Review Article

Evaluation of the Painful Total Knee

Arthroplasty
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Abstract
Michael A. Flierl, MD Total knee arthroplasty (TKA) has been associated with notable
Ali N. Sobh, MD improvements in health-related quality of life of patients with end-
stage knee arthritis. Although most patients experience substantial
Brian M. Culp, MD
symptomatic relief after TKA, up to 19% of patients are unsatisfied with
Erin A. Baker, PhD their outcome. With the dramatic, projected increase in the number of
Scott M. Sporer, MD TKAs performed annually, it is crucial to appreciate the various modes
of failure associated with this procedure. A comprehensive
understanding of the symptomatology and thorough clinical
examination aid in identifying the etiology of ongoing knee pain.
Ancillary testing including conventional laboratory analyses, imaging
studies, and diagnostic injections supplement a thorough history and
physical examination. In addition, novel laboratory markers, RNA/
DNA-based tests, and novel imaging modalities are emerging as
beneficial tools in evaluating patients with a painful TKA. A well-
structured, algorithmic approach in the management of these patients
is essential in correctly diagnosing the patient and optimizing clinical
outcomes.

S ymptomatic osteoarthritis and

From the Beaumont Health,
Departments of Orthopaedic Surgery
and Research, Royal Oak, MI
(Dr. Flierl, Dr. Sobh, and Dr. Baker),
the Princeton HealthCare System,
Department of Orthopaedic Surgery,
Princeton, NJ (Dr. Culp), and the Rush
University Medical Center, Midwest
Orthopaedics at Rush, Chicago, IL
(Dr. Sporer).
None of the following authors or any
immediate family member has
received anything of value from or has
stock or stock options held in a
commercial company or institution
related directly or indirectly to the
subject of this article: Dr. Flierl,
Dr. Sobh, Dr. Culp, Dr. Baker, and
Dr. Sporer.
J Am Acad Orthop Surg 2019;00:1-9
DOI: 10.5435/JAAOS-D-18-00083
Copyright 2019 by the American
Academy of Orthopaedic Surgeons.
rheumatoid arthritis commonly
affect the knee and can present with
pain, stiffness, and loss of mobility.
Total knee arthroplasty (TKA) is a
safe, effective intervention with
favorable outcomes for patients with
end-stage knee arthritis who have
failed nonsurgical management.1
Although contemporary prosthesis
designs, novel surgical techniques,
and enhanced recovery protocols
have improved outcomes over the
years, nearly 20% of patients expe-
rience suboptimal results after
TKA.2 Common patient complaints
postoperatively include persistent
residual pain, stiffness, and func-
tional limitation with activities of
daily living.
The demand for primary and revi-
sion TKA is projected to markedly
increase in the near future. Inacio
et al3 estimated a 143% increase in
the number of TKA procedures
performed in the United States alone
by 2050, largely because of the
increase in the average lifespan of the
general population and increased
expectations for improved mobility
among elderly patients. The sub-
stantial increase in numbers of pri-
mary TKA will likely result in a
notable growth in patients with
painful TKA, requiring a compre-
hensive understanding of inherent
modes of TKA failure.4
A thorough evaluation through
patient history collection, physical
examination, imaging modalities,
laboratory analysis, and ancillary
testing are useful in identifying the
cause of continuing pain after TKA.
An algorithmic approach to evaluate
pain after TKA is paramount because
revision in the setting of an uncertain
diagnosis yields poor outcomes.5
This review aims to serve as a guide

Month 2019, Vol 00, No 00 1

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Evaluating the painful TKA

Table 1
Intrinsic, Extrinsic, and Rare Causes of Pain After TKA
Intrinsic Causes Extrinsic Causes Rare Causes

Infection Hip pathology Synovitis

Implant malpositioning, loosening, and Spine pathology Recurrent hemarthrosis
catastrophic failure
Knee instability Vascular pathology Nerve related (eg, cutaneous neuroma/complex
regional pain syndrome, fibromyalgia,
tourniquet palsy)
Extensor mechanism disorders (eg, Tendinitis and bursitis Worker’s compensation
quadriceps/patellar tendon rupture,
periprosthetic patellar fractures)
Arthrofibrosis Metal sensitivity Heterotopic ossification
Minimal preoperative knee Psychiatric disorder
osteoarthritis

