Structural damage in rheumatoid arthritis: comparison between tendon damage evaluated by ultrasound and radiographic damage.

OBJECTIVE: To compare structural damage assessed by conventional radiography and tendon damage assessed by musculoskeletal US (MSUS) at wrist and ankle in RA patients. METHODS: We evaluated 72 consecutive patients [56 (77.8%) females] with RA. The MSUS evaluation consisted in a B-mode examination of bilateral extensor carpi ulnaris and tibialis posterior tendons. Tendon damage was defined and scored according to OMERACT. A total score for the tendon damage score (TDS) was calculated by summing the grades for each tendon. For the radiographic evaluations we used the van der Heijde score; a total radiographic score (RTS) was calculated by summing a bone erosion score (ERS) and a joint space narrowing score (JSNS). RESULTS: We evaluated 288 tendons. The mean (s.d.) of TDS was 2.3 (1.8). Fifty-four (75%) patients presented tendon damage of at least one tendon. From all evaluated tendons, 134 (46.5%) had no tendon damage, 146 (50.7%) had grade 1 and 8 (2.8%) had grade 2 tendon damage. The mean (s.d.) for RTS was 91.4 (97), for ERS was 47.3 (61.9) and for JSNS was 44.1 (37.2). We found a significant correlation between disease duration and both TDS and RTS (r = 0.413 and r = 0.560, respectively; P < 0.0001). We found a good significant correlation between TDS and all variables of radiographic structural damage (RTS, r = 0.65; ERS, r = 0.637; JSNS, r = 0.618; P < 0.001). CONCLUSION: The MSUS assessment of only four tendons can be an additional feasible method to assess structural damage in RA patients.

To what extent is foot pain related to biomechanical changes and ultrasound-detected abnormalities in rheumatoid arthritis?

OBJECTIVES: To investigate the presence of biomechanical abnormalities and ultrasound (US)-detected inflammation and damage in low disease or remission status rheumatoid arthritis (RA) patients with foot complaints. METHODS: We recruited 136 subjects with foot complaints. Sixty-two were biologic disease-modifying antirheumatic drug-treated RA patients presenting Disease Activity Score-determined remission or low disease activity while the remaining 74 were gender matched controls without rheumatic or musculoskeletal disorders. Both groups underwent a comprehensive podiatric, biomechanical and B-mode and Doppler US assessment of the feet. RESULTS: Most RA patients and controls were female (77.4% and 83.8%, respectively). There was no statistical difference in the proportion of obese subjects in either group (p=0.792). Inappropriate shoes were used by 50.0% of RA patients and 33.8% of controls (p=0.080). Talalgia, particularly heel pain, was more frequent in the control group, with associated talalgia and metatarsalgia being more prevalent in the RA group (p<0.05). The RA patient group was also more likely to present greater foot deformity, more limited joint movement and biomechanical abnormalities than the controls (p<0.05). US inflammatory and structural changes were significantly more frequent in RA patients than in controls (p<0.05). US structural involvement was significantly associated with limited joint mobility and pathologic biomechanical tests only in RA patients (p<0.05). CONCLUSIONS: RA foot complaints seemed to be linked to US-detected RA involvement and biomechanical abnormalities. Podiatric and US assessments can be useful to help the clinician to optimise the management of RA patients in remission/low disease activity with foot complaints.

Ultrasound-detected activity in rheumatoid arthritis on methotrexate therapy: Which joints and tendons should be assessed to predict unstable remission?

The aim of the study was to investigate the predictive value of different reduced joint ultrasound (US) assessments of synovitis and tenosynovitis in relation to unstable remission in a cohort of rheumatoid arthritis (RA) patients on methotrexate therapy. Forty-seven RA patients (38 women, 9 men), being treated with methotrexate (MTX), in clinical remission as judged by their consultant rheumatologist were evaluated for disease activity according to the Disease Activity Score (DAS) 28 at baseline and 6 months. Sustained remission and unstable remission were defined according to the baseline and 6-month DAS28 and changes in RA therapy during the follow-up. Each patient underwent at baseline a B-mode and power Doppler (PD) assessment of 44 joints and 20 tendons/tendon compartments by a rheumatologist blinded to the clinical and laboratory data. B-mode synovial hypertrophy (SH), synovial PD signal, B-mode tenosynovitis, and Doppler tenosynovitis were scored 0-3. The presence and index of synovial PD signal in 44 joints [odds ratio (OR) 8.21 (p = 0.016) and OR 2.20 (p = 0.049), respectively] and in 12 joints [OR 5.82 (p = 0.041) and OR 4.19 (p = 0.020), respectively], the presence of SH in wrist and MCP joints [OR 4.79 (p = 0.045)], and the presence of synovial PD signal in wrist-MCP-ankle-MTP joints [OR 4.62 (p = 0.046)] were predictors of unstable remission. The 12-joint or wrist-hand-ankle-MTP US assessments can predict unstable remission in RA patients in apparent clinical remission being treated with MTX.

