Background:Systemic lupus erythematosus (SLE) can affect almost any organ system. Nevertheless, Lupus nephritis and neuropsychiatric manifestations (NPSLE) are associated with increased mortality (1). Therapeutic options include glucocorticoids, often pulse methylprednisolone (MP), and other immunosuppressive therapies. In refractory cases, therapeutic plasma exchange, rituximab, or intravenous immunoglobulins are often used (2). However, an optimal therapeutic strategy has not been established because NPSLE is an exclusion criterion in most clinical trials. In addition, NPSLE can present with a broad spectrum of manifestations ranging from cognitive dysfunction to severe and life-threatening disease with choreoathetosis or transverse myelitis (TM). In primary Sjögren’s syndrome (pSS), neurological manifestations most often include peripheral neuropathies, but TM has also been reported.Objectives:To analyze the clinical presentation and outcomes after treatment in severe, life-threatening NPSLE.Methods:We retrospectively analyzed clinical, laboratory, and imaging features in severe NPSLE manifestations in SLE and pSS patients at two tertiary academic centers (University Medical Center Göttingen, Germany, and ASST Spedali Civili Brescia, Italy) with a high volume of SLE patients. Severe NPSLE was defined as either severe movement disorder or extensive tetra- or paraplegia secondary to (longitudinally extensive) transverse myelitis.Results:Our retrospective chart review resulted in seven patients fulfilling the inclusion criteria (six with SLE and 1 with pSS). Of these, five were females (71.4%). Median age was 26 (16-55) years. Three were of Asian origin, four were of European descent. Median disease duration was 15 (2-228) months. Three patients presented with severe choreoathetosis, all had positive ANA, anti-dsDNA antibodies (abs), and complement consumption. Of note, all three had at least one positive antiphospholipid antibody (APLA). All patients received IV MP 1g x 3 and mycophenolate mofetil and achieved complete remission. Of the four patients with longitudinally extensive TM, all were ANA positive, only two had anti-dsDNA abs. None of them had APLA, and only one tested positive for anti-aquaporine-4 abs. Of all patients, only one had positive ribosomal P-abs. Patients with TM received IV MP 1g x 5 and either RTX (4 cycles with 375 mg/m2 or IVIg 0.4 g/kg/d x 5). All four TM patients improved; two improved markedly, two only moderately with residual deficits as assessed by EDMUS-grading scale and functional independence measure.Conclusion:Severe NPSLE, defined as choreoathetosis or TM require intensive treatment. While the former patients achieved complete remission, two of four patients with TM only achieved partial remission. Our data support the use of early and aggressive immunosuppressive therapy. Nevertheless, therapy for TM in the context remains insufficient and should be assessed in a controlled clinical trial setting.References:[1]Monahan RC, et al. Mortality in patients with systemic lupus erythematosus and neuropsychiatric involvement: A retrospective analysis from a tertiary referral center in the Netherlands. Lupus. 2020 Dec;29(14):1892–901.[2]Papachristos DA, et al. Management of inflammatory neurologic and psychiatric manifestations of systemic lupus erythematosus: A systematic review. Semin Arthritis Rheum. 2020 Dec 17;51(1):49–71.Disclosure of Interests:PETER KORSTEN Consultant of: PK has received honoraria by Abbvie, Bristol-Myers-Squibb, Chugai, Gilead, Glaxo Smith Kline, Janssen-Cilag, Pfizer, and Sanofi-Aventis, all unrelated to this study., Grant/research support from: PK has received research grants from GSK, unrelated to this study., Marlene Plüß: None declared, Stefanie Glaubitz: None declared, Ala Jambus: None declared, Radovan Vasko: None declared, Bettina Meike Göricke: None declared, Silvia Piantoni: None declared
Aquaporin-4 IgG antibody-related disorders in patients with juvenile systemic lupus erythematosus