TKA = total knee arthroplasty

in the evaluation and diagnosis of the
patient presenting with a painful TKA.
Etiology of the Painful Total
Knee Arthroplasty
Etiologies of pain after TKA can be
broadly categorized as intrinsic or
extrinsic.6 Intrinsic causes of pain
include pathology within the knee
joint, such as infection, implant
failure, implant loosening, instabil-
ity, subluxation/dislocation, arthro-
fibrosis, impingement, or disorders
of the extensor mechanism. Con-
versely, extrinsic pain after TKA in-
cludes pathology outside the knee.6
These include hip disease, spine
pathology, vascular insufficiency,
tendinitis, and bursitis (Table 1).
Intrinsic Causes of Painful
Total Knee Arthroplasty
Infection after TKA exists on a spec-
trum and ranges from mild surgical
site cellulitis to overt periprosthetic
joint infection (PJI) necessitating
various treatments.7 Aberrant
implant alignment may potentiate
postoperative pain, patellofemoral
maltracking, excessive polyethylene
wear with associated osteolysis,
aseptic loosening, and/or potentially
catastrophic implant failure.8 Insta-
bility of TKA with imbalance of
flexion/extension gaps may also be
the cause of persistent pain and knee
swelling postoperatively, which may
result in overt dislocation.9,10 Ar-
throfibrosis around the implanted
implants can lead to postoperative
stiffness and pain.11 Implant impinge-
ment, occurring when two prosthetic
surfaces abut one another, has been
associated with accelerated erosion
and wear with subsequent pain and
reduced range of motion (ROM).12
Disorders of the extensor mechanism
have been identified as a notable cause
of anterior knee pain and dysfunction
after TKA. These issues may occur in
resurfaced or unresurfaced patellae
and include patellar osteonecrosis and
fracture, patellar maltracking, or ten-
don ruptures.13
Extrinsic Causes of Painful
Total Knee Arthroplasty
Hip arthritis, osteonecrosis, or occult
fracture often manifests as referred
pain in the anterior thigh with radia-
tion down to the anterior knee and
therefore may be mistaken for knee
pain. Similarly, spinal stenosis and
degenerative disk disease with nerve
root impingement can be also sources
of postoperative pain after TKA.
Vascular disease, including claudica-
tion, insufficiency, thrombosis, or
aneurysm, is a rare cause of postop-
erative leg pain and swelling, yet must
be considered in the evaluation of
these symptoms.14 Periarticular bur-
sitis, tendinopathies, causalgia, neu-
roma, or iliotibial (IT) band friction
syndrome may also contribute to
postoperative pain after TKA.15-17
Overuse injuries may include peri-
prosthetic stress fractures and occur
concomitantly with intrinsic causes
of painful TKA, local osteolysis,
and/or implant impingement.18
Other Causes of Painful Total
Knee Arthroplasty
Rare causes of pain may stem from
the absence of notable knee arthritis
before TKA, use of a tourniquet
during surgery, synovitis, recurring
hemarthrosis, fibromyalgia, or metal
sensitivity19-23 (Table 1). Heterotopic
ossification may manifest as pain and
progressive loss of ROM after TKA.24
Patients presenting for surgery in
the setting of worker’s compensa-
tion or psychiatric diagnoses tend to
have decreased satisfaction after
TKA.25,26 An incongruent expecta-
tion of postoperative performance

2 Journal of the American Academy of Orthopaedic Surgeons

Copyright © the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.

and improvement after TKA may
also lead to dissatisfaction with
associated weakness, balance issues,
and aching, which are all within the
expected range for a well-functioning
joint; thus, adequate preoperative
surgical education is crucial for all
TKA.
Prodromes of Total Knee
Arthroplasty Failure
Prodromal symptoms of TKA failure
can vary widely from patient to
patient. Lonner et al27 retrospectively
reviewed 102 complicated TKA cases
and assessed symptoms and associ-
ated radiographic findings. Pain and
swelling were present in 84% and
76%, respectively. Other complaints
included progressive varus/valgus
deformity, instability, stiffness, click-
ing, catching, and subluxation. Nota-
bly, however, this study excluded
acute infection and trauma cases and
included patients with at least a 1-year
period without symptoms.
Workup of the Painful Total
Knee Arthroplasty
Successful treatment of the patient
with a painful TKA relies on an
