Background/Purpose: To study the prevalence of Herpes Zoster (HZ) reactivation in patients with biopsy confirmed lupus nephritis (LN) undergoing immunosuppressive therapies.

Methods: Patients who had biopsy confirmed active LN (2003-2018) were retrospectively reviewed for the occurrence of HZ infection.  The following data were collected: age, 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 baseline and 6 months post-therapy that included lupus serology, albumin, globulin, IgG/A/M levels, white cell counts, histological classes of LN and renal response.  The incidence of HZ reactivation at 2 years of LN treatment and on 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).  Histological LN classes were: III/IV±V(69%), I/II/V/VI(31%).  Induction regimens were: moderate/high dose prednisolone in combination with cyclophosphamide (17%), azathioprine (11%), mycophenolate mofetil (MMF) (42%), tacrolimus (25%).  Renal response at 6m was: complete response (CR) (59%), partial response (PR) (27%) and non-response (NR) (15%). Within 2 years of therapies, 55(18%) episodes of LN were complicated by HZ infection (incidence: 8.84/100 patient-year).  The median time for HZ reactivation since LN therapy was 11 months.  28 patients had HZ infection beyond 2 years (overall prevalence: 3.24/100 patient-years).  The distribution of HZ lesions was: head and neck (15%), lower limbs (27%), trunk (55%) and upper limbs (4%).  75% of the episodes were treated by oral acyclovir.  Secondary bacterial infection or significant neuralgia occurred in 18% of the episodes.  Disseminated disease or mortality was not reported.  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).  A trend of higher SLEDAI, higher anti-dsDNA, lower C3/albumin  but more refractory disease was observed in HZ-infected patients.  Histological LN classes, 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) at induction.  Higher doses of other immunosuppressive drugs had also been used in patients with HZ reactivation but the difference was not statistically significant.  Logistic regression revealed first-time LN (OR 2.25[1.08-4.71]; p=0.003), peak MMF 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 at 2 years.

Conclusion: HZ reactivation is fairly common in LN patients undergoing immunosuppressive therapies but unpredictable from clinical parameters.  Minimization of immunosuppression and HZ vaccination may help reduce the risk of HZ infection.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/prevalence-and-risk-factors-of-herpes-zoster-reactivation-in-patients-with-biopsy-proven-lupus-nephritis-undergoing-immunosuppressive-therapies/