Copyright © 2009 by The Journal of Bone and Joint Surgery, Inc.
Commentary & Perspective
Commentary & Perspective by
Michael A. Mont, MD*,
The Sinai Hospital of Baltimore, Baltimore, Maryland
Posted October 2009
Knee arthroscopy is one of the most common procedures that orthopaedic surgeons
perform in the United States each year. Recently, the need for performing some
of these procedures has been questioned1,2. One of the primary indications
is clinically important meniscal tears. We typically rely on a combination of
history, physical examination, and magnetic resonance imaging to diagnose these
tears3,4. However, it is well-known that magnetic resonance imaging
may diagnose meniscal injuries in more than 50% of the asymptomatic population,
especially in patients who are more than forty years of age5,6. There
have been few other laboratory or diagnostic tools that have been used to further
evaluate symptomatic joints, except in the presence of infection or inflammatory
conditions. It is not clear why some patients with meniscal injuries have clinically
important pain while others remain asymptomatic.
In the study "Diagnostic Utility of Cytokine Biomarkers in the Evaluation
of Acute Knee Pain," Cuellar et al. analyzed thirty-two patients who had knee
pain for less than six months and who had elected to undergo an arthroscopy after
nonoperative treatment had failed. They analyzed the joint fluid aspirate from
this group of knees (preoperatively) and from twenty-three of the contralateral
noninvolved knees and compared the findings to those from fifteen asymptomatic
control knees. They measured the concentrations of seventeen inflammatory cytokine-chemokines.
They then compared magnetic resonance imaging findings with these assay results
as well as with the intraoperative findings. The authors found that intra-articular
concentrations of inflammatory cytokines correlated with pain in patients with
symptomatic meniscal tears but were markedly lower in the asymptomatic normal
knees and in asymptomatic knees with meniscal tears. On the basis of this study,
they concluded that the cytokines may be involved in the generation of pain following
meniscal injury.
The importance of this work is that this may be a first step in the development
of a more sensitive and specific test for symptomatic meniscal tears. The sensitivity
and specificity of using history, physical examination, and magnetic resonance
imaging are extremely low. It appears that, on the basis of the results of this
preliminary study, (in this reviewer's opinion) these tests could lead to a much
better differentiation of asymptomatic and symptomatic individuals, and perhaps
more clearly define the indications for surgery. Therefore, these types of tests
might determine which patients are best suited for continued nonoperative treatment
and which may be best served by surgical intervention. In this study, the tests
were 100% sensitive and specific for symptomatic meniscal tears.
In addition, knowledge of the specific cytokines that are involved in meniscal
injuries, as well as the pain pathway, may lead to further insights concerning
meniscal or cartilage pathophysiology. Various inflammatory cytokines have been
implicated in the local production of knee pain. Some of these cytokines may
sensitize nociceptors, resulting in pain. In addition, blockade of tumor necrosis
factor-alpha leads to pain relief in patients with rheumatoid arthritis7.
These various cytokines may be related to the inflammatory or healing process
in the knee8.
A strength of this study is that it was performed prospectively on a well-defined
cohort of patients. All thirty-two patients had magnetic resonance imaging of
the lavaged knee preoperatively along with the performance of appropriate tests,
and the results could easily be compared with the intraoperative findings. The
study was well planned, with independent observation of the magnetic resonance
imaging scans as well as the intraoperative findings.
There were certain limitations of the study, including that this was a small
sampling of patients (n = 32) from a single center. Two of the patients who underwent
surgery did not have meniscal injury despite positive findings on magnetic resonance
imaging and, in some cases, there was sample loss. In addition, what could be
a major problem is that it may be hard to create a standardized system for lavaging
and aspirating joints. Certainly, sometimes one patient may have a much larger
effusion in the knee joint than another patient does (by an order of tenfold
or more), which can certainly dilute any cytokines. For this test to be clinically
useful, a much more sophisticated analysis of the concentration of the cytokines,
corrected for the amount of effusion that is present, will need to be performed.
This may not be only a concentration effect, but it may also be a function of
the total amount of cytokines that are present, which would be overexpressed
as a concentration in joints that have a minimal amount of fluid. In some patients,
the joint aspirations may be contaminated with blood, which may affect the measurements.
It is good that the authors have pointed out many of the potential biases in
their study, such as the possibility of greater dilution of cytokines in patients
with an effusion than in patients without an effusion.
In summary, the authors have found a greater concentration of four inflammatory
cytokines and/or chemokines from intra-articular aspirates from painful knees
with operatively confirmed meniscal injuries as compared with the concentrations found in nonpainful control
knees as well as age-matched atraumatic control knees. These tests might be useful
in the future to add information about clinical judgments concerning meniscal
injuries and the further development of a diagnostic test. In addition, it is
possible that increased understanding of these cytokine factors in the knee may
lead to the development of additional antinociceptives, pain medications, or
other intra-articular reagents for treatment.
*The author did not receive any outside funding or grants in support of his research for or preparation of this work. The author, or a member of his immediate family, received, in any one year, payments or other benefits in excess of $10,000 or a commitment or agreement to provide such benefits from a commercial entity (Stryker, Wright Medical).
References
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2. Spahn G, Muckley T, Kahl E, Hofmann GO. Factors affecting the outcome of arthroscopy in medial-compartment osteoarthritis of the knee. Arthroscopy. 2006;22:1233-40.
3. Solomon DH, Simel DL, Bates DW, Katz JN, Schaffer JL. The rational clinical examination. Does this patient have a torn meniscus or ligament of the knee? Value of the physical examination. JAMA. 2001;286:1610-20.
4. Reicher MA, Hartzman S, Duckwiler GR, Bassett LW, Anderson LJ, Gold RH. Meniscal injuries: detection using MR imaging. Radiology. 1986;159:753-7.
5. Zanetti M, Pfirrmann CW, Schmid MR, Romero J, Seifert B, Hodler J. Patients with suspected meniscal tears: prevalence of abnormalities seen on MRI of 100 symptomatic and 100 contralateral asymptomatic knees. AJR Am J Roentgenol. 2003;181:635-41.
6. Bhattacharyya T, Gale D, Dewire P, Totterman S, Gale ME, McLaughlin S, Einhorn TA, Felson DT. The clinical importance of meniscal tears demonstrated by magnetic resonance imaging in osteoarthritis of the knee. J Bone Joint Surg Am. 2003;85:4-9.
7. Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M, Smolen J, Emery P, Harriman G, Feldmann M, Lipsky P. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet. 1999;354:1932-9.
8. Steiner G, Tohidast-Akrad M, Witzmann G, Vesely M, Studnicka-Benke A, Gal A, Kunaver M, Zenz P, Smolen JS. Cytokine production by synovial T cells in rheumatoid arthritis. Rheumatology (Oxford). 1999;38:202-13.
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