Risk factors of Herpes zoster infection in patients with Lupus nephritis: a retrospective single-center study

In recent years, epidemiological data have shown an increase in the number of patients with herpes zoster (HZ) worldwide(peak age of onset: 70-80s). Patients with Systemic lupus erythematosus (SLE) are reported to have a higher risk of HZ infection compared to the general population. Moreover, within the SLE population, those with kidney involvement are at a particularly higher risk of HZ. This study aimed to identify risk factors for HZ in patients with lupus nephritis (LN). 

We conducted a retrospective analysis of patients who underwent kidney biopsy and were diagnosed with LN at Kanazawa University Hospital, Japan, between 2001 and 2024. We compared clinical features, histological activity of LN, and glucocorticoid (GC) and immunosuppressive drug regimens between patients who developed HZ (HZ patients) and those who did not (non-HZ patients). Pathologic lesions were evaluated based on the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification. We also examined factors associated with HZ development using survival analysis. 

108 patients with a median age of 35（interquartile range [IQR] 24-48） were included in this study. Based on the ISN/RPS classification, 37 patients (34%) had class III, 38 (35%) had class IV, and 18 (17%) had class III or IV+V. During the median observation period of 87 months (IQR 49-115), 17patients (15%) developed HZ. Two cases were severe, requiring hospitalization due to complications, including generalized rash or central nervous system infection. The median age at HZ onset was 34 years (IQR 31-45). The median time from initiation of SLE treatment to HZ onset was 44 months (IQR 4-161). Among patients with HZ infection, 4/17 (24%) patients developed HZ within 6 months of starting LN treatment. At the time of HZ onset, the median dose of prednisolone (PSL) was 10 (IQR 10-17.5) mg/day, and 15/17 patients (88%) were taking immunosuppressants, including cyclophosphamide, mycophenolate mofetil (MMF), and calcineurin inhibitors. The proportion of proliferative LN (class III/IV±V) patients was higher in HZ patients (88%) compared with non-HZ patients (66%), although not reaching significance (p=0.067). MMF was more frequently used in HZ patients (35%) compared with non-HZ patients (10%) (p=0.005). Kaplan-Meier survival analysis also showed significantly higher HZ incidence in patients with MMF administration (log-rank p<0.001). In multivariate Cox regression analysis adjusted for age and sex, MMF use was associated with a higher incidence of HZ infection (hazard ratio 16.9, 95% confidence interval 4.06-70.02, p<0.001). No significant difference between HZ patients and non-HZ patients was observed in age, gender, mPSL pulse therapy use of antimalarials, or other immunosuppressants, including cyclophosphamide and calcineurin inhibitors.

Patients with LN experienced HZ infection at a younger age compared to the general population. A high proportion of HZ patients had proliferative LN, and MMF use was associated with a higher risk of HZ infection among LN patients. Current guidelines of LN include MMF as one of the standard therapies. This study highlights the importance of close monitoring of HZ episodes and consideration for vaccination to prevent HZ infection in LN patients.