Clinical significance of endothelial vasodilatory function evaluated by EndoPAT in patients with systemic sclerosis.

Endothelial dysfunction is a hallmark of vasculopathy associated with systemic sclerosis (SSc). Reactive hyperemia peripheral arterial tonometry is a rapid and non-invasive technique to assess peripheral microvascular endothelial function by measuring changes in digital pulse volume during reactive hyperemia. Low scores of the reactive hyperemia index (RHI) imply an impaired vasodilatory response and, accordingly, impaired endothelial and vascular health.

Pharmacological Inhibition of Toll-Like Receptor-4 Signaling by TAK242 Prevents and Induces Regression of Experimental Organ Fibrosis.

Systemic sclerosis (SSc) is a poorly understood heterogeneous condition with progressive multi-organ fibrosis. Recent genetic and genomic evidence suggest a pathogenic role for dysregulated innate immunity and toll-like receptor (TLR) activity in SSc. Levels of both TLR4, as well as certain endogenous TLR ligands, are elevated in skin and lung tissues from patients with SSc and correlate with clinical disease parameters.

Prediction of therapeutic response before and during i.v. cyclophosphamide pulse therapy for interstitial lung disease in systemic sclerosis: A longitudinal observational study.

There have been no established parameters to predict responsiveness to i.v. cyclophosphamide (IVCY) pulse therapy in combination with corticosteroids in patients with interstitial lung disease (ILD) related to systemic sclerosis (SSc).

Gastroesophageal Reflux Disease-Related Disorders of Systemic Sclerosis Based on the Analysis of 66 Patients.

Background/aims: Gastroesophageal reflux disease (GERD)-related disorders of systemic sclerosis (SSc) patients have not been adequately investigated.

Methods: Sixty-six SSc patients (5 males and 61 females; 56.6 ± 14.

TLR4-dependent fibroblast activation drives persistent organ fibrosis in skin and lung.

Persistent fibrosis in multiple organs is the hallmark of systemic sclerosis (SSc). Recent genetic and genomic studies implicate TLRs and their damage-associated molecular pattern (DAMP) endogenous ligands in fibrosis. To test the hypothesis that TLR4 and its coreceptor myeloid differentiation 2 (MD2) drive fibrosis persistence, we measured MD2/TLR4 signaling in tissues from patients with fibrotic SSc, and we examined the impact of MD2 targeting using a potentially novel small molecule.

Clinical features of Stevens-Johnson syndrome and toxic epidermal necrolysis.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, but these conditions are associated with high mortality. There have been few reports of SJS and TEN in children. The aim of this study was to evaluate the clinical features and outcomes of SJS and TEN in a group of Japanese children.

A possible implication of reduced levels of LIF, LIFR, and gp130 in vasculopathy related to systemic sclerosis.

Leukemia inhibitory factor (LIF) is a member of IL-6 family, which serves as a potent chemoattractant for neutrophils as well as a potent angiostatic factor. LIF has been implicated in various autoimmune inflammatory diseases, but its role still remains elusive in systemic sclerosis (SSc). Therefore, we investigated the potential role of LIF in the development of SSc by evaluating the clinical correlation of serum LIF levels, the expression of LIF and its receptors in skin samples, and in vitro experiments with human dermal microvascular endothelial cells.

Efficacy and safety of oral propranolol for infantile hemangioma in Japan.

Background: There have been few reports on the efficacy and safety of oral propranolol at 3 mg/kg/day for infantile hemangioma (IH) in Japanese patients.

Methods: A multicenter, open-label phase III study was conducted to evaluate the efficacy and safety of oral propranolol solution in Japanese infants aged 35-150 days with proliferating IH. Thirty-two patients were enrolled in the study, received propranolol solution for 24 weeks at 3 mg/kg/day, and completed the study.

Plasma plasmin-α2-plasmin inhibitor complex levels may predict the effect of cyclophosphamide for systemic sclerosis-related interstitial lung disease.

Objectives: Intravenous pulse cyclophosphamide (IVCY) is the first-line treatment for systemic sclerosis-associated interstitial lung disease (SSc-ILD). So far, there is no useful predictive marker for IVCY efficacy against SSc-ILD, although potential candidates are parameters reflecting vascular activation. Since plasma levels of plasmin-α2-plasmin inhibitor complex (PIC) serve as a potential biomarker of SSc vasculopathy, we evaluated the usefulness of plasma PIC levels as an indicator for IVCY efficacy against SSc-ILD.

Tenascin-C drives persistence of organ fibrosis.

