Peripheral Neuropathies in Systemic Lupus Erythematosus: Clinical Features, Disease Associations, and Immunologic Characteristics Evaluated Over a Twenty‐Five–Year Study Period

Abstract

Objective. To characterize peripheral neuropathy subtypes, ancillary studies, and immunologic profiles associated with peripheral neuropathies in patients with systemic lupus erythematosus (SLE).Methods. In this 25-year study of 2,097 SLE patients, we characterized peripheral neuropathies due to SLE and compared clinical and SLE-related features in patients with versus those without neuropathy.Results. The prevalence of peripheral neuropathies was 5.9% (123 of 2,097 patients), and 66.7% of these patients (82 of 123) had peripheral neuropathies attributable to SLE. We noted that 17.1% of the patients with peripheral neuropathies due to SLE (14 of 82 patients) had small-fiber neuropathy, which is a painful neuropathy not included in the American College of Rheumatology (ACR) neuropsychiatric SLE (NPSLE) case definitions. SLE patients with small-fiber neuropathies could present with unorthodox neuropathic pain patterns not consistent with a stocking-glove distribution and had associated skin biopsy results suggestive of dorsal root ganglion neuronal cell loss. Compared to SLE patients without peripheral neuropathies, those with peripheral neuropathies had lower mean disease activity (P ‫؍‬ 0.01) and higher disease damage (P < 0.01) and were more likely to have a history of herpes zoster virus infection (P < 0.01), osteoporotic fractures (P < 0.01), and opportunistic infections (P < 0.01).Conclusion. Our findings indicate that smallfiber neuropathy is a frequently occurring peripheral neuropathy. The skin biopsy findings in small-fiber neuropathy patients support the notion that distinct mechanisms target the dorsal root ganglia as well as distal axons. SLE patients with peripheral neuropathy have lower mean disease activity scores and higher disease damage. Our findings suggest that revision of the ACR NPSLE case definitions, which currently do not include small-fiber neuropathies, is warranted.Peripheral neuropathies cause severe pain, weakness, and psychosocial morbidity (1). In the past decade, many studies of central nervous system (CNS) manifestations associated with systemic lupus erythematosus (SLE) have been conducted (2-5). Such studies have provided valuable insight into the spectrum of CNS manifestations and the association of distinct CNS syndromes with autoantibodies, immunologic markers, and aspects of SLE activity (5-7). In contrast, there have been a limited number of studies of the association of peripheral neuropathies with autoantibody patterns and aspects of SLE activity (8). However, such studies have, importantly, begun to emphasize that peripheral neuropathies in SLE may occur with equal or greater frequency compared to some CNS syndromes (2-5,8), and therefore constitute an important although poorly understood cause of morbidity.The 1999 American College of Rheumatology (ACR) case definitions for neuropsychiatric SLE (NPSLE) were an important advance in providing standardized definitions for both CNS and peripheral ner-

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