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[The concept of reactive arthritis].

More than fifty years after the clinical syndrome was described by Reiter, Fiessinger and Leroy, the diagnostic criteria of what has now been termed reactive arthritis are still under debate. Reactive arthritis can be defined as an aseptic inflammatory joint disease occurring either in a patient with a bacterial infection located in a distant organ or with a particular genetic predisposition. The lack of specific criteria has led to a certain degree of liberty in interpreting the three basic elements of reactive arthritis: clinical presentation, "distant" infection, genetic predisposition. It is generally accepted that limiting the diagnosis of reactive arthritis only to patients with the classic oculo-uretro-synovial manifestations is unsatisfactory. The question remains open as to whether only patients presenting both inflammatory joint disease and spondylarthropathy have reactive arthritis or whether any undetermined etiology of arthritis is sufficient if the patient also has a "distant" infection and a specific genetic predisposition (HLA B27). Two new elements further complicate the situation. The first is the recent demonstration that the synovial fluid in patients with reactive arthritis might contain microbial antigens. The second is that longterm antibiotics (more than 3 months) could have a beneficial effect. Asking when the diagnosis should be entertained is thus not a moot question. Although we still have no clear answer, it is reasonable to state that the diagnosis of reactive arthritis should be retained only in patients with both inflammatory joint disease and criteria compatible with spondylarthropathy. Clinical research is required to determine whether the germ is actually present or not within the joint and to assess the effect of long-term antibiotherapy.

Arthritis, Reactive↗

Reactive arthritis after Campylobacter jejuni enteritis.

Reactive arthritis of 1 or more peripheral joints developed after an enteric infection with Campylobacter jejuni in 6 adult patients. Other reactive signs, such as conjunctivitis, aphthous stomatitis, stranguria and sterile leukocyturia occurred in 4 patients. Five of the 6 patients possessed the HLA-B27 antigen. The history indicated previous joint disease in 4 of the 6 patients. The short-term follow-up showed a benign course of the arthritis. When a reactive arthritis syndrome is clinically suspected, investigations should include a search for Campylobacter jejuni infection by culture of the stool and by serological tests to demonstrate antibodies against Campylobacter jejuni.

Adult↗

[Reactive arthritis associated with infections and intestinal infestations].

Reactive arthritis is a non suppurative articular inflammation following an infection elsewhere in the body. It probably occurs by interaction of external infections agents and immunological factors that mediate the host's response to the agent's antigens. The authors reviewed the role of gastrointestinal infection and infestation as a cause of reactive arthritis. Since there are no good diagnostic criteria for reactive arthritis and the investigations in this area are difficult, it is possible that many of these cases are misdiagnosed.

Arthritis, Infectious↗

Cellular and humoral markers of systemic inflammation in acute reactive arthritis and early rheumatoid arthritis.

OBJECTIVE: To compare systemic inflammation in reactive arthritis (ReA), rheumatoid arthritis (RA), and sepsis using novel markers of systemic inflammation, and to study whether they are helpful in distinguishing between ReA and RA. METHODS: In 28 patients with acute ReA, 16 patients with early untreated RA, and 25 patients with blood culture-positive sepsis, phagocyte CD 11b expression was measured by flow cytometry, serum procalcitonin (PCT) levels by immunoluminometric assay, and soluble E-selectin (sE-selectin) levels by enzyme-linked immunosorbent assay (ELISA). RESULTS: Neutrophil and monocyte CD11b expression and serum levels of PCT and sE-selectin were higher in patients with sepsis than patients with ReA or RA, or in healthy subjects (all p < 0.01). They were comparable in healthy subjects, ReA, and RA. CONCLUSION: Patients with acute ReA and early RA have normal CD11b expression levels on phagocytes and normal PCT and sE-selectin levels in serum. Elevated levels suggest possible sepsis.

Acute Disease↗

Reactive arthritis and Reiter's syndrome following an outbreak of gastroenteritis caused by Salmonella enteritidis.

Reactive arthritis and Reiter's syndrome have been reported following gastroenteritis. Prevalence studies for these conditions are uncommon, and the prevalence of Reiter's syndrome after Salmonella enteritidis infection has not been previously reported. After a large outbreak of S. enteritidis gastroenteritis, a survey of persons exposed to the implicated food source was conducted, and those with reactive arthritis were evaluated for possible risk factors. Among 481 persons responding to the questionnaire, 217 cases of S. enteritidis gastroenteritis were identified (31 confirmed and 186 clinical cases; attack rate, 45%). Twenty-nine percent of the cases had symptoms of reactive arthritis, 3% had symptoms of Reiter's syndrome, and 10% had reactive arthritis with oral ulcers. Markers for severe illness (diarrhea > or =7 days, emergency room visit or hospitalization, and antibiotic treatment) were statistically significant but colinear factors associated with reactive arthritis. Increased awareness of postdysenteric reactive arthritis and Reiter's syndrome is recommended.

