3
Chlamydia-induced reactive arthritis: Hidden in plain sight?

https://doi.org/10.1016/j.berh.2011.05.001Get rights and content

Reactive arthritis belongs to the group of arthritidies known as the spondyloarthritides. There are two main types of reactive arthritis: post-venereal and post-enteric. Chlamydia trachomatis is felt to be the most common cause of reactive arthritis, in general. Until recently, even the terminology for the condition itself was unclear as multiple eponyms and names have been associated with reactive arthritis. In recent years, a great deal has been learnt about the epidemiology, pathophysiology and treatment of reactive arthritis and Chlamydia-induced reactive arthritis, specifically. Prospective epidemiologic data suggest that Chlamydia-induced reactive arthritis is underdiagnosed. Other truths being actively revealed include data suggesting that the pathogen itself (i.e., Chlamydia) might play an equally important role, or perhaps even more important, than the host with disease susceptibility; asymptomatic chlamydial infections might be a common cause of ReA and the two variants of reactive arthritis might respond differently to treatment in spite of the congruent clinical presentation. However, much about this syndrome remains shrouded in mystery. Data covered in this review suggest that Chlamydia-induced reactive arthritis might be a common condition that clinicians fail to recognise. An emphasis is placed on disease awareness since viable treatment options are emerging.

Section snippets

History of ReA

Paralleling the controversy regarding the exact role that the bacterial triggers play in disease maintenance of ReA, there has also been confusion over the proper terminology of the disease itself. The literature is replete with multiple terms and eponyms used to describe this condition. Two of the more popular eponyms used in the literature include Reiter syndrome and Feissinger Leroy syndrome. The former was first penned in 1942 when two Harvard researchers (Bauer and Engelmann) recognised

Epidemiology

In keeping with previous controversy regarding proper terminology, the true incidence and prevalence of ReA is enigmatic. The Office of Rare Diseases of the National Institutes of Health lists ReA as a ‘rare disease’. This means that ReA affects less than 200,000 people in the United States. Orphanet, who are a consortium of European partners for rare diseases and orphan drugs, also lists ReA as a ‘rare disease’, meaning that it affects less than 1 person in 2000. Two previous surveys have

Chlamydiae

All chlamydial species are obligate intracellular bacterial parasites of eukaryotic cells. For the most part, chlamydiae are incapable of generating their own energy; therefore, they rely on the host cell’s adenosine triphosphate (ATP) for energy. There are several different chlamydial species, but our focus will be on C. trachomatis and C. pneumoniae, as these are the only chlamydial species known to cause CiReA.

The term Chlamydia first appeared in the literature in 1945. It is derived from

Host response in CiReA

CiReA represents the classic interplay between host and environment in which both parties play a role in disease susceptibility. The exact role that each plays is still not clearly defined. Although the causative bacteria of ReA have been known for many years, the traditional focus in determining disease susceptibility has been on the host. HLA-B27 is a class I surface antigen, encoded in the major histocompatibility complex (MHC) on the short arm of chromosome 6 and presents antigenic peptides

C. trachomatis versus C. (Chlamydophila) pneumoniae ReA

Whereas both C. trachomatis and C. pneumoniae are known triggers of ReA, C. trachomatis is a much more common cause. Although both are very common causes of bacterial infections worldwide, it is widely accepted that C. pneumoniae is more prevalent. However, it is difficult to know the true incidence and prevalence of C. pneumoniae infections worldwide. Further, these rates could vary depending on the year or country studied.

