Rheumatic diseases constitute a major cause of chronic pain, functional impairment, and long-term disability worldwide. In rheumatic diseases, reliable assessment of structural damage and inflammatory activity is essential for diagnosis, disease monitoring, and treatment response evaluation, yet remains largely dependent on time-intensive expert image interpretation. In this study, we develop and evaluate a pipeline for automatic landmark detection and subsequent pathology scoring in hand magnetic resonance images for three main pathologies in rheumatic diseases, namely erosions, osteitis, and synovitis. We explicitly exploit two orthogonal acquisitions (coronal and transversal) by integrating multi-view information at different stages of the pipeline to assess their impact on automatic scoring performance. We train and compare two landmark detection models that utilize all three magnetic resonance imaging sequences to predict predefined landmarks annotated by experts. The YOLO model achieves better landmark predictions for both metrics and across all distances, with a successful detection rate of 94% for a clinically relevant distance of 6 mm and an overall mean Euclidean distance of 3 mm from ground truth landmarks to predicted landmarks. By using a super-resolution approach to fuse coronal and transversal images for the automatic scoring, we achieve an improved performance for synovitis detection. This paves the way for more fully automated precision medicine in magnetic resonance imaging, reducing the workload for physicians while enabling faster, more standardized results to support the decision-making process.

OBJECTIVES:Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic immune-mediated inflammatory diseases associated with progressive bone deterioration. Comparative longitudinal changes in bone density, microarchitecture, and biomechanical properties, and their association with disease activity, remain insufficiently elucidated in seronegative RA (RA-), seropositive RA (RA+), and PsA. METHODS:High-resolution peripheral quantitative computed tomography (HR-pQCT) was used to assess volumetric bone density (vBMD), microarchitecture, and biomechanical properties at the distal radius and the metacarpophalangeal (MCP) joint during routine follow-up. Generalised additive models, adjusted for age, sex, and body weight, were used to analyse the relationship between bone changes, diagnosis, and disease activity over time, spanning up to 7 years. RESULTS:We analysed 946 radius and 916 MCP scans from 482 patients (175 PsA, 221 RA+, and 86 RA-) over a mean ± SD follow-up period of 25 ± 27 months (maximum: 108) and 24 ± 30 months (maximum: 142), respectively. At all-time points compared, RA+ patients had lower trabecular vBMD than PsA (difference: 14.71 mg hydroxyapatite [HA]/cm³; 95% CI, 2.85-26.58; p = .003 at baseline) and RA- (difference: 16.92 mg HA/cm³; 95% CI, 0.97-32.86; p = .010 at baseline) patients. Longitudinally, total vBMD declined by -16.2 mg HA/cm³ (95% CI, -20.9 to -11.4; p < .001) in RA+ patients over 5 years, with smaller losses in RA- and PsA patients. PsA patients showed stable bone quality with cortical sparing; RA+ patients showed the most pronounced trabecular vBMD and microarchitectural loss; and RA- patients showed intermediate changes. Sustained remission preserved bone, while high disease activity was associated with deterioration. CONCLUSIONS:Longitudinal HR-pQCT shows site- and serostatus-dependent bone deterioration across inflammatory arthritides; RA+ patients have the worst trabecular changes, and those with PsA have relative cortical preservation. Sustained remission preserves bone structure and strength.

