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Objective To investigate whether sonographically determined subclinical enthesopathy in patients with moderate‐to‐severe psoriasis regresses with the use of ustekinumab therapy for skin disease. Methods Seventy‐three patients with moderate‐to‐severe psoriasis, who were not treated with systemic therapy and did not have symptoms of psoriatic arthritis (PsA), and 23 healthy volunteers were screened by ultrasound for subclinical enthesitis. Subsequently, 23 patients with psoriasis whose ultrasound results showed inflammatory changes were treated with ustekinumab for 52 weeks. The evolution of sonographic abnormalities of the upper and lower limb entheses was assessed using an extensive gray‐scale and power Doppler (PD) ultrasound protocol at weeks 0, 12, 24, and 52. For each parameter, a gray‐scale or PD ultrasound score of >0 was determined to be abnormal, and a summative score based on the Glasgow Ultrasound Enthesitis Scoring System was calculated. Results Of all the patients with psoriasis screened using ultrasound, 49.3% had at least 1 inflammatory entheseal abnormality. Mean ± SD inflammation scores were higher in the patients with psoriasis compared with the healthy volunteers (9.9 ± 6.6 versus 1.0 ± 1.4). With treatment, the mean inflammation scores decreased significantly by 42.2% from week 0 to week 24 (–4.2 [95% confidence interval –6.3, –2.1]; P < 0.001) and by 47.5% by week 42 (–4.7 [95% confidence interval –7.1, –2.3]; P = 0.001). Entheseal structural abnormalities did not change significantly during treatment. Conclusion Within 12 weeks of treatment, interleukin‐12 (IL‐12)/IL‐23 inhibition for psoriasis appears to suppress subclinical enthesopathy, and the suppression is maintained through week 52. Further longitudinal studies are needed to determine whether therapy initiated for skin disease may prevent the development of PsA.

Objective: Type I interferon (IFN ) responses are broadly associated with autoimmune diseases, including systemic lupus erythematosus (SLE ). Given the cardinal role of autoantibodies in SLE , this study was undertaken to investigate whether the findings of a B cell–specific IFN assay correlate with SLE activity. Methods: B cells and peripheral blood mononuclear cells (PBMC s) were stimulated with type I IFN and type II IFN . Gene expression was analyzed, and the expression of pathway‐related membrane proteins was determined. A flow cytometry assay for tetherin (CD 317), an IFN ‐induced protein ubiquitously expressed on leukocytes, was validated in vitro and then clinically against SLE diagnosis, plasmablast expansion, and the British Isles Lupus Assessment Group (BILAG ) 2004 score in a discovery cohort (n = 156 SLE patients, 30 rheumatoid arthritis [RA ] patients, and 25 healthy controls). A second, longitudinal validation cohort of 80 SLE patients was also evaluated for flare prediction. Results: In vitro, a close cell‐specific and dose‐response relationship between type I IFN –responsive genes and cell surface tetherin was observed in all immune cell subsets. Tetherin expression on multiple cell subsets was selectively responsive to stimulation with type I IFN compared to types II and III IFN s. In patient samples from the discovery cohort, memory B cell tetherin showed the strongest associations with diagnosis (SLE :healthy control effect size 0.11 [P = 0.003]; SLE :RA effect size 0.17 [P < 0.001]), plasmablast numbers in rituximab‐treated patients (R = 0.38, P = 0.047), and BILAG 2004. These associations were equivalent to or stronger than those for IFN score or monocyte tetherin. Memory B cell tetherin was found to be predictive of future clinical flares in the validation cohort (hazard ratio 2.29 [95% confidence interval 1.01–4.64]; P = 0.022). Conclusion: Our findings indicate that memory B cell surface tetherin, a B cell–specific IFN assay, is associated with SLE diagnosis and disease activity, and predicts flares better than tetherin on other cell subsets or whole blood assays, as determined in an independent validation cohort.

