Clinical value of autoantibodies for lupus myelitis and its subtypes: A systematic review
Introduction
Lupus myelitis (LM) is one of rare but serious complications in systemic lupus erythematosus (SLE), which is characterized by acutely progressive course of paralysis, sensory deficit, and sphincter dysfunction [1], [2], [3]. The pathogenesis remains unknown, and the treatment options of this devastating condition vary across experts [1], [2]. One-third of LM cases develops during low activity of lupus, suggesting that its development may not necessarily be explained by lupus itself [3]. Anti-phospholipid antibodies may be a promising candidate of its etiology, through its thromboembolitic effects in microcirculation of the spine [1]. However, a systematic review of case reports published in English showed that the frequency of anti-phospholipid antibodies (aPL) in LM (38 of 70 cases, 54%) was comparable to the overall prevalence of aPL in the general lupus population, and that anticoagulation therapy had no impact on neurological outcomes in LM patients and even in aPL-positive subgroup [2]. The review also suggested that paralysis at presentation was less frequent in LM with aPL (21%) compared with those without aPL (50%). However, that analysis was performed based solely on the presence or absence of aPL, and did not individually examine lupus anticoagulant (LA), anti-cardiolipin antibody, or anti-cardiolipin β2-glycoprotein-I (anti-β2GPI) antibody. Also, that systematic review included lupus cases before the revision of the classification criteria of the American College of Rheumatology (ACR) for SLE in 1997, which included aPL as one of the criteria [4], [5].
In 2009, Birnbaum et al. classified LM into two subtypes based on a retrospective investigation of 22 cases: grey matter myelitis characterized by flaccidity and hyporeflexia; and white matter myelitis characterized by spasticity and hyperreflexia [1]. Patients with neurological signs of grey matter dysfunction were more likely to rapidly deteriorate to a clinical nadir and to experience irreversible paraplegia, whereas those with white matter dysfunction were more likely to meet the criteria for neuromyelitis optica (NMO) and to have LA (0% vs. 54.5%, p = 0.01). Although the authors speculated a possible role of LA in the pathogenesis of white matter myelitis, the results may have been biased due to the retrospective design and small sample size [6].
We herein conducted a systematic review of cases with LM to investigate the clinical value of patient characteristics and autoantibodies, particularly lupus-specific antibodies, for the development of LM and associations with the grey and white matter subtypes. Our review focused on cases with LM reported after 1997, when the revised version of the ACR criteria introduced aPL as one of the criteria [4], and included cases published in English and non-English languages.
Section snippets
Data sources and search
Two of the authors (H.O. and A.K.) independently searched for case reports and case series of LM on PubMed and EMBASE, without language restrictions. We additionally searched ICHUSHI (“Igaku CHUo zasSHI,” meaning “Medical Central Journals”), that is the largest Japanese database of scientific literature and abstracts of scientific meetings, mainly written in Japanese, because we unintentionally found cases with LM in the database. Search words included “systemic lupus erythematosus,” “lupus,”
Results
Our search identified 224 LM cases (Fig) from 105 articles [1], [3], [6], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78],
Discussion
This systematic review provided several important findings regarding the clinical value of autoantibodies in LM. The diagnosis of SLE often preceded the onset of myelitis, by a median of 2 years, whereas simultaneous onset of both occurred in a significant proportion (31%) of the evaluable cases. Initial neurological signs comprising white matter dysfunction, rather than laboratory or imaging tests, predicted favorable functional outcome. Grey matter myelitis was also associated with LETM and
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H. Oiwa and A. Kuriyama contributed equally to this study.