Patient self-assessment and physician's assessment of rheumatoid arthritis activity: which is more realistic in remission status? A comparison with ultrasonography.

OBJECTIVE: The objective of this study was to compare disease activity assessed by the patient, the physician and musculoskeletal US in patients with RA in clinical remission. METHODS: We evaluated 69 patients with RA in clinical remission according to their attending rheumatologist. Tenderness and swelling in 28 joints were blindly assessed by patients and physicians. The presence of B-mode and Doppler synovitis was blindly investigated in the above joints. The DAS28 and Simplified Disease Activity Index (SDAI) were calculated. RESULTS: The percentage of patients in remission according to the self-derived DAS28 (26.1%) was significantly less than that according to the physician-derived DAS28 (52.2%) (P < 0.0005). There was no significant difference in the percentage of patients in remission according to the self-derived SDAI (14.5%) and the physician-derived SDAI (11.6%) (P = 0.172). We found moderate agreement between the patient-derived and physician-derived DAS28 and SDAI [intraclass correlation coefficient (ICC) = 0.620 and ICC = 0.678, respectively]. Agreement between patient and physician was better for the tender joint count (TJC; ICC = 0.509) than for the swollen joint count (SJC; ICC = 0.279). The mean (S.D.) count for B-mode synovitis [4.09 (3.25)] was significantly greater than the SJC assessed by both the patient and physician [2 (3.71) and 1.42 (2.03), respectively] (P < 0.0005 and P = 0.033, respectively). We found moderate agreement between the physician-assessed SJC and the joint count for Doppler synovitis (ICC = 0.528). CONCLUSION: Patient-assessed and physician-assessed overall RA activity showed acceptable agreement. Patient self-assessment overestimated disease activity determined by the DAS28. At the patient level, physician-assessed joint swelling showed an acceptable concordance with Doppler US synovitis.

Ultrasound intima media thickness cut-off values for cranial and extracranial arteries in patients with suspected giant cell arteritis.

Objective: To determine the optimal ultrasound (US) cut-off values for cranial and extracranial arteries intima media thickness (IMT) to discriminate between patients with and without giant cell arteritis (GCA). Methods: Retrospective observational study including patients referred to an US fast-track clinic. All patients underwent bilateral US examination of the cranial and extracranial arteries including the IMT measurement. Clinical confirmation of GCA after 6 months was considered the gold standard for diagnosis. A receiver operating characteristic (ROC) analysis was performed to select the cut-off values on the basis of the best tradeoff values between sensitivity and specificity. Results: A total of 157 patients were included, 47 (29.9%) with clinical confirmation of GCA after 6 months. 41 (87.2%) of patients with GCA had positive US findings (61.7% had cranial and 44.7% extracranial involvement). The best threshold IMT values were 0.44 mm for the common temporal artery; 0.34 mm for the frontal branch; 0.36 mm for the parietal branch; 1.1 mm for the carotid artery and 1 mm for the subclavian and axillary arteries. The areas under the ROC curves were greater for axillary arteries 0.996 (95% CI 0.991-1), for parietal branch 0.991 (95% CI 0.980-1), for subclavian 0.990 (95% CI 0.979-1), for frontal branch 0.989 (95% CI 0.976-1), for common temporal artery 0.984 (95% CI 0.959-1) and for common carotid arteries 0.977 (95% CI 0.961-0.993). Conclusion: IMT cut-off values have been identified for each artery. These proposed IMT cut-off values may help to improve the diagnostic accuracy of US in clinical practice.

Comparison between full and tapered dosages of biologic therapies in psoriatic arthritis patients: clinical and ultrasound assessment.

