What is the appropriate management for a patient presenting with hives and fever, potentially indicating anaphylaxis or an allergic reaction?

Management of Hives with Fever

The immediate priority is to determine whether this represents isolated urticaria with fever or anaphylaxis—if any systemic symptoms beyond skin findings are present (respiratory compromise, cardiovascular instability, gastrointestinal symptoms), administer intramuscular epinephrine 0.3-0.5 mg (1:1000 solution) immediately before any other treatment. 1, 2

Critical Initial Assessment

Rapidly assess for anaphylaxis criteria by evaluating three key organ systems beyond the skin 1:

• Respiratory system: Look for dyspnea, wheeze, bronchospasm, stridor, throat tightness, or oxygen desaturation 3
• Cardiovascular system: Check for hypotension, tachycardia, syncope, chest pain, or arrhythmias 3, 4
• Gastrointestinal system: Assess for cramping, abdominal pain, nausea, vomiting, or diarrhea 3, 4

The presence of hives plus fever alone does NOT automatically indicate anaphylaxis—fever with isolated urticaria may represent a febrile transfusion reaction, drug reaction, or infectious process rather than true anaphylaxis 3.

If Anaphylaxis is Present

Administer intramuscular epinephrine 0.3-0.5 mg (1:1000 solution) in the anterolateral thigh immediately as the first-line treatment before any other medications 1, 2. This is non-negotiable—antihistamines and corticosteroids should never replace epinephrine when anaphylaxis is suspected 1.

After epinephrine administration, provide adjunctive therapy 5, 6:

• Place patient supine with legs elevated (unless respiratory distress requires upright positioning) 6
• Administer high-flow oxygen 6
• Establish IV access and give normal saline bolus (20 mL/kg in children, 1-2 L in adults) for hypotension 6
• Add H1 antihistamine (diphenhydramine 1-2 mg/kg IV, max 50 mg) 1
• Add H2 antihistamine (ranitidine 1-2 mg/kg IV, max 150 mg) 1
• Consider corticosteroids (prednisone 1 mg/kg oral, max 60-80 mg) for severe cases, though these do NOT treat acute anaphylaxis or prevent biphasic reactions 5

Observe for 4-6 hours minimum, with extended observation up to 24 hours if the patient required multiple epinephrine doses, had severe initial hypotension, or has unknown trigger 5, 6. Biphasic reactions occur in 1-20% of cases, typically around 8 hours but can occur up to 72 hours later 5, 4.

If Isolated Urticaria with Fever (No Anaphylaxis)

For hives with fever but NO systemic symptoms, the approach differs significantly 3:

First-line treatment 1:

• H1 antihistamine: diphenhydramine 1-2 mg/kg per dose (max 50 mg) IV or oral 1
• Alternative: second-generation H1 antihistamine (cetirizine, loratadine) for less sedation 1

For moderate-severe urticaria, add 1:

• H2 antihistamine: ranitidine 1-2 mg/kg (max 75-150 mg) oral or IV 1
• The combination of H1 plus H2 antihistamines is more effective than either alone 1

Consider corticosteroids selectively (prednisone 1 mg/kg oral, max 60-80 mg) only for severe, extensive urticaria or anticipated prolonged symptoms 1.

Address the fever component 3:

• Intravenous paracetamol (acetaminophen) may be used for febrile reactions 3
• Investigate potential causes: transfusion reaction, drug hypersensitivity, or underlying infection 3
• Do NOT use steroids indiscriminately for febrile reactions, as repeated doses may suppress immunity in immunocompromised patients 3

Critical Pitfalls to Avoid

Never delay epinephrine if anaphylaxis is suspected—the most common cause of fatal anaphylaxis is delayed or absent epinephrine administration 1, 6. Death from anaphylaxis can occur within 30 minutes to 2 hours 5.

Do not rely on hives as a diagnostic criterion—20-30% of anaphylaxis cases have no cutaneous manifestations 4, 7. Conversely, isolated hives without systemic symptoms do not constitute anaphylaxis 1.

Recognize that fever distinguishes this from typical allergic urticaria—the combination of hives and fever should prompt investigation for drug reactions, transfusion reactions, or systemic mastocytosis rather than simple allergic urticaria 3.

Observation and Discharge

For isolated urticaria with fever that responds to treatment, observe for 2-4 hours minimum 1. Discharge only after complete symptom resolution and hemodynamic stability 5.

For anaphylaxis, observe 4-6 hours minimum, with extended observation for high-risk features 5, 6. Prescribe epinephrine auto-injector at discharge, provide emergency action plan, and refer to allergist 6, 7.

Continue post-discharge treatment for 2-3 days with H1 antihistamine, H2 antihistamine, and corticosteroid after anaphylaxis, though corticosteroids do not prevent biphasic reactions 5.