Clinical and experimental rheumatology最新文献

Objectives: The concept of Comprehensive Disease Control (CDC) underlines as the control of disease activity should be associated with damage inhibition. Recently, this concept has been proposed in Systemic Lupus Erythematosus (SLE) patients (LupusCDC) with long-standing disease. In the present analysis we evaluated the incidence of LupusCDC in a cohort of newly diagnosed patients.

Methods: We analysed data from the multicentre cohort of the Early Lupus Project. Disease activity was evaluated by ECLAM and chronic damage by SDI. At each available time point, the presence of remission condition was assessed, defined as: Complete remission in GCs (GCon): ECLAM=0, antimalarials and/or immunosuppressants, PDN ≤5 mg/day; and Complete remission without GCs (GCoff): ECLAM=0, antimalarials and/or immunosuppressants. The presence of LupusCDC was analysed, defined as remission in the absence of progression of chronic damage (LupusCDC-GCon and LupusCDC-GCoff).

Results: We included 239 patients [205F; mean±DS age 45.8±14.6 years] with a follow-up of 36 months. During this period, 33.08% of patients achieved LupusCDC-GCon, while 12.03% LupusCDC-GCoff in at least one evaluation. Univariate analysis showed the association between failure to achieve LupusCDC-GCon and musculoskeletal manifestations (p<0.001), activity in renal and neuropsychiatric domains (p=0.01, p<0.001, respectively), association confirmed by the multivariate analysis.

Conclusions: CDC in early onset SLE is not uncommon. Indeed, one-third of patients achieved LupusCDC-GCon in at least one evaluation. More severe disease, characterised by active renal and neuropsychiatric manifestations represented a risk factor for failure to achieve LupusCDC. The lower incidence of LupusCDC-GCoff suggested the difficulty in discontinuing GC treatment in early disease phase.

Objectives: Many patients with autoimmune/inflammatory syndrome induced by adjuvants due to breast implants (ASIA-BII) complain of dry eyes, which may be due to impaired tear production or increased tear evaporation. The clinical differences between ASIA-BII patients with dry eyes, compared to other rheumatic diseases (e.g. Sjögren's Disease (SjD)) are largely unknown. We aimed to better classify dry eye disease (DED) by determining if their symptoms stemmed from impaired tear production. We also explored whether common biomarkers present in SjD patients were detected in DED patients with ASIA-BII.

Methods: We utilised a cross-sectional design to enroll 78 consecutive patients with ASIA-BII, SjD (n=16), and healthy controls (HC) (n=17) from a single centre in our study. We assessed each participant using a Schirmer's test and the SjD Screening Questionnaire (SSSQ).

Results: 73.1% of ASIA-BII patients had impaired tear production (Schirmer test <15mm), with severe impairment of tear production (Schirmer's test <5mm) in 47.4%. Severely impaired tear production was similar in prevalence to the SjD patients (p=0.68). ASIA-BII and SjD patients had similar SSSQ scores and rates of abnormal SSSQ scores. Differences were, however, observed in the frequency of positive antinuclear antibodies, anti-Sjögren Syndrome-A (anti-SSA) and anti-Sjögren Syndrome-B (anti-SSB) antibodies between the two groups. When ASIA-BII patients with severely impaired tear production were compared to ASIA-BII patients with normal tear production, a reduction of circulating naive helper T cells (0.014) was observed suggesting a potential role for immune dysregulation in potentiating tear production in ASIA-BII patients.

Conclusions: ASIA-BII patients suffer from dry eyes due to impaired tear production. The SSSQ was unable to differentiate SjD patients from ASIA-BII patients, however, biomarkers such as autoantibodies differ between SjD and ASIA-BII patients. Further investigations are required to further characterise ASIA-BII patients with dry eyes.

Objectives: To verify the ability of super-resolution ultrasound (SRUS) microvascular imaging in assessing Takayasu's arteritis (TAK) activity and predicting prognosis.

Methods: Between November 2023 and July 2024, 70 patients with TAK were consecutively included; disease activity was assessed per the 1990 American College of Rheumatology classification criteria (26 active, 44 inactive). B-mode ultrasound (US), conventional contrast-enhanced ultrasound (CEUS), and SRUS microvascular imaging examinations were performed at the carotid site with maximal wall involvement using the Resona A20 system equipped with a SL10-3U linear transducer. We compared diagnostic performance of individual markers and combined models for disease activity and evaluated deterioration-free survival with Kaplan-Meier analysis.

