Artrite reumatóide tratada com enzimas sistêmicas -1

Transcription

1 Artrite reumatóide tratada com enzimas sistêmicas Clinical and immunological criteria of activity of different rheumatic arthritis courses and their treatment by Wobenzym. Siziakina L.P., Artemenko N.A. Clinical and immunological criteria of activity of different rheumatic arthritis courses and their treatment by Wobenzym. III. Internat. Congress on Immunorehabilitation and Rehabilitation in Medicine, Eilat, Israel,. Russian version Rheumatic arthritis (RA) is a chronical disease, its pathogenesity includes deep immune system disorders with a disbalance of qualitative and quantitative composition of immunocompetent cells including functional and cell cooperation disorders (8). Joint damage is the most obvious syndrome of rheumatic arthritis. But other symptoms than joint damage mostly determine an aggressivity of the disease and its prognosis. Role and place of different components of inflammation immune complex in a rheumatic arthritis process development is being currently discussed. A progresive character of the disease with a formation of irreversible joint and inner organ damage, an early invalidity of patients, and a decrease of working ability define a medical and social importance of this problem as well as a necessity of continuing study of clinicalpathogenetic peculiarities of rheumatic arthritis and a search for optimal treatment program. An important role in a rheumatic arthritis diagnosis plays a determination of IgGRF (rheumatic factor) which seems to be an autoantibody against IgG fragment (). Both an existence of serum negative variant of rheumatic factor and its detection in other rheumatic and nonrheumatic diseases determine a necessity to investigate RA serological markers, for example antibodies against cardiolipins (acl), associated with thromboses during rheumatic diseases, and antibody against native DNA (ndna) determining a formation of immunopathological component. In many cases a rheumatic arthritis course is complicated by systemic symptoms which cause a development of pathological process (3, 3). Various changes in rheological properties of blood during rheumatic arthritis cause damages of microcirculation and seem to be one of the factors which make the disease become chronic (, 0). Despite of different clinical symptoms of thrombohemorragical syndrome and expression of damages of rheological, coagulational, and fibrinolytical properties of blood (, 3, ), the most important way to diagnose changes in microcirculation is the use of immunological methods. Such methods include determination of antigen factor van Billebrand (FB) in blood plasma. FB is a macromolecular protein synthesized by the vascular endothelium cells which define a function of thrombocytes (TC) and an activity of VIII. coagulating factor structural part of which FB makes (). Except this, investigation of new pathogenetic mechanisms of a rheumatic arthritis formation, insufficient efficacy of existing preparations for treatment, and serious side effects (treatment by corticosteroids, nonsteroidal antirheumatic substances, cytostatics) show a need for new treatment methods of different types of rheumatic arthritis. patients ( men, 3 women) with reliable rheumatic arthritis (criteria of American Rheumatological Association, 8) were observed. An average age was. (from 3 to ) years. 38 patients were serum positive on IgMRF and were serum negative. patients showed activity of rheumatic arthritis corresponding to degree I, patients to degree II and patients to degree III. Confirmation of diagnosis by Xray for all patients is available (Table ). In 8 patients syndromes such as fever, rheumatic nodes, amiotrophic syndrome, damage of cardiovascular system, digestive system and others occured. In some cases concomitant diseases appeared: tuberculosis, malignant tumors, diabetes, periodical illness. During clinical observations of patients joint index, oedema index, joint sum (by Richi), functional test by Li and an intensity of hand clasp (mm.rt.st) were followed. All patients were subjected to a general clinical observation and also basic signs of immunological statute () were observed. Using IFA a titer of antibody against ndna was determined. IgMRF and a presence of antibody against cardiolipins and antigen factor von Billebrand (FB) were determined in patients serum (test of the AGAB system, Moscow).

2 Wobenzym (Mucos Pharma) was administred together with methotrexate mg on Sunday; 0 dragees three times a day, 0 minutes before meals days, then dragees three times a day days, followed by dragees three times a day 30 days. To observe an efficacy of the preparation, a group of 8 people (serum positive, joint form) was established. Control group included people treated with nonsteroidal antirheumatic substances and methotrexate ( mg). Results were evaluated statistically using nonparametrical criterium by MannWhitney. Observed group included 38 patients (8.%), positive on IgMRF, and (.%) serum negative patients. Comparison of clinical signs in both groups showed an absence of significant differences (Table II). In serum negative group dominated patients with inner organ damage 8.%, in serum positive group inner organ damage occured in.% patients. Presence of antibodies against cardiolipins was tested in serum positive group. A positive result was obtained in patients (3.%). In patients (0.8%) inner organ damage developed and only in patients (.%) joint form of rheumatic arthritis was diagnosed. Table I General clinical characterization of patients Signs Number of serum positive patients Number of serum negative patients Total number of patients Sex M F Age more than 0 Degree of activity I II III Functional I insufficiency II of joints III IV 3 0 Xray stadium I II III IV 3 Form joint with inner organ damage 8 Table II Basic clinical signs of joint syndrome Signs Serum positive patients Serum negative patients Joint index by Richi. + 0.* + 0.* Joint sum by Richi *. + 0.* Oedema index by Richi Functional index by Li * * Intensity of a hand clasp R. + 0.* *

