Comprehensive description of the prevalence, serological and clinical characteristics, and visceral involvement of systemic sclerosis (scleroderma) in a large cohort from the United Arab Emirates Systemic Sclerosis Registry.

Systemic sclerosis is an autoimmune condition characterized by a wide range of clinical presentations. Registries may serve to expand understanding about systemic sclerosis and aid in patient care and follow-up. The objective of this study was to analyze the prevalence of systemic sclerosis in a large cohort from the United Arab Emirates Systemic Sclerosis Registry and find the significant similarities and differences between the different subsets. All scleroderma patients in the United Arab Emirates were included in this multicenter national retrospective analysis. Data on demographics, comorbidities, serological characteristics, clinical aspects, and treatment were collected and analyzed, highlighting the most common traits identified. A total of 167 systemic scleroderma patients from diverse ethnic backgrounds were enrolled. Overall, 54.5% (91/167) of the patients were diagnosed with diffuse cutaneous systemic sclerosis, and 45.5% (76/167) with limited cutaneous systemic sclerosis. The prevalence of systemic sclerosis was 1.66 per 100,000 for the total registry and 7.78 per 100,000 for United Arab Emirates patients. Almost all patients in the diffuse cutaneous systemic sclerosis and limited cutaneous systemic sclerosis groups tested positive for the immunofluorescence antinuclear antibody. Antibodies against Scl-70 were significantly more associated with diffuse cutaneous systemic sclerosis, whereas anticentromere antibodies were significantly more associated with the limited cutaneous systemic sclerosis group (p < 0.001). Sclerodactyly, shortness of breath, and digital ulcers were more common in diffuse cutaneous systemic sclerosis patients compared with the limited cutaneous systemic sclerosis subtype in terms of clinical symptoms and organ involvement. Telangiectasia was much more common in the limited cutaneous systemic sclerosis group. Furthermore, diffuse cutaneous systemic sclerosis patients had more lung fibrosis (interstitial lung disease) than limited cutaneous systemic sclerosis patients (70.5% vs 45.7%), and pulmonary arterial hypertension was twice as common in limited cutaneous systemic sclerosis patients as it was in diffuse cutaneous systemic sclerosis patients. Local registries are paramount to understanding the clinical/serological characteristics of scleroderma. This study emphasizes the importance of raising disease awareness and distinguishing between the various systemic sclerosis subsets to implement patient-tailored strategies for early detection, better management, and higher quality of care.

Ultrasound to identify systemic lupus erythematosus patients with musculoskeletal symptoms who respond best to therapy: the US Evaluation For mUsculoskeletal Lupus longitudinal multicentre study.

OBJECTIVES: To determine whether SLE patients with inflammatory joint symptoms and US synovitis/tenosyovitis achieve better clinical responses to glucocorticoids compared with patients with normal scans. Secondary objectives included identification of clinical features predicting US synovitis/tenosynovitis. METHODS: In a longitudinal multicentre study, SLE patients with physician-diagnosed inflammatory joint pain received intramuscular methylprednisolone 120 mg once. Clinical assessments, patient-reported outcomes and bilateral hand/wrist USs were collected at 0, 2 and 6 weeks. The primary outcome (determined via internal pilot) was the early morning stiffness visual analogue scale (EMS-VAS) at 2 weeks, adjusted for baseline, comparing patients with positive (greyscale ≥2 and/or power Doppler ≥1) and negative US. Post hoc analyses excluded FM. RESULTS: Of 133 patients, 78 had a positive US. Only 53 (68%) of these had one or more swollen joint. Of 66 patients with one or more swollen joint, 20% had a negative US. A positive US was associated with joint swelling, symmetrical small joint distribution and serology. The primary endpoint was not met: in the full analysis set (N = 133) there was no difference in baseline-adjusted EMS-VAS at week 2 [-7.7 mm (95% CI -19.0, 3.5); P = 0.178]. After excluding 32 patients with FM, response was significantly better in patients with a positive US at baseline [baseline-adjusted EMS-VAS at 2 weeks -12.1 mm (95% CI -22.2, -0.1); P = 0.049]. This difference was greater when adjusted for treatment [-12.8 mm (95% CI -22, -3); P = 0.007]. BILAG and SLEDAI responses were higher in US-positive patients. CONCLUSION: In SLE patients without FM, those with a positive US had a better clinical response to therapy. Imaging-detected synovitis/tenosynovitis may be considered to decide on therapy and enrich clinical trials.

