Increased Risk for Herpes Simplex Virus Infection Noted in Systemic Lupus Erythematosus

Herpes simplex viruses, computer artwork.
Risk factors included older age, history of mucocutaneous infection, and intravenous or oral steroid therapy.

According to study data published in Annals of Rheumatic Disease, patients with systemic lupus erythematosus (SLE) were at higher risk for severe herpes simplex virus (HSV) infection, with older age, history of HSV mucocutaneous infection, and intravenous or oral steroid therapy increasing likelihood of infection.   

Investigators conducted a nationwide cohort study with data abstracted from the National Health Insurance Research Database (NHIRD) in Taiwan. Patients who had received SLE illness certification between January 1997 and December 2012 were selected for inclusion. As the primary end point, investigators captured new incidence of severe HSV infection, described as infection at an uncommon site that could lead to significant morbidity or mortality. Non-severe HSV infection during follow-up was also recorded.

The non-SLE control group was selected from the 2000 Longitudinal Health Insurance Database, a cohort of randomly sampled individuals from the NHIRD’s Registry of Beneficiaries in 2000. Each patient with SLE was age- and sex-matched with 4 controls. Cox proportional hazard models were used to estimate the hazard ratios (HRs) for associations among patient characteristics and severe HSV infection.

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The final study cohort comprised 24,504 patients with SLE and 98,016 controls. Patients had a mean age of 36.3 years, and the majority (88.4%) were women. Severe HSV infection was observed in 0.5% of patients with SLE and 0.2% of controls, for a nearly 4-fold higher incidence rate in the SLE group (P <.001). The most common types of severe infection were meningoencephalitis and keratitis, which were present in 0.029% and 0.33% of patients with SLE, respectively, compared with 0.004% (P =.002) and 0.12% (P <.001) of controls.

Non-severe HSV infection was also more common among patients compared with controls (2.8% vs 2.2%; P <.001). Independent risk factors for severe HSV in patients with systemic lupus erythematosus included previous oral and genital infection (HR, 2.29; 95% CI, 1.01-5.23; P =.049), intravenous steroid pulse therapy (HR, 5.32; 95% CI, 3.42-8.29; P <.001), and daily oral dose >7.5 mg prednisolone (HR, 1.59; 95% CI, 1.06-2.36; P =.024). Conversely, age ≤18 years (HR, 0.45; 95% CI, 0.22-0.92; P =.029) was a protective factor.

These data highlight additional risk factors for severe HSV infection among patients with SLE. In particular, early treatment for HSV may help prevent complications in patients undergoing steroid therapy.


Li T-H, Lai C-C, Wang W-H, et al. Risk of severe herpes simplex virus infection in systemic lupus erythematosus: analysis of epidemiology and risk factors analysis in Taiwan [published online April 6, 2019]. Ann Rheum Dis. doi:10.1136/annrheumdis-2018-214844