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

Abstract

Objective: To determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) disease in a multiethnic/multiracial, prospective inception cohort of systemic lupus erythematosus (SLE) patients.

Methods: Patients were evaluated annually for 19 neuropsychiatric (NP) events including 7 types of PNS disease. SLE disease activity, organ damage, autoantibodies, and patient and physician assessment of outcome were measured. Time to event and linear regressions were used as appropriate.

Results: Of 1,827 SLE patients, 88.8% were female, and 48.8% were white. 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 (7.6%) of 1,827 patients. The predominant events were peripheral neuropathy (66 of 161 [41.0%]), mononeuropathy (44 of 161 [27.3%]), and cranial neuropathy (39 of 161 [24.2%]), and the majority were attributed to SLE. Multivariate Cox regressions suggested longer time to resolution in patients with a history of neuropathy, older age at SLE diagnosis, higher SLE Disease Activity Index 2000 scores, and for peripheral neuropathy versus other neuropathies. Neuropathy was associated with significantly lower Short Form 36 (SF-36) physical and mental component summary scores versus no NP events. According to physician assessment, the majority of neuropathies resolved or improved over time, which was associated with improvements in SF-36 summary scores for peripheral neuropathy and mononeuropathy.

Conclusion: PNS disease is an important component of total NPSLE and has a significant negative impact on health-related quality of life. The outcome is favorable for most patients, but our findings indicate that several factors are associated with longer time to resolution.

Figure 1:

The estimated cumulative incidence of all peripheral nervous system (PNS) disease and that attributed to SLE using attribution model B.

Figure 2:

Physician determined change in peripheral neuropathy, mononeuropathy or cranial neuropathy (n=149) attributed to SLE and non-SLE using attribution model B. Top panel: Survival curves for resolution of all neuropathies (left) and individual neuropathies (right). Lower panel: Likert scale scores for physician assessment of outcome over the duration of followup are shifted to the right indicated improvement and this is most pronounced for cranial neuropathies (right).

Figure 3:

Association of SF-36 summary and subscale scores with neuropathy (peripheral neuropathy, mononeuropathy, cranial neuropathy) attributed to SLE and non-SLE using attribution model B for the following 3 patient groups: (i) neuropathy events which occurred at or prior to the study assessment; (ii) any NP event other than neuropathy event occurring at or prior to the study assessment;(iii) patients who never had any NP event up to the study assessment. Upper two panels: SF-36 physical component summary (PCS) and mental component summary (MCS) scores with neuropathy over time. Bottom panel: comparison of individual subscale scores in the 3 patient groups. The SF-36 subscales are VT = Vitality, SF = Social function, RE = Role emotion, MH = Mental health, PF = Physical function, RP = Role physical, BP = Bodily pain, GH= General health.

Figure 4:

The change in SF-36 physical component summary (PCS) and mental component summary (MCS) scores following resolution of neuropathy (peripheral neuropathy, mononeuropathy, cranial neuropathy) attributed to SLE and non-SLE using attribution model B for the following patient groups: (i) peripheral neuropathy events (n=235) which occurred at or prior to the study assessment up to its resolution; (ii) resolved peripheral neuropathy (n=130) up to their last follow-up or recurrence of peripheral neuropathy; (iii) mononeuropathy events (n=135) which occurred at or prior to the study assessment up to its resolution; (iv) resolved mononeuropathy (n=120) up to their last follow-up or recurrence of mononeuropathy; (v) cranial neuropathy events (n=89) which occurred at or prior to the study assessment up to its resolution; (vi) resolved cranial neuropathy events (n=130) up to their last follow-up or recurrence of cranial neuropathy; (vii) any NP event (n=2718) other than peripheral neuropathy, mononeuropathy or cranial neuropathy events occurring at or prior to the study assessment; (viii) resolved any NP event (n=2307)other than peripheral neuropathy, mononeuropathy or cranial neuropathy up to their last follow-up or recurrence; (ix) patients who never had any NP event (n=6064) up to the study assessment.