Systemic sclerosis (SSc) is a severe autoimmune disease, with occupational exposure being a significant risk factor. Because CD146 was recently identified as a driver of fibrosis in SSc through regulation of the Wnt/reactive oxygen species interplay, we hypothesized that it is a major autoimmune target in this disease. We developed an in-house ELISA test to detect anti-CD146 autoantibodies (AACD146), which was confirmed by immunoprecipitation and Western blotting. AACD146 positivity was assessed in the sera of patients with SSc compared with healthy controls. A validation cohort of workers exposed to asbestos or silica was evaluated and compared to patients with pulmonary cancer and healthy controls without any occupational exposure. Detection of AACD146 was assessed by ELISA and confirmed with Western blot and an absorption test. In the first cohort, the prevalence of positive AACD146 was significantly higher in patients with SSc (n = 14 of 93; 15%) than in controls (n = 2 of 40; 5%). Interestingly, among patients with SSc, positive AACD146 were associated with male sex (P = 0.04) and occupational exposure to silica (P = 0.009), with a sensitivity of 57% and specificity of 88% for occupational exposure. Results were confirmed in a validation cohort, in which positive AACD146 were found in 57% (n = 13 of 23) of patients with professional exposure. The frequency of AACD146 was significantly higher compared to controls (P = 0.03) and to patients with a history of cancer (P = 0.02). We demonstrated that AACD146 are detectable in patients with SSc and are linked to male workers with occupational dust exposure. AACD146 are the first biomarkers associated with occupational exposure in SSc, with potential implications for preventive medicine.

Juvenile dermatomyositis (JDM) is a rare childhood inflammatory myopathy, whereas spondyloarthritis (SpA) is an inflammatory arthropathy characterized by enthesitis and peripheral or axial involvement. We describe a series of patients diagnosed with JDM in childhood who later fulfilled classification criteria for SpA, a sequential phenotype that has not been well characterized. This institutional review board-exempt retrospective study (2024-180) reviewed demographics, clinical features, laboratory tests, imaging, treatments, and outcomes in a convenience sample of patients who met criteria for JDM before age 18 and subsequently fulfilled the Assessment of Spondyloarthritis International Society (ASAS) or Classification for Psoriatic Arthritis (CASPAR) criteria. Patients with SpA preceding JDM were excluded. Descriptive statistics were used to explore potential predictors of SpA development. Seven patients met the inclusion criteria; 57% were female and 86% were White. The median age at JDM diagnosis was 8 years (interquartile range [IQR] 5-10 years). The median interval time to SpA diagnosis was 7 years (IQR 5-14 years). All tested patients had elevated neopterin and magnetic resonance imaging evidence of myositis; 71% experienced complications before SpA onset. All met ASAS criteria for peripheral SpA, and 29% met CASPAR criteria. HLA-B27 was positive in 20% of those tested. Most (83%) responded to standard SpA therapies; one required rituximab and azathioprine for calcinosis. This preliminary small study highlights a possible evolution from JDM, an adaptive immune disease, to SpA, an innate-driven illness. These findings suggest potential predictors of disease overlap and warrant future studies to clarify mechanisms and inform predictive models.

