Reiter's syndrome--disease of young men-- analysis of 312 patients.

INTRODUCTION: Reiter's syndrome is reactive arthritis occurring after acute urogenital (urethritis, cervicitis) or enterocolitis infections. The associated ophthalmological and/or mucocutaneous changes are full clinical manifestations of this disease. This paper was aimed at analyzing clinical and radiological characteristics and findings of possible etiological factors and protocol for Reiter's syndrome therapy. MATERIAL AND METHODS: Of 312 patients included in the study, 279 were men and 33 were women, the ratio between them being 8.5:1. The disease was diagnosed based on clinical evidence of two basic characteristics of Reiter's syndrome: arthritis preceded by acute urogenital or enteral infection. RESULTS: Urogenital and enterocolitic form of disease was found in 242 (77.5%) and 52 (16.5%) patients, respectively; whereas the initial cause was not discovered in 18 patients (6%). Three or two main signs of Reiter's syndrome were present in approximately the same number of patients (41.7% and 44.2%), whereas all four signs of disease were present in 14.1% of the patients. Acute or sub-acute form was present in 40.5%, while recurrent and chronic disease was diagnosed in 31% and 28.5% of the patients, respectively. The most frequent clinical manifestation of this disease was on the locomotor system as asymmetrical oligoarthritis localized in lower extremities, present in 69.4% of the patients. Chlamydia trachomatis was found in the synovial fluid in 54% of patients (20/37), ureaplasma or mycoplasma was isolated in the synovial tissue of 73.1% of patients (30/41) and in the peripheral blood mononuclear cells in 93.2% of patients (41/44). Human leukocyte antigen B27 was present in 83.3% of patients. CONCLUSION: Reiter's syndrome is a multisystem disease, predominantly occurring in human leukocyte antigen B27 positive young males. The fact that the causative agents are found in the synovial membrane or synovial fluid is indicative of infectious rather than reactive arthritis.

[Progressive course of hypophosphatemic osteomalacia during 25-year follow up].

INTRODUCTION: Hypophosphatemic osteomalacia is defined as mineralization of the newly formed bone matrix (osteoids) in adults as a consequence of the phosphate deficiency. CASE REPORT: A female from Belgrade, aged 62 years fell ill in 1982. when she was 36. She first felt pains in bones associated with chronic fatigue. In 1986. during her hospitalization the presence of neoplastic hematologic, endocrinologic, urogenital and gastroenterologic system deseases was excluded. Hypophosphatemic osteomalacia was diagnosed on the basis of the history, clinical presentation, physical examination, radiologic finding and laboratory analyses (lower serum phosphorus level). The initial therapy included a mixture of phosphates, vitamin D and calcium. The doses were several times corrected over the following four years. In 1990 she had a mild clinical deterioration requiring recorrection of the mentioned therapy. In 1993 bilateral femoral neck fractures occurred and subsequent osetosynthe as was performed. The disease had a progressive character in spite of the administered drug therapy so that multiple fractures occurred in 2000. During the last hospitalization in 2008. neither new pseudo fractures nor fractures were found although biochemical profile of the hypophosphatemic osteomalacia was still present. CONCLUSION: The aim of this study was to emphasize the complexity in both diagnostic and therapeutic approach in the case of hypophosphatemic osteomalacia. In the presented case the patient showed a complicated and progressive course. In our opinion such course was a consequence of impossible etiologic treatment and discontinued therapy

[Lung involvement in systemic connective tissue diseases].

BACKGROUND/AIM: Systemic connective tissue diseases (SCTD) are chronic inflammatory autoimmune disorders of unknown cause that can involve different organs and systems. Their course and prognosis are different. All of them can, more or less, involve the respiratory sistem. The aim of this study was to find out the frequency of respiratory simptoms, lung function disorders, radiography and high-resolution computerized tomography (HRCT) abnormalities, and their correlation with the duration of the disease and the applied treatment. METHODS: In 47 non-randomised consecutive patients standard chest radiography, HRCT, and lung function tests were done. RESULTS: Hypoxemia was present in nine of the patients with respiratory simptoms (20%). In all of them chest radiography was normal. In five of these patients lung fibrosis was established using HRCT. Half of all the patients with SCTD had simptoms of lung involment. Lung function tests disorders of various degrees were found in 40% of the patients. The outcome and the degree of lung functin disorders were neither in correlation with the duration of SCTD nor with therapy used (p > 0.05 Spearmans Ro). CONCLUSION: Pulmonary fibrosis occures in about 10% of the patients with SCTD, and possibly not due to the applied treatment regimens. Hypoxemia could be a sing of existing pulmonary fibrosis in the absence of disorders on standard chest radiography.

