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The incidence and outcome of Herpes zoster (HZ) in systemic lupus erythematosus (SLE) are not completely defined as well as the relevance to HZ of disease and therapy factors.To determine HZ features in SLE.SLE patients (1997 update of the American College of Rheumatology classification criteria) with definitive HZ infection were identified from our Lupus Clinic computerized database of 1145 patients.HZ was diagnosed in 51 SLE patients (4.45%) with an annual incidence rate of 6.4 events/1000 patient-years. At HZ diagnosis, mean disease duration was 9.78 ± 8.37 years, median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was 1, and only 17.6% had SLEDAI ≥8. Frequency of manifestations and immunosuppressor use were similar between patients with and without HZ. Forty-two patients (82.5%) with HZ were under prednisone with concomitant immunosuppressive therapy in 66.7%. Thirty-five patients (68.6%) were using immunosuppressors: azathioprine (39.2%), cyclophosphamide (9.8%), and mycophenolate mofetil (9.8%). The mean lymphocyte count was 1219 ± 803/mm3 (43.1% <1000/mm3 and 17.6% <500/mm3). Only patients using azathioprine and cyclophosphamide had lymphocyte counts <500/mm3 (15% and 40%).All patients received acyclovir, 19.6% had postherpetic neuralgia, and recurrence occurred in only 7.8%. Thoracic nerves were the most involved site (56.8%) followed by lumbar (23.5%). Bacterial suprainfection occurred in 11.7% but was not associated with therapy, lymphocyte count, or SLEDAI scores (P > 0.05).This is the largest cohort to determine that HZ is a late SLE complication with some peculiar features, such as good prognosis and typical dermatomal distribution. In addition, we have identified that the major trigger factor for this viral infection in SLE is therapy, particularly the concomitant use of corticosteroid and immunosuppressors, and not active disease.