be issues with falsely low CRPs in the setting
of a patient on DMARDS, 6 Cox-2 inhibitors and
corticosteroids.
Procalcitonin is a precursor to the hormone
calcitonin and rises in response to bacterial
infection. Interest in procalcitonin as a specific
marker for bacterial infection has increased and
there is some evidence to show that it is not
affected by corticosteroids. 7 A meta-analysis
looking at serum procalcitonin in differentiating
between septic and inflammatory arthritis
showed a specificity of 95% (CI 87–98%) and
a sensitivity of 54% (38–62%) compared with
serum CRP and a sensitivity of 45% (CI 35–55%)
and specificity of 7.9% (CI 2.1–2.5%). 8
Unfortunately there is little published data
on the effects of DMARDs on other serological
biomarkers, for example, IL-1 or PTX-3, and their
ability to distinguish between rheumatological
inflammation and infection. However, this may
be an interesting area for future research, as
these markers are not yet commercially available.
Joint fluid biomarkers are also being developed
as another method to try to differentiate between
inflammation and infection, particularly in the
setting of prosthetic joint infection. One systemic
review and meta-analysis comparing 13 different
tests determined that alpha defensin was the
optimal synovial marker and that there may be
scope to use others in combination. However the
effect of immunosuppressive therapies on this is
unknown. 9
Radiological investigation
With regards to the radiological diagnosis of
VOM, the IDSA 10 recommends MRI spine as
first-line modality followed by technicium
gallium scan CT or PET CT if there are
contraindications to MR. MRI has a sensitivity
of 97% and specificity of 93%; however, it is well
known that radiological changes can be absent
early on in infection and there can be artefact
effect in the presence of prosthesis. Gallium
scan combined with a bone scan is reported
as having a sensitivity of 91% and specificity
of 90%.
CT PET is also useful for the diagnosis of
osteomyelitis and detecting metastatic infection;
however, it would be difficult to differentiate
between increased uptake due to inflammation,
malignancy or infection. Nevertheless, there is
evidence to show that CT PET is more sensitive
and specific in the setting of chronic vertebral
osteomyelitis than labelled WCC. CT PET has also
been evaluated and found to be useful in serial
scans in both the post-surgical setting and in the
general follow up of patients, whereas with MRI,
it is known that radiological change can lag
behind clinical cure.
Unfortunately data evaluating this modality
in the setting of the rheumatological patient are
lacking, and the obvious concern would that be
the areas of increased uptake could be due to
either the underlying inflammatory disease or
infection.
Management
Septic arthritis of a native joint can be life-
threatening and cause permanent joint damage
if left untreated. In most cases, surgical washout
is required, as well as appropriate antimicrobials,
which might need to be initiated before a joint
aspirate is taken if there is going to be
a significant delay. Empirical antimicrobials are
based on local sensitivities, patient risk factors
(for example, allergy) and pharmacokinetics and
dynamics (such as bone penetration and patient’s
renal function). In general terms, empirical
coverage is aimed at Staphylococcus aureus and
Streptococcus species as these are the most
common causes of infection. After appropriate
source control the duration of antimicrobials of
a native joint is usually two to four weeks.
If clinical suspicion of infection remains high,
but initial bacterial culture is negative, cases
should be discussed with an infection specialist
to guide ongoing testing. This is particularly
important for those with risk factors for more
unusual pathogens, as listed in Table 1.
For pyogenic vertebral osteomyelitis, if the
patient is not septic and there is no neurological
compromise (either clinically or radiologically),
the initiation of antimicrobials can be deferred
until appropriate cultures are taken and a
microbiological diagnosis is confirmed. 10 Cultures
to be taken include blood cultures and, where
amenable, a biopsy. There are no clinical studies
regarding duration of antimicrobials in patients
with rheumatoid arthritis but a recent study has
shown non-inferiority of six weeks’ duration of
antimicrobials compared with 12 weeks in
pyogenic infection. 11
The type of antimicrobial depends on the
pathogen and sensitivities. However, in patients
with inflammatory arthritis who may be on a
number of medications, a careful assessment of
drug interactions and their risk versus benefit
should be assessed. Common interactions are
listed in Table 2. This is not an exhaustive list
and a risk–benefit analysis needs to be made
with a rheumatologist, infection specialist and
the patient as to which chosen antimicrobial
regimen is the most safe and most potent. Other
considerations specific to the rheumatology
patient in the face of an invasive infection is
whether immunosuppressive medications should
be reduced or stopped and, more importantly,
when these should be restarted. Interestingly
a recent meta-analysis in the paediatric, non-
rheumatological population has shown favourable
outcomes in corticosteroid use in septic arthritis,
although it should be highlighted this might not
be generalisable to the adult rheumatological
population. 12
Conclusions
The assessment, investigation and management
of a patient with bone and joint infection and
inflammatory arthritis is complex and requires a
multidisciplinary approach. This should include
rheumatology, infectious diseases, radiology and
orthopaedics with expertise and special interest
in managing the challenges with which this
cohort of patients present.
More research is required into specific
biomarkers and radiological modalities for
this group of patients in order to deliver high
quality and evidence-based care. It is likely
that the prevalence of infection in
rheumatological patients with complex infection
will continue to rise with increasing use of
immunosuppressives.
19
HHE 2019 | hospitalhealthcare.com
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