accurate diagnosis. An algorithmic
approach with thorough history
assessment, vigilant physical exami-
nation, and obtaining appropriate
radiographic studies and laboratory
tests are instrumental in obtaining the
correct diagnosis.
History
Patients with symptomatic TKA
often present with pain, swelling,
instability, and/or stiffness. A thor-
ough history should include an eval-
uation of the length of time the
patient experienced pain before TKA,
if there were any surgical inter-
ventions of the knee before TKA,
assessment of previous injuries to the
Month 2019, Vol 00, No 00
Copyright © the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
knee, and preoperative ROM. Addi-
tional questions should entail poten-
tial complications around the time of
the index procedure, such as repeat
surgery, prolonged antibiotic intake,
or wound healing difficulties. Every
effort should be made to obtain pre-
vious office notes, including previous
surgical reports including implant
information (eg, cemented versus
noncemented, posterior-stabilized
[PS] versus cruciate-retaining [CR]
knee).
The onset, nature, and location or
radiation of pain and the temporal
course of symptoms, including alle-
viating and aggravating factors, can
narrow pain etiology. Pain exacer-
bated with initial weight bearing and
alleviated with rest, for instance, can
be a sign of implant loosening, bur-
sitis, or tendinopathy.8 In contrast,
PJI typically presents with acutely
worsening and constant pain re-
gardless of the activity level.7
Unchanged symptoms after surgery
may be related to an extrinsic source
of pain (eg, radiculopathy, hip
pathology),28 whereas different chronic
pain may be related to chronic PJI.7
Additional acutely worsening pain in
the postoperative period may also be
related to venous thrombotic embolism
or periprosthetic fracture; however,
pain months to years postoperatively
in a previously well-functioning TKA
may indicate polyethylene wear, os-
teolysis, implant loosening, and/or
acute hematogenous PJI.8 Implant
malalignment or flexion/extension gap
unbalance can result in continued pain
and a subjective sense of instability or
stiffness postoperatively.8 Finally, a
recent history of infection (eg, dermal,
urinary tract, respiratory tract, gas-
trointestinal tract) or recent dental
procedures, with subsequent acute-
onset knee pain in a previously well-
functioning TKA, can be a sign of
acute hematogenous PJI.7 In general, it
can be valuable to inquire whether the
currently experienced pain is similar
or dissimilar to the preoperatively
Michael A. Flierl, MD, et al
experienced pain, and an assessment
of immediate- versus delayed-onset
pain after TKA can provide impor-
tant clues regarding the etiology of
pain (Table 2).
Physical Examination
A comprehensive physical examina-
tion is also essential in the process of
diagnosing a painful TKA. Key com-
ponents of the examination include
visual inspection, palpation, ROM,
patellar tracking with ROM, assess-
ment of stability in coronal and sagittal
planes throughout ROM, evaluation
of gait, and examination of the ipsi-
lateral hip and the spine.
Evaluation should include inspec-
tion of the surgical scar and peri-
incisional erythema. An effusion may
be indicative of infection, seroma,
recurrent hemarthrosis, or peri-
prosthetic fracture.7,22 Evaluation of
the quadriceps musculature can
allow detection of atrophy and
peripheral edema. The joint should
also be carefully palpated for areas
of point tenderness, such as the pes
anserine, the biceps femoris and
patellar tendons, and the distal IT
band15,16; particularly, pain with
palpation of the calf can be a sign of
venous thromboembolism. Cutane-
ous neuroma formation may occur
from surgical dissection and present
with point tenderness or reproduc-
tion of symptoms with the Tinel
percussion test.29 Although rare,
bony deformity may also be a man-
ifestation of matured heterotopic
ossification causing impingement of
surrounding soft tissues.24 Next,
assessment of active and passive
ROM and comparison to the
contralateral side is crucial; specifi-
cally, stability in the coronal and
sagittal planes with individual liga-
ment testing are applied to assess
collateral and cruciate ligament
integrity in full extension, 30°, and
90°. During the ROM examination,
patellar tracking, patellofemoral
3
Evaluating the painful TKA