Adolescent↗

Reactive arthritis due to Salmonella enteritidis complicated by carditis.

Reactive arthritis following infection with enteropathogenic bacteria is usually a self-limiting disease that disappears after a few months without sequela. We describe two girls who developed carditis shortly after the onset of reactive arthritis due to infection with Salmonella enteritidis. The carditis presented with fatigue and arrhythmia and involved the aortic valve in both patients leading to definite aortic regurgitation in one. A similar pattern of cardiac involvement is found in other spondyloarthropathies, including Reiter's syndrome and ankylosing spondylitis. We conclude that Salmonella reactive arthritis may be complicated by carditis.

Adolescent↗

Reiter's syndrome and reactive arthritis: a current view.

This paper reviews advances in the understanding of the pathogenesis of reactive arthritis that have occurred over the last decade. Inflammatory aseptic joint disease has been linked with prior infection initiated by many different species of microorganisms. The presence of intra-articular bacterial antigens has now been firmly established with the demonstration of bacteria, bacterial fragments, DNA, RNA, and bacterial lipopolysaccharide in joints of patients with reactive arthritis. Chlamydia trachomatis, Salmonella enteritidis, and Shigella flexneri have all been detected in the joint by immunological techniques, although there is still some doubt as to the form in which they reach the joint and whether or not they persist. A number of phlogistic bacterial components could be acting as arthritogens. Negative joint culture results from patients with reactive arthritis make it unlikely that bacteria in the joint are viable, although chlamydial DNA has been shown in the joints of patients with sexually acquired reactive arthritis using the polymerase chain reaction. The use of antimicrobial therapy in the treatment of reactive arthritis is under review; data suggests that long-term antibiotic treatment warrants further study. The role of HLA-B27 in disease pathogenesis is discussed as are possible mechanisms of interplay between germ and gene. HLA-B27 might confer disease susceptibility by affecting immune mechanisms other than classical antigen presentation. The immunopathogenesis of joint inflammation in reactive arthritis is explored with reference to studies of humoral and cellular immune responses. Serological evidence to support the concept of molecular mimicry is far from conclusive; the results of relevant studies are summarized. Lymphocyte proliferation experiments suggest that antigen presenting cells play an important role. Finally, our views on reactive arthritis in the 1990s, and areas of new and potentially fruitful future research are presented.

Antigens, Bacterial↗

Predominance of Th1-type T cells in synovial fluid of patients with Yersinia-induced reactive arthritis.

The pathogenetic mechanisms underlying the development of reactive arthritis and the functional capacities of synovial T cells specific for Yersinia enterocolitica are still unclear. In this study we have determined the cytokine secretion patterns of 24 CD4+ synovial fluid (SF)-derived T cell clones from 2 patients with Yersinia-induced reactive arthritis, 16 clones specific for different Yersinia antigens and 8 clones as controls. The clones specific for Yersinia antigens predominantly belong to the T helper cell 1 (Th1) subset with production of interferon (IFN)-gamma and interleukin (IL)-2, but no IL-4, whereas SF T cells not reactive with Yersinia antigens produce IL-2, IL-4 and IFN-gamma and thus belonged to the Th0 subset. Moreover, short-term T cell lines established from SF and peripheral blood showed the same pattern. To further analyze the functional relevance of these data we investigated the influence of IFN-gamma and IL-4 on the intracellular killing of Yersinia in a human glioblastoma cell line. Our data show that the Th1 cytokine IFN-gamma promotes intracellular killing of Yersinia, whereas this effect is antagonized by the Th2 cytokine IL-4. Furthermore, the Th2 cytokine IL-10 inhibited the antigen-specific proliferative response and IFN-gamma and IL-2 production by the Th1 cells. These results provide insight into the antibacterial mechanisms at work in reactive arthritis after infection with Yersinia enterocolitica and, for the first time, reveal the cross-regulatory properties of cytokines derived from Th1 and Th2 cells in a human immune response to bacterial antigens.

Adult↗

The value of isotype determination of serum antibodies against Chlamydia for the diagnosis of Chlamydia reactive arthritis.

In clinical rheumatology, the diagnosis of Chlamydia reactive arthritis is difficult because an incomplete form of the disease can closely resemble an undifferentiated seronegative mono/oligoarthritis. We investigated whether measuring specific isotypes of anti-Chlamydia antibodies in serum can improve the diagnosis, by comparing such antibody concentrations in the serum of patients with well-defined disease, i.e. Chlamydia trachomatis sexually acquired reactive arthritis (CT-SARA), with other arthritides. Antibody levels were determined by enzyme-linked immunosorbent assay (ELISA). When considering two different isotypes and their combination, the best sensitivity (63%) was obtained for IgM and/or IgA results with a specificity of 81%. The patients with CT-SARA and SARA had the highest levels of antibodies of all isotypes tested. It is concluded that, in our experimental conditions, only very high values of specific isotypes could indicate a diagnosis of Chlamydia reactive arthritis.