Results: Carotid vasa vasorum was detected by SRUS microvascular imaging in 14 patients (11 active, 3 inactive), while it was not observed in the remaining 56 cases (41 inactive, 15 active). Presence of vasa vasorum correlated strongly with disease activity (p<0.001), demonstrating 42.3% sensitivity, 93.2% specificity, and 74.3% accuracy. The prediction model constructed based on clinical and US characteristics demonstrated high accuracy in assessing TAK activity (area under the curve=0.900). Among 41 patients completing follow-up (17 active, 24 inactive; mean 8.7±2.7 months), patients with inactive TAK maintained stable disease (only 1 relapsed to active phase). Among patients with active TAK, those with vasa vasorum demonstrated significantly poorer outcomes: only 2/7 (28.6%) achieved remission versus 9/10 (90%) without vasa vasorum (p=0.036).

Conclusions: SRUS detection of carotid vasa vasorum serves as a useful indicator for assessing the activity and severity of TAK.

Muscle dysfunction presenting with weakness and elevated muscle enzymes poses a significant diagnostic challenge for rheumatologists, particularly in differentiating idiopathic inflammatory myopathies (IIM) from other mimicking conditions. This review systematically categorises non-inflammatory muscle diseases, including drug-induced myopathies, endocrine myopathies, genetic muscular dystrophies, metabolic and mitochondrial myopathies, and neuromuscular junction disorders, that can clinically and histologically resemble myositis. We emphasise the importance of a detailed clinical evaluation, including history, pattern of muscle involvement, extramuscular features, and comprehensive laboratory and biopsy investigations, to avoid misdiagnosis. Awareness of these mimickers is crucial for guiding appropriate diagnostic workup and management, given the distinct therapeutic approaches required for each condition. This framework aims to assist rheumatologists in improving diagnostic accuracy, optimising patient management, and enhancing referral decisions in patients presenting with muscle weakness.

Objectives: Myositis specific autoantibodies (MSAs) correlate with a distinct clinical phenotype of juvenile dermatomyositis (JDM). This study aims to compare the clinical features of JDM patients with positive anti-NXP2, anti-MDA5 and anti-TIF1γ autoantibodies, and differences in juvenile (JDM) and adult dermatomyositis.

Methods: This study included 18 NXP2+ JDM patients, 12 MDA5+ JDM patients, 12 TIF1γ+ JDM patients, and 20 NXP2+ adult DM patients. Repeated measures analysis was performed to track longitudinal changes in creatine kinase (CK) levels, Childhood Myositis Assessment Scale (CMAS) scores, and IL-10/γ-interferon ratios. Kaplan-Meier survival and Cox regression analysed relapse rates and recurrence factors.

Results: NXP2+ JDM patients exhibited significantly elevated serum creatine kinase levels compared to MDA5+ JDM (3792 vs. 180; p<0.001), adult NXP2+DM (3792 vs. 437.5; p=0.003), and TIF1-γ+ JDM (3792 vs. 189; p<0.001). Concurrently, NXP2+ JDM patients also showed lower CMAS scores compared to MDA5+ (31.33 vs. 43.25; p<0.001) and TIF1-γ+ JDM groups (31.33 vs. 42.67; p=0.004). The NXP2+ JDM patients presented with a high frequency of macrophage activation syndrome (MAS), myocardial damage, dysphagia, and calcinosis. Repeated measures analysis showed that NXP2+ JDM patients had more severe muscle damage throughout the disease course compared with MDA5+ JDM patients and TIF1γ+ JDM patients. Furthermore, significant interaction effects of Group and Time on CK were observed in JDM patients. A three-year follow-up study revealed a higher relapse risk in NXP2+ JDM patients compared to MDA5+ JDM, TIF1γ+ JDM and NXP2+ adult DM patients.

Conclusions: The NXP2+ JDM patients experience more severe muscle damage, systemic complications, and higher relapse risks. Monitoring dynamic changes in CK and CMAS is essential for predicting disease progression and relapse risk.

Objectives: To prospectively address the predictive features of refractory dermatomyositis (DM) and to construct and internally validate a clinical predictive index to timely identify patients at risk of this complication.