Table 2
Assessment of Pain Character and Onset
Different Pain Versus Same Pain versus Immediate-Onset
Preoperative Preoperative Pain Delayed-Onset Pain

Infection Hip pathology Infection (acute Infection (hematogenous/chronic)

postoperative)
Implant malpositioning, loosening, Spine pathology Periprosthetic Implant malpositioning,
and catastrophic failure fracture loosening, and catastrophic
failure
Knee instability Vascular pathology Severe implant Knee instability
malpositioning
Extensor mechanism disorders Tendinitis and bursitis Polyethylene liner Extensor mechanism disorders
dislocation
Arthrofibrosis Minimal preoperative knee Venous Arthrofibrosis
osteoarthritis thromboembolism
Rare causes Ligamentous injury Rare causes

crepitus, and patellar clunk syn-
drome may also be carefully as-
sessed. Motor strength, sensory, and
vascular examination of the lower
extremity complete the assessment.
Finally, gait analysis and dedicated
examinations of the ipsilateral hip
and spine are performed because
radiating or referred pain may be
experienced in the anterior thigh or
knee.
Imaging Studies
A thorough diagnostic evaluation of
the painful TKA also depends on
imaging modalities, such as plain
radiography, CT, and nuclear stud-
ies. Obtaining and reviewing preop-
erative radiographs before the index
procedure can demonstrate risk fac-
tors for postoperative complications.
For instance, preoperative valgus
knees appear more susceptible to
implant malposition because of lat-
eral femoral condyle hypoplasia, and
Polkowski et al30 noted that a high
incidence of unexplained pain after
undergoing TKA may be attributed
to the mild to moderate arthritis
before index TKA. CT and nuclear
studies are infrequently required for
rare etiologies of pain after TKA;
however, CT can be useful in eval-
uating implant malrotation, and
nuclear studies can provide infor-
mation regarding implant loosening.
A standard panel of radiographs
should include weight-bearing AP
and lateral views and a Merchant
view to assess the patellofemoral joint
(Figure 1). In addition, an assessment
of overall knee alignment via full-
length, weight-bearing hip, knee,
and ankle radiographs is valuable
to accurately assess the overall
knee alignment because spot films of
the knee can result in erroneous
appearance of varus/valgus align-
ment of the TKA. Radiographic
imaging may allow osteolysis, loos-
ening, or periprosthetic fractures and
pain originating from implant mal-
positioning, malrotation, over- or
under-sized implants, and patellar
maltracking to be assessed and/or
ruled out of the diagnostic evalua-
tion (Supplemental Figure 1, Sup-
plemental Digital Content 1, http://
links.lww.com/JAAOS/A340).
Radiographs also allow a detailed
assessment of implant positioning,
sizing, and the tibial slope to be
performed.31 Weight-bearing radio-
graphs provide an accurate assess-
ment of asymmetric wear patters,
implant dislocation, and progressive,
thin radiolucent lines or larger
radiolucent defects with surrounding
osteolysis. An examination of the
bone-cement-implant interfaces may
be more challenging to assess
radiographically, depending on the
imaging quality, because minor
changes in beam direction may alter
the appearance of this interface.31 In
cases of possible implant loosening
with radiolucent lines, particularly in
the setting of painful noncemented
TKA, stress radiographs may also be
valuable.32
CT can be a useful modality for
evaluation of implant malrotation.
Following a standardized protocol,
an assessment of femoral and tibial
implant rotation relative to the
transepicondylar axis and tibial
tubercle, respectively, can be esti-
mated.33 Nuclear studies are sensi-
tive, but nonspecific, in the setting of
TKA pathology. Technetium-99m
(99mTc)-, gallium-67 (67Ga)-, and
indium-111 (111In)-labeled bone
scans are used in diagnosing TKA
pathology, but, again, lack specific-
ity.34 In addition, nuclear studies
may detect a normal inflammatory
physiology for up to 2 years after
undergoing TKA and can yield false-
positive results during that time
frame.31 As a result, routine use of
nuclear studies in the evaluation of
painful TKA is not recommended.

