Fractalkine (FKN) and its receptor CX3CR1 are critical mediators in the vascular and tissue damage of several chronic diseases, including systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH). Interestingly, the V249I and T280M genetic polymorphisms influence CX3CR1 expression and function. We investigated whether these polymorphisms are associated with PAH secondary to SSc. CX3CR1 genotypes were analyzed by PCR and sequencing in 76 patients with limited SSc and 204 healthy controls. PAH was defined by colorDoppler echocardiography. Homozygosity for 249II as well as the combined presence of 249II and 280MM were significantly more frequent in patients with SSc compared to controls (17 vs 6%, p = 0.0034 and 5 vs 1%, p = 0.0027, respectively). The 249I and 280M alleles were associated with PAH (odd ratio [OR] 2.2, 95% confidence interval [CI] 1.01-4.75, p = 0.028 and OR 7.37, 95%CI: 2.45-24.60, p = 0.0001, respectively). In conclusion, the increased frequencies of 249I and 280M CX3CR1 alleles in a subgroup of patients with SSc-associated PAH suggest a role for the fractalkine system in the pathogenesis of this condition. Further, the 249I allele might be associated with susceptibility to SSc.

Aims: It is increasingly important to determine the economic consequences of diseases considering the policy of limited health–care budgets. In this study we evaluated the annual direct and indirect costs of Systemic Sclerosis (SSc) and we tried also to identify any cost predictors. Methods: We studied 106 patients (103 female, 3 male), 57 affected by Limited Systemic Sclerosis (LSSc) and 49 affected by Diffuse Systemic Sclerosis (DSSc). Mean age was 57 years (SD±13,8) and mean disease duration was 8,9 years (SD±7,2). Direct costs: data were calculated referring to DRG (Disease Related Group) expenses for the in-patients. We referred to national pharmacopoeia to calculate the pharmaceutical cost for the out-patients. Indirect costs: we estimated the expense comparing our cases to literature data. Intangible costs: these are attributable to pain and psychological suffering. It is very difficult to express the intangible costs in monetary terms and they are often conveyed as disability and poorer quality-of-life. We used the Health Assessment Questionnaire “HAQ” and the Short Form-36 “SF-36” to evaluate this issues. Results: Our study confirms, the extremely high costs caused by Systemic Sclerosis (total cost’s 2001 year is € 1.173.842,93, and average yearly patient cost is € 11.073,99). Considering an estimated prevalence of 375 cases/106, the total yearly economic impact of SSc in Italy should be € 249.000.000,00. Intangible costs were calculated as modifications of the health status. Average value of the HAQ was significantly higher than the control population (0,94±0,72), average values in the SF-36 were significantly lower than the control population (49,99±19,16 for physical dimension and 58,42±27,71 for mental dimension). The diffuse form of SSc, positivity for anti-Scl 70 antibodies, high skin score and a poor health status (HAQ and SF-36) were found to be cost predictors. Conclusions: As reported in the literature, our study confirms, the extremely high costs for total and single patients caused by Systemic Sclerosis. The DSSc are more expensive than the LSSc approximately 11% (p=0,0067). The direct costs are 30% higher in the DSSc than the LSSc (p<0.001). The indirect and intangible costs are not significantly different. Moreover, our study shows also the possibility of identifying different cost predictors

Aims: to evaluate the quality of life of patients affected by systemic sclerosis (SSc) through the application of the Medical Outcome Survey Short-Form 36 (SF-36) questionnaire and to correlate the results with the disability index of the health assessment questionnaire (HAQ-DI) and the systemic involvement. Methods: we studied 95 (3 M, 91 F) patients affected by SSc (mean age 60 years, range 39-83, mean duration of disease 6 years, range 1-34). The organ system involvement was evaluated by skin score, chest High Resolution Computed Tomography (HRCT), electrocardiography according to Holter, Doppler-echocardiography and oesofagogram. Results: considering the values of the 8 question groups of the SF-36 the most different between the patients and the control population are the values relevant to the physical dimension. The general health values estimating the physical and social dimension are significantly lower in the patients than in the control population (t=9,324; p<0,0001). A very good correlation was found between the DI (r = -0,7903 ; p <0.0001) and all the scores of SF-36. The skin involvement showed a statistically significant correlation with the DI (r=0.3709; p=0.0002) and the PA score of the SF- 36 (r =0.2853; p=0.0051). No other statistically significant correlation was found between any of the SF-36 dimensions and involvement of a specific organ. Conclusion: SF-36 showed to be a valid instrument to evaluate the quality of life and the disability of patients with SSc and it seems to correlate with extent of skin involvement

Heart disease is a frequent and often severe feature of systemic sclerosis (scleroderma). Cardiomyopathy, with ventricular diastolic dysfunction and arrhythmias, is the most important form, since it is associated with a very poor prognosis. The current challenge is to define its pattern and identify individuals at risk, but evaluation in vivo may be hard to perform. The aim of this review is to provide an update on the clinical aspects of scleroderma heart disease and the early pivotal role that coronary microcirculation dysfunction plays in its development. A discussion of the diagnostic tools now available for this frequently asymptomatic condition will be provided. Treatment options will be reviewed, even though no cure for systemic sclerosis exists, and the current therapy of diastolic dysfunction remains unsatisfactory.