Scleroderma Systematica Research Articles

Characteristics of clinical, laboratory, and immunological manifestations in patients with anticentromere antibody-associated Sjögren's disease

Objective: to study clinical and laboratory features in patients with anticentromere antibody (ACA)-positive SjЪgren's disease (SD), as well as the sensitivity of different methods for determination of ACA, and to elaborate an algorithm for differential diagnosis in ACA-positive patients.Patients and methods. The V.A. Nasonova Research Institute of Rheumatology followed up 136 patients who were highly positive for ACA. The investigators used the 2001 Russian criteria for the diagnosis for SD; the 2013 ACR/European League Against Rheumatism (EULAR) criteria for that of scleroderma systematica (SDS); the guidelines of the American Association for the Study of Liver Diseases, the Russian Gastroenterological Association, and the Russian Society for the Study of the Liver for that of primary biliary cholangitis (PBC)/biliary duct epitheliitis in the presence of SD. Lymphomas were diagnosed by biopsies of affected organs according to the WHO classification. SD was diagnosed in 119 patients; SDS in 49 cases (37 with SDS concurrent with SD and 12 with isolated SDS), PBC/biliary duct epitheliitis in 23 (all cases with PBC/biliary duct epitheliitis concurrent with SD and/or SDS); 5 patients were excluded from the investigation. Further analysis included 131 ACA-positive patients. The patients were divided into three groups: SD (n=82 or 62.6%); SD+SDS (n=37 or 28.24%); SDS (n=12 or 9.16%).Results and discussion. Autoantibodies to centromere peptide (CENP) A and CENP-B in the same titers were detected in all ACA-positive patients, regardless of diagnosis. Comparative analysis of three patient groups revealed no statistically significant differences in the frequency of laboratory deviations. The signs characteristic of classical SD (rheumatoid factor (RF)), anti-Ro and anti-La antibodies, leukopenia, higher ESR values, hypergammaglobulinemia, and elevated IgG/IgA levels) were found in a small proportion of patients. The frequency and severity of glandular manifestations did not differ in SD and SD + SDS. PBC/biliary duct epitheliitis was present in 17.5% of ACA-positive patients (in most antimitochondrial antibody-positive cases); no statistically significant differences in its frequency were found between the groups. Other extraglandular manifestations in SD and SD + SDS were identified in a smaller number of patients. All sclerodermic spectrum manifestations were more common in SD and SD + SDS than in BS. Pulmonary arterial hypertension was not diagnosed in any patient from the SD group. MALT lymphomas were detected in 19 ACA-positive patients. Those were present only in BS patients and absent in the SDS group. MALT lymphomas developed in the first 10 years after the onset of SD. The transformation of MALT lymphoma into diffuse large B-cell lymphoma was observed in 2 patients. The main signs of lymphomas in SD patients were persistent parotid salivary gland enlargement, decreased levels of complement C4 and peripheral blood CD19+ cells, as well as cryoglobulinemic vasculitis, serum monoclonal secretion, lymphoid infiltration in the minor salivary glands (a focus score of >4), and severe damage to the salivary and lacrimal glands.Conclusion. ACA-associated SD is an independent disease subtype characterized by an increased risk for SDS, PBC, and MALT lymphomas and by a low frequency of the systemic manifestations and laboratory signs characteristic of classical SD. Regardless of the detected type of antibodies and the presence or absence of extraglandular manifestations, damage to the salivary and lacrimal glands progresses in SD, which often leads to lymphomas; therefore, the therapy that may prevent this complication should be initiated as soon as possible after SD diagnosis. The lymphoproliferation signs identified in this investigation should be taken into account in all ACA-positive patients with SD for the early diagnosis of lymphoid tumors before therapy is prescribed. An algorithm for differential diagnosis in seropositivity for ACA is presented. Determination of autoantibodies to CENP-A and CENP-B does not allow the differential diagnosis in ACA-positive patients.

