Real-world efficacy of belimumab in achieving remission or low-disease activity in systemic lupus erythematosus: A retrospective study.

OBJECTIVES: We investigated the effect of belimumab (BEL) on achieving low disease activity (LDA) and remission as an additive molecular-targeting agent to standard of care (SoC) in patients with SLE. METHODS: Clinical information was retrospectively collected from patients with SLE who received BEL additive to SoC (BEL+SoC), and from patients treated with SoC alone as a control arm. Disease activity was measured by SLE-disease activity score (SLE-DAS). The proportion of patients in LDA and remission at 12 months was compared after propensity score matching. The factors contributing to LDA and remission achievement was identified by Cox proportional hazard model. RESULTS: BEL+SoC significantly reduced SLE-DAS at 6 months, with a significantly higher proportion of patients achieving LDA and remission at 12 months compared to SoC alone. The presence of arthritis at baseline was significantly associated with achieving LDA and remission. Additionally, both treatment groups experienced a significant reduction in daily glucocorticoid dose. CONCLUSIONS: Adding BEL to SoC was beneficial for patients with arthritis, leading to higher proportion of achieving LDA and remission, while also reducing their glucocorticoid dose. Our results indicate the utility of BEL in a treat-to-target approach for SLE patients in a real-world setting.

The pathogenic role of lupus-specific autoantibodies and Interleukin-6 on demyelination of the brainstem and spinal cord in systemic lupus erythematosus.

OBJECTIVES: Demyelinating syndromes that result in brainstem and/or spinal cord lesions similar to those observed in neuromyelitis optica spectrum disorder (NMOSD) as neuropsychiatric syndromes in systemic lupus erythematosus (NPSLE) occasionally develop in patients with SLE. Cerebrospinal fluid (CSF) interleukin (IL)-6 is a known biomarker for NMOSD; however, its application in patients with SLE with brainstem and/or spinal cord lesions is unknown. Additionally, the breakdown of blood-brain barrier (BBB) integrity by autoantibodies is another mechanism of NMOSD; however, it is not elucidated in SLE. Therefore, this study was designed to clarify the use of CSF IL-6 and investigate whether autoantibodies contribute to BBB breaches and the development of brainstem and/or spinal cord lesions. METHODS: Data from patients with NPSLE who had NMOSD-like demyelinating lesions in the central nervous system (CNS), including brainstem and/or spinal cord lesions, were retrospectively analyzed. We retrospectively investigated the interval changes in CSF IL-6 and clinical and serological factors related to BBB permeability using CSF/serum albumin ratio (QAlb). RESULTS: Twelve patients with NPSLE who had demyelinating lesions in the brainstem and/or spinal cord were recruited. Before treatment, CSF IL-6 levels were 29.1 pg/mL and significantly decreased to 3.8 pg/mL by treatment (p = 0.008). Before treatment, CSF IL-6 was significantly correlated with the anti-dsDNA antibody titer (p = 0.027). Furthermore, before treatment, QAlb was significantly correlated with the serum anti-Smith antibody titer. In patients with atypical NMOSD who had specific lesions defined in the NMOSD diagnostic criteria but were negative for antiaquaporin four antibody, a significant correlation was observed between the serum anti-Smith antibody titer and CSF IL-6 (p = 0.025) and QAlb (p = 0.033) values before treatment. CONCLUSION: CSF IL-6 could be a surrogating marker for disease activity, and serum anti-Smith antibody permeabilizes the BBB in patients with NPSLE, supporting the development of NMOSD-like CNS lesions.

A case of rheumatoid arthritis with bilateral shoulder bursitis accompanied by gas image.

We experienced a case of bilateral shoulder bursitis with gas images in a rheumatoid arthritis (RA) patient. A 60-year-old man with RA had been treated with weekly methotrexate 10 mg and daily prednisolone (PSL) 10 mg for 7 months. Generalized pain, especially in the bilateral shoulder joints, developed and exacerbated daily with increased C-reactive protein (CRP) level. Despite the initiation of biweekly sarilumab 200 mg, joint symptoms and CRP level continued to worsen. Computed tomography (CT) scan to determine the cause of severe shoulder inflammation revealed low absorption areas with contrast effects at the margins around the bilateral shoulder joints, accompanied by internal gas images. In addition, magnetic resonance imaging demonstrated subacromial bursae and coracoid bursae and bursitis, leading to the suspicion of abscess formation depending on the presence of gas image. In spite of antimicrobial therapy, arthralgia did not improve, and a CT-guided arthrocentesis of the left shoulder joint resulted in negative findings of infection in culture and pathological examinations. Switching treatment to intensive anti-inflammatory therapy with high-dose steroids and etanercept finally improved symptoms and CRP levels associated with the reduction of low absorption areas and disappearance of gas images at bilateral shoulder joints. Our case indicated that bursitis with gas image in RA patients involves unusual pathophysiology and requires intensive anti-rheumatic treatment.

