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Reactive Arthritis

(Reiter's Syndrome)


Definition and Pathology

Etiology: HLA-B27 and Bacteria


Dr. Hans Reiter


Web Resources

Gray Lyons



Definition and Pathology

            Reactive arthritis (Reiter’s Syndrome) is a systemic illness characterized by a combination of arthritis (inflammation of the joints), conjunctivitis (inflammation of the conjunctiva, a membrane in the eye), and urethritis (inflammation of the urethra).  Reactive arthritis is a type of seronegative spondyloarthropathy, meaning that the rheumatic factor is serologically negative and has a rheumatic effect on the spine.  Other diseases in this category include anklyosing spondylitis, psoriatic arthritis, and enteropathic arthritis (Sigal, 2001).

            The disease is formed in reaction to an infectious agent (thus the name, reactive arthritis).  Infections are usually gastronomical (Campylobacter jejuni, Salmonella enteritidis, Salmonella typhimurium, Yersinia enterocolitica, Yersina typhimurium, and Shigella flexneri) or urogenital (Chlamydia trachomatis) (Sibilia and Limbach, 2002).  Reactive arthritis may derive within 4 weeks of contraction of one of these diseases.  Patients are usually diagnosed when they return to the hospital complaining of joint and eye discomfort (Amor, 1998). 

            Various studies have indicated that the prevalence rate of reactive arthritis ranges between 3.5 and 40 cases per 100,000 individuals (Parker and Thomas, 2000).  The disease is most common in individuals ages 20-40, most likely due to the prevalence of urogenitally induced reactive arthritis.  Studies also indicate that males contract the disease slightly more often than females, though some researchers speculate these data reflect a reporting bias – females may be less likely to report a venereal disease (Bryant 1998).


Etiology: HLA-B27 and Bacteria

            The most thoroughly studied reactive factor is the bacteria Chlamydia trachomatis.  This bacterium enters the body through the urogenital mucosal layers and is engulfed by dendritic cells.  These cells disseminate to many places in the body, including the joints (Kuipers et al., 1998).  Clamydia evades the normal host defense through several mechanisms: inhibiting host cell apoptosis, inducing T cell apoptosis, downregulating expression of MHC and IFN-g molecules, and changing from productive to persistant infection modes (Yu and Kuipers, 2003). 

            HLA-B27 (Figure 1) is an allele of the human leukocye antigen (HLA) class I which presents peptides to CD8+ T cells.  It is thought that eleven or more Chlamydia peptide when displayed on HLA-B27 forms a binding site which is morphologically similar to some normal human peptide presentations (Kuon et al., 2001).  It therefore follows that the antigenic peptides are cross-reactive with certain autologous peptides found in the joints which leads to an autoimmune response.  This theory is most strongly supported by the fact that there is a high degree of clonal similarity in T cell receptors of T lympocytes found in the joints, even in T cells derived from different patients with reactive arthritis (Dulphy et al., 1999). 

This image requires the free Chime plug-in. http://www.mdli.com/chime

Figure 1.  Chime image of Human HLA-B27 (MHC Class I) beta-2 microglobulin and alpha-3 domain,

from Structural Classification of Proteins.  The Chime plug-in is required to view this image.

            Unfortunately, reactive arthritis is not as simple and clear as the findings listed above suggest.  Mice which have a knockout of the beta-2 microglobulin gene may still develop reactive arthritis in nonsterile conditions (Khare et al., 1998).  Since this microglobulin is essential for the structure of HLA, this suggests that there may be an entirely different etiology for this disease other than the CD8+ mediated response. 

            Some alternately proposed mechanisms include altered cellular signaling or a CD4+ mediated response.  Some groups have found that the very presence of the HLA-B27 allele alters normal cellular signal transduction, especially in response to bacterial infection.  Though this is not directly linked to reactive arthritis, the relationship between HLA and reactive arthritis is worth pursuing – over 95% of Caucasian patients with reactive arthritis also have the HLA-B27 allele (Bowness, 2002).  Additionally, one research group has identified three Chlamydia antigens recognized by CD4+ T cells.  These antigens, when recognized by CD4+ cells, were found to cause inflammation in reactive arthritis patients though the mechanism for this pathology is not well understood (Goodall et al., 2001).

            A complete hypothesis for reactive arthritis has not been thoroughly outlined.  Rather, the research community is made of smaller subsets of researchers focused on one particular aspect of the disease.  As information proliferates, the relationship between CD8+ T cells, CD4+ T cells, HLA-B27, and various cytokines will be synthesized into a cohesive model.  The most recent attempt to integrate these ideas (Yu and Kuipers, 2003) has implicated CD8+ T cells as the primary cause of reactive arthritis.  In this model, the fundamental concept is that the reactivity of T cells is modified by HLA-B27 when complexed with certain bacterial peptides.  Other factors, including CD4+ T cells and cytokine secretion may have an effect in the amplification of the inflammatory (arthritic) response.


            There is no cure for reactive arthritis.  Management of the disease follows one of two approaches: anti-inflammatory drugs or immunosuppressive drugs.  Anti-inflammitory drugs such as indomethican and tolmetin tend to function better than regular asprin or corticosteroids.  Immunosuppressive drugs are rarely used to alleviate symptoms because often the risk of opportunistic infection is too high.  Occasionally, surgery will be employed in cases where effusions and cysts are common.  Often, bed rest, weight reduction, and physical therapy are prescribed and help alleviating some symptoms.