Panniculitis: rheumatological aspects

Different types of panniculitis (Pn) can be one of the symptoms of rheumatic diseases (RDs). Pn is a group of heterogeneous inflammatory diseases that are characterized by subcutaneous adipose tissue (SAT) lesion and often occur with musculoskeletal and visceral involvements. There is no single concept of the etiology and pathogenesis of Pn. Infections, injures, hormonal and immune disorders, drug intake, pancreatic disease, malignant neoplasms, etc. can play a role in the development of Pn. The latter is associated with RDs in a fairly large group of patients. There have recently been reports of about 200 and 50 cases of only idiopathic lobular Pn in the world and Russian literature, respectively. There have also been publications on other types of Pn, such as erythema nodosum, eosinophilic fasciitis, superficial migratory thrombophlebitis, lupus Pn, dermatomyositis Pn, scleroderma systematica, gout, psoriatic arthritis, etc. There is now a need to study skin changes and SAT lesions in the context of RDs, which will be able to estimate the true clinical and prognostic value of Pn in RDs. Based on recent literature data, this review characterizes the main types of Pn, their clinical and histological signs, and diagnostic methods.

Diagnosis and treatment of interstitial lung disease in scleroderma systematica

Scleroderma systemitica (SDS) is an autoimmune connective tissue disease characterized by excessive fibrosis of the skin and viscera. SDS is prone to be chronic and progressive, is accompanied by the deterioration in quality of life and working ability and has an unfavorable prognosis. Interstitial lung disease (ILD) is one of the most common causes of death due to SDS. The lecture deals with the clinical and laboratory instrumental features of ILD in SDS. SDS-associated ILD occurs in 65–80% of patients and is highly diverse in the degree of severity and the tendency to progression. In the majority of patients, the fibrous process in the lung occurs in the early years of the disease, is limited and progresses slowly. Severe lung damage with rapid progression develops only in 10–15% of cases. Evaluation of lung damage in SDS includes pulmonary function tests, lung diffusing capacity determination, Doppler echocardiography analysis, multispiral computed tomography (MSCT) of the chest, bronchoalveolar lavage, lung biopsy with morphological examination of its specimens, as well as right heart catheterization. The best technique for detecting ILD is MSCT, as chest radiography has a low sensitivity in the early stages of the disease. IPL is treated in accordance with the 2017 ACR/EULAR guidelines; the leading role is played by immunosuppressive drugs, such as cyclophosphamide and mycophenolate mofetil. Antifibrotic drugs (pirfenidone, nintedanib) are being tested now .

Positivity for antiribonucleoprotein antibodies in rheumatic diseases: focus on scleroderma systematica

The review deals with the problem of antibody production in scleroderma systematica (SDS), with a focus on antiribonucleoprotein (RNP) antibodies: frequency, structure, and clinical associations. SDS is a progressive polysyndromic disease with characteristic lesion of the skin, locomotor apparatus, viscera (heart, lungs, digestive tract, and kidneys), and common vasospastic disorders as Raynaud's syndrome, the basis for which are the processes of connective tissue disorganization with a predominance of fibrosclerotic changes and vascular pathology as peculiar endarteritis obliterans. The presence of antibodies to different autoantigens is a distinguishing feature of SDS. Among the patients who meet the classification criteria for SDS, there is a subgroup of patients who are not found to have SDS-specific antinuclear antibodies, but have antibodies to soluble nuclear autoantigens, namely, antibodies to RNP. This type of autoantibodies is described in various systemic connective tissue diseases: systemic lupus erythematosus, dermatomyositis, polymyositis, and SDS. The detection rate of anti-RNP antibodies in SDS varies from 5 to 30% in different ethnic groups. In addition, positivity for anti-RNP antibodies is a characteristic feature of mixed connective tissue disease. A more detailed study of anti-U1-RNP antibody-positive patients with SDS, by identifying a new subtype of SDS, comparing, and searching for dissimilarities of anti-U1-RNP antibody carriers from other well-described phenotypes of SDS, is of interest today. This problem is relevant, by taking into account the personalized approach to following up patients, which is actively being elaborated in rheumatology.

