[Reactive arthritis: inflammation or true infection?]. / Arthrites réactionnelles: réactions inflammatoires ou vraie infection?

Reactive arthritis has been classically defined as an aseptic arthritis induced by a bacterial infection in another organ. If the classical form of reactive arthritis is in fact a spondyloarthritis triggered by a urogenital or intestinal bacterial infection, it is not necessarily sterile, and in some cases it may be worthwhile to treat a chronic infection with long-term antibiotherapy. In a broader definition, the concept of reactive arthritis is widened to other post-infectious rheumatism, such as post-streptococcal arthritis or post-viral arthritis.

Psoriatic arthritis: phenotypic variance and nosology.

Psoriatic arthritis (PsA) has been recognized as a distinct entity different from rheumatoid arthritis. Classification and phenotyping of PsA have progressed substantially since the first classification criteria of the disease were published in 1973 by Moll and Wright. The initial disease patterns described by Moll and Wright have been found to overlap and change over time. There has been controversy about whether these should be maintained or whether the phenotype of PsA should include peripheral and axial disease only. PsA is a multifaceted disease that can present as different clinical phenotypes: peripheral arthritis, axial disease, skin and nail disease, dactylitis, and enthesitis. Development of the high-sensitivity and high-specificity CASPAR criteria was the first step to conducting high-quality trials and observational studies in the field.

Diagnosis and classification in spondyloarthritis: identifying a chameleon.

Spondyloarthritis (SpA) defines a group of interrelated diseases, including ankylosing spondylitis (AS), psoriatic arthritis, reactive arthritis, enteropathic-related spondylitis and arthritis, and undifferentiated SpA. The clinical presentation of SpA is heterogeneous, and no single shared distinguishing feature exists for the conditions comprising SpA; in daily practice, diagnosis is usually made on the basis of a combination of symptoms, the findings of physical examination, imaging and laboratory investigations. Several classification criteria have been developed for AS and SpA, which are useful in a research setting but cannot be automatically applied to the diagnosis of individual patients. Currently, MRI is the most sensitive imaging modality available for detection of sacroiliitis, often enabling detection of axial inflammation long before structural lesions are observed radiographically, thus facilitating early diagnosis of axial SpA. However, MRI will never capture all facets of SpA and the expert opinion of a rheumatologist will remain the crucial step in recognition of this disease. In this Review, we discuss diagnosis and classification of AS and SpA, and highlight how MRI might facilitate both processes.

The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general.

OBJECTIVE: To evaluate new classification criteria for peripheral spondyloarthritis (SpA) in patients with SpA with peripheral manifestations only. METHODS: In this Assessment of SpondyloArthritis international Society (ASAS) study, two prespecified sets of criteria were compared against the European Spondylarthropathy Study Group (ESSG) and Amor criteria in newly referred consecutive patients with undiagnosed peripheral arthritis, and/or enthesitis, and/or dactylitis that usually began before 45 years of age. The clinical diagnosis (SpA vs no SpA) made by the ASAS rheumatologist served as reference standard. RESULTS: In all, 24 ASAS centres included 266 patients, with a final diagnosis of SpA being made in 66.2%. After adjustments a final set of criteria showed the best balance between sensitivity (77.8%) and specificity (82.9%): arthritis and/or enthesitis and/or dactylitis plus (A) one or more of the following parameters: psoriasis, inflammatory bowel disease, preceding infection, human leucocyte antigen B27, uveitis, sacroiliitis on imaging, or (B) two or more other parameters: arthritis, enthesitis, dactylitis, inflammatory back pain in the past, family history of SpA. The new criteria performed better than modified versions of the ESSG (sensitivity 62.5%, specificity 81.1%) and the Amor criteria (sensitivity 39.8%, specificity 97.8%), particularly regarding sensitivity. In the entire ASAS population of 975 patients the combined use of ASAS criteria for axial SpA and ASAS criteria for peripheral SpA also had a better balance (sensitivity 79.5%, specificity 83.3%) than the modified ESSG (sensitivity 79.1%, specificity 68.8%) and Amor criteria (sensitivity 67.5%, specificity 86.7%), respectively. CONCLUSIONS: The new ASAS classification criteria for peripheral SpA performed well in patients presenting with peripheral arthritis, enthesitis and/or dactylitis.

Is the enthesitis-related arthritis subtype of juvenile idiopathic arthritis a form of chronic reactive arthritis?

