Vol 82, No 5 (2010)


Rheumatic diseases: Current technologies and perspectives of laboratory diagnosis

Nasonov E.L., Aleksandrova E.N., Nasonov E.L., Aleksandrova E.N.


The problems of the laboratory diagnosis of rheumatic diseases (RD), by determining a broad spectrum of biomarkers at the cellular and humoral levels, are considered. Serological assays aimed at detecting circulating autoantibodies are noted to hold a central position in the laboratory diagnosis of RD. Measurement of the blood levels of inflammatory markers maintains its diagnostic value; it is shown to be important to multiplex analysis, a fundamentally new laboratory technique in rheumatology.
Terapevticheskii arkhiv. 2010;82(5):5-9
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Prevalence of rheumatoid arthritis in Russia (according to epidemiological findings)

Galushko E.A., Erdes S.F., Bazorkina D.I., Bol'shakova T.Y., Vinogradova I.B., Lesnyak O.M., Men'shikova L.V., Myasoedova S.E., Protopopova R.N., Chernykh T.M., Galushko E.A., Erdes S.F., Bazorkina D.I., Bolshakova T.Y., Vinogradova I.B., Lesnyak O.M., Menshikova L.V., Myasodoyeva S.E., Protopopova R.N., Chernykh T.M.


Aim. To define the prevalence of rheumatoid arthritis (RA) from the data of an epidemiological study. Subjects and methods. During a questionnaire survey of 37057 adults of Russia, patients with complaints of articular swelling (n = 4975) were selected; of the latter a group (n = 3420) was randomly formed to be clinically examined by rheumatologists in order to detect RA. The 1987 ACR criteria were used for its diagnosis. Results. According to the data of the questionnaire survey, RA was diagnosed in 159 (4.6%) of the 3420 patients with complaints of articular swelling. The prevalence of RA in Russia averaged 0.61%. Among the respondents who complained about articular swelling during the questionnaire survey, 258 (7.5%) respondents considered to have RA before rheumatological examination. While comparing the diagnoses reported by the respondents during the survey and the final diagnosis established by a specialist, RA was confirmed only in 61 (24%) patients. Out of all the identified patients with RA (n = 159), only 61 (38%) were aware of their diagnosis. In RA patients with less than one-year articular complaints (n = 24), 17% were familiar with their diagnosis; the diagnosis was first made in the others (n = 20). Among the patients with long-term articular complaints (n = 135), 42% were aware of their diagnosis. Conclusion. The epidemiological survey indicated that the number of patients with RA were twice higher than those given in the official statistics of the Russian Federation (671,000 versus 300,000, respectively). In outpatient practice, RA is correctly diagnosed only in 38% of cases. There is a significant hyperdiagnosis of this disease. The duration of articular complaints affects the establishment of the diagnosis of RA.
Terapevticheskii arkhiv. 2010;82(5):9-14
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Magnetic resonance imaging of the hand as an early diagnostic method for rheumatoid arthritis

Rapoport I.E., Luchikhina E.L., Pogozheva E.Y., Smirnov A.V., Karateev D.E., Rapoport I.E., Luchikhina E.L., Pogozheva E.Y., Smirnov A.V., Karateyev D.E.


Aim. To provide the qualitative and quantitative characteristics of changes revealed by the data of magnetic resonance imaging (MRI) of the hand and by those of X-ray study of the hand and foot in patients with early rheumatoid arthritis (ERA). Subjects and methods. The study enrolled 110 patients (90 females, 20 males; age 49.6 ± 12.2 years) examined in the framework of the RADICAL program at the Research Institute of Rheumatology, Russian Academy of Medical Sciences. The mean duration of the disease was 5.61 ± 3.17 months. The diagnosis of rheumatoid arthritis was established by the 1987 ARA criteria in all the patients on primary standard examination comprising X-ray study of the hand and feet and evaluation by the modified Sharp method. MRI of the hand was performed in all the patients, by assessing the result by the OMERACT-RAMRIS procedure. Results. Destructive changes (cysts and erosions) evidenced by X-ray study were found in the wrists, metacarpophalangeal articulations (MPA), and foot in 7.27, 8.2, and 13.64%, respectively. MRI revealed destructions in the wrist, MPA, and metacarpal bone base in 50, 60, and 16.36%, respectively. Overall, erosions could be seen on X-ray films and MRI scans in 20.91 and 67.27%, respectively (p < 0.001). MRI revealed bone edema (osteitis) in 46.4% of the patients; there was no difference in the detection rate between the extremities. MRI synovitis was found in 99% of the patients, the right hand being significantly more commonly affected. Detailed characterization of the changes revealed by MRI and X-ray was obtained in patients with ERA. Conclusion. MRI detected erosions significantly more frequently than did X-ray (p < 0.001), which confirms the high value of low-field MRI diagnosis on primary examination of patients with ERA and supports the opinion that the results of this study should be included into the diagnostic criteria of ERA.
Terapevticheskii arkhiv. 2010;82(5):14-22
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Retrospective analysis of the course and outcomes of juvenile arthritis in adult patients

Salugina S.O., Salugina S.O.


