Printer Friendly

Reiter's syndrome--disease of young men--analysis of 312 patients/Rajterov sindrom--bolest mladih muskaraca--analiza 312 pacijenata.


Reiter's syndrome (RS) is probably as old as the human race. Articular complications following dysentery were known even to Caelius Aurelianus, who lived at the beginning of the fifth century before Christ. This disease was named after the German bacteriologist Hans Reiter, who described it in 1916, although the same disease had been described by the French physicians Feissinger and Leroy a week earlier. The English physician Benjamin Brodie, however, described five patients with triad (urethritis, arthritis, conjunctivitis), and two with iritis as far back as 1818 [1].

The synonym for Reiter's syndrome is "reactive arthritis". The term is primarily used to describe spondylarthritis that occurs after intestinal and urogenital infections mainly in the patients with positive human leukocyte antigen B27 (HLA--B27) [2].

The responsibility for the etiology and pathogenesis of the RS lies with infectious agents, genetic predisposition and immunological mechanisms [3.4]. It is believed that chlamydia (Chlamydia trachomatis--Ct) is the main cause of urogenital Reiter's syndrome, rarely ureaplasma (Ureaplasma urealyticum--Uu) and mycoplasmas (Mycoplasma hominis--Mh), and Shigella enteropathic shape (Shigella), Salmonella (Salmonella), Yersinia and Campylobacter [3-6].

Although Reiter's syndrome was thought to belong to the group of reactive arthritis for years, the growing evidence emerged during last two decades suggesting that RS is infectious arthritis. Immunocytochemical and immunohistochemical methods were applied to detect Chlamydia and its particles in the synovial tissue and/or synovial fluid [5-7]. Polymerization chain reaction (PCR) and hybridization techniques demonstrated the presence of nucleic acid of known microorganisms inducted in the synovial tissue and fluid of patients with post-enterocolitis and post-urethritis reactive arthritis [6-10].

Chlamydia trachomatis is believed to be the main cause of urogenital form of RS in genetically predisposed individuals, but it is not clear how Chlamydia infections lead to the development and relapse of chronic arthritis [10, 11]. There is compelling evidence that bacteria and microbial antigens, which induce reactive arthritis, persist in the joints and other reservoirs as the front door of infection. Due to the intensive immunological and immunogenetic investigations of reactive arthritis over the past decades, current understanding of the mechanism of this disease is mainly based on the possible role of immune response [11, 12]. It is believed that the imbalance of cytokines and the interaction of bacteria and HLA--B27 play a major role in the failure to eliminate bacteria and microbial antigen (inductors) from the body, which leads to the manifestation of disease and chronicity. On the other hand, the microbiological and molecular etiopathogenesis of bacterial persistence is not so well explained although the researchers succeeded in getting the insight into the persistence of Chlamydia on several occasions in previous years [12-16].

The role of HLA--B 27 in the pathogenesis is unclear. Reiter's disease affects about 20% of HLA--B 27 positive cases after acute urogenital or enteric infections. It is assumed that the lower part of the B-27 antigen has the same layout of amino acid as microorganisms that are the drivers of pathological process (the theory of molecular mimicry) [6, 11, 17]. According to the literature, HLA--B27 is found in 60 to 92% of patients, and it is responsible for the slower elimination of pathogens, their antigens, and development of the chronic form of Reiter's syndrome [6, 16, 18, 19].

Clinical manifestations are of the utmost importance for diagnosing this disease. Typical RS starts with urogenital infections, which are more common in men than in women in the third decade of life [6, 11, 17]. General signs and symptoms and other manifestations of disease may occur in the period of 1-4 weeks until the appearance of arthritis. Arthritis begins suddenly; it is usually asymmetrical, oligoarticular, localized in the lower extremities. The acute course of the disease is followed by the sub-acute phase, which lasts from two to 12 months. It may recur in some patients in different time intervals; however, if it persists for more than 12 months, it is considered chronic and usually creates functional problems [6, 17]. The disease can manifest itself in different ways: the affection of the locomotor system as the only clinical manifestation of the disease, called monosymptomatic form and incomplete form by Mladenovic and Arrnet, respectively [20, 21], whereas in a smaller number of patients it is manifested in the complete form: urethritis, arthritis, conjunctivitis / uveitis and mucocutaneous changes [6, 17, 20, 21].

Laboratory tests usually reveal the cause of the initial infection and the presence of inflammation [11, 12, 17]. Radiographic changes in the musculoskeletal system have their topographical and morphological features. The lower extremities (mostly II and III metatarsophalangeal ankle and calcaneus) and sacroiliac joints are most frequently affected, and the spinal cord is rarely affected. Treatment is performed by administering appropriate antibiotics for the initial infection to prevent relapse, and the therapy of chronic arthritis includes non-steroidal anti-inflammatory drugs (NSAIL) and physical procedures. More severe forms of the disease require administration of drugs from the group of basic and / or biological agents. Radiation synovectomy and surgical methods of treatment are sometimes applied (arthroscopic synovectomy) [6, 11, 17, 21]. The aim of this study was to analyze the clinical, radiological and other characteristics, and to identify potential etiologic factors and ways of treatment of patients with RS.

