Forearm porphyrin levels evaluated by digital imaging system are increased in patients with systemic sclerosis compared with patients in pre-clinical stage.

We hypothesized that changes in skin characteristics on the forearm could be useful for early diagnosis of systemic sclerosis (SSc). We used VISIA digital imaging system to investigate this possibility for the first time. Twenty-eight Japanese patients who were diagnosed with typical or very early diagnosis of SSc (VEDOSS) were enrolled in this study, and ten age- and gender-matched patients with other disorders were included as a control group. Eight skin characteristics were analyzed. Our method of evaluating forearm skin characteristics was shown to be reproducible. The scores of WRINKLES, TEXTURE, PORES, and PORPHYRINS were higher in SSc subjects with sclerotic forearm skin (SSc forearm+; 11.004, 5.116, 3.230, and 0.084, respectively) and those without (SSc forearm-: 11.915, 4.898, 2.624, 0.0616, respectively) than in the non-SSc control subjects (10.075, 4.496, 2.459, 0.0223, respectively). Also, the scores of SPOTS, TEXTURE, PORES, UV SPOTS, BROWN SPOTS, and PORPHYRINS were elevated in SSc forearm+ (3.182, 5.116, 3.230, 5.761, 6.704, 0.084, respectively) and SSc forearm- patients (2.391, 4.898, 2.624, 9.835, 5.798, 0.0616, respectively) compared with those with VEDOSS (2.362, 4.738, 2.234, 5.999, 4.898, 0.0169, respectively). We found statistical significance in the difference in score of PORPHYRINS between SSc forearm- and VEDOSS groups (p = 0.044), and between SSc forearm+ and VEDOSS groups (p = 0.012). Therefore, they can be used to differentiate VEDOSS from early or mild SSc cases, which is sometimes clinically problematic. Our study also suggests that the porphyrin research will lead to a better understanding of SSc pathogenesis.

Up-regulation of IGF-1, RANTES and VEGF in patients with anti-centromere antibody-positive early/mild systemic sclerosis.

OBJECTIVE: Multiple cytokine network may control the pathogenesis of vasculopathy in patients with systemic sclerosis (SSc). We aimed at comparing angiogenic cytokine profile among SSc patients at various clinical stage. METHODS: We divided nine patients with anti-centromere antibody (ACA) who were suspected of SSc and diagnosed as having SSc into three groups (group1: pre-clinical stage of SSc, group2: mild/early SSc and group3: typical lcSSc) according to the ACR/EULAR2013 classification criteria or ACR1980 preliminary classification, and serum sample were obtained from them. We evaluated the expression levels of 20 cytokines by membrane array. RESULTS: Average values of EGF, ENA-78, bFGF, IGF-I, IL-8, MCP-1, TGF-ß1, thrombopoietin, VEGF and VEGF-D in group2 were increased compared as those of group1 more than twofold. Statistically significant difference was found in serum levels of IGF-1, RANTES and VEGF between group1 and group2. There was also significant difference in the value of VEGF between group1 and group3. There were mild and significant correlations between serum IGF-1 and RANTES levels (r = 0.721, p = .028). CONCLUSION: IGF-1, RANTES and VEGF are thought to be involved in the disease development from pre-clinical stage of SSc to early/mild SSc. Thus, these cytokines may be utilized as a biomarker for early diagnosis.

2019 Diagnostic criteria for mixed connective tissue disease (MCTD): From the Japan research committee of the ministry of health, labor, and welfare for systemic autoimmune diseases.

OBJECTIVE: To update and revise the diagnostic criteria for mixed connective tissue disease (MCTD) issued by the Japan Research Committee of the Ministry of Health, Labor, and Welfare (MHLW), a round table discussion by experts from rheumatology, dermatology, and pediatric medicine was conducted in multiple occasions. METHODS: The definition of MCTD, and items included in the diagnostic criteria were generated by consensus method and evaluation using clinical data of typical and borderline cases of MCTD, by applying to the diagnostic criteria for MCTD proposed in 1996 and 2004 by the Research Committee of MHLW. RESULTS: To the end, all committee members reached consensus. Then, the criteria were assessed in an independent validation cohort and tested against preexisting criteria. The revised criteria facilitate an understanding of the overall picture of this disease by describing the concept of MCTD, common manifestations, immunological manifestation and characteristic organ involvement. Conditions with characteristic organ involvement include pulmonary arterial hypertension, aseptic meningitis and trigeminal neuropathy. Even if the overlapping manifestations are absent, MCTD can be diagnosed based on the presence of the characteristic organ involvement. Furthermore, the criteria were validated for applicability in actual clinical cases, and public comments were solicited from the Japan College of Rheumatology and other associated societies. CONCLUSION: After being reviewed through public comments, the revised diagnostic criteria have been finalized.

The effects of bolus supplementation of branched-chain amino acids on skeletal muscle mass, strength, and function in patients with rheumatic disorders during glucocorticoid treatment.

