What is the approach to diagnosis and treatment of hypersensitivity reactions in pediatric patients, particularly those with a history of allergies, asthma, or eczema?

Approach to Hypersensitivity Reactions in Pediatric Patients

Immediate Recognition and Emergency Management

Epinephrine is the first-line medication for anaphylaxis in children and must be administered immediately when anaphylaxis is suspected—delayed administration increases risk of hospitalization, hypoxic-ischemic encephalopathy, and death. 1

Recognizing Anaphylaxis in Children

Anaphylaxis is highly likely when any ONE of these criteria is met:

• Acute onset (minutes to hours) with skin/mucosal involvement (urticaria, flushing, swollen lips/tongue) PLUS either respiratory compromise (dyspnea, wheeze, stridor) OR hypotension/end-organ dysfunction (syncope, incontinence) 1

• Two or more systems involved (skin, respiratory, gastrointestinal, cardiovascular) after exposure to a likely allergen 1

• Hypotension alone after exposure to a known allergen for that patient 1

Critical First Steps

• Administer intramuscular epinephrine immediately (0.01 mg/kg of 1:1000 solution, maximum 0.3 mg for children, 0.5 mg for adolescents) into the anterolateral thigh 1, 2

• Position patient supine with legs elevated (if tolerated and no respiratory distress) 1

• Call emergency medical services—transport to emergency facility even after epinephrine administration 1

• Administer supplemental oxygen if available 1

• Consider albuterol for bronchospasm (though epinephrine remains primary treatment) 3

Common Pitfall: Antihistamines and corticosteroids are NOT first-line treatments for anaphylaxis and should never delay epinephrine administration 1

Diagnostic Approach by Reaction Type

Immediate Hypersensitivity Reactions (IgE-Mediated)

Timing: Occur within minutes to 2 hours of exposure 1

Clinical Features to Document:

• Urticaria, angioedema, flushing, pruritus 1, 4
• Respiratory symptoms: wheeze, stridor, dyspnea, throat tightness 1
• Gastrointestinal: nausea, vomiting, cramping, diarrhea 1
• Cardiovascular: hypotension, tachycardia, syncope 1
• Most pediatric anaphylaxis involves mucocutaneous (skin), respiratory, and gastrointestinal systems 4

Diagnostic Testing:

• Skin prick testing (SPT) has high negative predictive value (>95%) but low positive predictive value (40-60%)—negative tests effectively rule out IgE-mediated allergy 1
• Serum-specific IgE testing is preferred when extensive eczema, dermatographism, or recent antihistamine use precludes skin testing 1
• Positive tests indicate sensitization only, NOT clinical allergy—must correlate with clinical history 1, 5
• Oral food challenges remain the gold standard for confirming food allergy when testing is equivocal 1

Critical Point: Only 31-68% of children with suspected NSAID hypersensitivity and 19.6% with suspected drug reactions have positive challenges, demonstrating poor reliability of history alone 1

Delayed Hypersensitivity Reactions (Non-IgE-Mediated)

Timing: Occur 6-48 hours or longer after exposure 1

Benign Delayed Reactions:

• Maculopapular exanthems (most common) 1
• Often manageable with symptomatic treatment (oral antihistamines) while continuing the medication 1

Severe Cutaneous Adverse Drug Reactions (REQUIRE IMMEDIATE DISCONTINUATION):

• Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN) 1
• Drug reaction with eosinophilia and systemic symptoms (DRESS) 1, 6
• Acute generalized exanthematous pustulosis (AGEP) 1, 6
• These are NOT amenable to desensitization and indicate permanent contraindication 1

Diagnostic Approach:

• Atopy patch testing (APT) for delayed eczematous reactions has limited utility—higher specificity than SPT for some foods (wheat) but difficult interpretation and not routinely recommended 1
• Patch testing may identify culprit in delayed drug reactions 6

Risk Stratification

High-Risk Pediatric Populations

Children at elevated risk for severe reactions:

• Coexisting asthma (strongest predictor of severe/fatal anaphylaxis, especially with peanut/tree nut allergy) 1
• Moderate-to-severe atopic dermatitis (up to 37% have IgE-mediated food allergy) 1
• Previous severe reaction requiring epinephrine 1
• Adolescents (poorest compliance with carrying epinephrine) 1

Important: 80% of children with anaphylaxis have other atopic comorbidities that correlate with reaction severity 4

Identifying Triggers

Most Common Triggers in Children:

• Foods (leading cause in pediatrics): milk, egg, peanut, tree nuts, soy, wheat, fish, shellfish 1, 4
• Medications: Beta-lactam antibiotics most common (78.4% of drug reactions), followed by other antimicrobials 1, 7, 6
• Biologics: Increasing recognition of hypersensitivity reactions in children receiving biologic therapies 8

When to Test for Food Allergy:

• Children <5 years with moderate-to-severe atopic dermatitis AND persistent disease despite optimized topical therapy 1
• Reliable history of immediate reaction after specific food ingestion 1
• Test only for milk, egg, peanut, wheat, and soy in young children—broad panel testing without clinical correlation leads to false positives 1, 5

Critical Pitfall: Broad allergy panel testing without clinical history has poor positive predictive value and leads to unnecessary dietary restrictions 5

Treatment Algorithms

Acute Management of Anaphylaxis

1. Recognize anaphylaxis using clinical criteria (see above) 1
2. Administer IM epinephrine immediately to anterolateral thigh 1, 2
3. Position patient appropriately (supine with legs elevated) 1
4. Call emergency services 1
5. May repeat epinephrine every 5-15 minutes if no improvement 1
6. Transport to emergency facility for observation (minimum 4-6 hours) even if symptoms resolve 1

Secondary Treatments (AFTER epinephrine):

• H1-antihistamines for urticaria/pruritus 1
• Albuterol for persistent bronchospasm 1, 3
• IV fluids for hypotension 1
• Corticosteroids may reduce biphasic reactions but should never delay epinephrine 1, 9

Management of Non-Anaphylactic Cutaneous Reactions

Mild to Moderate Hypersensitivity Rashes:

1. First-line: Mild-to-moderate potency topical corticosteroids applied as thin film once or twice daily for 3-7 days 10

   • Hydrocortisone 1% for mild reactions 10
   • Low-to-medium potency for moderate reactions 10
   • Avoid high/ultra-high potency in infants and young children due to HPA axis suppression risk 10

2. Sensitive areas (face, genitals): Tacrolimus 0.03% ointment or pimecrolimus 1% cream 10

3. Adjunctive therapy:

   • Regular emollients (steroid-sparing effect) 10
   • Sedating antihistamines for severe pruritus (short-term only) 10
   • Non-sedating antihistamines have minimal benefit 10

4. Complications requiring specific treatment:

   • Secondary bacterial infection (usually S. aureus): flucloxacillin or erythromycin if penicillin-allergic 10
   • Eczema herpeticum: oral acyclovir (IV if febrile/ill) 10

Drug Allergy Management Algorithm

For Suspected Drug Hypersensitivity:

1. Document reaction details: timing, symptoms, severity, treatments received 1, 6

2. Classify reaction type:

   • Immediate (<2 hours): likely IgE-mediated 1
   • Delayed (>6 hours): likely T-cell mediated 1
   • Severe cutaneous reactions: permanent contraindication 1

3. For immediate reactions to beta-lactams:

   • Refer to allergist for skin testing 1, 7
   • If testing negative: can use beta-lactams 1
   • If testing positive: use alternative antibiotics (see below) 11

4. For NSAID hypersensitivity:

   • Challenge with COX-2 inhibitor (most frequently tolerated) 1
   • If specific NSAID allergy suspected: challenge with different structural group 1
   • Note: NSAID hypersensitivity patterns in children may not fit adult mechanistic understanding 1

Safe Alternatives for Penicillin-Allergic Patients:

• Cephalosporins with dissimilar side chains (cefazolin, ceftriaxone, cefepime, cefuroxime) have only 1-2% cross-reactivity and can be used regardless of reaction severity 11
• Azithromycin and macrolides have no structural relationship to penicillins—completely safe 11
• Trimethoprim-sulfamethoxazole for appropriate infections (UTIs, some skin infections) 11