Material and Methods

This study included 312 patients with RS examined and treated at the Department of Rheumatology of Military Medical Academy during the period of 42 years (from 1970 to 2011). There were 279 male and 33 females (the ratio being 8.5:1), whose average age was 27.2 years, ranging from 14 to 65 years.

Reiter's syndrome was diagnosed in our patients according to the applicable criteria [22]: arthritis and/or sacroiliitis, which developed one to four weeks after the previous enteric or urogenital infection. In addition to the two main clinical criteria, arthritis and prior infection, the presence of ophthalmic (acute conjunctivitis, acute anterior uveitistrias) and/or mucocutaneous changes (balanitis, stomatitis, keratodermia-tetrads) were necessary to diagnose the complete form of Reiter's syndrome [17, 22].

The patients who had had reactive arthritis (arthritis of peripheral joints, dactylitis, enthesitis, sacroiliitis) for more than 12 months were classified as having the chronic form of disease [12, 17].

The disease was diagnosed based on the tests and examinations of blood, urine, stool, synovial membrane, synovial fluid and conjunctival swabs, urethra and/or cervix, i.e. prostatic exprimate as well as the determination of antibody titers to Chlamydia, Salmonella and Yersinia and human leukocyte antigen (HLA) typization.

Chlamydia trachomatis was identified in McCoy cell culture treated by cycloheximide and genital mycoplasmas (Ureaplasma urealyticum and Mycoplasma hominis) were determined according to their biochemical properties in liquid selective medium from the swab of the cervix, urethra and prostatic exprimate. The polymerization chain reaction was used for the detection of genital mycoplasma and chlamydia in peripheral blood, synovial fluid and synovial joint of the patient [7-9]. Some patients underwent histological and/or immunofluorescence examination of their biopsy material (skin, affected synovial joints, kidneys), and radiography of affected parts of the musculoskeletal system, ultrasound examination of the heart, joints and tendons (transducer of 3.5 and 7.5 MHz, Diasonix--USA), electrocardiography and bone scintigraphy with Tc99 calculating the index sacroiliac (SI--index). SI--index is the ratio of accumulation of radiolabel in the sacroiliac joints and bones. Normal values in our population amount to 1.38. Statistical analysis included descriptive measurements: the average value, arithmetic mean, standard deviation (SD), range and analytical measurements. General linear model for repeated measures was used to estimate the statistical significance of the parameter data (laboratory Mc Nemar's test was used to evaluate the statistical significance of frequency of positive bacterial findings in the patients before and after therapy). Hi-square test was used to assess the statistical significance of positive findings in different bacterial samples, before and after treatment. The threshold of statistical significance was set at 0.05. Statistical analyses were performed by the following software: the Statistical Package for the Social Sciences (SPSS) for Windows v. 11.5 (SPSS Inc. Chicago, IL).


Clinical Characteristics

Acute or sub-acute form, recurrent and chronic form of RS was found in 126 (40.5%), 97 (31%), and 89 (28.5%) patients, respectively. The disease with four, three and two main signs was diagnosed in 44 (14.1%), 130 (41.7%) and 138 (44.2%) patients respectively. According to the initial infection, 242 (77.5%) patients had urogenital form, 52 (16.5%) had enterocolitis and the cause was not determined in 18 (6%) patients. Arthritis, often asymmetric, was present in all patients. It was localized only in the lower extremities in 179 (57.4%) patients, in the lower and upper extremities in 130 (41.6%) patients, and in the upper extremities only in 3 (1%) patients. Oligoarticular arthritis was present in 214 patients (69%), polyarticular in 44 (14%), monoarticular in 53 (16.7%) patients. Dactylitis on lower extremitis was found in 43 (17.6%) patients. Out of twelve (3.8%) patients who had dactylitis on the upper extremitis, nine patients had dactylitis of the second and third finger, and three patients had it on the third and fifth finger.

Of 125 (40%) patients who had pain in the spinal column, 110 had radiographic signs of inflammation. Clinical manifestations of the musculoskeletal system by frequency of occurrence are shown in Table 1.

The following types of urogenital events were found in 246 (78.8%) patients: the most common was urethritis/uretrocistitis in 71.6% of patients, then prostatitis in 18.8% of the patients, cervicitis in 6.6%, hemorrhagic cystitis in 1.9% and epididymitis in 1.1% of patients. Fifty (16.1%) patients had a prior infection of enterocolitis or enteritis. Eye changes occurred in 139 (44.5%) patients, of which the most frequent was conjunctivitis in 110 (79%), acute iridocyclitis in 21 (15%), and other changes (keratoconjunctivitis, episcleritis) in eight (6%) patients. Changes in the skin, nails and mucous membranes were manifested in 57 (18.2%) patients, of which the most common was balanitis in 42 (13.4%) and five patients had simultaneously two types of such changes. General signs developed in 190 (61.5%) patients: a significant loss in body weight (3-17 kg in a month) in 37 (12%) and subfebrile temperature or fever in 124 (39.7%) patients. As for other manifestations, changes on the heart developed in nine patients (2.8%) and kidney damage was pathologically and histologically verified in four patients beyond doubt.