OBJECTIVES:To assess the clinical and imaging characteristics associated with fibroblast activation detected by 68Gallium-labelled fibroblast activation protein inhibitor positron emission tomography/CT (68Ga-FAPI-PET/CT) in patients with psoriasis and whether 68Ga-FAPI uptake correlates with the risk of progression to psoriatic arthritis (PsA). METHODS:Psoriasis patients with arthralgia underwent 68Ga-FAPI-PET/CT and were followed up prospectively. 68Ga-FAPI uptake was assessed at 71 articular sites and patients with ≥1 joint with 68Ga-FAPI uptake and PET/CT Joint Index≥2 were considered FAPI positive. The associations between FAPI uptake and clinical and ultrasound (US) findings were investigated. Survival analyses were conducted to assess the association between 68Ga-FAPI uptake and progression to PsA. RESULTS:45 patients with psoriasis were enrolled, 37 of whom (82%) were FAPI positive. FAPI-positive psoriasis patients had significantly higher body mass index (BMI) (p=0.036) and Disease Activity Score 28-C reactive protein (p=0.033) compared with FAPI-negative patients. 68Ga-FAPI uptake was most frequent in large joints and mechanically stressed sites and was more likely in the presence of low-grade synovial hyperplasia (OR: 1.77, 95% CI 1.08 to 2.89), entheseal Power Doppler (OR: 3.80, 95% CI 1.66 to 8.72) and concomitant osteoarthritis (OA). FAPI-positive patients showed a higher risk of progression to PsA compared with FAPI-negative patients (HR 7.1, 95% CI 0.9 to 53.6) (log-rank p=0.028). Only 1/8 patients with psoriasis (12.5%) without 68Ga-FAPI uptake developed PsA, as opposed to 18/37 (49%) of FAPI-positive patients. CONCLUSIONS:In psoriasis patients with arthralgia, 68Ga-FAPI uptake, indicating fibroblast activation, is associated with higher BMI, more pain, subclinical US changes and concomitant OA. Pathological 68Ga-FAPI uptake at articular sites was indicative of higher risk of progression to PsA in our cohort, suggesting fibroblast activation as a crucial step to develop PsA.

Abstract Background/Purpose A subset of psoriasis (PsO) patients exhibits subclinical entheseal inflammation and bone remodeling placing them at higher risk of developing psoriatic arthritis (PsA). Whether early pharmacological interventions during this phase can modulate these inflammatory and structural changes remains largely unclear. Methods In this single-arm, open-label trial (EPos, EUDRACT 2018-000335-27) PsO patients with moderate-to-severe psoriasis, arthralgia, subclinical inflammatory and/or structural bone changes assessed by hand MRI and/or HR-pQCT were included. Patients who had current or past signs of PsA or prior b/tsDMARD exposure were excluded. Participants received apremilast 30 mg BID over 24 weeks. The primary endpoint was the change in structural entheseal lesions (SEL) (number, density and structure) at hand joints assessed by HR-pQCT (week 24). Secondary endpoints were change in bone and inflammatory alterations assessed by MRI (PsAMRIS) as well as clinical response.Safety was monitored Results Twenty patients (50.0±11.6 years;9 women) were included, all with long-standing PsO and frequent nail and scalp involvement. Over 24 weeks no significant progression in the SEL number was detected while entheseal cortical density and cortical thickness also remained stable. No progression in number and volume of erosions was observed. Total PsAMRIS as marker of inflammation remained stable. Significant improvements in skin disease activity (PASI: 10.9±6.7 vs. 5.2±6.6,p=0.013) and tender joint count (3.2±3.4 vs. 0.8±1.8,p=0.006) was seen. No new safety signals emerged. Conclusion In PsO patients at increased risk of PsA, no significant change in subclinical entheseal bone or inflammatory imaging was observed over 24 weeks of apremilast treatment, while skin disease activity and pain outcomes improved. These findings support further investigation of disease-interception strategies in early psoriatic disease.