Purpose There is currently no standardized method for muscle shear wave elastography (SWE). The objective of this study was to investigate the effect of unit of measurement, depth, and probe load on the reliability of muscle SWE. Methods The vastus lateralis, biceps femoris, biceps brachii, and abductor digiti minimi muscles were scanned on 20 healthy participants. The SWE readings were measured in shear wave velocity (m/s) and Young's modulus (kPa). Three acquisitions of varying depths were acquired from vastus lateralis. Minimal probe load was compared with the use of a standoff gel layer. Three repeated measurements were acquired to assess reliability using intraclass correlations (ICC). Results The mean elasticity varied across muscle groups and ranged from 1.54 m/s for biceps femoris to 2.55 m/s for abductor digiti minimi (difference = 1.01 m/s [95% confidence interval, CI = 0.92, 1.10]). Reporting readings in meters per second resulted in higher ICC of 0.83 (0.65, 0.93) in comparison to 0.77 (0.52, 0.90) for kilopascal for the vastus lateralis muscle only. Variance increased proportionally with depth reaching 0.17 (equivalent to ±0.82 m/s) at 6 cm. Using a standoff gel decreased ICC to 0.63 (0.20, 0.84) despite similar mean elasticity readings to minimal probe load. Conclusions Different acquisition and technical factors may significantly affect the reliability of SWE in skeletal muscles. Readings acquired in the unit of shear wave velocity (m/s) from depths less than 4 cm using a minimal probe load without a standoff gel yielded the best reliability.

OBJECTIVE: To evaluate predictors of serious infection events (SIEs) during rituximab (RTX) therapy and effects of hypogammaglobulinemia on SIE rates, and humoral response and its persistence after discontinuation of RTX in the treatment of rheumatic and musculoskeletal diseases (RMDs).METHODS: A retrospective longitudinal study of 700 RMD patients treated with RTX in a single center was conducted. Immunoglobulin levels were measured at baseline and at 4-6 months after each treatment cycle. Baseline predictors of SIEs were assessed using multivariable logistic regression; for RTX cycles 2-4, a mixed-effects logistic regression model was used.RESULTS: A total of 507 patients (72%) had rheumatoid arthritis, 94 (13%) had systemic lupus erythematosus, 49 (7%) had antineutrophil cytoplasmic antibody-associated vasculitis, and 50 (7%) had other RMDs. The number of SIEs recorded was 281 in 176 patients (9.8 per 100 person-years). Predictors of SIEs included non-RTX-specific comorbidities (previous history of SIE, cancer, chronic lung disease, diabetes mellitus, and heart failure), higher corticosteroid dose, and RTX-specific factors, including low IgG (CONCLUSION: Immunoglobulin levels should be monitored at baseline and before each RTX cycle to identify patients at risk of SIEs. Individualized risk-benefit assessment should be undertaken in those with lower IgG as this is a consistent SIE predictor and may increase infection profiles when RTX is switched to different therapies.

OBJECTIVES To evaluate quantitative sonoelastography of benign and malignant musculoskeletal soft tissue masses. METHODS We conducted a prospective study of 50 patients from a specialist sarcoma center who had extremity soft tissue masses referred for biopsy. After consent, the quantitative shear wave velocity (meters per second) was measured in longitudinal and transverse planes (3 readings in each plane and mean calculated). All masses subsequently underwent biopsy, excision, or both, with the histologic diagnosis taken as the reference standard. At a subsequent sitting, all anonymized B-mode sonograms were scored independently by 2 radiologists as benign or malignant with agreement by consensus if necessary. RESULTS Of the 50 masses, 15 were malignant and 35 benign. Nine masses had incomplete velocity readings. Intraclass correlation coefficients for intra-reader reliability of velocity measurements were highly repeatable. There was preliminary evidence that the longitudinal shear wave velocity of malignant masses was on average 30% slower than that of benign masses (P< .10). Longitudinal and transverse shear wave measurements were moderately associated with each other (P = .003). There was no evidence that shear wave velocity varied with patient age, sex, or mass volume. For B-mode assessment of malignancy, sensitivity (Wilson 90% confidence interval) was 73.3% (52.1%, 87.4%), and specificity was 77.1% (63.8%, 86.6%). Interobserver agreement was substantial (κ= 0.86). Four of 15 malignant masses (26.6%) were incorrectly classified as benign on B-mode assessment (all grade 1 liposarcomas). CONCLUSIONS These data suggest that shear wave velocity measurement is reproducible and that malignant masses may have slower longitudinal shear wave velocities than benign masses. The sample size of this pilot study precludes adjusted analysis but should form the basis for larger study designs.