Antibodies against post-translationally modified vimentin peptides in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is the most common autoimmune rheumatic disease (ARD) associated with the production of broad-spectrum antibodies, the detection of which is of important diagnostic and prognostic values. The problems of RA diagnosis are associated with the limited sensitivity of currently used serological markers. Objective : to evaluate the diagnostic informative value of autoantibodies against different post-translationally modified (PTM) vimentin peptides in patients with RA and other ARDs. Patients and methods . The frequency of autoantibodies against different isoforms of vimentin was estimated in 144 patients with RA, in 36 patients with other ARDs (ankylosing spondylitis and scleroderma systematica), and in 25 patients of a control group, who had no rheumatic diseases. Antibodies against different PTM vimentin peptides obtained using citrullination, carbamylation/homocitrullination, and acetylation were determined. Anti-citrullinated vimentin (anti-CitVim) peptide, anti-carbamylated vimentin (anti-CarVim) peptide, and anti-acetylated vimentin (anti-AcVim) peptide autoantibodies of IgG and IgA classes were estimated in the serum by enzyme immunoassay. Results. The results of the study showed that IgG and IgA anti-CitVim had the maximum area under the ROC curve (AUC) (0.859 and 0.855, respectively). A slightly smaller AUC was seen in IgG anti-CarVim (0.85), IgG anti-AcVim (0.784), and IgA anti-AcVim (0.651). The diagnostic sensitivity and diagnostic specificity were 66.2 and 96.77% for IgG anti-CitVim, 60.56 and 91.94% for IgA anti-CitVim, 91.55 and 53.23% for IgG anti-CarVim, 63.38 and 93.55% for IgG anti-AcVim, and 49.3 and 70.97%, IgA anti-AcVim, respectively. Positivity for IgG anti-CitVim, IgG anti-CarVim, and IgG anti-AcVim, and anti-IgA CitVim was significantly more frequently detected in patients with RA than in those with other ARDs and in the control group (p<0.05). Thus, the identified autoantibodies against modified vimentin peptides proved to be diagnostically useful serological markers in RA. IgA anti-CarVim and IgA anti-AcVim can also be used in the diagnosis of RA in patients who are seronegative for rheumatoid factor and anti-cyclic citrullinated peptide antibodies. Conclusion. When the upper reference limits are set for IgG anti-CitVim (20 U/ml), IgA anti-CitVim (8.95 U/ml), IgG anti-CarVim (6.25 U/ml), IgG anti-AcVim (17.1 U/ml), and IgA anti-AcVim (9.85 U/ml), antibodies against different isoforms of vimentin are recommended for use as additional laboratory tests to diagnose RA.

Bone mineral density in patients with scleroderma systematica

To study the frequency and magnitude of a reduction in bone mineral density (BMD) and its association with clinical parameters in patients with scleroderma systematica (SDS). Fifty-six postmenopausal women aged 45-71 years (58.1±7.1 years) with a valid diagnosis of SDS and 44 age-matched healthy women were examined. Dual-energy X-ray absorptiometry (Hologic QDR 4500, Waltham, MA) was performed in all the included patients to measure BMD in the lumbar spine (L(I)-L(IV)), femoral neck, and proximal femur. The patients with SDS and the healthy women showed no differences in body mass index (BMI) (24.7±4.6 and 25.7±3.5 kg/m(2), respectively) and postmenopause duration (9.6±6.4 and 9.5±7.0 years, respectively); menopause occurred earlier in the patients with SDS than in the healthy women (46.9±3.6 and 49.7±3.0 years, respectively (p<0.001). The patients with SDS versus the controls had a significantly lower BMD in the lumbar spine (0.821±0.121 and 0.861±0.092 g/cm(2); р<0.05), femoral neck (0.620±0.129 and 0.736±0.112 g/cm(2); p<0.0001), and proximal femur (0.736±0.148 and 0.884±0.124 g/cm(2); р<0.0001). Osteoporosis (OP) was detected in 29 (52%) of the 56 patients and in only 5 (11%) of the 44 control women (р<0.0001). The patients with diffuse SDS displayed a much greater reduction in BMD in all the regions than those with circumscribed SDS. BMD was significantly lower in the patients treated with glucocorticosteroids (GCS) than in the untreated ones. In the control group, BMD was associated with age, duration of menopause, and BMI. In the patients with SDS, BMD was correlated with BMI and inversely correlated with duration of menopause, and the magnitude of a BMD reduction was closely related to disease duration. The patients also showed an inverse correlation of BMD with the daily dose of GCS. The postmenopausal women with SDS were found to have a lower BMD in 80% of cases. In this category of women, the reduction in BMD was significantly commoner and more pronounced than in the age-matched healthy women. Low BMI, diffuse SDS, disease duration, and GCS use are risk factors for reduced BMD and OP.

