3Chlamydia-induced reactive arthritis: Hidden in plain sight?
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)
Bacterial agents in spondyloarthritis: a destiny from diversity?
Best Practice Research and Clinical Rheumatology
(2010)- et al.
Reactive arthritis: clinical aspects and medical management
Rheumatic Disease Clinics of North America
(2009) - et al.
Chlamydia trachomatis and reactive arthritis: the missing link
Lancet
(1987) - et al.
Differential expression of three Chlamydia trachomatis hsp60-encoding genes in active vs. persistent infections
Microbial Pathogenesis
(2004) - et al.
Patients with Chlamydia-associated arthritis have ocular (trachoma), not genital, serovars of C. trachomatis in synovial tissue
Microbial Pathogenesis
(2010) - et al.
The pathogenic role of HLA-B27 and its subtypes in ankylosing spondylitis
Autoimmunity Reviews
(2007) - et al.
Reactive arthritis following an outbreak of Salmonella bovismorbificans infection
Journal of Infection
(1998) - et al.
Campylobacter reactive arthritis: a systematic review
Seminars in Arthritis and Rheumatism
(2007) - et al.
In vitro infection and pathogenesis of Chlamydia pneumoniae in endovascular cells
American Heart Journal
(1999) - et al.
The use of serologic tests for the diagnosis of chlamydial infections
Journal of Microbiol Methods
(2000)