Clinical and Pathogenetical Peculiarities of the Secondary Raynaud’s Syndrome and Their Pharmacological Correction

• Main Author: Leontyeva S.
• Format: Article
• Language: English
• Published: Publishing House "Kyrylytsya" 2015-12-01
• Series: Львівський клінічний вісник
• Subjects: candesartan; factors of humoral regulation; immunological disorders; secondary Raynaud's syndrome; structural and functional vascular changes
• Online Access: http://lkv.biz/clinical-and-pathogenetical-peculiarities-of-the-secondary-raynauds-syndrome-and-their-pharmacological-correction/

Introduction. The prevalence of Raynaud’s syndrome in different countries ranges from 2.1 – to 16.8 %. Secondary Raynaud’s syndrome (SRS) occurs in case of more than 70 diseases. However, there is no consensus about the pathogenic mechanisms of its origin, and the modern diagnosis algorithms, without which it is difficult to choose the correct treatment that influences the patients’ disability prognosis and his life quality, are not elaborated. The purpose of the study is to ascertain the clinical and pathogenetic peculiarities of SRS of different severity degrees, to work out the algorithms for its diagnosis and increase the effectiveness of treatment with candesartan. Materials and research methods. The work is based on the results of the survey of 120 patients with SRS. The diagnosis of SRS is carried out using the criteria of E. Allen, G. Brown. Statistical analysis was performed using the package STATISTICA for Windows 5.5 (Statsoft, USA). Results of the investigation and their discussion. Among the 120 surveyed patients there were 101 women and 19 men, average age – 48,5 (17,0–73,0) [34,0–56,0] years in the ratio of 5:1. The first group consisted of 44 (36.7 %) patients with mild severity. In this group were observed the skin colour changes with minimal subjective disorders, such as numbness or tingling while infrequent episodes of vasospasm without trophic changes have occurred. It was found, that the mild course of SRS was characterized by the absence of the visible changes of the major humoral factors of vasodilatative and vasoconstrictive action (ET-1, AT II, ​​6-keto-PG F1α) before the start of pharmacological correction. The method of widefield capillaroscopy revealed angiodystonic changes of capillaries in such patients. The second group of patients consisted of 53 persons (44.2 %) with moderate severity of SRS, that was characterized by the presence of attacks, mainly in the cold season, with more pronounced than in the first group subjective disorders such as tingling or pain in fingers with manifestations of trophic changes in most of them. Changes of the humoral vascular tone regulators in this group were more pronounced than in the group with mild severity, and primarily were characterized by the elevated levels of both ET-1 and AT II, comparing to the control group. During the capillaroscopic examination in patients with the moderate severity degree of SRS, there were found similar changes as in the patients of the first group, but with a reduction of the capillary net. The third group consisted of 23 patients (19.2 %) with severe severity degree of SRS, that was characterized by the frequent bouts of vasospasm and was accompanied by severe pain, with the presence of digital scars, single ulcers and atrophic changes of the phalanges. The indices of the humoral regulation factors in patients with severe SRS were characterized by the considerably pronounced growth of ET-1 and AT II. In severe course of SRS, the vasoconstrictor response was more pronounced, that was confirmed by the high performance levels of humoral regulators of the vasoconstrictor action. There were found pronounced capillaroscopic changes: spastic and atonic state of capillaries, resize and form changing of the capillary loops, reduction of capillary grid, the presence of megacapillaries and non-vascular fields, local ischemia, an acute deceleration of the blood flow, venous stasis. These indices were studied in the patients in dynamics after the treatment with candesartan during one and four months (short-term and long-term courses of treatment). For the patients there was conducted written survey within a month using a questionnaire, which showed subjective improvement of the clinical status of respondents with moderate and severe courses of SRS. Whereas we studied the pathogenic features of SRS and their clinical parallels, pathogenetic correction with candesartan, proposed by us, had a positive influence, that manifested in the decrease of the amount and duration of SRS attacks, the intensity of pain according to VAS, significant strengthening of vasodilatation (increase of 6-keto PG F1α), decrease of ET-1 and PG F2α levels, slowing the proliferative processes, increase of prostacyclin and its active metabolites levels, that, in its turn, increases the positive influence effect on the blood vessels. The mentioned effect of treatment found confirmation in the results of ultrasonography examination, during conducting of which the reduce of the peripheral vascular resistance was seen. In our view, this can be explained by the property of candesartan to influence the arterio-venous shunts, that have a direct impact on the properties of compensatory peripheral resistance. Conclusions. The study found an advantage of vascular tone humoral regulation factors of vasoconstrictive action, such as ET-1 and AT II, increased antinuclear factor level that are directly proportional to the increase of the disease severity degree of the mentioned pathology, and the presence of the asymmetry coefficient elevation in case of the mild SRS, changes of the reosystolic index and “intima – media” complex. The least pronounced clinical signs were observed in patients with neurocirculatory dystonia and essential crioglobulinemic vasculitis and were characterized by the mild severity degree, whereas in case of systemic scleroderma systemic lupus erythematosus and rheumatoid arthritis there were dominated the moderate and severe degree of its course. The conducted by us pathogenetic correction of SRS with candesartan favorably influenced, in the first place, the state of the bloodstream of the upper limbs at all clinical degrees of its severity. These positive changes were confirmed by the data obtained from the patients’ questionnaire, that showed the reduced levels of pain in case of the moderate and severe course, according to VAS, and the index of attacks’ duration in case of severe course of SRS.