Para médicos · reumatologia
Resumos de artigos, podcasts e newsletters sobre Fenômeno de Raynaud, para atualização médica.
A newsletter destaca que a hidroxicloroquina não previne a progressão para artrite reumatoide em pacientes anti-CCP positivos e que a plasmaférese deve ser reservada como terapia de resgate em miosites graves. Além disso, discute o benefício do AAS na redução de eventos isquêmicos na arterite de células gigantes, apesar do aumento do risco hemorrágico, e explora a relação entre tofacitinibe e microbiota na espondiloartrite.
A newsletter discute como o sequenciamento genômico pode revelar doenças raras monogênicas disfarçadas de condições comuns, explicando casos de refratariedade ao tratamento. Apresenta atualizações cruciais na Doença de Sjögren, destacando a estratificação por clusters de risco e a emergência de novas terapias como o dazodalibep. Além disso, alerta para a toxicidade renal por antimaláricos e o uso de proteômica urinária para monitorar a inflamação na nefrite lúpica.
This study aimed to identify interferon (IFN)-related key genes in patients with Sjögren's Disease (SjD) and to elucidate their specific associations with the heterogeneous clinical phenotypes and laboratory parameters of the disease. Bioinformatics analyses, including differentially expressed gene (DEG) screening, weighted gene co-expression network analysis (WGCNA), and machine learning, were conducted on dataset GSE84844 to identify IFN-related key genes. Based on the EULAR Sjögren's syndrome disease activity index (ESSDAI), SjD patients with low, moderate, and high disease activity were enrolled, with 20 in each subgroup. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed on peripheral blood mononuclear cells (PBMCs) from the 60 SjD patients and 15 healthy controls (HCs). Expression levels were compared between SjD patients and HCs, across disease activity subgroups, and correlated with clinical phenotypes and laboratory indicators. DEGs in SjD were significantly enriched in IFN-related signaling pathways. Five IFN-related hub genes were identified: CXCL10, DDX60L, IFIH1, JAK2, and NMI. qRT-PCR validation confirmed that all five genes were significantly upregulated in SjD patients compared to HCs (P < 0.05). However, their expression did not significantly differ among SjD subgroups with varying levels of overall disease activity (P > 0.05). Importantly, these genes were differentially expressed in distinct clinical manifestations. For instance, elevated CXCL10 expression was observed in patients with interstitial lung disease (ILD), leukopenia, and anemia; JAK2 expression differed in rheumatoid arthritis comorbidity; IFIH1 expression also showed differences in those with Raynaud's phenomenon and ILD. Furthermore, certain genes were highly expressed in specific laboratory abnormalities: elevated erythrocyte sedimentation rate with CXCL10 and JAK2; hyperglobulinemia with CXCL10, DDX60L, IFIH1, and JAK2; and elevated immunoglobulin G with CXCL10, DDX60L, and IFIH1 (all P < 0.05). This study identifies five IFN-related
To investigate the clinical and immunological features of primary Sjögren's disease (pSjD) patients with anti-centromere protein B (CENP-B) antibody positivity and to evaluate its prognostic significance. This ambispective cohort study included 1,222 patients with pSjD from the China-Japan Friendship Hospital between February 2014 and February 2023, with follow-up through February 2024. Patients were categorized into anti-CENP-B positive and negative groups based on serum testing. Clinical characteristics, immunological features, and outcomes were compared between groups. A subgroup analysis compared patients with isolated CENP-B positivity to those with additional autoantibodies. Statistical analyses were conducted using SPSS 26.0 and R 4.2.3, including descriptive statistics, univariate tests, and Kaplan-Meier survival analysis. In this study, 100 patients (8.2%) were positive for anti-CENP-B antibody, while 1,122 patients (91.8%) were negative. Compared with the negative group, positive patients were older, more often female, and have higher rates of xerostomia and Raynaud's phenomenon, but lower frequency of dyspnea. They showed lower platelet counts, higher aspartate aminotransferase, gamma glutamyl transferase, lactate dehydrogenase, total bilirubin, and lower estimated glomerular filtration rate, with reduced frequencies of elevated Immunoglobulin (Ig) G, but increased IgM levels and slightly lower EULAR Sjögren's Syndrome Disease Activity Index scores. Among anti-CENP-B positive patients, those with isolated anti-CENP-B positivity had milder immunologic abnormalities than those with concomitant autoantibodies. Among patients with available LSGB data, focal lymphocytic infiltration counts were higher in the anti-CENP-B-positive group. Anti-CENP-B positivity was not significantly associated with mortality, cancer, or interstitial lung disease. Anti-CENP-B positivity in pSjD may identify a different baseline serological and clinical profile, characterized by relatively milder immunologic abnormalities and lower disease activity. However, its prognostic and clinical significance remains uncertain and requires further validation.