Responsiveness of clinical and ultrasound outcome measures in musculoskeletal systemic lupus erythematosus.

OBJECTIVE: To assess the responsiveness of clinical outcome measures in musculoskeletal SLE compared with US. METHODS: A prospective pilot study was conducted in consecutive SLE patients with inflammatory musculoskeletal symptoms. Clinical assessments including SLEDAI, BILAG, 28 tender and swollen joint counts, physician and patient visual analogue scales (VAS), and US were performed at 0, 2 and 4 weeks following 120 mg i.m. methylprednisolone acetate. Responsiveness was analysed using changes and effect sizes using Cohen's criteria. RESULTS: Twenty patients were recruited. Fifteen out of 20 had clinical swelling at baseline. All clinical and US parameters were significantly improved at week 4 (all P ⩽ 0.01). Musculoskeletal-BILAG score improved in 16/20. Musculoskeletal-SLEDAI improved in 7/20. SLE responder index 4 criteria were assessed in 19 patients with SLEDAI ⩾4 at baseline and were met in 9/19 at 4 weeks. Effect sizes at 4 weeks were large (>0.5) for US, physician VAS and BILAG, and medium (>0.3) for joint counts and SLEDAI. Large effect sizes for improvement in US grey-scale and power Doppler were observed in both SLE responder index 4 responders (r = -0.51 and -0.56, respectively) and non-responders (r = -0.62 and -0.59, respectively) at 4 weeks. CONCLUSION: This is the first study to measure the responsiveness of clinical outcome measures in musculoskeletal SLE against an objective inflammation measure. BILAG and physician VAS were the most responsive clinical instruments. US was highly responsive in musculoskeletal SLE, while SLEDAI and joint counts appeared suboptimal for detection of improvement. These results suggest that clinical trials based on the SLEDAI and SLE responder index 4 may underestimate the efficacy of therapy in SLE.

Defining inflammatory musculoskeletal manifestations in systemic lupus erythematosus.

Objective: To define the prevalence and clinical associations of clinical and imaging definitions of synovitis in unselected SLE patients with musculoskeletal (MSK) symptoms. Methods: 112 patients with SLE (excluding RF and CCP positive patients); 88 consecutive with inflammatory MSK symptoms and 24 asymptomatic SLE controls were recruited. Patients had clinical assessment (BILAG, SLEDAI, joint counts, patient and physician visual analogue score), routine laboratory tests and US of two hands and wrists (synovitis and tenosynovitis, OMERACT definitions). Results: Overall, 68% (60/88) of symptomatic patients had US inflammation (grey scale ⩾ 2 and/or PD ⩾ 1 or tenosynovitis) compared with 17% (4/23) of asymptomatic patients. In symptomatic patients, clinical inflammation was seen defined by BILAG A or B in 38% (34/88) or defined by the SLEDAI-MSK criterion in 32% (28/88). BILAG A/B had sensitivity (95% CI) of 56% (41, 69%) and specificity of 89% (72, 96%) for US-confirmed inflammation. SLEDAI-MSK criterion had sensitivity of 44% (31, 59%) and specificity of 89% (72, 96%). In patients with inflammatory symptoms, 27% (24/88) had subclinical inflammation (abnormal US but no clinically swollen joints) and 35% (31/88) had no clinical or US inflammation. Subclinical tenosynovitis and PD were associated with significantly higher IgG, physician visual analogue score, tender joint count. Conclusion: In SLE patients with MSK symptoms, a large proportion of objective, clinically meaningful inflammation is only identifiable by US. The existing classification of MSK SLE using disease activity instruments based on joint swelling is inaccurate to guide patient selection for clinical trials, biologic therapy, or treat-to-target protocols.

Prediction of autoimmune connective tissue disease in an at-risk cohort: prognostic value of a novel two-score system for interferon status.

