RU2366365C1 - Method of differentiated severity estimation of raynaud's syndrome in diffuse scleroderma - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to therapy. Before and after occlusive test, and then before and after sublingual introduction of nitroglycerine 0.5 mg, laser Doppler sonogram is recorded within left forearm in a point above the base of styloid processes of ulna and radius. The following indices are calculated: vasomotor activity (VA), high- and low-frequency oscillations amplitude ratio (HF/LF), transcapillary flow reaction in occlusive test (TFRocc), flow decrease percent on 2-5 minute after introduction of nitroglycerine (FDng), endothelium-dependent component (EDC). The calculated index is scored 1 to 3 points considering abnormality degree. The points are summed. If the total value is 5-9 points, reversible Raynaud's syndrome is determined. The total value of 10-14 points shows partially reversible form, and irreversible disease is indicated by total score 15 points and more.

EFFECT: method extends range of means for differentiated estimation of Raynaud's syndrome severity in diffuse scleroderma.

7 tbl, 7 ex

Description

The present invention relates to medicine, namely to therapy, and can be used in the diagnosis and treatment of Raynaud's syndrome in patients with systemic scleroderma.

Among diffuse diseases of connective tissue, second place in frequency is occupied by systemic scleroderma (SJS), which, along with pathognomonic progressive changes in the skin, musculoskeletal system and internal organs (lungs, heart, digestive tract), is characterized by a typical common Raynaud's vasospastic syndrome. Reynaud's syndrome, described by Maurice Reynaud in 1862, in the population reaches 10%, but in patients with SJS it occurs in 95%, reaching pronounced manifestations in 85%, and represents phase changes in the vessels of the skin with a predominance of spastic phenomena (digital ischemia) and the gradual formation trophic disorders in the tissues. In most patients with SJS, Raynaud's syndrome precedes the clinical manifestations of the disease, and with a long course it can cover not only the peripheral vasculature, but also the terminal sections of the vascular bed in the lungs, heart, kidneys, nervous system, determining the working capacity of patients and requiring special approaches to treatment.

Separate reports indicate a possible connection of Raynaud's syndrome with arterial hypertension, osteolysis of the nail phalanges, cerebral vasculitis, lido angiitis, glomerulonephritis, and, according to V.A. Nasonova et al. (1989), early development and persistence of SR has an unfavorable prognostic value, since in patients with this phenomenon, active forms of nephritis and damage to the vessels of the brain were significantly more frequently detected. It was shown that a more severe course of SR also corresponds to a greater degree of decrease in blood flow in the kidneys, and patients with severe nephropathy have the most severe manifestations of SR.

The presence of tissue disorders of vascular genesis in patients with SJS with SR is confirmed by the work of A.V.Smirnov (1987), who revealed pronounced disturbances in capillary blood flow with a decrease in oxygen supply in this cohort of patients.

Vascular damage in SJS is associated with fibrotic changes in the connective tissue and the formation of obliterating endarteriolitis, and some authors point to the heterogeneity of microcirculatory disorders in SR. Changes in endothelial function with thickening of the walls of larger arteries, in particular, of the brachial artery in patients with SJS (Karoli N.A., Rebrov A.P., Orlova E.E. Endothelial dysfunction in patients with systemic scleroderma. Abstracts of the 4th Congress of Rheumatologists of Russia. 23 -26 May 2005, Kazan No. 215).

Despite a long period of study of both scleroderma itself and Raynaud's syndrome, objective methods for assessing the severity of vascular disorders, as well as a method for monitoring the effectiveness of vascular therapy, including choosing the most optimal drug, have not yet been developed.

The severity of Raynaud's syndrome is determined by visual assessment of vascular and tissue disorders of the skin of the hands, using microcirculation studies using bulbar angioscopy or computer capillaroscopy, using dynamic infrared thermography. However, all these methods have their drawbacks, the most significant of which are the subjectivity of the assessment and insufficient consideration of the characteristics of the patient's response to vascular therapy.

There is a method of visual assessment of the severity of SR taking into account the color of the skin and the severity of trophic disorders of the tissues of the hand (A.B.Sherbakov. Reynaud’s syndrome in SJS: clinical and pathogenetic features and treatment. Diss. Candidate of Medical Sciences, M., 1987) .