OBJECTIVE: Enteric organisms are known to trigger reactive arthritis. The enthesitis-related arthritis (ERA) form of juvenile idiopathic arthritis (JIA) clinically resembles reactive arthritis. Therefore, we looked for a role of enteric bacteria in ERA. METHODS: Synovial fluid (SF) was obtained from 26 patients with ERA and 10 patients with rheumatoid arthritis (RA). Blood specimens were also obtained from patients with ERA and from 10 normal individuals. Lymphocyte proliferation assays were done on whole blood and SF mononuclear cells using as antigens crude lysates of the enteric bacteria Salmonella typhimurium, Yersinia enterocolitica, Shigella flexneri and Campylobacter jejuni. Crude lysate of Escherichia coli was used as a control antigen. HLA-B27 typing was done using the polymerase chain reaction. Homing of gut-specific T cells (CD103+) to the synovial compartment was studied using tri-colour flow cytometry. The antigen-specific cytokine profile was determined by flow cytometry. RESULTS: Antigen-specific lymphoproliferative responses were observed in 14 of 26 patients. Among these patients, 12 showed a response in SF (four each to S. typhimurium and C. jejuni, and in two each to S. flexneri and Y. enterocolitica), and two patients in blood (S. typhimurium in both). None of the healthy controls showed a response in the blood. Lymphoproliferative responses in SF were more frequent in patients with JIA (12/26) than in controls with RA (1/10, P < 0.05). Patients with an antigen-specific response had a higher ratio of SF/blood CD103+ T cells compared with those with no antigen-specific response (P < 0.01). Antigen-specific as well as mitogen-stimulated cytokine production showed a Th1 bias. CONCLUSION: Enteric bacteria may have a role in exacerbation of disease in patients with ERA. The immune response in patients with ERA is Th1-dominant.

[Expert assessment of patients with seronegative spondyloarthropathies]. / Begutachtung von Patienten mit seronegativen Spondylarthropathien.

Besides rheumatoid arthritis, seronegative spondyloarthropathies are one of the most common inflammatory musculoskeletal diseases. The main clinical manifestations are spondylitis and sacroiliitis, but peripheral arthritis and involvement of other organ systems are known as well. The typical ankylosis of the spine is resulting in a marked loose of the functional capacity. During the course of disease, work disability is progressing and finally the patient may become permanent disabled. Patients with ankylosing spondylitis can be viewed by experts for several reasons. To guarantee an objective medical expert view, a detailed clinical examination and use of clinical indices are mandatory.

Reactive arthritis.

During the past year, no big advances were reported in understanding the pathogenesis or treatment of reactive arthritis (ReA). The need for generally accepted diagnostic criteria has become a central issue. Regarding pathogenesis, attention has been drawn to a similarity between ReA and the experimental antigen-induced arthritis. Molecular mechanisms of the HLA-B27-associated pathogenesis have remained, in spite of intensive research, so far a mystery. It is apparent that antibiotics have no effect on the fully developed reactive arthritis, with the exception of patients with Chlamydia-triggered ReA, who might benefit from a course of antibiotics.

[Classification of idiopathic juvenile arthritis]. / Klassifisering av idiopatiske juvenile artritter.

We present a review of the criteria for the classification of juvenile arthritides. Historical aspects, the present situation and proposals for new criteria are outlined. The most commonly used classification criteria today are the European juvenile chronic arthritis criteria (JCA), the European League Against Rheumatism (EULAR) criteria, and the American juvenile rheumatoid arthritis (JRA), the American Rheumatoid Association (ARA) criteria. They differ in nomenclature and have different inclusion and exclusion demands. This has made it difficult to compare studies using different criteria. Neither of them can define homogeneous subgroups of disease. The most recent proposal for new classification criteria of juvenile arthritides is that of the International League Against Rheumatism, ILAR. They are primarily designed to define homogeneous subgroups of disease. The goal is also to obtain an international consensus. Advantages and disadvantages are discussed in this article. The criteria have not yet been validated, and should not be used by clinicians until they have been approved by the international scientific society. We also present guidelines recommended for the classification of juvenile arthritis in Norway today. We recommend using the term juvenile arthritis. Disease duration of arthritis must be at least six weeks. A diagnosis of arthritis should not be made on painful and restricted joint movement alone, as is the case in both the EULAR and ARA criteria today, but at least be based on definite swelling of joints verified by either clinical examination and/or by imaging techniques such as ultrasound, X-ray or EMR.

Two forms of reactive arthritis?

Inflammatory arthritides developing after a distant infection have so far been called reactive or postinfectious, quite often depending on the microbial trigger and/or HLA-B27 status of the patient. For clarity, it is proposed that they all should be called reactive arthritis, which, according to the trigger, occurs as an HLA-B27 associated or non-associated form. In addition to the causative agents and HLA-B27, these two categories are also distinguished by other characteristics. Most important, HLA-B27 associated arthritis may occur identical to the Reiter's syndrome with accompanying ureteritis and/or conjunctivitis, whereas in the B27 non-associated form this has not been clearly described. Likewise, only the B27 associated form belongs to the group of spondyloarthropathies.

Reactive arthritis.

