Background Effective new therapies are needed for rheumatoid arthritis. Current therapies target the products of activated macrophages; however, T cells also have an important role in rheumatoid arthritis. A fusion protein — cytotoxic T-lymphocyte–associated antigen 4–IgG1 (CTLA4Ig) — is the first in a new class of drugs known as costimulation blockers being evaluated for the treatment of rheumatoid arthritis. CTLA4Ig binds to CD80 and CD86 on antigen-presenting cells, blocking the engagement of CD28 on T cells and preventing T-cell activation. A preliminary study showed that CTLA4Ig may be effective for the treatment of rheumatoid arthritis. Methods We randomly assigned patients with active rheumatoid arthritis despite methotrexate therapy to receive 2 mg of CTLA4Ig per kilogram of body weight (105 patients), 10 mg of CTLA4Ig per kilogram (115 patients), or placebo (119 patients) for six months. All patients also received methotrexate therapy during the study. The clinical response was assessed at six mo...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa035075

Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig.

Within the past decade, musculoskeletal ultrasound (US) has become an established imaging technique for the diagnosis and follow up of patients with rheumatic diseases.1-5 This has been made possible through technological improvements, resulting in faster computers and higher frequency transducers. US is most commonly used in the assessment of soft tissue disease or detection of fluid collection and can also be used to visualise other structures, such as cartilage and bone surfaces.6 7 Owing to the better axial and lateral resolution of US, even minute bone surface abnormalities may be depicted. Thus destructive and/or reparative/hypertrophic changes on the bone surface may be seen before they are apparent on plain x rays or even magnetic resonance imaging.8 However, US wave frequencies cannot penetrate into bone, therefore imaging of intra-articular disease is usually not possible. The “real time” capability of US allows dynamic assessment of joint and tendon movements, which can often aid the detection of structural abnormalities. Advantages of US include its non-invasiveness, portability, relative inexpensiveness, lack of ionising radiation, and its ability to be repeated as often as necessary, making it particularly useful for the monitoring of treatment. US can also be used for guidance of aspiration, biopsy, and injection treatment.9 Most musculoskeletal work is performed using “grey scale”, which means images are produced in a black and white format; each white dot in the image represents a reflected sound wave. Sound waves travel in a similar way to light waves and therefore the denser a material is—for example, bone cortex, the more reflective it is and the whiter it appears on the screen. Water is the least reflective body material and therefore appears as black as the sound waves travel straight through it.

Newer US techniques, which are currently being evaluated, include colour and power …

https://ard.bmj.com/content/annrheumdis/60/7/641.full.pdf

Guidelines for musculoskeletal ultrasound in rheumatology

The association between corticosteroid therapy and subsequent infections was calculated by pooling data from 71 controlled clinical trials. The overall rate of infectious complications was 12.7% in the 2,111 patients randomly allocated to systemic corticosteroids and 8.0% in the 2,087 controls (relative risk [RR], 1.6; 95% confidence interval [CI], 1.3-1.9; P less than .001). The risk of infection was particularly high in patients with neurologic diseases (RR, 2.8; 95% CI, 1.9-4.3; P less than .001) and less pronounced in patients with intestinal (RR, 1.4; 95% CI, 1.1-1.7; P = .02), hepatic (RR, 1.4; 95% CI, 0.9-2.3; P = .25), and renal (RR greater than 1; P = .03) diseases. The rate was not increased in patients given a daily dose of less than 10 mg or a cumulative dose of less than 700 mg of prednisone. With increasing doses the rate of occurrence of infectious complications increased in patients given corticosteroids as well as in patients given placebo, a finding suggesting that not only the corticosteroid but also the underlying disease state account for the steroid-associated infectious complications observed in clinical practice.

/pdf/risk-of-infectious-complications-in-patients-taking-2spbhgubty.pdf

Risk of infectious complications in patients taking glucocorticosteroids.

