Peripheral Nervous System Disease in Systemic Lupus Erythematosus: Results from an International, Inception Cohort Study

Abstract

Background/Purpose: Although there is a large body of work on central nervous system (CNS) disease in SLE patients, involvement of the peripheral nervous system (PNS) is less well established. The objective of our study was to determine the frequency, clinical characteristics, associations and outcomes in different types of PNS disease in a prospective, multi-ethnic/racial, inception cohort study of SLE patients.

Methods: Patients were evaluated annually for 19 neuropsychiatric (NP) events, including seven types of PNS disease using standardized case definitions. Attribution models were used to determine if the PNS events were due to SLE or other causes. SLE disease activity (SLEDAI-2K), organ damage (SLICC/ACR damage index), autoantibodies, patient (SF-36) and physician (Likert score) assessment of outcomes were measured. Statistical analyses included time to event and linear regressions as appropriate.

Results: Of 1,827 SLE patients enrolled, 88.8% were female and 48.8% Caucasian. The mean ± SD age was 35.1 ± 13.3 years, disease duration at enrollment was 5.6 ± 4.2 months and follow-up was 7.6 ± 4.6 years. There were 161 PNS events in 139/1,827 (7.6%) patients. The predominant events were peripheral neuropathy [66/161 (41.0%)], mononeuropathy [44/161 (27.3%)] and cranial neuropathy [39/161 (24.2%)] and the remaining 4 types of PNS disease accounted for only 12/161 (7.5%) events. The majority of PNS events [118/161 (73.3%)] in 104/139 (74.8%) patients were attributed to SLE. Multivariable Cox regression [HR, (95%CI)] indicated a negative association with Asian race/ethnicity [0.42 (0.19, 0.93)] and a positive association with other concurrent NP events attributed to SLE [2.74 (1.49, 5.03)]. By physician assessment, the majority of neuropathies resolved or improved over time. Multivariable analysis indicated that a longer time to resolution was associated with recurrent PNS events [0.38 (0.16, 0.90)], older age at SLE diagnosis [0.76 (0.60, 0.98)], higher SLEDAI-2K scores excluding NP variables [0.71 (0.51, 0.99)] and peripheral neuropathy [0.45 (0.25, 0.82)]. Patients with neuropathy reported significantly lower SF-36 physical and mental component summary scores compared to patients without NP events. Resolution was associated with improvements in SF-36 physical component summary scores that were both clinically and statistically (p< 0.01) significant in patients with peripheral neuropathy (mean change: +8.74) and mononeuropathy (mean change: +9.27).

Conclusion: PNS disease is a manifestation of NPSLE and has a significant negative impact on health related quality of life. The outcome is favourable for most patients, but several factors associated with longer time to resolution were identified.