3 (mm.rt.st.) L *. +.* * statistically significant differences p< 0.0 as compared to control A degree of autoimmune process activity can be derived from a titer of antibody against ndna. Among serum positive patients antibody against ndna was detected in patients (.%) 8 (3.%) with the joint form and (3.%) with the inner organ damage. In the serum negative group acl were detected in 8.% of patients (83.3% with the inner organ damage and only.% of patients with the joint form of rheumatic arthritis). Among observed patients antibody against ndna was detected in patients (.%). Interestingly, all of them had a rheumatic arthritis with inner organ damage (Table III). Table III Changes in signs of immunological statute dependent on a type of rheumatic arthritis course Groups Signs of immunological statute Sedimentation mm/hour CIC Titer of antibody against ndna, lg acl % Serum positive (IgM RF (+)) Serum negative (IgM RF ()) *. + 0.* * *.3 8. * statistically significant differences p< 0.0 From obtained results it can be concluded that acl occur in rheumatic arthritis patients sufficiantly frequently in.% of cases. In patients with inner organ damage acl were detected more often in 3.3%. In the groups of serum negative and serum positive patients on IgM RF, acl occured with the same frequency in 83.3% and 0.8%, respectively (Figure ). Figure : Frequency of an acl occurance in patients with rheumatic arthritis with different courses. Analysis of antibody against ndna showed that higher titer of the antibody appeared in rheumatic arthritis patients with inner organ damage.3%. When compared serum positive and serum negative groups, antibody against ndna was detected in approximately same number of patients.% and.%, resp. Based on the results of our investigation it could be concluded that inner organ damage (accompanied with an increase of polyclonal hyperglobulinemy, CIC level and of the titer of antibodies against ndna and acl) is considered to be an undesirable symptom caused by a high activity of autoimmune process. Therefore, there is a need for an improvement of the current treatment therapy. Serum negativity on IgMRF does not presume a favourable course of rheumatic arthritis with a high titer of antibody against ndna, high value of CIC and a presence of acl. Additionally, in such cases a positivity on IgG or IgARF is possible.

4 Clinical sign analysis of rheumatic arthritis patients, administred with methotrexate and Wobenzym, gave following results. In patients treated with Wobenzym a faster reduction of joint swelling, reduction of a degree of morning tightness and a lessening of Li index was observed compared to a control group (Figure ). Analysis of immunological statute signs showed that in patients treated with Wobenzym a more significant lessening of IgM level occured as well as a faster normalization of sedimentation. CIC degree remained higher ( Figure ). A faster clinical and immunological remission in patients treated with Wobenzym and methotrexate enabled to lessen a dosage of methotrexate to. mg. Two patients voluntarily gave up on methotrexate. During next three months an activation of pathological process did not occur. In the case of one patient an effect of Wobenzym treatment was negligible, glucocorticoids were therefore administred. Comparison of a treatment efficacy in Wobenzym group and a control group is shown in Figure 3. Figure : Signs of immunological statute in RA patients treated with and without Wobenzym. Figure 3: Effect of Wobenzym in the rheumatic arthritis treatment.

5 With regard to a higher CIC values after Wobenzym administration it is necessary to include a plasmapheresis during first month of treatment. Based on all above mentioned facts it can be concluded that a presence of antibodies against cardiolipins and ndna is associated with inner organ damage at IgMRF serum positive and serum negative rheumatic arthritis Rheumatic arthritis with inner organ damage, accompanied with an increased titer of antibody against ndna, CIC level and a presence of an antibody against cardiolipins, is considered a unfavourable course which needs a therapy improvement. An increase of ndna antibody titer, CIC level and a presence of antibodies against cardiolipins appear to be a more informative signs of an autoimmune process activity in comparison to general clinical observations. Therefore, it is suggested to use these immunological tests for prognosis of a disease course and for control of the therapy efficacy.