To characterize clinical and transcriptomic differences in juvenile scleromyositis overlap (jOverlap) compared to juvenile systemic sclerosis (jSSc) and juvenile dermatomyositis (JDM), focusing on autoantibody profiles, organ involvement, treatment, and peripheral blood gene expression. Peripheral blood bulk RNA sequencing was performed on children with jSSc (n=25), JDM (n=25), and jOverlap (n=26), and healthy controls (HCs; n=21) from two tertiary referral centers. Disease category was assigned by treating physicians. Clinical data and autoantibody profiles were collected. RNA was sequenced using the Illumina NextSeq 500 platform. Differentially expressed genes (DEGs) were identified using Partek Flow and DESeq2, applying a log2 fold change cutoff of ±1.5 and a false discovery rate of <0.1. Patients with jOverlap, predominantly White girls, had distinct autoantibody patterns enriched for PM-Scl, U1-RNP, and U3-RNP. Compared to HCs, patients with jSSc, JDM, and jOverlap demonstrated a unique gene expression profile, with up-regulation of type-1 interferon-related genes, specifically SIGLEC1 and IFI27. Compared to patients with JDM, patients with jOverlap showed higher expression of RAB13 (linked to sclerosing neurodegenerative disease), MMEL1 (inflammatory arthritis), and MMP19 (pulmonary fibrosis). t-distributed stochastic neighbor embedding clustering revealed that although HC, jSSc, and JDM samples each formed distinct clusters, jOverlap samples were distributed across all clusters, highlighting their heterogeneity. Patients with jOverlap exhibited a distinct immunophenotype and clinical profile compared to patients with jSSc and JDM. Their broad transcriptional heterogeneity suggests disease category alone does not explain gene expression patterns. Further analysis correlating DEGs with autoantibodies, age, and clinical features is warranted to better define this overlapping disease entity.

We report a 49‐year‐old male patient with a normal serum uric acid and recent diagnosis of acute promyelocytic leukemia (APL) who developed a severe polyarticular gout flare during treatment with arsenic trioxide (ATO). Unlike conventional chemotherapies, ATO acts through the generation of reactive oxygen species (ROS), leading to APL cell apoptosis. The gout flare in our patient was initially treated with high‐dose intravenous glucocorticoids with no clinical response and was subsequently treated with interleukin‐1β receptor blockade, which resulted in complete clinical resolution of his gout. Our case offers insights into inflammatory pathways in gout, including the evolving role of ROS in autoinflammation.

ObjectiveSystemic lupus erythematosus (SLE) commonly affects women during their childbearing years, making pregnancy experiences especially important to understand. This is particularly true for US Hispanic women, who face a higher SLE burden, more unplanned pregnancies, and frequent language or cultural discordance with clinicians. This study explores their perspectives, focusing on emotional dualities, logistical challenges, and views on unplanned pregnancies.MethodsWe conducted semistructured interviews with 30 Hispanic women aged 18 to 45 with SLE, recruited from Los Angeles General Medical Center and LupusLA. Eligible participants were heterosexually active or considering pregnancy within three years. Interviews were analyzed using grounded theory to identify themes related to pregnancy experiences, whether actual or hypothetical.ResultsThree core themes emerged: (1) pregnancy with SLE was marked by a variety of emotions (primarily hope and anxiety); (2) navigating frequent appointments and complex care created logistical strain but also reassurance; and (3) unplanned or poorly timed pregnancies led to a desire for immediate, trusted guidance from their rheumatologist, with most participants preferring continuation if medically feasible.ConclusionFindings highlight the emotional complexity and logistical challenges faced by Hispanic women with SLE. Many of the themes mirror those seen in other chronic disease populations, underscoring that US Hispanic women with SLE, their cultural and linguistic barriers notwithstanding, share many of the same hopes, fears, and needs as other women navigating pregnancy with chronic illness. These results emphasize the need for empathetic, patient‐centered reproductive health care that addresses their emotional, medical, and informational needs.

