ObjectivePatients with systemic lupus erythematosus (SLE) are susceptible to herpes simplex virus (HSV) infection, which occasionally leads to severe complications including meningoencephalitis and keratitis. However, few attempts to analyse the associated incidence and risk factors have been made.MethodsWe enrolled patients with SLE recorded between 1997 and 2012 and compared the incidence rate (IR) of severe HSV infection, including meningoencephalitis, septicaemia, ocular and visceral involvement, and other specific complications demanding hospitalisation, with that of a non-SLE cohort. A Cox multivariate proportional hazards model was applied to analyse the risk factors of severe HSV infection in patients with SLE.ResultsA total of 122 520 subjects (24 504 patients with SLE and 98 016 age-matched and sex-matched non-SLE controls) were included, and a higher IR of severe HSV infection was revealed in the SLE group (IR ratio=3.93, p<0.001). In patients with SLE, previous oral and genital infection (HR=2.29, p=0.049), intravenous steroid pulse therapy (HR=5.32, p<0.001) and daily oral dose of over 7.5 mg of prednisolone (HR=1.59, p=0.024) were independent risk factors for severe HSV infection, whereas age of ≤18 (HR=0.45, p=0.029) was a protective factor.ConclusionsPatients with SLE are at higher risk of severe HSV infection, and related risk factors include being older than 18 years, having a history of HSV mucocutaneous infection, recent receipt of steroid pulse therapy and a daily oral dose of steroid over 7.5 mg prednisolone.