New-onset of rheumatic diseases following COVID-19 vaccination: the report of three cases and a literature review.

Vaccines against coronavirus disease 2019 (COVID-19) have been distributed in most countries for the prevention of onset and aggravation of COVID-19. Recently, there have been increasing numbers of reports on new-onset autoimmune and autoinflammatory diseases following COVID-19 vaccination, however, only little information is available on the long-term safety of these vaccines. Here, we experienced three cases of new-onset rheumatic diseases following COVID-19 vaccination, one case each of rheumatoid arthritis (RA), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE). The symptom onset ranged from one day to a few days following vaccination. The patients of AAV and SLE were treated successfully with glucocorticoid therapy, and the patient of RA died due to COVID-19. In the literature review of new-onset rheumatic diseases following COVID-19 vaccination, which including seven cases of RA, 37 cases of AAV and 18 cases of SLE, the mean time from vaccination to onset was approximately 11 to 12 days. Most cases improved with glucocorticoid, immunosuppressive drugs and biologic agents. Although such adverse effects are rare, and vaccines are useful in prevent onset and severity of infections, continued accumulation of similar cases is important in terms of examining the long-term safety and understanding pathogenic mechanism of rheumatic diseases.

Successful Treatment of Diffuse Large B-cell Lymphoma Involving Multiple Renal and Bone Infiltrations Presenting with Giant Cell Arteritis-like Manifestations: A Case Report.

We herein report a case of diffuse large B-cell lymphoma (DLBCL) involving multiple renal and bone infiltrations presenting with giant cell arteritis-like (GCA)-like manifestations. One month prior, the present patient had left-sided temporal headache, jaw claudication, and renal failure. The patient was diagnosed with DLBCL based on a renal biopsy. After rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) plus intrathecal methotrexate/cytarabine/prednisone and rituximab, high-dose methotrexate, and cytarabine (R-MA) chemotherapy, the patient's clinical manifestations improved, and complete remission was achieved. DLBCL rarely but occasionally presents with GCA-like manifestations or multiple renal and bone infiltrations, highlighting the need for prompt and aggressive combination chemotherapy.

New-onset Immune-mediated Necrotizing Myopathy and Trigeminal Neuropathy after SARS-CoV-2 mRNA Vaccination in a Patient with Rheumatoid Arthritis and Sjögren's Syndrome.

We present the case of a 42-year-old woman with rheumatoid arthritis and Sjögren's syndrome treated with adalimumab who developed immune-mediated necrotizing myopathy (IMNM) and trigeminal neuropathy after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. Trigeminal neuralgia and elevated serum creatine kinase levels emerged 12 days post-vaccination, followed by myalgia in the femoral muscles. IMNM was histologically diagnosed. The pathogenesis may involve molecular mimicry between the SARS-CoV-2 spike glycoprotein and autologous tissues triggered by vaccination. This case emphasizes the association between SARS-CoV-2 vaccination, tumor necrosis factor inhibitor, IMNM, and trigeminal neuropathy, as well as the importance of monitoring immune-mediated adverse events following SARS-CoV-2 vaccination in patients with autoimmune disease.

Encapsulating Peritoneal Sclerosis in Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Systemic Sclerosis.

We encountered a 57-year-old Japanese woman with encapsulating peritoneal sclerosis (EPS) in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis. The patient was admitted to our hospital because of ascites retention. Administration of tocilizumab, an anti-interleukin-6 receptor antibody, for her RA reduced the refractory ascites remarkably; however, she developed sudden acute gastrointestinal bleeding and died a year later. On autopsy, sclerotic thickening of the peritoneum showed diffuse infiltration of podoplanin-positive fibroblast-like cells, and a diagnosis of EPS was made. EPS rarely occurs in SLE, and tocilizumab may be a new treatment candidate for EPS.

New-onset Adult-onset Still's Disease Following COVID-19 Vaccination: Three Case Reports and a Literature Review.

