15.1 Anaphylaxis: Recognition & Emergency Management

Allergy, angioedema, and immunodeficiency encompass a broad spectrum of acute medical emergencies and chronic multisystem diseases. Mastery of immunoglobulin-mediated pathways, mast cell and bradykinin biology, drug desensitization protocols, and primary/secondary immunodeficiency syndromes is critical for the internal medicine physician.

1. Anaphylaxis: Recognition & Emergency Resuscitation

Anaphylaxis is an acute, life-threatening, systemic hypersensitivity reaction resulting from the sudden, massive release of inflammatory mediators (histamine, tryptase, leukotrienes, prostaglandins, and platelet-activating factor) from tissue mast cells and circulating basophils.

Clinical Diagnostic Criteria (NIAID / FAAN Consensus)

Anaphylaxis is highly likely when ANY ONE of the following 3 clinical criteria is fulfilled:

1. Criterion 1 (Acute Skin/Mucosa + Respiratory or Cardiovascular Compromise):
   • Acute onset (minutes to several hours) of symptoms involving the skin, mucosal tissue, or both (e.g., generalized hives, intense pruritus, flushing, swollen lips/tongue/uvula),
   • PLUS AT LEAST ONE of the following:
     • Respiratory compromise: Dyspnea, wheeze-bronchospasm, stridor, hypoxemia, reduced peak expiratory flow (PEF).
     • Reduced Blood Pressure or End-Organ Dysfunction: Hypotension (systolic BP < 90 mmHg or > 30% decline from baseline), syncope, hypotonia, loss of consciousness, incontinence.
2. Criterion 2 (Two or More Systems After Exposure to a LIKELY Allergen):
   • Rapid onset (minutes to hours) of >= 2 of the following after exposure to a likely allergen for that patient:
     • (a) Cutaneous/mucosal involvement (hives, pruritus, angioedema).
     • (b) Respiratory compromise (dyspnea, wheezing, stridor).
     • (c) Reduced blood pressure or end-organ dysfunction (syncope, collapse).
     • (d) Persistent gastrointestinal signs/symptoms (severe cramping abdominal pain, repetitive vomiting).
3. Criterion 3 (Isolated Hypotension After Exposure to a KNOWN Allergen):
   • Reduced blood pressure rapidly after exposure to a known allergen for that specific patient (systolic BP < 90 mmHg or > 30% decrease from baseline in adults).

Common Allergenic Triggers

• Foods: Peanuts, tree nuts (walnuts, almonds, cashews), shellfish, finned fish, cow's milk, eggs, soy, wheat, sesame.
• Insect Venoms (Hymenoptera): Yellow jackets, honeybees, hornets, wasps, fire ants.
• Medications: Beta-lactam antibiotics (penicillins, cephalosporins), NSAIDs/Aspirin, neuromuscular blocking agents (succinylcholine, rocuronium), monoclonal antibodies/biologics, platinum-based chemotherapeutics.
• Other Triggers: Natural rubber latex, seminal fluid, radiocontrast media (non-IgE anaphylactoid), idiopathic.

Emergency Pharmacotherapy Algorithm

                                [ PATIENT IN ANAPHYLAXIS ]
                                             │
                                             ▼
                     ┌───────────────────────────────────────────────┐
                     │ FIRST-LINE & ONLY LIFE-SAVING INTERVENTION:   │
                     │  INTRAMUSCULAR (IM) EPINEPHRINE               │
                     │  • Adult Dose: 0.3 to 0.5 mg (1:1,000)        │
                     │  • Site: ANTEROLATERAL THIGH (vastus lateralis)│
                     │  • Repeat every 5 to 15 minutes as needed     │
                     │  • NO ABSOLUTE CONTRAINDICATIONS              │
                     └───────────────────────┬───────────────────────┘
                                             │
                         ┌───────────────────┴───────────────────┐
                         ▼                                       ▼
          [ Hemodynamically Unstable / Shock ]        [ Secondary Adjunctive Therapies ]
          • Rapid IV Crystalloid Bolus (1-2 L)        (NEVER DELAY EPINEPHRINE)
          • Elevate lower extremities (Trendelenburg) • IV H1 Blocker: Diphenhydramine 25-50 mg
          • Continuous IV Epinephrine Infusion        • IV H2 Blocker: Famotidine 20 mg
          • Refractory on Beta-Blockers:             • Inhaled Albuterol 2.5-5 mg (bronchospasm)
            ➜ IV GLUCAGON (1-5 mg over 5 min)        • Systemic Steroid: Methylprednisolone 1-2 mg/kg