Successful treatment of postvenereal reactive arthritis with synovectomy and 3 months' azithromycin.

BACKGROUND: The effects of antibiotic therapy on the course of postvenereal reactive arthritis have not yet been elucidated. OBJECTIVE: The objective of this study was to observe the clinical course and outcome of synovectomy and 3 months of azithromycin therapy in patients with reactive arthritis and previously diagnosed triggering bacteria. METHODS: We performed an open, prospective study on 20 (14 male/6 female) patients with postvenereal reactive knee arthritis, aged 36.7 +/- 14.8 years, and with 16.5 +/- 20.4 months' duration of the disease. Detection of bacteria triggers was done by polymerase chain reaction, isolation and identification, and electron microscopy. Synovectomy was performed in all patients at entry into the study. Azithromycin was given at a dose of 500 mg per day for 5 days, and then 500 mg twice a week, during a 3-month period. Patients without remission were treated with combined antibiotic therapy using a macrolide, quinolone, and tetracycline for the next 4 months. Outcome evaluations of therapeutic efficacy and azithromycin safety were done after 1 and 3 months and 2 years of follow up. RESULTS: Remission, defined by the absence of joint swelling and tenderness, and extraarticular signs, was reached after 3 months in 15 of 20 (75.0%) patients (P = 0.025). Of 5 patients with persistent knee arthritis, remission was achieved with combined antibiotic therapy in 4. Visual analog scale scores (P < 0.01), the number of patients (P = 0.002), and the number of samples (P = 0.01) with a positive finding of bacteria or their DNA were significantly lower after 3 months of therapy. During the azithromycin therapy, there were no significant adverse effects. CONCLUSIONS: These patients with reactive arthritis did extremely well on the regimen described. In our study group, the number of patients and the number of samples with positive findings of bacteria or their DNA were lower after the antibiotic treatment combined with surgery, although not all bacteria were eradicated. Adverse effects of prolonged azithromycin administration were insignificant. This open treatment approach is recommended but does need a study with controls.

Psoriatic arthritis: a retrospective study of 162 patients.

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.

[The cellular immune reaction in synovial fluid lymphocytes to Ureaplasma antigens in patients with Reiter's syndrome]. / Celularni imunski odgovor limfocita sinovijske tecnosti na antigen Ureaplazme kod bolesnika sa Rajterovim sindromom.

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.

Isolation of Chlamydia trachomatis or Ureaplasma urealyticum from the synovial fluid of patients with Reiter's syndrome.

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.

[Diagnostic significance of synovial biopsy in patients with Reiter's syndrome]. / Dijagnosticki znacaj biopsije sinovije kod bolesnika sa Rajterovim sindromom.

INTRODUCTION: Arthritis in Reiter's syndrome (RS) is a reactive synovitis associated with a localized infection of the urogenital or gastrointestinal tract with a genetic predisposition. The pathogenetic mechanisms for synovitis in RS are still unknown. Our aim was to examine some of the pathogenetic mechanisms in Reiter's syndrome looking for morphologic changes, immunoprotein deposits and microorganism antigens in synovial biopsies and to determine whether synovial biopsy is useful in diagnosis of RS. MATERIAL AND METHODS: Thirty patients with urogenital form of RS were examined within a four-year period. Table 1 illustrates laboratory findings in our patients. We performed synovial biopsies looking for histopathological changes, deposits of immunoproteins and microorganism antigens. Analysis of synovial biopsy specimens was performed using light and immunofluorescence microscopy and fluorescein-labelled monoclonal antibodies to Chlamydia trachomatis. RESULTS: Histopathological examination of synovial membrane revealed marked proliferation of the synovial lining cells (SLC) with less or more abundant papillary projections, hypertrophic and edematous tissue with marked vascularisation in 28 (93.3%) cases. Fibrinoid necrosis foci were seen on the surface of synovial tissue. Chronic inflammatory cells (CIC) were diffusely distributed. Edema of the vessel walls, swollen endothelial cells, fibrinoid necrosis in vessel walls as well as multilaminated basement membranes were observed. All histopathologic changes are presented in Table 2. Immunofluorescent techniques in 12 out of 30 (40%) synovial membranes showed immunoglobulin deposits: IgG and IgA deposits were found in vessel walls in 7 cases each and IgM in 10 biopsy specimens. C3 was present perivascularly or within the vessel wall in 4 (13.3%) cases. Sections treated using fluorescein-conjugated antibody revealed Chlamydia in the synovial tissue in 2 patients. CONCLUSION: Biopsy specimens with previously described changes in patients with suspected Reiter's syndrome can be useful to confirm the diagnosis. According to our experience, multiple biopsies of abnormal synovia are recommended in these patients.