Vol 86, No 5 (2014)

Progress in the laboratory diagnosis of systemic autoimmune rheumatic diseases (SRAD) is caused by the ever increasing clinical introduction of new highly productive methods for immune analysis using computer-aided systems and multiplex proteomic technologies. The urgent problem in the laboratory diagnosis of SRAD is the standardization of current methods for the detection of autoantibodies (autoAb), including the preparation of international reference materials for the calibration and external quality assessment of immunological assay. New autoAb technologies have a higher analytical validity than the previously used classical techniques immunodiffusion, agglutination, and immunofluorescence; however, their diagnostic sensitivity and specificity for SRAD have been poorly studied. Particular emphasis is laid on the standardization of the methods for examining antinuclear antibodies (ANAb), the major serologic marker of SRAD. According to the EULAR/ACR guidelines, indirect immunofluorescence reaction (IIFR) using human HEp-2 cells as substrate is the gold standard and a primary screening ANAb method. New methods for solid-phase analysis (enzyme immunoassay, multiplex test systems, etc.) cannot substitute the primary screening of ANAb using IIFR-HEp-2 as they identify antibodies to the limited number of antigens, increasing the number of false- negativ/RESULTS: The computer-aided systems for interpreting cell fluorescence tests contribute to the standardization and enhancement of the efficiency of detection of ANAb and other autoAb by IIFR. The use of complex diagnostic indices based on the multiparametric analysis of laboratory biomarkers in the serum makes it possible to most fully and objectively assess complex molecular mechanisms for the pathogenesis of SRAD, thus radically improving the early diagnosis, the estimation of the activity and severity of disease, the prediction of the outcomes of a pathological process and the response to treatment.

AIM: To study the associations of the concentration of interleukins (IL) 1Β, 6, 8, 10, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α, vascular endothelial growth factor (VEGF) in the serum and urine with the clinical features of scleroderma systematica (SDS)/MATERIAL AND METHODS: The investigation enrolled 51 patients with a valid SDS diagnosis. The serum and urinary concentrations of interleukins, TNF-α, MCP-1, and VEGF were measured by solid-phase enzyme immunoassay/RESULTS: The patients with SDS were found to have higher serum and urine concentrations of proinflammatory cytokines and VEGF than in the comparison group. There were relationships between the levels of VEGF and proinflammatory cytokines and the disease duration, clinical forms, and clinical manifestation of SDS/CONCLUSION: Higher serum VEGF levels in patients with SDS may be used to estimate the magnitude of endothelial dysfunction. Estimation of serum IL-6 concentrations may be employed to determine the degree of sclerosis progression; that of MCP1 for the activity of fibrosing alveolitis. Quantitative analysis of urinary IL-6, IL-8, and VEGF levels in patients with SDS may be used to evaluate tubulointerstitial inflammation and to predict the development of interstitial fibrosis.

AIM: To evaluate the short-term efficacy of the nonselective endothelin receptor antagonist bosentan in the treatment of pulmonary hypertension (PH) associated with diffuse connective tissue diseases (CTD), as well as its effect on survival in both monotherapy and in combination with other PH-specific agents/MATERIAL AND METHODS: The study included 20 CDT-associated PH patients who had been hospitalized in 2009-2013. All the patients had valid diagnoses of scleroderma systematica (SDS) (n=18) or systemic lupus erythematosus (SLE) (n=2). Bosentan was given in an initial dose of 62.5 mg/day twice for 4 weeks, then 125 mg/day twice/RESULTS: Eighteen patents completed therapy at 16 weeks. One patient with Functional Class (FC) IV PH associated with SDS died after 10 weeks of treatment because of PH progression; bosentan was discontinued in another patient following 4 weeks because of the enhanced activity of transaminases. The patients who had completed the investigation showed a significant FC decrease (from 2.9±1.0 to 2.4±1.0 following 16 weeks; р=0.03), an increase in 6-minute walking distance (from 298±140 to 375±94 m; р<0.002), a significant reduction in mean pulmonary artery pressure (from 48.2±15.0 to 42.8±12.0 mm Hg; p=0.002), and pulmonary vascular resistance (PVR) (from 819±539 to 529±220 din/sec/cm-5; p=0.003). Right atrial pressure fell from 9.8±7.0 to 8.8±7.0 mm Hg; however, the changes were insignificant. There was a significant rise in cardiac index from 2.64±0.95 to 3.26±0.75 l/min/m2 (p=0.005) and a significant decrease in uric acid levels from 562±254 to 469±194 µmol/l (р=0.006). Overall 1-, 3-, and 5-year survival rates in patients with PH in the presence of CTD from PH onset were 100, 93, and 72%, respectively, in their treatment with endothelin receptor antagonists and differed significantly from the historical control group (87, 30, and 4%, respectively) when PH-specific therapy was unavailable/CONCLUSION: The survival of the bosentan-treated patients with SDS and PH becomes similar to that in the patients with classical SDS. Analysis of the findings revealed the association of survival with lower PVR at 16 weeks of bosentan therapy, which is indicative of the need for hemodynamic monitoring of therapeutic effectiveness.

