Evaluation of environmental risk factors in primary Raynaud’s phenomenon (RP) and systemic sclerosis (SSc)-associated RP through a self-administered questionnaire

Background: Raynaud’s phenomenon (RP) is characterized by recurrent and reversible episodes of vasospasm involving peripheral small vessels, frequently induced by exposure to cold temperature and emotional stress. In 80% of cases is an idiopathic condition and is defined as primary RP. Causes of secondary RP include mainly connective tissue diseases (SSc, MCTD, SLE, RA), medications (e.g. beta blockers) and surgical condition (e.g. tunnel carpal syndrome). Among connective tissue disease, Raynaud’s phenomenon (RP) is present in more than 95% of patients with SSc and typically precedes the onset of systemic disease by months to several years (1). The etiopathogenesis and risk factors of RP have not been fully delineated yet. There is a general agreement that the environmental risk factors can play a role in the genesis of the phenomenon, as indicated by the increased incidence of RP episodes after occupational exposure to cold temperature, hand-arm transmitted vibrations and exposure to chemicals (e.g. vinyl chloride monomer) (2). A pilot study evaluating the exposure to organic solvents (e.g. benzene) in 88 SSc patients, living in a urban Italian residence, before and after the onset of disease, has showed a directed correlation with development of a diffuse SSc and possibly with high occurrence of ulcers (3). A prospective case-control study on 100 patients with SSc vs 300 healthy subjects (4) has showed a relevant impact of crystalline silica, white spirit, aromatic solvent, chlorinated solvents, trichloroethylene, ketones and welding fumes on disease. Finally, mice submitted to s.c. injections of oxidative substances (hydroxyl radicals, hypochlorous acid, peroxynitrites, superoxide anions) developed different autoantibodies profiles (diffuse or limited cutaneous SSc), the effect depending on the accumulation of high amounts of oxidized protein products (AOPP) (5). Design of the study: Based on these observations, we are settling up a questionnaire on RP to be administered to about 500 patients affected by primary RP and SSc-RP and to an equal number of otherwise healthy individuals in order to accumulate one of the largest Italian patients data banks currently available. This self-administered questionnaires analyzes several characteristics of RP patients (e.g. clinical features, its influence on the quality of life, disease activity), family history of disease (e.g. for autoimmune diseases or RP), socioeconomic features / aspects of social life (e.g. social status, place of residence), medical history (e.g. thryroid disorders, arthritis, dermatitis, carpal tunnel syndrome), voluptuary habits (drugs, smoke), habits of daily living (pro-oxidative or chlorous-based compounds, nail polish), sport practiced (e.g. tennis, golf, cycling), exposure to implants (prosthesis, silicon implants, intrauterine device and contact lenses), work history and possible exposure to pollutants (type of work and exposure to pollutants and chemicals). Statistical analysis: Data will be collected in as Microsoft Office Excel sheet and transferred onto SPSS statistical analysis software. Association between variables and the disease will be evaluated with Fisher exact test corrected for alpha error; variables found to be statistically associated to the disease (or its clinical and laboratory features) will be analyze by linear regression to establish their interdependences.