What is the approach to managing hypersensitivity reactions in dermatology?

Hypersensitivity Reactions in Dermatology: Approach to Management

The management of hypersensitivity reactions in dermatology requires prompt recognition, accurate classification of reaction type and severity, and implementation of appropriate treatment protocols tailored to the specific reaction pattern. 1

Classification of Hypersensitivity Reactions

Immediate Hypersensitivity Reactions (Type I)

• Occur within 1 hour of exposure
• Clinical manifestations:
  • Urticaria
  • Angioedema
  • Anaphylaxis
  • Flushing
• Mechanism: IgE-mediated mast cell and basophil degranulation

Delayed Hypersensitivity Reactions

• Occur >1 hour after exposure (often 24-72 hours)
• Clinical manifestations:
  • Maculopapular exanthems
  • Fixed drug eruptions
  • DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms)
  • SJS/TEN (Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis)
  • Exfoliative dermatitis
• Mechanisms: T-cell mediated (Type IV) or other immune mechanisms

Diagnostic Approach

Clinical Assessment

1. Detailed medication history:

   • All medications (prescription, OTC, supplements)
   • Timing of drug initiation relative to reaction onset
   • Previous exposure and reactions
   • Route of administration

2. Morphological evaluation:

   • Distribution pattern
   • Primary lesion type
   • Mucosal involvement
   • Systemic symptoms

3. Laboratory investigations:

   • Complete blood count with differential
   • Liver function tests
   • Renal function tests
   • Inflammatory markers (ESR, CRP)
   • Specific tests based on suspected syndrome:
     • Eosinophil count (DRESS)
     • Tryptase levels (anaphylaxis)

4. Skin biopsy:

   • Indicated for severe or atypical reactions
   • Histopathologic features may include:
     • Perivascular lymphocytic infiltrates with eosinophils
     • Epidermal changes (spongiosis, necrosis)
     • Vasculitis

5. Specialized testing:

   • Skin testing (patch, prick, intradermal) when appropriate
   • Lymphocyte transformation tests (research tool)
   • HLA typing for specific drug reactions (e.g., HLA-B*5701 for abacavir)

Management Protocol

1. Immediate Actions

• Discontinue the suspected causative agent immediately
• Document the reaction thoroughly in the electronic health record, including:
  • Specific symptoms and timeline
  • Causative agent (when identified)
  • Severity classification
  • Treatment provided 1

2. Treatment Based on Reaction Severity

Mild Reactions (localized cutaneous involvement)

• Oral antihistamines (cetirizine/loratadine 10mg daily or hydroxyzine 10-25mg QID)
• Topical moderate-potency corticosteroids (clobetasone butyrate 0.05% or hydrocortisone 1%) applied 1-2 times daily for 1-2 weeks
• Regular emollients and soap substitutes 2

Moderate Reactions (extensive cutaneous involvement without organ dysfunction)

• Oral antihistamines
• Systemic corticosteroids (prednisone 0.5-1mg/kg/day)
• Topical corticosteroids for symptomatic relief
• Consider gabapentin or pregabalin for severe pruritus 2

Severe Reactions (with mucosal involvement or organ dysfunction)

• Hospital admission
• Epinephrine 0.01mg/kg (1:1000 concentration) IM for anaphylaxis (maximum single dose 0.5mg)
• IV fluid resuscitation
• Systemic corticosteroids (prednisone 1-1.5mg/kg/day)
• Supportive care based on affected organ systems
• Consider IVIG for SJS/TEN 1

3. Corticosteroid Tapering Protocol

For moderate to severe reactions requiring systemic corticosteroids:

• Initial dose: 1-1.5mg/kg for at least one month
• Slow taper over 3 months to prevent rebound inflammation
• Add colchicine (1mg/day) during and after the taper
• Continue colchicine for at least 3 months after prednisone discontinuation 2

4. Long-term Management

Documentation and Prevention

• Clear documentation of the reaction in medical records
• Patient education about avoiding the culprit medication
• Medical alert identification
• Cross-reactivity assessment for related medications 1

Specialized Testing

• Consider referral for skin testing after reaction resolution
• Patch testing may be useful for confirming specific drug hypersensitivity
• HLA testing for specific drug reactions (e.g., HLA-B*5701 for abacavir) 1

Rechallenge and Desensitization

• Rechallenge is contraindicated for severe reactions (SJS/TEN, anaphylaxis)
• Desensitization protocols may be considered when:
  • The medication is essential
  • No suitable alternatives exist
  • The initial reaction was not life-threatening
  • Performed under specialist supervision with emergency facilities available 3

Special Considerations

1. Radiocontrast Media Reactions

• For patients with history of mild immediate reactions:

  • Premedication is not recommended
  • Switch contrast agent when the inciting agent is known 1

• For patients with history of severe immediate reactions:

  • Consider alternative imaging studies first
  • If contrast is necessary, use premedication AND switch contrast agent
  • Perform study in hospital setting with emergency response capabilities 1

• No premedication needed for:

  • Chemotoxic or physiologic reactions
  • Isolated shellfish or iodine allergy
  • Povidone-iodine sensitivity 1

2. HIV Medication Reactions

• HLA-B*5701 testing prior to abacavir initiation
• Nevirapine should be initiated only in:
  • Antiretroviral-naive men with CD4 <400 cells/ml
  • Antiretroviral-naive women with CD4 <250 cells/ml
• Avoid prophylactic use of corticosteroids or antihistamines for nevirapine reactions 1

3. SGLT2 Inhibitor Reactions

• Discontinue medication and consider alternative antidiabetic agents
• Treatment based on body surface area (BSA) affected:
  • <10%: Antihistamines and topical treatments
  • 10-30%: Add neuromodulators (gabapentin/pregabalin)

  • 30%: Consider immunomodulators and dermatology referral 2

Common Pitfalls and Caveats

1. Misdiagnosis of reaction type: Carefully distinguish between immediate and delayed hypersensitivity reactions, as management differs significantly.

2. Inappropriate premedication: Premedication is not universally beneficial and may delay appropriate management. For example, premedication is not recommended for mild radiocontrast media reactions or nevirapine reactions.

3. Inadequate documentation: Poor documentation leads to future re-exposure. Document specific agent, reaction characteristics, and severity.

4. Premature rechallenge: Rechallenge with medications causing severe reactions can be fatal, particularly with abacavir.

5. Overlooking cross-reactivity: Consider potential cross-reactivity between structurally similar medications.

6. Rapid corticosteroid tapering: Too-rapid tapering of systemic corticosteroids can lead to rebound inflammation; follow a slow taper protocol over 3 months for severe reactions.

7. Delayed recognition of anaphylaxis: Early administration of epinephrine is critical for anaphylaxis management; delay increases mortality risk.

8. Misattribution to "iodine allergy": Shellfish allergy and iodine sensitivity are not predictive of radiocontrast media reactions and should not dictate management.

By following this systematic approach to hypersensitivity reactions in dermatology, clinicians can effectively diagnose, treat, and prevent these potentially serious adverse events.