AIM: To determine the specific feature of gout at its onset in the elderly/MATERIAL AND METHODS: The investigation included 100 patients (74 men and 26 women) with primary gout on the basis of the criteria proposed by S. Wallace et al. (1977). The patients were divided into 2 groups: 1) 51 patients aged over 60 years; 2) 49 patients aged less than 60 years. In Groups 1 and 2, the mean age at gout onset was 66.1±4.8 and 41.6±10.0 years, respectively. A comparative retrospective analysis was made to analyze the detection rate for the site of onset gout, the pattern of arthritis, the number of tophus forms, the use of diuretics, small-dose acetylsalicylic acid (ASA), comorbidities, such as hypertension, type 2 diabetes mellitus (T2DM), obesity, chronic renal failure, coronary heart disease, chronic heart failure, and prior myocardial infarction/RESULTS: The disease duration in both groups averaged 8 years. In Groups 1 and 2, first metatarsophalangeal joint arthritis was diagnosed at its onset in 77 and 61%, respectively. In these groups, chronic arthritis was also diagnosed in 19 (37%) and 19 (39%). Examinations revealed tophi in 21 and 37% of cases in Groups 1 and 2, respectively. The administration of diuretics was recorded in 25 (49%) and 17 (35%) patients in these groups. Group 1 patients took low-dose ASA more frequently than Group 2 ones (19 (37%) and 7 (14%) patients, respectively; p=0.013). Hypertension was identified in 23 (45%) examinees in Group 1 and 17 (40%) ones in Group 2. Both groups were matched for the number of patients with obesity (41 and 43%) and for that of patients with T2DM (15 and 10%, respectively). There were significant differences between the compared groups in the incidence of coronary heart disease, myocardial infarction, and chronic heart disease/CONCLUSION: The patients' age of gout onset does not affect substantial differences in the clinical features of gout with its comparable duration in the young and elderly patients. The main clinical features of gout are unique to both young and elderly patients. Cardiovascular diseases are more common at gout onset in the elderly.

AIM: To provide the clinical, laboratory, radiological, morphological, and immunomorphological signs that permit the differential diagnosis to be made in patients with involvement of the nasal cavity and accessory sinuses (NCAS)/MATERIAL AND METHODS: In the period 2009 to 2013, the Laboratory for Intensive Therapy for Rheumatic Diseases, V.A. Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences, associated the disease onset with NCAS involvement in 39 (7.6%) of 512 examinees. NCAS involvement was present at disease onset in 100% of the patients with natural killer (NK) cell lymphoma (NK/T lymphoma), in 84.5% of those with Wegener granulomatosis (WG), in 29.5% of those with IgG4-related disease (IgG4-RD), and in 17.5% of those with sarcoidosis. Such an onset could be extremely rarely observed in histiocytosis/RESULTS: Despite the similar clinical manifestations, NCAS involvements in NK/T lymphoma of nasal type and WG at disease onset show clear differences in the laboratory and systemic manifestations of these diseases. The patients with lymphoma have no characteristic laboratory abnormalities at disease onset, except the 100% presence of Epstein-Barr virus (EBV) DNA in blood and, only as a tumor grows, fever appears and there are elevated C-reactive protein and lactate dehydrogenase levels and pronounced destructive changes in the facial bones with mandatory hard palate destruction; at the same time the signs of systemic involvement are virtually absent. The patients with WG at disease onset have fever, high erythrocyte sedimentation rate, elevated C-reactive level, significant anemia, leukocytosis and 90% are found to have anti-neutrophil cytoplasmic antibodies with the rapid development of systemic manifestations: involvements of the lung, kidney, and peripheral nervous system. Destructive changes in the facial bones are minimal and hard palate destructions are absent. The patients with IgG4-RD, sarcoidosis, and juvenile xanthogranuloma have similar clinical and laboratory manifestations in the absence of hemorrhagic nasal discharge, nasal septal perforation, and facial bone destruction, with the practically involvement of the salivary/lacrimal glands and orbital regions. A third of the patients are observed to have different allergic manifestations, moderate eosinophilia, and signs of autoimmune disorders (the presence of rheumatoid and antinuclear factors, hypergammaglobulinemia). Elevated serum IgG4 levels are characteristic of IgG4-RD/CONCLUSION: Blood anti-neutrophil cytoplasmic antibodies, EBV DNA, and IgG4 levels should be determined in all patients with NCAS involvement. Mini-invasive incision biopsies of the nasal mucosa, orbital regions, and major salivary glands should be done, by morphologically verifying the diagnosis of sarcoidosis, histiocytosis, and WG and by making an immunomorphological examination to diagnose NK/T lymphoma and IgG4-RD.

