What is the management approach for Lamotrigine (lamotrigine)-induced DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms)?

Management of Lamotrigine-Induced DRESS Syndrome

The immediate discontinuation of lamotrigine is the first and most crucial step in managing lamotrigine-induced DRESS syndrome, followed by prompt dermatology consultation and initiation of systemic corticosteroids. 1, 2

Initial Management

• Immediately discontinue lamotrigine as the suspected causative drug 1, 2
• Obtain prompt dermatology consultation for all suspected cases 1
• Perform a complete workup including:
  • Total body skin examination
  • Complete blood count with differential to assess for eosinophilia
  • Liver and kidney function tests
  • Urinalysis
  • Blood cultures
  • Skin biopsy if diagnosis is uncertain 1, 3

Treatment Protocol

• For severe DRESS syndrome:

  • Admit to a burn unit or ICU with dermatology and wound care services consultation 1
  • Initiate IV methylprednisolone 1-2 mg/kg/day 1, 2
  • Provide supportive care:
    • Manage fluid and electrolyte balance
    • Minimize insensible water losses
    • Implement infection prevention measures
    • Provide topical treatment and oral antihistamines for symptomatic relief 1, 2

• For cases not responding to systemic steroids:

  • Consider intravenous immunoglobulin (IVIG) at a total dosage of 1-2 g/kg 1
  • Cyclosporine may also be considered in severe or steroid-unresponsive cases 1

Specialized Care Based on Organ Involvement

• Consult appropriate specialists based on organ involvement:

  • Hepatology for liver involvement (lamotrigine-induced DRESS can cause fulminant hepatic failure requiring liver transplantation in severe cases) 4
  • Nephrology for kidney involvement (acute interstitial nephritis with tubular necrosis has been reported) 5
  • Neurology for neurological manifestations (autoimmune limbic encephalitis has been reported) 6
  • Other specialists as needed based on specific organ involvement 1

• Monitor closely using serial clinical photography to track skin manifestations 1

Duration of Treatment

• Wean systemic corticosteroids slowly over at least 4 weeks 1, 2
• Prolonged immunosuppression may be necessary due to the T-cell immune-directed toxicity of DRESS syndrome 1, 2
• Monitor for potential relapse, which can occur in approximately 12% of cases, particularly with DRESS associated with viral reactivation 2

Special Considerations

• Unlike in Stevens-Johnson syndrome, corticosteroids are not contraindicated in DRESS syndrome 1
• Be aware of potential cross-reactivity between lamotrigine and other anticonvulsants, such as lacosamide 7
• DRESS typically occurs after a latent period of 2-6 weeks following exposure to lamotrigine, which distinguishes it from other drug reactions 2, 3
• Monitor for syndrome of inappropriate antidiuretic hormone secretion (SIADH), which has been reported in lamotrigine-induced DRESS 6

Prognosis and Follow-up

• DRESS syndrome has an estimated mortality rate of approximately 10%, highlighting the importance of prompt recognition and treatment 7
• Close follow-up is essential to monitor for resolution of symptoms and potential complications 1, 2
• Patients should be counseled to avoid lamotrigine in the future and to inform all healthcare providers about this severe drug reaction 2