Detailed Pharmacotherapy Guidance

• 1. Intramuscular (IM) Epinephrine (First-Line Standard of Care):
  • Dose & Formulation: 0.3 to 0.5 mg (0.3 to 0.5 mL) of 1:1,000 (1 mg/mL) aqueous solution administered intramuscularly.
  • Anatomical Site: Anterolateral mid-thigh (vastus lateralis muscle). Pharmacokinetic studies show that IM injection into the vastus lateralis achieves significantly higher and faster peak plasma concentrations (within 8 minutes) compared to subcutaneous or deltoid intramuscular administration.
  • Frequency: Repeat every 5 to 15 minutes if symptoms fail to improve or progress.
  • Safety: There are NO absolute contraindications to epinephrine administration during a life-threatening anaphylactic episode (even in elderly patients or those with coronary artery disease).
• 2. Aggressive Intravenous Fluid Resuscitation:
  • Rapid IV infusion of 1 to 2 Liters of isotonic crystalloid (0.9% Normal Saline or Plasmalyte) via large-bore peripheral IV lines for distributive/hypovolemic shock resulting from massive vascular permeability and third-spacing (up to 35% of intravascular volume can extravasate within 10 minutes).
• 3. Secondary Adjunctive Medications (Administer ONLY AFTER Epinephrine):
  • H1-Antihistamines: IV Diphenhydramine (25–50 mg) or IV Cetirizine (reduces urticaria and pruritus; does not relieve airway edema, bronchospasm, or hypotension).
  • H2-Antihistamines: IV Famotidine (20 mg; combined H1 + H2 blockade provides superior cutaneous symptom relief compared to H1 blockade alone).
  • Inhaled Beta-2 Agonists: Inhaled Albuterol (2.5–5.0 mg nebulized) for persistent wheezing and bronchospasm refractory to epinephrine.
  • Systemic Corticosteroids: IV Methylprednisolone (1–2 mg/kg) or oral Prednisone (40–60 mg). Corticosteroids have a delayed onset of action (4–6 hours) and do not treat acute shock or laryngeal edema; their primary traditional role is to decrease the severity of biphasic reactions.
• 4. Refractory Anaphylaxis in Patients on Beta-Blockers:
  • Patients taking chronic beta-adrenergic blockers (e.g., Metoprolol, Atenolol, Propranolol) are prone to severe, refractory anaphylaxis characterized by profound bradycardia, severe hypotension, and resistance to epinephrine (beta-blockade blunts cardiac inotropy/chronotropy and allows unopposed alpha-adrenergic vasoconstriction, increasing afterload and precipitating cardiovascular collapse).
  • Specific Antidote: Intravenous Glucagon (1 to 5 mg IV administered over 5 minutes, followed by a continuous infusion of 5 to 15 mcg/min).
  • Mechanism: Glucagon binds to specific non-adrenergic G-protein-coupled glucagon receptors, stimulating intracellular adenylate cyclase and increasing cyclic AMP (cAMP) independently of beta-adrenergic receptors, restoring myocardial contractility, heart rate, and vascular tone.
• 5. Biphasic Anaphylaxis & Post-Discharge Care:
  • Biphasic Anaphylaxis: A recurrence of anaphylaxis symptoms occurring without re-exposure to the allergen in 10% to 20% of patients, typically arising within 1 to 72 hours (median 8–10 hours) after complete resolution of the initial attack.
  • Observation Period: Minimum 4 to 8 hours of continuous medical observation for mild, rapidly responsive anaphylaxis; 12 to 24 hours for patients with severe initial presentation (hypotension, severe airway edema, or requiring > 1 dose of epinephrine).
  • Discharge Plan: Prescribe two Epinephrine Auto-Injectors (0.3 mg) with hands-on demonstration; provide a written Emergency Anaphylaxis Action Plan; refer to an Allergist/Immunologist for confirmatory testing and potential Venom Immunotherapy (VIT) (which reduces recurrent severe venom anaphylaxis risk from > 60% to < 5%).