 5

• 0.3 to 0.5 mg (0.3 to 0.5 mL of 1 mg/mL solution) intramuscularly
• Repeat every 5-10 minutes as necessary

Children <30 kg (66 lbs): 5

• 0.01 mg/kg (0.01 mL/kg), up to maximum 0.3 mg (0.3 mL) intramuscularly
• Repeat every 5-10 minutes as necessary

Route Superiority:

Intramuscular injection in the vastus lateralis achieves peak plasma concentrations in 8±2 minutes, compared to 34±14 minutes (range 5-120 minutes) with subcutaneous deltoid injection. 1

• The anterolateral thigh provides rapid, reliable absorption. 1
• Never inject into buttocks, digits, hands, or feet. 5
• Intravenous epinephrine should only be considered in very severe cases or surgical settings due to arrhythmia risk. 6

Mechanism and Rationale:

Epinephrine is a direct-acting sympathomimetic agent that: 1

• Increases vasoconstriction and reverses hypotension
• Decreases mucosal edema
• Increases cardiac inotropy and chronotropy
• Produces bronchodilation
• Downregulates further mast cell mediator release (histamine, tryptase)

Delayed epinephrine administration is associated with poor outcomes including fatality. 1, 3

Adjunctive Medications (Only AFTER Epinephrine):

• H1 antihistamines (intravenous preferred): Slow onset (≥1 hour), primarily relieve cutaneous symptoms, do not address respiratory compromise or shock. 1, 7
• Corticosteroids: Prevent biphasic or protracted reactions but provide minimal acute benefit. 6, 7
• Inhaled beta-2 agonists (albuterol): Adjunctive for bronchospasm in patients with asthma, but do not replace epinephrine. 1
• Volume resuscitation: Crystalloids initially, colloids for severe shock. 6
• Glucagon: For patients on beta-blockers who may not respond to epinephrine. 7

Critical Pitfalls:

• Do not use oral H1 antihistamines as first-line therapy—they are too slow and ineffective for life-threatening symptoms. 1
• Patients on beta-blockers or ACE inhibitors are at higher risk for severe reactions and may require higher epinephrine doses or glucagon. 1, 5
• Observe patients for 4-12 hours for biphasic reactions (recurrence in 4-5% of cases). 1, 6, 7

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Four Types of Hypersensitivity Reactions (Gell and Coombs Classification)

Type I: IgE Antibody-Mediated (Immediate Hypersensitivity) 1

• Mechanism: IgE-mediated mast cell and basophil degranulation
• Timing: Minutes to hours after exposure
• Examples: Anaphylaxis, allergic rhinitis, food allergies, insect sting reactions, urticaria, allergic asthma 1, 8

Type II: Antibody-Mediated Cytotoxic Reactions 1

• Mechanism: IgG or IgM antibodies directed against cell surface antigens, leading to complement activation and cell destruction
• Examples: Hemolytic anemia, thrombocytopenia, blood transfusion reactions, Goodpasture syndrome 1

Type III: Immune Complex-Mediated Hypersensitivity 1

• Mechanism: Antigen-antibody immune complexes deposit in tissues, activating complement and causing inflammation
• Examples: Serum sickness, vasculitis, systemic lupus erythematosus, post-streptococcal glomerulonephritis 1

Type IV: Delayed T Cell-Mediated Responses 1

• Mechanism: T lymphocyte-mediated cellular immune response
• Timing: 24-72 hours after exposure
• Examples: Allergic contact dermatitis (poison ivy), tuberculin skin test reaction, psoriasis, maculopapular exanthema, erythema multiforme, toxic epidermal necrolysis 1

Clinical Distinction:

Anaphylaxis is exclusively a Type I hypersensitivity reaction, though the term "anaphylactoid" has been used historically for clinically identical reactions triggered by non-IgE mechanisms (direct mast cell activation by drugs like vancomycin or radiographic contrast media). 1, 8 Modern nomenclature distinguishes "allergic anaphylaxis" (IgE-mediated) from "non-allergic anaphylaxis" (non-IgE-mediated), but treatment is identical regardless of mechanism. 1