Background/Objectives: Early identification of vasculitic acute kidney injury (AKI) is crucial for timely immunosuppression and improved renal outcomes; however, noninvasive adjunctive diagnostic tools remain limited. Renal elastography, a noninvasive technique that quantifies renal cortical stiffness, has been primarily investigated in chronic kidney disease, whereas evidence in acute kidney injury is scarce. This study aimed to evaluate the diagnostic utility of renal shear wave elastography for differentiating vasculitic from non-vasculitic AKI and to explore the association between baseline renal cortical stiffness and vasculitic renal outcomes. Materials and Methods: This prospective observational study included three groups: vasculitic AKI, non-vasculitic AKI, and healthy controls. Renal cortical stiffness was measured at admission using two-dimensional shear-wave elastography (2D-SWE) by radiologists blinded to clinical information. After clinicopathological confirmation of definitive diagnoses, between-group comparisons were performed and the diagnostic performance of elastography was evaluated. Additionally, in a biopsy-confirmed immunoglobulin A vasculitis nephritis (IgAVN) cohort (n = 12), baseline elastography measurements were examined in relation to one-year renal outcomes to explore potential prognostic associations. Results: The vasculitic AKI group exhibited significantly higher mean renal cortical stiffness values (9.5 ± 1.9 kPa) compared with both healthy controls (5.53 ± 0.92 kPa) and the non-vasculitic AKI group (6.61 ± 1.89 kPa) (both p < 0.01). Mean renal cortical stiffness demonstrated good diagnostic performance for distinguishing vasculitic from non-vasculitic AKI (AUC 0.86, 95% CI 0.73-0.97), with an optimal threshold of 6.79 kPa yielding 91% sensitivity and 72% specificity. In the prospective one-year follow-up of the IgAVN subcohort (n = 12), patients with unfavorable renal outcomes tended to have higher baseline renal cortical stiffness compared with those with favorable outcomes [median (min-max), 11.2 (10.8-13.3) vs. 9.1 (5.6-11.2), p = 0.046]. Conclusions: These findings suggest that renal elastography may aid in distinguishing vasculitic from non-vasculitic acute kidney injury and may provide exploratory information on the relationship between baseline cortical stiffness and renal outcomes in IgAVN.

Objective To evaluate the long-term efficacy of interleukin (IL)-17A inhibition with secukinumab on structural bone changes and clinical outcomes in psoriatic arthritis (PsA).Methods We conducted a phase-IV non-interventional study on adult patients with active PsA using high-resolution peripheral quantitative CT (HR-pQCT) and MRI of the hand over 48 months. All participants received secukinumab treatment and were followed up according to clinical practice, with repeated HR-pQCT and MRI. Number and volume of erosions, bone density, cortical and trabecular microarchitecture and bone biomechanical properties were assessed based on HR-pQCT scans. MRI synovitis, tenosynovitis, osteitis, periarticular inflammation, erosions and osteoproliferation were quantified by Psoriatic Arthritis MRI Score (PsAMRIS)-Outcome Measures in Rheumatology (OMERACT) score. Study outcomes included drug survival and changes from baseline in disease activity, functional status and imaging-detected inflammation and damage.Results 32 patients with PsA (40.6% female, mean age 56±7.5 years) were enrolled. Drug survival rate was 68.8% at 48 months. Secukinumab was highly effective in all PsA disease domains, with significant improvements in Disease Activity Score 28 (p<0.001), Leeds Enthesitis Index (p=0.027), Psoriasis Area and Severity Index (p=0.001), C reactive protein (p=0.09), Psoriatic Arthritis Impact of Disease (p<0.001) and pain (p<0.001). Functional status measured by the Health Assessment Questionnaire remained stable. On HR-pQCT, bone density, microarchitecture and biomechanics were preserved. There was no progression of bone erosions (all changes were not significant). On MRI, PsAMRIS erosion and osteoproliferation subitems increased marginally (+1.4 and +0.8, respectively), while inflammatory changes remained stably low. No major safety signals emerged.Conclusion Multimodal imaging with HR-pQCT and MRI showed no relevant progression of structural bone damage over 48 months in patients with PsA treated with secukinumab, suggesting that anti-IL-17A therapy induces sustained osteoprotective effects in PsA.

Objectives Abatacept (ABA) is a selective costimulation modulator that inhibits T cell activation. It is approved for rheumatoid arthritis (RA) and psoriatic arthritis (PsA). While its efficacy in RA is well established, its effect on structural joint damage in PsA remains uncertain. This study evaluated the effects of ABA on erosive and proliferative bone changes in PsA using high-resolution peripheral quantitative computed tomography (HR-pQCT) over 24 weeks. Methods ABA bone effects in PsA with bone biomarkers is a prospective, single-arm, open-label, phase IV trial including patients with active PsA (≥2 swollen/tender joints and ≥1 hand joint erosion at baseline). Participants received weekly subcutaneous ABA (125 mg) for 24 weeks; those with good clinical response at week 12 continued treatment. Bone changes were assessed by HR-pQCT and magnetic resonance imaging (MRI) at baseline and week 24. The primary endpoint was change in erosion volume. Results Fifteen patients (mean age 59.5 ± 9 years) were enrolled; 8 continued treatment through week 24. ABA led to a reduction in clinical disease activity. Imaging showed no new erosions or significant erosion progression, and no new structural entheseal lesions on HR-pQCT or MRI. Inflammatory MRI changes persisted in some cases. ABA was well tolerated with no new safety signals. Conclusions ABA prevented new erosions and structural entheseal lesions over 24 weeks, indicating a potential osteoprotective effect. These results suggest ABA may modulate bone remodelling in PsA and help preserve joint structure alongside clinical improvements.