4 Journal of the American Academy of Orthopaedic Surgeons

Copyright © the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.

Figure 1
Standardized radiographic evaluation of the painful TKA should include weight-bearing radiographs, including AP (A), lateral
(B), and patellar (C) views. These radiographs should be carefully evaluated for overall knee alignment, implant sizing and
positioning, tibial slope, patellar tracking, and radiographic signs of loosening/osteolysis. TKA = total knee arthroplasty
Laboratory Analyses
Several useful laboratory studies
should be considered in the evaluation
of a painful TKA because it is impera-
tive to rule out PJI as a source of
symptoms. The American Academy of
Orthopaedic Surgeons in 2010 issued
clinical practice guidelines outlining the
diagnosis and treatment of hip and knee
PJI.35 Erythrocyte sedimentation rate
(ESR) and C-reactive protein (CRP) are
useful screening tools for PJI, whereas
standard complete blood count is no
longer routinely used.35 If ESR
and/or CRP are elevated, aspiration
of the knee with subsequent synovial
fluid analysis is recommended; if
there is a high clinical index of sus-
picion, aspiration of the knee should
be performed even in the absence of
ESR/CRP elevation.
According to the American Acad-
emy of Orthopaedic Surgeons Clini-
cal Practice Guidelines, sterilely
obtained synovial fluid should be sent
for aerobic, anaerobic, fungal, and
acid-fast bacilli cultures, synovial
white blood cell (WBC) count, and
differential cell count. Routine Gram
Month 2019, Vol 00, No 00
Copyright © the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
stains are no longer recommended in
ruling out PJI, and antibiotics should
be discontinued for a minimum of
2 weeks before obtaining synovial
fluid samples. On the basis of a ret-
rospective analysis of 452 patients,
the synovial WBC count was deter-
mined to be the most reliable marker
for infection.36 Various ideal cutoff
values for synovial WBC count have
been reported, including as low as
1,100 WBC/mL and a 64% neutrophil
differential with a combined negative
predictive value on 99.6%.37 Notably,
these cutoff values required for PJI
diagnosis change in the early postop-
erative phase. Within 3 weeks, acute
PJI can be diagnosed with 100%
sensitivity and 98.9% specificity when
setting the synovial WBC set at 11,200
cells/mL.38 Yi et al39 indicated an
optimal cutoff value of 12,800 WBC/
mL, followed by the CRP of 93 mg/L,
and synovial fluid differential of 89%
polymorphonuclear for diagnosis of
PJI within the first 6 weeks after
surgery.
A recent meta-analysis examined
the utility of various synovial fluid
markers in the diagnosis of PJI, such
Michael A. Flierl, MD, et al
as CRP, alpha-defensin, leukocyte
esterase, interleukin (IL)-6, IL-8,
vascular endothelial growth factor,
and granulocyte colony-stimulating
factor.40 All markers showed a sensi-
tivity of .0.8 and specificity of .0.9,
with alpha-defensin emerging as the
best diagnostic synovial marker,
demonstrating the highest diagnostic
odds ratio in identifying PJI. In addi-
tion, commercially available DNA-
based kits have recently emerged as
diagnostic tools for PJI with pre-
sumed high sensitivity, specificity,
and antibiotic profiles. Although
such advanced diagnostic tests are
rarely required for routine diagnosis
of PJI, because serum ESR/CRP in
conjunction with synovial fluid
analysis and culture are typically
sufficient in establishing a diagnosis,
these tests may be used as a tie breaker
in the setting of equivocal results
despite repeat standard aspiration.
Diagnostic Injections
Diagnostic injections may be benefi-
cial when distinguishing between
an intra-articular or extra-articular
5
Evaluating the painful TKA
source of pain. Local anesthetics can
be injected intra-articularly, and the
patient can subjectively compare pain
levels before and after (ie, several
minutes) injection. Subjective notable
reduction of pain within minutes of
intra-articular local anesthetic injec-
tion may indicate an intra-articular
source of pain, whereas lack of pain
improvement after intra-articular
analgesia may be due to an extrinsic
source of pain.
Algorithmic Evaluation of
the Painful Total Knee
Arthroplasty
Is It the Knee?
Initial diagnostic efforts should focus
on determining whether the knee
or extrinsic sources of pain are
responsible for symptoms. Using a
combination of a precise history,
radiographic review, and thorough
clinical assessment, intrinsic versus
extrinsic causes of pain may be deter-
mined. If pain appears to originate
outside the knee, pain should be treated
according to the presumed etiology.
Is the Knee Infected?
Any painful TKA should be consid-
ered infected until proven otherwise.
As described, screening for PJI should
include evaluation of any perioperative
complications at the time of index
surgery, radiographic analysis, a thor-
ough examination of the knee, and
serum ESR/CRP. If either or both
