Clinical value of autoantibodies for lupus myelitis and its subtypes: A systematic review

https://doi.org/10.1016/j.semarthrit.2018.02.004Get rights and content

Abstract

Objective

We conducted a systematic review to investigate the clinical value of clinical characteristics and autoantibodies, especially lupus-specific antibodies, for lupus myelitis and its subtypes.

Methods

We searched PubMed, EMBASE, and ICHUSHI without language restrictions for case reports or series of lupus myelitis. We focused on cases reported since 1997, when the revised classification criteria for systemic lupus erythematosus were published. Associations between patient characteristics including autoantibodies and functional outcome, survival, subtypes of myelitis (grey and white matter myelitis), and treatment were examined. We attempted to contact authors to supplement missing information for analysis.

Results

Our search identified 224 cases from 105 articles. White matter myelitis predicted favorable function (odds ratio = 15.18; 99% confidence interval, 3.09–151.31; p < 0.0001). Grey matter myelitis was associated with longitudinally extensive transverse myelitis (p < 0.001) and anti-double-stranded DNA (p = 0.003), and tended to be associated with anti-β2-glycoprotein I (p = 0.011). White matter myelitis tended to be associated with optic neuritis and anti-neuromyelitis optica antibodies. Although our study might be susceptible to under-reporting of original cases and selection bias, we aimed to provide a conservative interpretation by setting the statistical significance threshold at p < 0.01.

Conclusions

This systematic review confirmed that grey matter myelitis predicted poor functional outcome and was associated with longitudinally extensive transverse myelitis and anti-double-stranded DNA antibodies. White matter myelitis was associated with favorable functional outcomes and may partially represent a complication of neuromyelitis optica.

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

References (117)

  • N.M. Orzechowski et al.

    Longitudinal myelitis

    Mayo Clin Proc

    (2008)
  • M.L. Velloso+Feijoo et al.

    Transverse myelitis in systemic lupus erythematosus

    Reumatol Clin

    (2007)
  • E. Bathelier et al.

    Lupus profundus and myelopathy

    Ann Dermatol Venereol

    (2006)
  • H.C. Chen et al.

    Longitudinal myelitis as an initial manifestation of systemic lupus erythematosus

    Am J Med Sci

    (2004)
  • O. Moranne et al.

    Longitudinal myelitis in a pregnant patient with SLE

    Am J Med

    (2004)
  • F.M. Rodríguez Núñez et al.

    Clinical course and response to therapy in a case of transverse myelitis and SLE

    Rev Clin Esp

    (2002)
  • T. Zenone et al.

    Myelopathy revealing lupus. Two cases and review of the literature

    Rev Med Interne

    (2000)
  • D.V. Inslicht et al.

    Three women with lupus transverse myelitis: case reports and differential diagnosis

    Arch Phys Med Rehabil

    (1998)
  • J. Birnbaum et al.

    Distinct subtypes of myelitis in systemic lupus erythematosus

    Arthritis Rheum

    (2009)
  • C.G. Katsiari et al.

    Acute transverse myelitis and antiphospholipid antibodies in lupus. No evidence for anticoagulation

    Eur J Neurol

    (2011)
  • X.Y. Li et al.

    Myelitis in systemic lupus erythematosus frequently manifests as longitudinal and sometimes occurs at low disease activity

    Lupus

    (2014)
  • M.C. Hochberg

    Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus

    Arthritis Rheum

    (1997)
  • E.M. Tan et al.

    The 1982 revised criteria for the classification of systemic lupus erythematosus

    Arthritis Rheum

    (1982)
  • H. Oiwa et al.

    A report of three cases with lupus myelitis

    Eur J Rheumatol

    (2017)
  • M.J. Sweeting et al.

    What to add to nothing? Use and avoidance of continuity corrections in meta-analysis of sparse data

    Stat Med

    (2004)
  • F. Conti et al.

    Acute longitudinal myelitis following Cryptococcus laurentii pneumonia in a patient with systemic lupus erythematosus

    Lupus

    (2015)
  • L. Hamming et al.

