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Incidence and risk factors of prosthetic joint infection after total hip or knee replacement in patients with rheumatoid arthritis.

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Arthritis & Rheumatism (Arthritis Care & Research)
Vol. 59, No. 12, December 15, 2008, pp 1713–1720
DOI 10.1002/art.24060
© 2008, American College of Rheumatology
ORIGINAL ARTICLE
Incidence and Risk Factors of Prosthetic Joint
Infection After Total Hip or Knee Replacement in
Patients With Rheumatoid Arthritis
TIM BONGARTZ, CHRISTINE S. HALLIGAN, DOUGLAS R. OSMON, MEGAN S. REINALDA,
WILLIAM R. BAMLET, CYNTHIA S. CROWSON, ARLEN D. HANSSEN, AND ERIC L. MATTESON
Objective. Prosthetic joint infection is one of the most dreaded complications after total joint arthroplasty, a common
procedure in patients with rheumatoid arthritis (RA). We conducted a study to evaluate potential risk factors of prosthetic
joint infection and to clarify if RA is an independent predictor of this complication.
Methods. This study included all patients with RA who underwent total hip or knee replacement at the Mayo Clinic
Rochester between January 1996 and June 2004. The association of potential risk factors with prosthetic joint infection
was examined using Cox models. A matched cohort of patients with osteoarthritis (OA) was assembled to determine
whether RA is an independent risk factor for prosthetic joint infection.
Results. We identified 462 patients with RA who underwent a total of 657 hip or knee replacements. Overall, 23 (3.7%)
joint arthroplasties were complicated by an infection during a mean ⴞ SD followup of 4.3 ⴞ 2.4 years. Revision
arthroplasty (hazard ratio [HR] 2.99, 95% confidence interval [95% CI] 1.02– 8.75) and a previous prosthetic joint
infection of the replaced joint (HR 5.49, 95% CI 1.87–16.14) were significant predictors of postoperative prosthetic
joint infection. Comparison of RA patients with a matched cohort of OA patients identified an increased risk of prosthetic
joint infections (HR 4.08, 95% CI 1.35–12.33) in patients with RA.
Conclusion. Patients with RA who undergo total hip or knee replacement are at increased risk of prosthetic joint
infection, which is further increased in the setting of revision arthroplasty and a previous prosthetic joint infection. These
findings highlight the importance of perioperative prophylactic measures and vigilance during the postoperative period.
INTRODUCTION
Joint replacement surgery is used extensively to alleviate
pain and improve mobility in patients who develop severe
Supported by the NIH (grant 1-K24-AR-47578-01A1), the
David A. Oreck and L. A. Eaton Research Awards, and the
Mayo Foundation.
Tim Bongartz, MD, Christine S. Halligan, MD (current
address: Orthopedic Institute, Sioux Falls, South Dakota),
Douglas R. Osmon, MD, Megan S. Reinalda, BS, William R.
Bamlet, MS, Cynthia S. Crowson, MS, Arlen D. Hanssen,
MD, Eric L. Matteson, MD, MPH: Mayo Clinic College of
Medicine, Rochester, Minnesota.
Dr. Bongartz has received consultant fees, speaking fees,
and/or honoraria (more than $10,000) from Wyeth, and educational grants (more than $10,000) from Amgen. Dr. Matteson has received consultant fees (less than $10,000 each)
from Abbott and Amgen, and grants (more than $10,000
each) from Wyeth and Amgen.
Address correspondence to Tim Bongartz, MD, Mayo
Clinic College of Medicine, Division of Rheumatology, 200
1st Street SW, Rochester, MN 55905. E-mail: bongartz.
tim@mayo.edu.
Submitted for publication April 4, 2008; accepted in revised form July 11, 2008.
destructive changes of their joints as a result of inflammatory or degenerative musculoskeletal diseases. Among the
most dreaded complications of these procedures is prosthetic joint infection. This complication causes significant
morbidity and accounts for a substantial amount of health
care expenditures for patients. Although the use of rigorous preventive measures such as perioperative antimicrobial prophylaxis has reduced the rate of postoperative
prosthesis infections to less than 2%, the frequent use of
this procedure in more than 600,000 Americans per year
suggests a projected infection rate of 12,000 implants per
year (1).
Prosthetic joint infection often requires removal of the
infected prosthesis and prolonged intravenous antimicrobial therapy and has a mortality rate of 2.7–18%. The cost
of each infection episode is estimated to be in excess of
$50,000 (2,3).