Objective The characteristic joint damage and disability of rheumatoid arthritis (RA) increase slowly over 10-20 yr. Although it is generally believed that persisting inflammatory synovitis causes joint damage and subsequent disability, the strength of their relationship has not been systematically evaluated. This review describes their progression and interrelationship in treated RA. Methods MEDLINE and Current Contents databases were searched for the combined terms of rheumatoid arthritis AND X-rays, Health Assessment Questionnaire, slow-acting anti-rheumatic drugs and all identifiable synonyms. This search identified 1303 articles and from these we evaluated in detail 23 reports on the progression of joint damage, 12 reports on the progression of disability and 25 reports dealing with their interrelationship. Additional information was obtained from four data sets comprising 725 RA patients studied cross-sectionally and 33-126 cases followed prospectively for 1-5 yr. X-ray damage was primarily assessed by Larsen and Sharp indices, and disability by the Health Assessment Questionnaire (HAQ). Results Joint damage and disability both increase throughout the duration of RA. Although disability (HAQ score) is correlated with disease duration (correlation coefficients between 0.27 and 0.30), the link between X-ray damage and disability is stronger (correlation coefficients between 0.30 and 0.70). In the earliest phases of RA, X-ray damage and HAQ scores are not related. By 5-8 yr, there are significant correlations with correlation coefficients between 0.30 and 0.50. In late RA (>8 yr), most studies show highly significant correlations between 0.30 and 0.70. Conclusions Joint damage progresses constantly over the first 20 yr of RA. It accounts for approximately 25% of disability in established RA. The link between damage and disability is strongest in late (>8 yr) RA. However, avoiding or reducing joint damage in both early and established/late RA is likely to maintain function.

The links between joint damage and disability in rheumatoid arthritis

Objectives. To establish the usefulness of ultrasonography (US) for diagnosing gout and to determine whether there are sonographic features that are characteristic for gout but not for other arthropathies. Methods. We retrospectively compared joint images of gout patients with matching images from patients with other rheumatic conditions. Images of 37 joints of 23 patients with monosodium urate (MSU) crystal-proven gout were reviewed. MSU crystals were identified in at least one joint in each patient. Our control group had 23 randomly selected patients with 33 examined joints with rheumatic conditions other than gout. Results. Specific diagnostic features included a hyperechoic, irregular band over the superficial margin of the articular cartilage described as a double contour sign in 92% of gouty joints and in none of the controls (P < 0.001); hypoechoic to hyperechoic, inhomogeneous material surrounded by a small anechoic rim, representing tophaceous material, was seen in all gouty metatarsophalangeal (MTP) joints, in all metacarpophalangeal (MCP) joints and in none of the controls (P < 0.001); erosions adjacent to tophaceous material were seen in 65% of MTP joints and in 25% of MCP joints. One erosion was seen in a MTP joint in a control patient with psoriatic arthritis. Conclusions. US can detect deposition of MSU crystals on cartilaginous surfaces (P < 0.001) as well as tophaceous material and typical erosions. US may serve as a non-invasive means to diagnose gout.

/pdf/diagnosis-of-gout-by-ultrasound-hdzd6p2r9m.pdf

Diagnosis of gout by ultrasound

The clinical features of rheumatoid arthritis

Sonographic imaging of normal and osteoarthritic cartilage.

OBJECTIVE The aim of this pictorial essay is to describe the sonographic guided approach to investigation and local injection therapy of a small joint in a patient with psoriatic arthritis (PA). METHODS Sonographic pictures are obtained using a high frequency ultrasonography apparatus equipped with a 13-MHz transducer. RESULTS Ultrasonography allows a careful morphostructural assessment of soft tissue involvement in PA patients. Sonographic findings include joint cavity widening, capsular thickening, synovial proliferation, synovial fluid changes, tendon sheath widening. Ultrasound guided placement of the needle within the joint and injection of corticosteroid under sonographic control can be easily performed. CONCLUSIONS High frequency ultrasonography is a quick and safe procedure that allows a useful diagnostic and therapeutic approach in patients with arthritis of small joints.

https://ard.bmj.com/content/annrheumdis/58/10/595.full.pdf

Synovitis of small joints: sonographic guided diagnostic and therapeutic approach

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The clinical features of rheumatoid arthritis

Sonographic imaging of normal and osteoarthritic cartilage.

Synovitis of small joints: sonographic guided diagnostic and therapeutic approach