ObjectiveThe synovial tissue pathotype may determine the treatment response in rheumatoid arthritis (RA); however, biopsies are not widely available. Synovial fluid is a promising tissue surrogate. Our purpose was to compare RA synovial fluid cell counts with histopathology and use synovial fluid to predict tissue inflammation.MethodsSynovial fluid and tissue were collected during knee arthroplasty. Patients were stratified based on their medication treatment history. Synovial lymphocytic inflammation (SLI) was graded from low to high. Synovial fluid white blood cell (WBC) count and differentials were performed in the clinical laboratory. Descriptive statistics, correlations, receiver operating characteristic curve analysis, and multivariable regression were performed to determine the associations with tissue SLI.ResultsSixty‐four patients with RA had paired synovial tissue and synovial fluid data available. The mean Clinical Disease Activity Index (CDAI) score was 17.9. High tissue SLI was observed in 29 patients, and low SLI was observed in 35 patients, with roughly equal distribution among treatment groups. The mean synovial fluid WBC count was 5,661 cells/μL and was not correlated with CDAI but correlated positively with SLI and percentage polymorphonuclear cells (PMN%). Synovial fluid WBC count ≥1,400 cells/μL was sensitive (0.86) and specific (0.91) for high SLI (area under the curve 0.91). In a multivariable regression, PMN% was associated with high SLI (odds ratio [OR] 1.46 [95% confidence interval (CI) 1.14–1.85]). Synovial fluid monocyte percentage was negatively associated with high SLI (OR 0.44 [95% CI 0.27–0.73]).ConclusionSynovial fluid WBC count is sensitive and specific for differentiating high and low lymphocytic synovial inflammation. Further analysis of the synovial fluid as it relates to the adjacent tissue in different cohorts is needed.

To assess differences in perception between patients and physicians regarding the determinants of the burden of systemic lupus erythematosus (SLE) in France. An online survey was conducted by IPSOS, a market research company, among adult patients with SLE and physicians (internists, rheumatologists, nephrologists, and dermatologists) involved in SLE care. The questionnaires were designed by a committee of lupus experts and patient research partners to cover key areas: symptoms experienced by patients with SLE, social and economic impact of the disease, and needs and expectations for the improvement of care pathways. Most questions were formulated to assess comparatively how they were perceived by patients and physicians. Responses from 107 patients and 101 physicians were analyzed. Regarding experienced symptoms, a patient-physician discordance was observed on the number of reported symptoms (P < 0.001) and in terms of prioritization, especially with the impact of extreme fatigue (76% vs 51%; P < 0.001) and anxiety and depression (45% vs 13%; P < 0.001), even outside flare-up periods. Physicians rarely reported that SLE significantly impacts all areas of their patients' lives, including physical, psychological, social, professional, sexual, and emotional aspects, whereas most patients expressed a lack of medical advice on areas such as sexual and emotional health, family life, professional life, and anxiety. Most patients also declared a perceived lack of information about treatment adverse effects, available therapeutic options, and potential causes of SLE. This survey highlights the significant patient-physician discordances about the burden of SLE in France and supports the need for specific interventions to improve patient information and holistic care.

To evaluate the clinical characteristics and serum cytokine profiles of patients with anti-MDA5 antibody-positive dermatomyositis with interstitial lung disease (MDA5+ DM-ILD) treated with JAK inhibitors and to compare survivors and nonsurvivors. Six patients diagnosed with MDA5+ DM-ILD at Nagasaki University Hospital (from 2018 to 2023) were analyzed. All patients received high-dose glucocorticoids, intravenous cyclophosphamide, and plasma exchange. Five patients received calcineurin inhibitors. JAK inhibitors (tofacitinib, n=3; baricitinib, n=3) were added to the treatment regimen. Clinical data, including serum ferritin levels, hypoxemia status, and lymphocyte counts, were recorded at initial presentation and during JAK inhibitor treatment. Serum cytokine levels were analyzed using multiplex assays. The mean patient age was 66.6 years, and four patients were women. Three patients died within six months of starting JAK inhibitor therapy. Nonsurvivors had higher initial ferritin levels than survivors (mean 3,413 vs 809 ng/mL). Hypoxemia was present in five patients at JAK inhibitor initiation, and four patients had low lymphocyte counts. Serum cytokine analysis revealed elevated levels of granulocyte colony-stimulating factor, interferon-α, interleukin-4, interleukin-13, and CXCL8 in nonsurvivors compared with survivors. Serum cytokine profiles may serve as prognostic markers in patients with MDA5+ DM-ILD treated with JAK inhibitors. The persistent elevation of multiple cytokines in nonsurvivors may reflect inadequate suppression of the cytokine storm despite treatment. Further research is needed to determine the optimal selection and timing of JAK inhibitor therapy.

