Vol 78, No 5 (2003)

Aim. To evaluate implications of pathomorphological alterations of synovial membrane at an early stage of rheumatoid synovitis (RS) for further course of rheumatoid arthritis (RA) and prognosis of the disease. Material and methods. 92 new cases of RA (22 males, 70 females, mean age 31.1 + 10.5 years, mean duration of RA 5.99 ± 3.27) subjected to puncture biopsy of the synovial membrane of the knee joint in 1967-1983. At admission to hospital 54.3, 45.7 and 29.3% patients had polyarthritis, monoand oligoarthritis, rheumatoid factor, respectively. The RA diagnosis was confirmed in 68 (73.9%) patients, 26 (28.3%) of them were observed for 1-2 years, 42 (45.6%) -for 11.8 + 8.8 years, on the average. In 9 (9.8%) patients the diagnosis was changed for Bechterew's disease (n = 6), polymyositis (n - 1), rheumatism (n = 1), reactive arthritis (n = 1), 15 (16.3%) patients with seronegative oligoarthritis of large joints were lost for follow-up. Now (the beginning of 2002) synovial biopsies were investigated in "blind" mode by one morphologist (using the semiquantitative method) and compared to clinical and x-ray evidence. Results. The most frequent changes were the following: proliferation of lining synovial cells (82.6%), lymphoid infiltration (64.1%), angiomatosis (60.9%), fibrinoid changes (60.9%). Accumulation of large amounts of macrophages and lymphocytes in the infiltrate was detected in RA significantly more often than in non-RA patients. Among 68 patients with definite RA morphological picture in biopsies obtained from the knee joints with manifest synovitis (69.1%) and from clinically intact joints (30.9%) was practically the same. The most important morphological sign was angiomatosis associated with early polyarticular involvement, early development of joint erosions and early disability (patients with marked angiomatosis were disabled after 4 years of illness, on the average, without angiomatosis - after 11 years). Statistically significant associations of parameters of RA development with other histological signs of synovitis were not detected. Conclusion. Angiomatosis in the synovial membrane occurs at early (including preclinical) stages of RA and, as a manifestation of angiogenesis, is an unfavorable prognostic factor of early polyarticular involvement, early development of joint erosions and early disability. Synovial biopsy at an early stage of arthritis is of differential-diagnostic value and helps to define a long-term outcome. Therefore, synovial biopsy of the knee joint must be in the list of standard examinations of patients with early RA.

Aim. To study clinical and morphological variants and frequency of renal involvement in patients with rheumatoid arthritis (RA). Material and methods. Routine laboratory tests, device (urography, dynamic scintigraphy of the kidneys) and ultrasound investigations, lifetime and postmortem examinations of renal tissue using histological, immunohistochemical and electron-microscopic techniques, biopsy of gingival and rectal mucosa for amyloid detected renal lesions in 268 (46.2%) of RA patients followed up for 25 years meeting the ARA criteria. In 98 (37%) patients renal lesions were verified morphologically. Lifetime renal biopsies were made for 60 of them. Results. The diagnosis of chronic pyelonephritis was made in 117 patients, 42 patients had nephrolithiasis, nephroptosis and papillary necrosis were found in 49 and 3 patients, respectively. Arterial hypertension was present in 96 examinees, nephrotic syndrome was diagnosed in 19 and chronic renal failure - in 67 patients. Drug-related nephropathy occurred in 35 cases, in 26 cases symptoms of pyelonephritis arose prior to RA. Combination of renal diseases was found in 197 patients. Renal pathology was not verified morphologically only in 5 cases. Glomerulonephritis (GN) variants were present in 35 patients: mesangioproliferative (n = 27), membraneous (n = 5), mesangiocapillary (n = 3). 12 of them took Au preparations or D-penicillamin, therefore diagnosis of true rheumatoid GN was feasible only in 23 of them. GN was combined with renal amyloidosis (n = 28), minimal morphological changes (n = 19), interstitial/tubulointerstitial nephritis (n = 4), pyelonephritis (n = 4), arteriolosclerotic nephrosclerosis (n = 3). 41 patients with diagnosed pyelonephritis were found morphologically to have amyloidosis (n = 16), GN (n = 10), minimal morphological changes of renal tissue (n - 6), tubulointerstitial nephritis (n = 3), pyelonephritis, pyelonephritis alone (n = 4). Conclusion. The above morphological findings point to high occurrence of renal pathology in RA. In many cases morphological signs are more serious than clinical symptoms. If RA activity is not controlled, nephritis of any type may transform into amyloidosis. When it is impossible to formulate morphological diagnosis in RA patients, it is proposed to use the term "nephropathy". Unrelated to RA nephropathy 's diagnosis is valid in cases when renal pathology manifested before RA. Renal diseases arising in the presence of RA may be associated with this disease and should be reflected in its classification.

