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Role of Synovial Fluid Analysis and
Synovial Biopsy in Joint Diseases
Sangeeta B Kulkarni (Bhide)*, Ila M Vora**, Subhash
Abraham***, Shanu Srivastava*, Jignesh Sheth+, Rakesh Chaturvedi++ |
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Synovial Biopsies (SBx) are usually
done to diagnose joint diseases. However, synovial fluid (SF)
analysis may provide an easier, non-invasive option. The aim
is to determine the utility of SF tests and to correlate the
results with synovial biopsies (SBx).
Prospectively 30 cases of joint diseases were studied
on whom SBx was done during arthroscopy and in 50% cases SF
was analysed following arthrocentesis.
SF analysis in 15 cases showed Noninflammatory-3 (all Baker’s
cyst) and inflammatory 12 cases which included Rheumatoid arthritis
- three (serologically Rheumatoid Factor positive), Tuberculosis
- two, Noninfective - seven.
SBX was categorized as Noninflammatory three cases
(all Baker’s cyst). Chronic nonspecific inflammation 20
cases, Tuberculosis - four cases and Rheumatoid arthritis -
three cases.
This study revealed SF analysis and SBx are complementary
to each other for arriving at a specific diagnosis. Mucin clot
and string test (MCST) correlates well with biopsy. However,
synovial fluid analysis alone could help in differentiating
inflammatory and non-inflammatory conditions.
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| INTRODUCTION |
Arthrocentesis is generally a simple, relatively non-invasive
way to gather critical information in patients of mono
or polyarticular arthropathy.1-3 Sampling of
synovial fluid is among the most useful tests available
to the clinician evaluating the patient.2 Synovial
biopsy procedure is also easy and carried out at the same
time.4 It helps to distinguish between various
inflammatory, non-inflammatory, traumatic and crystal
induced arthropathies.5 In this study we have
tried to predict the aetiology of a joint pathology by
synovial fluid analysis as compared to synovial biopsy
in order to determine the usefulness of simple tests done
on synovial fluid. |
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| Material and Methods |
A prospective study of synovial fluid analysis and
synovial biopsy were carried out in cases of joint diseases
from July 2001 to June 2002 at Terna Medical College,
Nerul, Navi Mumbai.
Arthrocentesis was performed using aseptic techniques
after the patient was kept fasting for eight hours.5-7
Synovial fluid was aspirated from knee joints in 15 cases
and analysed after collecting into three tubes:
a. Five ml in plain bulb for biochemical studies.
b. 2.5 ml in anticoagulant bulb (EDTA) for TLC, DLC,
wet preparation and mucin clot and string tests.
c. Five to ten ml in sterile tube for microbiological
studies.
Examination of synovial fluid was done as early as possible
and following tests were done on each sample.1,6,8,9
i. Gross examination : Volume, colour and clarity.
ii. Chemical analysis : Glucose estimation done by GOD-POD
method. Protein estimation done by Biuret method.
iii. Mucin clot and String tests for viscosity.
iv. Microscopic examination : Total leucocyte count done
by the standard haematological counting chamber method
using isotonic saline with methylene blue as the diluent.
Differential
Mucin clot test (MCT)2,7 : It reflects the
depolarization of hyaluronic acid and demonstrated by
the precipitation of hyaluronate by acetic acid into the
mucin clot. One part of synovial fluid is added to four
parts of 2% acetic acid. After stirring briskly the nature
of clot produced is noted and interpreted as shown in
Table 1.
String Test (ST) / Falling drop test1,6,7,9
: Synovial fluid is allowed to drop from a Pasteur pipette
while noting the length of the string formed. Normal length
of string is 4 to 6 cm (average 5 cm). Abnormal string
less than 3 cm indicating low viscosity.
Other test parameters used to differentiate between inflammatory
and noninflammatory categories2,5,6,8 are given
in Table 2.