Laboratory Findings

Human leukocyte antigen typization revealed HLA-B27 in 83.3% of patients. Erythrocyte sedimentation rate was higher in 64.4% of the patients, being over 50 mm/h in 57.7%. Non-specific proteins of the acute phase of inflammation were most frequently increased: fibrinogen in 48.3%, C-reactive protein in 40.5%, haptoglobin in 46% of the patients.

The increase in immunoglobulin (IgG, IgA, IgM) was present in 17.6%. Rheumatoid factor (RF) was positive in 2.6%. Anemia was found in 38 patients (12.2%); 26 patients (8.3%) had leukocytosis, 10 (5.3%) patients had thrombocytosis, and an increase in the concentration of uric acid was recorded in 3 (0.9%) patients. Other biochemical tests were within normal limits.

The following pathological findings in urine were recorded in 135 patients: leukocyturia in 81 patients, erytrocyturia in 47 and proteinuria over 150 mg/d in 7 patients.

Urethral, cervical and/or conjunctival as well as prostatic swabs were positive for Chlamydia in 39.7%, for Ureaplasma in 28.5%, and for Mycoplasma in 8% of the patients. Of those patients who were diagnosed to have postenterocolitic form of Reiter's syndrome, Yersinia was isolated in 48%, Salmonella in 36%, Shigella in 12%; whereas, the cause remained undiscovered in other patients. Several types of microorganisms, triggers of the infection, were identified in 8.9% of patients. The analysis of synovial fluid by seeding substrate was performed in 54 patients, and it proved to be positive for Chlamydia and/or genital mycoplasmas in 29.6% (16/54). The polymerase chain reaction method was applied to identify bacteria in blood and/or the target site (synovium and synovial fluid) in 44 patients. All patients had a trigger, the presence of bacteria in at least one of isolated causes. In synovial fluid, one or more bacteria (Chlamydia trachomatis, genital mycoplasmas, Ureaplasma) was isolated in 54% (20/37) of the patients, in the synovium in 731% (30/41) of the patients and in the peripheral blood in 93.2% (41/44) of the patients (Table 2).

Radiographic and Other Findings

Radiographic changes in the musculoskeletal system were found in 185 (59.3%) patients. Table 3 shows the changes commonly seen, whereas 89 (67.9%) patients had findings of Sacroiliitis (SI index exceeding 1.38).


The therapeutic approach to patients is focused on the treatment of acute arthritis and the infection. All patients with arthritis were treated with NSAID and followed by physical therapy. Glucocorticoids were administered in the acute phase, in severe forms, systemically and/or locally intra-articularly or in the insertion of the affected tendon. Once the cause of the initial infection had been identified, antibiotic therapy was introduced. Surgical treatment (arthroscopic synovectomy or front open method) or radiation synovectomy was applied in refractory chronic synovitis. Treatment of 44 patients with chronic post-urethritis Reiter's disease included arthroscopic synovectomy and different antibiotic protocols. The first group of 22 patients underwent arthroscopic synovectomy, using a three-month treatment with azithromycin, which resulted in remission in 77% of the patients (p=0.023). The second group of 22 patients received the combined therapy consisting of arthroscopic synovectomy and triple alternating antibiotic: quinolone 500 mg/d, tetracycline 1 g/d, roxitromicin 300 mg/d for 10 days in the first month then each of the above-mentioned antibiotics for 10 days during the next three months. After the therapy, the remission was achieved in 63.3% of patients (p = 0.437) PCR method was done to identify bacteria in blood in all patients before and after treatment and in the synovium and synovial fluid in the patients with synovitis at the beginning and the end of therapy (Table 2). By analyzing the results it was concluded that the frequency of patients with the appearance of bacteria in any sample taken before and after treatment with hemomycin significantly differ (McNemar's test, p=0.002). Before treatment, the finding was positive in 95% of the respondents and negative in 5%, whereas after treatment, it remained positive in 30% and turned negative in 65% out of 19 patients with positive finding before treatment. However, the negative finding before treatment turned positive in 5% of the patients after treatment (Graph 1). The frequency of patients with the appearance of bacteria in any sample taken before and after triple antibiotic therapy was statistically significantly different (McNemar's test, p = 0.002). This antibiotic therapy resulted in statistically significant increase in the number of patients with the negative finding. The finding that had been positive in 22 patients before treatment, remained positive in 12 (54.5%) and turned negative in 10 (45.5%) after treatment (Graph 2).

In chronic forms of the disease, in which the conventional form of treatment had failed, the basic drugs were applied particularly in patients with cutaneous and nail changes. The drug of choice was metoterxat at a dose of 10 to 15 mg per week. Sulfasalazine was administered to the patients with a more severe form of disease and the intolerance to methotrexate. In recent years, glucocorticoids with prolonged action have been applied intermittently in 128 patients, while the implantation gave a good but transient therapeutic effect in some patients. Four patients received a maximum of colloidal gold to 1250 mg., but with no effect, 26 methotrexate 10-15 mg weekly. Remission was achieved in 12 patients. Sixty-three patients used sulfasalazine 2-3 g daily for 6 months, and the effect was favorable in 23 of them (36%), and one used to take cyclophosphamide 100 mg per day to achieve remission. Radiation synovectomy of the knee was performed with Yttrium 90 (185 MBq) in six (1.9%) patients, with the resulting remission; surgery (arthroscopic or open method) was performed in 61 (19.5%) patients, while knee arthroplasty was done in one patient.