Aim. To assess the course and outcomes, functional and social status in long ill patients with juvenile arthritis (JA). Subjects and methods. The study included 213 patients aged 16 to 60 years (mean age 23.9 ± 6.5 years) with JA with its duration of 10 to 53 years (mean 17.4 ± 6.8 years). Ninety-seven patients were examined at the Institute of Rheumatology; the others filled in the social status and health assessment questionnaires (HAQ). Results. Polyarthritis and oligoarthritis were found in 72.9 and 17.7%, respectively; no articular changes were seen in 9.4%. Systemic signs were noted in 3.1%. A fourth of the patients developed uveitis. Articular functional limitations were minimal or absent (functional class (FC) I, II and HAQ = 0-1.0 score) in 71-81.2%; 18.8-29% needed assistance by other persons (FC III, IV and HAQ = 2.1-3.0 scores). The FC correlated with the clinico-laboratory indicators. Mild or moderate JA persisted in 87.8% of the patients. A third of the patients were found to have erosions; 31.9% presented with ankylosis; 27.8% had aseptic necrosis of predominantly the femoral head. The health status was appraised as good or very good, satisfactory, or bad by 43.3, 39.8, and 16.9% of the patients, respectively. 78.9% of the patients worked or studied; 48.2% graduated from or continued their education at the institute; 31.7% were married; 46 patients had children. Conclusion. In most adult patients with childhood-onset JA, the activity of the disease reduced; a good functional outcome was noted. The health status made it possible to obtain profession and to be adapted to routine life and social environment. The patients with the severer course and outcome of the disease with the formation of significant functional limitations needed treatment and further medical follow-up.
Terapevticheskii arkhiv. 2010;82(5):22-29
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Pneumonia in patients with rheumatoid arthritis: the frequency of development, the specific features of its course and risk factors

Polyanskaya M.V., Belov B.S., Balabanova R.M., Polyanskaya M.V., Belov B.S., Balabanova R.M.


Aim. To study the frequency of development of pneumonia, the specific features of its course and risk factors (RF) in inpatients with rheumatoid arthritis (RA). Materials and methods. The archival records (a total of 9059 case histories) of patients with RA treated at the Institute of Rheumatology, Russian Academy of Medical Sciences, during 7 calendar years (1994-1996, 2003-2006) were retrospectively studied. Case histories containing evidence for pneumonia sustained during the patient's hospital stay were selected for analysis. During the analysis, the authors took into account the clinical characteristics of RA, laboratory and X-ray parameters, and comorbidity, including pneumonia. Results. In the inpatients, the frequency of development of pneumonia was 0.8%. The risk factors of pneumonia were the high activity of RA, its systemic manifestations and no use of essential antirheumatic drugs. In 70% of RA patients developing pneumonia, the body temperature was normal or subfebrile; productive cough was absent in 50% of the patients; a third had no cough. Clear X-ray lung tissue infiltration was seen in 48% of cases. Clinical leukocytosis was absent in 50% of the patients; at the same time, there were statistically significant increases in the count of stab neutrophils and erythrocyte sedimentation rate. Conclusion. The inpatients with RA develop pneumonia in about 0.8% of cases, which is characterized by an obliterated course and usually develops with the high activity of RA, its systemic manifestations and no use of essential antirheumatic drugs.
Terapevticheskii arkhiv. 2010;82(5):29-33
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Recurrences of thromboses and hemorrhagic complications in patients with antiphospholipid syndrome during therapy with warfarin plus aspirin

Kondrat'eva L.V., Patrusheva N.L., Patrushev L.I., Aleksandrova E.N., Kovalenko T.F., Ostryakova E.V., Reshetnyak T.M., Kondratyeva L.V., Patrusheva N.L., Patrushev L.I., Aleksandrova E.N., Kovalenko T.F., Ostryakova E.V., Reshetnyak T.M.


