What is the difference between anaphylaxis and anaphylaxis-like episodes?

Difference Between Anaphylaxis and Anaphylaxis-Like Episodes

Anaphylaxis is a true acute life-threatening systemic reaction resulting from sudden mast cell and basophil mediator release, while anaphylaxis-like episodes (anaphylactoid reactions) present with identical clinical manifestations but occur through non-IgE-dependent mechanisms. 1

Key Distinctions

Underlying Mechanisms

• Anaphylaxis (true anaphylaxis): IgE-dependent mechanism triggered by allergen cross-linking of IgE antibodies on mast cells and basophils 1
• Anaphylaxis-like episodes (anaphylactoid reactions): Non-IgE-dependent mechanisms that directly activate mast cells or trigger complement activation 1, 2

Clinical Presentation

• Both conditions present with identical clinical manifestations, making them clinically indistinguishable at the time of presentation 1
• Common symptoms in both include:
  • Cutaneous manifestations (90% of cases): urticaria, angioedema, flushing, pruritus 1
  • Respiratory symptoms (40-60%): dyspnea, wheezing, upper airway angioedema 1
  • Cardiovascular symptoms (30-35%): dizziness, syncope, hypotension 1
  • Gastrointestinal symptoms (25-30%): nausea, vomiting, diarrhea, cramping pain 1

Common Triggers

• Anaphylaxis (IgE-mediated):

  • Foods (especially nuts, peanuts, fish, shellfish) 2
  • Insect venoms (hymenoptera stings) 2
  • Medications (particularly penicillin and other beta-lactam antibiotics) 2
  • Latex 3

• Anaphylaxis-like episodes (non-IgE-mediated):

  • Radiographic contrast media 2
  • Certain medications (vancomycin, quinolone antibiotics) 2
  • Physical factors (exercise, cold, heat) 1
  • Direct mast cell activators 2

Diagnostic Considerations

Laboratory Testing

• Serum tryptase levels may help differentiate between true anaphylaxis and anaphylaxis-like episodes in unclear cases 1
• In true anaphylaxis, β-tryptase is secreted in large amounts during the reaction 1
• The ratio of total tryptase (α plus β) to β-tryptase can help distinguish between:
  • Ratio ≤10: Anaphylactic episode not related to systemic mastocytosis 1
  • Ratio ≥20: Consistent with systemic mastocytosis 1

Differential Diagnosis

• Both conditions must be differentiated from other conditions that mimic anaphylaxis 1:
  • Vasodepressor (vasovagal) reactions 1
  • Panic attacks 1
  • Flushing syndromes (carcinoid, postmenopausal) 1
  • Scombroidosis (histamine fish poisoning) 1
  • Vocal cord dysfunction syndrome 1
  • Systemic mastocytosis 1

Management Approach

Acute Treatment

• Management is identical for both conditions 1
• First-line treatment is intramuscular epinephrine regardless of whether the reaction is IgE-mediated or not 1, 4
• Additional measures include:
  • Airway management and oxygen administration 1
  • Fluid resuscitation for hypotension 1
  • H1 antihistamines and corticosteroids as adjunctive therapy 4

Long-term Management

• For true anaphylaxis:

  • Allergen identification and avoidance 3
  • Allergen-specific immunotherapy when available (e.g., for insect venom anaphylaxis) 5
  • Self-injectable epinephrine prescription 3

• For anaphylaxis-like episodes:

  • Avoidance of triggers when possible 2
  • Premedication protocols may be used for unavoidable exposures (e.g., contrast media) 5
  • Combined H1 and H2 antihistamines for prophylaxis 5

Clinical Pitfalls and Caveats

• The absence of cutaneous symptoms does not rule out anaphylaxis; severe episodes with rapid cardiovascular collapse can occur without skin manifestations 1
• Both conditions can present with biphasic reactions (recurrence of symptoms 8-12 hours after initial resolution) requiring extended observation 1
• Bradycardia can occur in anaphylaxis due to the Bezold-Jarisch reflex, potentially confusing it with vasovagal reactions 1
• Antihistamines alone are insufficient treatment for either condition; epinephrine remains the first-line therapy 4
• Laboratory tests are not helpful in the acute situation; diagnosis is primarily clinical 5