Reactive arthritis is one of the spondyloarthropathy family of clinical syndromes. The clinical features are those shared by other members of the spondyloarthritis family, though it is distinguished by a clear relationship with a precipitating infection. Susceptibility to reactive arthritis is closely linked with the class 1 HLA allele B27; it is likely that all sub-types pre-dispose to this condition. The link between HLA B27 and infection is mirrored by the development of arthritis in HLA B27-transgenic rats. In this model, arthritis does not develop in animals maintained in a germ-free environment. Infections of the gastrointestinal, genitourinary and respiratory tract appear to provoke reactive arthritis and a wide range of pathogens has now been implicated. Although mechanistic parallels may exist, reactive arthritis is distinguished from Lyme disease, rheumatic fever and Whipple's disease by virtue of the distinct clinical features and the link with HLA B27. As in these conditions both antigens and DNA of several micro-organisms have been detected in joint material from patients with reactive arthritis. The role of such disseminated microbial elements in the provocation or maintenance of arthritis remains unclear. HLA B27-restricted T-cell responses to microbial antigens have been demonstrated and these may be important in disease pathogenesis. The importance of dissemination of bacteria from sites of mucosal infection and their deposition in joints has yet to be fully understood. The role of antibiotic therapy in the treatment of reactive arthritis is being explored; in some circumstances, both the anti-inflammatory and anti-microbial effects of certain antibiotics appear to be valuable. The term reactive arthritis should be seen as a transitory one, reflecting a concept which may itself be on the verge of replacement, as our understanding of the condition develops. Nevertheless it appropriately describes arthritis that is associated with demonstrable infection at a distant site without traditional evidence of sepsis at the affected joint(s). Although several forms of disease could be described as "reactive", particularly acute rheumatic fever, post-meningococcal septicaemia arthritis and Lyme disease, in clinical practice the term is restricted to an acute spondyloarthritis, usually, but not exclusively, linked to acute genitourinary or gastrointestinal infection. A proportion of patients fulfil criteria for Reiter's Syndrome [1].

A proposal for the classification of patients for clinical and experimental studies on reactive arthritis.

OBJECTIVE: To propose classification criteria for patients entering clinical and basic studies on reactive arthritis (ReA). METHODS: From a MEDLINE search of articles published between 1980 and 1996, we identified reports on HLA-B27 related ReA and Reiter's syndrome as study groups and analyzed the items that constituted the diagnostic, classification, and inclusion (or entry) criteria of patients. We developed disease categories that constituted our classification proposal. RESULTS: We reviewed 175 articles containing 110 study groups of patients with ReA and 94 with Reiter's syndrome. Most articles (89.7%) relied on arthritis for diagnosis, but only 48.0% relied on infection. Only 22.5% of articles used published criteria for diagnosis. Articles including a bacterial name to further describe a group of patients with ReA relied on cultures at the site of infection, serum antibodies, or both to confirm the diagnosis. There were inter/intra-group variations and overlapping of diagnostic criteria, at least 32 different terms referring to ReA or Reiter's syndrome, and 6 patterns of disease. According to these data, we propose 3 categories of disease for patients entering clinical and basic studies on ReA: probable ReA (2 subgroups); definite ReA triggered by bacteria (2 subgroups); and bacterial-associated undifferentiated oligoarthritis or spondyloarthropathy. CONCLUSION: This proposal provides a rationale for reducing the heterogeneity found in criteria for including patients with ReA in research and to facilitate scientific communication. In contrast to diagnostic criteria, this proposal does not restrict the study population to a minority of patients, but allows the investigator to include several forms of disease and to analyze results according to different categories.

Is undifferentiated seronegative spondyloarthropathy a forme fruste of reactive arthritis?

Undifferentiated spondyloarthropathy (USpa) may either represent a forme fruste of other spondyloarthropathies like reactive arthritis or be a different disease entity. To study the link between USpa and reactive arthritis, we studied the presence of IgA antibodies to Yersinia enterocolitica, Salmonella typhimurium, Shigella flexneri, Campylobacter jejuni and Chlamydia trachomatis in sera from 14 patients with USpa (European Spondyloarthropathy Study Group criteria) using ELISA. Escherichia coli was used as a control antigen. An OD value of more than the mean +/- 2 S.D. of 51 blood donors was considered positive. Five patients had elevated IgA antibodies to S. flexneri, while two patients each had elevated antibody levels to S. typhimurium and Chlamydia. No patient had elevated antibodies to Y. enterocolitica, C. jejuni and E. coli. Among 51 normals, 1, 4, 3, 2 and 3 had elevated antibodies to S. flexneri, S. typhimurium, Y. enterocolitica, C. jejuni and E. coli, respectively. Nine of 14 patients with USpa had antibodies to one of the bacteria implicated in reactive arthritis: of these, antibodies to Shigella were the most frequent. Thus, a proportion of patients with USpa may in fact have reactive arthritis.