Risk factors and predictive score for phenytoin-induced cutaneous reactions

Neurol Sci. 2025 Dec 29;47(1):63. doi: 10.1007/s10072-025-08779-3.

Abstract

Background: Phenytoin continues to be widely used in a number of countries as an antiseizure medication despite the introduction of newer agents. However, cutaneous adverse drug reactions (CADRs) associated with phenytoin remain a significant clinical concern, with manifestations ranging from mild maculopapular rashes to severe, life-threatening dermatological conditions.

Objective: This study aimed to evaluate clinical risk factors and develop a clinical prediction score for phenytoin-induced CADRs in hospitalized patients.

Methods: A retrospective cohort study included 447 patients aged ≥ 15 years who received phenytoin for the first time and were followed for at least 12 weeks. Data on demographics, clinical characteristics, comorbidities, concomitant drugs, and CADR occurrence were collected. Logistic regression identified independent risk factors, and a clinical prediction score was developed and evaluated using the area under the receiver operating characteristic curve (AuROC).

Results: Forty-seven (10.5%) patients developed CADRs. Multivariable analysis identified malignancy (adjusted OR = 6.27), HIV infection (adjusted OR = 47.1), alcohol dependence (adjusted OR = 37.14), concomitant diazepam use (adjusted OR = 11.07), and concomitant carbapenem use (adjusted OR = 9.88) as independent risk factors. The prediction score exhibited good discrimination with an AuROC of 0.856 (95% CI: 0.790-0.922). Internal validation yielded a consistent AuROC of 0.896 (95% CI: 0.836-0.955).

Conclusion: This study developed a clinical prediction score for phenytoin-induced CADRs in hospitalized patients, demonstrating good predictive ability using readily available clinical factors. This tool may help clinicians identify high-risk individuals for closer monitoring. External validation through prospective studies is needed to confirm its clinical utility.

Keywords: Cutaneous adverse drug reactions (CADRs); Phenytoin; Predictive score; Risk factors; Stevens-Johnson syndrome (SJS); Toxic epidermal necrolysis (TEN).

MeSH terms

  • Adult
  • Aged
  • Anticonvulsants* / adverse effects
  • Cohort Studies
  • Drug Eruptions* / diagnosis
  • Drug Eruptions* / epidemiology
  • Drug Eruptions* / etiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phenytoin* / adverse effects
  • Retrospective Studies
  • Risk Factors
  • Young Adult

Substances

  • Phenytoin
  • Anticonvulsants