The primary objective of this study was to describe and compare clinical and musculoskeletal (MS) ultrasound (US) features between psoriatic arthritis (PsA) patients treated with full and tapered dosage of biologic (b) disease-modified antirheumatic drugs (DMARDs). The secondary objective was to compare clinical and MSUS features between PsA patients treated with bDMARDs with and without concomitant synthetic (s) DMARDs. We evaluated 102 patients with PsA treated with bDMARDs. The bDMARD dosage tapering had been made in patients with a maintained remission or minimal disease activity (MDA) according to their attending rheumatologist and with the patient acceptance. The bDMARD tapering consisted of the following: increase the interval between doses for subcutaneous bDMARDs or reduction of the dose for intravenous bDMARDs. The clinical evaluation consisted of a dermatologic and rheumatologic assessment of disease activity. The presence of B-mode and Doppler synovitis, tenosynovitis, enthesopathy, and paratenonitis was investigated by a rheumatologist blinded to drug dosage, clinical assessments, and laboratory results. Seventy-four (72.5 %) patients received full dosage of bDMARDs and 28 (27.5 %) received tapered dosage. The duration with biologic therapy and with current biologic therapy was significantly higher in patients with tapered dosages (p = 0.008 and p = 0.001, respectively). We found no significant differences between clinical, laboratory, and US variables, both for BM and CD between patients with full and tapered dosage and between patients with and without concomitant sDMARD. Clinical assessment, MSUS variables, and MDA status are similar in patients receiving full and tapered dosage of bDMARDs.

Treatment options for juvenile-onset systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an inflammatory chronic disease characterized by the presence of activated helper T-cells that induce a B-cell response, resulting in the secretion of pathogenic autoantibodies and the formation of immune complexes. SLE in children is a disease of low prevalence with a wide range of clinical manifestations, which means that the number of randomized controlled studies are few and usually involve a small number of patients. In recent years, new therapeutic agents have appeared and the role of older treatments has been clarified. Many of these treatments are designed to reduce inflammation. The spectrum is broad and ranges from traditional nonsteroidal anti-inflammatory drugs (NSAIDs) to cytotoxic agents that have anti-inflammatory effects. The current treatment of children or adults depends on the clinical expression of the disease. Minor manifestations usually respond to the administration of NSAIDs, low doses of corticosteroids, hydroxychloroquine, or methotrexate. Thalidomide could be used for refractory skin lesions. Major manifestations can endanger the patient's life and require early, aggressive treatment. Kidney disease and other manifestations have been related to the formation or deposit of tissular immune complexes. Therefore, for years the main aim of treatment has been to suppress the immune response. The immunosuppressant treatments used in children with SLE include high doses of corticosteroids, azathioprine, methotrexate, cyclosporine, and cyclophosphamide. Several combinations of medications have been used to obtain a rapid remission or to reduce the risk of toxicity of prolonged administration of cytotoxic agents. Intravenous gamma-globulin has been successfully used in the treatment of lupus nephritis, vasculitis, and acute thrombocytopenia. In spite of numerous published studies, the use of these drugs is still controversial. The immunosuppression achieved with these treatments is nonspecific, not always effective, and associated with significant toxicities; the most significant being growth retardation, accelerated atherosclerosis and severe infectious complications. The purpose of new biological therapies is to achieve specific immunosuppression, which makes it possible to design more effective and less toxic therapeutic strategies. Mycophenolate mofetil is a promising alternative in patients who do not respond to high doses of cyclophosphamide or azathioprine. Some recently developed monoclonal antibodies such as anti-CD40L or anti-IL-10, or other molecules such as LJP394 may prove useful in the near future. Finally, stem cell transplantation may be proposed in patients with severe juvenile-onset SLE who do not respond to any treatment.

Ultrasound joint inflammation in rheumatoid arthritis in clinical remission: how many and which joints should be assessed?