Aim. To estimate the frequency of relapses of thrombotic and hemorrhagic complications during moderately intensive therapy for antiphospholipid syndrome (APS) with warfarin with and without aspirin. Subjects and methods. Eighty-two patients diagnosed as having the antiphospholipid syndrome were examoned. Group 1 patients (n = 49) received warfarin alone as an antithrombotic drug; Group 2 patients (n = 33) had a combination therapy with warfarin plus aspirin. The efficiency of therapy was evaluated from the number and rate of recurrences of thromboses and transient ischemic attacks (TIA) and its safety was assessed from the frequency and number of hemorrhages during the study. The genetic variants of cytochrome P450 CYP2C9 were determined in 52 of the 82 patients; mutations in the gene for vitamin K epoxide reductase complex 1 (VCORC1) were revealed in 22 patients. Results. During the follow-up, antithrombotic therapy was ineffective in 18.4 and 36.6% of the Groups 1 and 2 patients, respectively (p = 0.07). The rate of poor outcomes (thromboses and TIA) was 7 and 14.8 cases per 100 person-years, respectively. The first six months of warfarin therapy proved to be most risky for thrombotic events to occur - this period was responsible for 37% of bleedings. Hemorrhagic complications of antithrombotic therapy developed in 46.9 and 60.6% of Groups 1 and 2 patients, respectively (p = 0.26). Major hemorrhages were observed more frequently in the combination (warfarin plus low-dose aspirin) therapy group than in the warfarin monotherapy group. Mutant cytochrome P450 gene variants (CYP2C9*2 and CYP2C9*3) were present in 38.5% of the patients; VCORC1 gene mutations were observed in 27.3%. The number of nasal and gingival hemorrhages was increased in patients with CYP2C9*3 and homozygous VCORC1 gene mutations. Conclusion. Moderately intensive warfarin therapy (international normalized ratio 2.0-3.0) could generally reduce the frequency of recurrent thrombotic events by at least 2-fold as compared with that before warfarin administration. The efficiency of using warfarin alone or in combination with aspirin in APS was found to be similar; and its safety was higher during monotherapy therefore it is undesirable to combine warfarin with antiaggregants in real clinical practice. The determination of CYP2C9 and VCORC1 genotypes in patients with APS before warfarin use allows excessive hypocoagulation and related hemorrhages to be avoided.
Terapevticheskii arkhiv. 2010;82(5):33-39
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Arterial hypertension in patients with systemic connective tissue diseases and hemorrhagic vasculitis

Shilkina N.P., Yunonin I.E., Stolyarova S.A., Dryazhenkova I.V., Shilkina N.P., Yunonin I.E., Stolyarova S.A., Dryazhenkova I.V.


Aim. To study the specific features of 24-hour blood pressure (BP) profile and its association with plasma renin activity in patients with systemic connective tissue diseases and hemorrhagic vasculitis (HV). Subjects and methods. One hundred patients aged 22 to 58 years, including 45 patients with systemic lupus erythematosus (SLE), 25 with scleroderma systematica (SDS), and 30 with HV, were examined. A control group included 30 healthy individuals. 24-hour BP profile, renal function, and plasma renin activity were studied. Results. Arterial hypertension (AH) was revealed in 53% of patients. AH occurred in 62% of patients with SLE, in 40% of those with SDS, and in 50% of those with HV. In patients with systemic connective tissue diseases and HV, the 24-hour BP profile was characterized with increases in the mean values and indices of pressure load and with a predominance of subjects with inadequate decreases in nocturnal BP (non-dippers), and with the higher values of its variability in the presence of elevated plasma renin concentrations in patients with SLE. In all the patients, the elevation of BP and its circadian dynamics depended on the renal functional status that correlated with the activity of a systemic inflammatory process. Conclusion. The patients with systemic connective tissue diseases and HV were found to have prognostically poor types of 24-hour BP profile (night-peaker, non-dipper), the magnitude of which elevation depended on renal function and plasma renin activity.
Terapevticheskii arkhiv. 2010;82(5):40-45
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Behcet's disease and associations with HLA-B5 antigen (a review of literature and the authors' findings)

Goloeva R.G., Alekberova Z.S., Guseva I.A., Krylov M.Y., Goloyeva R.G., Alekberova Z.S., Guseva I.A., Krylov M.Y.