Since December 2020, coronavirus disease 2019 (COVID-19) vaccines have been distributed in most countries to prevent the onset and aggravation of COVID-19. There is little information regarding the long-term safety of the vaccines. We report three cases and a literature review of new-onset adult-onset Still's disease (AOSD) that occurred following COVID-19 vaccination. Our cases include moderate to severe AOSD, and two were complicated with macrophage activation syndrome. Seventeen cases of new-onset or relapse of AOSD following COVID-19 vaccination, including 14 identified in the literature review and our 3 patients, were all treated successfully with glucocorticoid therapy, immunosuppressive drugs, or biologic agents.

Detection of synovial inflammation in rheumatic diseases using superb microvascular imaging: Comparison with conventional power Doppler imaging.

AIM: Superb microvascular imaging (SMI), a novel ultrasonography, is based on the sensitivity of Doppler technology. This study evaluated power Doppler (PD) ultrasound signals in patients with rheumatic disease using SMI and conventional PD imaging (cPDI) and compared the correlations of these signals to clinical assessments. METHODS: Thirty-nine patients with rheumatic disease (27 rheumatoid arthritis [RA] and 12 non-RA) were enrolled. We investigated SMI and cPDI signals in 26 joints using an Aplio 300. Individual scores were summed to calculate total SMI and cPDI scores. RESULTS: Total SMI scores were significantly higher than total cPDI scores in patients with RA, but not in those with the non-RA disease. Total SMI score was associated with serum levels of C-reactive protein (CRP) and matrix metalloproteinase-3; disease activity score 28-CRP and health assessment questionnaire disability index scores, and SMI were more sensitive to detect active synovitis than cPDI in RA patients. Among the joint regions, the wrists and metacarpophalangeal joints were more sensitive to the detection of synovial inflammation using SMI in patients with RA. CONCLUSION: SMI was more sensitive in detecting synovial inflammation than cPDI in patients with RA. SMI could be a potentially useful imaging modality for accurately diagnosing and monitoring the disease activity of RA.

Histone Methylation and STAT-3 Differentially Regulate Interleukin-6-Induced Matrix Metalloproteinase Gene Activation in Rheumatoid Arthritis Synovial Fibroblasts.

OBJECTIVE: Synovial fibroblasts (SFs) produce matrix-degrading enzymes that cause joint destruction in rheumatoid arthritis (RA). Epigenetic mechanisms play a pivotal role in autoimmune diseases. This study was undertaken to elucidate the epigenetic mechanism that regulates the transcription of matrix metalloproteinases (MMPs) in RASFs. METHODS: MMP gene expression and histone methylation profiles in the MMP promoters were examined in RASFs. The effect of WD repeat domain 5 (WDR5) silencing on histone methylation and MMP gene expression in RASFs was analyzed. MMP gene expression, surface expression of the interleukin-6 (IL-6) receptor, phosphorylation of STAT-3, and binding of STAT-3 in the MMP promoters were investigated in RASFs stimulated with IL-6. RESULTS: The MMP-1, MMP-3, MMP-9, and MMP-13 genes were actively transcribed in RASFs. Correspondingly, the level of histone H3 trimethylated at lysine 4 (H3K4me3) was elevated, whereas that of H3K27me3 was suppressed in the MMP promoters in RASFs. The decrease in H3K4me3 via WDR5 small interfering RNA reduced the levels of messenger RNA for MMP-1, MMP-3, MMP-9, and MMP-13 in RASFs. Interestingly, IL-6 signaling significantly increased the expression of MMP-1, MMP-3, and MMP-13, but not MMP-9, in RASFs. Although the IL-6 signaling pathway was similarly active in RASFs and osteoarthritis SFs, STAT-3 bound to the MMP-1, MMP-3, and MMP-13 promoters, but not the MMP-9 promoter, after IL-6 stimulation in RASFs. CONCLUSION: Our findings indicate that histone methylation and STAT-3 regulate spontaneous and IL-6-induced MMP gene activation in RASFs. The combination of chromatin structure and transcription factors may regulate distinct arthritogenic properties of RASFs.