Scleromyxedema concurrent with dermatomyositis and paraproteinemia: A case report

The paper describes the case of a female patient who had at least three diseases: scleromyxedema, dermatomyositis/polymyositis (DM/PM), and paraproteinemia (monoclonal gammopathy). The concurrence of these diseases determines the atypism of their clinical and morphological patterns, as well as refractoriness to performed therapy. Scleromyxedema preceded DM followed by paraproteinemia, which does not rule out its presence in an earlier period when the patent was not carefully examined. The specific feature of this case is scleromyxedema concurrent with DM that was prevalent in the clinical picture of the disease, by determining the severity of the patient’s status and the need to be treated with high-dose glucocorticoids in combination with immunosuppressive drugs. There was no evidence for scleroderma systematica that was supposed to be present in the patient who had scleroderma-like skin involvement. The authors have repeatedly mentioned the concurrency pattern of scleroderma diseases, which reflects the close mechanisms of their development and hinders the identification of specific nosological entities. In this observation, the concurrence of scleromyxedema and DM complements a group of overlap diseases observed in dermatology and rheumatology. Paraproteinemia characteristic of scleromyxedema is occasionally encountered in systemic connective tissue diseases. The patient had monoclonal gammopathy that is most common in scleromyxedema. No signs of myeloma and tumors were seen. Classical paraneoplastic DM/PM was not detected either, which does not rule out the fact that the mechanism responsible for the development of this syndrome and the disease is similar in the patient described.

Clinical value of surfactant protein D as a biomarker of pulmonary fibrosis in patients with scleroderma systematica in relation to the presence of gastroesophageal reflux

To study the role of serum surfactant protein D (SP-D) as a biomarker of lung injury in scleroderma systematica (SDS) in relation to the presence of gastroesophageal reflux (GER). Fifty-six patients (mean age 46±14 years) with diffuse and circumscribed SDS were examined and underwent pulmonary functional tests, X-ray and, if lung injury was present, high-resolution computed tomography of the lung, echocardiography, gastroduodenoscopy, and barium X-ray of the esophagus; an enzyme-linked immunosorbent assay was used to determine serum SP-D levels. SP-D concentrations significantly correlate with the presence of lung injury in SDS and are significantly higher in the presence of pulmonary fibrosis and the signs of frosted glass and honeycomb lung patterns. SP-D levels were higher in the patients with lung injury and SDS in the group of those with pulmonary fibrosis and GER than in the group of pulmonary fibrosis patients without the latter. Serum SP-D may be considered in a number of biomarkers for the severity of lung injury in SDS, including GER-associated lung injury.

Angiogenesis and its association with inflammation and fibrosis in course of the development of scleroderma systematica

Scleroderma systematica (SDS) is a chronic autoimmune disease characterized by severe fibrosis of the skin and visceral organs. Vascular disorders are an important component of the disease, but the mechanisms of vascular injury and their prevention are unknown. Angiogenesis in SDS is accompanied by the apparent expression of angiogenic factors, such as vascular endothelial growth factor and basal or fibroblast growth factor. Imbalance of these markers with endostatin expression is noted. This disease is characterized by inflammation and the intensity of neoangiogenesis correlates with its activity. The fact that there may be a pathogenic relationship between the processes of angiogenesis and the intensity of further fibrosis is shown. There is a vicious circle of the induction and maintenance of the processes of angiogenesis, inflammation, and fibrosis in SDS.