Acute infections with C. pneumoniae cause bronchitis or pneumonia;

Phenotypic convergence

Although the focus of this review is CiReA, it should be noted that the two main types of ReA, that is, post-venereal and post-enteric, share clinical features. Clearly, post-chlamydial and post-enteric ReA are triggered by different organisms, yet the phenotypic expression of the resulting clinical disease is congruent. The clinical features of ReA are well described. They include inflammation not only in the synovium (articular and tendon), but also the eye, mucosal membranes, skin and

Treatment of CiReA

As is the case with CiReA in general, the treatment of CiReA is equally complex, continuing to evolve and currently unresolved. In keeping with the apparent underdiagnosis of the condition itself, prospective trials analysing various therapeutic agents are few compared with the other types of SpA. Paralleling the opposing schools of thought regarding the true role of persistent chlamydiae in the pathophysiology of CiReA, both traditional disease-modifying anti-rheumatic drugs (DMARDs) and

Lack of a diagnostic test

The role that Chlamydia plays in the genesis of CiReA has been known for years. The mystery of how this same organism might function in terms of disease perpetuation is beginning to be solved. Along with this, the treatment of CiReA is becoming more defined. In spite of these advances, underdiagnosis of CiReA remains a significant problem. The lack of a universally available diagnostic test for CiReA and persistent chlamydial infections, in general, represents a roadblock to accurate disease

CiReA: hidden in plain sight?

Have we come full circle? As stated, rather clear descriptions of CiReA exist in the literature as far back as the early 1500s. It is even possible that a description of CiReA dates back to circa 460 B.C. when Hippocrates wrote: “A youth does not suffer from gout until sexual intercourse” [117]. Could this be the earliest description of CiReA? C. trachomatis has been a known trigger of ReA for approximately 50 years. Mirroring this clinical knowledge were EMstudies in the 1970s and 80s that

References (117)

  • D. Flores et al.

    Reactive arthritis: newer developments

    Rheumatic Disease Clinics of North America

    (2003)
  • H. Reiter

    Uber eine bisher unerkannate Spirochateninfektion (Spirochetosis arthritica)

    Deutsche Medizinische Wochenschrift

    (1916)
  • M. Fiessinger et al.

    Contribution a l’etude d’une epidemie de dysenterie dans le somme

    Bulletins et mémoires de la Société médicale des hôpitaux de Paris

    (1916)
  • J.T. Sharp

    Reiter’s syndrome

  • T. Sydenham
    (1848)
  • M. Stoll

    De l’arthrite dysenterique

    Archives of General Medicine

    (1869)
  • A.U. Yvan

    Observation sur une metastase de gonorrhee

    Annales de la Soc Med Prat de Montpellier

    (1806)
  • M.P.E. Launois

    Arthropaties recidivantes amythrophie generalize troubles trophiques multiples. D’origine blennofthalmique

    Bulletins et mémoires de la Société médicale des hôpitaux de Paris

    (1897)
  • A. Cooper

    On gonorrhoeal rheumatism. On gonorrhoeal ophthalmia

    Lancet

    (1824)
  • B.C. Brodie

    Pathological and surgical observations on diseases of the joints

    (1818)
  • C.J. Michet et al.

    Epidemiology of Reiter’s Syndrome in Rochester, Minnesota: 1950–1980

    Arthritis & Rheumatism

    (1988)
  • T.K. Kvien et al.

    Reactive arthritis: incidence, triggering agents and clinical presentation

    Journal of Rheumatology

    (1994)
  • E. Rich et al.

    Reactive arthritis in patients attending and urban sexually transmitted disease clinic

    Arthritis & Rheumatism

    (1996)
  • J.A. Whittum-Hudson et al.

    Human chlamydial infections: persistence, prevalence, and prospects for the future

    Natures Sciences Societes

    (2005)
  • M.F. Doran et al.

    Trends in incidence and mortality in rheumatoid arthritis in Rochester, Minnesota, over a forty-year period

    Arthritis & Rheumatism

    (2002)
  • M.K. Soderlin et al.

    Annual incidence of inflammatory joint disease in a population based study in southern Sweden

    Annals of the Rheumatic Diseases

    (2002)
  • J.D. Carter et al.