Reiter's syndrome is the most common reactive arthritis among younger men caused by microorganisms such as urogenital form of Chlamydia, rarely by ureaplasma and Mycoplasma hominis and enterocolitic forms of Shigella (S. flexneri, S. disenteriae etc.), Salmonella, Yersinia, Campylobacter, Clostridium difficile [6, 12, 17]. According to the literature, this disease is most common in males in the third decade of life [6, 17, 20]. In our group of 312 patients, 89.4 % were men, their average age being 26.8 years. The highest number of 78.8 % of our patients had urogenital form of disease, which is consistent with the findings of other authors [6, 17]. The most common causes were Chlamydia and Ureaplasma, and Yersinia and Salmonella among enterobacteria. The most frequent infections of urogenital tract were urethritis and urethrocystitis (62.1 %), prostatitis, cervicitis and hemorrhagic cystitis, and rarely epididymitis, which is in accordance with literature [6, 19, 21].

Chlamydia trachomatis is considered the major cause of urogenital form of RS in genetically predisposed individuals, surviving in the synovia in the persistent form [14, 17, 23, 24]. The analysis of synovial fluid by seeding substrate, which had been performed in 54 patients, showed that 29.6% (16/54) of findings were positive for Chlamydia, and/or genital mycoplasmas, that being indisputable evidence of the presence of bacteria in the knee in a certain number of affected persons, which is in accordance with literature data [6-8, 17, 25].

Bacteria in blood and target location (the synovium and synovial fluid) were identified by PCR method in 44 patients. All patients were proved to have "trigger" bacteria in at least one of mentioned samples. In this study, Chlamydia trachomatis was the most common cause (71.4%) of post-urethritis reactive arthritis, which is in accordance with data from the literature [6, 12, 17]. To assess the course of disease and treatment outcomes the following questions had to be answered: what their number was, whether the bacteria were alive (viable) and the extent to which certain genes were active [17, 25, 2628]. Real-time polymerase chain reaction (RT--PCR) tests [27, 28] were performed to assess the viability of bacteria, which was proved in joints and blood in all patients who were positive for Chlamydia after treatment.

The role of HLA--B 27 in the pathogenesis is unclear [12, 17-19]. HLA--B27 is more important as a predictor of the severity of a disease and the localization of arthritis than as a factor in genetic predisposition to the disease [14, 17, 19]. In this study sample, HLA--B27 was positive in 83.3% of patients, which is consistent with the findings of other authors [6, 14, 27].

The main lesions in Reiter's syndrome are found in the musculoskeletal system [6, 11, 17, 20, 21]. Arthritis is localized in a single joint, usually in the knee, in 10-20% of patients. In our group, arthritis was present in all patients, it was usually asymmetrical, oligoartricular in 69%, polyarticular in 13.7%, monoarticular in 16.7%, and sacroiliitis without peripheral arthritis in one patient. Acute onset and sub-acute course of disease was identified in 41.5%, relapse in 36% and it was chronic in 28.5% of the patients.

Sacroillitis was seen in 71/185 (38.3%) by radiography of sacroiliac joints. According to the literature, sacroiliitis occurs most frequently in HLA--B27 positive patients [6, 17]. In our patients with sacroiliitis, HLA--B27 was positive in 80%. Dactylitis (sausage finger), a diffuse swelling of fingers, was present in 20.4% of patients from this study sample and in the group of 918 patients, who were analyzed by Mladenovic et al., it was described in 26% of patients [17]. Pain in the heel was reported by 36.2 % of our patients. In the literature, there are different data on how many patients had pain in the heel, their number ranging from 5.8% to 65.2% [6, 12, 17, 20]. Conjunctivitis occurs after urethritis, and it usually does not last long. Eye changes developed in 44.5% of our patients, and 79% of them were conjunctivitis, short lasting and in one eye in most cases, and iridocyclitis in 15% of patients. Mladenovic reported the incidence of conjunctivitis to be 35.6% [6, 17, 20]. Mucocutaneous changes are manifested in the skin, mucous membranes of the mouth and the glans penis. Of 18.2% of patients who had changes in the skin, 8.7% had two types of changes. Circinate balanitis and stomatitis was diagnosed in 11.2% and 3.2% of the patients, respectively. The frequency of circinate balanitis in studies with a large number of patients ranges from 17 to 25.6% [6, 17]. Studies conducted in recent years confirm the presence of bacteria or their particles in synovial fluid and/or synovial joints affected by inflammation, bringing into question the view that reactive arthritis is sterile [4, 6, 14, 25, 29-31].

Antibiotics were recommended as the therapy of choice in the patients found to have bacteria, the "trigger" of reactive arthritis. It has been shown that several months (at least 3 to 6) of antibiotic therapy can significantly shorten the time required to achieve remission [29-32].