Clinical and hemodynamic characteristics and possibilities for therapy in patients with severe (functional class IV) pulmonary arterial hypertension associated with diffuse connective tissue diseases

To study the clinical and hemodynamic characteristics of a group of patients with Functional Class (FC) IV pulmonary arterial hypertension (PAH) developing in the presence of diffuse connective tissue diseases (DCTD) and to evaluate the efficacy of intravenous iloprost. The study enrolled 59 patients with PAN-DCTD, including 7 who had FC IV and 8 who developed this condition during a follow-up. The diagnosis of PAH was based on pulmonary artery catheterization findings. FC IV was diagnosed using the conventional New York Heart Association classification. All the patients received PAH-specific therapy (bosentan, sildenafil); the patients with FC IV had combined therapy; 4 patients were treated with intravenous iloprost calculated with reference to 0.5-2.5 ng/kg/min for 15 days. In addition to the patients with FC IV, 3 patients with unstable FC Ill were given iloprost. Besides targeted therapy, all the patients received standard treatment, including diuretics, and ionotropic therapy. Evaluation of hemodynamics in patients with different FCs revealed the most important differences in right atrial pressure, cardiac output, cardiac index, and pulmonary vascular resistance. A linear relationship was seen between the level of this indicator and FC, the closest correlation being for hemodynamic parameters characterizing right ventricular systolic function. There were no changes in mean pulmonary artery pressure; only the patients with FC IV were found to have its slight elevation (from 52 ± 15 to 55 ± 11 mm Hg). Pulmonary artery wedge pressure remained unchanged regardless of FC. Intravenous iloprost was noted to have an obvious positive effect on both clinical and hemodynamic parameters. Catheterization verified improvement in 6 out of the 7 patients; no hemodynamic changes were found in 1 patient during 15-day therapy. The patients with FC IV PAH-DCTD have clinical and hemodynamic features responsible for a fatal prognosis. The results of using intravenous iloprost in patients with decompensated PAH associated with scleroderma systematica convince to use its PAH-specific tablets in cases of verified clinical deterioration when taking its dosage form.

NEW CLASSIFICATION CRITERIA FOR SCLERODERMA SYSTEMATICA (a lecture)

In 1980, the American College of Rheumatology proposed the first criteria as tentative for the diagnosis of scleroderma systematica (SDS). These criteria were aimed at revealing the comprehensive picture of mainly the diffuse form of the disease. They could not timely make a diagnosis in the low manifestive forms of the disease or virtually reveal its early stages that were most therapeutically promising. The review traces the evolution of approaches to diagnosing SDS and considers the novel classification criteria elaborated to select patients for epidemiological surveys and clinical trials. They include 8 parameters, each having scores. Skin thickening on both hands above the metacarpophalangeal articulations was highest (9 scores). The clinical variants of skin thickening on the fingers as its swelling (2 scores) or sclerodactyly (4 scores) are estimated from the maximum scores, as digital ischemia (sores, 2 scores; cicatricles, 3 scores). Teleangiectasias and characteristic capillaroscopic changes, as well as leading lung injury (pulmonary hypertension and/or interstitial lung disease) are rated as 2 scores each. Three scores are added to the total amount when Raynaud's syndrome is present and SDS-specific (anti-Scl-70, anti-centromere, and anti- RNA polymerase III) autoantibodies are detected. The patients gaining a total of 9 scores or more are classified as having definite SDS. Testing the novel criteria on a validation sample of 405 people showed that their sensitivity and specificity were 91 and 92%, respectively.

RITUXIMAB TREATMENT FOR INTERSTITIAL LUNG INJURY IN SCLERODERMA SYSTEMATICA

Objective: to study the efficiency and tolerance of rituximab (RTM) treatment in patients with scleroderma systematica (SDS) with interstitial lung injury (ILI). Subjects and methods. The trial included 27 patients (26 women and 1 man) (mean age 45.7±13.0 years), with diffuse (n=13) and circumscribed (n = 14) forms and a disease duration of > 5 years in 63%. All the patients underwent chest computed tomography; examination of external respiratory function, including forced vital capacity (FVC) and diffusing capacity of the lung (DCL), as well as echocardiographic study. The efficiency of the treatment was evaluated from changes in FVC, skin score, and disease activity index. The indicators were compared prior to the treatment and one year after the first administration of RTM. The latter was injected with premedication (125–500 mg of methylprednisolone intravenously) 500–1000 mg per administration. The mean dose of RTM was low and amounted to 1.3 g per year. Results. As estimated by the physician, good, satisfactory, no effects were seen in 81.5, 14.8, and 3.7% of the patients, respectively. There was a significant increase in mean FVC one year after the first administration of RTM and a reduction in the total activity of the disease, including skin syndrome. DCL was substantially unchanged in the entire group. In the diffuse and circumscribed forms of the disease, FVC increased significantly and to the same extent. A clinically significant increase in FVC (by 11%) was achieved in patients with a disease duration of ≤5 years and mild lung injury. In people with a more than 5-year disease duration, FVC was initially decreased to a greater extent and the treatment-induced increase was only 3.7%. A significant and permanent decline in peripheral blood B lymphocytes was noted when both the standard dose (2 g) of RTM and its lower doses (0.5–1 g) were administered. RTM treatment was well tolerated, but complicated by mild intercurrent infections in 11% of cases within the first 2 months after RTM administration. Conclusion. The findings substantiate the indications for RTM use primarily in the early stage of the disease. The admittedly low doses of RTM have an inadequate effect if the disease is long-lasting. Further study of dosage regimens for RTM is required within the framework of controlled trials.