AIM: To study the effect of the daytime anxiolytic adaptol on the efficiency and tolerability of combination treatment for atopic dermatitis (AD)/MATERIAL AND METHODS: Eighty patients with different clinical forms of AD were examined and then divided into 2 identical groups. The patients' mean age was 30.7±11.2 years; the mean disease duration was 20.2±12.8 years. Group 1 patients (n=40) received standard treatment involving disintoxication therapy, prednisolone 30-60 mg/day, antihistamines, phototherapy (20 sessions), topical steroids and topical emollients. Group 2 patients (n=40) took additionally adaptol as 3 tablets (1500 mg) daily. The efficiency of therapeutic measures was evaluated in 2 steps: by taking into account the changes in the scoring atopic dermatitis index (SCORAD) and the Dermatology Life Quality Index (DLQI) scores 4 weeks following the initiation of treatment and once more after 12 weeks/RESULTS: There was a tendency for the more pronounced decrease in SCORAD scores in Group 2 (using adaptol) versus Group 1 (standard treatment) to 9.8±2.57 and 10.8±2.64, respectively. There were drops in SCORAD scores by 4.1 and 3.6 times, respectively. Twelve weeks after 12 weeks of treatment initiation was 7.1±2.13 scores in the adaptol group; on the contrary, this indicator increased slightly due to evolving recurrences and amounted to as many as 11.9±2.41 scores on the average. In Group 1, DLQI improved by 73% following 4 weeks and decreased by 1% after 12 weeks while in Group 2, it improved by 81% following 4 weeks and continued to improve up to 85% after 12 weeks/CONCLUSION: Comparison of examined dermatology indices in AD patients receiving standard treatment and treatment including adaptol gives proof to the great value and efficiency of using adaptol during an exacerbation and in the postrecurrence period.

By panniculitides is meant a group of heterogeneous inflammatory diseases characterized by the involvement of subcutaneous adipose tissue. A diversity of their forms and variants of their course determines the need for careful patent examination to verify the diagnosis. The lecture gives a diagnostic algorithm and outlines principles in the differential diagnosis of panniculitides and its treatment approaches in current clinical practice.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are most commonly used to treat acute and chronic pain in locomotor system (LMS) diseases. However, their administration may be accompanied by the development of dangerous complications as organic and functional disorders of the cardiovascular system (CVS) and gastrointestinal tract (GIT). Physicians have currently a wide range of NSAIDs at their disposal; but none of the representatives of this group can be considered the best. Thus, highly selective cyclooxygenase-2 inhibitors (Coxibs) are substantially safer for GIT; however, their use is clearly associated with the increased risk of severe cardiovascular events. Nonselective NSAIDs, such as naproxen or ketoprofen, are safer for CVS, but more frequently cause significant GIT organic and functional disorders. Moderately selective NSAIDs, such as meloxicam (movalis), conceivably could be the most acceptable choice for treating the majority of patients in this situation. This drug has been long and extensively used in global clinical practice and has gained the confidence of physicians and patients. The major benefits of meloxicam are its proven efficacy, convenient treatment regimen, relatively low risk of complications as organic and functional disorders of the GIT and CVD and good compatibility with low-dose aspirin.

Antisynthetase syndrome encompassing a symptom complex with severe interstitial lung disease is the severest subtype of polymyositis and dermatomyositis. The characteristic feature of antisynthetase syndrome is the insufficient efficiency of traditional therapy with glucocorticosteroids and cytostatics, which determines the prognosis of the disease and the need for new therapeutic approaches to treating these patients.

The history of the Kazan School of Therapists numbers two centuries of scientific achievements and discoveries. German Professors F.H. Erdman and K.F. Fuks laid the groundwork for clinical teaching continued by Russian therapists N.A. Skandovsky, N.A. Vinogradov, A.P. Kazem-Bek, N.K. Goryaev, and other distinguished scientists. The prominent scientists of the 20th century made great contributions to the development of modern therapy; the names of M.N. Cheboksarov, Z.I. Malkin, A.G. Teregulov, and I.G. Salikhov are known and they are respected by the world medical public.