The factors responsible for maintaining persistent organ fibrosis in systemic sclerosis (SSc) are not known but emerging evidence implicates toll-like receptors (TLRs) in the pathogenesis of SSc. Here we show the expression, mechanism of action and pathogenic role of endogenous TLR activators in skin from patients with SSc, skin fibroblasts, and in mouse models of organ fibrosis. Levels of tenascin-C are elevated in SSc skin biopsy samples, and serum and SSc fibroblasts, and in fibrotic skin tissues from mice.

A potential contribution of antimicrobial peptide LL-37 to tissue fibrosis and vasculopathy in systemic sclerosis.

Background: LL-37 is an antimicrobial peptide with pleiotropic effects on the immune system, angiogenesis and tissue remodelling. These are cardinal pathological events in systemic sclerosis (SSc).

Objectives: To elucidate the potential role of LL-37 in SSc.

Association of anti-RNA polymerase III antibody and silicone breast implants in patients with systemic sclerosis.

Systemic sclerosis (SSc) is believed to be caused by a complex interplay between genetic factors and environmental influences. Although silicone has been considered to be a candidate of environmental agents, clinical data presented so far fail to show a significant association between silicone breast implant (SBI) and the development of SSc. Because we recently experienced two consecutive SSc patients with anti-RNA polymerase III (RNAP III) antibody who underwent SBI, we here investigated the association of SBI history with the development of SSc positive for anti-RNAP III antibody.

Scleroderma en coup de sabre with recurrent episodes of brain hemorrhage.

We report a 39-year-old man referred to our facility with linear sclerotic lesions along the several Blaschko's lines of the scalp. A year before the referral, he had had an episode of brain hemorrhage, although there was no evidence of vascular malformation or any other risk factors of brain hemorrhage for his young age. On the diagnosis of scleroderma en coup de sabre, prednisolone intake was initiated, and the skin lesions were well controlled.

Serum omentin levels: A possible contribution to vascular involvement in patients with systemic sclerosis.

Adipokines have been shown to be potentially involved in various pathological processes of systemic sclerosis (SSc), including inflammation, vasculopathy and fibrosis, through their pleiotropic effects. Omentin is a member of the adipokines, and has a protective effect against vascular inflammation and pathological remodeling leading to atherosclerosis as well as a vasodilatory effect. To assess the potential role of omentin in the development of SSc, we determined serum omentin levels by enzyme-linked immunosorbent assay in 66 SSc and 21 control subjects and evaluated their clinical correlation.

Association of anti-RNA polymerase III antibody and malignancy in Japanese patients with systemic sclerosis.

Patients with systemic sclerosis (SSc) have an increased risk of malignancy compared with the general population. Recently, SSc patients with anti-RNA polymerase III antibody have been reported to have an increased risk of malignancy as compared with those with other disease-specific autoantibodies in US, European and Australian populations. Therefore, we studied the relationship between disease-specific autoantibodies and malignancy in 261 Japanese SSc patients.

Serum vaspin levels: A possible correlation with digital ulcers in patients with systemic sclerosis.

Vaspin is an adipokine implicated in vascular inflammation and remodeling. We herein evaluated the clinical correlation of serum vaspin levels in systemic sclerosis (SSc). Consistent with previous reports, 12% of subjects exhibited serum vaspin levels over 10 ng/mL, likely due to genetic effects.

A possible contribution of endothelial CCN1 downregulation due to Fli1 deficiency to the development of digital ulcers in systemic sclerosis.

CCN1 is a pleiotropic molecule involved in angiogenesis and postnatal vasculogenesis, both of which are impaired in systemic sclerosis (SSc). To elucidate the potential role of CCN1 in the development of SSc, we investigated CCN1 expression in the lesional skin of SSc patients and SSc animal models and the clinical correlation of serum CCN1 levels. CCN1 expression was markedly decreased in dermal small blood vessels of SSc patients compared with those of healthy controls, while comparable between normal and SSc dermal fibroblasts.

Late-onset anaphylactic reactions following i.v. cyclophosphamide pulse in a patient with systemic sclerosis and systemic lupus erythematosus overlap syndrome.

Late-onset anaphylactic reaction is a rare adverse effect of i.v. cyclophosphamide pulse (IVCY), which is caused by cyclophosphamide metabolites.

Serum levels of matrix metalloproteinase-13 in patients with eosinophilic fasciitis.

Matrix metalloproteinase-13 (MMP-13), a member of the collagenase family, has been implicated in the pathogenesis of connective tissue diseases characterized by extracellular matrix remodeling. Since serum MMP-13 levels reflect disease severity of systemic sclerosis and localized scleroderma, we evaluated the clinical significance of serum MMP-13 levels in eosinophilic fasciitis (EF). All the EF patients had serum MMP-13 levels lower than the mean - 2SD of healthy controls.