Inflammatory arthritis in systemic sclerosis is associated with elevated C-reactive protein and requires musculoskeletal ultrasound for reliable detection.

OBJECTIVES About 25% of patients with systemic sclerosis (SSc) have elevated C-reactive protein (CRP) levels. Specific causes of CRP elevation are unknown so far. We aimed to investigate whether inflammatory arthritis is associated with CRP elevation. Furthermore, we evaluated the sensitivity and specificity of clinical examination compared to musculoskeletal ultrasound (MSUS) for detection of arthritis. METHODS Sixty-five patients with SSc (51 females) were enrolled and allocated into a CRP-positive (CRP+, n = 20; CRP elevated for at least two years prior to enrollment) and a CRP-negative (CRP-; n = 45) cohort. All patients were examined clinically (modified Rodnan Skin Score, mRSS; swollen/tender joint count 66/68), received a comprehensive MSUS of their hands and feet, as well as laboratory testing (antibody status; CRP). Statistical analyses were performed using non-parametrical tests without adjustments. RESULTS Patient with a disease duration 10. CONCLUSION Arthritis is more frequent in CRP + compared to CRP- SSc patients. Compared to MSUS sensitivity of clinical examination is low for the detection of arthritis; this is likely due to skin fibrosis and soft tissue edema. Therefore, regular monitoring via MSUS should be considered as routine assessment in SSc patients

Inflammatory arthritis in systemic sclerosis is associated with elevated C-reactive protein and requires musculoskeletal ultrasound for reliable detection

ObjectivesAbout 25% of patients with systemic sclerosis (SSc) have elevated C-reactive protein (CRP) levels. Specific causes of CRP elevation are unknown so far. We aimed to investigate whether inflammatory arthritis is associated with CRP elevation. Furthermore, we evaluated the sensitivity and specificity of clinical examination compared to musculoskeletal ultrasound (MSUS) for detection of arthritis.MethodsSixty-five patients with SSc (51 females) were enrolled and allocated into a CRP-positive (CRP+, n = 20; CRP elevated for at least two years prior to enrollment) and a CRP-negative (CRP−; n = 45) cohort. All patients were examined clinically (modified Rodnan Skin Score, mRSS; swollen/tender joint count 66/68), received a comprehensive MSUS of their hands and feet, as well as laboratory testing (antibody status; CRP). Statistical analyses were performed using non-parametrical tests without adjustments.ResultsPatient with a disease duration <3 years had higher CRP levels (p = 0.042). Anti-centromere antibodies dominated in CRP- patients (p = 0.013), and anti-Scl70 antibodies in CRP + patients (p = 0.041). Joint effusion and B-mode synovitis prevailed in male (p < 0.00001; p < 0.0001) and CRP + (p = 0.001; p < 0.00001) patients. Power Doppler (PD)-synovitis predominated in patients with diffuse SSc (p = 0.0052). Joint effusion and B-/PD-synovitis were mostly confined to wrists, MTPs and talo-navicular joints. Compared to MSUS, sensitivity of clinical examination was as low as 14.6%; specificity was 87.7%. Sensitivity was reduced by the presence of soft tissue edema or a mRSS > 10.ConclusionArthritis is more frequent in CRP + compared to CRP- SSc patients. Compared to MSUS sensitivity of clinical examination is low for the detection of arthritis; this is likely due to skin fibrosis and soft tissue edema. Therefore, regular monitoring via MSUS should be considered as routine assessment in SSc patients

Induction of Raf kinase inhibitor protein contributes to macrophage differentiation

Differential gene expression analysis of human blood monocytes has identified the Raf kinase inhibitor protein (RKIP) as a continuously upregulated gene in macrophage and dendritic cell maturation. Using realtime RT-PCR and Western blot analysis we were able to confirm the initial DNA-microarray findings of RKIP induction on mRNA and protein levels. RKIP upregulation in primary cells and overexpression in THP-1 cells did not alter ERK activity but strongly reduced the amount of the NFkappaB subunit p65 in the nucleus. mRNA levels and cell surface expression of maturation markers including the integrin CD11c and the scavenger receptor CD36 were significantly increased in RKIP transfected THP-1 cells. Our data show for the first time that RKIP is upregulated during macrophage and dendritic cell differentiation on mRNA and protein levels and we conclude that RKIP contributes to the monocytic differentiation process via inhibition of the NFkappaB signaling cascade independent from the canonical Ras/Raf/MEK/ERK pathway

Femoral condyle insufficiency fractures: associated clinical and morphological findings and impact on outcome.