New areas of the pharmacotherapy of rheumatic diseases are inhibition of interleukin-6 and interleukin-17

Significant progress related particular to the use of interleukin (IL)-6 and IL17 inhibitors has been made in the pharmacotherapy of rheumatic diseases. IL-6 is a cytokine that has a wide range of biological activity and affects different types of cells. There is evidence for the important role of IL-6 hyperproduction not only in rheumatoid arthritis (RA), but also in other immune inflammatory rheumatic diseases (systemic lupus erythematosus (SLE), scleroderma system atica, idiopathic inflammatory myopathies, giant cell arteritis, etc.). IL-6 inhibition primarily with humanized monoclonal antibodies against IL-6 receptors (tocilizumab – TCZ)) is considered as one of the promising areas of pharmacotherapy for these diseases. The successful results of TCZ use have created pre requisites for the design of other medicaments that can form a novel class of IL-6 inhibitors, genetically engineered biological agents, in the future. There is another new area in the treatment of immune inflammatory rheumatic diseases, which is the inhibition of the cytokine IL17A that provides interaction between innate and acquired immunity and is synthesized by a wide range of immunocompetent cells, the socalled Th17 ones in particular. IL-17A is implicated in the immunopathogenesis of a broad spectrum of immune inflammatory diseases, including RA, psoriasis, psoriatic arthritis, inflammatory bowel diseases, SLE, allergic diseases, transplantation immunity, obesity, carcinogenesis, etc. Elevated IL-17A concentrations correlate with the activity and severity of a pathological process. The pathogenetic effects of IL-17 in RA may be associated with its involvement in the development of synovial inflammation and joint destruction. The therapeutic efficiency of inhibition of Th17 cells and IL-17A synthesis in autoimmune diseases was first indirectly demonstrated in psoriasis. This provided the basis for the elaboration of therapeutic approaches associated with the direct inhibition of IL-17 effects in these patients. Thus, the use of IL-6 inhibitors (primarily TCZ) and, probably, IL-17 will make significant progress in the treatment of not only RA, but other severe potentially deadly immune inflammatory rheumatic diseases in the future.

Assessment of lung ultrasound in patients with scleroderma systematica and interstitial lung disease

Objective: to estimate the informative value and reproducibility of ultrasound study (USS) in interstitial lung disease (ILD) in patients with scleroderma systematica (SDS) and to compare ultrasound lung comet (ULC) scores with the data of multislice spiral computed tomography (MSCT) of the lung and its function tests. Subjects and methods. Forty patients with SSD and ILD were examined. According to the extent of lung injury, the patients were divided into two groups: 1) 12 patients with significantly pronounced changes (>20% lung involvement, as evidenced by MSCT); 2) 28 patients with just noticeable changes (<20% lung involvement). ULC scoring was used to record the results of lung USS. Results. In the SDS patients from Group 1, the ULC scores were significantly higher than those in Group 2 (113.6+48.3 and 35.3+32.7, respectively; р < 0.0005). Those in the entire group were inversely correlated with forced vital capacity (r = -0.56; р < 0.05) and diffuse lung capacity (r = -0.57; р < 0.05). Assessment of the reproducibility of ULC scoring disclosed no significant differences in the data obtained by two investigators; the Kendall concordance coefficient turned out to be rather high (r = 0.81; p < 0.001). Conclusion. Lung USS may be used as a simple, well-reproducible additional study of ILD in SDS, which can identify lung fibrosis and estimate its extent.