Objectives Although patients with immune-mediated inflammatory diseases (IMID) are thought to be more susceptible to viral infections, it is unclear whether their presentation differs between patients with IMID and healthy controls. This study aimed to investigate the symptom pattern of common viral infections in patients with IMID and compare it with controls without IMIDs.Design A cross-sectional study conducted between 1 February and 30 April 2020, using a questionnaire.Setting Seven tertiary regional care centers in Germany, which specialised in the care of patients with IMID (namely, in gastroenterology, dermatology, rheumatology and immunology clinical care).Participants One thousand nine hundred nine participants completed the survey (757 patients with IMID; 1152 non-IMID controls).Primary outcome measure The occurrence of 11 common viral illness symptoms within the preceding 3 months in patients with IMID and non-IMID controls.Results Symptom data were clustered, based on number and co-occurrance, into 3 major clusters and 2 subclusters ranked by the average number of symptoms. Patients with inflammatory bowel disease and psoriasis were significantly overrepresented in the lower-frequency subcluster of the polysymptomatic cluster. Patients with rheumatoid arthritis were overrepresented in the lower-frequency subclusters of the intermediate and oligo-/asymptomatic clusters. Controls were over-represented only in the higher-frequency subclusters of each major cluster where none of the IMIDs were over-represented. Spondyloarthritis and other IMIDs were also overrepresented in the low-frequency subcluster, but the results were not significant. Overall, patients with rheumatoid arthritis patients reported fewer symptoms (rate ratio=0.68, 95% CI, 0.59 to 0.80) than non-IMID controls.Conclusion Patients with IMID are over-represented in low-frequency subclusters, even among individuals who have reported a broad range of viral infection symptoms. This pattern suggests that the manifestations of viral infections are different between patients with IMID and controls, thus challenging the accurate and early diagnosis of infections.

Objective: Interstitial lung disease (ILD) is one of the most challenging involvement of autoimmune rheumatic diseases (ARDs) and could lead to significant morbidity and mortality. In this article, a collaborative work of tertiary rheumatology and pulmonology centers describing demographic, serological, and radiological findings of patients with ARD associated with ILD (ARD-ILD) is presented. Methods: A descriptive, retrospective study, and data related to demographics, clinical, laboratory, radiologic, or histopathological findings of ILD were collected from the study participants' charts. Results: Around 212 patients with ARD-ILD were evaluated. Of the patients, 172 (81.1%) were female and 40 (18.9%) were male. The distribution of the rheumatic diseases was as follows: systemic sclerosis in 114 (53.8%), rheumatoid arthritis in 47 (22.2%), Sjögren's syndrome in 14 (6.6%), inflammatory myopathy in 16 (7.5%) patients, interstitial pneumonia with autoimmune features (IPAF) in 9 (4%) patients, undifferentiated connective tissue disease in 8 (3.8%), and systemic lupus erythematosus in 4 (1.9%). According to the radiological patterns, 71.7% of the patients had nonspecific interstitial pneumonia (NSIP), 13.7% had definite usual interstitial pneumonia (UIP), 8.5% had probable UIP, 3.8% had lymphocytic interstitial pneumonia, 1.9% had organizing pneumonia, and 0.5% had an atypical pattern. Conclusion: This study showed that the most common rheumatic disease causing ILD is still systemic sclerosis, and NSIP is more prominent as a radiological pattern. IPAF, a disease that has entered the literature in recent years, is also an important type of ILD. Given the multisystemic involvement of ARDs, collaboration among different disciplines is undoubtedly crucial in the diagnosis and management of these diseases.