Total joint replacement is a common procedure in patients with rheumatoid arthritis (RA). This patient population has been identified to have a higher baseline risk of
infectious diseases compared with the general population
(4,5). In addition, the immunosuppressive drugs used in
the treatment of RA may further increase the risk of infec1713
1714
Bongartz et al
tion (5,6). Identification of patients with RA as being at
higher risk for prosthetic joint infection compared with
non-RA patients would be an important first step toward
improved preoperative assessment and development of
preventive strategies.
Several studies have explored the risk of prosthetic joint
infection in patients with RA (7–18), but most of these
studies were conducted between 1969 and 1993. Patients
who undergo total joint replacement at present may differ
significantly from these early cohorts because the utilization of preventive measures, such as perioperative antibiotics, has changed over time. New treatment approaches
for patients with RA, including earlier use of diseasemodifying antirheumatic drugs (DMARDs) and the advent
of biologic drugs such as anti–tumor necrosis factor (antiTNF) inhibitors, may have significantly altered the risk of
perioperative complications in these patients. More importantly, the validity of many existing trials is limited by
methodologic problems such as no application of acknowledged criteria for a diagnosis of RA by a rheumatologist (7–18), lack of an explicit definition of prosthetic
joint infection (8,9,11–13,15), and no matching or adjustment for known risk factors such as age, site, or primary
versus revision arthroplasty (8 –12,15). Not surprisingly,
conclusions reached by these studies differ widely: while
some studies reported an increased risk of prosthetic joint
infection in patients with RA (7,8,10,11,13,15,17), others
did not support this conclusion (9,14,16,18). Assessments
of potential risk factors such as maintenance of DMARD
therapy were inconclusive, with some trials arguing in
favor (19,20) and some against (21,22) an association between DMARD therapy and prosthesis infection.
In light of conflicting results presented in these studies
and based on the identification of their potential sources of
bias, we formulated the following methodologic standards
for a study of infection risk in patients with RA undergoing
joint arthroplasty: modern cohort of patients with RA after
Food and Drug Administration licensing and approval of
anti-TNF treatment, verified diagnosis of exposure status
(RA/osteoarthritis [OA]), documented followup for at least
1 year, reproducible criteria for outcome (prosthesis infection), and adjustment/matching for potential confounders
when comparing patients with OA and those with RA.
Based on these standards, we aimed to determine the
cumulative and 1-year incidence of prosthetic joint infection in total hip arthroplasty (THA) and total knee arthroplasty (TKA) in a modern cohort of patients with RA and
to further explore potential risk factors for these infections.
In addition, we intended to evaluate whether this complication is more frequent in patients with RA as compared
with patients with OA who undergo the same type of
surgery.
Board approval was obtained for the study prior to its
commencement. All surgeries were performed by trained
Mayo Clinic staff orthopedists in a single facility. By medical record review, patients were followed for at least 1
year after surgery. Cases of THA or TKA infection were
recorded to calculate a cumulative incidence of this complication and to evaluate potential associations with clinical variables.
To compare the infection risks of patients with RA versus patients with OA, a second, matched cohort was assembled consisting of patients with OA who underwent a
THA or TKA within the same time period.
PATIENTS AND METHODS
Verification of diagnosis in the OA cohort. ACR criteria
for hip and knee OA (25,26) proved to be not useful for
retrospective assessment because these criteria contain
several clinical, radiographic, and laboratory data that
were not documented in the medical records in a majority
of cases. Therefore, the diagnosis of OA was verified during chart review using the following alternative criteria:
Overview of the study design. We conducted a retrospective, single-center, double-cohort study that included
all patients with a diagnosis of RA who underwent a THA
or TKA at the Mayo Clinic Rochester between January
1996 and June 2004. Mayo Clinic Institutional Review
Patients. The Mayo Clinic Total Joint Registry includes
all patients who have undergone total joint surgery at the
Mayo Clinic Rochester since 1969 (23). In addition to
patient demographic data, the underlying disease diagnosis leading to surgery, site of joint replacement, year of
surgery, and perioperative complications are recorded in
this registry. All patients are followed up by surgeon examination at least twice in the first postsurgical year and
then at least every 5 years thereafter. If followup examination at the Mayo Clinic was not possible, patients were
contacted by letter and/or telephone and asked to complete a standardized data collection form.
The records of all patients with a registry diagnosis of
RA who underwent a THA or TKA at the Mayo Clinic
between January 1, 1996 and June 30, 2004 were retrieved.
Verification of RA diagnosis. A medical record review
of all patients with a diagnosis of RA in the total joint
registry was performed. Each patient’s diagnosis of RA was
verified using validated RA classification criteria. This
step was mandatory because some patients were expected
to be incorrectly coded as having RA in the database.