Septic arthritis was considered when TLC was greater
than 50,000 cell/cumm with greater than 75% neutrophils.2,3,6,10
| Table 1 : Interpretation of mucin clot
test |
| Grade |
Clot |
Solution |
| Good |
Tight ropy mass |
Clear |
| Fair |
Softer, shreddy |
Clear/Hazy |
| Poor |
Shreddy |
Turbid |
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| Table 2 : Test parameters
differentiating inflammatory and non-inflammatory
lesions |
| Disease |
Less than or |
Less than or |
Greater than 25 |
Less than or |
| |
equal to 2000 |
equal to 25 |
equal to 40 |
equal to 2.5 |
| Inflammatory |
Greater than 2000 |
Greater than 25 |
Less than 40 |
Greater than 25 |
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| Table 3 : Synovial
fluid analysis |
| Diagnosis |
No.of
cases |
Appearance |
TLC
cells/cumm |
% of
Neutrophils |
*MCT |
+ST
in cm |
Protein
gm/dl |
Glucose
mg/dl |
| 1Non Inflammatory |
|
|
|
|
|
|
|
|
| a. Baker’s cyst |
3 |
Clear |
100-2100 |
18-28 |
Good |
5-5.2 |
1.2-2.4 |
71.5-90 |
| 2. Inflammatory |
|
|
|
|
|
|
|
|
| Rheumatoid |
3 |
Turbid |
4500-30000 |
51-76 |
Fair to Poor |
3-3.5 |
4.2-6.4 |
26-40 |
| Arthritis |
|
|
|
|
|
|
|
|
| b.Tuberculosis |
2 |
Turbid |
10500-14800 |
55-61 |
Fair |
2-2.2 |
4.3-4.5 |
30-40 |
| Non infective |
7 |
Turbid |
4800-17250 |
51-82 |
Fair to Poor |
1-1.38 |
2.4-4.2 |
28-98 |
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| Results |
ICrystals were not detected in wet preparation in any
case. Grams and Ziehl-Neelsen stains were negative for
organisms. Cultures failed to show any growth.
Synovial biopsies revealed Non-inflammatory conditions
- 3 (all Baker’s cyst) and Inflammatory Conditions
- 27 where (Non specific inflammation - 20, Tuberculosis
- 4 and Rheumatoid arthritis - 3). |
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| Discussion |
Of
the 15 cases of synovial fluid analyzed, 3 were noninflammatory
and the remaining 12 were inflammatory. Prompt examination
of synovial fluid is required to avoid problems of misdiagnosing
borderline inflammatory conditions, missing calcium pyrophosphatedihydrate
crystals that dissolve with time or over interpreting
new artifactual findings.3,11 Good clarity with good mucin
clot test signifies non-inflammatory conditions whereas
turbid appearance with fair to poor Mucin clot test were
indicative of inflammatory conditions. These results were
similar to that of Broderick et al and other workers.1,2,6,12
Total leucocyte count ranging between 100 and 2100 cells/cumm
with polymorphonuclear 18 to 23% in non-inflammatory joint
diseases were in line with the observations of other workers.2,6,8,12
However, there was a frequent overlap of TLC with that
of various inflammatory arthropathies.
Findings
in rheumatoid arthritis were similar to those of other
workers.2,3,6,12 Except in one case where Neutrophils
were 76% of a total count of 30,000 cells/cumm. High neutrophil
count is known in acute stage of rheumatoid arthritis
similar to septic arthritis.13,14 However total
leucocyte count greater than 50,000 cells/cumm is required
for the diagnosis of septic arthritis
Counts in cases of tuberculosis were similar to Wallace
et al.15 In general the appearance of joint
fluid in tuberculous arthritis depends on the stage of
the disease with the diagnosis dependent on demonstration
of acid fast bacilli in smear of culture.15
Wallace et al found 20% of patients of tuberculous arthritis
to be positive for acid fast bacilli and 80% on synovial
fluid culture.15 Both were negative in our
study but surmised by typical appearances obtained on
biopsy.
High neutrophil counts on DLC are sometimes obtained
which were not categorized as septic arthritis in our
study since TLC was less than the required number of 50,000
cells/cumm and no organisms on Gram stain or culture could
be demonstrated.