A patient with Castleman's disease initially manifesting symmetrical synovitis with pitting oedema.

Castleman's disease (CD), especially multicentric CD (MCD) has been known to manifest a variety of clinical features such as fatigue, anaemia, fever, and hypergammaglobulinaemia. Here, we report a 72-year-old female patient who had complicated severe synovitis, as an initial manifestation of the disease, lastly diagnosed as MCD. Initially, she had been diagnosed as remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome because of bilateral leg pitting oedema with significant C-reactive protein and matrix metalloproteinase-3 elevation but no disease-specific autoantibodies. Promptly, corticosteroid and additionally weekly methotrexate were introduced, but her leg oedema and inflammatory findings did not adequately come to be a remission. A lymph node biopsy from the groin region was performed because multiple lymph node swelling in ultrasound examination appeared even after introducing treatments, which revealed mixed-type CD. Multiple lymphadenopathies were observed in the axilla and inguinal region; finally, we diagnosed her as idiopathic MCD and introduced tocilizumab, which significantly improved leg oedema as well as inflammatory findings. As is shown in this case, manifestations included in RS3PE syndrome could be one of the clinical phenotypes in MCD, which should be considered as a differential diagnosis of MCD.

Anti-ribosomal P protein antibodies in patients with systemic lupus erythematosus is associated with hyperferritinemia.

AIM: Anti-ribosomal P protein antibodies (anti-ribo P) have been reported as one of the specific autoantibodies in patients with systemic lupus erythematosus (SLE) and has been demonstrated to bind and activate macrophages in vitro. Clinically, hyperferritinemia has been known to be a biomarker for macrophage activation. The aim of this study is to clarify the relationship of anti-ribo P and clinical characteristics and biomarkers including serum ferritin in patients with SLE. METHODS: Clinical parameters and laboratory data were measured in patients with active SLE (N = 127) in our university hospital. The risk factors affected by anti-ribo P were retrospectively calculated by logistic regression analysis, and the correlation of anti-ribo P and clinical factors was demonstrated. RESULTS: Anti-ribo P was significantly elevated in active SLE compared to non-SLE diseases (P < .0001). Sensitivity and the specificity of anti-ribo P in patients with SLE were 32.0% and 99.3%, respectively. Patients positive for anti-ribo P had the highest risk for elevated serum ferritin (odds ratio: 8.432). Accordingly, anti-ribo P positive patients had significantly elevated serum ferritin compared to negative patients (P = .024). A significant positive correlation was observed between the anti-ribo P titer and the serum ferritin level (r2  = .07, t = 5.22, P = .0081), but not serum interleukin (IL)-6 in SLE patients. CONCLUSION: The presence of anti-ribo P is a risk factor for higher ferritin levels that is independent of systemic inflammation regulated by IL-6. We speculate that anti-ribo P could be directly associated with macrophage activation leading to hyperferritinemia in patients with SLE.

A case of anti-MDA5 antibody-positive dermatomyositis developing reversible cerebral vasospasm syndrome successfully treated by multi-immunosuppressant combination including mycophenolate mofetil.

A 39-year-old woman admitted with multiple joint pain, hand rashes, and shortness of breath was diagnosed with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) with interstitial pneumonia (IP). Because of progressive dyspnoea and hypoxaemia, her IP was considered rapidly progressive interstitial lung disease. Initially, prednisolone 60 mg/day, cyclosporine A (CyA), and intravenous cyclophosphamide (IVCY) were initiated. A few days following the initiation of treatment, she experienced massive thunderclap headache, which was diagnosed as reversible cerebral vasospasm syndrome based on the findings of contraction in cerebral arteries with brain magnetic resonance imaging. Treatment with CyA and IVCY was discontinued, and diltiazem and mycophenolate mofetil (MMF) were initiated as an alternative immunosuppressant. Considering IVCY as the cause of Reversible cerebral vasospasm syndrome based on her clinical course, tacrolimus was commenced, which improved both DM and IP. DM patients who are anti-MDA5 antibody-positive are considered to have poor prognosis and require aggressive immunosuppressive treatments. In patients experiencing adverse events with standard IVCY, MMF with high-dose steroids and alternative calcineurin inhibitor should be considered.