Mixed connective tissue disease (MCTD) is characterized by positivity for anti-U1-RNP antibodies and a combination of symptoms of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and inflammatory myositis (IIM). The aim of this study was to elucidate the similarities and differences in gene expression profiles of peripheral blood immune cells between MCTD and its related diseases, as well as their association with clinical parameters. Transcriptome analysis was performed in peripheral blood immune cells from 19 MCTD patients, 58 SLE patients, 63 SSc patients, 64 IIM patients, and 79 healthy controls (HC), comprising a total of 283 individuals across 27 immune cell subsets. Differential gene expression and enrichment analyses were conducted to compare MCTD with related diseases and HC. The association between dysregulated pathways in MCTD and clinical parameters was assessed. Gene modular and machine learning analyses were employed to identify related gene signatures in other immune cells. MCTD exhibited a higher number of differentially expressed genes (DEGs) in Th1 cells compared to other related diseases and HC. Although the DEGs between MCTD and SLE were limited, Th1 cells in MCTD shared common DEGs with each disease, and enrichment analysis revealed upregulation of cell cycle pathways in MCTD Th1 cells. This gene signature showed upregulation in high disease activity and in anti-U1-RNP antibody positive patients in related diseases, and it was associated with severity of Raynaud's phenomenon. Furthermore, the Th1 cell cycle signature correlated with interferon signature in other immune cells. Transcriptome analysis of peripheral blood immune cells revealed that MCTD Th1 cells share many transcriptional features with those in SLE, yet display distinctive cell cycle signature. Particularly, upregulation of cell cycle pathways was associated with characteristic clinical features of MCTD,
To characterize the clinical and serological correlates of cardiovascular magnetic resonance (CMR)-confirmed myocarditis in idiopathic inflammatory myopathies (IIM), evaluate the diagnostic performance of high-sensitivity cardiac troponin I (hs-TnI), and quantify the independent prognostic impact of myocarditis relative to interstitial lung disease (ILD). Single-center retrospective cohort study (STROBE-compliant) of 142 consecutive adults with IIM (2019-2025). Myocarditis was confirmed by CMR according to the 2018 Lake Louise Criteria, performed both at diagnosis and during follow-up (with or without immunosuppression) upon clinical suspicion and/or elevated hs-TnI. Myositis-specific antibodies (MSA), myositis-associated antibodies (MAA), anti-Ro52 and antiphospholipid antibodies (aPL, Sydney criteria: ≥40 GPL/MPL units confirmed at ≥ 12 weeks) were systematically recorded. Associations were assessed with Fisher's exact test and logistic regression; multivariable models were pre-specified as parsimonious (two predictors) given the limited event count. Overall survival was analyzed with Kaplan-Meier curves, the log-rank test and Cox proportional-hazards regression. Myocarditis was confirmed in 9/142 patients (6.3%), without significant association with IIM class (P = 0.303) or with the antisynthetase antibody subgroup (anti-Jo-1 + PL-12 + PL-7 + EJ; 5.8% vs. 6.7%, P = 1.000). In univariable analyses, myocarditis was associated with Raynaud phenomenon (OR 13.6, 95% CI 2.3-80.0), aPL positivity (OR 10.7, 95% CI 2.6-43.9), anti-Ro52 coexisting with MSA/MAA (OR 8.7, 95% CI 2.2-34.8), anti-PM/Scl (OR 7.1, 95% CI 1.6-30.3), fever (OR 7.1, 95% CI 1.6-30.3) and ILD (OR 4.7, 95% CI 1.1-20.3). hs-TnI was markedly higher in myocarditis (median 366 vs. 3.5 ng/L; P < 0.001) with an area under the receiver-operating characteristic curve (AUROC) of 0.91 (95% CI 0.83-0.98). In the event-constrained multivariable model, Raynaud phenomenon (adjusted OR 13.1, 95% CI 1.5-112.7) and aPL (adjusted OR 7.2, 95% CI 1.4-36.0) remained independently associated. All-cause mortality was higher in myocarditis (44% vs. 9%; OR 7.95, 95% CI