With this method, the severity of CP is evaluated as follows:

1. the degree is determined in the presence of changes only in the color of the skin, without trophic and subjective disorders;

2. the degree is established if during the attack the patient feels numbness or tingling in the fingers, single digital scars may remain outside the attack;

3. the degree characterizes the expressed pain during the attack and the presence of single active ulcerations;

4. the degree is established in the presence of multiple ulcerations or gangrene.

The disadvantages of this method are:

- subjectivity (the results may be different in the assessment of different researchers);

- the lack of analysis of the response to drug exposure, which does not allow us to recommend it for the examination of the severity and irreversibility of vascular damage;

- a visual assessment is used (taking into account the patient’s stories) by the color and extent of whitening of the skin during seizures (spontaneous or provoked by cold influences), which includes the need for the patient to participate and his subjective story;

- prolongation of the examination period for the objectification of medical observations (with rare attacks);

- requires long-term follow-up of the patient with repeated repeated visits to the doctor to assess the effectiveness of therapy, if it is impossible to predict the effect.

Classification of G.L. Ratner and G.E. Slutsker, 1990 [G.E. Slutsker, G.L. Ratner. Comprehensive treatment of Raynaud's phenomenon. Guidelines. Kuibyshev, 1990; G.E.Slutsker. Pharmacotherapy of Raynaud's syndrome // Clinical Pharmacology and Therapy, 1995, No. 4 (2), pp. 49-51] uses three main signs: the color of the skin, the presence of swelling of the fingers, the presence of signs of necrosis of the fingers, followed by a severity designation in the form of a set of letters and numbers. Wherein:

C - the color of the skin:

1 - blanching of the skin of the fingers during an attack;

2 - blanching and / or blue skin of the fingers during an attack;

3 - persistent discoloration of the skin of the fingers outside the attack.

O - swelling of the fingers:

0 - lack of edema;

1 - edema after the attack or unstable, drug-resistant edema outside the attacks;

2 - persistent edema outside the attack, the development of lymphadema and fibrodema of the fingers of the hands (sclerodactyly).

N - necrosis:

0 - lack of skin necrosis;

1 - the presence of an ulcer;

2 - gangrene of the phalanx of the finger.

Disadvantages:

- subjectivity, in connection with which the results can be different when different researchers evaluate the same case (it allows ambiguous interpretation of changes within the same stage);

- the response to medication is not taken into account, which can lead to an erroneous opinion about the possible ineffectiveness of vascular therapy;

- does not allow you to choose the most effective method of drug correction;

- treatment is offered to all patients with the same vascular preparations (tranquilizers, nicotinic acid, short-acting calcium antagonists (corinfar), reopoliglyukin, pentoxifylline, troxevasin, ascorutin, heparin, HBO);

- the choice of a medicinal product does not take into account the effectiveness of each individual patient and does not depend on the stage of damage.

There is also a known method of Druzhinin S.O. (Ultrasound dopplerography and photoplethysmography in the diagnosis of Raynaud's syndrome // Rheumatology, 1989, No. 4, 54-59), in which obliteration of the digital artery is determined with a pressure gradient of more than 20 mm Hg. With an increase in the amplitude of the photoplethysmogram by 2 or more times, a positive reaction to medication is established (prognostically favorable data for treatment).

Disadvantages:

- allocate only the extremely severe (irreversible) stage of SR and patients whose amplitude increases by more than 2 times, while it is unclear whether those patients who responded with a smaller increase in amplitude should be treated;

- there is no differentiated choice of drugs.

The method of video capillaroscopy was adopted as the closest analogue (T.A. Nevskaya, N.G. Guseva. Characterization of microcirculatory disorders in patients with primary Raynaud's syndrome according to video capillaroscopy // Clinical Rheumatology, 2007, No. C).

The method involves the study of a capillaroscopic picture of the nail bed using a Leica MZ6 video microscope at a magnification of 20x and 800x. Quantitative (on 4 fingers of both hands) and qualitative (2-4 fingers of both hands) parameters are evaluated. The quantitative method [modification of Y. Kabasakal et al. 1996, A.Scheja et al., 1996] includes:

1) the density of capillaries, defined as the average number of capillary loops in the distal row per 1 mm (cap / mm);

2) the average diameter of the capillary loop (μm);

3) the diameter of the maximum expanded capillary (μm);

4) the relative increase (UE) of the diameter of the maximally expanded capillary (compared with the surrounding unexpanded capillaries);

5) the average length of the capillary (μm).