OBJECTIVE: To evaluate clinical, interferon and imaging predictors of progression from 'At Risk' to autoimmune connective tissue diseases (AI-CTDs). METHODS: A prospective observational study was conducted in At-Risk of AI-CTD (defined as antinuclear antibody (ANA) positive; ≤1 clinical systemic lupus erythematosus (SLE) criterion; symptom duration <12 months and treatment-naïve). Bloods and skin biopsy (non-lesional) were analysed for two interferon-stimulated gene expression scores previously described (IFN-Score-A and IFN-Score-B). Forty-nine healthy controls (HCs) and 114 SLE were used as negative and positive controls. Musculoskeletal ultrasound was performed. Progression was defined by meeting classification criteria for AI-CTDs at 12 months. RESULTS: 118 individuals with 12-month follow-up were included. Of these, 19/118 (16%) progressed to AI-CTD (SLE=14, primary Sjogren's=5). At baseline, both IFN scores differed among At-Risk, HCs and SLE groups (p<0.001) and both were elevated in At-Risk who progressed to AI-CTD at 12 months versus non-progressors, to a greater extent for IFN-Score-B (fold difference (95% CI) 3.22 (1.74 to 5.95), p<0.001) than IFN-Score-A (2.94 (1.14 to 7.54); p=0.018). Progressors did not have significantly greater baseline clinical characteristics or ultrasound findings. Fold difference between At-Risk and HCs for IFN-Score-A was markedly greater in skin than blood. In multivariable logistic regression, only family history of autoimmune rheumatic disease, OR 8.2 (95% CI 1.58 to 42.53) and IFN-Score-B, 3.79 (1.50-9.58) increased the odds of progression. CONCLUSION: A two-factor interferon score and family history predict progression from ANA positivity to AI-CTD. These interferon scores may allow stratification of individuals At-Risk of AI-CTD permitting early intervention for disease prevention and avoid irreversible organ damage.

The role of ultrasound in assessing musculoskeletal symptoms of systemic lupus erythematosus: a systematic literature review.

OBJECTIVES: Musculoskeletal symptoms are common in SLE and are associated with significant morbidity. However, assessing their nature can be challenging, with implications for treatment decisions and measuring response. US has been shown to be valid and reliable for the assessment of other inflammatory arthritides, but data in SLE are more limited. The objectives of this systematic literature review were to determine the characteristics of musculoskeletal US abnormalities in SLE and to evaluate the metric properties of US in the detection and quantification of musculoskeletal symptoms. METHODS: We systematically searched the literature using the PubMed, Embase and Cochrane Library databases for studies using musculoskeletal US for assessing SLE. Studies were assessed for quality using the Quality Assessment of Diagnostic Accuracy Studies tool and for their metric qualities, including reliability and validity. RESULTS: Nine studies were identified. Most studies investigated construct validity. Rates of abnormality were highly variable: synovitis and tenosynovitis were reported in 25-94% and 28-65% of patients, respectively; power Doppler and erosions were reported in 10-82% and 2-41% of patients, respectively. There was poor to moderate association between US abnormalities and disease activity indices and immunological findings. There was moderate to high risk of bias and there were concerns about applicability in most studies. CONCLUSION: US has potential value in the assessment of musculoskeletal symptoms in SLE. However, there is methodological variation between studies that may account for lack of consensus on US abnormalities. Studies that address these problems are required before US can used as an outcome measure in SLE.

The specificity of ultrasound-detected bone erosions for rheumatoid arthritis.

BACKGROUND: Bone erosion is one of the hallmarks of rheumatoid arthritis (RA), but also seen in other rheumatic diseases. The objective of this study was to determine the specificity of ultrasound (US)-detected bone erosions (including their size) in the classical 'target' joints for RA. METHODS: Patients fulfilling the diagnostic criteria for RA, psoriatic arthritis, osteoarthritis or gout in addition to healthy volunteers were included. The following areas were examined by US: distal radius and ulna, 2nd, 3rd and 5th metacarpophalangeal (MCP), 2nd and 3rd proximal interphalangeal (PIP) and 1st and 5th metatarsophalangeal (MTP) joints. All joints were scanned in four quadrants using both semiquantitative (0-3) and quantitative (erosion diameter) scoring systems. RESULTS: 310 subjects were recruited. The inter-reader and intrareader agreements were good to excellent. US-detected bone erosions were more frequent but not specific for RA (specificity 32.9% and sensitivity 91.4%). The presence of erosions with semiquantitative score ≥2 in four target joints (2nd, 5rd MCP, 5th MTP joints and distal ulna) was highly specific for RA (specificity 97.9% and sensitivity 41.4%). Size of erosion was found to be associated with RA. Erosions of any size in the 5th MTP joint were both specific and sensitive for RA (specificity 85.4% and sensitivity 68.6%). CONCLUSIONS: The presence of US-detected erosions is not specific for RA. However, larger erosions in selected joints, especially 2nd and 5rd MCP, 5th MTP joints and distal ulna, were highly specific for and predictive of RA.

