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Objectives: The aim of this article is to investigate the efficacy and safety of tocilizumab in Japanese patients with systemic sclerosis. Methods: Post hoc subgroup analysis of a global, randomised, controlled trial in patients treated with weekly tocilizumab 162 mg or placebo subcutaneously in a 48-week double-blind period (tocilizumab and placebo groups) followed by tocilizumab for 48 weeks in an open-label extension (continuous-tocilizumab and placebo-tocilizumab groups). Results: Among 20 patients, 12 were randomised to tocilizumab (all had interstitial lung disease) and eight were randomised to placebo (six had interstitial lung disease). The modified Rodnan skin score improved in both treatment groups. The mean change in percent-predicted forced vital capacity was 3.3% [95% confidence interval (CI), −2.5 to 9.0] for tocilizumab and −3.8% (95% CI, −9.9 to 2.2) for placebo in the double-blind period and 2.0% (95% CI, −0.7 to 4.6) for continuous-tocilizumab and −1.4% (95% CI, −6.7 to 4.0) for placebo-tocilizumab in the open-label extension. Rates of serious adverse events per 100 patient-years were 19.3 for tocilizumab and 26.8 for placebo in the double-blind period and 0.0 for continuous-tocilizumab and 13.6 for placebo-tocilizumab in the open-label period. Conclusions: The efficacy and safety of tocilizumab in patients with systemic sclerosis were consistent between the Japanese subpopulation and the global trial population. [ABSTRACT FROM AUTHOR]

Objective: To assess the utility of serum chemokine levels as a prognostic indicator of disease progression in systemic sclerosis (SSc) patients with early onset disease. Methods: Seventy Japanese patients with early onset SSc presenting with diffuse skin sclerosis and/or interstitial lung disease were registered in a multicenter, observational study. Concentrations of CCL2, CCL5, CXCL8, CXCL9, and CXCL10 in serum samples from all patients were measured using cytometric beads array. In 33 patients, chemokine levels were measured each year for 4 years. The ability of baseline chemokine levels to predict changes in clinical features were evaluated statistically by multiple regression analysis. Results: At their first visit, serum levels of CCL2, CCL5, CXCL8, CXCL9, and CXCL10 were significantly elevated in patients with SSc compared with healthy controls. There were significant associations between CCL2 and CXCL8 levels and between CXCL9 and CXCL10 levels in patients. The initial serum CXCL8 levels were significantly associated with the HAQ-DI at the fourth year while the %VC of baseline tended to be negatively associated with HAQ-DI at the fourth year. Initial chemokine levels were not associated with other clinical features including skin thickness score and the respiratory function. Conclusion: Serum CXCL8 level may serve as a prognostic indicator of the physical dysfunction in SSc. Further longitudinal studies of larger populations are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Objective: To clarify those clinical characteristics dependent on patient age at onset of Japanese systemic sclerosis (SSc). Methods: A total of 329 SSc patients treated at Kanazawa University Hospital were enrolled in the study and subsequently categorized into four subgroups depending on age at SSc onset: childhood-onset, young-onset, normal age-onset, and late-onset. The clinical features at the first visit were compared between groups. Factors that correlated with age at onset were also analyzed. Results: The childhood-onset subgroup was characterized by a higher male:female ratio, higher anti-topoisomerase I antibody (Ab) and anti-U3 RNP Ab levels, a higher frequency of pitting scars, and a lower frequency of anticentromere Ab and interstitial lung disease (ILD). The young-onset patients had an increased frequency of anti-U1 RNP Ab and anti-U3 RNP Ab, overlap with other connective tissue diseases, digital ulcers, and pitting scars and a reduced frequency of anticentromere Ab. Patients with late-onset SSc showed a shorter disease duration and an increased frequency of anti-RNA polymerase Ab. Multiple regression analysis showed that anti-topoisomerase I Ab, anti-U1 RNP Ab, pitting scars, and long disease duration were associated with onset at a younger age, whereas anticentromere Ab and ILD were associated with onset at an older age. Conclusions: The clinical phenotype of SSc in Japanese patients showed a tendency to be dependent on age at onset. [ABSTRACT FROM AUTHOR]

