Recombinant human erythropoietin stimulates vasculogenesis and wound healing in a patient with systemic sclerosis complicated by severe skin ulcers

Systemic sclerosis (SSc) is often complicated by severe skin ulcers that are unresponsive to traditional treatments. Vascular alterations are responsible for the ischaemic features of the disease in both the skin and visceral organs. Defective neoangiogenesis correlates with an abnormally reduced quantity of circulating endothelial progenitor cells (EPCs) caused by impaired maturation potential and proliferative capacity of bone-marrow endothelial stem cells. We report a patient with nonhealing cutaneous ulcers successfully treated with recombinant human erythropoietin (rHuEPO). The possible biological effects of this drug were also investigated. Before rHuEPO treatment, the bone-marrow sample contained reduced numbers of EPCs, which were functionally impaired. After a 6-month rHuEPO cycle, a marked increase in endothelial progenitor markers was seen, along with a significant reduction in their apoptotic rates. The clinical and laboratory data variations before and after rHuEPO treatment give new insights into the pathogenetic role of impaired endothelial stem-cell maturation and defective neoangiogenesis in patients with SSc.     

Th1 and Th2 chemokine serum levels in systemic sclerosis in the presence or absence of autoimmune thyroiditis

OBJECTIVE: We evaluated contemporarily serum alpha and beta chemokines in patients with newly diagnosed systemic sclerosis (SSc) in the presence or absence of autoimmune thyroiditis (AT). METHODS: Serum levels of CXCL10 and CCL2 chemokines, prototypes of the 2 major subclasses (Th1 and Th2), were measured in patients with newly diagnosed SSc with (n = 40; SSc-II) or without (n = 50; SSc-I) AT, in comparison with 50 normal controls (control-I) and 40 AT controls without SSc (control-II) (sex- and age-matched). RESULTS: Serum CXCL10 levels were significantly higher in control-II, SSc-I, and SSc-II than in control-I (150 +/- 131, 196 +/- 137, 254 +/- 98, 83 +/- 42 pg/ml, respectively; p < 0.001 for all). SSc-I had serum CXCL10 levels significantly higher than control-II (p = 0.03), and significantly lower than SSc-II (p = 0.04). SSc-II had serum CXCL10 levels significantly higher than control-II (p = 0.002). Serum CCL2 levels were significantly higher in SSc-I and SSc-II than in control-I (378 +/- 192, 403 +/- 131, 316 +/- 113 pg/ml, respectively; p = 0.03 and p < 0.01, respectively). SSc-II had serum CCL2 levels significantly higher than control-II (327 +/- 123 pg/ml; p = 0.04). CONCLUSION: Our study demonstrates high serum levels of both CXCL10 (Th1) and CCL2 (Th2) chemokines in patients with SSc, and suggests a prevalence of Th1 immune response in the early phase of the disease. A further increase of serum CXCL10, but not of CCL2, is observed in SSc patients with AT.     

Systemic sclerosis evolution of disease pathomorphosis and survival. Our experience on Italian patients' population and review of the literature

The clinical spectrum and prognosis of systemic sclerosis (SSc) seem to vary among patients' populations recruited during different time periods. In order to verify this possible evolution we investigated the clinico-serological and survival rate in a large Italian SSc series (821 patients; 746 females, 75 males; mean age 53.7 ± 13.9 SD years) recruited between 2000 and 2011. The observed findings were compared with previous studies of the world literature.Compared to older Italian SSc series, the present patients' population showed a significantly increased prevalence of limited cutaneous SSc (from 72 to 87.5%; p ≤ .0001) and serum anti-centromere antibodies (from 39 to 47,4%; p ≤ .001), with a significant reduction of lung (from 81 to 63.7%; p ≤ .0001), heart (from 35 to 20.5%; p ≤ .0001), and renal involvement (from 10 to 3.8%; p ≤ .0001), and skin ulcers (from 54 to 16.5%; p ≤ .0001). Cumulative 10th-year survival showed a clear-cut increase (80.7%) compared to our previous series (69.2%). These findings were mirrored by the results of survival studies published during the last five decades, grouped according to the time periods of patients’' recruitment at the referral centers. A clear progression of 10th-year survival rates was detectable, from the 54% median survival of the oldest studies (1935–1974) to 74% and 83.5% of the more recent SSc series, 1976–1999 and after 1999, respectively. In conclusion, the favorable evolution of SSc pathomorphosis and prognosis during the last decades might be related to more diffuse physician/patient awareness of this harmful disease and availability of diagnostic tools, the consequent wider recruitment of patients in the early stages of the disease, as well as to the improved therapeutic strategies.     

Serum 25-OH vitamin D levels in systemic sclerosis: analysis of 140 patients and review of the literature

Hypovitaminosis D is increasingly reported in autoimmune diseases. We investigated the 25-OH-vitamin D (25-OH-vitD) levels in systemic sclerosis (SSc) patients, in correlation with disease’s features. We measured the 25-OH-vitD serum levels in 140 consecutive patients (F/M 126/15; mean age 61 ± 15.1 years), 91 without (group A) and 49 with (group B) 25-OH-cholecalciferol supplementation. Patients of group A invariably showed low 25-OH-vitD levels (9.8 ± 4.1 ng/ml vs. 26 ± 8.1 ng/ml of group B); in particular, 88/91 (97%) patients showed vitamin D deficiency (<20 ng/ml), with very low vitamin D levels (<10 ng/ml) in 40 (44%) subjects. Only 15/49 (30.6%) patients of group B reached normal levels of 25-OH-vitD (≥30 ng/ml), whereas vitamin D deficiency persisted in 12/49 (24.5%) individuals. Parathormone levels inversely correlated with 25-OH-vitD (r = ?0.3, p < 0.0001). Of interest, hypovitaminosis D was statistically associated with autoimmune thyroiditis (p = 0.008), while calcinosis was more frequently observed in patients of group A (p = 0.057). Moreover, we found significantly higher percentage of serum anticentromere antibodies in group B patients with 25-OH-vitD level ≥30 ng/ml (8/15 vs. 6/34; p = 0.017). In literature, hypovitaminosis D is very frequent in SSc patients. An association with disease duration, calcinosis, or severity of pulmonary involvement was occasionally recognized. Hypovitaminosis D is very frequent in SSc and severe in a relevant percentage of patients; furthermore, less than one third of supplemented subjects reached normal levels of 25-OH-vitD. The evaluation of 25-OH-vitD levels should be included in the routine clinical work-up of SSc. The above findings expand previous observations and may stimulate further investigations.