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Cutaneous Drug Reactions

Basics

  • Adverse skin reactions from drug administration; rashes most common ADR form
  • Severity: mild eruptions to severe skin and multiorgan damage
  • Morbilliform and urticarial eruptions account for ~94% of cases
  • Severe, life-threatening reactions ~2%

Epidemiology

  • Affects all ages; immunosuppressed and elderly at higher risk for severe forms
  • US incidence: 1-3% hospitalized patients; 1 in 1,000 have severe cutaneous reaction

Etiology & Pathophysiology

  • ADR classified as:
  • Predictable (Type A): dose-dependent, known pharmacologic effect or drug-drug interaction
  • Unpredictable (Type B): drug intolerance, idiosyncrasy, allergy, pseudoallergy
  • Immunologically mediated reactions include:
  • Type I (IgE-mediated hypersensitivity)
  • Type II (cytotoxic IgG/IgM)
  • Type III (immune complexes)
  • Type IV (delayed T-cell mediated)
  • Common causative drugs: carbamazepine, phenytoin; >700 drugs implicated
  • Genetic predisposition linked to specific HLA alleles (e.g., HLA-B*5801 with allopurinol SJS/TEN)

Prevention

  • Careful drug history including prior reactions
  • Awareness of high-risk medications and interactions

Diagnosis

History

  • Document drug timeline: start, dose, duration, onset of eruption

Physical Exam: Common eruption types

  • Morbilliform eruptions: most frequent (75-95%), symmetric pruritic macules/papules on trunk/extremities; spares face, palms, soles, mucosa; often antibiotics related
  • Urticaria: pruritic wheals anywhere including mucosa; angioedema may threaten airway
  • Acneiform eruptions: folliculocentric pustules, lack comedones; atypical sites like forearms, legs
  • Fixed drug eruptions: solitary/few well-demarcated plaques with dusky center; rapid onset (30 min–8 hr)
  • Acute generalized exanthematous pustulosis (AGEP): rapid sterile pustules, fever, leukocytosis; resolves 1-3 days after drug withdrawal
  • DRESS syndrome: pruritic papules, fever, eosinophilia, multiorgan involvement; onset 2-8 weeks after exposure; symptoms may worsen post-withdrawal
  • Erythema multiforme: target lesions, mucosal involvement in 25-60%; mostly viral (HSV)
  • Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN): extensive epidermal necrosis, mucosal erosions; SJS <10% BSA, TEN >30%; high mortality (TEN 25-35%)
  • Lichenoid eruptions: violaceous pruritic papules on extensor/sun-exposed skin; chronic after drug stopped
  • Photosensitivity: phototoxic and photoallergic patterns
  • Hypersensitivity vasculitis: palpable purpura on lower legs; biopsy shows vessel wall inflammation
  • Sweet syndrome: tender violaceous papules/plaques with fever and neutrophilia

Differential Diagnosis

  • Viral exanthem
  • Primary dermatoses (pustular psoriasis)
  • Bacterial infections

Diagnostic Tests

  • CBC with differential (eosinophilia in DRESS)
  • LFTs, urinalysis, creatinine for organ involvement
  • Chest x-ray if vasculitis suspected
  • Specific testing by reaction type (e.g., skin tests, Coombs, ANA, patch testing)
  • Histopathology in severe or atypical cases (e.g., SJS/TEN)

Treatment

  • Immediate cessation of offending drug
  • Symptomatic treatment usually sufficient for mild cases
  • Anaphylaxis/angioedema: IM epinephrine, corticosteroids (prednisone taper)
  • Urticaria: 2nd generation antihistamines; add H2 blockers if needed
  • Erythema multiforme: supportive; HSV prophylaxis if recurrent
  • SJS/TEN: supportive care; multidisciplinary consult; controversial use of corticosteroids; consider IVIG; avoid debridement, preserve epidermis as dressing
  • DRESS: systemic corticosteroids (prednisolone 1 mg/kg/day) with slow taper (6-12 weeks); topical steroids and antihistamines for rash
  • AGEP: topical steroids shorten hospitalization; systemic steroids generally not recommended

Admission Criteria

  • Extensive skin involvement (>60%), bullae, necrosis, mucosal erosions, positive Nikolsky sign
  • High fever, lymphadenopathy, systemic symptoms
  • Eosinophilia >1000/mm³ or organ dysfunction

Ongoing Care

  • Provide EpiPen for anaphylaxis patients
  • Medical alert identification and documentation of offending drug
  • Consider graded drug challenges or desensitization if needed

Prognosis

  • Most reactions self-limited upon drug withdrawal
  • Severe reactions (anaphylaxis, DRESS, SJS/TEN) can be fatal
  • SCORTEN score guides TEN severity and prognosis

ICD10: - L27.1 Local skin eruption due to drugs - L50.0 Allergic urticaria - R21 Rash and other nonspecific skin eruption

Clinical Pearls: - Any drug can cause cutaneous reactions; antibiotics, anticonvulsants, and NSAIDs are common culprits - Severe symptoms like mucosal erosions, angioedema, and skin necrosis require urgent care - Drug Eruption Reference Manual by Jerome Litt is a useful resource - Careful drug history and prompt withdrawal of offending agents are key to management