The patients from both study groups reacted well to the combined surgical and antibiotic therapy. The total number of patients and samples positive for bacteria and bacterial deoxyribonucleic acid (DNA) were lower after treatment, although the eradication of bacteria was not achieved in all cases. Remission of the disease occurred in 77% of patients from the first study group where synovectomy had been performed and in 63.3% of patients (p = 0.437) from the second group of 22 patients treated with synovectomy and triple antibiotic therapy.

In conventional therapy with NSAI, glucocorticoids, basic drugs and short-term antibiotic therapy, remission occurred in 35-45% of patients during the first year [6, 12, 17, 30-32].

Synovectomy contributed significantly to remission in our patients because hypertrophic synovium with infectious agents was removed, thus decreasing the amount of antigenic tissue, and the pathogenicity of bacteria in the joint.

Basic drugs were administered in chronic forms of disease with radiographic changes in the joints and mucocutaneous changes. In the group of patients treated with sulfasalazine, remission was achieved in 36% of patients after 6 months. Such a situation does not give the basis to conclude that remission occurred spontaneously or resulted from the administered therapy (33). Remission was achieved in 58% (14/24) of patients with chronic arthritis and/or keratodermia treated with Methotrexate, which corresponds to the literature data [17, 34].

If the treatment described above fails to give good results, biological therapy, including inhibitors of tumor necrosis factor (TNF-alpha) and interleukins, should be opted for [35].


Reiter's syndrome is a multisystem disease which occurs predominantly in Human Leukocyte Antigen -B27 positive young men. It is most frequently manifested in incomplete form (post-urethritis arthritis). The course of disease is acute or subacute in the majority of patients. Arthritis is usu ally expressed as oligoarthritis of the lower extremities. The presence of bacterial pathogen genomes and their viability was proved by the modern polymerase chain reaction test for identification of bacteria in the synovium and synovial fluid of the patients having post-urethritis form of Reiter's syndrome

The results of this study showed a statistically significant reduction in the number of patients with positive findings of bacteria in any of the monitored sites and a significant increase in the number of patients who achieved remission after completion of antibiotic therapy and synovectomy.

All this suggests that Reiter's syndrome, although defined as reactive arthritis, has the characteristics of infectious arthritis.

Prolonged antibiotic therapy should be administered in all patients with proven infectious agents at the entry point, whereas diagnostic and therapeutic arthroscopic synovectomy along with nonsteroidal anti-inflammatory drugs, physical therapy and, if necessary corticosteroid therapy, should be applied in patients having arthritis lasting longer than a year as well as proven synovitis.

RS         --Reiter's syndrome
DNA        --deoxyribonucelic acid
HLA B      --27 human leukocyte antigen B-27
PCR        --polymerase chain reaction
NSAID      --non-steroidal anti-inflammatory drugs
SI index   --sacroiliac index

The paper has been received: 14. IV 2013.

The paper has been reviewed: 21. XII 2013.

The paper has been accepted for publication: 27. XII 2013.


DOI: 10.2298/MPNS1408222B


[1.] Wallace DJ, Weisman MH. The physician Hans Reiteras prisoner of war in Nuremberg: a contextual review of his interrogations (1945-1947). Semin Arthritis Rheum. 2003; 32:208-30.

[2.] Lu DW, Katz KA. Declining use of the eponym Reiter's syndrom in the medical literature, 1998-2003. J Am Acad Dermatol. 2005; 53:720-3.

[3.] Rohecar S, Pope J. Epidemiologic approaches to infection and imunity: the case of reactive arrthritis. Curr Opin Rheumatol. 2009; 21:386-90.

[4.] Carter JD, Gerard HC, Espinoza LR, Ricca LR, Valeriano J, Snelgrove J, et al. Chlamydiae as etiologic agents in chronic undifferentiated spondylarthritis. Arthritis Rheum 2009; 60:1311-6.

[5.] Schumacher HR, Maage S, Cherian PV. Light and electron microscopic studies on the synovial membrane in Reiter's syndrome: immunocytochemical identification of chlamydial antigen in patients with early disease. Arthritis Rheum 1988; 31:937-46.

[6.] Yu DT. Reactive arthritis (formerly Reiter syndrome) [Internet]. Available from:

[7.] Branigan PJ, Gerard HC, Hudson AP, Comparision of synovial tissue and synovial fluid as source of nucleic acids for detection of Chlamydia trachomatis by polymerase chain reaction. Arthritis Rheum 1996; 39:1740-6.

[8.] Pavlica Lj. Znacaj predhodne infekcije hlamidijom i ureaplazmom u posturetritisnom obliku Reiterovog sindroma (disertacija). Beograd: Vojnomedicinska akademija; 1997.

[9.] Jalava J, Skurnik M, Toivanen A, Eerola E. Bacterial PCR in the diagnosis of joint infection. Ann Rheum Dis 2001; 60:287-9.

[10.] Granfors K, Jalkanen S, Toivanen P, Koski J, Lindberg AA. Bacterial lipopolysaccharide in synovial fluid cells in Shigella triggered reactive arthritis. J Rheumatol 1992:19:500.

[11.] Keat A, Toivanen A. Reactive arthritis: clinical features and treatment. In: Hochberg M, Silman A, Smolen J, Weinblat M, Weisman M, editors. Rheumatology. Philadelphia: Elsevier; 2008. p. 1083-96.