Aim. To assess efficacy of intraarticular administration oflornoxicam (xefocam) in patients with rheumatoid arthritis (RA). Material and methods. Xefocam was injected into the knee joints of 58 patients with RA once a week for 3 weeks in a dose 8 mg. The treatment efficacy was evaluated by changes in the severity of arthralgias, pain in the joints at palpation, circumference of the knee joints at the level of the upper edge of the patella, ultrasound and thermography of the knee joints. Results. Xefocam relieved arthralgia (in 44 patients at least by 30%), pain in the joints at palpation and joint circumference. Ultrasound investigation registered a significant thinning of the synovial membrane and amount of exudates. Conclusion. If local steroid therapy is not definitely indicated, intraarticular administration of xefocam can be effectively used for suppression of moderate inflammation in the joints in RA patients.

Aim. To examine microcirculation in patients with systemic lupus erythematosus (SLE) showing clinical signs which may deteriorate hemodynamic indices: arterial hypertension (AH), atherosclerosis, antiphospholipid syndrome (APS). Material and methods. Microcirculatory changes were studied in 63 patients with SLE using biomicroscopy of bulbar conjunctival vessels (Zeiss slit-lamp, 32 times magnification). The following conjunctival indices were estimated : general (GCI), vascular (VCI), intravascular (IVCI), extravascular or perivascular. Results. Microcirculatory changes in SLE patients covered disturbances of microvascular architectonics, microvascular blood flow. VCI, IVCI, GCI were significantly higher than in control subjects : 6.16 + 0.31, 3.69 + 0.36 and 9.87 + 0.57 scores vs 3.20 ± 0.50; 120 ± 0.20 and 4.20 ± 0.50 scores, respectively. The degree of structural changes in the vessels depended on the disease duration while intravascular changes depended on the activity of lupus process. In patients with AH and atherosclerosis microcirculatory disturbances were similar and related to vascular architectonics. In APS there were marked intravascular disorders (IVCI was 7.50 ± 0.59 scores, GCI was 16.13 ± 1.41 scores). Conclusion. In SLEpatients with AH and/or atherosclerosis microcirculatory changes involved primarily structure of the vascular wall and may be brought about by compensatory-adaptive mechanisms of the microcirculatory bed in high hemodynamic load. Intravascular microcirculatory changes were most pronounced, first of all as sludge-phenomenon, in APS and high SLE activity.

Aim. To investigate the influence of pulse-therapy on anticoagulant system of the endothelium in patients with nonspecific aortoarteritis. Material and methods. Eleven patients (9 females and 2 males, mean age 33.4 ± 8.8 years, the disease duration 5.8 ± 5.7 years) with nonspecific aortoarteritis were examined. 9 patients had the third anatomic type of the disease with affection of the aortic arch and abdominal aorta vessels, 2 patients had the first anatomic type with isolated affection of the aortic arch. The patients received a standard three day course of pulse-therapy (PT) with glucocorticosteroids (GCS) (metipred in a dose 1000 mg/ day or dexametasone in a dose 2 mg/kg/day) with a single dose of cytostatic (CS) (cyclophosphamide in a dose 10 mg/kg b.w.) during the first infusion. Further PT consisted of monthly single infusion of GCS and CS in the above doses for 9 to 12 months. Examination of the patients was carried out before the treatment and on the treatment day 4 and 20 and follow-up month 3, 6 and 12. Estimation of clinical activity was carried out according to BVAS. Levels of protein C, S, antithrombin III were measured by ELISA in plasma. Activities of protein C, antithrombin III and plasminogen were determined by the optical assay with chromogenic substrates. Results. Before the start of the treatment BVAS was 6.8 ± 4.3. During the follow-up mean scores of BVAS were significantly lower than before the pulse-therapy (2.7 ± 2.2; 2.5 ± 3.9; 3.1 ± 5.1; 1.8 ± 2.6 and 1.7 ± 1.7, respectively; p < 0.05). Prior to the treatment, a mean level of protein С was 86.6 ± 37.5% and range of its activity 175.2 ± 112.9%. On the fourth day after pulse-therapy a mean concentration of protein С increased (128.8 ± 29.0%; p < 0.05) while activity of protein С tended to a decrease on the 20th day (99.2 ± 17.6; p > 0.05). There were no significant differences in the levels of protein S, antithrombin HI and its activity, activity of plasminogen in the course of PT. Conclusion. PT has a good anti-inflammatory effect in the absence of unfavorable influence on anticoagulant system of the endothelium in patients with nonspecific aortoarteritis.