OBJECTIVES: To test the effects of bolus supplementation of branched-chain amino acids (BCAA) on skeletal muscle mass, strength, and function in patients with rheumatic disorders taking glucocorticoid (GC). METHODS: Patients with rheumatic disorders treated with prednisolone (≥10 mg/day) were randomized to ingest additional daily 12 g of BCAA (n = 9) or not (n = 9) for 12 weeks. At baseline, and 4, 8, and 12 weeks, they underwent bioelectrical impedance analysis, muscle strength and functional tests, and computed tomography analysis for cross-sectional area of mid-thigh muscle. RESULTS: Disease activities of the patients were well controlled and daily GC dose was similarly reduced in both groups. Limb muscle mass was recovered in both groups. Whole-body muscle mass and muscle strength and functional mobility were increased only in BCAA (+) group. The effects of BCAA supplementation on recovering skeletal muscle mass were prominent in particular muscles including biceps femoris muscle. CONCLUSIONS: This trial is the first-in-man clinical trial to demonstrate that BCAA supplementation might be safe and, at least in part, improve skeletal muscle mass, strength, and function in patients with rheumatic disorders treated with GC.

Elevated Serum IgG4 Complicated by Pericardial Involvement with a Patchy (18)F-FDG Uptake in PET/CT: Atypical Presentation of IgG4-related Disease.

IgG4-related pericardial involvement has rarely been reported and its clinical features remain unknown. We herein report a case of a 50-year-old woman with pericarditis who presented with a fever, elevated C-reactive protein levels, elevated serum IgG4 concentrations, and thickened pericardium with a patchy (18)F-fluorodeoxyglucose (FDG) uptake. A biopsy specimen of (18)F-FDG accumulated in the mediastinal lymph nodes revealed an abundant infiltration of IgG4-bearing plasma cells without fibrosis. Moderate-dose glucocorticoids promptly resolved the physical, serological, and imaging abnormalities, thus indicating a relatively acute and reversible nature of IgG4-related pericardial involvement.

A muscle-liver-fat signalling axis is essential for central control of adaptive adipose remodelling.

Skeletal muscle has a pleiotropic role in organismal energy metabolism, for example, by storing protein as an energy source, or by excreting endocrine hormones. Muscle proteolysis is tightly controlled by the hypothalamus-pituitary-adrenal signalling axis via a glucocorticoid-driven transcriptional programme. Here we unravel the physiological significance of this catabolic process using skeletal muscle-specific glucocorticoid receptor (GR) knockout (GRmKO) mice. These mice have increased muscle mass but smaller adipose tissues. Metabolically, GRmKO mice show a drastic shift of energy utilization and storage in muscle, liver and adipose tissues. We demonstrate that the resulting depletion of plasma alanine serves as a cue to increase plasma levels of fibroblast growth factor 21 (FGF21) and activates liver-fat communication, leading to the activation of lipolytic genes in adipose tissues. We propose that this skeletal muscle-liver-fat signalling axis may serve as a target for the development of therapies against various metabolic diseases, including obesity.

Quantitative analysis of skeletal muscle mass in patients with rheumatic diseases under glucocorticoid therapy--comparison among bioelectrical impedance analysis, computed tomography, and magnetic resonance imaging.

OBJECTIVES: To determine the availability of bioelectrical impedance analysis (BIA), computed tomography (CT), and magnetic resonance imaging (MRI) for measurement of skeletal muscle mass in patients with rheumatic diseases and quantitatively assess skeletal muscle loss after glucocorticoid (GC) treatment. METHODS: The data from 22 patients with rheumatic diseases were retrospectively obtained. The muscle mass of body segments was measured with a BIA device in terms of skeletal muscle mass index (SMI). Cross-sectional area (CSA) was obtained from CT and MRI scans at the mid-thigh level using the image analysis program. We further assessed the data of three different measurements before and after GC treatment in 7 patients with rheumatic diseases. RESULTS: SMI of whole body was significantly correlated with estimated muscle volume and mid-thigh muscle CSA with CT and MRI (p < 0.01). Significant correlations between SMI and mid-thigh muscle CSA of each leg were also found (p < 0.01). All the three measurements were negatively correlated with GC dosage (p < 0.01). Significant decline in mid-thigh muscle CSA with CT and MRI was found after GC treatment in 7 patients (p < 0.02). Those patients showed significant decline in SMI of whole body after GC treatment, but not in SMI of each leg. On the other hand, significant correlations between mid-thigh muscle CSA with CT and MRI were found before and after GC treatment (p < 0.01). CONCLUSIONS: GC-related skeletal muscle loss could be quantitatively assessed with BIA, CT, or MRI in patients with rheumatic diseases, and CT and MRI appeared to be more accurate than BIA.

[Glucocorticoids].

The established evidence of the rapid effects, along with the growing recognition of their disease-modifying properties has led us to reconsider the potential of glucocorticoids in the treatment of rheumatoid arthritis. Given their acceptable safety profile, especially when used at low dosages, several glucocorticoid-based therapeutic approaches have been explored in order to optimize their clinical benefits, while limiting the adverse effects. Encouraging results on the clinical and sub-clinical effects of low dosages are going to lead to a shift in usual daily practice. Optimizing the use of key non-biologic drugs including glucocorticoids may prolong disease control, thereby delaying the need for costly biologic therapies.