Dr. Hans Reiter

            The term “Reiter’s Syndrome” has recently fallen out of favor among the medical community for two reasons: Reiter was not the first to describe the illness and Reiter himself was an avid supporter of the Third Reich.

The earliest description of reactive arthritis preserved today is found in the writings of Hippocrates: “A youth does not suffer from gout until after sexual intercourse.”  (Amor, 1998).  Using historical records, scientists today speculate that Christopher Columbus suffered from reactive arthritis pursuant to a syphilis infection (Allison, 1980).  The Englishman Sir Benjamin Brodie noted the disease in modern times in his Diseases of the Bones and Joints.  He described several patients who contracted acute arthritis after venereal infection.  Dr. Hans Reiter, a German physician, gave an account of a patient who presented with nongonococcal urethritis, conjunctivitis, and arthritis following a venereal infection (Parker and Thomas, 2000).  He incorrectly surmised that the disease was a type of spirochetal infection and named it spirochetosis arthritica.  The symptoms were finally recognized as a syndrome in 1942 by the Harvard researchers Bauer and Engleman. 

Dr. Hans Reiter was arrested by Soviet authorities after World War II and was tried briefly at Nuremberg.  He had been an active member of the Nazi party since 1931, and was appointed by Hitler as President of the Reich Health Administration shortly thereafter.  Reiter was also a member of the Nazi Schutzaffel (SS).  Reiter openly supported sterilization and euthanasia, though in later interrogations he only admitted to “recording the numerical count” of those victims.  Only one link to an overt war crime was ever proven: Dr. Reiter designed a study to inject experimental typhus vaccine into concentration camp prisoners.  Several hundred people died as a result of this experiment.  Dr. Reiter was interned in an American prison camp after the war (Wallace and Weisman, 2003).  As a result, there is a movement among various medical groups to permanently change the name of Reiter’s Syndrome to reactive arthritis except when used for historical purposes.



Click the "P" icon next to each periodical reference to view the abstract on PubMed.


Allison, DJ.  (1980).  Christopher Columbus: first case of Reiter's disease in the Old World?  Lancet.  2: 1309.


Amor, B.  (1998).  Reiter's Syndrome: diagnosis and clinical features.  Rheumatic Disease Clinics of North America.  24: 677-95.


Bowness, P.  (2002).  HLA-B27 in health and disease: a double-edged sword?    Rheumatology.  41: 857-868.


Bryant, GA.  (1998).  Reiter's Syndrome.  Orthopaedic Nursing.  17: 57-62.


Dulphy, N, MA Peyrat, V Tieng, C Douay, C Rabian, R Tamouza, S Laoussadi, F Berenbaum, A Chabot, M Bonneville, D Charron, and A Toubert.  (1999).  Common intra-articular expansions in patients with reactive arthritis: identical beta-chain junctional sequences and cytotoxicity toward HLA-B27.  Journal of Immunology.  162: 3830-9.


Goodall, JC, G Yeo, M Huang, R Raggiaschi, and JS Gaston.  (2001).  Identificatio of Chlamydia trachomatis antigens recognized by human CD4+ lymphocytes by screening an expression library.  European Journal of Immunology.  31: 1513-22.


Khare, SD, J Hansen, HS Luthra, and CS David.  (1996).  HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27/human beta2-microglobulin (beta2m) double transgenic mice with disrupted mouse beta2m.  Journal of Clinical Investigation.  98: 2746-55.


Kuipers, JG, B Jurgens-Saathoff, A Bialowons, J Wollenhaupt, L Kohler, H Zeidler.  (1998).  Detection of Chlamydia trachomatis in peripheral blood leukocytes of reactive arthritis patients by polemerase chan reaction.  Arthritis and Rheumatism.  141: 1894-5.


Parker, CT and D Thomas.  (2000).  Reiter's Syndrome and reactive arthritis.  Journal of the American Osteopathic Association.  100: 101-04.


Sibilia, J and FX Limbach.  (2002).  Reactive arthritis or chronic infectious arthritis?  Annals of the Rheumatic Diseases.  61: 580-87.


Sigal, LH.  (2001).  Update on reactive arthritis.  Bulletin on the Rheumatic Diseases.  50: 1-4.


Wallace, DJ and MH Weisman.  (2003).  The physician Hans Reiter as prisoner of war in Nuremberg: a contextual review of his interrogations (1945-1947).  Seminars in Arthritis and Rheumatism.  32: 208-30.


Yu, D and JG Kuipers.  (2003).  Role of bacteria and HLA-B27 in the pathogenesis of reactive arthritis.  Rheumatic Disease Clinics of North America.  29: 21-36.



Web Resources

(Disclaimer: The following web pages are not associated with this author or Davidson College.  No statement is expressed or implied concerning the accuracy, validity, or applicability of these pages.  As always, use web resources with discretion and consult your physician before making decisions related to your health.)


Reiter's Information and Support Group

Reiter's Syndrome Information Hub

MEDLINEplus Medical Encyclopedia - Reiter's Syndrome

Discovery Channel Health - Reiter's Syndrome

Arthritis Foundation - Reiter's Syndrome (Reactive Arthritis)

CancerWeb Dictionary - Reiter's Syndrome

About Reiter's Syndrome - University of Washington

Reiter's Syndrome - Medical College of Wisconsin


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