ESR and CRP are elevated or if there
is a high clinical index of suspicion
despite normal serum inflammatory
markers, sterile knee aspiration is
warranted. Samples should be ob-
tained for cell count with differen-
tial and cultures. Equivocal results
mandate a repeat aspiration and use
of novel biomarkers, such as alpha-
defensin, neutrophil elastase, or com-
mercially available DNA-based kits
as a tie breaker. If PJI is confirmed,
6 Journal of the American Academy of Orthopaedic Surgeons
Copyright © the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
treatment includes irrigation and
débridement polyethylene liner ex-
change, 1-stage or 2-stage exchange,
or chronic antibiotic suppression in
patients who are too sick to undergo
or refuse surgery.
Is the Extensor Mechanism
Intact?
Extensor mechanism disruptions are
devastating injuries after TKA. Usu-
ally, patients experience an acute incit-
ing event resulting in sudden inability to
extend the knee against gravity. Quad-
riceps or patellar tendon ruptures can
often be palpated clinically, whereas
patella alta/baja or an overt patellar
fracture can be noted radiographically.
Further imaging such as ultrasonog-
raphy or MRI with metal suppression
sequencing can confirm the diagno-
sis. Extensor mechanism disruptions
should be treated according to their
etiology (Figure 2).
Implant Assessment
A thorough clinical and radiographic
evaluation of the TKA implants can
supplement precise history taking
regarding the assessment of loose or
malaligned implants. Overall coronal
alignment of TKA implants should be
evaluated using full-length weight-
bearing hip to ankle radiographs.
Radiographic lucency, osteolysis,
and osteolytic defects paired with
activity-dependent pain can be a sign
of implant loosening. Patellofemoral
maltracking, patellar osteonecrosis,
and pain that never improved after
surgery may indicate implant malro-
tation and should be further evalu-
ated with dedicated CT. Initially,
treating either pathology with
NSAIDs and physical therapy can be
initiated, but revision TKA should be
considered in refractory cases.
Is the Knee Stable?
Although radiographic modalities
often provide a clear indication of the
underlying pathology, patients often
present with a painful TKA while
radiographs appear normal. This
phenomenon presents a problematic
issue for both the surgeon and the
patient because the diagnostic
workup may require extension past
routine imaging and laboratory
modalities. Clinically, the surgeon
must recognize the possibility of soft-
tissue imbalance during the index
procedure. Having tight, loose, or
unbalanced flexion and/or extension
gaps may lead to a patient’s subjec-
tive feeling of instability or lack of
trust in their knee; paired with
objective laxity to coronal or sagittal
stress on physical examination, these
may be signs of knee instability.
According to one scheme, TKA may
be classified as unstable with the
knee flexed, extended, or both in
flexion or extension.41 Severity can
range from mild instability to cata-
strophic implant failure with liner
dislocation (Supplemental Figure 2,
Supplemental Digital Content 2,
http://links.lww.com/JAAOS/A341).
Song et al42 categorized etiologies of
TKA instability into six groups:
flexion/extension gap mismatch,
implant malposition, isolated liga-
ment insufficiency, extensor mech-
anism insufficiency, implant loosening,
and global instability. A stability
assessment of the midflexion range,
which is a common cause of patient
dissatisfaction and distinguishable
when walking downstairs or rising
from a seated position, is particularly
important. Midflexion instability is
best examined by applying var-
us/valgus stress in approximately 20°
of knee flexion, which results in
relaxation of the medial collateral
ligament and distal IT band during
the examination. Flexion instability
can be assessed in the seated posi-
tion, with the knee dangling off the
examination table and the examiner
applying varus/valgus stress and
anterior/posterior shuck to a relaxed
knee. Instability may also result in
 Michael A. Flierl, MD, et al

recurrent knee effusions that are not Figure 2

associated with infection. Increased
activity of the hamstring tendons
subsequent to instability can cause pes
anserine bursitis, patellar tendinitis, or
distal IT band bursitis. The unstable
TKA can be initially treated with
physical therapy and NSAIDs; racing
can also be considered. Revision TKA
to a higher level of constraint and
improvement of overall soft-tissue
balance should be considered if non-
surgical measures fail. If a CR implant
design was used in the index proce-
dure, revision may include PS con-
structs, condylar-constrained designs,
or, in extreme cases, constrained im-
plants. During revision surgery, it is
important to recognize the necessity of
restoring the joint line to its natural
position because raising the joint line
can result in midflexion instability,
particularly in CR TKA.