Patients were only enrolled in the RA cohort if they met
the American College of Rheumatology (ACR; formerly the
American Rheumatism Association) classification criteria
(24). If the information available through chart review was
not sufficient for the verification of diagnosis, the treating
rheumatologist/primary physician was contacted to complete the clinical information assessment.
Matching of the control cohort of patients with OA.
Patients with RA were matched to patients with OA. The
records of patients with a diagnosis of OA and no diagnosis of RA were retrieved from the total joint registry. Using
a computer matching algorithm, a 1:1 matching was performed according to patient age (⫾ 5 years), site (hip or
knee), type (revision/primary arthroplasty), and time point
of first Mayo surgery.
Risk Factors of Prosthetic Joint Infection in RA Patients
Table 1. Time definitions for perioperative diseasemodifying antirheumatic drug therapy to be considered
as stopped
Medication
No. days
medication not
administered
Methotrexate
Leflunomide
Oral gold
Intramuscular gold
Sulfasalazine
Hydroxychloroquine
Azathioprine
Cyclosporine
Cyclophosphamide
D-penicillamine
Etanercept
Adalimumab
Infliximab
Anakinra
8
85 or 14*
8
29
8
85
8
8
8
15
8
15
57
8
* With cholestyramine wash-out.
physician’s diagnosis of hip and/or knee OA and absence
of a physician’s diagnosis of an inflammatory joint disease.
These criteria were validated against patients with a
diagnosis of RA and a diagnosis of OA according to the
following reference standard: radiograph consistent with
OA, no previous diagnosis of RA or other inflammatory
joint disease, and at least 1 year of followup information
after the initial OA diagnosis from the primary physician
of each patient by telephone interview. Based on 2 random
samples of 60 patients for each group drawn from the total
joint registry, we calculated the following test characteristics for our OA classification criteria: sensitivity 95.08%
(95% confidence interval [95% CI] 86.08 –98.96%) and
specificity 96.67% (95% CI 88.47–99.59%).
Data collection. Data in both cohorts were collected by
medical record review for each patient. In case of missing
information or followup ⬍1 year after first surgery, direct
telephone interviews with primary care providers and/or
treating rheumatologists were performed. Data were abstracted during the review process by 3 abstractors. Multiple variables were ascertained through this process: date
of birth, sex, time of prosthesis implantation, site of surgery, type of surgery (primary or revision arthroplasty),
comorbidities (according to physician’s diagnosis), Steinbrocker functional class criteria (27), and use of steroids at
time of surgery.
If DMARD therapy was withheld around the time of
surgery, the stop and start dates were abstracted. Based on
the pharmacokinetic half-life and/or data on the biologic
activity of each DMARD, criteria for a strict definition of
withheld versus maintained were developed (Table 1).
According to these criteria, perioperative DMARD use was
judged as either withheld or maintained.
Outcome variable. An established set of criteria (28,29)
was used to detect and verify the diagnosis of prosthetic
1715
joint infection. At least 1 of the following had to be
present: isolation of the same microorganism from ⱖ2
cultures of joint aspirates or intraoperative tissue specimens, acute inflammation consistent with infection on
histopathologic examination (as determined by the pathologist), cutaneous sinus tract communicating with the joint
prosthesis, and/or purulence in the joint space (as determined by the surgeon).
The Total Joint Registry provides a thorough followup of
patients who underwent total joint replacement at the
Mayo Clinic, ensuring almost complete ascertainment of
adverse events related to the joint replacement. Again, for
outstanding or unclear issues as well as for a followup ⬍1
year, primary physicians were contacted.
Statistical analysis. The proportion of surgeries complicated by a prosthetic joint infection was estimated using
Kaplan-Meier techniques (30). Cox proportional hazards
models were used to examine the association between the
risk of prosthetic joint infection for several explanatory
variables including age at surgery date, sex, type of surgery (revision versus primary), site of surgery (hip versus
knee), presence of comorbidities, RA disease duration,
patient functional status, and DMARD therapy at time of
surgery (withheld/maintained). Cox models were also used
to compare the risk of infection between the RA and OA cohorts. For these models, only the first surgery at our institution was used for each patient, and followup was censored at the time of a subsequent surgery or last followup.