    Chlamydiae as etiologic agents in chronic undifferentiated spondylarthritis

    Arthritis & Rheumatism

    (2009)
  • J. Braun et al.

    On the difficulties of establishing a consensus on the definition of and diagnostic investigations of reactive arthritis. Results and discussion of a questionnaire prepared for the 4th International Workshop on Reactive Arthritis, Berlin, Germany, July3–6, 1999

    Journal of Rheumatology

    (2000)
  • J. Lin et al.

    The diagnosis of reactive arthritis in the real world and factors that might contribute to its under/misdiagnosis

    Arthritis & Rheumatism

    (2010)
  • J. Schachter et al.

    Isolation of bedsoniae from the joints of patients with Reiter’s syndrome

    Proceedings of the Society for Experimental Biology and Medicine

    (1966)
  • R.J. Gilbert et al.

    Antibiotic therapy in experimental bedsonial arthritis

    Arthritis & Rheumatism

    (1973)
  • P.B. Wyrick

    Cell biology of chlamydial infection: a journey through the host epithelial cell by the ultimate cellular microbiologist

  • T.P. Hatch

    Developmental biology

  • T. Hackstadt

    Cell biology

  • M.E. Ward

    Mechanisms of Chlamydia-induced disease

  • J.W. Moulder

    Interaction of Chlamydiae and host cells in vitro

    Microbiological Reviews

    (1991)
  • W.L. Beatty et al.

    Persistent Chlamydiae, from cell culture to a paradigm for chlamydial pathogenesis

    Microbiological Reviews

    (1995)
  • F.B. Gordon et al.

    Chlamydial isolates from Reiter’s syndrome

    British Journal of Venereal Diseases

    (1973)
  • W.L. Norton et al.

    Light and electron microscopic observation on the synovitis of Reiter’s disease

    Arthritis & Rheumatism

    (1966)
  • H. Ishikawa et al.

    Arthritis presumably caused by chlamydia in Reiter’s syndrome. Case report with electron microscopic studies

    Journal of Bone and Joint Surgery [America]

    (1986)
  • L.K. öhler et al.

    Ultrastructural and molecular analysis of the persistence of Chlamydia trachomatis (serovar K) in human monocytes

    Microbial Pathogenesis

    (1997)
  • R.J. Belland et al.

    Transcriptome analysis of chlamydial growth during IFN-gamma-mediated persistence and reactivation

    Proceedings of the National Academy of Sciences of the United States of America

    (2003 Dec 23)
  • U. Zugel et al.

    Role of heat shock proteins in protection from and pathogenesis of infectious diseases

    Clinical Microbiology Reviews

    (1999)
  • U. Zugel et al.

    Immune response against heat shock proteins in infectious diseases

    Immunobiology

    (1999)
  • D. Dean et al.

    Persistent Chlamydia trachomatis infections resist apoptotic stimuli

    Infection and Immunity

    (2001)
  • A.J. Curry et al.

    T lymphocyte lines isolated from atheromatous plaque contain cells capable of responding to Chlamydia antigens

    Clinical and Experimental Immunology

    (2000)
  • H.C. Gerard et al.

    Cytokine and chemokine mRNA produced in synovial tissue chronically infected with Chlamydia trachomatis and C. pneumoniae

    Journal of Rheumatology

    (2002)
  • A. Mittal

    Serovar distribution of Chlamydia trachomatis isolates collected from the cervix: use of the polymerase chain reaction and restriction endonuclease digestion

    British Journal of Biomedical Sciences

    (1998)
  • K.A. Workowski et al.

    Clinical manifestations of genital infection due to Chlamydia trachomatis in women: differences related to serovar

    Clinical Infectious Diseases

    (1994)
  • N.Z. Wilkinson et al.

    The detection of DNA from a range of bacterial species in the joints of patients with a variety of arthritidies using a nested, broad-range polymerase chain reaction

    Rheumatology

    (1999)
  • Cited by (0)

    View full text