New Therapeutic Strategies for Systemic Sclerosis—a Critical Analysis of the Literature

Systemic sclerosis (SSc) is a multi-system disease characterized by skin fibrosis and visceral disease. Therapy is organ and pathogenesis targeted. In this review, we describe novel strategies in the treatment of SSc. Utilizing the MEDLINE and the COCHRANE REGISTRY, we identified open trials, controlled trials, for treatment of SSc from 1999 to April 2005. We used the terms scleroderma, systemic sclerosis, Raynaud's phenomenon, pulmonary hypertension, methotrexate, cyclosporin, tacrolimus, relaxin, low-dose penicillamine, IVIg, calcium channel blockers, losartan, prazocin, iloprost, N-acetylcysteine, bosentan, cyclophosphamide, lung transplantation, ACE inhibitors, anti-thymocyte globulin, and stem cell transplantation. Anecdotal reports were omitted

Imaging Lung Disease in Systemic Sclerosis

Interstitial lung disease and pulmonary hypertension (PH) are the most common cardiopulmonary findings in patients with systemic sclerosis (SSc). About two thirds of patients suffering from SSc develop scleroderma interstitial lung disease. PH is present in about 20% of SSc patients and is typically associated with severe lung disease, although it may be an isolated manifestation of SSc. High-resolution CT scanning is a key method for evaluating chest involvement. There are four roles of imaging in scleroderma interstitial lung disease: 1) detection of lung involvement, 2) identification of patients likely to respond to treatment, 3) assessment of treatment efficacy, and 4) exclusion of other significant diseases to include PH and cardiac and esophageal abnormalities

Comparative qualitative and quantitative analysis of scleroderma (systemic sclerosis) serologic immunoassays

The heterogeneity of autoantibody specificities occurring in sera from patients with systemic sclerosis (SSc) raised the necessity of developing various methodologies for their detection. A cohort of 150 SSc patients were selected and tested by Indirect Immunofluorescence (IIF), Counterimmunoelectrophoresis (CIE), Immunoblot (IB) using various extracts as antigenic source and RNA precipitation. By preparing a nuclear (IB-nuclear) and a metaphase chromosomal-enriched extract (IB-MC-pellet) from HeLa cells as well as a nucleolar (IB-nucleolar) and a histone (IB-histone) extract from rat liver nuclei, we assessed their sensitivity and specificity for anti-Topo I, anti-U3RNP, anti-H1, anti-snRNPs antibodies and ACA. IB-nuclear revealed the highest frequency of anti-Topo I antibodies, while CIE, IB-nucleolar and IB-MC-pellet, when compared to IB-nuclear showed a sensitivity of 89%, 87% and 95%, respectively. IB-MC-pellet was unique for ACA recognition, while IB-nucleolar and IB-MC-pellet showed excellent sensitivity for anti-U3RNP and anti-H1 antibody detection. We conclude that IB-nuclear is a highly sensitive system for anti-Topo I antibodies determination, but CIE reveals a good sensitivity to be used as a first screening test. IB-nucleolar or IB-MC-pellet are important techniques to detect the variety of antibodies to nucleolus and chromatin-related constituents. A novel specificity against a 28 kD nucleolar protein, non-associated with RNAs is also presented. © 2008 Elsevier Ltd. All rights reserved

Systemic scleroderma in Greece: low mortality and strong linkage with HLA-DRB1*1104 allele

OBJECTIVE—Description of Greek patients with scleroderma with reference to (a) major organ disease, (b) autoantibodies, (c) survival rate, and (d) HLA associations.
METHODS—The clinical files of 254 patients were analysed retrospectively and a standardised clinical chart was completed with age at disease onset, sex, date of first and last visit, clinical and serological findings, organs affected, reasons for death, and HLA class II alleles. HLA class II alleles (DRB1, DQA1, DQB1, DPB1) were determined by polymerase chain reaction amplification using oligopeptide probes. DNA was extracted from 98 patients and 130 Greek controls.
RESULTS—124 patients (49%) had limited systemic sclerosis (lSSc), 114 (45%) had diffuse systemic sclerosis (dSSc), and 16 (6%) had overlap syndromes. Patients with dSSc, compared with lSSc, were characterised by a higher prevalence of lung disease (p=0.0011), oesophageal, heart, and peripheral vessel disease (p=0.027, p=0.0025, and p=0.012, respectively). Anticentromere antibodies (ACA) occurred exclusively in lSSc (34%), whereas antibodies to topoisomerase I (anti-topo I) were associated with dSSc (p<0.0001). Anti-topo I were associated with interstitial pulmonary fibrosis, oesophageal and peripheral vessel disease (p=0.028, p=0.012, and p=0.01, respectively). The HLA-DRB1*1104 allele was associated with the disease (p<0.0001) and anti-topo I (p<0.001), whereas it was not associated with ACA serum reactivity (p<0.001). Renal disease occurred in 4% of patients with SSc. The estimated survival probability for this cohort of patients with SSc, four years after the first visit, is 94.8%.
CONCLUSION—SSc among Greek subjects has the same pattern of organ disease as in other white populations. However, the prevalence of kidney disease is low. The HLA class II DRB1*1104 allele is associated with the disease, with anti-topo I, and not associated with ACA serum reactivity.