Grade 2 Allergic Reaction Dosing
For a Grade 2 allergic reaction (symptoms involving more than one organ system), epinephrine is NOT routinely required as first-line treatment; instead, use H1 antihistamines as primary therapy with close monitoring for progression. 1
Understanding Grade 2 Reactions
Grade 2 reactions are defined as symptoms/signs involving more than one organ system, which may include: 1
- Generalized pruritus, urticaria, flushing, or sensation of heat
- Angioedema (not involving larynx, tongue, or uvula)
- Mild asthma symptoms (cough, wheezing, shortness of breath) that respond to inhaled bronchodilators
- Rhinitis, conjunctival symptoms
- Nausea, metallic taste, or headache
Critical distinction: Grade 2 does NOT include lower respiratory symptoms unresponsive to bronchodilators, hypotension, or severe respiratory compromise—those are Grade 3-4 reactions requiring immediate epinephrine. 1
Primary Treatment Protocol
H1 Antihistamine Dosing (First-Line for Grade 2)
- Dose: 1-2 mg/kg per dose
- Maximum single dose: 50 mg
- Route: IV or oral (oral liquid absorbs faster than tablets)
- Frequency: Every 6 hours for 2-3 days post-discharge
Alternative: Second-generation antihistamines may be used when sedation is problematic, though diphenhydramine remains standard for acute reactions. 2
Adjunctive H2 Antihistamine (Enhances Efficacy)
Ranitidine (or alternative H2 blocker): 1
- Dose: 1-2 mg/kg per dose
- Maximum dose: 75-150 mg oral or IV
- Rationale: The combination of H1 + H2 antihistamines is superior to H1 alone for urticaria relief 1, 3
Evidence note: For urticaria specifically, diphenhydramine plus cimetidine showed significantly more relief (mean score 55.3) compared to diphenhydramine alone (30.7, P=0.006). 3
When to Escalate to Epinephrine
Administer epinephrine immediately if: 1
- Symptoms progress despite antihistamine therapy
- Lower respiratory symptoms develop that don't respond to bronchodilators
- Any signs of hypotension, severe bronchospasm, or laryngeal edema appear
- Patient has risk factors: history of severe reactions, asthma, cardiovascular disease, or peanut/tree nut allergy 4
Epinephrine dosing (if escalation needed): 1
- Weight 10-25 kg: 0.15 mg IM (epinephrine auto-injector)
- Weight >25 kg: 0.3 mg IM (epinephrine auto-injector)
- Alternative: 0.01 mg/kg IM (1:1,000 solution), maximum 0.5 mg
- Site: Anterolateral thigh (vastus lateralis muscle)
- Repeat: Every 5-15 minutes as needed
Additional Supportive Measures for Grade 2
If mild bronchospasm present: 1
- Albuterol nebulized: 1.5 mL (child) or 3 mL (adult) every 20 minutes as needed
- Albuterol MDI: 4-8 puffs (child) or 8 puffs (adult)
Corticosteroids (consider for prevention of biphasic reactions): 1
- Prednisone: 1 mg/kg oral, maximum 60-80 mg
- Methylprednisolone: 1 mg/kg IV, maximum 60-80 mg
- Note: Corticosteroids don't help acutely but may prevent protracted or biphasic reactions 1
Critical Monitoring Requirements
Observation period: Must be individualized, but typically 4-12 hours depending on: 4
- Severity of initial presentation
- Response to treatment
- Risk factors for biphasic reactions (10-20% of cases)
- Distance from home to emergency facility
Watch for progression: Grade 2 reactions can rapidly evolve to Grade 3-4, especially within the first 30 minutes. 1
Common Pitfalls to Avoid
Never use antihistamines alone for Grade 3-4 reactions (lower respiratory distress, hypotension)—these require immediate epinephrine. 1
Don't delay epinephrine if uncertain—it's safer to give epinephrine for a Grade 2 that might progress than to wait for clear Grade 3-4 symptoms. 4
Avoid subcutaneous epinephrine—IM administration in the thigh provides faster, more reliable absorption. 1
Don't discharge without observation—biphasic reactions can occur hours later without re-exposure to allergen. 1
In elderly patients (>85 years), reduce diphenhydramine doses due to anticholinergic sensitivity and increased risk of delirium and falls. 2
Discharge Planning
All patients with Grade 2 reactions should receive: 1
- Epinephrine auto-injector prescription (2 doses) with administration training
- Emergency action plan
- Referral to allergist-immunologist
- Education on trigger avoidance
- Instructions to return immediately if symptoms recur