Objective: Autoreactive B cells play a key role in tissue injury in systemic autoimmune disease, and therefore a treatment resulting in B cell depletion could have benefit. This open‐label study was undertaken to evaluate the efficacy of the anti‐CD20 monoclonal antibody rituximab in the treatment of lupus nephritis.Methods: Lupus patients with active proliferative nephritis (4 with focal disease and 6 with diffuse disease) received rituximab (4 weekly infusions of 375 mg/m²) combined with oral prednisolone. Clinical, laboratory, and immunologic responses, including peripheral lymphocyte subsets measured by flow cytometry, were prospectively assessed at monthly intervals for 12 months. Complete remission of nephritis was defined as normal serum creatinine and albumin levels, inactive urine sediment, and 24‐hour urinary protein 50% improvement in all renal parameters that were abnormal at baseline.Results: B cell depletion lasted from 1 month to 7 months and was well tolerated. Partial remission was achieved in 8 of 10 patients within a median of 2 months (range 1–4 months); in 5 of them, complete remission was subsequently established (at a median of 3 months from baseline), and it was sustained at 12 months in 4. As early as 1 month from baseline, the expression of the costimulatory molecule CD40 ligand on CD4+ T cells was decreased by 4‐fold, and it was almost blocked when partial remission was clinically evident. The expression of T cell activation markers CD69 and HLA–DR was significantly decreased at time points when partial remission was observed, and was further decreased during complete remission. In contrast, in patients who did not exhibit a response or when relapse was detected in patients in whom an initial remission had been achieved, such decreases were not prominent. Serum concentrations of double‐stranded DNA autoantibodies were decreased in all patients, regardless of clinical outcome.Conclusion: Following B cell depletion, clinical remission of lupus nephritis is associated with a decrease in T helper cell activation, suggesting an additional role for B cells, independent of autoantibody production, in promoting disease. A controlled trial to confirm these promising clinical results is warranted.

Objectives To identify overall disease course, progression patterns and risk factors predictive for progressive interstitial lung disease (ILD) in patients with systemic sclerosis-associated ILD (SSc-ILD), using data from the European Scleroderma Trials And Research (EUSTAR) database over long-term follow-up. Methods Eligible patients with SSc-ILD were registered in the EUSTAR database and had measurements of forced vital capacity (FVC) at baseline and after 12±3 months. Long-term progressive ILD and progression patterns were assessed in patients with multiple FVC measurements. Potential predictors of ILD progression were analysed using multivariable mixed-effect models. Results 826 patients with SSc-ILD were included. Over 12±3 months, 219 (27%) showed progressive ILD: either moderate (FVC decline 5% to 10%) or significant (FVC decline >10%). A total of 535 (65%) patients had multiple FVC measurements available over mean 5-year follow-up. In each 12-month period, 23% to 27% of SSc-ILD patients showed progressive ILD, but only a minority of patients showed progression in consecutive periods. Most patients with progressive ILD (58%) had a pattern of slow lung function decline, with more periods of stability/improvement than decline, whereas only 8% showed rapid, continuously declining FVC; 178 (33%) experienced no episode of FVC decline. The strongest predictive factors for FVC decline over 5 years were male sex, higher modified Rodnan skin score and reflux/dysphagia symptoms. Conclusion SSc-ILD shows a heterogeneous and variable disease course, and thus monitoring all patients closely is important. Novel treatment concepts, with treatment initiation before FVC decline occurs, should aim for prevention of progression to avoid irreversible organ damage.

Behçet's disease (BD) is a multisystem, chronic-relapsing, inflammatory disorder classified among the vasculitides [ 1 , 2 ]. It has a worldwide distribution being more prevalent in the Middle East, Far East and the Mediterranean basin [ 3 ]. The diagnosis is entirely based on clinical grounds since no pathognomonic laboratory findings exist. International study group classification criteria used for BD patients participating in research protocols depend on the presence of recurrent oral ulceration plus any two of the following: recurrent genital ulcerations, ocular lesions (anterior or posterior uveitis, or cells in the vitreous on slit lamp examination, or retinal vasculitis), typical skin lesions (erythema nodosum, pseudofollicullitis) and a positive pathergy (skin hyperreactivity) test [ 4 , 5 ]. The clinical picture of BD is diverse and while recurrent mucocutaneous lesions are usually the only symptoms at the onset of the disease, most patients develop ocular and/or articular, vascular, central nervous system and gastrointestinal inflammation later on. Vital organ involvement may lead, despite treatment, not only to severe morbidity but also to increased mortality especially among young males [ 1 , 2 , 6 ].