Aim. To estimate the distribution of HLA Class I (A, B) antigens in patients with Behcet's disease (BD) and the association of HLA-B5 antigen with the clinical manifestations of the disease in different ethnic and population groups in relation to gender. Subjects and methods. The study covered 93 patients (68 males, 25 females) from the representatives of 24 ethnicities with the verified disease. HLA Class I antigens were typed by the microlymphocytotoxic technique, by applying an antileukocytic serum kit (GISANS, Saint Petersburg). Results. In patients with BD, the prevalence of HLA-B5 antigen proved to be significantly higher than that in the controls (72.0 and 21%, respectively) and to be similar in patients of different ethnicities living in the Caucasus and Transcaucasus (80-83%) while the number of HLA-B5 antigen-positive patients with BD was thrice less in the Russian population than in other BD patients (p < 0.01). There was a significant correlation of HLA-B5 antigen with ocular lesion (retinal angiitis) predominantly in male patients with BD. Conclusion. The prevalence of HLA-B5 antigen was higher in patients with BD than in the population-based control. The diagnostic value of this antigen is not so great, for example, in the Russian population of patients with BD. The presence of HLA-B5 antigen in the phenotype of male patients with BD may be regarded as a prognostically poor marker of development of eye diseases.
Terapevticheskii arkhiv. 2010;82(5):45-49
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Carbohydrate metabolic disturbances in gout: detection rate and clinical featureS

Eliseev M.S., Barskova V.G., Eliseev M.S., Barskova V.G.


Aim. To study the clinical features of gout concurrent with carbohydrate metabolic disturbances. Subjects and methods. One hundred and ninety-five patients with gout were examined. Their mean age was 54.8 ± 10.4 years; disease duration was 10 (6-15) years. Anthropometry was estimated; the levels of uric acid (UA), creatinine, and lipid metabolic parameters were measured fasting; the concentrations of glucose were estimated fasting and 2 hours after use of 75 g of glucose; UA excretion and glomerular filtration rate were calculated. Results. Carbohydrate metabolic disorders were found in 112 (57.4%) patients with gout: type 2 diabetes (T2D) in 67 (34.3%); impaired fasting glycemia in 23 (11.8%); impaired glucose tolerance in 22 (11.3%); the diagnosis of T2D was first detected in 35 patients with gout, in 12 of the 35 (34%) cases after oral glucose tolerance test (OGTT). The detection rate of carbohydrate metabolic disturbances was in direct proportion to serum UA levels. This value was 513.7 ± 122.2 μmol/l in gouty patients with carbohydrate metabolic disturbances and 472.4 ± 121.9 μmol/l in normoglycemic patients (p = 0.026). High body mass index and elevated serum were significantly determined in hyperglycemic patients; coronary heart disease (CHD) and arterial hypertension were more frequently diagnosed. Conclusion. OGTT causes a 34% increase in the detection rate of T2D in patients with gout. Carbohydrate metabolic disturbances are revealed in the majority of patients with gout and associated with obesity, hypertriglyceridemia, high serum UA levels, chronic disease forms, the high incidence of CHD and arterial hypertension.
Terapevticheskii arkhiv. 2010;82(5):50-54
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Clinicoinstrumental AND laboratory characteristics of early stages of gonarthrosis

Svetlova M.S., Vezikova N.N., Svetlova M.S., Vezikova N.N.


Aim. To provide rationale for early basic therapy in patients with gonarthrosis. Subjects and methods. Three hundred and eight female and male patients with early stages of gonarthrosis and 50 healthy individuals were examined. Clinical, X-ray, and arthrosonographic studies were performed; the levels of interleukin (IL) 1β, IL-1B receptor antagonist, and IL-6 were measured and quality of life was assessed. Results. The findings have led to the conclusion that the early stages of gonarthrosis are characterized by significant clinical symptomatology and lower femur condylar cartilage height; synovitis is frequently revealed by arthrosonography; there is IL-1β hyperproduction; the quality of life in the patients is worse than that in the healthy individuals from the control group. Conclusion. Therapy aimed at alleviating the symptoms of gonarthrosis and local inflammation and reducing the rate of articular cartilage degradation and X-ray progression of the disease should be initiated at the earliest, including pre-X-ray, stages of the pathological process.
Terapevticheskii arkhiv. 2010;82(5):54-58
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Osteoarthrosis and lower extremity peripheral vein diseases: the specific features of concomitant pathology

Salikhov I.G., Lapshina S.A., Myasoutova L.I., Kirillova E.R., Mukhina R.G., Salikhov I.G., Lapshina S.A., Myasoutova L.I., Kirillova E.R., Mukhina R.G.