Qualitative assessment takes into account the homogeneity of the capillaroscopic picture, the uniformity of density and expansion of capillaries; polarity (orientation) of capillaries; perivascular edema; expansion and hypervisualization of the papillary plexus; expansion of the knees or capillary apex; the presence of megacapillaries (exceeding 10 times the average diameter of the capillary in the control), convoluted, bushy capillaries (more than 3 loops), visually detectable avascular fields and extravasates. Classification of extravasates: type 1 - less than 2 point hemorrhages on a finger; Type 2 - more than 2 hemorrhages per finger or areas of drain hemorrhages. At the same time, a whole spectrum of capillary changes is revealed, most of which are non-specific. Determine the structural changes in the microvasculature in the form of a homogeneous expansion and lengthening of the capillaries with a predominant expansion of the venular part of the loop, massive hemorrhages.

Disadvantages:

- a very cumbersome study (assess changes on the 4th and 2nd fingers of both hands), the diagnosis takes a lot of time, the method does not provide correction of treatment tactics, therapy does not always achieve the expected result, which in turn increases costs, the duration of the examination and treatment, reduces patient compliance to treatment.

Tasks:

1. To develop an optimal method for assessing the severity of Raynaud's syndrome in patients with SJS, which allows an objective assessment of the severity and irreversibility of vascular damage, which can be used in the examination of disability.

2. To develop criteria for the medical correction of SR depending on the stage of vascular lesions.

SUMMARY OF THE INVENTION

When assessing the severity of SR in the complex, significant indicators are revealed: vasomotor activity (VA), the ratio of the amplitudes of high-frequency and low-frequency oscillations (HF / LF), the response of capillary blood flow in an occlusal test (RKKokk), a decrease in blood flow 2-5 minutes after taking nitroglycerin (SKng ), the endothelium dependent component (EZK), and depending on the degree of deviation from the norm, each indicator is assigned a value from 1 to 3 points - with a value of 5-9 units. determine the completely reversible stage of CP, with a value of 10-14 units. - partially reversible stage, and with a value of 15 units and more - the irreversible stage of CP.

Technical result

The proposed method allows you to:

- reduce the time of examination of patients with the initial stages of the disease and spontaneous vasospastic reactions;

- determine the stage of SR and, depending on this, prescribe drug treatment, which will shorten the time for selecting individual therapy and increase patient adherence to treatment;

- determine the initial severity of vascular damage in patients with SR, the effect of vasodilator therapy, which will provide a differentiated choice of drugs and lower material costs, improve the quality of treatment;

- the method can be recommended for the examination of the severity and irreversibility of vascular damage.

The method is as follows.

An SSD patient is examined with a laser dopplerography (LDF) microcirculation system using the LAKK-01 apparatus (CJSC LAZMA Russia) in accordance with the instructions for use (Kozlov V.I. et al., 2002) at an air temperature of 21-24 degrees. In this case, the patient lies on the couch, the studied area (in this case, the forearm) is at the level of the heart, the sensor is located in the area of the back (outer) surface of the left forearm at a point located above the base of the styloid processes of the ulnar and radius bones by 3-4 cm in the middle line [Branko V.V. et al., 1998; Makolkin V.I. et al., 1999; Seifalian A.M., et al. 1994]. Record LDF - grams spend at least 15 minutes. The initial state of the microcirculation system is evaluated and functional tests are performed: occlusal and nitroglycerin, followed by computer data processing.

A computer program (V.I. Kozlov, E.S. Mach, F.B.Litvin, O.A.Terman, V.V. Sidorov) evaluates and calculates the following indicators of LDF-grams: microcirculation index (PM), mean square deviation (RMS), coefficient of variation (Kv), amplitude of low-frequency fluctuations (A _LF ), amplitude of pulse fluctuations of skin blood flow (A _CF ), amplitude of fast waves of fluxmotions (A _HF ); microcirculation efficiency index (IEM), neurogenic tonus (NT) of the walls of microvessels (RMS / A _LF × 100%), their myogenic or vasomotor (VA) activity (A _LF / PM × 100%), intravascular resistance (CC), defined as A _CF / PM × 100%. Endothelial activity is assessed by the corrected index of super slow rhythm (Aα / 3CO), the endothelium dependent component was calculated as the ratio of the standard deviation to the amplitude of the endothelial component of LDF.