Results from clinical trials of biologic anti-TNF drugs performed in the late 1990s confirmed the biological relevance of TNF function in the pathogenesis of chronic noninfectious inflammation of joints, skin and gut, which collectively affects 2–3% of the population. Up to April 2009, more than two million patients worldwide have received the first marketed drugs, namely the monoclonal anti-TNF antibodies infliximab and adalimumab and the soluble TNF receptor etanercept. All three are equally effective in rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, but, for not clearly defined reasons, only the monoclonal antibodies are effective in inflammatory bowel disease. About 60% of patients who do not benefit from standard nonbiologic treatments for these diseases respond to TNF antagonists. Less than half of responding patients achieve complete remission of disease. Importantly, some of those patients with rheumatoid arthritis in whom long-term anti-TNF therapy induced disease remission remain disease-free after discontinuation of any kind of treatment. There are not yet reliable predictors of which patients will or will not respond on anti-TNF therapy, whereas subsequent loss of an initial clinical response occurs frequently. The spectrum of efficacy anti-TNF therapies widens to include diseases such as systemic vasculitis and sight-threatening uveitis. While paradoxical new adverse effects are recognized, i.e. exacerbation or development of new onset psoriasis, reactivation of latent tuberculosis remains the most important safety issue of anti-TNF therapies. Clinical practice guidelines and consensus statements on the criteria of introduction, duration of treatment and cessation of TNF antagonists, including safety issues, are under constant revision as data from longer periods of patient exposure accumulate. It is hoped that more efficacious drugs that will ideally target the deleterious proinflammatory properties of TNF without compromising its protective role in host defense and (auto)immunity will be available in the near future.

Background: Ultrasonography of temporal arteries is not commonly used in the approach of patients with suspected giant cell arteritis (GCA) in clinical practice. A meta-analysis of primary studies available through April 2004 concluded that ultrasonography could indeed be helpful in diagnosing GCA. We specifically re-examined the diagnostic value of the ultrasonography-derived halo sign, a dark hypoechoic circumferential thickening around the artery lumen, indicating vasculitic wall edema, in GCA. Methods: Original, prospective studies in patients with suspected GCA that examined ultrasonography findings of temporal arteries using the ACR 1990 classification criteria for GCA as reference standard, published through 2009, were identified. Only eight studies involving 575 patients, 204 of whom received the final diagnosis of GCA, fulfilled technical quality criteria for ultrasound. Weighted sensitivity and specificity estimates of the halo sign were assessed, their possible heterogeneity was investigated and pooled diagnostic odds ratio was determined. Results: Unilateral halo sign achieved an overall sensitivity of 68% (95% CI, 0.61-0.74) and specificity of 91% (95% CI, 0.88-0.94) for GCA. The values of inconsistency coefficient (I²) of both sensitivity and specificity of the halo sign, showed significant heterogeneity concerning the results between studies. Pooled diagnostic odds ratio, expressing how much greater the odds of having GCA are for patients with halo sign than for those without, was 34 (95% CI, 8.21-138.23). Diagnostic odds ratio was further increased to 65 (95% CI, 17.86-236.82) when bilateral halo signs were present (sensitivity/specificity of 43% and 100%, respectively). In both cases, it was found that DOR was constant across studies. Conclusion: Temporal artery edema demonstrated as halo sign should be always looked for in ultrasonography when GCA is suspected. Providing that currently accepted technical quality criteria are fulfilled, halo sign's sensitivity and specificity are comparable to those of autoantibodies used as diagnostic tests in rheumatology. Validation of revised GCA classification criteria which will include the halo sign may be warranted.