Adolescent↗

Chlamydia pneumoniae--a new causative agent of reactive arthritis and undifferentiated oligoarthritis.

OBJECTIVE: To examine whether reactive arthritis (ReA) known to occur after a urogenital infection with Chlamydia trachomatis can also follow an infection with Chlamydia pneumoniae, a recently described species of Chlamydiae that is a common cause of respiratory tract infections. METHODS: Specific antibodies (microimmunofluorescence test) and lymphocyte proliferation to C trachomatis and C pneumoniae in paired samples of peripheral blood and synovial fluid were investigated in 70 patients with either reactive arthritis (ReA) or undifferentiated oligoarthritis (UOA). RESULTS: Five patients with acute ReA after an infection with C pneumoniae are reported. Three had a symptomatic preceding upper respiratory tract infection and two had no such symptoms. In all patients a C pneumoniae-specific lymphocyte proliferation in synovial fluid and a high specific antibody titre suggesting an acute infection was found. CONCLUSION: C pneumoniae needs to be considered a new important cause of reactive arthritis.

Acute Disease↗

Sexual and enteric bacterial infections eliciting reactive arthritis.

In this review synonymous definitions of reactive arthritis are discussed first. Major clinical symptoms, their infectious etiology and epidemiology define post-dysenteric and post-veneral forms of reactive arthritis. Classical (smear, culture, biochemistry, antigen detection) and molecular (DNA and RNA detections) techniques are used in the routine microbial diagnosis that is retrospective in the majority of cases. In the pathomechanism of this disorder, HLA-B27 antigen positivity of patients is a frequent risk factor. Molecular mimicry between microbial and self-antigens, abnormal antigen presentation leading to incomplete CD8+ T lymphocyte activation might contribute to the persistence of microbial antigens that elicit clinical symptoms. Treatment is rarely successful with antimicrobial chemotherapy.

Anti-Infective Agents↗

[Reactive arthritis induced by Clostridium difficile enteritis].

This article reports the case of an acute monoarthritis of the ankle occurring in a HLA-B27 positive female patient who presented with diarrhea and fever. We retained the hypothesis of a Clostridium difficile colitis, as she had previously received an antibiotic treatment. The culture of the synovial fluid remained sterile, which postulated that this arthritis was reactive. The diagnosis was confirmed by the presence of toxins A and B in the stool and positive culture. The outcome was satisfactory with metronidazole therapy.

Ankle Joint↗

Cytochrome P450 1A1 and manganese superoxide dismutase genes polymorphisms in reactive arthritis.

To investigate the role of cytochrome P450 1A1 (CYP1A1) and manganese superoxide dismutase (Mn SOD) genes polymorphisms in the susceptibility to reactive arthritis, the polymorphisms of CYP1A1 and Mn SOD genes were determined in 43 patients with reactive arthritis following Chlamydia trachomatis infection and 92 healthy controls by polymerase chain reaction (PCR)/restriction fragment length polymorphisms (RFLP) method. The frequencies of CYP1A1 4887C/A and C/A+A/A were significantly higher in patients with reactive arthritis than in controls. Moreover, the increased frequency of CYP1A1 4887A in patients with reactive arthritis is independent of HLA-B27. The frequency of Mn SOD 1183T/T tended to be increased in patients with reactive arthritis. We also found that the frequency of CYP1A1 4887A was significantly increased in Mn SOD 1183T/T(+) reactive arthritis patients compared with 1183T/T(+) controls. CYP1A1 4887A may be a risk factor for the development of reactive arthritis, especially in the presence of Mn SOD 1183T/T.

Arthritis, Reactive↗

Staphylococcus aureus triggered reactive arthritis.

OBJECTIVES: To report two patients who developed reactive arthritis in association with Staphylococcus aureus infection. METHODS: A review of the case notes of two patients. RESULTS: Two adult female patients have developed sterile arthritis in association with Staph aureus infection. The first patient has had two episodes of arthritis; the first followed olecranon bursitis, the second followed infection of a central venous catheter used for dialysis. The second patient developed sterile arthritis while being treated for pyomyositis. Both patients had a self limited arthritis and were HLA-B27 negative. CONCLUSION: Reactive arthritis may rarely follow Staph aureus infection. HLA-B27 negativity may be associated with a self limited arthritis in these cases.

Adult↗