Objective Arthritis activity assessments in psoriatic arthritis (PsA) have traditionally relied on tender and swollen joint counts, but in rheumatoid arthritis, multiple studies have demonstrated subclinical inflammation using modern imaging. The aim of this study was to compare clinical examination and ultrasound (US) findings in an early PsA cohort. Methods Forty-nine disease-modifying antirheumatic drug–naive patients with recent-onset PsA (median disease duration 10 months) underwent gray-scale (GS) and power Doppler (PD) US of 40 joints plus tender and swollen joint counts of 68/66 joints. GS and PD were scored on a 0–3 semiquantitative scale for each joint. Clinically active joints were defined as tender and/or swollen and US active joints were defined as a GS score ≥2 and/or a PD score ≥1. Results The most common sites for subclinical synovitis were the wrist (30.6%), knee (21.4%), metatarsophalangeal (MTP) joints (26.5–33.7%), and metacarpophalangeal joints (10.2–19.4%). Excluding MTP joints and ankles, 37 (75.5%) of 49 patients had subclinical synovitis with a median of 3 (interquartile range [IQR] 1–4) joints involved. In contrast, clinical overestimation of synovitis occurred most commonly at the shoulder (38%) and ankle (28.6%). Twelve of 49 patients were classified clinically as having oligoarthritis; of these, subclinical synovitis identified 8 (75%) as having polyarthritis with an increase in their median joint count from 3 (IQR 1–4) to 6 (IQR 5–7). Conclusion This study has demonstrated that subclinical synovitis, as identified by US, is very common in early PsA and led to the majority of oligoarthritis patients being reclassified as having polyarthritis. Further research is required into the relationship of such subclinical synovitis to structural progression.

Objective For patients with rheumatoid arthritis (RA) in remission who are receiving disease-modifying antirheumatic drugs (DMARDs), radiographic progression correlates with imaging-detected synovitis as measured by power Doppler activity. In contrast, patients with disease in remission who are receiving the combination of tumor necrosis factor (TNF) blockade with methotrexate (MTX) (combination treatment) have reduced radiographic damage for the equivalent clinical state. We undertook this study to determine whether the difference in radiographic outcome is a result of more complete suppression of imaging-detected synovitis. Methods One hundred patients with RA in remission (Disease Activity Score in 28 joints [DAS28]

Objective To evaluate the efficacy of infliximab in HLA–B27–positive patients with magnetic resonance imaging (MRI)–determined early sacroiliitis, using both clinical and MRI assessments. Methods Forty patients with recent-onset inflammatory back pain, as assessed by the Calin criteria, HLA–B27 positivity, clinical disease activity as measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), pain and morning stiffness, and magnetic resonance imaging (MRI)–determined sacroiliac joint bone edema were randomized in a double-blind manner to receive infliximab 5 mg/kg or placebo at 0, 2, 6, and 12 weeks. MRI scans were performed at baseline and 16 weeks and scored by 2 observers (blinded to both the order of the scans and to treatment group), using the Leeds scoring system. Clinical assessments included the BASDAI, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Ankylosing Spondylitis Quality of Life (ASQoL) instrument, the ASsessment in Ankylosing Spondylitis International Working Group criteria (ASAS) for improvement, and markers of inflammation. Results The mean reduction in the total MRI score from week 0 to week 16 was significantly greater in infliximab-treated patients compared with placebo-treated patients (P = 0.033). On average, significantly more lesions resolved in the infliximab group (P < 0.001), while significantly more new lesions developed in the placebo group (P = 0.004). Significantly greater improvement in the infliximab group versus the placebo group was also observed for changes from week 0 to week 16 in the BASDAI (P = 0.002), BASFI (P = 0.004), and ASQoL (P = 0.007) scores. Responses according to the ASAS criteria for 40% improvement, the ASAS criteria for 20% improvement in 5 of 6 domains, and ASAS partial remission were achieved by 61%, 44%, and 56% of infliximab-treated patients, respectively. Infliximab was well tolerated, and no serious adverse events were observed. Conclusion Infliximab was an effective therapy for early sacroiliitis, providing a reduction in disease activity by week 16. This study is the first to show that infliximab is effective for reducing clinical and imaging evidence of disease activity in patients with MRI-determined early axial spondylarthritis.