ObjectiveTo determine the characteristics of femoral condyle insufficiency fracture (FCIF) lesions and their relative associations with the risk of clinical progression.Materials and methodsThis HIPAA-compliant retrospective study was approved by our Institutional Review Board. Seventy-three patients (age range, 19-95) were included after excluding patients with post-traumatic fractures, bone marrow infarct, osteochondritis dissecans, or underlying tumor. Two board-certified musculoskeletal radiologists classified morphologic findings including lesion diameter, associated bone marrow edema pattern, and associated cartilage/meniscus damage. Electronic medical charts were evaluated for symptoms, risk factors, and longitudinal outcomes, including total knee arthroplasty (TKA). Imaging characteristics were correlated with clinical findings, and comparison of outcome groups was performed using a regression model adjusted for age.ResultsThe majority of patients with FCIF were women (64.4%, 47/73), on average 10 years older than men (66.28 ± 15.86 years vs. 56.54 ± 10.39 years, p = 0.005). The most common location for FCIF was the central weight-bearing surface of the medial femoral condyle; overlying full thickness cartilage loss (75.7%, 53/70) and ipsilateral meniscal injury (94.1%, 64/68) were frequently associated. Clinical outcomes were variable, with 23.9% (11/46) requiring TKA. Cartilage WORMS score, adjacent cartilage loss, and contralateral meniscal injury, in addition to decreased knee range of motion at presentation, were significantly associated with progression to TKA (p < 0.05).ConclusionsFCIF are frequently associated with overlying cartilage loss and ipsilateral meniscal injury. The extent of cartilage loss and meniscal damage, in addition to loss of knee range of motion at the time of presentation, are significantly associated with clinical progression

Central osteophytes develop in cartilage with abnormal structure and composition: data from the Osteoarthritis Initiative cohort.

ObjectiveTo investigate the natural history of central osteophytes (COs) by analyzing the structure and matrix composition of CO-associated cartilage using 3-T MRI at and 1-3 years before the onset of COs.Materials and methodsBaseline, 4- and 6-year knee MRIs of 400 participants in the Osteoarthritis Initiative were screened for the appearance of new COs. Twenty-eight subjects developed 31 COs. Using MRIs at CO onset and 1-3 years before CO onset, cartilage T2 values were calculated for the local cartilage preceding COs and the surrounding cartilage. Cartilage lesions local to the site of COs and bone marrow edema like lesions (BMELs) subjacent to COs were graded using whole organ MRI scores (WORMS). Wilcoxon tests were used to compare T2 values from the local and the surrounding cartilage at each time point and to compare T2 and WORMS between time points. Knee symptoms were recorded during this period.ResultsAll subjects showed local cartilage lesions before the development of COs. Mean cartilage WORMS increased from 1.56 ± 0.66 a period of 3 years before to 2.39 ± 0.75 with onset of COs (p = 0.008). Local T2 values in the area of the later-appearing COs were significantly higher compared with T2 values of the surrounding cartilage 3 (p = 0.044) and 2 years earlier (p = 0.031) and with the onset of COs (p = 0.025). No significant increase in symptoms was found with the onset of COs.ConclusionThis study provides evidence that focal cartilage structural and compositional degeneration precedes COs. No significant aggravation of knee symptoms was reported during the evolution of COs

Central osteophytes develop in cartilage with abnormal structure and composition: data from the Osteoarthritis Initiative cohort.

ObjectiveTo investigate the natural history of central osteophytes (COs) by analyzing the structure and matrix composition of CO-associated cartilage using 3-T MRI at and 1-3 years before the onset of COs.Materials and methodsBaseline, 4- and 6-year knee MRIs of 400 participants in the Osteoarthritis Initiative were screened for the appearance of new COs. Twenty-eight subjects developed 31 COs. Using MRIs at CO onset and 1-3 years before CO onset, cartilage T2 values were calculated for the local cartilage preceding COs and the surrounding cartilage. Cartilage lesions local to the site of COs and bone marrow edema like lesions (BMELs) subjacent to COs were graded using whole organ MRI scores (WORMS). Wilcoxon tests were used to compare T2 values from the local and the surrounding cartilage at each time point and to compare T2 and WORMS between time points. Knee symptoms were recorded during this period.ResultsAll subjects showed local cartilage lesions before the development of COs. Mean cartilage WORMS increased from 1.56 ± 0.66 a period of 3 years before to 2.39 ± 0.75 with onset of COs (p = 0.008). Local T2 values in the area of the later-appearing COs were significantly higher compared with T2 values of the surrounding cartilage 3 (p = 0.044) and 2 years earlier (p = 0.031) and with the onset of COs (p = 0.025). No significant increase in symptoms was found with the onset of COs.ConclusionThis study provides evidence that focal cartilage structural and compositional degeneration precedes COs. No significant aggravation of knee symptoms was reported during the evolution of COs