[12.] Inman RD, Stone MA. Reactive artritis: ethiology and pathogenesis. In: Hocberg M, Silman A, Smolen J, Weinblatt M, Weisman M, editors. Rheumatology. Philadelphia: Elsevier; 2008. p. 1081-8.

[13.] Gerard HC, Branigan PJ, Schumacher HR, Hudson AP. Synovial Chlamydia trachomatis in patients with reactive arthritis/Reiter's syndrome are viable but show aberrant gene expression. J Rheumatol 1998; 25:734-42.

[14.] Rihl M, Kohler L, Klos A, Zeidler H. Persistent infection of Chlamydia in reactive arthritis. Ann Rheum Dis. 2006; 65(3):281-4.

[15.] Gerard H, Whittum-Hudson JA, Schumacher HR, Hudson AP. Synovial Chlamydia trachomatis up regulates expression of a panel of genes similar to that transcribed by Mycobacterium tuberculosis during persistent infection. Ann Rheum Dis. 2006; 65:321-7.

[16.] Sieper J. Disease mechanisms in reactive arthritis. Curr Rheumatol Rep 2004; 6:110-6.

[17.] Mladenovic V. Kerimovic-Morina DJ. Reiterova bolest (reaktivni artritis). Beograd: Institut za reumatologiju; 2007. str. 94-9.

[18.] Khan MA. HLA B27 polymorphism and association with disease. J Rheumatol. 2000; 27:1110-4.

[19.] Young JL, Smith L, Matyszak MK, et al. HLA-B27 expression does not modulate intracellular Chlamydia trachomatis infection of cell lines. Infect Immun. 2001; 69(11):6670-5.

[20.] Mladenovic V. Incomplete (monosymptomatic) form of Reiter's syndrome. XVI International Congress of Rheumatology, Paris 1981. Rev Rhum 1981; abstr 258.

[21.] Arnett FC. Incomplete Reiter's syndrome: clinical comparisons with clasical triad. Ann Rheum Dis 1979; 38 Suppl 1:S73-8.

[22.] Braun J, Kingsley G, van der Heijde D, Sieper J. On the difficulties of establishing a consensus on the definition of and diagnostic investigations for reactive arthritis. Results and discussion of a questionnaire prepared for the 4th International Workshop on Reactive Arthritis, Berlin, Germany, July 3-6, 1999. J Rheumatol 2000; 27:2185-92.

[23.] Carter JD, Hudson AP. Reactive arthritis: clinical aspects and medical management. Rheum Dis Clin North Am. 2009; 35:21.

[24.] Sieper J, Rudwaleit M, Braun J, Heijde, D. Diagnosing reactive arthritis: role of clinical settings in the value of serologic and microbiologic assays. Arthritis Rheum. 2002; 46:319-27.

[25.] Gerard HC, Whittum-Hudson JA, Schumacher HR, Hudson AP. Differential expresssion of three Chlamydia trachomatis hsp60-encoding genes in active vs. persistent infections. Microb Pathog. 2004; 36:35-9.

[26.] Zarco Montejo P. Diagnosis and treatment of Chlamydia-induced reactive arthritis. Reumatol Clin. 2012; 8 Suppl 1:S20-5.

[27.] Hammer M, Nettelnbreker E, Hopf S, et al. Chlamydial rRNA in the joints of patients with chlamydia-induced arthritis and undifferentiated arthritis. Clin Exp Rheumatol. 1992; 10:63-6.

[28.] Peuchant O, Duvert JP, Clerc M, Effects of antibiotics on Chlamydia trachomatis viability as determined by real-time quantitative PCR. J Med Microbiol. 2011; 60:508-14.

[29.] Peterson EM, Oda R, Alexander R, Greenwood JR, de la Maza ML. Molecular techniques for the detection of Chlamydia trachomatis. J Clin Microbiol. 1989; 27:2359-63.

[30.] Carter JD, Espinoza LR, Inman RD. Combination antibiotics as a treatment for chronic Chlamydia: induced reactive arthritis. Arthritis Rheum. 2010; 62:1298-307.

[31.] Kvien TK, Gaston JSH, Bardin Tae, et al. Three month treatment of reactive arthritis with azithromicin. Ann Rheum Dis. 2004; 63:1113-9.

[32.] Laasila K, Laasonen L, Leirisalo-Repo M. Antibiotic treatment and long term prognosis of reactive arthritis. Ann Rheum Dis. 2003; 62:655-8.

[33.] Clegg DO, Reda DJ, Weisman MH, et al. Comparison of sulfasalazine and placebo in the treatment of reactive arthritis (Reiter's syndrome). A department of veterans affairs cooperative study. Arthritis Rheum. 1996; 39(12):2021-7.

[34.] Meyer A, Chatelus E, Wendling D, et al. Safety and efficacy of anti-tumor necrosis factor alpha terapy in ten patients with recent-onsent refractory rectivae arrthritis. Arthritis Rheum. 2011; 63:1274-80.

[35.] Kaipiainen-Sepannen O, Ninisalo I, Korpilahde T, et al. Treatment of reactive arthritis with infliximab. Scand J Rheumatol. 2003; 32:122-4.

