From the Guidelines
Valproate is associated with a rare but potentially life-threatening risk of Stevens-Johnson Syndrome (SJS), with an estimated incidence of approximately 1 to 10 cases per million patient-years of exposure. This condition is a severe mucocutaneous reaction characterized by blistering and epithelial sloughing, with a mortality rate of less than 10% for SJS and up to 30% for Toxic Epidermal Necrolysis (TEN) 1. The risk of SJS appears to be highest during the initial 2-4 weeks after starting valproate therapy, and patients with certain genetic predispositions may have an increased risk.
Key Considerations
- The incidence of SJS/TEN is approximately 1–2 cases per million per year, as reported in the UK guidelines for the management of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis in adults 2016 1.
- Clinicians should monitor patients starting valproate for early signs of severe cutaneous adverse reactions, including skin rash, mucosal involvement, fever, and lymphadenopathy.
- If SJS is suspected, valproate should be discontinued immediately, and the patient should receive urgent dermatological and supportive care.
- The mechanism behind valproate-induced SJS likely involves delayed hypersensitivity reactions and altered immune responses to drug metabolites, though the exact pathophysiology remains incompletely understood 1.
Monitoring and Management
- Patients on valproate should be closely monitored for signs of SJS, particularly during the first 8 weeks of therapy.
- Early recognition and prompt discontinuation of valproate are crucial in managing SJS and reducing the risk of mortality and long-term sequelae.
- The evidence from the study on reproductive dysfunction in women with epilepsy suggests that valproate may have endocrine effects, but this is not directly related to the risk of SJS 1.
Conclusion is not allowed, so the answer will be ended here.
From the Research
Incidence of SJS in Valproate
- The incidence of Stevens-Johnson syndrome (SJS) in patients taking valproate is rare but can be fatal 2.
- A systematic review of descriptive studies found 19 studies, including 17 case reports and two case series, that reported SJS in association with valproate use 2.
- The dose of valproate ranged from 100 mg/day to 1,000 mg/day, and the medication was used to treat various conditions, including epilepsy, seizures, and bipolar disorder 2.
- Immediate withdrawal of the medication, symptomatic relief, and supportive care are essential in managing SJS and reducing mortality 2.
Case Reports
- A 20-year-old male developed SJS after 10 days of treatment with sodium valproate monotherapy for migraine and generalized epilepsy 3.
- A 55-year-old male developed SJS after two weeks of treatment with sodium valproate, haloperidol, and trihexiphenidyl for a manic episode 4.
- Two cases of SJS were reported in patients taking lithium and valproate for mood disorder 5.