Objectives: IgG4-related skin disease is not widely recognized. This prompted us to investigate the clinical and pathological features of five patients we encountered with IgG4-related disease (IgG4-RD) affecting the skin. Methods: We investigated the clinical and pathological features of these five patients, including the distribution, onset, and morphology of eruptions, their pathological and immunohistochemical characteristics, and the occurrence of disease in other organs. Results: The skin lesions were typically erythematous nodules and papules and brown papules like prurigo nodularis, which developed on the face or in the head and neck areas in four patients. Skin lesions were the first clinical manifestation in three patients. All five patients had sialadenitis and/or dacryoadenitis. The mean serum IgG4 concentration was 665.6 ± 410.0 mg/dl. Infiltrations of IgG4-positive plasma cells were observed in both the dermis and subcutaneous tissue. Germinal center formations were seen in three patients. Mild to moderate fibrosis was observed in all patients, and focal obliterative phlebitis in one. The average count of IgG4-positive cells was 67.3/high-power field (23.0-128.6). Wide variation in the numbers of infiltrating IgG4-positive cells was noted. Conclusion: IgG4-RD appears to have a distinctive clinicopathological presentation in the skin, differentiating it from other cutaneous disorders. [ABSTRACT FROM AUTHOR]

We report the first case of a Japanese patient with anti-155/140 antibody-positive juvenile dermatomyositis (JDM). Her clinical features included severe cutaneous involvement. Serum B cell-activating factor levels were significantly increased. Mature class-switched memory B cells accumulated in inflamed muscle tissue but decreased in peripheral blood. These findings indicate that loss of B cell tolerance and accumulation of mature B cells in inflamed muscle tissue play an important role in the pathogenesis of JDM. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prevalence of primary biliary cirrhosis (PBC) and PBC-associated autoantibodies in Japanese systemic sclerosis (SSc) patients. Methods: Clinical data from 225 Japanese SSc patients were retrospectively obtained. Serum samples from these patients were examined for PBC-associated autoantibodies, anti-mitochondrial M2 antibodies (AMA), anti-sp100 antibodies (anti-sp100), and anti-gp210 antibodies (anti-gp210) by enzyme-linked immunosorbent assay. Results: Of 225 patients, 37 (16.4%) had AMA, 13 (5.8%) had anti-sp100, and 3 (1.3%) had anti-gp210. Three patients were positive for both AMA and anti-sp100, and 2 were positive for both AMA and anti-gp210. PBC was found in 22 (9.8%) patients positive for AMA with or without anti-sp100 or anti-gp210, but not in those with anti-sp100 or anti-gp210 without AMA. Furthermore, 13 patients lacking these three antibodies were diagnosed with or suspected of PBC by liver biopsy and/or their clinical manifestation. Multivariable analysis revealed that AMA and anti-centromere antibodies were independently associated with PBC in SSc patients, while anti-sp100 and anti-gp210 were not. Conclusions: This study has demonstrated even higher prevalence of both PBC-associated autoantibodies and PBC in the Japanese SSc population than in the Caucasian SSc population. AMA and anti-centromere antibodies are likely to indicate increasing risk of PBC in SSc patients. [ABSTRACT FROM AUTHOR]

Objective. Although findings of nail-fold capillary changes and reduced red blood cell velocity in SSc patients are well established, studies in adult-onset DM patients are scarce. Our objective was to assess the changes and red blood cell velocity in finger nail-fold capillaries using nail-fold video capillaroscopy (NVC) in patients with adult-onset DM.Methods. This study included 50 patients with adult-onset DM and 20 healthy subjects. A semi-quantitative rating scale was used to score capillaroscopy changes. Red blood cell velocity was evaluated using frame-to-frame determination of the position of capillary plasma gaps.Results. Thirty-seven (74%) patients showed the scleroderma NVC pattern. Patients with the scleroderma pattern exhibited elevated serum creatine kinase levels more frequently and increased visual analogue scale of muscle disease activity. Scores of loss of capillaries were associated with muscle and global disease activity, whereas scores of haemorrhages were associated with skin disease activity. However, NVC findings were not significantly associated with lung involvement. The scores of irregularly enlarged capillaries, haemorrhages and loss of capillaries were reduced after stabilization of disease activity by treatment. The mean red blood cell velocity was not significantly reduced in DM patients compared with healthy controls and was not changed by treatment.Conclusion. Our results suggest that changes in nail-fold capillaries reflect disease activity in DM. Furthermore, the differences found in red blood cell velocity may reflect somewhat distinct microcirculation injuries in DM and SSc. [ABSTRACT FROM PUBLISHER]