Is the Knee Stiff?

Progressive knee stiffness, pain, and
lack of ROM can represent arthro-
fibrosis and usually occur in the early
postoperative course. Within the first
12 weeks after surgery, patients can
undergo a manipulation under anes-
thesia to improve postoperative
ROM in patients with arthrofib-
rosis.43 Late arthrofibrosis should be
evaluated carefully for implant
malalignment and patellofemoral
maltracking; if nonsurgical treatments
fail, revision TKA with scar excision
may be required.
Patellar clunk syndrome is specific
to the posterior-stabilized TKA.11
Fibrous tissue deposition in the form
of a nodule accumulates on the
posterior surface of the quadriceps
tendon within the knee joint. This
tissue then impinges within the
femoral cam in the PS TKA during
knee extension, causing an audible A diagnostic algorithm for workup of TKA. TKA = total knee arthroplasty
and often painful clunk. This syn-
drome can be treated with excision If the above-described algorithm be considered, such as synovitis,
of the nodule, in either an open or fails to result in a definitive diagnosis, recurrent hemarthrosis, neuralgia,
arthroscopic fashion.44 rarer causes of painful TKA can worker’s compensation, fibromyalgia,

Month 2019, Vol 00, No 00 7

Copyright © the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
Evaluating the painful TKA
tourniquet-induced thigh pain, psy-
chiatric disease, or metal sensitivity.
Recently, metal hypersensitivity
has been reported as a cause of pain
and swelling after TKA and also has
been suggested as a diagnosis of
exclusion in the symptomatic patient
postoperatively.45 Patients may pre-
sent with a history of allergy to nickel
or other metals; however, nonallergic
patients have also been reported to
sustain this complication. Nam et al46
demonstrated metal allergy as a risk
factor for reduced functional out-
comes in patients undergoing elective
total joint arthroplasty. Other studies
describe a lack of evidence indicating
that metal hypersensitivity is directly
linked to implant failure.47 Rather, an
allergic response to metal implants
may indirectly lead to accelerated rates
of loosening and then propagating
implant failure. Currently, there is a
paucity of evidence conclusively
demonstrating that metal hypersensi-
tivity causes accelerated failure after
TKA. If metal sensitivity is suspected,
cutaneous patch testing should not be
used; instead, lymphocyte transfor-
mation test is recommended.
Future Directions
Biomarkers to diagnose PJI and early
wear/osteolysis after TKA are cur-
rently under investigation. Next-
generation RNA sequencing, ranging
from targeted to whole transcriptome
analyses, has been reported as a useful
adjunct to the workup of PJI48; how-
ever, such advanced testing may not
be ubiquitously available and may
be limited by financial constraints.
Numerous studies have reported bio-
marker identification of bone turnover
associated with wear-induced os-
teolysis, and a meta-analysis pre-
sented potential candidates, such as
N-telopeptide collagen fragments,
osteoprotegerin, receptor activator
of nuclear factor kappa-B ligand,
and various ILs.49 Another meta-
8 Journal of the American Academy of Orthopaedic Surgeons
Copyright © the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
analysis concluded that no specific
biomarker has been reproducibly
validated as an indicator or diagnostic
tool for periprosthetic wear.50 Further
studies identifying the expression of
serum and synovial biomarkers in
these pathologic processes are needed.
Novel imaging modalities, such as
positron emission tomography with
18F-fludeoxyglucose (FDG) and 11C-
PK11195 with CT, have been used to
assess loosening (ie, septic versus
aseptic) in a rodent model showing
that tracer uptake of C-PK11195 was
greater in animals with aseptic (versus
septic) loosening, whereas F-FDG was
greater in animals with septic (versus
aseptic) loosening.51 An analysis of
tracer distribution in 18F-sodium
fluoride (NaF) positron-emission
tomography/CT in TKA was corre-
lated with implant stability in eight
zones around the TKA implants up to
25 months postoperatively.52
Summary
Evaluation of the painful TKA is a
complex clinical challenge. Precise
history taking paired with a thorough
clinical examination, thoughtful use
of imaging modalities, laboratory
analyses, and ancillary testing, and a
stepwise diagnostic approach are
crucial tools for correctly identifying
the etiology and origin of pain in the
postoperative setting of TKA. The
authors recommend a detailed, algo-
rithmic approach to the painful TKA,
which results in the best chance of
successfully determining the source of
pain. Once a diagnosis is confirmed,
treatment may range from nonsurgical
measures to complex revision TKA.
References
References printed in bold type are
those published within the past 5
years.
1. Núñez M, Lozano L, Núñez E, et al: Total
knee replacement and health-related quality
of life: Factors influencing long-term
outcomes. Arthritis Rheum 2009;61:
1062-1069.
2. Bourne RB, Chesworth BM, Davis AM,
Mahomed NN, Charron KDJ: Patient
satisfaction after total knee arthroplasty:
Who is satisfied and who is not? Clin
Orthop Relat Res 2010;468:57-63.
3. Inacio MCS, Paxton EW, Graves SE,
Namba RS, Nemes S: Projected increase in
total knee arthroplasty in the United States:
An alternative projection model.
Osteoarthr Cartil 2017;25:1797-1803.
4. Bozic KJ, Lau E, Ong K, et al: Risk factors
for early revision after primary TKA in
Medicare patients. Clin Orthop Relat Res
2014;472:232-237.
5. Mont MA, Serna FK, Krackow KA,
Hungerford DS: Exploration of
radiographically normal total knee
replacements for unexplained pain. Clin
Orthop Relat Res 1996;216-220.
6. Dennis DA: Evaluation of painful total knee
arthroplasty. J Arthroplasty 2004;19:
35-40.
7. Kapadia BH, Berg RA, Daley JA, Fritz J,
Bhave A, Mont MA: Periprosthetic joint
infection. Lancet 2016;387:386-394.
8. Scott RD: Femoral and tibial component
rotation in total knee arthroplasty:
Methods and consequences. Bone Joint J
2013;95-B:140-143.
9. Vince KG: Diagnosis and management of
patients with instability of the knee. Instr
Course Lect 2012;61:515-524.
10. Hagedorn J, Levine BR: Revision surgery
for a dislocated constrained total knee
arthroplasty. Orthopedics 2012;35:
e1099-e1103.
11. Su EP, Su SL, Della Valle AG: Stiffness after
TKR: How to avoid repeat surgery.
Orthopedics 2010;33:658.
12. Maeno S, Kondo M, Niki Y, Matsumoto H:
Patellar impingement against the tibial
component after total knee arthroplasty.
Clin Orthop Relat Res 2006;452:265-269.
13. Petersen W, Rembitzki IV, Brüggemann
GP, et al: Anterior knee pain after total knee
arthroplasty: A narrative review. Int
Orthop 2014;38:319-328.
14. Hozack WJ, Cole PA, Gardner R, Corces A:
Popliteal aneurysm after total knee
arthroplasty: Case reports and review of the
literature. J Arthroplasty 1990;5:301-305.
15. Pandher DS, Boparai RS, Kapila R: Biceps
tendinitis as a cause of acute painful knee
after total knee arthroplasty. J Arthroplasty
2009;24:1292-1298.
16. Tensho K, Aoki T, Morioka S, Narita N,
Kato H, Saito N: Snapping pes syndrome
after total knee arthroplasty. Knee Surg
Sports Traumatol Arthrosc 2014;22:
192-194.

