Rheumatoid Arthritis: Pavlica L

Andjelkovic Z, Vojinovic J, Pejnovic N, Popovic M, Dujic A, Mitrovic D, Pavlica L, Stefanovic D. · Department of Rheumatology, Military Medical Academy, Belgrade, Yugoslavia. · Clin Exp Rheumatol. · Pubmed #10464556 No free full text.

Abstract: OBJECTIVE: Vitamin D analogues such as 1 alpha (OH) D3 (alphacalcidiol) have a possible physiological paracrine effect on cell proliferation and differentiation. Experimentally established possibilities to prevent autoimmune diseases suggest that alphacalcidiol may have therapeutic value as an immunomodulatory agent in patients with rheumatoid arthritis. METHODS: We organized a 3-month open-label trial on 19 patients being treated with standard DMARD therapy for acute RA. They were divided into 2 subgroups, those with highly active RA and those with moderately active RA. Their regular drug regimen was maintained during the trial and oral alphacalcidiol 2 micrograms/day was added. Therapy results were evaluated by ESR, CRP, morning stiffness, the Richie index, and the Lee index. Immunomodulatory effects were investigated by measuring lymphocyte proliferation and apoptosis both in the patients and in vitro in 10 nM alphacalcidiol-supplemented culture medium. RESULTS: After 3 months, high dose oral alphacalcidiol therapy showed a positive effect on disease activity in 89% of the patients (45% or 9 pts. with complete remission and 44% or 8 pts. with a satisfactory effect). Only two patients (11%) showed no improvement, but no new symptoms occurred. No side effects were observed. CONCLUSION: These results suggest that alphacalcidiol is a powerful immunomodulatory agent with fairly low hypercalcemic activity. Clinical improvement was strongly correlated with the immunomodulating potential of this agent. We noticed dual effects on lymphocyte proliferation and apoptosis according to the prior cell activation state. Alphacalcidiol could therefore possibly be used as an adjunct therapy with DMARDs in patients with rheumatoid arthritis.

Pavlica L, Perić-Hajzler Z, Jovelić A, Sekler B, Damjanović M. · Military Medical Academy, Clinic of Rheumatology and Clinical Immunology, Belgrade. · Vojnosanit Pregl. · Pubmed #16229202 No free full text.

Abstract: AIM: The aim of our study was to determine the prevalence of psoriatic arthritis in the patients with psoriasis and to analyze retrospectively the results of a 34-year multidisciplinary management of the patients with psoriatic arthritis. METHODS: The study included 162 out of 183 treated patients with psoriatic arthritis, aged 48 +/- 15 years. All the patients satisfied the current diagnostic criteria for psoriasis and psoriatic arthritis according to the American College of Rheumatology. RESULTS: Psoriatic arthritis developed in 183 (9.3%) out of 1976 patients with psoriasis. Time interval for establishing the diagnosis was 4 years. A positive family history of the disease had 15.0% of the studied patients. Its onset was most often at 42 years of age in 70.4% of the cases, and 2 months to 59 years after the appearance of psoriasis. Psoriatic arthritis without psoriasis appeared in 1.8% of the patients. A severe form of arthritis had 64.2% of the patients, mainly the patients with scalp psoriasis (chi2 = 3.2; p < 0.05). Nail changes had 35% of the patients. Distal interphalangeal joints were involved in 63.6%, axial skeleton in 36.4%, oligoarthritis in 45.0%, polyarthritis in 55.0%, and mutilating form in 6.8% of the patients. Elevated Erythrocyte Sedimentation Rate was reveald in 61.7% of the patients. Immunoglobulin M (IgM) rheumatoid factor was altered in 4.3% of the patients. The human leukocyte antigen (HLA) typing in the 28 patients were: A2 32.0%, A3 18.0%, Al and A9 14.0%, A28 and A29 3.5%, B8 and B16 14.0%, B5 and B12 11.0%, B13, B15, B18, B27 and B35 7.0%. Radiologic changes were most often in hand and foot joints, less frequently in the knees and quite infrequently in hips and shoulders joints. Sacroiliitis was found in 46.4% of the patients. Psoriasis was treated with topical corticosteroids and salicylic ointments in all the patients, ultraviolet (PUVA therapy) in 5.6% and retinoids in 4.3% of them. Artrithis was treated with nonsteroidal anti-inflammatory drugs, with systemic corticosteroids 41.3% and with disease modified antirheumatic drugs, most frequently methotrexate, 59.9% of the patients. Radionuclide synovectomy was performed in 6.8%, surgery in 6.2% and physical therapy in all the patients. CONCLUSION: Psoriatic arthritis developed in 9.3% of the psoriatic patients. Time interval for establishing the diagnosis was long, and there were no specific laboratory findings. All the synovial joints could be involved in the psoriatic process. Scintigraphy should be used only in case of early suspected sacroiliitis. The treatment of psoriatic arthritis was the teamwork between the dermatologist, rheumatologist, physiatrist and orthopedic surgeon.

Pavlica L, Pejnović N, Drasković N. · Clinic of Rheumatology and Clinical Immunology, Military Medical Academy, Belgrade. · Srp Arh Celok Lek. · Pubmed #14692140 No free full text.

