Withey: Infections of Bone and Joint Flashcards
If infecting organisms reach and colonize the joint in both septic arthritis and Chlamydiaassociated
reactive arthritis, what then is the difference between the two diseases?
Although it is certainly true that the immediate etiologic agents for both septic and
Chlamydiaassociated
reactive arthritis reach the joint and successfully colonize that site, the
diseases are profoundly different. One of the most important differentiation points lies in the
biology of the infecting organisms, and therefore in the mechanisms of pathogenesis
involved; i.e., in septic arthritis an overt and productive infection of the synovium is the
rule, whereas in reactive arthritis resulting from C. trachomatis, following infection of the
urogenital tract, productive infection of the synovium is virtually never seen in either acute or
chronic forms of the disease.
Recent research has demonstrated, however, that in the case of C. trachomatis infection of
the joint, the infecting organism is, in-fact, viable and metabolically active, even though it is
not culturable. This suggests that reactive arthritis due to this organism results from a persistent
infection of the synovium, and that the biology of the bacterium is unusual in that circumstance. This suggestion carries with it significant implications for use of antimicrobial therapy, as indicated in the lecture outline.
A 30 year-old Caucasian female presents with severe pain of the left knee. Upon taking a
history from this individual, you learn that she has no history of urethritis, no history of
uveitis, has not had any hint of a gastrointestinal infection within the last year, and has not
suffered a wound of-any consequence for at least six months. She cannot recall the last time she
was prescribed anantibiotic, but it was not recent.
Further investigation reveals that her husband of six months did have nongonococcal urethritis
ten years previously when he served in the US Navy; he said he was given an antibiotic and the
infection went away; he has had no symptoms or similar infections since. What would be the
best first step in management of this patient?
This patient almost certainly does not have a septic arthritis of any sort. However, it
is not only possible, but is rather likely, that she has developed reactive arthritis from C.
trachomatis. Recent studies have indicated that urethral infections with this organism quite
frequently generate persistent infections with few or no overt symptoms, even after proper
antibiotic treatment. Moreover, research has suggested that such persistent infections can be
transmitted to sexual partners with reasonable efficiency. Genital chlamydial infections in
women are very frequently subclinical and essentially asymptomatic. Thus, the proper first
step to take would probably be to investigate the possibility of a cervical infection by C.
trachomatis; this would involve taking a cervical swab and having a laboratory culture
performed on that swab. Assessing the swab for C. trachomatis DNA by PCR in the clinical
laboratory would also be a reasonable idea.
A patient presents to you with severe monoarthritis of the right knee. The patient has no
history of urethritis or gastrointestinal infection, and there is no evidence of a recent wound of
any sort. The patient has been taking ciprofloxacin for two weeks for an unrelated illness.
Urethral cultures from the patient are completely negative, and synovial cultures from fluid are
similarly negative. However, histopathology of a synovial biopsy done by a rheumatologist
indicates intense inflammation of the joint and extensive infiltration of mononuclear cells.
PCR analysis of total DNA prepared from a portion of the synovial biopsy tissue clearly
demonstrates chromosomal DNA sequences from C. trachomatis but no other organisms.
What would your diagnosis be, and why?
By current diagnostic criteria of the American College of Rheumatology, reactive
arthritis can only be diagnosed if the patient has a verifiable history of relevant infection.
Technically, therefore, the proper diagnosis is one of undifferentiated monoarthritis; this
specification simply means that the patient has all or most symptoms associated with reactive
arthritis except for the definite history of relevant urogenital or gastrointestinal infection.
However, a positive PCR for C. trachomatis from synovial tissue strongly indicates that this is
probably the organism causing the joint inflammation. Recall that chlamydial infections are
frequently subclinical and essentially asymptomatic in both men and women, and thus a
documented genital infection with the organism may not be possible. Incidentally, ciprofloxacin
is relatively ineffective at clearing Chlamydia, and indeed some studies show that treatment
with this drug tends to promote the transition from overt to persistent infection.
OSTEOMYELITIS:
Cause:
How do organisms reach the bone? (2)
Cause: active and overt bacterial infection in the head of a growing bone (usually a weight bearing bone)
Organisms reach the bone by blood mediated dissemination from:
o Local site of infection (more common)
o Distant site of infection (rare)
OSTEOMYELITIS
Description:
Young or old?
Affects only one joint
Swelling?
Pain?
- Disease of young people (in growing bones)
- Mono-articular (affects only 1 joint)
- Usually no visible swelling of the joint or significant discoloration
- Joint pain can be severe, especially during active use
OSTEOMYELITIS
Organisms:
Most common:
Others (2):
In immunosuppressed:
Almost always:
- S.aureus is the most common
- Others: E.coli, Pseudomonas aeruginosa
- With increase in immunosuppression/aging population: mycobacteria, fungi and various parasites can also be the cause
- Almost always mono-microbial
OSTEOMYELITIS
Pathogenesis:
Due to toxin and proteolytic enzyme mediated degradation of cartilage OR epiphyseal plate (more serious)
OSTEOMYELITIS
Clinical ID:
Blood cultures:
Synovial fluid:
Anti-microbial susceptibility testing:
X-ray/NMR:
- Blood cultures usually positive for causative organism
- Synovial fluid MAY be culture-positive
- Anti-microbial susceptibility testing
- X-ray and/or NMR frequently used for diagnosis: prior to invasive sampling of bone
OSTEOMYELITIS
Treatment:
- Anti-inflammatory drugs given to relieve pain
- Standard antibiotic treatment often effective
SEPTIC ARTHRITIS
Cause:
Organisms reach joint by (2):
Cause: active and overt bacterial infection of the joint
Organisms reach joint by:
o Direct inoculation as a result of trauma
o Migration from a distant focus of infection (rare)
SEPTIC ARTHRITIS
Description:
How many joints involved?
Mostly what areas?
Presentation:
Pain:
- Most are mono-articular (one joint involved), but can be poly-articular
- Mostly knee and ankle joints
- Joints are swollen, warm to touch and discolored
- Pain occurs all the time (even at rest), but can be worsened by movement
SEPTIC ARTHRITIS
Organisms:
Most common:
Others:
With increased immunosuppression:
Mono- or poly-microbial?
- S.aureus most common
- Others: H.influenzae, E.coli, Klebsiella spp.
- With increase in immunosuppression/aging population: mycobacteria, fungi and various parasites can also be the cause (infection will appear very much like one caused by S.aureus, but will be much more difficult to treat)
- Infection can be mono-microbial (usually) or poly-microbial; depends on origin of bacteria
SEPTIC ARTHRITIS
Pathogenesis:
Where do the organisms multiply once in the joint? Pathogenesis from (2):
- Once in the joint, organisms multiply in the synovial fluid (great medium to grow in)
- Pathogenesis from:
o Toxins and other molecules produced by the bacterium (induce inflammatory response in the joint)
o Proteolytic enzymes (degrade cartilage and other synovial structures)
SEPTIC ARTHRITIS
Clinical ID:
Blood cultures;
Synovial fluid:
Anti-microbial susceptibility testing:
X-rays/NMR:
- Blood cultures usually positive for causative organism
- Synovial fluid usually shows infecting organism (+ higher leukocyte counts)
- Anti-microbial susceptibility testing
- Rarely use X-rays or NMR
SEPTIC ARTHRITIS
Treatment:
Anti-inflammatory drugs given to relieve pain
Standard antibiotic treatment often effective