Methods: We recruited 168 patients with DM in a tertiary care centre in Mexico, and prospectively followed them, looking for the primary outcome, which was the diagnosis of refractory disease, defined as persistent disease activity three months after an adequate treatment course with glucocorticoids and at least one immunosuppressant. A logistic regression analysis was performed to calculate the odds ratios (OR) with 95% confidence interval (95% CI) of each predictive feature and to construct the Refractory DermatoMyositis Index (ReDMI).

Results: One hundred twenty-one (72%) patients were women, and the most frequent myositis-specific antibody was Mi2 (23.9%). Fifty-seven patients (33.9%) developed refractory disease. The positivity for anti-TIF1-g (3.76 (1.17-13.3), p=0.029), the gastrointestinal disease activity (visual analogue scale) (1.11 (1.004-1.249), p=0.04), and alopecia (2.5 (1.11-5.7), p=0.026) were the refractoriness predictive factors. ReDMI predicted refractory disease with an OR of 3.57 (95% CI 1.71-7.59), an optimism corrected area under the curve of 0.67 with good internal validity and calibration.

Conclusions: After external validation, the ReDMI may be a useful clinical tool to timely detect DM patients at risk of developing refractory disease who may be candidates to receive an early more aggressive therapy.

Objectives: The dorsal root ganglia (DRG) may play an important role in fibromyalgia pain. The DRG house the nucleus of somatosensory neurons carrying painful stimuli from different body parts. Each neuronal soma interacts with its enveloping immune-competent satellite glial cells (SGCs). Different mediators may activate SGCs, inducing stronger SGCs-neuron coupling and leading to chronic pain. Mice injected with immunoglobulin G of patients suffering from fibromyalgia develop hyperalgesia and neuropathy; in these instances, immunoglobulin G is deposited in DRG SGCs. Our aim was to determine whether the serum of women suffering from fibromyalgia induces more immediate stimulation of DRG neurons and/or their SGCs than does the serum of healthy women.

Methods: Sera from 6 women suffering from fibromyalgia and from 6 healthy controls were tested on Wistar rat DRG neuron and SGCs primary cultures. Fluo-4 was used as intracellular calcium concentration reporter.

Results: Among the 1477 DRG neurons studied, 625 were activated by human serum. Neuronal activation in patient serum was not different from that in control serum. A total of 558 SGCs were activated by human serum. Compared with that in control serum, a greater proportion of ATP-insensitive SGCs were stimulated by patients' serum (45% vs. 34%. Fisher's exact test, p=0.0092). Furthermore, patients' serum induced significantly greater SGCs calcium influx.

Conclusions: Serum of patients suffering from fibromyalgia induces more intense and widespread acute stimulation on ATP-insensitive SGCs. DRG SGCs may play a role in the pathogenesis of fibromyalgia.

Objectives: To explore the heterogeneity and the corresponding clinical significance of lymphocyte subsets in dermatomyositis patients with anti-melanoma differentiation-associated gene 5 positive autoantibody (anti-MDA5+ DM).

Methods: 268 anti-MDA5+ DM patients and 536 gender-age matched healthy controls (HCs) were retrospectively enrolled. Patients' clinical data, serological parameters, peripheral blood lymphocyte subsets, imagological examinations, treatment regimens and follow-up were collected. Cluster analysis based on peripheral blood lymphocyte subsets was conducted in anti-MDA5+ DM patients.

Results: The absolute number of CD3+ T lymphocytes, CD3+CD4+ T cells, CD3+CD8+ T cells, CD3-CD19+ B cells and CD16+CD56+ NK cells were significantly reduced in anti-MDA5+ DM patients compared with HCs. The absolute counts of the above cell subsets were remarkably reduced in non-survivors compared to the survivors of anti-MDA5+ DM. Cluster analysis based on lymphocyte subsets divided anti-MDA5+ DM patients into cluster 1(n=125) and cluster 2 (n=143). Patients in cluster 1 presented with lower counts of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, CD3-CD19+ B cells and NK cells compared with cluster 2. Notably, RP-ILD rate, three-month and six-month death rate in cluster 1 were dramatically higher than in cluster 2, p<0.001, respectively.

Conclusions: Lymphocytes and their subsets were significantly altered in anti-MDA5+ DM patients. There was remarkable heterogeneity of lymphocyte subsets in anti-MDA5+ DM patients between survivors and non-survivors. Anti-MDA5+ DM patients were divided into two groups with distinct symptoms and survival rate by cluster analysis based on lymphocyte subsets.