Objective. To evaluate the effects of i.v. CYC on the number of circulating endothelial progenitor cells (EPCs) in patients with SSc, and the potential association of the EPC response with CYC’s effect for treating interstitial lung disease (ILD).Methods. This open-label, prospective study involved 12 patients with SSc and alveolitis (CYC group). All patients received six courses of i.v. CYC (0.5 g/m2) at 4-week intervals in combination with low-dose prednisolone. Ten patients were followed for 24 months. Seven SSc patients treated with low-dose prednisolone alone were used as a control for the EPC measurement (control group). Five patients with non-SSc CTD who received i.v. CYC and prednisolone also served as disease controls. EPCs were quantified by the partial enrichment of CD34+ cells followed by three-colour flow cytometry. The circulating levels of vascular injury markers were measured by immunoassay.Results. The EPC count was significantly increased at 2 weeks after treatment in the CYC group (P = 0.02), but not in the control group, while CYC increased EPC count in all disease controls. The SSc patients in the CYC group were divided into five EPC responders and seven EPC non-responders. Circulating vascular injury markers were reduced in the responders, but not in the non-responders. During the 24-month follow-up, 3 of 10 patients developed end-stage lung disease, and all of them were EPC non-responders.Conclusion. A low-dose i.v. CYC induces EPC mobilization, which may contribute to the efficacy for treating SSc-associated ILD. [ABSTRACT FROM PUBLISHER]

Objectives. The purpose of this study was to determine the prevalence of anti-CCP antibodies (anti-CCP Abs) and to assess associations between the presence of anti-CCP Ab and arthritis or arthralgia in SSc patients.Methods. Serum samples were obtained from 146 SSc patients. Anti-CCP Ab, anti-agalactosyl (AG) IgG Ab, IgM-RF, IgG-RF and MMP-3 were determined, respectively.Results. The presence of anti-CCP Ab was found in 18/146 (12%) patients with SSc. Elevated levels of anti-AG IgG Abs, IgM- and IgG-RFs were observed in 50/146 (34%), 17/146 (12%) and 4/146 (3%), respectively. Serum anti-CCP Ab levels were significantly elevated in SSc–RA overlap patients compared with SSc patients with or without arthralgia (P < 0.05 or P < 0.001, respectively). Serum MMP-3 levels did not correlate with the presence of arthritis or arthralgia but were significantly associated with modified Rodnan total skin thickness score. In SSc–RA overlap patients, 10/11 (91%) patients were positive for two or more RA-related Abs.Conclusions. The serum titre of anti-CCP Ab is higher in SSc–RA overlap patients than in SSc patients with or without arthralgia. The finding of high titres of anti-CCP Abs and the elevated levels combinatory with other RA-related Abs may help to define the diagnosis of SSc–RA overlap. MMP-3 might be a better marker to assess skin involvement rather than joint involvement in SSc patients. [ABSTRACT FROM PUBLISHER]

Objective. To assess red blood cell velocity in finger nail-fold capillaries using video capillaroscopy in patients with SSc and other collagen diseases. Methods. This study included 127 patients with SSc as well as patients with SLE (n = 33), DM/PM (n = 21), RA (n = 13) and APS (n = 12), and 20 healthy subjects. Red blood cell velocity was evaluated using frame-to-frame determination of the position of capillary plasma gaps. Results. The mean red blood cell velocity was significantly decreased in patients with SSc compared to healthy controls (63.0% reduction) and patients with other conditions. Mean blood velocity was similar between patients with dcSSc and lcSSc. Importantly, even SSc patients with normal or non-specific nail-fold video capillaroscopic (NVC) patterns or a scleroderma early NVC pattern exhibited a significantly lower red blood cell velocity compared to healthy controls (51.7 and 61.4% reduction, respectively) or patients with other conditions, despite normal or mild capillary changes. Patients with the scleroderma active and late NVC pattern showed a more decreased blood velocity (65.5 and 66.2% reduction, respectively). This reduced blood velocity was significantly associated with NVC findings, including capillary ramification and capillary loss. Although remarkably reduced velocity was observed in SSc patients with intractable digital ulcers (72.1% reduction), it was significantly improved by lipo-prostaglandin E1 (lipo-PGE1) infusion. Conclusion. Our results suggest that reduced blood velocity is a hallmark of SSc. Furthermore, measurement of red blood cell velocity may be useful in evaluating therapeutic effects on microcirculation. [ABSTRACT FROM AUTHOR]