Renal cell carcinoma-associated adult dermatomyositis treated laparoscopic nephrectomy.

A 77-year-old female, who suffered from rheumatoid arthritis and hypothyroidism, developed severe muscle weakness. Clinical features, blood results and muscle biopsy suggested a possible diagnosis of dermatomyositis. A computed tomography of the chest, abdomen and pelvis showed a solid mass in the left kidney. She underwent a left laparoscopic nephrectomy and histology confirmed conventional (clear cell) renal cell carcinoma. She recovered slowly and almost back to normal life after 6 months. Early appreciation of the typical skin rash may provide a clue to the diagnosis and screening for neoplasm may improve prognosis.

Does joint position affect US findings in inflammatory arthritis?

OBJECTIVE: Musculoskeletal US is being increasingly used for the assessment of synovitis, although questions remain about its reliability. One potential factor affecting reliability is the lack of consensus of image acquisition methods such as using different joint positions. This may have an implication on the reproducibility of studies that use US as an outcome measure. The aim of this study was to determine whether a change in joint position might significantly alter the quantification of US-detected synovitis in patients with inflammatory arthritis (IA). METHODS: IA patients with clinically swollen wrists, MCP and/or knee joints were recruited. These joints were assessed quantitatively for the presence of synovitis when they were placed in different positions. RESULTS: Seventy-five patients with IA were assessed. The greatest grey scale (GS) and power Doppler (PD) scores for the MCP joints were found in the flat (0°) position (91 and 100% of cases, respectively) compared with other positions (P < 0.001). Similar results were found in the wrist joints. The greatest GS and PD scores for the knee joint were found in 30° flexion [100 and 95.6% of cases, respectively, compared with other positions (P < 0.001)]. The inter- and intra-reader reliability was good to excellent. CONCLUSION: The position in which a joint is scanned for synovitis appears to significantly influence the US assessment of synovitis. Our study suggests that the standardized scanning of the hand joints in a flat position and the knees in a 30° position are associated with the highest GS and PD scores.

Do non-steroidal anti-inflammatory drugs have a significant effect on detection and grading of ultrasound-detected synovitis in patients with rheumatoid arthritis? Results from a randomised study.

OBJECTIVES: To determine whether non-steroidal anti-inflammatory drugs (NSAIDs) have a significant effect on ultrasonographic (US) grey scale (GS) and power Doppler (PD) assessment of synovitis in rheumatoid arthritis (RA). METHODS: Patients with RA taking NSAIDs were randomised to either stopping (for a minimum of 5 drug half-lives) or continuing the drug. All patients had a clinical assessment and US examination of both hands and wrists before and after stopping/continuing the NSAID. Changes at follow-up were compared between groups using Mann-Whitney U tests. RESULTS: A total of 58 patients with RA were recruited. All the clinical assessment parameters (including disease activity, pain, general state of health and physician global visual analogue score and tender and swollen joints count) showed an increase in the group who stopped their NSAID treatment. The total GS and PD score showed median (first to third quartiles) increase of 9.5 (5.75 to 19.0) and 4.0 (2.0 to 6.0) per patient, respectively, in the patients who stopped their NSAID in comparison with 1.0 (-1.0 to 2.25) and 0.0 (-2.0 to 3.0), respectively, in the patients who continued their NSAID (p<0.001). There was an increase in the number of joints scoring >0 for GS and PD in the patients who stopped the NSAID. The inter- and intrareader agreement was good to excellent for the US examination. CONCLUSION: NSAID usage may mask the GS and PD signal and result in lower scoring despite continuing disease activity. Consideration should be given to the NSAID effect in designing clinical studies which use US to assess response to therapeutic.