Microcirculatory disorders in scleroderma systematica: an association with vascular wall stiffness

Objective: to study the specific features of regulation of peripheral vascular tone and their association with the endothelial structure and function of large vessels in patients with scleroderma systematica (SDS). Subjects and methods. The investigation enrolled 25 patients with SDS (mean age, 47±2.6 years; mean disease duration, 8.3+1.7 years) and 15 apparently healthy individuals matched for age and gender. Comprehensive examination involved laboratory and instrumental studies, laser Doppler study to evaluate endothelium-dependent and endothelium-independent vasodilation, as well as applanation tonometry calculating the pulse wave velocity and augmentation index. Results. All the patients were found to have impaired peripheral vascular responsiveness as compared to the controls. The examination established a relationship between the magnitude of endothelium-dependent vasodilation and the stiffness index of large vessels. There was no association between endothelium-independent vasodilation and vascular elasticity parameters.

A case of osteopoikilia in a female patient with scleroderma systematica

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

ESOPHAGEAL PATHOLOGY IN SCLERODERMA SYSTEMATICA: CLINICAL AND ENDOSCOPIC FINDINGS

Esophageal lesion is a characteristic visceral manifestation of scleroderma systematica (SDS). Sclerodermic esophagitis complications, such as ulcers and Barretts esophagus (BE), bring a threat to life and require active and long-term therapy. Objective: to evaluate the incidence, clinical symptoms, and endoscopic picture of esophageal pathology in patients with SDS, as well as the efficiency of therapy with proton pump inhibitors (PPIs). Subjects and methods. Three hundred and fifty-six patients (women, 92.6%; men, 7.4%) aged 47.8±19.7 years with SDS and 1018 patients (women, 89.0%; men, 11.0%) aged 44.1±16.3 years with rheumatoid arthritis (RA) were examined. Out of them, 66.7 and 52.6% took glucocorticoids (GC), 21.6 and 82.9% received nonsteroidal antiinflammatory drugs (NSAIDs), 13.2 and 0% had D-penicillamine, 15.7 and 56.5% had cytotoxic drugs, and 23.7 and 8.7% had PPIs, respectively. All the patients underwent endoscopic study of the upper gastrointestinal tract. Results. The subjective symptoms of esophageal pathology were in 64.0 and 33.9% of the patients with SDS or RA, respectively (p < 0.001). Dysphagia and retrosternal pain were observed in 10.1 and 7.0% of the patients with SDS, respectively, and in only 1.7% of the patients with RA. Endoscopy revealed mucosal hyperemia in 27.4 and 1.5% of the patients, erosive esophagitis in 21.9 and 2.2%, and esophageal ulcers in 4 (1.1%) and 0%, respectively (p = 0.000). Esophageal mucosal biopsy was performed in 92 of the 356 patients with SDS, which could identify BE (intestinal metaplasia) in 19 (20.1%) cases. There was a significant correlation between the clinical symptoms of the esophagus and the endoscopic signs of erosive esophagitis (p = 0.001). There was no relationship between esophageal pathology, age, and the use of drugs (NSAIDs, GC, cytotoxic drugs). Erosive esophagitis and BE were detected in 35.0 and 36.8% of the SDS patients (n = 90) during their regular use of PPIs. All 4 patients with esophageal ulcers regularly took PPIs. Conclusion. Esophageal pathology is noted in the majority of patients with SDS and in only individual patients with RA. BE is a common complication of SDS, which requires a regular endoscopic examinations in all patients with this disease. PPIs are not always rather effective, which determines it necessary to use large doses of these drugs or combination therapy.

EXTRACELLULAR DNA AND THE LEVEL OF ITS METHYLATION IN DIFFERENT RHEUMATIC DISEASES

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

The first Russian experience with the endothelin 1 receptor inhibitor traclir used in patients with pulmonary hypertension associated with systemic connective tissue diseases

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

Scleroderma systematica concurrent with neoplasm

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.