Moderate reduction or normal glucose levels were seen
in cases of inflammatory joint diseases but are usually
linked to the levels in the serum. Glucose levels in synovial
fluid are usually less than that of the serum by about
10 mg/dl in normal and in noninflammatory conditions but
may be 20-60 mg/dl in septic arthritis. However, frequent
overlaps are seen limiting the usefulness of glucose levels
of synovial fluid.2,3,6,8
Protein is not an accurate marker to distinguish inflammatory
from noninflammatory diseases.2,3,6,8 These
findings are summarized in Table 3. Protein levels of
synovial fluid involve multiple determinants like synovial
microvessels, increased permeability and production and
consumption of protein by the synovium. With other factors
like local blood supply, lymphatic drainage and serum
concentration.16
Rheumatoid arthritis may be RA positive but more characteristically
shows typical histological appearances in the synovium
including villous hypertrophy, proliferation of superficial
synovial cells, infiltration with chronic inflammatory
cells like lymphocytes and plasma cells, formation of
lymphoid follicles, deposition of fibrin and foci of necrosis4,5,13,14
(Fig. 1). Rheumatoid nodules may be present (Fig. 2).
They were present in 7.6% cases of seropositive cases
studied by Fassbender and 13% in other series.5
In the inflammatory group, the majority were chronic
non-specific inflammation and showed mild to moderate
villous hypertrophy, proliferated synovial cells and infiltration
of chronic inflammatory cells. Accurate diagnosis of a
particular disease in this broad group is difficult in
routinely strained sections.
A better understanding of the pathogenesis may be achieved
by immunohistochemical methods.5
In the non-inflammatory group, Baker’s cyst showed
a typical histopathologic appearance and all were from
the popliteal area.4 |
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| Conclusion |
Synovial fluid analysis helps to identify inflammatory
conditions by virtue of the following-
- Total leucocyte count greater than 2000 cells/cumm
- Polymorphonuclears greater than 25%
- Mucin clot and string test showing fair to poor viscosity.
However, due to frequent overlap of synovial fluid findings,
the above mentioned parameters are of limited usefulness
to distinguish among the various aetiologies of the inflammatory
group which still need to be biopsied to arrive at a specific
diagnosis. |
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A Coxib a Day Won’t Keep the Doctor
Away
The first agents to block cyclo-oxygenase 2 (COX2)
were commercially introduced 5 years ago as new
alternatives to existing non-steroidal anti-inflammatory
drugs (NSAIDs). In particular, rofecoxib was associated
with an unanticipated five-fold increase in myocardial
infarctions compared with naproxen.
A second generation of agents with improved COX2
selectivity has been developed that includes valdecoxib,
etoricoxib, and lumiracoxib. Unlike other coxibs,
lumiracoxib is not a tricyclic compound; its molecular
phenyl acetic acid structure represents an analogue
of diclofenac. Despite diclofenac’s marked
popularity in Europe and it being the most frequently
used NSAID worldwide, it is hepatotoxic in about
4% of patients. Thus, whether lumiracoxib carried
any analogous adverse potential and what the improved
COX2 selectivity would achieve insofar as safety
and efficacy remained to be established.
Furthermore, patients were stratified on the basis
of their taking low-dose aspirin.
The results of TARGET again raise concern of an
excess of myocardial infarctions with lumiracoxib
compared with naproxen. In patients who were not
taking low-dose aspirin, the hazard ratio climbed
even higher.
In a recent small randomised trial comparing valdecoxib
and parecoxib with placebo in coronary artery bypass
surgery, there was a clustering of myocardial infarction
and stroke events in patients assigned to receive
coxibs. Furthermore, recent studies with rofecoxib
have shown its propensity to raise blood pressure
and its capacity to precipitate congestive heart
failure.
The cardiovascular implications of the present
trial bear direct relevance to the interpretation
of the gastrointestinal effects of lumiracoxib.
As in other coxib trials, there was a significant
decrease in the frequency of upper gastrointestinal
ulcer complications in patients not taking low-dose
aspirin. Beyond the salutary effects on ulcer complications
the hepatotoxicity of lumiracoxib was manifest.
TARGET quantifies lumiracoxib’s narrow benefit
over two NSAIDs with a trade-off.
The coxib field has been marked by intensive direct
to consumer advertising in the USA, and sales of
these drugs exceed US$7 billion per year. Yet, it
is hard to imagine the justification for this extraordinary
adoption and coxibs in light of marginal efficacy,
heightened risk, and excessive cost compared with
traditional NSAIDs.
The continued commercial availability of rofecoxib,
without a black-box warning for cardiovascular patients
is indeed troubling
Eric J Topol, Gary W Falk, Lancet, 2004;
364 : 639-40. |
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