Jaroslav BOJOVIC (1), Natasa STRELIC (2) and Ljiljana PAVLICA (1)

Military Medical Academy, Belgrade

Department of Rheumatology (1)

Institute for Medical Research, Belgrade (2)

Corresponding Author: Dr Jaroslav Bojovic, Vojnomedicinska akademija, Klinika za reumatologiju, 11000 Beograd, Crnotravska 17, E-mail:
Table 1. Clinical characteristics of patients with Ryter's syndrome

Tabela 1. Klinicke karakteristike Rajterovog sindroma

Signs of the musculoskeletal system               Number of patients
Znaci na lokomotornom sistemu                    Broj pacijenata (%)

Arthritis : number of patients and %                  312 (100%)
  Artritis: broj pacijenata i %
Knee joints/Kolenski zglobovi                        228 (73.1%)
Ankle joints/Skocni zglobovi                         187 (59.9%)
Sacroiliac joints ([dagger])/Sakroilijacni           110 (35.0%)
  zglobovi ([dagger])
Wrists/Rucni zglobovi                                 70 (22.4%)
spondylitis , spondylodiscitis                        15 (4.8%)
  spondilodiscitis ([dagger])
Metatarsophalangeal/Metatarzofalangealni              94 (30.1%)
PIP joints of the foot/PIP zglobovi stopala           44 (14.1%)
PIP joints of the hand of/PIP zglobovi saka           30 (9.6%)
Metacarpophalangeal/Metakarpofalangealni              22 (7.0%)
The sensitivity of the heel:/Osetljivost pete:       113 (36.2%)
Dactylitis/Daktilitis:                                55 (17.6%)
Lower extremities/Donji ekstremiteti                  43 (17.6%)
Upper extremities/Gornji ekstremiteti                 12 (3.8%)
Bursitis/Burzitis                                     18 (5.7%)
Elbow/Lakat                                            9 (2.8%)
Knee/Koleno                                            4 (1.2%)
Hip/Kuk                                                4 (1.2%)
Heel/Peta                                              5 (1.6%)

Signs of the musculoskeletal system              (%) One Localization
Znaci na lokomotornom sistemu                        Jednostrana

Arthritis : number of patients and %
  Artritis: broj pacijenata i %
Knee joints/Kolenski zglobovi                         149 (79) *
Ankle joints/Skocni zglobovi                          120 (67) *
Sacroiliac joints ([dagger])/Sakroilijacni            85 (25) *
  zglobovi ([dagger])
Wrists/Rucni zglobovi                                  36 (5) *
spondylitis , spondylodiscitis
  spondilodiscitis ([dagger])
Metatarsophalangeal/Metatarzofalangealni              76 (18) *
PIP joints of the foot/PIP zglobovi stopala            36 (8) *
PIP joints of the hand of/PIP zglobovi saka            19 (11)
Metacarpophalangeal/Metakarpofalangealni               13 (9) *
The sensitivity of the heel:/Osetljivost pete:        70 (43) *
Lower extremities/Donji ekstremiteti                   38 (5) *
Upper extremities/Gornji ekstremiteti                  11 (1) *
Elbow/Lakat                                             7 (2)
Knee/Koleno                                             3 (1)
Hip/Kuk                                                 2 (2)
Heel/Peta                                               3 (1)

* Number of patients with bilateral localization/* broj bolesnika sa
obostranom lokalizacijom

([dagger]) localization according to radiological findings/([dagger])
lokalizacija na osnovu radioloskog nalaza PIP--proximal
interphalangeal joint/proksimalni interfalangealni zglob

Table 2. PCR analysis of bacterial DNA in the samples of synovial
tissues, synovial fluid and peripheral blood mononuclear cells
(PBMC), before and after (PBMC samples) treatment with azitomicinom
and combined  anti-biotic therapy in patients with post-urethritis
reactive arthritis

Tabela 2. PCR analize bakterijske DNK u uzorcima sinovijalnog tkiva,
sinovijske tecnosti i mononuklearnih celija periferne krvi(PBMC), pre
i posle (PBMC uzorci) azitomicinom i kombinovanom antibiotskom
terapijom kod pacijenata sa postvenericnim reaktivnim artritisom

                   Azithromycin therapy/4zitromicin

Patients        ST         SF       PBMCb      PBMCa

1               nd       Ct,Uu      Ct ,Uu       --
2               --         Uu         --         --
3               --         --       Ct, Uu       Ct
4               --         --       Ct, Mh     Ct, Mh
5               --         Ct       Ct ,Mh       --
6               Uu         Uu         Uu         --
7               --         --         Ct        Ct,
a8              --         --         Mh         Mh
9               --         Mh         Mh         --
10              Uu         Uu         Uu         --
11            Mh, Uu       --       Mh Uu       , Uu
12              Uu         Uu         Uu         --
13              Ct         --       Ct, Mh       --
14            Uu,Ct        --       Ct,,Uu       --
15            Mh, Uu       --       Mh,Uu        --
16              Mh         --         Mh         Mh
17              Mh         --         Mh         --
18              Uu         --         Uu         --
19            Ct, Cp       --         Ct         Ct
20            Cp, Mh       --       Ct ,Mh       --
21            Ct ,Uu       Ct       Ct, Uu       --
22              Uu         Uu         Uu         --

