oxide synthase 1 gene as significantly correlated with RP in the general population. 4 Major risk factors for primary RP include, in addition to the female sex and family history, a previous sensation of cold hands, migraine, cardiovascular diseases, decreased body mass index, manual occupation (not including vibration tool use), and estrogen replacement therapy. 3-6 Cigarette smoking and alcohol consumption are still of unclear significance when concerning the prevalence of primary RP. 7 Secondary RP associated with a known disease, mainly with systemic sclerosis (SSc) (>80% of patients) or other connective tissue diseases (CTDs), is rare and accounts for 10% to 20% of all RP cases. 8 Other common causes of secondary RP include diseases of arteries in the upper limbs (60% of RP occurring in individuals older than 60 years), malignancies, endocrine diseases, occupational syndromes, hematologic disorders, and infections (TABLE 1). 8,9 In addition, several Introduction Raynaud phenomenon (RP) is defined as recurrent, reversible episodes of vasospasm involving peripheral small vessels of the fingers and toes, at times also of the other acral sites (nose, ears, oral mucosa, lips, or nipples), when exposed to a cold environment or stressful situation. 1 This is characterized by a series of color changes in the affected area: first white (lack of blood flow), then bluish (deoxygenation of remaining blood), and red (reperfusion). Attacks can cause distal pain, burning, numbness, and paresthesia. 2 Regarding its etiology, RP is classified as primary (idiopathic) or secondary. Primary RP, which is an isolated finding without an underlying pathology, is common, occurring in about 5% of the general population living in areas with cold climates. 3 The prevalence of RP is higher in women (female-to-male ratio of 9 to 1). There is an associated genetic predisposition: one polymorphic variant was identified within the nitric