Aim. To estimate the prevalence and impact of lower extremity peripheral vein diseases on the course of articular syndrome in osteoarthrosis (OA), to reveal the specific features of concomitant pathology, and to substantiate the necessity of its therapeutic correction. Subjects and methods. One hundred and fifty-eight patients with the valid diagnosis of OA (by the American College of Pheumatology criteria) were followed up. Their mean age was 56.4 ± 9.6 years. Lower extremity peripheral vein diseases were detected in 51.3% of the patients with OA, which permitted identification of 2 patient groups comparable for the major parameters. During the examination, the clinical parameters of articular syndrome were assessed at the start and 2 months after therapy. Results. The higher intensity of the pain syndrome, lowered functional activity, and more common synovitis were observed in the patients with concomitant diseases of joints and veins as compared with those without signs of venous insufficiency. After therapeutic measures, joint pain, synovitis, and lower functional activity persisted in the patients with concomitant diseases. Reexamination showed that most patients with concomitant pathology needed analgesic therapy; in Group 2 without a history of vein diseases, the dose of nonsteroidal anti-inflammatory drugs (NSAID) could be halved in 21 (27.3%) patients; 37 (48.0%) patients were in no need of continuous use of NSAID. Conclusion. Impaired peripheral venous blood flow reduces the efficiency of therapy for OA, which makes it necessary to timely detect lower extremity varices and to perform goal-oriented therapy in such patients.
Terapevticheskii arkhiv. 2010;82(5):58-60
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Osteoporosis in patients with end-stage lung disease

Kochetkova E.A., Massard Z., Kessler R., Maystrovskaya Y.V., Kochetkova E.A., Massard G., Kessler R., Maistrovskaya Y.V.


Aim. To estimate the bone mineral density (BMD) in end-stage lung disease (ESLD) and to determine risk factors for reduced BMD and correlations between lung functional parameters and pretransplantation bone mass. Materials and methods. Sixty-five case histories were retrospectively analyzed in patients with ESLD who were to undergo lung transplantation. BMD in the lumbar spine (LS) and femoral neck (FN) was estimated by dual-energy X-ray absorptiometry. External respiratory function was investigated; gasometry and six-minute walk test (SMWT) were carried out. Results. Osteopenic syndrome was recorded in 89% of the patients. Normal LS and FN BMD was found only in 7 (11%) patients. T-scores (in both LII-LIV and FN) were directly related to the body mass index. There was a direct correlation of BMD with forced expiratory volume in one second and an inverse correction with arterial blood pCO2. There was no significant relationship between the results of SMWT and BMD in both LII-LIV. Conclusion. Osteoporosis is a common severe systemic manifestation in patients with ESLD.
Terapevticheskii arkhiv. 2010;82(5):61-64
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New approaches to pharmacotherapy for rheumatoid arthritis: perspective for use of tocilizumab (monoclonal antibodies to interleukin-6 receptor)

Nasonov E.L., Nasonov E.L.


The author considers a role of interleukin-6 (IL-6) as a cytokine, elevated concentrations of which in serum and synovial fluid correlate with the activity of articular inflammation and the development of systemic manifestations in rheumatoid arthritis (RA). There is strong evidence suggesting that effective treatment with gene-engineering biologicals causes a reduction in IL-6 concentrations. Detailed information is given on the novel drug tocilizumab that is humanized monoclonal antibodies (IgG1) and the first and only agent that is able to suppress IL-6-dependent inflammatory reactions and is permitted for use in RA.
Terapevticheskii arkhiv. 2010;82(5):64-71
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Early rheumatoid arthritis: Clinical and immunological aspects

Demidova N.V., Guseva I.A., Karateev D.E., Demidova N.V., Guseva I.A., Karateyev D.E.


Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by a systemic inflammatory and destructive joint lesion that is manifested by the involvement of various organs and systems into the pathological process. Whether the variants of the course and outcomes of RA may be predicted early is the most important inadequately studied problem. HLA-DRB1* genotypes affect disease severity; however, different alleles encoding the identical amino acid sequence have a varying association with the disease and their combinations can differently increase the risk of RA. Total epitope (SE) is associated not only with the risk of RA as a whole, but also with the development of the severe course of the disease to a greater extent. A number of studies have demonstrated that if a patient has concurrently antibodies to cyclic citrullinated peptide (CCP) and rheumatoid factor, as well as HLA-DRB1 alleles, the likelihood of rapid X-ray progression is 10 times greater than that in a patient without these markers. The paper considers the course of early RA depending on the combined determination of immunological and immunogenetic markers (SE and CCP antibodies). Each of them makes a substantial contribution to the development of a destructive process in early RA, which necessitates the assessment of a combination of the factors.
Terapevticheskii arkhiv. 2010;82(5):71-77
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