How do you differentiate and treat a potential allergic reaction versus an infection?

Differentiating and Treating Allergic Reactions vs Infection

When a patient presents with symptoms that could represent either an allergic reaction or infection, prioritize immediate assessment for anaphylaxis first—if present, administer intramuscular epinephrine 0.01 mg/kg (max 0.5 mg) into the anterolateral thigh without delay, as this is the only first-line treatment with no substitute. 1, 2, 3

Immediate Differentiation: Life-Threatening vs Non-Life-Threatening

Recognize Anaphylaxis Immediately (Severe Allergic Reaction)

Anaphylaxis requires epinephrine first—never delay for antihistamines or other medications. 1, 3

Look for these specific criteria 4:

• Acute onset (minutes to hours) with skin/mucosal involvement (generalized hives, flushing, lip/tongue swelling) PLUS at least one of:

  • Respiratory compromise (dyspnea, wheeze, stridor, hypoxemia)
  • Hypotension or end-organ dysfunction (syncope, collapse, incontinence)
  • Severe GI symptoms (severe crampy pain, repetitive vomiting)

• OR acute hypotension/bronchospasm/laryngeal involvement after known allergen exposure, even without skin findings 4

Key Clinical Distinctions

Timing is critical for differentiation 4:

• Immediate-type allergic reactions: Onset within minutes to 2 hours of exposure, involving urticaria, angioedema, bronchospasm, or anaphylaxis 4
• Delayed-type allergic reactions: Onset >6 hours after exposure, typically maculopapular rash, may include severe cutaneous adverse reactions (SCARs) 4
• Infections: Gradual onset over hours to days, with fever, purulent discharge, localized warmth/tenderness, elevated inflammatory markers 4

Specific features favoring allergy over infection 4:

• Pruritus (itching) is prominent in allergic reactions, rare in infections
• Urticaria (hives) that are migratory and blanch with pressure
• Rapid onset after drug/food exposure
• Absence of fever (though severe allergic reactions can have fever >38.5°C in DRESS/AGEP) 4

Specific features favoring infection over allergy 4:

• Fever with rigors/chills
• Purulent drainage or exudate
• Localized tenderness and warmth
• Elevated WBC with left shift, elevated CRP/ESR
• Gradual symptom progression over days

Treatment Algorithm

For Severe Reactions (Anaphylaxis)

Step 1: Epinephrine immediately 1, 5, 2, 3

• 0.01 mg/kg intramuscular (1:1,000 solution), maximum 0.5 mg per dose
• Inject into anterolateral thigh
• May repeat every 5-15 minutes if needed

Step 2: Second-line adjunctive therapy AFTER epinephrine 1, 5:

• H1 antihistamine: Diphenhydramine 1-2 mg/kg (max 50 mg) IV or oral 1, 6
• H2 antihistamine: Ranitidine 1-2 mg/kg (max 75-150 mg) or famotidine 1, 5
• Corticosteroid: Prednisone 1 mg/kg (max 60-80 mg) orally to prevent biphasic reactions 1, 5

Step 3: Observation 5

• Minimum 6 hours for severe reactions or until stable
• 4-6 hours for moderate reactions

For Non-Severe Allergic Reactions

Immediate-type, non-severe 4:

• Single organ system involvement (cutaneous urticaria, nasal symptoms, conjunctival symptoms)
• Treatment: Oral H1 antihistamine (loratadine 10 mg or cetirizine 10 mg) 7, 5
• Observe until symptoms resolve 7

Delayed-type, non-severe 4:

• Maculopapular exanthema without organ involvement
• Discontinue culprit drug
• Symptomatic treatment with antihistamines
• Document reaction for future antibiotic selection 4

For Suspected Infection

• Initiate appropriate antibiotic therapy based on suspected source
• If patient has documented antibiotic allergy, follow cross-reactivity guidelines 4

Managing Antibiotic Allergy When Infection Treatment Is Needed

Critical principle: Most reported antibiotic allergies are not true IgE-mediated reactions—less than 10% are confirmed on formal testing. 4

Penicillin Allergy Management 4

For non-severe delayed-type reactions:

• Avoid all penicillins including culprit drug
• Avoid cephalosporins with similar side chains
• All other beta-lactams allowed if indication is vital (discuss with multidisciplinary team)

For severe delayed-type reactions (e.g., Stevens-Johnson syndrome, DRESS):

• Avoid all penicillins and cephalosporins with similar side chains
• Avoid all beta-lactam antibiotics
• Consider non-beta-lactam alternatives 5

For non-severe immediate-type reactions:

• Avoid all penicillins
• Avoid cephalosporins with similar side chains
• All other beta-lactams allowed

Cross-Reactivity Considerations 4

Carbapenems and aztreonam are generally safe in penicillin allergy 4:

• No cross-reactivity observed in delayed-type reactions
• Can be administered in clinical setting for immediate-type reactions

Ceftazidime, cefiderocol, and aztreonam share identical side chains 4:

• High cross-reactivity risk
• Avoid aztreonam if allergic to ceftazidime or cefiderocol

Critical Pitfalls to Avoid

Never use antihistamines as primary treatment for anaphylaxis—this is the most common reason for not using epinephrine and significantly increases risk of life-threatening progression 1, 3

Do not confuse viral exanthema with drug allergy 4:

• Viral rashes are common in children on antibiotics
• True drug allergy requires immune-mediated mechanism
• Document timing, morphology, and associated symptoms carefully

Do not assume all beta-lactams are contraindicated in penicillin allergy 4:

• Side chain similarity determines cross-reactivity, not drug class alone
• Carbapenems have <1% cross-reactivity with penicillins

First-generation antihistamines can worsen hypotension—use cautiously in hemodynamically unstable patients 5

For patients on beta-blockers with anaphylaxis, have glucagon available (20-30 μg/kg for children, 1-5 mg for adults) as they may have reduced response to epinephrine 1

Post-Reaction Management

After any severe allergic reaction 1, 5:

• Continue H1 antihistamine every 6 hours for 2-3 days
• Continue H2 antihistamine and corticosteroid
• Prescribe epinephrine auto-injector (2 doses) with training
• Provide anaphylaxis emergency action plan
• Arrange allergist follow-up for formal allergy testing

Adjust antibiotic allergy labels after formal workup or direct challenges 4:

• Document which antibiotic was given and whether tolerated
• Communicate adjustments to all healthcare institutions (primary care, pharmacy, nursing homes)