Objective Few studies have examined hand osteoarthritis (OA) pathology using sensitive imaging techniques. The aim of this study was to determine the extent of ultrasound (US)–detected pathology and investigate its relationship with symptoms in hand OA. Methods Subjects with symptomatic hand OA and controls were recruited. All underwent clinical and US examination of the small joints of both hands and completed a range of measures of hand pain, stiffness, and function. Results Thirty-six subjects with symptomatic OA and 19 control subjects with similar demographics were recruited. US-detected pathology (osteophytes, joint space narrowing, gray-scale synovitis, and power Doppler signal) occurred frequently in symptomatic hand OA (41%, 40%, 46%, and 7% of joints, respectively), and significantly less often in controls (P < 0.001 for all comparisons). Symptomatic joints were more likely to demonstrate US-detected changes of gray-scale synovitis, power Doppler signal, or osteophytes (P < 0.001, P = 0.002, and P < 0.001, respectively). Neither the number of affected joints per individual nor the summative semiquantitative scores for synovitis per individual correlated with symptoms (pain visual analog scale [VAS], global VAS, or Australian/Canadian Osteoarthritis Hand Index). Conclusion This study demonstrated extensive synovitis changes as well as the traditional structural radiographic findings of hand OA. Symptomatic joints were significantly more likely to demonstrate US-detected structural changes or inflammation in symptomatic hand OA; however, the extent of changes in individual joints or in individuals did not correlate with the degree of symptoms, which may relate to both the assessment tools and the complex nature of pain.

Objective Magnetic resonance imaging (MRI) is increasingly used to detect sacroiliitis earlier. This study was undertaken to investigate what proportion of patients with MRI-evident sacroiliitis develop ankylosing spondylitis (AS) in the long term and whether there are predictors of outcome. Methods Consecutive undiagnosed patients with early inflammatory back pain (IBP) (of

Objective Achieving remission is the aim of treatment in rheumatoid arthritis (RA). This should represent minimal arthritis activity and ensure optimal disease outcome. However, we have previously demonstrated a high prevalence of imaging-detected synovial inflammation in RA patients who were in clinical remission. The purpose of this study was to evaluate the long-term significance of subclinical synovitis and its relationship to structural outcome. Methods We studied 102 RA patients receiving conventional treatment who had been judged by their consultant rheumatologist to be in remission, as well as 17 normal control subjects. Subjects underwent clinical, laboratory, functional, and quality of life assessments over 12 months. In addition to standard radiography of the hands and feet, imaging of the hands and wrists was performed with musculoskeletal ultrasonography (US) and conventional 1.5T magnetic resonance imaging (MRI) at baseline and 12 months, using validated acquisition and scoring techniques. Results Despite their being in clinical remission, 19% of the patients displayed deterioration in radiographic joint damage over the study period. Scores on musculoskeletal US synovial hypertrophy, power Doppler (PD), and MRI synovitis assessments in individual joints at baseline were significantly associated with progressive radiographic damage (P = 0.032, P < 0.001, and P = 0.002, respectively). Furthermore, there was a significant association between the musculoskeletal US PD score at baseline and structural progression over 12 months in totally asymptomatic metacarpophalangeal joints (P = 0.004) and 12 times higher odds of deterioration in joints with increased PD signal (odds ratio 12.21, P < 0.001). Conclusion Subclinical joint inflammation detected by imaging techniques explains the structural deterioration in RA patients in clinical remission who are receiving conventional therapy. Our findings reinforce the utility of imaging for the accurate evaluation of disease status and the prediction of structural outcome.

Objective The anatomic basis for joint disease localization in polymyalgia rheumatica (PMR) is poorly understood. This study used contrast-enhanced and fat suppression magnetic resonance imaging (MRI) to evaluate the relationship between synovial and extracapsular inflammation in PMR and early rheumatoid arthritis (RA). Methods Ten patients with new-onset PMR and 10 patients with early RA underwent dynamic contrast-enhanced MRI and conventional MRI of affected metacarpophalangeal (MCP) joints. Synovitis and tenosynovitis were calculated based on the number of enhancing voxels, initial rate of enhancement, and maximal enhancement of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Periarticular bone erosion and bone edema were scored according to the OMERACT (Outcome Measures in Rheumatology Clinical Trials) scoring system in both groups. The degree of extracapsular Gd-DTPA enhancement was assessed in both conditions using semiquantitative scoring. Results No significant differences were seen in the volume of synovitis (P = 0.294), degree of flexor tenosynovitis (P = 0.532), periarticular erosions (P = 0.579), or degree of bone edema (P = 0.143) between RA and PMR joints. However, despite comparable degrees of synovitis, the proportion of MCP joints showing extracapsular enhancement was higher in the PMR group (100%) than in the RA group (50%) (P = 0.030). One PMR patient, but none of the RA patients, had bone edema at the capsular insertion. Conclusion Despite degrees of synovitis and tenosynovitis comparable with those in RA, PMR-related hand disease is associated with prominent extracapsular changes, suggesting that inflammation in these tissues is more prominent than joint synovitis, which is common in both conditions. This suggests that the anatomic basis for joint disease localization differs between RA and PMR.