17. Levinger P, Menz HB, Morrow AD, Feller
JA, Bartlett JR, Bergman NR: Lower limb
biomechanics in individuals with knee
osteoarthritis before and after total knee
arthroplasty surgery. J Arthroplasty 2013;
28:994-999.
18. Lemaire R: Fatigue fracture of the femoral
component in a mobile bearing knee
prosthesis. Acta Orthop Belg 2010;76:
274-281.
19. Granchi D, Cenni E, Tigani D, Trisolino G,
Baldini N, Giunti A: Sensitivity to implant
materials in patients with total knee
arthroplasties. Biomaterials 2008;29:
1494-1500.
20. Worland RL, Arredondo J, Angles F,
Lopez-Jimenez F, Jessup DE: Thigh pain
following tourniquet application in
simultaneous bilateral total knee
replacement arthroplasty. J Arthroplasty
1997;12:848-852.
21. Thakur RR, Ast MP, McGraw M, Bostrom
MP, Rodriguez JA, Parks ML: Severe
persistent synovitis after cobalt-chromium
total knee arthroplasty requiring revision.
Orthopedics 2013;36:e520-e524.
22. Saksena J, Platts AD, Dowd GS: Recurrent
haemarthrosis following total knee
replacement. Knee 2010;17:7-14.
23. D’Apuzzo MR, Cabanela ME, Trousdale
RT, Sierra RJ: Primary total knee
arthroplasty in patients with fibromyalgia.
Orthopedics 2012;35:e175-e178.
24. Roth KE, Salzmann G, Maier GS,
Schmidtmann I, Rompe JD, Babin K: Risk
factors for heterotopic ossification and spur
formation after total knee arthroplasty.
Arch Orthop Trauma Surg 2014;134:
991-996.
25. Saleh K, Nelson C, Kassim R, Yoon P, Haas
S: Total knee arthroplasty in patients on
workers’ compensation: A matched cohort
study with an average follow-up of 4.5
years. J Arthroplasty 2004;19:310-312.
26. Lopez-Olivo MA, Landon GC, Siff SJ, et al:
Psychosocial determinants of outcomes in
knee replacement. Ann Rheum Dis 2011;
70:1775-1781.
27. Lonner JH, Siliski JM, Scott RD:
Prodromes of failure in total knee
arthroplasty. J Arthroplasty 1999;14:
488-492.
28. Al-Hadithy N, Rozati H, Sewell MD,
Dodds AL, Brooks P, Chatoo M: Causes
of a painful total knee arthroplasty: Are
patients still receiving total knee
Month 2019, Vol 00, No 00
Copyright © the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.
arthroplasty for extrinsic pathologies? Int
Orthop 2012;36:1185-1189.
29. Nahabedian MY, Johnson CA: Operative
management of neuromatous knee pain:
Patient selection and outcome. Ann Plast
Surg 2001;46:15-22.
30. Polkowski GG, Ruh EL, Barrack TN,
Nunley RM, Barrack RL: Is pain and
dissatisfaction after TKA related to early-
grade preoperative osteoarthritis? Clin
Orthop Relat Res 2013;471:162-168.
31. Math KR, Zaidi SF, Petchprapa C, Harwin
SF: Imaging of total knee arthroplasty.
Semin Musculoskelet Radiol 2006;10:
47-63.
32. Behery OA, Kearns SM, Rabinowitz JM,
Levine BR: Cementless vs cemented tibial
fixation in primary total knee arthroplasty.
J Arthroplasty 2017;32:1510-1515.
33. Berger RA, Crossett LS, Jacobs JJ,
Rubash HE: Malrotation causing
patellofemoral complications after total
knee arthroplasty. Clin Orthop Relat Res
1998;144-153.
34. Palestro CJ: Nuclear medicine and the failed
joint replacement: Past, present, and future.
World J Radiol 2014;6:446-458.
35. Parvizi J, Della Valle CJ: AAOS clinical
practice guideline: Diagnosis and treatment
of periprosthetic joint infections of the hip
and knee. J Am Acad Orthop Surg 2010;18:
771-772.
36. Christensen CP, Bedair H, Della Valle CJ,
Parvizi J, Schurko B, Jacobs CA: The
natural progression of synovial fluid white
blood-cell counts and the percentage of
polymorphonuclear cells after primary total
knee arthroplasty. J Bone Joint Surg 2013;
95:2081-2087.
37. Parvizi J, Ghanem E, Sharkey P, Aggarwal
A, Burnett RS, Barrack RL: Diagnosis of
infected total knee: Findings of a
multicenter database. Clin Orthop Relat
Res 2008;466:2628-2633.
38. Kim SG, Kim JG, Jang KM, Han SB, Lim
HC, Bae JH: Diagnostic value of synovial
white blood cell count and serum C-reactive
protein for acute periprosthetic joint
infection after knee arthroplasty. J
Arthroplasty 2017;32:3724-3728.
39. Yi PH, Cross MB, Moric M, Sporer SM,
Berger RA, Della Valle CJ: The 2013 Frank
Stinchfield Award: Diagnosis of infection in
the early postoperative period after total hip
arthroplasty. Clin Orthop Relat Res 2014;
472:424-429.
Michael A. Flierl, MD, et al
40. Lee YS, Koo K-H, Kim HJ, et al: Synovial
fluid biomarkers for the diagnosis of
periprosthetic joint infection: A systematic
review and meta-analysis. J Bone Joint Surg
Am 2017;99:2077-2084.
41. Vince KG, Abdeen A, Sugimori T: The
unstable total knee arthroplasty. J
Arthroplasty 2006;21:44-49.
42. Song SJ, Detch RC, Maloney WJ,
Goodman SB, Huddleston JI: Causes of
instability after total knee arthroplasty. J
Arthroplasty 2014;29:360-364.
43. Issa K, Banerjee S, Kester MA, Khanuja HS,
Delanois RE, Mont MA: The effect of
timing of manipulation under anesthesia to
improve range of motion and functional
outcomes following total knee arthroplasty.
J Bone Joint Surg Am 2014;96:1349-1357.
44. Lucas TS, DeLuca PF, Nazarian DG,
Bartolozzi AR, Booth RE: Arthroscopic
treatment of patellar clunk. Clin Orthop
Relat Res 1999;226-229.
45. Lachiewicz PF, Watters TS, Jacobs JJ:
Metal hypersensitivity and total knee
arthroplasty. J Am Acad Orthop Surg 2016;
24:106-112.
46. Nam D, Li K, Riegler V, Barrack RL:
Patient-reported metal allergy: A risk factor
for poor outcomes after total joint
arthroplasty? J Arthroplasty 2016;31:
1910-1915.
47. Middleton S, Toms A: Allergy in total knee
arthroplasty: A review of the facts. Bone
Joint J 2016;98-B:437-441.
48. Tarabichi M, Shohat N, Goswami K, et al:
Diagnosis of periprosthetic joint infection. J
Bone Jt Surg 2018;100:147-154.
49. Bauer TW, Shanbhag AS; Implant Wear
Symposium 2007 Biologic Work Group:
Are there biological markers of wear? J Am
Acad Orthop Surg 2008;16(suppl 1):
S68-S71.
50. Sumner DR, Ross R, Purdue E: Are there
biological markers for wear or corrosion? A
systematic review. Clin Orthop Relat Res
2014;472:3728-3739.
51. Ren W, Muzik O, Jackson N, et al:
Differentiation of septic and aseptic
loosening by PET with both 11C-PK11195
and 18F-FDG in rat models. Nucl Med
Commun 2012;33:747-756.
52. Son HJ, Jeong YJ, Yoon HJ, et al: Visual
pattern and serial quantitation of 18F-
sodium fluoride PET/CT in asymptomatic
patients after hip and knee arthroplasty.
Nucl Med Mol Imaging 2016;50:308-321.
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