Occlusal test. After recording the dopplerogram in the initial state, which is recorded for 5 minutes, without changing the patient’s posture (in the supine position, the forearm is at the heart level, the LDF probe is fixed at a standard point), the air pressure is pumped into the cuff of the tonometer up to 250- 300 mmHg To avoid registration of artifacts that occur during air injection, recording is stopped, then recording is resumed, maintaining occlusion for 3 minutes, after which air is quickly released from the cuff without interrupting recording, and recording continues until the initial microcirculation parameters are restored. Subsequent computer processing determines the range of possible changes in blood flow after occlusion: base blood flow, “biological zero”, time before the post-ischemic response begins, recovery time to the level of basic blood flow, time until the maximum post-ischemic blood flow appears, and the maximum post-ischemic blood flow. The response of capillary blood flow to occlusion (RCC) is calculated.

Nitroglycerin test. After the PM returns (microcirculation parameters) to the initial values (after the occlusal test), the initial level is recorded for 1 minute. Then the recording is stopped and 2 doses of nitromint aerosol (Aegis) or 1 tablet (0.5 mg) of nitroglycerin are used sublingually. Resume recording after 2 minutes and continue for 5-8 minutes (maximum action of nitroglycerin) with an assessment of the degree of increase in capillary blood flow (endothelium independent dilatation).

The above study is carried out in the initial state (before treatment) and after iv administration of a vasodilator (100 mg of alprostan or 5 ml of pentoxifylline), followed by an assessment of these indicators in the initial state, as well as the severity and direction of their changes after the administration of medications. After a preliminary analysis of all the studied parameters, we identified (VA - vasomotor activity, HF / LF - the ratio of the amplitudes of high-frequency and low-frequency oscillations, RKKokk - the response of capillary blood flow to occlusion, EZK - endothelium-dependent component, SCng - reduction of blood flow at 2-5 minutes after nitroglycerin), which allow to conditionally, but clearly distinguish 3 significantly different groups of patients in the initial state and after trial therapy (iv administration of pentoxifylline 5 ml or 100 mg of alprostan dissolved in 200 ml physiologically of solution). The studied parameters are converted into arbitrary units, which are then summed.

It was established that 3 groups of patients who after treatment had the full effect of therapy, a partial effect or lack of effect can be conditionally distinguished.

The data obtained are presented in table 1.

Indicator 1 group 2 group 3 group Before after before after before after Hf / lf 0.45 0.6 (+ 33.3%) 0.35 0.46 (31.4%) 0.40 0.44 (10%) VA 19.0 10.5 (-44.7%) 13.3 10.1 (-24.1%) 14.6 13.5 (-7.5%) RKKok 285 226.7 508.6 288 264.1 194.0 (atony) Ezk 4.9 2.7 (-44.9%) 1.9 1.8 (-5.3%) 7.5 8.1 (+ 8%) SKng 59.8% 18.5 (-69.1%) 31% 29.5% (-4.8%) 9.3% 18% (+ 93.5%) Scoring 5 10 fifteen

1 g - reversible stage (good response to therapy) 5–9 points;

2 gr - partially reversible stage 10-14 points;

3 gr - irreversible stage (negative effect of the use of vasodilators) 15 or more points.

VA - vasomotor activity

1 g - reversible stage (good response to therapy) - (-44.7%) - (1 conventional unit)

2 g - partially reversible stage - (-24.1%) - (2 conventional units)

3 gr - irreversible stage (poor effect of the use of vasodilators) - (-7.5%) - (3 conventional units).

HF / LF - the ratio of the amplitudes of high-frequency and low-frequency oscillations

1 g - reversible stage (good response to therapy) - (+ 33.3%) - (1 conventional unit)

2 g - partially reversible stage - (31.4%) - (2 conventional units)

3 gr - irreversible stage (poor effect of the use of vasodilators) - (10%) - (3 conventional units)

RKKokk - the reaction of capillary blood flow to occlusion.

