Osteopontin, osteoprotegerin and musculoskeletal ultrasound findings in first-degree relatives of rheumatoid arthritis: potential markers of preclinical disease.

BACKGROUND: First-degree relatives (FDRs) of rheumatoid arthritis (RA) patients are known to have increased risk of developing the disease. The detection of altered bone metabolism in FDRs could be a predictor of the disease. Musculoskeletal ultrasound (MSUS) is known for its ability to detect subclinical joint inflammation in RA, but changes in FDRs are not yet described. We aimed to study serum Osteopontin (OPN) and Osteoprotegerin (OPG) levels in FDRs of RA patients as markers of altered bone metabolism in relation to clinical, laboratory and musculoskeletal ultrasound (MSUS) findings. METHODS: Fifty-five individuals were included, 20 had definite RA, 25 were first degree relatives (FDRs) of RA patients, and 10 healthy controls. Clinical evaluation for joint swelling/tenderness was performed for all. ESR, CRP, rheumatoid factor (RF), anti-citrullinated antibodies (ACPA), OPN, OPG, and Musculoskeletal ultrasound (MSUS) by the US7 score were evaluated. RESULTS: Osteoprotegerin was significantly higher in RA (143.89 pg/ml ± 365.47) than in FDRs (22.23 pg/ml ± 65.73; p = 0.009) and controls (6.20 pg/ml ± 12.43; p = 0.003). OPN was also higher in RA (3.66 ng/ml ± 4.20) than in FDRs (1.97 ng/ml ± 1.04) and controls (2.81 ng/ml ± 1.31), though not significant (p = 0.102). Eight of 25 FDRs (32%) had arthralgia without clinical arthritis and 17/25 (68%) were asymptomatic. FDRs with arthralgia had significantly higher ESR and CRP levels than asymptomatic FDRs (9.82 mm/h ± 4.13; p = 0.003, and 3.93 mg/l ± 3.58; p = 0.003). Osteoprotegerin was higher in FDRs than in controls, and also in those with arthralgia (51.55 pg/ml ± 114.68) than in those without (8.44 pg/ml ± 9.67), though without significant difference. OPN was higher in FDRs with arthralgia (2.09 ng/ml ± 1.19) than in asymptomatic (1.70 ng/ml ± 0.55), also without significant difference. Pathologic findings by US7 were detected in 10/25 (40%) FDRs, of which three (12%) had arthralgia and seven (28%) were asymptomatic. CONCLUSIONS: The raised OPG and lower OPN in FDRs than in controls reflect an altered bone metabolism which could precede clinical disease phase. OPN and OPG could serve as markers of altered preclinical bone metabolism in FDRs of RA. US7 score might be a useful screening tool to identify 'at-risk' individuals.

Quality of life and its relation to periarticular bone changes in psoriatic patients with or without joint involvement.

OBJECTIVES: To assess periarticular bone changes in psoriasis patients with or without joint involvement and its effect on patients' quality of life (QoL). METHODS: This cross-sectional study enrolled 50 patients with psoriasis (25 only with skin psoriasis (PsO) and 25 with psoriatic arthritis (PsA)), as well as 25 healthy controls. All participants were analyzed by high-resolution computed tomography (HR-CT) scans of the dominant hand (second and third metacarpophalangeal joints) for detection of new bone formation (enthesophytes) and erosions. Demographic, laboratory, clinical, and disease-specific data, including physical function and QoL, were collected. RESULTS: Physical function and QoL scores were significantly worse in the PsA patients than in the PsO patients. All 25 PsA patients (100%), 18 PsO patients (72%), and 5 healthy individuals (20%) had periarticular bone changes. Statistically significant higher erosion number and volume as well as higher enthesophyte number and height were found in PsA patients compared to both PsO patients and controls, and in PsO patients compared to controls. In PsO patients, the number of erosions and enthesophytes had a negative correlation with some Short Form (SF)-36 sub-scores. In the PsA patients, the number of erosions had a positive correlation with psoriasis disability index, while the number of enthesophytes had a negative correlation with the general health SF-36 sub-score. CONCLUSION: In PsO patients, there may be subclinical periarticular inflammation (erosions and enthesophytes) that raise the suspicion of occult PsA or the possibility of PsO transition to PsA and these periarticular bone changes may worsen QoL in PsO patients. Key Points • Skin psoriasis patients may have subclinical PsA. • Periarticular bone changes in PsO patients may be the early sign for uploading PsA disease. • Quality of life is highly affected in PsA than in PsO patients.

Local infliximab injection of sacroiliac joints in non-radiographic axial spondyloarthritis: Impact on clinical and magnetic resonance imaging parameters of disease activity.

OBJECTIVES: To evaluate the effectiveness of infliximab (IFX) injection into sacroiliac joints (SIJs) of non-radiographic axial spondyloarthritis (nr-axial SpA) and its impact on clinical and MRI parameters of disease activity. METHODS: Thirty-seven patients fulfilling the Association of Spondyloarthritis International Society (ASAS) criteria for axial SpA were initially studied, with disease duration not exceeding 1 year and failed to respond to non-steroidal anti-inflammatory drugs (NSAIDs). Only SpA having active sacroiliitis on MRI without spondylitis (number = 7) were selected to receive bilateral SIJ injection of 20 mg IFX. Follow-up MRI was done at 24 weeks post-injection. Patients were clinically evaluated before, and 12 and 24 weeks after SIJ injection. Evaluation included back pain and stiffness scores, and Bath Ankylosing Spondylitis (BAS) Disease indices and C-reactive protein (CRP) levels. ASAS response criteria were also assessed. RESULTS: Twelve and twenty-four weeks after injection, there was significant decrease in back pain, stiffness, and BAS Disease Activity and Global indices. BAS Functional index, CRP, and mean bone marrow edema score of SIJs were decreased without reaching statistical significance. All patients achieved ASAS20 and five (71.4%) achieved ASAS40. CONCLUSION: SIJ injection of IFX could be a therapeutic option in early nr-axial SpA who failed to respond to NSAIDs.

Angiopoietin-2, endothelial dysfunction and renal involvement in patients with systemic lupus erythematosus.

BACKGROUND: Angiopoietin-2 (ang-2) that activates endothelial cells and increases vascular inflammation might have significant roles in the pathogenesis of glomerular diseases. This study aimed at assessing the level of ang-2 as a marker of renal involvement in SLE patients to elucidate its correlation with disease activity and endothelial dysfunction. METHODS: This study included 81 subjects. The control group included 21 healthy subjects. The patients group included 60 SLE patients, 24 patients without lupus nephritis (LN) and 36 patients with LN. Clinical examination and laboratory investigations including 24 hours urinary protein, estimation of serum ang-2 and creatinine and calculation of estimated glomerular filtration rate (eGFR). Measurement of SLE disease activity index (SLEDAI), flow mediated dilatation (FMD) and carotid intima media thickness (CIMT) were done. Renal biopsy was done for patients with LN. RESULTS: Ang2 level was significantly higher in subjects with FMD <=10%, than in subjects with FMD >10%. Ang2 level was significantly increased in SLE patients than controls, and it was significantly higher in patients with LN than in patients without nephritis. Ang2 was significantly positively correlated with SLEDAI, 24 hours urinary protein and histological activity index, and was negatively correlated with C3, eGFR and FMD. There were no significant differences between patients with proliferative and non proliferative LN regarding Ang2 level. CONCLUSIONS: Ang2 can reflect the extent of endothelial activation and may be used as a biomarker of both disease activity and renal involvement in SLE patients. Ang2 level cannot distinguish between proliferative and non proliferative lesions in LN.