Aim. To evaluate efficacy and safety ofnimesil, a selective inhibitor of cyclooxigenase-2, in gouty arthritis (GA). Material and methods. Nimesil was given to 20 male patients with GA (mean age 53.8 years, mean duration of the disease 8.1 years) in a dose 100 mg twice a day for 14 or 21 days depending on positive clinical changes (13 and 6patients, respectively). The articular swelling index, supraarticular skin hyperemia, the articular index, pain in rest and movement were estimated on the treatment day 1, 5, 14 and 21. Arterial pressure was controlled in all the patients. ESR, uric acid, seromucoid, ALT, AST, gamma-GTP, glucose levels were measured before and after the treatment. Results. Nimesil relieved pain and inflammation (ESR and seromucoid level lowered significantly). Effects on the other estimates were not registered. One patient developed generalized urticaria on the treatment day 5. The drug was discontinued in him. Conclusion. Nimesil can be used as monotherapy of an acute attack of gout. In a dose 200 mg/day nimesil provides an effective and fast treatment of gout, is well tolerated and safe.

Aim. To examine gastroduodenal mucosa in patients treated with nonsteroidal anti-inflammatory drugs (NSA1D), to evaluate the rate and severity of gastrointestinal hemorrhage (GIH) as NSAIDgastropathy manifestation by the results of clinical and device tests. Material and methods. A retrospective analysis of 2042 case histories of patients admitted to the surgical department of the Moscow city hospital N 1 in 1997-2001 with diagnosis GIH confirmed at esophagogastroduodenoscopy (EGDS). 989 patients (566 males and 423 females) had acute GIH from the upper gastrointestinal tract. Results. Relationship between intake of N SAID and GIH was documented in 342 patients (16. 7% of overall number of the examinees and 34.6% of patients with acute GIH). According to EGDS, GIH was provoked by gastric lesions (68%), duodenal lesions (20%), gastroduodenal lesions (9%), esophageal erosions (3%). GIH was caused primarily by low-dose aspirin, indometacin, diclofenak and ibuprofen. Severe GIH occurred in 28.9% cases, moderate and mild ones in 20.8 and 50.3%, respectively. Conclusion. To reduce the incidence of GIH, it is necessary to take preventive measures against NSAId-gastropathies.

Aim. To study the pattern of lethal outcomes due to rheumatic diseases (RD) in Moscow. Material and methods. Annual reports of 38 pathological departments of Moscow have been analysed for 1999 and 2000. Results. RD accounted for 1.8% diagnosis at autopsies (n = 784). RD as the main diagnosis was in 668 cases (1.53%). Diseases of the bone-muscle system caused death 3.5 times less often than rheumatism. As concomitent diseases RD were encountered in 118 cases (0.27%), diseases of the bonemuscle system were registered 2 times less frequently than rheumatism. Chronic rheumatic diseases of the heart were diagnosed in 590 cases (98.5%), rheumatic fever was detected in 9 (1.5%) patients. The main diagnosis of RA, seronegative arthritides, systemic vasculitides, SLE, osteoarthrosis was made in 49, 10 9.3, 12.7, 1.3%, respectively. Such nosological entities as osteoporosis, gout and other microcrystalline arthritides were referred to the group "other rheumatic diseases" and made up 12.7%. As concomitant pathology RA, OA, seronegative spondyloarthritides, SLE, other RD occurred in 54, 8.1, 27, 2.7, 2.7%, respectively. Conclusion. The share of RD in autopsy diagnosis accounts for 1.8% of the total number of necropsies. These figures seem to underestimate the real situation and may be explained by poor registration of RD at autopsy and a fall in the total number of autopsies for the last 10 years. For Moscow and Russia as a whole there is a prevalence of rheumatism mortality (76%), primarily deaths of chronic rheumatic cardiac diseases, over mortality due to diseases of the bone-muscular system (24%).