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Volume 4, Number 3—September 1998

Letter

Classification of Reactive Arthritides

Suggested citation for this article

To the Editor: We read with interest J.A. Lindsay's article on sequelae of foodborne disease (1). However, we believe that there are errors in the classification of the reactive arthritides. Lindsay states that ankylosing spondylitis (AS) is a "rheumatoid inflammation of synovial joints and entheses within and distal to the spine." Although not the primary focus of the article, the classification and etiopathogeneses of rheumatoid arthritis (RA) and the seronegative spondyloarthropathies, including AS, should be clarified. The term spondylitis, from the Greek spondylos, for vertebra, means inflammation of the vertebrae. The term rheumatoid is generally taken to apply to rheumatoid arthritis, while rheumatic is a more general term applying to all connective tissue diseases.

AS is a chronic, systemic, inflammatory disorder primarily affecting the axial skeleton, with sacroiliac joint involvement as its hallmark. Back pain is the first clinical manifestation in approximately 75% of the patients (2). The backache is usually insidious in onset, dull, and difficult to localize. After several months, it generally becomes bilateral and persistent. The ache is often worse in the morning or after periods of inactivity and improves with movement. The course is highly variable. Involvement of peripheral joints other than hips and shoulders is uncommon.

AS is strongly associated with human leukocyte antigen (HLA) B27, a major histocompatibility complex (MHC) class I allele, and may show familial aggregation. More than 90% of patients with AS have the HLA-B27 allele (3). HLA-B27 is believed to be directly involved in disease pathogenesis. Transgenic rats expressing human HLA-B27 develop a broad spectrum of disease closely resembling human disease. These rats have peripheral and axial arthritis, gastrointestinal inflammation, and diarrhea. Psoriatic-like skin changes and inflammation of the heart and male genitalia are also seen. Histologically, the joint, gut, skin, and heart lesions resemble those seen in HLA-B27-related disease in humans (4).

The inflammatory process in AS involves the synovial and cartilaginous joints, as well as the osseous attachments of tendons and ligaments (entheses). Much of the skeletal pathology of AS can be explained by the changes that take place at the entheses. After an initial inflammatory, erosive process involving the entheses, there is healing in which new bone is formed. The final outcome of this process is an irregular bony prominence with sclerosis of the adjacent cancellous bone (5). This can be contrasted with the pathology of RA, in which there is a greater tendency to affect cartilaginous joints such as the intervertebral discs and symphysis pubis. The process in RA is one of bony erosion rather than new bone formation.

The term ankylosing spondylitis, derived from the Greek for "bent spinal vertebrae," by definition requires exclusion of the other spondyloarthropathies, such as Reiter syndrome and reactive arthritides due to enteric (or urogenital) organisms. Spondylitis may occur in reactive arthritis, psoriatic arthritis, or the arthropathy associated with inflammatory bowel disease, but is less common in these diseases (approximately 50% in reactive arthritis, 20% in enteric arthritis or psoriatic arthritis). All of these diseases can be viewed as seronegative spondyloarthropathies in that, by definition, rheumatoid factor is not present.

RA is a systemic autoimmune disorder of unknown etiology. It is a chronic symmetric arthropathy of peripheral joints, associated with erosive synovitis. Enthesopathy is generally not found. The majority of patients have elevated titers of serum rheumatoid factor, as opposed to the seronegative spondyloarthropathies. Spinal involvement in RA is seen but most often involves the cervical spine. The pathogenesis of the spinal disease is that of synovitis of the odontoid-atlas joints. The major HLA association is with HLA-DR4, an MHC class II allele.

Reactive arthritis is so named because it is felt that the arthritis and other inflammatory manifestations are an immune reaction to a distant infection. There is an association with HLA-B27 but less so than that found in AS (60% to 80%, compared with more than 90% in AS). While bacterial antigens can be found within the joint, the offending infectious process most often subsides before the onset of arthritis, and no living organisms are found in the joint (2). In many cases, no infectious trigger can be identified. Persistence of microbial antigens has been demonstrated and is likely to play a prominent role in the pathogenesis of acute and chronic inflammation. Antigens to several gastrointestinal pathogens have been isolated from the synovial fluid in patients with reactive arthritis. Salmonella, Shigella, Yersinia, Campylobacter, and Borrelia are the most common pathogens capable of initiating reactive arthritis (2). The arthritis is generally an asymmetric oligoarthritis predominantly affecting the lower extremities and typically develops 6 to 14 days after a bout of diarrhea. However, onset can occur up to 3 months later. Diarrhea can also be absent, and there is no relationship between the severity of the arthritis and the severity of the diarrhea.

Reiter syndrome is in fact a reactive arthritis. In 1916, Hans Reiter described a triad of arthritis, urethritis, and conjunctivitis in a soldier with dysentery. However, the disease was actually first described by Sir Benjamin Brodie in the early 1800s (6). The complete triad is actually seen in only a minority of patients. Arthritis develops 1 to 3 weeks after the diarrhea or urethritis. It is generally asymmetric, involving large joints, especially in the lower extremities. The term Reiter syndrome actually refers only to the triad of arthritis, urethritis, and conjunctivitis. Reiter syndrome is both clinically and historically more accurately termed reactive arthritis. Nevertheless, the term reactive arthritis does not reflect the systemic nature of the disease.

In summary, while both reactive arthritis and ankylosing spondylitis are seronegative spondyloarthropathies, they are separate entities. Both are distinct from rheumatoid arthritis.

Darren R. Blumberg and Victor S. Sloan
Author affiliations: Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

References

  1. Lindsay JA. Chronic sequelae of foodborne disease. Emerg Infect Dis. 1997;3:44352. DOIPubMed
  2. Veys EM, Mielants H. Enteropathic arthropathies. In: Klippel JH, Dieppe PA, editors. Rheumatology. St. Louis: 1994; 3.35.
  3. Khan MA. Seronegative spondyloarthropathies. In: Schumache HR, editor. Primer on rheumatic diseases. Atlanta (GA): Arthritis Foundation; 1993.
  4. Hammer RE, Maika SD, Richardson JA, Tang J-P, Taurog JD. Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human a2m: an animal model of HLA-B27-associated human disorders. Cell. 1990;63:1099112. DOIPubMed
  5. El-Khoury GY, Kathol MH, Brandser EA. Seronegative spondyloarthropathies. Radiol Clin North Am. 1996;34:34357.PubMed
  6. Toivanen A. Reactive arthritis. In: Klippel JH, Dieppe PA, editors. Rheumatology. St. Louis: 1994: 4.9.

Suggested citation: Blumberg DR, Sloan VS. Classification of Reactive Arthritides [letter]. Emerg Infect Dis [serial on the Internet]. 1998, Sep [date cited]. Available from http://wwwnc.cdc.gov/eid/article/4/3/98-0350

DOI: 10.3201/eid0403.980350

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Table of Contents – Volume 4, Number 3—September 1998

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