The Study of Oxidative Stress in Fibrotic and Non-Fibrotic Skin of Patients with Systemic Sclerosis

Background and Objectives Systemic Sclerosis (SSc) is a chronic multisystemic connective tissue disease characterized by progressive fibrosis affecting skin and internal organs. Despite serious efforts to unveil the pathogenic mechanisms of SSc, they are still unclear. High levels of Reactive Oxygen Species (ROS) in affected patients have been shown, and ROS are suggested to play a role in fibrosis pathogenesis. In this study we evaluate ROS levels in non-fibrotic and fibrotic skin of patients with SSc and we compare them with those obtained from healthy controls. Patients and Methods We enrolled 9 SSc patients fulfilling the EULAR/ACR classification criteria and 7 healthy controls. Patients included were 4 men and 5 women with mean age of 46 ±10 yrs. Controls were matched by sex and age. All patients were affected by diffuse cutaneous form of SSc and the ANA pattern anti-Scl70. Mean disease duration was 7.5±5 yrs. Skin involvement was evaluated by modified Rodnan Skin Score (mRSS). Skin samples (4mm punch biopsy) were taken from fibrotic skin and non-fibrotic skin of patients and from healthy controls as well. To detect ROS, specimens were analyzed immediately after sampling by electron paramagnetic resonance spectroscopy. Blood samples have been drawn from all patients and controls to assess oxidative stress biomarkers. Results ROS levels (expressed as median and range, unit of measurement was nmol/l/min/mg of dry weight) were 24.7 (10.9– 47.0) in fibrotic skin, 18.7 (7.3–34.0) in non-fibrotic skin and 7.7 (3.5–13.6) in healthy controls skin. ROS levels in Fibrotic and Non-fibrotic skin of SSc patients were significantly higher than in Healthy Controls (p=0.002 and p=0.009, respectively). ROS levels in fibrotic skin were raised in comparison to non-fibrotic skin, when samples related to each patient were compared (p=0.01). ROS levels in fibrotic skin were correlated with forced vital capacity (r= -0.75, p=0.02) and erythrocyte sedimentation rate (r=0.70, p=0.04). All other clinical and lab parameters showed no significant correlation. When compared to controls, blood from SSc patients showed lower ascorbate (vitamin C) levels (8 [3.8-9.8] vs. 10.5 [9-19.1] mg/L, p=0.004) and higher lipid peroxides (873.5 [342-1973] vs. 422 [105-576] μmol/L, p=0.004). Conclusion Our results indicate the presence of high oxidative stress both in non-fibrotic skin and fibrotic skin of SSc patients, but with higher tendency in the latter. Raised ROS levels in non-fibrotic skin of SSc patients might be a hint of early involvement in skin fibrogenesis. However, a longitudinal prospective study is necessary for such proof

Evaluation of right ventricular function performed by 3d-echocardiography in scleroderma patients

The impairment of the right ventricle (RV) in systemic sclerosis (SSc) is usually related to pulmonary arterial hypertension (PAH). New echocardiographic techniques, such as 3-dimensional echocardiography (3DE) and 2-dimensional speckle tracking (2DSTE), allow an accurate evaluation of the RV function. The aim of this study was to evaluate the RV function using 3DE and 2DSTE in SSc patients with no history of heart disease and no PAH. Forty-five SSc patients, 42 females and 3 males, 28 with limited cutaneous SSc (lcSSc) and 17 with diffuse cutaneous SSc (dcSSc), were studied. Forty-three age- and gender-matched healthy subjects were enrolled as controls. All of them underwent a 3DE and 2DSTE ecocardiographic evaluation of the RV function. Systolic pulmonary arterial pressure (sPAP) and total pulmonary vascular resistance (tPVR) were also estimated by power doppler. RV echocardiographic parameters were compared in the different subsets of SSc patients. A statistical analysis was performed by t-test, ANOVA and multiple logistic regression. RV areas in 2DSTE and volumes in 3DE were higher and RV function parameters were reduced in SSc patients compared with controls. Also sPAP and tVPR were higher, but they did not reach pathological values. Echocardiographic alterations were more pronounced in patients with lcSSc. 3DE and 2DSTE echocardiography allowed us to detect morphological and functional alterations of the RV in a group of SSc patients with no clinical signs of heart disease and no PAH. These patients had significantly higher sPAP and tPVR than healthy controls without reporting values compatible with PAH. These data suggest that RV alterations are related to a pressure overload rather than to an intrinsic myocardial involvement in SSc

The Study of Oxidative Stress in Fibrotic and Non-Fibrotic Skin of Patients with Systemic Sclerosis