To improve and validate a convolutional neural network (CNN)-based model for the automated scoring of nail psoriasis severity using the modified Nail Psoriasis Severity Index (mNAPSI) with adequate accuracy across all severity classes and without dependency on standardized conditions. Patients with psoriasis (PsO), psoriatic arthritis (PsA), and non-psoriatic controls including healthy individuals and patients with rheumatoid arthritis were included for training, while validation utilized an independent cohort of psoriatic patients. Nail photographs were pre-processed and segmented and mNAPSI scores were annotated by five expert readers. A CNN based on Bidirectional Encoder representation from Image Transformers (BEiT) architecture and pre-trained on ImageNet-22k was fine-tuned for mNAPSI classification. Model performance was compared with human annotations by using area under the receiver operating characteristic curve (AUROC) and other metrics. A reader study was performed to assess inter-rater variability. In total, 460 patients providing 4,400 nail photographs were included in the training dataset. The independent validation dataset included 118 further patients who provided 929 nail photographs. The CNN demonstrated high classification performance on the training dataset, achieving mean (SD) AUROC of 86% ± 7% across mNAPSI classes. Performance remained robust on the independent validation dataset, with a mean AUROC of 80% ± 9%, despite variability in imaging conditions. Compared with human annotation, the CNN achieved a Pearson correlation of 0.94 on a patient-level, which remained consistent in the validation dataset. We developed and validated a CNN that enables the automated, objective scoring of nail psoriasis severity based on mNAPSI with high reliability and without need of image standardization. This approach has potential clinical utility for enabling a standardized time-efficient assessment of nail involvement in the psoriatic disease and possibly as a self-reporting tool.

Objectives To train, test and validate the performance of a convolutional neural network (CNN)-based approach for the automated assessment of bone erosions, osteitis and synovitis in hand MRI of patients with inflammatory arthritis.Methods Hand MRIs (coronal T1-weighted, T2-weighted fat-suppressed, T1-weighted fat-suppressed contrast-enhanced) of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients from the rheumatology department of the Erlangen University Hospital were assessed by two expert rheumatologists using the Outcome Measures in Rheumatology-validated RA MRI Scoring System and PsA MRI Scoring System scores and were used to train, validate and test CNNs to automatically score erosions, osteitis and synovitis. Scoring performance was compared with human annotations in terms of macro-area under the receiver operating characteristic curve (AUC) and balanced accuracy using fivefold cross-validation. Validation was performed on an independent dataset of MRIs from a second patient cohort.Results In total, 211 MRIs from 112 patients (14 906 region of interests (ROIs)) were included for training/internal validation using cross-validation and 220 MRIs from 75 patients (11 040 ROIs) for external validation of the networks. The networks achieved high mean (SD) macro-AUC of 92%±1% for erosions, 91%±2% for osteitis and 85%±2% for synovitis. Compared with human annotation, CNNs achieved a high mean Spearman correlation for erosions (90±2%), osteitis (78±8%) and synovitis (69±7%), which remained consistent in the validation dataset.Conclusions We developed a CNN-based automated scoring system that allowed a rapid grading of erosions, osteitis and synovitis with good diagnostic accuracy and using less MRI sequences compared with conventional scoring. This CNN-based approach may help develop standardised cost-efficient and time-efficient assessments of hand MRIs for patients with arthritis.

B cell generation of autoantibodies is a crucial step in the pathogenesis of systemic lupus erythematosus (SLE). After their differentiation in the bone marrow, B cells populate the secondary lymphatic organs, where they undergo further maturation leading to the development of memory B cells as well as antibody-producing plasmablasts and plasma cells. Targeting B cells is an important strategy to treat autoimmune diseases such as SLE, in which B cell tolerance is disturbed and autoimmune B cells and autoantibodies emerge. This review discusses the functional aspects of antibody- and cell-based B cell-depleting therapy in SLE. It thereby particularly focuses on lessons learned from chimeric antigen receptor (CAR) T cell treatment on the role of B cells in SLE for understanding B cell pathology in SLE. CAR T cells model a deep B cell depletion and thereby allow understanding the role of aberrant B cell activation in the pathogenesis of SLE. Furthermore, the effects of B cell depletion on autoantibody production can be better described, ie, explaining the concept of different cellular sources of (auto-) antibodies in the form of short-lived plasmablasts and long-lived plasma cells, which differ in their susceptibility to B cell depletion and require different targeted therapeutic approaches. Finally, the safety of deep B cell depletion in autoimmune disease is discussed.

