Effect of monthly cyclophosphamide pulses on skin sclerosis in systemic sclerosis

The scleroderma spectrum of disorders includes a number of diseases that have Raynaud’s phenomenon or skin sclerosis in common, comprising (1) limited cutaneous scleroderma; (2) systemic sclerosis (SSc)—the most important form of scleroderma—limited cutaneous SSc, diffuse cutaneous SSc, and overlap syndromes (with features of another autoimmune rheumatic disease, e.g. systemic lupus erythematosus); (3) Raynaud’s phenomenon—autoimmune (with antinuclear or other SSc-associated antibodies) or primary. These conditions affect women four times as often as men, most often beginning in the fifth decade....

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Systemic sclerosis

Oxford Textbook of Rheumatology ◽

10.1093/med/9780199642489.003.0121_update_001 ◽

2013 ◽

pp. 971-988 ◽

Cited By ~ 1

Author(s):

Christopher P. Denton ◽

Pia Moinzadeh

Keyword(s):

Systemic Sclerosis ◽

Cell Injury ◽

Rna Polymerase Iii ◽

Systematic Investigation ◽

Clinical Markers ◽

Topoisomerase 1 ◽

Skin Sclerosis ◽

Female Predominance ◽

Organ Manifestations ◽

Pulmonary Arterial

The term ’scleroderma’ describes a group of conditions in which the development of thickened, fibrotic skin is a cardinal feature. This includes localized forms of scleroderma (e.g. morphoea) and also systemic forms of the disease that are more correctly termed systemic sclerosis. Systemic sclerosis (SSc) is a multiorgan, autoimmune disease that has a high clinical burden and mortality, due to affecting the skin as well as internal organs. As with other related diseases there is a female predominance and marked clinical diversity. The pathogenesis of SSc is not fully elucidated; it includes endothelial cell injury fibroblast activation and autoimmunity that lead to skin and internal organ manifestations. The majority of cases exhibit characteristic serum autoantibodies. Some of these antibodies are scleroderma-specific reactivities including anti-centromere (ACA), anti-topoisomerase-1 (ATA or Scl 70) or anti-RNA polymerase III antibodies. These anti-nuclear antibody (ANA) patterns are generally mutually exclusive and serve as useful clinical markers of disease subgroups. Additional subsetting of scleroderma cases, based on the extent of skin sclerosis, permits classification into limited and diffuse subsets. Because of the heterogeneity of the disease patients may suffer from different organ manifestations, such as lung fibrosis, hypertensive renal crisis, severe cardiac disease, gastrointestinal involvement, and pulmonary arterial hypertension. Although outcomes have improved recently, systemic sclerosis still has the highest case-specific mortality of any of the autoimmune rheumatic diseases and requires careful and systematic investigation, management and follow-up. Treatment includes symptomatic strategies with attention to each involved organ system; it is still an area where therapeutic progress and better understanding of pathogenesis is increasingly anticipated.

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Circulating Tissue Inhibitor of Matrix Metalloproteinase-4 (TIMP-4) in Systemic Sclerosis Patients with Elevated Pulmonary Arterial Pressure

Mediators of Inflammation ◽

10.1155/2008/164134 ◽

2008 ◽

Vol 2008 ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Gialafos J. Elias ◽

Moyssakis Ioannis ◽

Psaltopoulou Theodora ◽

Papadopoulos P. Dimitrios ◽

Perea Despoina ◽

...

Keyword(s):

Systemic Sclerosis ◽

Lung Fibrosis ◽

Pulmonary Function Tests ◽

Systolic Pressure ◽

Serum Levels ◽

Cross Sectional Study ◽

Pulmonary Artery Systolic Pressure ◽

Cross Sectional ◽

Skin Sclerosis ◽

Pulmonary Arterial

Decreased levels of matrix metalloproteinases (MMPs) or excess levels of their tissue inhibitors (TIMPs) may contribute to dysregulation of extracellular matrix turnover in systemic sclerosis (SSc). In a cross-sectional study of 106 SSc patients, we measured serum levels of TIMP-4 which is preferentially expressed in cardiovascular structures and searched for correlations with simultaneously performed echocardiography measurements of pulmonary artery systolic pressure (PASP), myocardial performance, and pulmonary function tests. TIMP-4, but not MMP-9, levels were significantly raised in patients with SSc than controls. However, in the subgroup of patients with PASP measurements lower to 40 mmHg (n=69), TIMP-4 levels were comparable to controls irrespective of the presence of diffuse or limited skin involvement, or lung fibrosis. Individual PASP measurements suggestive of pulmonary hypertension were associated with increased TIMP-4 serum levels (P=.03), independently of age, extent of skin sclerosis, or lung fibrosis, suggesting a cardiopulmonary vasculature-specific role of TIMP-4 activation in SSc.

