How should I manage a patient who develops an allergic reaction to prednisone?

Management of Allergic Reaction to Prednisone

Immediately discontinue prednisone and administer intramuscular epinephrine 0.3-0.5 mg (1:1000 dilution) into the anterolateral thigh if the patient exhibits signs of anaphylaxis or systemic involvement, as epinephrine is the only first-line treatment and must not be delayed. 1

Initial Assessment and Severity Grading

• Assess the severity of the allergic reaction immediately to determine appropriate intervention, recognizing that reactions range from isolated cutaneous symptoms (Grade I) to life-threatening cardiovascular collapse (Grade IV). 2
• Look for multi-organ involvement including skin manifestations (urticaria, angioedema, flushing), respiratory symptoms (bronchospasm, throat tightness, stridor), cardiovascular signs (hypotension, tachycardia), and gastrointestinal symptoms (nausea, vomiting, abdominal pain). 3
• Measure vital signs immediately including pulse, blood pressure, and oxygen saturation, but do not delay epinephrine administration to obtain these measurements if the reaction appears severe. 3, 1

Immediate Management Based on Severity

For Anaphylaxis or Severe Reactions (Multi-organ involvement, respiratory distress, or hypotension):

• Administer epinephrine 0.3-0.5 mg intramuscularly (1:1000 dilution) into the anterolateral thigh immediately as this is the only first-line treatment. 1
• Repeat epinephrine every 5-15 minutes if symptoms persist or progress, as delayed administration is associated with fatalities. 1, 3
• Position the patient supine with legs elevated unless respiratory distress is present, in which case use position of comfort. 1
• Establish IV access and administer crystalloid bolus of 500-1000 mL for adults or 20 mL/kg for children. 1, 3
• Provide supplemental oxygen and monitor oxygen saturation continuously. 1, 3

Adjunctive Medications (After Epinephrine):

• Administer H1-antihistamine: diphenhydramine 25-50 mg IV/IM (1-2 mg/kg) after epinephrine administration. 1, 3
• Administer H2-antihistamine: ranitidine 50 mg IV (or famotidine 20 mg IV if unavailable), as the combination of H1 + H2 antagonists is superior to H1 alone. 1, 3
• Consider corticosteroids for severe reactions: methylprednisolone 1-2 mg/kg IV or hydrocortisone 100 mg IV, though these do not treat the acute phase and are given to potentially prevent biphasic reactions. 3, 4

For Mild to Moderate Reactions (Isolated urticaria, mild angioedema, or flushing without systemic symptoms):

• Discontinue prednisone immediately. 5
• Administer oral H1-antihistamines such as loratadine 10 mg or cetirizine 10 mg orally. 5, 3
• Consider adding H2 blockers such as ranitidine 1-2 mg/kg for moderate reactions. 5
• Maintain close observation for 4-6 hours to ensure lack of progression to anaphylaxis, and if progression occurs, administer epinephrine immediately. 3, 4

Special Considerations for Corticosteroid Allergy

• Recognize that true IgE-mediated allergic reactions to corticosteroids are rare but well-documented, with an estimated prevalence of 0.3-0.5% in the general population. 6, 7
• Understand that cross-reactivity exists among corticosteroids, but patients sensitized to one corticosteroid do not necessarily react to all types. 7, 8
• Perform skin testing with a panel of alternative corticosteroids when the patient is stable to identify safe alternatives for future use, as this is the best way to select safe corticosteroids. 7, 6
• Consider alternative corticosteroids from different structural groups: patients who react to prednisolone may tolerate methylprednisolone or dexamethasone, as demonstrated in case reports. 7, 8

Observation and Monitoring

• Observe all patients for a minimum of 4-6 hours after symptom resolution for mild to moderate reactions. 1, 5
• Extend observation to at least 6-24 hours for severe reactions, as biphasic reactions can occur up to 72 hours after the initial reaction (average 11 hours). 1
• Monitor vital signs and perform physical examination every 15 minutes or more frequently as needed until symptoms resolve, then every 30-60 minutes until discharge. 3

Discharge Planning and Follow-up

• Prescribe two epinephrine auto-injectors (0.15 mg if 10-25 kg, 0.3 mg if ≥25 kg) with hands-on training demonstration for any patient who experienced anaphylaxis or severe reaction. 1
• Provide continuation therapy: prednisone 1 mg/kg daily (maximum 60-80 mg) for 2-3 days (no taper needed), H1-antihistamine for 2-3 days, and H2-antihistamine twice daily for 2-3 days. 1, 3
• Arrange urgent allergy/immunology referral for comprehensive evaluation including skin testing to identify safe alternative corticosteroids for future use. 7, 6
• Document the reaction clearly in the medical record and ensure the patient receives medical identification jewelry or an anaphylaxis wallet card. 3
• Educate the patient on allergen avoidance, early recognition of anaphylaxis symptoms, and proper epinephrine auto-injector administration. 3

Critical Pitfalls to Avoid

• Never delay epinephrine administration while waiting for IV access or other interventions in anaphylaxis, as delayed injection is associated with fatalities. 1
• Never substitute antihistamines or alternative corticosteroids for epinephrine as first-line treatment in anaphylaxis. 1, 4
• Never assume all corticosteroids will cause cross-reactivity—careful challenge testing can identify safe alternatives. 7
• Never discharge patients prematurely without adequate observation for biphasic reactions, especially those requiring multiple epinephrine doses. 1
• Do not use systemic corticosteroids indiscriminately in the acute setting when the patient has a documented corticosteroid allergy; prioritize epinephrine, antihistamines, and supportive care first. 4