1 g - reversible stage (good response to therapy) - at least 200 - (1 conventional unit)

2 gr - partially reversible stage - at least 200 - (2 conventional units)

3 gr - irreversible stage (poor effect from the use of vasodilators) - less than 200 - (3 conventional units)

EZK (endothelium dependent component)

1 g - reversible stage (good response to therapy) - initially above 2-6, decrease after treatment more than 30% - (1 conventional unit)

2 gr - partially reversible stage - not higher than 2 conventional units, slight decrease or without change (2 conventional units)

3 gr - irreversible stage (poor effect of the use of vasodilators) - above 6 conventional units with an increase after treatment - (3 conventional units)

SKng (decrease in blood flow at 2-5 minutes after nitroglycerin (NG)

1 g - reversible stage (good response to therapy) - ref. above 40% (decrease of more than 60% after treatment) - (1 conventional unit)

2 g - partially reversible stage - initially above 30% (slight change after treatment) - (2 conventional units)

3 gr - irreversible stage (poor effect of the use of vasodilators) - initially less than 10% (increase after treatment) - (3 conventional units)

The method is tested

We examined 58 patients with a reliable diagnosis of systemic scleroderma (SJS) aged 28-46 years with clinical signs of Raynaud's syndrome, the prescription of which was 2-12 years. Along with a general clinical examination, all patients underwent a study of peripheral blood flow (microcirculation system). The state of the microcirculation system was assessed by laser Doppler flowmetry (LDF) on a LAKK-01 apparatus (NPP LAZMA, Russia) in accordance with the instructions for use (V. Kozlov et al., 2002) at an air temperature of 21-24 degrees C the above methodology. All patients underwent occlusal and nitroglycerin functional tests. The results of testing are summarized in table No. 1.

The same patients were assessed for the severity of SR using the classification of G.L. Ratner and G.E. Slutsker, 1990 [G.E. Slutsker, G.L. Ratner. Comprehensive treatment of Raynaud's phenomenon. Guidelines. Kuibyshev, 1990; G.E.Slutsker. Pharmacotherapy syndrome. Raynaud // Clinical Pharmacology and Therapy, 1995, No. 4 (2), pp. 49-51], use three main signs: the color of the skin, the presence of swelling of the fingers, the presence of signs of necrosis of the fingers.

Examples

1) Patient K., 58 years old, suffers from SJS for about 12 years, has severe damage to the esophagus (atony, reflux esophagitis, stenosis from the lower third), heart (myocardiosclerosis), skin (sclerodactyly). Raynaud's syndrome according to the classification of G.L. Ratner and G.E. Slutsker (1990) can be assessed as stage III with a transition to IV. The skin of the hands is cold to the touch, swollen; single scars, multiple ulcerations. Prior therapy with chimes, nifedipine was not significantly improved.

Using our method, a total of 14 points were calculated in a patient, which explains the lack of effect - vasodilators increase vascular atony and increase stagnation on the periphery (the results are shown in the table).

Indicators Originally After treatment Δ% Score VA 13.1 15.7 27.7% 2 Hf / lf 0.34 0.31 8.8% 3 RKKok 158 156 3 Ezk 1.7 4.4 83.4% 3 SKng 29.7% 16% 3 Total: fourteen

Conclusion: vasodilators were not used in the treatment of this patient, which allowed to achieve a positive response to therapy.

2) Patient Yu.: The severity of the syndrome can be assessed as stage IV (according to the classification of G.L. Ratner and G.E. Slutsker).

Using our proposed method, a total of 15 points was calculated, which corresponds to group 3 - treatment with vasodilators is not advisable, as it will cause vascular atony and increase blood stasis on the periphery.

Indicators Originally After treatment Δ% Score VA 4.36 4.27 2.06% 3 Hf / lf 0.63 0.65 3.07% 3 RKKok 170.6 190.4 3 Ezk 10.96 12.1 9.42% 3 SKng 4.3% 5.5% 21.8% 3 Total: fifteen

Conclusion: vasodilators were not used in the treatment, which had a positive effect on the results of therapy.

3) Patient D.: in the initial state, the severity of SR (according to the classification of G.L. Ratner and G.E. Slutsker) can be assessed as stage IV.

Using our method (the results are shown in the table), a total of 10 points are calculated, which corresponds to group 2 - a partial effect of therapy.

Indicators Originally After treatment Δ% Score VA 5,4 3.9 27.8% 2 Hf / lf 0.38 0.63 78.9% 2 RKKok 964 264 83% 2 Ezk 1.8 1.13 37.2% 2 SKng 37% 25% 32.4% 2 Total: 10

Conclusion: the use of vasodilators is possible and will lead to clinical improvement, although according to the classification of G.L. Ratner and G.E. Slutsker, the patient corresponds to stage IV, which means the futility of treatment.