    Myelopathy in systemic lupus erythematosus: a case report and a review of the literature

    Neth J Med

    (2015)
  • A. Loster-Niewinska et al.

    Acute transverse myelitis as the first clinical manifestation of systemic lupus erythematosus

    Neurology India

    (2014)
  • D. Modjinou et al.

    A case of systemic lupus erythematosus associated with longitudinal extensive transverse myelitis, cerebral neutrophilic vasculitis, and cerebritis

    Bull Hosp Jt Dis (2013)

    (2014)
  • Y.J. Dai et al.

    Myelopathy associated with systemic lupus erythematosus: a clinical analysis of 10 cases and review of literature

    Zhonghua Nei Ke Za Zhi

    (2013)
  • D.C. Gude et al.

    Transverse myelitis in antiphospholipid antibody negative systemic lupus erythematosus

    J Indian Med Assoc

    (2013)
  • L.K. Huang et al.

    Systemic lupus erythematosus presented as extensive longitudinal myelitis

    Acta Neurol Taiwan

    (2013)
  • D.X. Jiang et al.

    Successful treatment for neuromyelitis optica with systemic lupus erythematosus

    Chin Med J (Engl)

    (2013)
  • R. Yachoui et al.

    Intractable vomiting as an initial presentation of lupus-related neuromyelitis optica

    J Clin Rheumatol

    (2013)
  • J. Závada et al.

    Seroprevalence and specificity of NMO-IgG (anti-aquaporin 4 antibodies) in patients with neuropsychiatric systemic lupus erythematosus

    Rheumatol Int

    (2013)
  • Y. Katsumata et al.

    Semiquantitative measurement of aquaporin-4 antibodies as a possible surrogate marker of neuromyelitis optica spectrum disorders with systemic autoimmune diseases

    Mod Rheumatol

    (2012)
  • C. White et al.

    Longitudinally extensive transverse myelitis: a catastrophic presentation of a flare-up of systemic lupus erythematosus

    CMAJ

    (2012)
  • L.F. Tan et al.

    Clinical analysis of 6 cases of systemic lupus erythematosus complicated by transverse myelitis

    J South Med Univ

    (2011)
  • Y. Ye et al.

    Rituximab in the treatment of severe lupus myelopathy

    Clin Rheumatol

    (2011)
  • J. Katchanov et al.

    Longitudinal brainstem involvement in systemic lupus erythematosus

    Lupus

    (2010)
  • H.L. Pellkofer et al.

    Thirty-one episodes of myelitis and optic neuritis in a woman with neuromyelitis optica and systemic lupus erythematosus

    Arch Neurol

    (2010)
  • P. Zotos et al.

    Lupus related longitudinal myelitis

    J Rheumatol

    (2010)
  • H. Almoallim et al.

    Transverse myelitis as a presenting feature of late onset systemic lupus erythematosus

    Ann Saudi Med

    (2009)
  • W. Ammouri et al.

    Myelitis complicating systemic lupus erythematosus: successfully treated with corticosteroids and cyclophosphamide

    South Med J

    (2009)
  • P. Mottaghi et al.

    Devic's syndrome concomitant with nephritis in a young woman

    Clin Rheumatol

    (2009)
  • M. Mula et al.

    SLE-related longitudinal myelitis with favorable outcome

    Can J Neurol Sci

    (2009)
  • J.M. Gómez-Argüelles et al.

    Mielitis transversa aguda en siete pacientes con lupus eritematoso sistémico

    Rev Neurol

    (2008)
  • X. Lu et al.

    Prognostic factors of lupus myelopathy

    Lupus

    (2008)
  • L.R. Mehta et al.

    Neuromyelitis optica spectrum disorder in a patient with systemic lupus erythematosus and antiphospholipid antibody syndrome

    Mult Scler

    (2008)
  • C.C. Mok et al.

    Immunoablative cyclophosphamide for refractory lupus-related neuromyelitis optica

    J Rheumatol

    (2008)
  • Cited by (0)

    1

    H. Oiwa and A. Kuriyama contributed equally to this study.

    View full text