Desensitization Protocols

When to Consider Desensitization:

• Patient requires specific drug with no suitable alternatives 1, 8
• Previous immediate hypersensitivity reaction documented 1
• NOT appropriate for severe cutaneous reactions (SJS/TEN, DRESS, AGEP) 1

Pediatric Considerations:

• Desensitization protocols adapted from adult experience are safe and effective in children 8, 12
• Requires multidisciplinary team (allergist, pediatrician, pharmacist, specialist) 8
• Successfully performed for chemotherapeutics, biologics, and other essential medications 8, 12
• Seventeen successful MTX desensitizations reported in pediatric patients 12

Critical Point: Desensitization induces temporary tolerance only—continuous therapy required to maintain tolerance 1

Long-Term Management and Prevention

Patient and Family Education

Essential Education Components:

1. Allergen avoidance strategies:

   • Reading food labels and ingredient lists 1
   • Inquiring about ingredients in restaurants 1
   • Understanding cross-reactive foods (e.g., various shellfish) 1
   • Creating allergen-free environment at meals 1

2. Epinephrine autoinjector training:

   • Must be available at ALL times 1, 5
   • Demonstrate proper technique to patient and caregivers 1, 5
   • Check expiration dates regularly 5
   • Compliance most difficult in adolescents and young adults 1

3. Recognition of anaphylaxis symptoms:

   • Early signs: oral pruritus, nausea often initial complaints 1
   • Progression to respiratory or cardiovascular involvement 1
   • Even small amounts of allergen can precipitate anaphylaxis 1

4. School and daycare management:

   • Provide written anaphylaxis emergency action plan 1, 5
   • Identify specific allergens to school personnel 1
   • Ensure epinephrine availability at school (covered by Americans with Disabilities Act) 1
   • Construct allergen-free environment at mealtime 1

Follow-Up and Monitoring

Ongoing Evaluation:

• Report all reactions to physician promptly while details are fresh 1
• Annual follow-up for retesting—some food allergies resolve over time 5
• Reassess for development of asthma in children with allergic rhinitis or atopic dermatitis 1
• Consider allergen immunotherapy when appropriate (e.g., stinging insect venom) 1

Monitoring for Comorbidities:

• Children with food allergy are 2-4 times more likely to have asthma, atopic dermatitis, and respiratory allergies 1
• Evaluate for asthma symptoms (difficulty breathing, cough, wheezing, exercise limitation) at each visit 1
• Perform spirometry when asthma suspected 1

Prevention Strategies

For At-Risk Infants (family history of atopy):

• Consider hydrolyzed infant formulas instead of cow's milk formula for non-exclusively breastfed infants 1
• Insufficient evidence to recommend routine allergy testing before introducing highly allergenic foods 1
• No need to limit exposure to environmental allergens or cross-reactive foods 1

For Children with Atopic Dermatitis:

• Optimize topical therapy first 1
• Consider food allergy evaluation only if persistent despite treatment or reliable history of reaction 1
• Proactive twice-weekly topical corticosteroid application to previously affected areas may prevent flares 10

Key Clinical Pearls

• Epinephrine underutilization remains a major problem—administered in only a minority of pediatric anaphylaxis cases despite being life-saving 4

• History alone is unreliable—only 19.6-68% of suspected reactions confirmed on challenge 1, 6

• Positive allergy tests indicate sensitization, not clinical allergy—must correlate with symptoms before dietary restriction 1, 5

• Iodine is NOT an allergen—"iodine allergy" is a misnomer and not an indication for contrast media premedication 1

• Viral infections in children complicate drug allergy diagnosis—common trigger for rashes that may be misattributed to medications 7

• Incidence of suspected drug hypersensitivity in hospitalized children is approximately 1.1%, with antimicrobials as leading cause 6

• Twenty-four percent of suspected culprit drugs can be safely continued or readministered during hospitalization with close monitoring or desensitization 6