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Risk of severe herpes simplex virus infection in systemic lupus erythematosus: analysis of epidemiology and risk factors analysis in Taiwan
  1. Tzu-Hao Li1,2,3,
  2. Chien-Chih Lai2,3,4,
  3. Wen-Hsiu Wang5,6,
  4. Wei-Sheng Chen4,
  5. Yen-Po Tsao4,
  6. Chang-Youh Tsai2,4,
  7. Yu-Sheng Chang7,8,9
  1. 1 Division of Allergy, Immunology, and Rheumatology, Department of Medicine, Chiayi Branch, Taichung Veterans General Hospital, Chiayi City, Taiwan
  2. 2 Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei City, Taiwan
  3. 3 Institute of Clinical Medicine, National Yang-Ming University, Taipei City, Taiwan
  4. 4 Divisionof Allergy, Immunology, and Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
  5. 5 Division of Allergy, Immunology and Rheumatology, Mackay Memorial Hospital, Taipei, Taiwan
  6. 6 Medicine, Mackay Medical College, Sanzhi, Taiwan
  7. 7 Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan
  8. 8 Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan
  9. 9 Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan
  1. Correspondence to Dr Yu-Sheng Chang, Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan; risea65{at}


Objective Patients 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.

Methods We 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.

Results A 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.

Conclusions Patients 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.

  • herpes simplex virus
  • keratitis
  • meningoencephalitis
  • systemic lupus erythematosus

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  • Handling editor Josef S Smolen

  • Contributors T-HL, C-CL and Y-SC conceived and planned the study. W-HW, W-SC, Y-PT and C-YT contributed to data acquisition and processing. T-HL, C-CL and Y-SC took the lead in writing the manuscript. All authors provided critical feedback and shaped the research, analysis and the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Information that potentially identified any individual was encrypted and properly reviewed by the Institutional Review Board of Taipei Veterans General Hospital, alongside approval from the National Health Research Institutes.

  • Provenance and peer review Not commissioned; externally peer reviewed.