Background and Objectives Systemic Sclerosis (SSc) is a chronic multisystemic connective tissue disease characterized by progressive fibrosis affecting skin and internal organs. Despite serious efforts to unveil the pathogenic mechanisms of SSc, they are still unclear. High levels of Reactive Oxygen Species (ROS) in affected patients have been shown, and ROS are suggested to play a role in fibrosis pathogenesis. In this study we evaluate ROS levels in non-fibrotic and fibrotic skin of patients with SSc and we compare them with those obtained from healthy controls. Patients and Methods We enrolled 9 SSc patients fulfilling the EULAR/ACR classification criteria and 7 healthy controls. Patients included were 4 men and 5 women with mean age of 46 ±10 yrs. Controls were matched by sex and age. All patients were affected by diffuse cutaneous form of SSc and the ANA pattern anti-Scl70. Mean disease duration was 7.5±5 yrs. Skin involvement was evaluated by modified Rodnan Skin Score (mRSS). Skin samples (4mm punch biopsy) were taken from fibrotic skin and non-fibrotic skin of patients and from healthy controls as well. To detect ROS, specimens were analyzed immediately after sampling by electron paramagnetic resonance spectroscopy. Blood samples have been drawn from all patients and controls to assess oxidative stress biomarkers. Results ROS levels (expressed as median and range, unit of measurement was nmol/l/min/mg of dry weight) were 24.7 (10.9– 47.0) in fibrotic skin, 18.7 (7.3–34.0) in non-fibrotic skin and 7.7 (3.5–13.6) in healthy controls skin. ROS levels in Fibrotic and Non-fibrotic skin of SSc patients were significantly higher than in Healthy Controls (p=0.002 and p=0.009, respectively). ROS levels in fibrotic skin were raised in comparison to non-fibrotic skin, when samples related to each patient were compared (p=0.01). ROS levels in fibrotic skin were correlated with forced vital capacity (r= -0.75, p=0.02) and erythrocyte sedimentation rate (r=0.70, p=0.04). All other clinical and lab parameters showed no significant correlation. When compared to controls, blood from SSc patients showed lower ascorbate (vitamin C) levels (8 [3.8-9.8] vs. 10.5 [9-19.1] mg/L, p=0.004) and higher lipid peroxides (873.5 [342-1973] vs. 422 [105-576] μmol/L, p=0.004). Conclusion Our results indicate the presence of high oxidative stress both in non-fibrotic skin and fibrotic skin of SSc patients, but with higher tendency in the latter. Raised ROS levels in non-fibrotic skin of SSc patients might be a hint of early involvement in skin fibrogenesis. However, a longitudinal prospective study is necessary for such proof.Introduzione La sclerosi sistemica (SSc) è una malattia multisistemica cronica del tessuto connettivo caratterizzata dalla fibrosi progressiva della cute e degli organi interni. Sebbene i meccanismi patogenetici coinvolti nella malattia sono poco chiari, è stato dimostrato che i pazienti affetti da SSc presentano alti livelli di stress ossidativo (Reactive Oxygen Species [ROS]) tale da suggerire un ruolo nella fibrogenesi. In questo studio valutiamo i livelli di ROS sia nella cute indurita che quella apparentemente sana dei pazienti affetti da SSc e li confrontiamo con dei controlli sani. Metodi Sono stati arruolati 9 pazienti (4 uomini e 5 donne) con dcSSc soddisfacendo i criteri diagnostici (EULAR/ACR) e 7 controlli sani abbinati per età e sesso. L’età media dei pazienti era 46±10 anni e la durata media della malattia era 7.5±5 anni. Tutti i pazienti erano ANA (Scl-70) positivi. Il coinvolgimento cutaneo è stato valutato con lo score di Rodnan modificato (mRSS). Al momento dello studio, da ciascun paziente sono state prelevate 2 biopsie cutanei (punch biopsy 4 mm), una da pelle indurita (con mRSS 2-3) e un’altra da pelle apparentemente sana (con mRSS 0). Contemporaneamente, sono stati prelevati campioni di sangue per l’analisi dello stress nel siero. Per l’analisi dei ROS nella cute è stata utilizzata la metodica spettrometrica altamente sensibile EPR (Electron Paramagnetic Resonance). Invece, diverse metodiche spettrofotometriche sono stati utilizzati per l’analisi dello stress nel siero. Risultati I livelli dei ROS (mediana e range, in nmol/l/min/mg di peso secco) erano 24.7(10.9-47.0) nella cute indurita, 18.7(7.3-34.0) nella cute apparentemente sana e 7.7(3.5-13.6) nella cute dei controlli sani. Lo stress era significativamente più alto nei pazienti (sia cute indurita che cute apparentemente sana) rispetto ai controlli (p<0.05). Inoltre, la cute indurita mostrava livelli di stress più alti della cute apparentemente sana dello stesso paziente (p=0.01). lo stress nella cute indurita si correlava con la capacità vitale forzata (FVC) (r= -0.75, p=0.02) e la velocità di eritrosedimentazione (VES) (r=0.70, p=0.04). Rispetto ai controlli, il siero dei pazienti affetti da SSc ha mostrato livelli di acido ascorbico più basso (8 [3.8-9.8] vs. 10.5 [9-19.1] mg/L, p=0.004) e livelli di perossidi lipidici più alti (873.5 [342-1973] vs. 422 [105-576] μmol/L, p=0.004). Conclusioni I risultati del nostro studio indicano la presenza di alto stress ossidativo sia nella cute indurita che in quella apparentemente sana dei pazienti affetti di SSc, con una tendenza più alta nella cute indurita. La presenza di alto stress nella cute apparentemente sana può indicare un precoce ruolo dello stress nella fibrogenesi. Per approvare quest’ipotesi necessitiamo di studi longitudinali prospettici

Rheumatic and autoimmune thyroid disorders: a causal or casual relationship?

A number of dysfunctions may affect the thyroid gland leading either to hyper- or hypothyroidism which are mediated by autoimmune mechanisms. Thyroid abnormalities may represent an isolated alteration or they may be the harbinger of forthcoming disorders as is the case of well-characterized polyendocrine syndromes. Also, they may precede or follow the appearance of rheumatic manifestations in patients affected with connective tissue diseases or rheumatoid arthritis. The mechanisms by which autoimmune thyroid disorders may be linked to systemic autoimmune diseases have not been fully unraveled yet, however alterations of common pathways are suggested by shared genetic variants affecting autoantigen presentation and regulation of the immune response. On the other hand, the higher prevalence of autoimmune thyroid disorders over rheumatic diseases compels the chance of a mere causal concomitancy in the same patient. The aim of our paper is to provide an overview of available data on thyroid involvement in different rheumatic diseases and to go over the main rheumatic manifestations in the context of autoimmune thyroid diseases