OBJECTIVE: To investigate the sensitivity for detecting subclinical synovitis of different reduced joint ultrasound (US) assessment models as compared with a comprehensive US assessment in rheumatoid arthritis (RA) patients in clinical remission. METHODS: Sixty-seven RA patients (50 women, 17 men) in clinical remission as judged by their consultant rheumatologist and treated with methotrexate were prospectively recruited. Patients were evaluated for disease activity according to the Disease Activity Score in 28 joints (DAS28) and the Simplified Disease Activity Index (SDAI) by the same investigator. Each patient underwent a 44-joint B-mode and power Doppler (PD) assessment by a rheumatologist blinded to the clinical and laboratory data. B-mode synovial hypertrophy (SH) and synovial PD signal were scored from 0-3 at each joint. Global indices for SH and PD signal were calculated for the 44-joint and different joint combination models for each patient. RESULTS: SH was detected in 87.8% of patients with a DAS28 <2.6 and in 81.8% of patients with an SDAI <3.3. Synovial PD signal was detected in 46.3% of patients with a DAS28 <2.6 and in 36.4% of patients with an SDAI <3.3. Wrist, second through fifth metacarpophalangeal (MCP), ankle, and second through fifth metatarsophalangeal (MTP) joint and 12-joint US assessments showed the highest correlations with the comprehensive US assessment. The wrist, MCP, ankle, and MTP joint US assessment showed the highest sensitivity for detecting SH and synovial PD signal in patients in remission according to the DAS28 and SDAI as compared to the comprehensive US assessment. CONCLUSION: US assessment of the wrist, MCP, ankle, and MTP joints can be highly sensitive for detecting residual B-mode and Doppler joint inflammation in RA patients.

Association between anti-cyclic citrullinated peptide antibodies and ischemic heart disease in patients with rheumatoid arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease that may not always be related to the presence of traditional cardiovascular risk factors. The aim of this study was to determine if anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with cardiovascular disease in patients with RA. METHODS: Anti-CCP antibodies were determined by enzyme-linked immunosorbent assay in the earliest serum sample available from 937 patients with a diagnosis of RA. We studied the relationship between anti-CCP antibodies with traditional cardiovascular risk factors and cardiovascular events. RESULTS: We found positive anti-CCP antibodies (>25 units/ml) in 672 patients (71.7%). There was no association between the anti-CCP antibodies and cardiovascular risk factors such as smoking, hypertension, dyslipidemia, being overweight, or diabetes mellitus. However, patients who had positive anti-CCP antibodies experienced more frequent ischemic heart disease (6.5% versus 2.6%; odds ratio [OR] 2.58, 95% confidence interval [95% CI] 1.17-5.65) and had higher mortality rates (11.2% versus 6.8%; OR 1.72, 95% CI 1.01-2.91). Similar results were obtained when we considered anti-CCP titers 20-fold higher (>500 units/ml). Multivariable analysis showed that ischemic heart disease is independently associated with positive anti-CCP antibodies (OR 2.8, 95% CI 1.19-6.56; P = 0.009). CONCLUSION: Anti-CCP antibodies in patients with RA are independently associated with the development of ischemic heart disease.

Anti-Sa sera from patients with rheumatoid arthritis contain at least 2 different subpopulations of anti-Sa antibodies.

OBJECTIVE: Anti-Sa antibodies have been described to be a highly specific marker for rheumatoid arthritis (RA). We demonstrate the existence of 2 different subsets of anti-Sa antibodies, only one of which is specific for RA. Our objective was to purify the Sa antigen, and to achieve partial characterization of these proteins. METHODS: Saline extract and mitochondrial extract from human placenta were used as antigenic sources. Antigens were purified by immunoaffinity chromatography and studied by ELISA and immunoblotting. RESULTS: Three antigenically active bands of 68, 50, and 46 kDa were purified from the saline extract by immunoaffinity chromatography. Two other bands of 29 and 10 kDa that do not react with anti-Sa antibodies were obtained as well. The 68 kDa band was purified from a mitochondrial extract. These bands are not the same as other known mitochondrial autoantigens such as M2, M4, or M9. The amino terminal sequence of the 68 kDa Sa band is DEPKXEVP. The sequence of the 68 kDa Sa band is not compiled in the databases we searched, as either aminoterminal or internal sequence. Antibodies to 50/46 kDa anti-Sa bands detected by immunoblotting were highly specific for RA, while the 68 kDa antigen reacted in ELISA with sera from patients with RA and systemic lupus erythematosus, the latter showing a marked increase in features of RA. Antibodies directed against the 68 and 50/46 kDa Sa bands fluctuated with time, the 50/46 kDa anti-Sa antibodies present during the active period of the disease, and the 68 kDa anti-Sa antibodies during the remission period. CONCLUSION: At least 2 subsets of autoantibodies are present in anti-Sa sera, one directed against a 68 kDa Sa protein and another to the typical 50/46 bands of the Sa system.