            Combined antibiotic therapy/Kombinovana
                     antibiotska terapija

Patients        ST         SF       PBMCb      PBMCa

1               Ct         nd         --         --
2             Ct, Cp       --         Ct       Ct, Cp
3               Ct       Ct, Uu       Ct         Ct
4             Ct, Mh       nd     Ct, Cp, Mh     --
5               Ct       Ct, Uu   Ct, Cp, Mh    Ct,
6             Ct, Mh       Ct       Ct, Mh       --
7               nd         nd         Ct         --
8               nd         nd         Ct       Ct, Cp
9           Ct, Cp, Mh   Ct, Cp     Ct, Cp       --
10            Ct, Cp       Ct         --       Ct, Cp
11              CT         Ct     Ct, Cp, Uu     Ct
12            CT, Mh       --       Ct, Uu       --
13              --         nd       Ct, Uu       --
14              Ct         Ct       Ct, Uu       Ct
15              Ct         Ct     Ct, Uu --
16            Ct, Cp       Ct         Ct         --
17              nd         nd       Ct, Uu       Ct
18              nd         nd         Uu         --
19            Ct, Mh       --       Ct Uu        --
20              Ct         Ct         Ct         --
21              Ct       Ct, Uu       Ct         --
22              --         --         Ct         Ct

S ST--synovial tissue, SF--synovial fluid; PBMCb--peripheral blood
mononuclear cells before therapy; PBMC peripheral blood mononuclear
cells after therapy, Ct--Chlamydia trachomatis, Cp--Chlamydia
pneumoniae, Mh--Mycoplasma  hominis, Uu--Ureaplasma urealyticum;
ND--not done

ST--sinovijska membrana; SF--sinovijska tecnost; PBMCs--mononuklearne
celije periferne krvi pre terapije;  PBMCa-mononuklearne celije
periferne krvi posle terapije Ct-Chlamidia trachomatis;
Cp--Chlamydia pneumoniae;  Mh--Mico-plasma hominis; Uu--Ureaplasma
urealiticum; nd--nije raceno

Table 3. The most frequent radiographic changes in 185 (59.3%)
patients with RS

Tabela 3. Najcesce radioloske promene u 185 (59,3%) bolesnika sa RS

Localization of Changes                             Number of changes
Lokalizacija promena                                  Broj promena

Sacroiliac joints (narrowing, subchondral                  110
sclerosis) Sakroilijacni zglobovi (suzenje,
suphondralna skleroza)

Heel--(heel spur, Achilles tendon ossification)            75
Petna kost--(trn petne kosti, osifikacija pripoja
Ahilove tetive)

Knee joints--(osteoporosis, joint space                    45
narrowing, enthesitis, periostitis) Kolenski
zglobovi--(osteoporoza, suzenje zglobnog
prostora, entezitis, periostitis

Metatarsophalangeal II, III, and interphalangeal           23
joint of the thumb (osteoporosis, joint space
narrowing, cysts, subluxation,
periostitis)/'Metatarzofalangealni II, III i
mecufalangealni zglob palca (osteoporoza, suzenje
zglobnog prostora, ciste, subluksacije,

Ankle joints (osteoporosis, joint space                     9
narrowing, periostitis) Skocni zglobovi
(osteoporoza, suzenje zglobnog prostora,

Spinal cord (T and L/S)--(asymmetric                       16
syndesmophytes) Kicmeni stub (T i
L/S)--(asimetricni sindesmofiti)

Total/Ukupno                                               278

Graph 1. Frequency of patients with bacteria found in
any sample before and after treatment with Hemomycin

Grafikon 1. Ucestalost ispitanika sa pojavom bakterija
u bilo kom uzorku pre i posle terapije hemomicinom

                    Positive results/    Negative results/
                    Pozitivan rezultat   Negativan rezultat

Before treatment/   95,0%                35,0%
Pre terapije

After treatment/    35,0%                65,0%
Posle terapije

Note: Table made from bar graph.

Graph 2. Frequency of patients with bacteria found in
any sample before and after triple antibiotic therapy

Grafikon 2. Ucestalost ispitanika sa pojavm bakterija u
bilo kom uzorku pre i posle trojne antibiotske terapije

                    Positive results/    Negative results/
                    Pozitivan rezultat   Negativan rezultat

Before treatment/   100,0%               54,5%
Pre terapije

After treatment/    54,5%                45,5%
Posle terapije

Note: Table made from bar graph.
COPYRIGHT 2014 Drustvo Lekara Vojvodine
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2014 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Title Annotation:Original study/Originalni naucni rad
Author:Bojovic, Jaroslav; Strelic, Natasa; Pavlica, Ljiljana
Publication:Medicinski Pregled
Article Type:Report
Date:Jul 1, 2014
Previous Article:The relationship between posterior tibial slope and anterior cruciate ligament injury/Uticaj nagiba zglobne povrsine golenjace na povrede prednjeg...
Next Article:The relationship between atherosclerosis and pulmonary emphysema/Povezanost ateroskleroze i emfizema pluca.

Terms of use | Privacy policy | Copyright © 2022 Farlex, Inc. | Feedback | For webmasters |