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Serum CXCL16 Concentrations Correlate with the Extent of Skin Sclerosis in Patients with Systemic Sclerosis

The Journal of Rheumatology ◽

10.3899/jrheum.090108 ◽

2009 ◽

Vol 36 (9) ◽

pp. 1917-1923 ◽

Cited By ~ 11

Author(s):

KOICHI YANABA ◽

EIJI MUROI ◽

AYUMI YOSHIZAKI ◽

TOSHIHIDE HARA ◽

FUMIHIDE OGAWA ◽

...

Keyword(s):

Longitudinal Study ◽

Systemic Sclerosis ◽

Therapeutic Target ◽

Skin Fibrosis ◽

Healthy Controls ◽

Serum Concentrations ◽

Potential Therapeutic Target ◽

Skin Sclerosis ◽

Clinical Associations

Objective.To determine serum concentrations of soluble CXCL16 and its clinical associations in patients with systemic sclerosis (SSc).Methods.Serum CXCL16 levels from 89 patients with SSc were examined by ELISA. In a retrospective longitudinal study, 68 sera from 28 patients with SSc were analyzed (followup 1.3 to 7.3 yrs).Results.Serum CXCL16 levels were elevated in patients with SSc compared with healthy controls (n = 42). Patients with diffuse cutaneous SSc (n = 52) had higher levels of CXCL16 than those with limited cutaneous SSc (n = 37). Serum CXCL16 levels correlated positively with the extent of skin sclerosis. In the longitudinal study, CXCL16 levels generally decreased on a parallel with the improvement in skin sclerosis.Conclusion.CXCL16 levels were increased in patients with SSc, and correlated with the extent of skin sclerosis, suggesting that CXCL16 may have a role in the development of skin fibrosis in SSc. Blockade of CXCL16 interaction might be a potential therapeutic target in patients with SSc.

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An analysis of abnormalities in the B cell receptor repertoire in patients with systemic sclerosis using high-throughput sequencing

PeerJ ◽

10.7717/peerj.8370 ◽

2020 ◽

Vol 8 ◽

pp. e8370

Author(s):

Xiaodong Shi ◽

Tihong Shao ◽

Feifei Huo ◽

Chenqing Zheng ◽

Wanyu Li ◽

...

Keyword(s):

Systemic Sclerosis ◽

B Cell ◽

High Throughput ◽

High Throughput Sequencing ◽

Cell Receptor ◽

Receptor Repertoire ◽

Skin Sclerosis ◽

Cdr3 Length ◽

Gene Usage ◽

Cell Receptor Repertoire

Systemic sclerosis is a chronic multisystem autoimmune disease that is associated with polyclonal B cell hyperreactivity. The CDR3 of BCRs is the major site of antigen recognition. Therefore, we analyzed the BCR repertoire of patients with SSc. The BCR repertoires in 12 subjects including eight SSc patients and four healthy controls were characterized by high-throughput sequencing, and bioinformatics analysis were studied. The average CDR3 length in the SSc group was significantly shorter. The SSc patient displayed more diverse BCR. Moreover, SSc patients with mild skin sclerosis, anti-Scl70, interstitial lung disease or female sex were more diversified. B cells from the SSc patients showed a differential V and J gene usage. SSc patients had distinct BCR repertoires.These findings reflected the differences of BCR repertoires between SSc patients and controls. The higher-usage genes for the BCR sequence might be potential biomarkers of B cell-targeted therapies or diagnosis for SSc.

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Novel disease-modifying drugs against skin fibrosis of systemic sclerosis

Trends in Immunotherapy ◽

10.24294/ti.v2.i3.1050 ◽

2019 ◽

Vol 2 (3) ◽

Author(s):

Mana Nishiguchi ◽

Yuki Yamamoto ◽

Masatoshi Jinnin

Keyword(s):

Systemic Sclerosis ◽

Early Stage ◽

Autoimmune Disorder ◽

Skin Fibrosis ◽

Type I ◽

Internal Organs ◽

Disease Modifying Drugs ◽

Skin Sclerosis ◽

Disease Modifying ◽

Late Stages

Systemic sclerosis (SSc) or scleroderma is an autoimmune disorder characterized by tissue fibrosis of the skin and internal organs. The etiology of the skin fibrosis is thought to be thickened dermis due to uncontrolled excessive deposition of various extracellular matrix, mainly type I collagen.Systemic treatments with anti-inflammatory and cytotoxic immunosuppressive properties, such as corticosteroids and immunosuppressants, are usually considered for skin sclerosis of patients with SSc. However, their approach must be initiated at the early stage, before the fibrosis is completed, and the effects of the corticosteroids and immunosuppressants are known to be reduced in the late stages of the sclerosis. Furthermore, various significant adverse effects of these treatments must be considered.This paper discusses the present day understanding of therapeutic options using disease-modifying drugs against skin sclerosis of SSc patients and the possible mechanisms.

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