To investigate longitudinal trends in rheumatoid arthritis (RA) diagnosis and monitoring by physicians and advanced practice providers (APPs) as measured by laboratory testing. We conducted a retrospective review of RA-associated diagnostic and monitoring tests ordered through Labcorp by 7,026 physicians and 2,188 APPs in primary care and rheumatology between 2012 and 2024. Diagnostic tests include conventional markers (rheumatoid factor and anti-cyclic citrullinated peptide) and emerging markers (14.3.3 eta protein, anti-citrullinated α-enolase peptide 1, anti-carbamylated protein, and anti-citrullinated vimentin antibodies). Panel tests combine these markers to enhance diagnostic accuracy. Monitoring tests include the Vectra tests. From 2012 to 2024, rheumatology APPs who consistently ordered RA-associated tests annually through Labcorp increased by 411.8%, whereas rheumatology physicians who consistently ordered RA-associated tests through Labcorp grew by 58.5%. Compared with rheumatology physicians, rheumatology APPs ordered 37.9 fewer conventional markers (P = 2.7 × 10-12) and 2.4 more monitoring tests (P = 0.019). Between 2012 and 2024, conventional marker volumes increased by 3.0% among rheumatology physicians, 98.9% among rheumatology APPs, 36.2% among primary care physicians, and 75.6% among primary care APPs. The yearly average volume of RA panel tests ordered by rheumatology APPs increased by 2,948.5% compared with increases of 218.4% by rheumatology physicians, 128.0% by primary care physicians, and 203.7% by primary care APPs. The difference in the proportion of positive diagnostic test results between rheumatology physicians and rheumatology APPs narrowed from 3.0% in 2015 to 0.5% in 2024. We observed a rise in APP contributions to RA-diagnostic and RA-monitoring test ordering, consistent with their growing presence within the rheumatology workforce.

ObjectiveDespite advances in rheumatoid arthritis (RA) treatment, a considerable proportion of patients exhibit refractory disease, prompting the need for a comprehensive understanding of refractory RA. We aimed to analyze the burden and patient experiences associated with initiation of a third biologic or targeted synthetic disease‐modifying antirheumatic drugs (b/tsDMARDs) (BT3‐RA) in a large observational cohort.MethodsData were obtained from participants with RA in the FORWARD Databank from 1999 to 2019. Participants, stratified into BT3‐RA and a comparator BT1‐RA (first initiation of a b/tsDMARD) cohorts, were matched based on key demographic and disease‐specific parameters. Demographics, patient‐reported outcomes (PROs), comorbidities, and health care interactions were assessed at initiation of first advanced therapy and at the time of meeting BT3‐RA criteria.ResultsAfter matching, 1,384 participants were included in the study (692 each for BT3‐RA and BT1‐RA). The BT3‐RA cohort had worse PROs, greater comorbidity burden, and lower health satisfaction than BT1‐RA controls. Those with BT3‐RA had significantly higher odds of having a greater number of rheumatology visits in the previous six months than controls (>4 visits, 0–2 visit reference, odd ratio [OR] 3.8 [95% confidence interval (CI) 2.7–5.4], P < 0.001; 3–4 visits, 0–2 visit reference, OR 1.9 [95% CI 1.5–2.5]; P < 0.001). Those with BT3‐RA also had higher odds of concomitant glucocorticoid use (OR 1.5 [95% CI 1.2–2.0], P < 0.001) and gastrointestinal disorders (OR 1.5 [95% CI 1.1–1.9], P < 0.01).ConclusionExposure to three advanced RA therapies was associated with significant disease burden and unmet health care needs. These findings underscore the importance of well‐defined refractory criteria and the need for further investigation into this RA phenotype to identify targeted treatment strategies and ultimately improve outcomes.