Background: The accruing evidence about the efficacy of anti-IL-1 agents in Familial Mediterranean Fever (FMF) patients led to their widespread off-label use. Therefore, identifying precise indications and clinical characteristics of IL-1i-warranting patients are important. This study investigated the clinical characteristics and treatment indications of patients with FMF requiring interleukin 1 inhibition therapy (IL-1i). Methods: Hospital records of FMF patients attending a tertiary care center at the Department of Rheumatology, University of Health Sciences, Basaksehir Cam and Sakura City Hospital were retrospectively analyzed. Data on symptoms and disease manifestations, age of symptom onset, time to diagnosis, MEFV variants, type of treatment, and their indications were collected. Results: Between June 2020 and March 2023, 312 FMF patients were identified. The mean age at the onset of symptoms was 14.0, and the mean time to diagnosis was 11.9 years. In total, 87.1% of patients were receiving colchicine monotherapy, while the remaining 11.8% warranted IL-1i. Clinical symptoms and flare manifestations did not show a significant difference between the two groups. However, patients receiving IL-1i started having symptoms at younger age (11.5 vs. 14.5, p = 0.042) and time to diagnosis was longer (18.2 vs. 11.0, p < 0.01). M694V homozygosity was more common in patients receiving IL-1i. Indications for patients receiving IL-1i were colchicine resistance (8.0%), secondary amyloidosis (5.1%), and colchicine intolerance (2.2%). Conclusions: This study shows that a subset of FMF patients, particularly those with a more severe phenotype with an earlier disease onset and M694V homozygosity, require IL-1i treatment despite the overall good efficacy and tolerability of colchicine, primarily due to colchicine resistance, intolerance, or complications such as amyloidosis.

ObjectivesTo assess the presence and anatomical distribution of activated fibroblasts in the joints and entheses of patients with psoriasis with arthralgia and to test how fibroblast activation visualised by68gallium-labelled fibroblast activation protein inhibitor-04 (68Ga-FAPI-04)-positron emission tomography (PET)/CT correlates with clinical tenderness, musculoskeletal ultrasound findings and progression to psoriatic arthritis (PsA).MethodsWe conducted a prospective cohort study in patients with psoriasis and arthralgia who underwent clinical and ultrasound evaluation and whole-body PET/CT imaging with68Ga-FAPI-04.68Ga-FAPI-04 uptake at synovial and entheseal sites was assessed by maximal standardised uptake values (SUVmax) and PET/CT Joint Index (JI); logistic regression models were used to investigate its correlation with clinical and ultrasound findings. Survival analyses were performed on patients with at least 6 months of follow-up.Results36 patients with psoriasis were enrolled.68Ga-FAPI-04 uptake was found in 318 (7.9%) joints and 369 (7.3%) entheses in 29 (80.6%) participants, with a mean SUVmax (SD) of 3.2 (1.8) for joints and 2.9 (1.6) for entheses. Large joints and the lower limbs were predominantly affected. A significant positive relationship was found between68Ga-FAPI-04-PET/CT signal intensity and the 68 tender joint count (SUVmax: p<0.001; PET/CT-JI: p<0.001) and tender entheses count (SUVmax: p<0.001; PET/CT-JI: p=0.002). No correlations were found with ultrasound findings (SUVmax: p=0.969; PET/CT-JI: p=0.720). Patients with relevant synovio-entheseal68Ga-FAPI-04 uptake showed a statistically significant higher risk of developing PsA (p=0.02), independent of ultrasound findings.ConclusionsPatients with psoriasis presenting with arthralgia show localised signs of resident tissue activation in joints and entheses, which are associated with higher risk of developing PsA.