Raynaud's phenomenon (RP) is the first noticeable symptom of systemic sclerosis (SSc), appearing even years before other signs. Vascular and immune pathways, hallmarks in SSc pathogenesis, are implicated in primary RP. Hence, we aimed to define the shared genetic architecture between these conditions to explore pathogenic mechanisms and whether pleiotropic loci could help identify primary RP patients at increased genetic risk of developing SSc. We analysed genome-wide association study (GWAS) summary statistics for primary RP (4 986 cases and 850 981 controls) and SSc (10 654 cases and 18 043 controls). We performed a cross-trait meta-analysis (∼8.6M single nucleotide polymorphisms) to identify variants associated with both diseases. Functional annotation was used to prioritise potential causal genes. We also constructed a polygenic risk score (PRS) to assess clinical implications. Beyond the well-known HLA associations, we identified five additional pleiotropic loci, including MEOX2 as a novel association for both traits with opposing effects, ADRA2A representing a novel genetic factor for SSc, and IL12A, NFKB1 and TNIP1 as novel loci for primary RP. Functional annotation highlighted vascular and inflammatory pathways. Finally, the PRS model shows modest discrimination (area under the curve = 0.57). However, it allows the identification of primary RP individuals at high genetic risk of developing SSc (75th percentile, relative risk =1.29 [95% CI 1.02, 1.62]; P-value= 3.58 × 10-2). This study reveals a genetic link between primary RP and SSc, identifying five novel pleiotropic loci and supporting the potential of genetic profiling for early risk assessment and personalised monitoring strategies.
Mixed connective tissue disease (MCTD) is a rare entity in children. There is a paucity of studies on juvenile-onset MCTD (jMCTD) worldwide especially from Southeast Asia. To describe clinical and laboratory features of jMCTD diagnosed at pediatric rheumatology centers across India. A predesigned detailed case proforma in an excel format was prepared and was sent to all the Pediatric Rheumatology centers in India. Eleven centers provided the clinical and laboratory data of their jMCTD patients, which was then compiled and analyzed in detail. Thirty-one jMCTD patients from 11 centers were included in the study. Our cohort had 27 females and four male patients over 12 months (August 2021 to July 2022). The median age at presentation was 12 years (range 5-18 years) and the median duration of symptoms was 24 months at diagnosis (range 2-96 months). The common features included arthritis (90%), malar rash (70.9%), and Raynaud's phenomenon (70.9%). At a mean follow-up of 43 months (range 1-168 months), 45% of them were in remission. There were two deaths reported, due to macrophage activation syndrome and sepsis respectively. We present the largest multicenter experience on jMCTD from the Indian subcontinent. The study's findings serve as a crucial stepping stone toward unraveling the complexities of jMCTD and improving patient care and management strategies.
The very early diagnosis of systemic sclerosis (VEDOSS) criteria were developed to diagnose systemic sclerosis (SSc) at a very early stage. However, several studies have applied these criteria inconsistently, often using them to identify patients at a predisease stage. This use has created confusion between the concept of VEDOSS and pre-SSc. With growing interest in predisease states in autoimmunity, a consensus definition of pre-SSc is mandatory. As a preliminary step towards such definition, this scoping review aimed to map existing definitions of pre-SSc and VEDOSS in the literature, identify item combinations used and capture conceptual variations. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines, PubMed and Web of Science were searched using the terms 'VEDOSS' OR 'very early diagnosis of systemic sclerosis' OR 'pre-scleroderma' OR 'pre-systemic sclerosis' OR 'pre-SSc'. Of 106 records screened, 40 full texts were included (eight on pre-SSc and 32 on VEDOSS). Most articles (80%) originated from Europe. Three distinct definitions of pre-SSc were identified, alongside 13 different applications of VEDOSS criteria. Although 62.5% of studies cited the 2011 VEDOSS consensus, only 31.3% applied the complete definition incorporating the three step 1 essential items and step 2 confirmation tools. This scoping review highlights the variability of the definitions of VEDOSS and pre-SSc that have been used in the literature. The absence of a consensus definition for pre-SSc contributes to overlapping and blurring boundaries between these concepts. A consensus effort is warranted to select a core set of items for a standardised definition of pre-SSc.