What is the appropriate treatment for a patient experiencing a hypersensitivity reaction?

Treatment of Hypersensitivity Reactions

Immediately administer intramuscular epinephrine 0.3-0.5 mg into the anterolateral thigh for any patient presenting with anaphylaxis, activate emergency medical services, and provide supportive care with oxygen and IV fluids as needed. 1, 2

Immediate Management of Anaphylaxis

Epinephrine is the only first-line treatment for anaphylaxis and must never be delayed or substituted with antihistamines or corticosteroids. 1, 3

• Administer epinephrine 0.3-0.5 mg intramuscularly in the anterolateral thigh for adults (0.01 mg/kg for children, maximum 0.5 mg) 4, 1
• Repeat epinephrine every 5-15 minutes if symptoms persist or recur 1
• Call emergency medical services immediately after administering epinephrine, even if symptoms improve 4, 1
• Place patient in supine position with legs elevated (if tolerated and no respiratory distress) 1
• Provide supplemental oxygen to all patients with prolonged reactions, hypoxemia, or requiring multiple epinephrine doses 1
• Establish IV access and administer normal saline for hypotension 1

Fatal anaphylaxis is associated with delayed or absent epinephrine administration—there are no contraindications to epinephrine use in life-threatening anaphylaxis, even in patients with cardiovascular disease or taking beta-blockers. 3

Adjunctive Therapies (Secondary to Epinephrine)

After epinephrine administration, adjunctive medications may be given but should never replace or delay epinephrine 1, 3:

• H1-antihistamines (diphenhydramine 25-50 mg IV/IM or equivalent) for cutaneous symptoms 4, 1
• H2-antihistamines (famotidine 20 mg IV or ranitidine 50 mg IV) may provide additional benefit 4
• Corticosteroids (methylprednisolone 125 mg IV or hydrocortisone 200 mg IV) to potentially reduce biphasic reactions, though evidence is limited 4, 3
• Bronchodilators (albuterol) for persistent bronchospasm despite epinephrine 1

Antihistamines and corticosteroids are NOT substitutes for epinephrine and have no role in preventing or treating the life-threatening manifestations of anaphylaxis. 3

Management of Mild-to-Moderate Hypersensitivity Reactions

Cutaneous-Only Reactions

For isolated cutaneous symptoms (urticaria, pruritus, mild angioedema) without respiratory, cardiovascular, or gastrointestinal involvement 4:

• Initial treatment may include H1-antihistamines and close observation 4
• Have epinephrine immediately available and monitor for progression to anaphylaxis 4
• If symptoms progress beyond isolated cutaneous manifestations, immediately administer epinephrine 4, 1

Large Local Reactions (Insect Stings)

For extensive local swelling at sting sites 4:

• Apply cold compresses to reduce pain and swelling 4
• Administer oral antihistamines for pruritus 4
• Consider short course of oral corticosteroids (prednisone 40-60 mg daily for 3-5 days) for severe local swelling 4
• Antibiotics are usually not necessary as swelling is allergic inflammation, not infection 4

Drug-Specific Hypersensitivity Management

Chemotherapy Infusion Reactions

For platinum agents (carboplatin, cisplatin, oxaliplatin) and taxanes (paclitaxel, docetaxel): 4

First exposure (mild infusion reaction):

• Decrease or stop infusion rate 4
• Administer antihistamine 4
• If vital signs remain stable and symptoms resolve quickly, may rechallenge with slower infusion 4
• Premedicate with antihistamine, corticosteroids, and H2-blockers for subsequent infusions 4

Second or subsequent exposure with reaction:

• Administer antihistamine for symptoms 4
• Add corticosteroid ± IM epinephrine if symptoms do not quickly resolve 4
• Do not rechallenge until evaluated by allergist 4
• Consider desensitization protocol for subsequent infusions if drug is irreplaceable 4

Severe or life-threatening reactions:

• Discontinue infusion immediately 4
• Administer epinephrine, antihistamines, corticosteroids, and supportive care 4
• Refer to center with desensitization expertise if drug is essential 4

Radiocontrast Media Reactions

For patients with history of severe immediate hypersensitivity to iodinated contrast media: 4, 5

• First-line approach: Consider alternative non-contrast imaging (ultrasound, non-contrast CT, MRI without gadolinium) 5
• If contrast-enhanced imaging is essential: Switch to a different low- or iso-osmolar contrast agent (more effective than premedication alone) 4, 5
• Premedication (reserved for severe prior reactions when alternatives unavailable): Prednisone 50 mg at 13,7, and 1 hour before procedure PLUS diphenhydramine 50 mg 1 hour before procedure 5
• Perform procedure in hospital setting with personnel and equipment immediately available to treat anaphylaxis 4, 5

Critical pitfall: Patients with shellfish/seafood allergies or iodine allergies do NOT require premedication for contrast media—these are not risk factors for contrast reactions 4, 5

Antibiotic Hypersensitivity

For penicillin-allergic patients requiring beta-lactam therapy: 4

• Vancomycin may be substituted in patients with immediate-type hypersensitivity reactions to beta-lactams 4
• Cefazolin may be used in patients with non-immediate-type hypersensitivity reactions to penicillins 4
• Consider allergy consultation for skin testing and potential delabeling 4

Post-Reaction Management and Prevention

Immediate Post-Reaction Care

• Transport all patients who received epinephrine to emergency department for monitoring (minimum 4-6 hours observation) 4, 1
• Obtain serum tryptase level 30-120 minutes after reaction onset to confirm anaphylaxis 6
• Prescribe epinephrine auto-injectors (two devices) for any patient with history of anaphylaxis 4, 1
• Provide written anaphylaxis action plan 4, 1

Long-Term Management

• Refer all patients with systemic reactions to allergist-immunologist for comprehensive evaluation 1
• Perform skin testing 4-6 weeks after reaction to identify culprit agent and safe alternatives 6, 7
• Consider venom immunotherapy for insect sting anaphylaxis (reduces future reaction risk from 25-70% to <5%) 4, 1
• Educate patients on avoidance measures and proper epinephrine auto-injector technique 4, 1

Critical Pitfalls to Avoid

• Never delay epinephrine in favor of antihistamines or corticosteroids for anaphylaxis 1, 3
• Do not rely on premedication to prevent hypersensitivity reactions—it has very limited proven benefit (NNT 69-385 for most indications) and does not substitute for emergency preparedness 3
• Avoid extravasation when administering IV epinephrine—check infusion site frequently and treat extravasation with phentolamine 5-10 mg infiltrated locally 2
• Do not assume sulfite allergy contraindicates epinephrine use—epinephrine should still be used for life-threatening anaphylaxis even in sulfite-sensitive patients 2
• Monitor for biphasic reactions—up to 20% of anaphylaxis cases may have recurrent symptoms 4-12 hours after initial resolution, necessitating prolonged observation 1