From the Division of Neuroimmunology and Neurological Infections (J.D.K., A.G.F., P.B., C.A.P., E.S.S.), Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD; Multiple Sclerosis and Neuroimmunology Center (P.B.), Department of Neurology and Neurosurgery, Cedars-Sinai Medical Center, University of California, Los Angeles; and Division of Rheumatology (A.C.G.), Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Neurol Neuroimmunol Neuroinflamm. 2025 Jan;12(1):e200329. doi: 10.1212/NXI.0000000000200329. Epub 2024 Oct 23.
Previous reports of patients with myelitis associated with rheumatologic disease may have had unrecognized aquaporin-4 (AQP4)-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease (MOGAD). We clinicoradiologically and serologically characterized patients with myelitis associated with rheumatologic disease evaluated in the era of availability of MOG-IgG and more sensitive AQP4-IgG cell-based assays.
A retrospective cohort (2018-2023) at Johns Hopkins Medicine with diagnoses of myelopathy and rheumatologic comorbidity was identified by electronic medical record (EMR) query. All patients with myelitis unrelated to typical multiple sclerosis (MS) were included and analyzed by chart review.
Of 238 patients identified by EMR query, 197 were excluded (148 not meeting prespecified inclusion criteria, 49 had typical MS), resulting in 41 patients for review. The mean age at myelitis onset was 44 ± 15 years; 39 (95%) were female. Rheumatologic diagnoses included 17 (41.5%) with systemic lupus erythematosus (SLE), 10 (24.3%) Sjögren syndrome (SS), 6 (15%) undifferentiated connective tissue disease (UCTD), 5 (12%) combinations of SLE/SS/UCTD with antiphospholipid antibody syndrome, 1 (2.4%) rheumatoid arthritis, 1 (2.4%) psoriatic arthritis, and 1 (2.4%) Behçet disease. 20 patients (49%) were diagnosed with AQP4-IgG seropositive NMOSD, 3 (7%) with MOGAD, and 18 (44%) had "double-seronegative" myelitis. Of these 18, 3 were diagnosed with AQP4-IgG seronegative NMOSD, 1 neuro-Behçet disease, and 14 other (unclassifiable) myelitis. Excluding 1 patient with neuro-Behçet disease, 18 (90%) of 20 AQP4-IgG seropositive patients had longitudinally extensive cord lesions compared with 5 (29%; < 0.001) of 17 "double-seronegative" patients and 2 (67%) of 3 with MOGAD. "Double-seronegative" patients more commonly had CSF-restricted oligoclonal bands. Functional outcomes did not differ by diagnosis, and most patients received acute immunotherapy at the time of initial myelitis diagnosis with at least partial recovery over a median follow-up of 38 (interquartile range: 9-74) months.
Approximately half of our rheumatologic disease cohort with myelitis unrelated to MS had AQP4-IgG seropositive NMOSD while MOGAD accounted for a small but clinically relevant proportion of patients. Further research is needed to characterize myelitis etiology in patients who are seronegative for both AQP4-IgG and MOG-IgG.
既往报道的与风湿性疾病相关的脊髓炎患者可能存在未被识别的水通道蛋白 4（AQP4）-IgG 阳性视神经脊髓炎谱系疾病（NMOSD）或髓鞘少突胶质细胞糖蛋白（MOG）-IgG 相关疾病（MOGAD）。我们通过临床放射学和血清学特征对风湿性疾病相关脊髓炎患者进行了评估，这些患者是在 MOG-IgG 可及和更敏感的 AQP4-IgG 细胞检测时代进行评估的。
我们通过电子病历（EMR）查询，确定了约翰霍普金斯医学中心（Johns Hopkins Medicine）的回顾性队列（2018-2023 年），其中包括了脊髓病和合并风湿性疾病的诊断。所有与典型多发性硬化症（MS）无关的脊髓炎患者均通过图表审查进行分析。
通过 EMR 查询，共确定了 238 例患者，其中 148 例不符合预设纳入标准，49 例患有典型 MS，排除了 197 例患者，最终有 41 例患者进行了回顾。脊髓炎发病时的平均年龄为 44±15 岁；39 例（95%）为女性。风湿性疾病诊断包括 17 例系统性红斑狼疮（SLE）、10 例干燥综合征（SS）、6 例未分化结缔组织病（UCTD）、5 例 SLE/SS/UCTD 合并抗磷脂抗体综合征、1 例类风湿关节炎、1 例银屑病关节炎和 1 例贝赫切特病。20 例（49%）患者被诊断为 AQP4-IgG 阳性 NMOSD，3 例（7%）为 MOGAD，18 例（44%）为“双阴性”脊髓炎。在这 18 例中，3 例被诊断为 AQP4-IgG 阴性 NMOSD、1 例神经贝赫切特病和 14 例其他（未分类）脊髓炎。排除 1 例神经贝赫切特病患者后，20 例 AQP4-IgG 阳性患者中有 18 例（90%）存在纵向广泛的脊髓病变，而 17 例“双阴性”患者中仅有 5 例（29%；<0.001）和 3 例 MOGAD 患者中仅有 2 例（67%）存在这种情况。“双阴性”患者更常见脑脊液寡克隆带受限。功能结局与诊断无关，大多数患者在初次脊髓炎诊断时接受了急性免疫治疗，在中位数为 38（四分位距：9-74）个月的随访中至少有部分恢复。
我们风湿性疾病相关脊髓炎队列中约有一半患者与 MS 无关的脊髓炎患者存在 AQP4-IgG 阳性 NMOSD，而 MOGAD 则占一小部分，但具有重要的临床意义。需要进一步研究以明确血清学 AQP4-IgG 和 MOG-IgG 均阴性的患者的脊髓炎病因。
