Background: Herpes zoster (HZ) reactivation is fairly common in patients with systemic lupus erythematosus (SLE). However, there is a paucity of studies that reported the risk factors of HZ reactivation in well-defined subsets of SLE patients.

Objectives: To study the prevalence of HZ reactivation in patients with active biopsy confirmed lupus nephritis (LN) undergoing immunosuppressive therapies.

Methods: Patients who had biopsy proven active LN that was treated with immunosuppressive regimens in our unit between 2003 and 2018 were retrospectively reviewed for the occurrence of HZ reactivation within 2 years’ therapies. HZ was a clinical diagnosis based on history and physical signs by attending physicians. The following were collected: age and SLE duration at renal biopsy, sex, SLE disease activity scores, maximum daily dose and total duration of high-dose prednisolone and other immunosuppressive drugs in the induction period, maintenance therapies, laboratory parameters at renal biopsy and 6 months post-therapy that included lupus serology, albumin, globulin, immunoglobulin levels (IgG/A/M) and white cell counts (lymphocyte and neutrophil), histological classes of LN and clinical response at 6 month and 2 years. The incidence of HZ reactivation within 2 years of active LN treatment and the total prevalence of HZ infection over time until last follow-up was calculated. Risk factors for HZ reactivation were studied by logistic regression.

Results: 251 patients with 311 episodes of active LN were studied (92% women; age 34.2±14.2 years at first renal biopsy). The distribution of histological classes (WHO or ISN/RPS) was: class III/IV±V (69%), I/II/V/VI (31%). First-time renal disease occurred in 61% of patients. Induction treatment regimens were: prednisolone in combination with CYC (17%), azathioprine (11%), MMF (42%), tacrolimus (25%). Within 2 years of immunosuppressive therapies, 55 (18%) episodes of LN were complicated by HZ infection. The incidence of HZ reactivation was 8.84/100 patient-year. The median time for HZ reactivation since LN treatment was 11 months. 28 patients had HZ infection occurring longer than 2 years post-therapy, giving an overall prevalence of 3.24/100 patient-years. The distribution of HZ lesions was: head and neck region (15%), lower limbs (27%), trunk (55%) and upper limbs (4%). Fourteen episodes of HZ (25%) were treated by intravenous anti-viral drugs while others were treated at out-patient settings with oral acyclovir. Secondary bacterial infection occurred in 9% of the episodes. Disseminated disease or mortality was not reported in any patients. Significant post-herpetic neuralgia developed in 9% of the episodes. Patients with HZ reactivation were more likely to have first-time renal disease (76% vs 58%; p=0.02) and a shorter SLE duration at LN (31.4±50 vs 62.7±72 months; p=0.02) than those without HZ. A trend of higher SLEDAI score, higher anti-dsDNA titer, lower C3 and albumin level but higher rate of refractory renal disease was also observed in HZ-infected patients. Other clinical parameters such as histological classes of LN, neutrophil, lymphocyte counts and immunoglobulin levels at baseline and 6 months post-therapy were not significantly different between HZ-infected and control patients. HZ-infected patients had been treated with a significantly higher dose of prednisolone (0.72±0.40 vs 0.63±0.24 mg/kg/day) as induction therapy. Dosages of other immunosuppressive drugs were not associated with HZ reactivation. Logistic regression revealed first-time renal disease (OR 2.25[1.08-4.71]; p=0.003), peak MMF daily dose (OR 1.24[1.10-3.07]; p=0.02) and cumulative CYC dose (OR 1.14[1.01-1.28]; p=0.04) during induction therapy were significantly associated with HZ within 2 years.

Conclusion: HZ reactivation is fairly common in LN patients undergoing immunosuppressive therapies but unpredictable from histological and laboratory parameters. Higher doses of prednisolone, MMF and CYC were associated with a higher risk of HZ reactivation within 2 years.

Acknowledgments: NIL

Disclosure of Interests: None declared