The Pathogenesis of Systemic Sclerosis: The Origin of Fibrosis and Interlink with Vasculopathy and Autoimmunity

Systemic sclerosis (SSc) is an autoimmune disease associated with increased mortality and poor morbidity, impairing the quality of life in patients. Whilst we know that SSc affects multiple organs via vasculopathy, inflammation, and fibrosis, its exact pathophysiology remains elusive. Microvascular injury and vasculopathy are the initial pathological features of the disease. Clinically, the vasculopathy in SSc is manifested as Raynaud’s phenomenon (reversible vasospasm in reaction to the cold or emotional stress) and digital ulcers due to ischemic injury. There are several reports that medications for vasculopathy, such as bosentan and soluble guanylate cyclase (sGC) modulators, improve not only vasculopathy but also dermal fibrosis, suggesting that vasculopathy is important in SSc. Although vasculopathy is an important initial step of the pathogenesis for SSc, it is still unclear how vasculopathy is related to inflammation and fibrosis. In this review, we focused on the clinical evidence for vasculopathy, the major cellular players for the pathogenesis, including pericytes, adipocytes, endothelial cells (ECs), and myofibroblasts, and their signaling pathway to elucidate the relationship among vasculopathy, inflammation, and fibrosis in SSc

Interval between symptom onset and diagnosis among patients with autoimmune rheumatic diseases in a multi-ethnic Asian population

10.1111/1756-185X.14165INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES2481061-107

B-Cell Targeted Therapy With Rituximab for Thyroid Eye Disease: Closer to the Clinic

The management of thyroid eye disease (TED) remains a therapeutic challenge. The current established therapies are unsatisfactory in one-third of the patients and have many limitations. Rituximab (RTX) is a CD20+ B-cell depleting monoclonal antibody approved for the treatment of non-Hodgkin lymphomas, chronic lymphocytic leukemia, and rheumatoid arthritis. The early experience with RTX suggests that it is a promising alternative therapy for TED. Rituximab may compare favorably to the conventional glucocorticoid therapy and causes less collateral damage than retrobulbar orbital radiation and decompression surgery. In addition, the preliminary studies on RTX’s proposed mechanism of action have revealed new insights into the pathogenic role of B-cells in TED. We summarize the current literature on the clinical application of RTX in TED and discuss its putative mechanisms of action. (Surv Ophthalmol 58:252-265, 2013. (C) 2013 Elsevier Inc. All rights reserved.

Recommendations for COVID-19 vaccination in people with rheumatic disease: Developed by the Singapore Chapter of Rheumatologists

10.1111/1756-185X.14107INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES246746-75

Disease Characteristics of the Singapore Systemic Sclerosis Cohort

Introduction: Systemic sclerosis (SSc) has one of the worst prognoses among autoimmune diseases. Multi-ethnic Western cohorts have shown ethnic differences in disease characteristics. Due to a paucity of data in Asia, we aimed to describe the disease characteristics and autoantibody profile of Asian SSc patients. Methods: The Singapore SSc database consists of prevalent and incident cases from four institutions. Data were recorded annually according to a standardised protocol. Cumulative disease characteristics were analysed using descriptive statistics. Results: From 2008 to 2012, 200 patients (85.5% females; Chinese 78%, Malays 10.5%, Indians 6%) diagnosed at a mean age of 46 years, fulfilled the American College of Rheumatology (ACR) (88.0%) or the Very Early Diagnosis of SSc (VEDOSS) (12%) criteria. SSc subtypes include limited cutaneous SSc (LcSSc) (32%) or diffuse cutaneous SSc (DcSSc) (37.6%), SSc-overlap syndromes (27.4%) and sine scleroderma (3%). Predominant disease manifestations were Raynaud's phenomenon (n=161, 80.5%), gastrointestinal (GI) (n=125, 62.5%), joint pain (n=116, 58%) and interstitial lung disease (ILD) (n=99, 51.8%). Pulmonary arterial hypertension (PAH) by echocardiography was present in 23.2% (39/168) of patients (mean systolic pulmonary arterial pressure 55.0+19.7mmHg). Renal crisis was rare (n=4, 2%). Anti-nuclear antibodies (ANA) tested positive in 78.7% (155/197), with anti-Scl-70 (69/197, 35.0%), anti-ribonucleoprotein (RNP) (56/192, 29.2%) and anti-Ro60 (40/193, 20.7%) most frequently detected. Anti-centromere antibodies were infrequent (23/190, 12.1%). Treatment included corticosteroids (80.7%), for peripheral vasculopathy (61.4%), GI (68%), PAH (11.2%) and immunosuppression (62.9%). Conclusion: Compared to Caucasian patients, our predominantly Chinese Asian SSc patients were diagnosed at an earlier age, with more severe PAH, less frequent Raynaud's phenomenon, an autoantibody profile characterised by anti-Scl70, anti-RNP and anti-Ro60, infrequently anti-centromere and more patients had DcSSc