After a course of treatment with alprostan, significant clinical improvement was noted.

4) Patient G. - the results of the study are shown in the table. According to the classification of G.L. Ratner and G.E. Slutsker, stage II.

Using our method, a total score of 8 points was calculated, which allows the patient to be assigned to group 1 (completely reversible severity of CP) and to recommend vasodilating drugs (alprostan, pentoxifylline) for therapy.

Indicators Originally After treatment Δ% Score VA 8.0 7.9 1.25% 3 Hf / lf 0.32 0.41 28.1% 2 RKKok 287 264 one Ezk 8.5 4.6 45.9% one SKng 22.5% 14.7% 34.7% one Total: 8

Conclusion: after treatment, there is a clinical improvement in the course of the disease.

5) Patient M .: Raynaud’s syndrome according to the classification of G.L. Ratner and G.E. Slutsker (1990) can be assessed as stage II with transition to III, using our method the patient can be assigned to group 1 - with full effect after treatment .

Indicators Originally After treatment Δ% Score VA 3.16 5.2 39.2% one Hf / lf 0.43 0.68 36.7% one RKKok 180.56 200.54 2 Ezk 4.96 3,1 37.5% one SKng 39.7% 55.6% 28.6% one Total: 6

Conclusion: the use of vasodilators is recommended (alprostan 100 mg iv - drip). After a course of therapy - an improvement.

6) Patient D.: Reynaud’s syndrome according to the classification of G.L. Ratner and G.E. Slutsker (1990) can be assessed as stage 1, according to our method, the patient can be assigned to group 1 - with the full effect of treatment with vasodilatators.

Indicators Originally After treatment Δ% Score VA 2.46 5.18 52.5% one Hf / lf 0.33 0.56 41.07% one RKKok 218.56 364.0 one Ezk 3.96 2.1 46.9% one SKng 47.7% 70.6% 32.4% one Total: 5

Conclusion: the use of vasodilators is recommended (alprostan 100 mg iv - drip) with subsequent clinical improvement.

7) Patient D.: Reynaud’s syndrome according to the classification of G.L. Ratner and G.E. Slutsker (1990) can be assessed as stage 1, according to our classification - group 1 - with the full effect of treatment with vasodilators.

Indicators Originally After treatment Δ% Score VA 2,35 5.05 53.5% one Hf / lf 0.31 0.52 21.0% 2 RKKok 200,0 275.25 one Ezk 4.76 2.1 55.9% one SKng 42.3% 63.56% 33.4% one Total: 6

Conclusion: the patient was prescribed vasodilators (alprostan 100 mg iv - drip), which led to clinical improvement after a course of therapy.

The degree of coincidence of our proposed method with previously known methods for assessing the severity of CP (in particular, with the classification proposed by G.L. Ratner and G.E. Slutsker, 1990) was 65%; in 38% according to the classification of G.L. Ratner and G.E. Slutsker, a higher degree of SR was determined in contrast to our method, which did not allow previously recommending vasodilators for treatment; in 7% of cases, vasodilators were prescribed, which led to a worsening of the course of the disease.

Our proposed method allows us to more accurately determine the severity and reversibility of vascular changes in Raynaud's syndrome in SJS and, depending on the results, to correct the direction of drug exposure, which will reduce the choice of individual vasodilation therapy and lead to an improvement in the condition of patients, shorten the length of patients in hospital.

Claims (1)

A method for differential assessment of the severity of Raynaud's syndrome in systemic scleroderma, including dopplerography, characterized in that before and after the occlusal test and then before and after sublingual administration of 0.5 mg of nitroglycerin, a laser dopplerogram is recorded in the region of the left forearm at a point located above the base of the styloid processes ulnar and radial bones, indicators are calculated: vasomotor activity (VA), the ratio of the amplitudes of high-frequency and low-frequency oscillations (HF / LF), capillary blood reaction and occlusal sample (RKKok), percent reduction of blood flow at 2-5 minutes after administration of nitroglycerin (SKng), endothelium-dependent component (EZK); the obtained indicator is assigned a value from 1 to 3 points depending on the degree of deviation from the norm, the points are summarized and, with the value of the sum received 5-9 points, the reversible form of Raynaud's syndrome is determined, with the value of 10-14 points, it is partially reversible, and with the sum of points of 15 and more - an irreversible form of Raynaud's syndrome.