Abstract: INTRODUCTION: Reiter's syndrome (RS) is an seronegative arthritis that occurs after urogenital or enteric infection which in addition with occular and/or mucocutaneous manifestations presents complete form of disease. According to previous understanding arthritis in the RS is the reactive one, which means that it is impossible to isolate its causative agent. However, there are the more and more authors suggesting that arthritis in the urogenital form of disease is caused by the infective agent in the affected joint. This suggestion is based on numerous studies on the presence of Chlamydia trachomatis and Ureaplasma urealyticum in the inflamed joint by using new diagnostic methods in molecular biology published in the recent literature [1-3]. Besides, numerous studies of the humoral and cell-mediated immune response to "triggering" bacteria in the affected joint have supported previous suggestions [4-7]. Aim of the study was to determine whether synovial fluid T-cells specifically recognize the "triggering" bacteria presumably responsible for the Reiter's syndrome. METHOD: The 3H-thymidine uptake procedure for measuring lymphocyte responses was applied to lymphocytes derived concurrently from synovial fluid (SF) and from peripheral blood (PB) [8]. Ureaplasma antigen and mitogen PHA stimulated lymphocytes in 24 RS patients (24 PB samples, 9 SF samples) and the results were compared with those found in 10 patients with rheumatoid arthritis (RA) (10 PB samples, 5 SF samples). Preparation of ureaplasma antigen. Ureaplasma was cultured on cell-free liquid medium [9]. Sample of 8 ml was heat-inactivated for 15 minutes at 601C and permanently stirred with magnetic mixer. The sample was centrifuged at 2000 x g for 40 minutes and than deposits carefully carried to other sterile glass tubes (Corex) and recentrifuged at 9000 x g for 30 minutes. The deposit was washed 3 times in sterile 0.9% NaCl, and final sediment was resuspended in 1.2 ml sterile 0.9% NaCl. BACTERIOLOGY: Chlamydia trachomatis was isolated by cell culture using cycloheximide-treated McCoy cells [10], while Ureaplasma urealyticum was identified according to its biochemical properties grown on cell-free liquid medium [9]. RESULTS: Proliferative response of the PB lymphocytes to stimulation by mitogen and ureaplasma antigen did not differ between RS and RA patients. Also, there was no difference in proliferative response of SF lymphocytes to mitogen stimulation between RS and RA patients (Figure 1). However, proliferation of SF lymphocytes stimulated by ureaplasma antigen was significantly elevated in RS patients compared with the control group. This difference is statistically significant (p < 0.05) (Figure 2). Difference in proliferative response of the PB and SF lymphocytes stimulated by the ureaplasma antigen was not found in RS patients. DISCUSSION: It was found that SF lymphocytes of RS patients showed significantly elevated proliferative response to stimulation by the ureaplasma antigen compared with SF lymphocytes of the control group. There was no difference when the lymphocytes were stimulated by the mitogen. Our findings suggest that elevated proliferative response of lymphocytes is the sign of stimulation cell-mediated immunity to antigen present in inflamed joint. Hence, the main immune response to Ureaplasma is on the cell-mediated level in the affected joint. This confirms the earlier finding reported by Ford et al. who concluded that synovial rather than peripheral blood lymphocytes indicate the microbiological cause of arthritis [11, 12]. Horowitz et al. demonstrated the correlation between clinical remission after antibiotic therapy and eradication of Ureaplasma, together with a decrease in cellular immune response synovial fluid lymphocytes to ureaplasma antigen stimulation [13]. In that study Horowitz did not find statistically significant difference of ureaplasma proliferative response between PB and SF lymphocytes in patients with RS. We obtained the same results. Than we concluded that sensibilization of immune system exist in the presence of foreign antigen in RS patients. The other authors demonstrated higher stimulation indices than the ones we found in our patients [11-15]. This difference may be the result of different preparation of antigens, in other words selection of serotype of Ureaplasma for antigen preparation different conditions of lymphocyte cultivation. We concluded that the presence of antigen, antigen-specific T cells and efficient antigen-presenting cells (CD4+ T cells) in the joint of RS patients strongly suggests that a T-cell-mediated response to bacteria has the central role in the pathogenesis of Reiter's syndrome.

Pavlica L, Drasković N, Kuljić-Kapulica N, Nikolić D. · Military Medical Academy, Clinic of Rheumatology and Clinical Immunology, Belgrade. · Vojnosanit Pregl. · Pubmed #12688106 No free full text.

Abstract: BACKGROUND: The aim of this study was to contribute to the insight of the role of the infectious agent in ethiopathogenesis of the Reiter's syndrome development, which could directly influence the choice of treatment of these patients. METHODS: Eighteen patients with urogenital form of the Reiter's syndrome and 16 controls (6 with rheumatoid arthritis and 10 with pigmented villonodular synovitis) were included in the study. In all patients standard laboratory analyses of the blood, urine and stool were made; antibody titer to Chlamydia trachomatis and Ureaplasma urealyticum was determined in synovial fluid and serum; isolation of Chlamydia trachomatis and Ureaplasma urealyticum in urethral, cervical and conjunctival swabs, as well as in prostatic and synovial fluid, was also made. HLA typing was done, too. Chlamydia was isolated in the McCoy cell culture treated with cycloheximide, while Ureaplasma was identified according to its biochemical properties grown on cell-free liquid medium. RESULTS: Chlamydia trachomatis was isolated from the synovial fluid of 4 patients with Reiter's syndrome (22.2%), while Ureaplasma urealyticum was isolated in 7 of them (38.9%). These microorganisms were not found in any synovial fluid of the control group patients. CONCLUSION: Presence of these bacteria in the inflamed joint might be an important factor in etiopathogenesis of this disease, and it supports the hypothesis that arthritis in Reiter's syndrome is probably of the infectious origin.

Pavlica L. · No affiliation provided · Vojnosanit Pregl. · Pubmed #16605202 No free full text.

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