Objective. To assess the efficacy of rituximab (RTX) in SSc.Methods. Fourteen patients with SSc were evaluated. Eight patients were randomized to receive two cycles of RTX at baseline and 24 weeks [each cycle consisted of four weekly RTX infusions (375 mg/m2)] in addition to standard treatment, whereas six patients (control group) received standard treatment alone. Lung involvement was assessed by pulmonary function tests (PFTs) and chest high-resolution CT (HRCT). Skin involvement was assessed both clinically and histologically.Results. There was a significant increase of forced vital capacity (FVC) in the RTX group compared with baseline (mean ± s.d.: 68.13 ± 19.69 vs 75.63 ± 19.73, at baseline vs 1-year, respectively, P = 0.0018). The median percentage of improvement of FVC in the RTX group was 10.25%, whereas that of deterioration in the controls was 5.04% (P = 0.002). Similarly, diffusing capacity of carbon monoxide (DLCO) increased significantly in the RTX group compared with baseline (mean ± s.d.: 52.25 ± 20.71 vs 62 ± 23.21, at baseline vs 1-year respectively, P = 0.017). The median percentage of improvement of DLCO in the RTX group was 19.46%, whereas that of deterioration in the control group was 7.5% (P = 0.023). Skin thickening, assessed with the Modified Rodnan Skin Score (MRSS), improved significantly in the RTX group compared with the baseline score (mean ± s.d.: 13.5 ± 6.84 vs 8.37 ± 6.45 at baseline vs 1-year, respectively, P < 0.001).Conclusion. Our results indicate that RTX may improve lung function in patients with SSc. To confirm our encouraging results we propose that larger scale, multicentre studies with longer evaluation periods are needed.

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Objective. Dkk-1 is an inhibitory molecule that regulates the Wnt pathway, which controls osteoblastogenesis. This study was undertaken to explore the potential role of Dkk-1 in ankylosing spondylitis (AS), a prototypical bone-forming disease.Methods. Serum Dkk-1 levels were measured in 45 patients with AS, 45 patients with rheumatoid arthritis (RA), 15 patients with psoriatic arthritis (PsA), and 50 healthy subjects by sandwich enzyme-linked immunosorbent assay (ELISA). A functional ELISA was used to assess the binding of Dkk-1 to its receptor (lowdensity lipoprotein receptor-related protein 6). Furthermore, we studied the effect of sera from patients with AS and healthy subjects on the activity of the Wnt pathway in the Jurkat T cell model, with and without a neutralizing anti-Dkk-1 monoclonal antibody, by Western immunoblotting.Results. Serum Dkk-1 levels were significantly increased in patients with AS (mean ؎ SEM 2,730 ؎ 135.1 pg/ml) as compared with normal subjects (P ‫؍‬ 0.040), patients with RA (P ‫؍‬ 0.020), and patients with PsA (P ‫؍‬ 0.049). Patients with AS receiving anti-tumor necrosis factor ␣ (anti-TNF␣) treatment had significantly higher serum Dkk-1 levels than patients with AS not receiving such treatment (P ‫؍‬ 0.007). Patients with AS studied serially prior to and following anti-TNF␣ administration exhibited a significant increase in serum Dkk-1 levels (P ‫؍‬ 0.020), in contrast to patients with RA, who exhibited a dramatic decrease (P < 0.001). Jurkat cells treated with serum from AS patients exhibited increased Wnt signaling compared with cells treated with control serum. In that system, Dkk-1 blockade significantly enhanced Wnt signaling in control serum-treated, but not AS serum-treated, Jurkat T cells.Conclusion. Our findings indicate that in patients with AS, circulating bone formation-promoting factors functionally prevail. This can be at least partially attributed to decreased Dkk-1-mediated inhibition.

Spondyloarthropathies (SpA) include many different forms of inflammatory arthritis and can affect the spine (axial SpA) and/or peripheral joints (peripheral SpA) with Ankylosing spondylitis (AS) being the prototype of the former. Extra-articular manifestations, like uveitis, psoriasis and inflammatory bowel disease (IBD) are frequently observed in the setting of SpA and are, in fact, part of the SpA classification criteria. Bowel involvement seems to be the most common of these manifestations. Clinically evident IBD is observed in 6%-14% of AS patients, which is significantly more frequent compared to the general population. Besides, it seems that silent microscopic gut inflammation, is evident in around 60% in AS patients. Interestingly, occurrence of IBD has been associated with AS disease activity. For peripheral SpA, two different forms have been proposed with diverse characteristics. Of note, SpA (axial or peripheral) is more commonly observed in Crohn’s disease than in ulcerative colitis. The common pathogenetic mechanisms that explain the link between IBD and SpA are still ill-defined. The role of dysregulated microbiome along with migration of T lymphocytes and other cells from gut to the joint (“gut-joint” axis) has been recognized, in the context of a genetic background including associations with alleles inside or outside the human leukocyte antigen system. Various therapeutic modalities are available with monoclonal antibodies against tumour necrosis factor, interleukin-23 and interleukin-17, being the most effective. Both gastroenterologists and rheumatologists should be alert to identify the co-existence of these conditions and ideally follow-up these patients in combined clinics.

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