C56 Cutaneous Drug Reactions

Introduction

Use of prescription drugs in the United States

Incidence of cutaneous reactions

Pathogenesis of drug reactions

Nonimmunologic drug reactions

Immunologic drug reactions

Genetic factors and cutaneous drug reactions

Global considerations

Clinical presentation of cutaneous drug reactions

Nonimmune cutaneous reactions

Exacerbation or induction of dermatologic diseases

Photosensitivity eruptions

Pigmentation changes

Warfarin necrosis of skin

Drug-induced hair disorders

Drug-induced nail disorders

Toxic erythema of chemotherapy and other chemotherapy reactions

Immune cutaneous reactions: common

Maculopapular eruptions

Pruritis

Urticaria/angioedema/anaphylaxis

Anaphylactoid reactions

Irritant/allergic contact dermatitis

Fixed drug eruptions

Immune cutaneous reactions: rare and severe

Drug-induced hypersensitivity syndrome

  • Etiology
    • Type 1 reaction: beta lactam drugs (m/c), neuromuscular blocking agents, quinolones, platinum-containing chemotherapeutic agents, and foreign proteins (eg, chimeric antibodies)
  • Pathophysiology
    1. Some patients can form drug-specific IgE on exposure to a medication, although most do not.
    2. Once formed, the drug-specific IgE occupies receptors on mast cells and basophils
    3. If the drug is encountered again, these cells may activate, resulting in symptoms.
  • Clinical features
    • Type 1 reaction: onset is rapid (seconds to minutes) and symptoms can range from mild (eg, urticaria, pruritus, flushing) to more severe (eg, angioedema of the larynx, anaphylaxis)
  • Management
    • Urticaria and pruritus without systemic symptoms are usually treated with antihistamines

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)

  • SJS: <10% of BSA / TEN: >30% of BSA
  • Clinical features
    • 4-28 days after exposure to trigger (2 days after repeat exposure)
    • Acute influenza-like prodrome
    • Rapid-onset erythematous macules, vesicles, bullae
    • Necrosis & sloughing of epidermis
    • Mucosal involvement
  • Common triggers
    • Drugs
      • Allopurinol, antibiotics (eg, sulfonamides), anticonvulsants (eg, carbamazepine, lamotrigine, phenytoin), NSAIDs (eg, piroxicam), sulfasalazine
    • Other
      • M.pneumoniae, vaccination, graft-vs-host disease
  • Treatment
    • Aggressive fluid support d/t poor oral intake and profound cutaneous fluid loss.
    • Secondary infections are common ? antiseptic precautions

Pustular eruptions (AGEP)

Overlap hypersensitivity syndrome

Vasculitis

Management of the patient with suspected drug eruption

Early diagnosis of severe eruptions

DIAGNOSISMUCOSALLESIONSTYPICAL SKIN LESIONSFREQUENT SIGNSAND SYMPTOMSMOST COMMONCULPRIT DRUGS
Stevens-Johnson syndrome(SJS)Erosionsusually attwo ormore sitesSmall blisters form from dusky maculesor atypical targets; rare areas ofconfluence; detachment ?10% bodysurface areaMost cases involve feverSulfonamides,anticonvulsants,allopurinol, nonsteroidalanti- inflammatory drugs(NSAIDs)
Toxic epidermal
necrolysis (TEN)
Erosionsusually attwo ormore sitesIndividual lesions like those seen in SJS;confluent dusky erythema; large sheetsof necrotic epidermis; total detachmentof >30% body surface areaNearly all cases involvefever, “acute skin failure,”leukopeniaSame as for SJS
Drug-induced hypersensitivity syndrome/drug rash witheosinophilia and systemicsymptoms (DIHS/DRESS)Mucositisreported inas many as30%Diwuse, deep red morbilliform eruptionwith facial involvement; facial and acralswellingFever, lymphadenopathy,hepatitis, nephritis,myocarditis, eosinophilia,atypical lymphocytosisAnticonvulsants,sulfonamides,allopurinol, minocycline
Acute generalizedexanthematous pustulosis(AGEP)Oralerosions inperhaps20%Innumerable pinpoint pustules overlyinga diwuse erythematous eruption; maydevelop superficial erosionsHigh fever, leukocytosis(neutrophilia),hypocalcemia?-Lactamantibiotics, calciumchannel blockers,macrolide antibiotics

Confirmation of drug reaction

What drug(s) to suspect and withdraw

Recommendation for future use of drugs

Cross-sensitivity

Role of testing for causality and drug rechallenge

Reporting

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