RESULTS
Patient results. During the period from January 1, 1996
to June 30, 2004, 661 patients with a diagnosis of RA in the
Total Joint Registry underwent a THA or TKA at the Mayo
Clinic Rochester. After strict application of the 1987 ACR
consensus criteria for the classification of RA (24) during
chart review by a rheumatologist, 461 (69.7%) of these
patients could be classified as having RA. In 19 cases,
medical records did not provide sufficient information to
either reject or confirm a diagnosis of RA. Primary physicians and/or rheumatologists of these patients were contacted by telephone to request information on classification criteria. In 9 of these 19 patients, a diagnosis of RA
could be confirmed. As a result, 470 patients with a reliable diagnosis of RA were included in our RA cohort.
Followup. Medical charts provided sufficient information for at least 1 year of followup in the vast majority of
patients. However, in 18 patients, followup information
was not sufficient. In 10 of these patients, followup data
could be obtained through telephone interviews with
treating rheumatologists or primary physicians.
In 8 cases, followup data could not be obtained and
patients were excluded from our cohort, for a total of 462
patients. The flow of patients into our RA cohort is depicted in Figure 1.
Patient characteristics. The cohort comprised 462 patients with RA with a mean age of 64 years at their first
1716
Bongartz et al
The most common organism isolated from infected prosthetic joints was Staphylococcus aureus in 15 (65.2%)
cases, followed by 4 (17.4%) cases of streptococcal infection, 2 (8.7%) gram-negative bacilli infections, and 1 fungal infection. Sixteen patients were treated with prosthesis
removal, and 6 of these patients had a subsequent prosthesis reimplantation. Seven patients were treated with debridement and long-term antibiotic suppression therapy.
The details of prosthetic joint infections that occurred in
our cohort are summarized in Table 3.
Figure 1. Flow of patients into the rheumatoid arthritis (RA)
cohort. SpA ⫽ spondylarthritis; SLE ⫽ systemic lupus erythematosus; GCA ⫽ giant cell arteritis; ACR ⫽ American College of
Rheumatology.
total joint surgery between 1996 and 2004 at the Mayo
Clinic Rochester. The mean disease duration was 21.1
years, with a mean followup of 4.3 years after the first
surgery. The majority of patients were female (78.6%).
Surgery characteristics. The 462 patients with RA underwent a total of 657 THA or TKA surgeries during the
study period. Of these surgeries, 61.2% were primary and
38.8% were revision surgeries. There were almost equal
numbers of THA (328 [50.0%]) and TKA (329 [50.0%]).
Approximately one-third of the surgeries were performed
with antibiotic impregnated cement. The functional status
of the majority of patients at the time of surgery was
classified as class 2 (40.3%) or class 3 (39.3%). Surgery
characteristics are summarized in Table 2.
Immunosuppressive medication use at the time of surgery. Patients were receiving DMARDs prior to surgery in
429 cases. During 222 (33.8%) surgeries, at least 1 of these
DMARDs was withheld perioperatively according to the
definitions given above. In 341 (51.9%) procedures, patients received steroids on the day of surgery in a median
dosage of 10 mg/day. The differing mean value of 29 mg/
day reflects the application of a steroid bolus at the time of
surgery in some patients and the subsequent skewedness
of steroid doses to higher values.
Incidence of prosthesis infections. Overall, 23 (3.7%) of
657 surgeries in patients with RA were complicated by a
prosthetic joint infection. This included 14 (2.2%) prostheses that became infected during the first postoperative
year. The majority of prosthetic joint infections occurred
after revision arthroplasties: 255 revision arthroplasties
were complicated by 15 (5.9%) infections as compared
with 8 (2.0%) infections in 402 primary procedures. Seven
(30.4%) of the 23 infections were observed in joints that
had been affected by a previous prosthetic joint infection.
Twelve (52.2%) infections were in the hip and 11 (47.8%)
infections were in the knee.
Predictors associated with prosthesis infections in patients with RA. Considering the first surgery at our institution for each patient, univariate analysis revealed 3 statistically significant predictors of an increased prosthesis
infection risk: revision arthroplasty (hazard ratio [HR]
2.99, 95% CI 1.02– 8.75), previous infection of the replaced
joint (HR 5.49, 95% CI 1.87–16.14), and operation time
(HR 1.36 per 60-minute increase, 95% CI 1.02–1.81). Other
potential risk factors such as age, disease duration, site
of surgery, and functional class were not significantly associated with the occurrence of prosthesis infections
(Table 4).
Perioperative management of immunosuppressive therapies was highly heterogeneous and did not show any
apparent association with patient age, disease severity, or
comorbidities. In 336 of 657 surgeries, patients were receiving at least 1 DMARD within 3 months prior to the
procedure. DMARD therapy was withheld perioperatively
in 57% of these procedures according to the definitions
given in the Patients and Methods section.
Stopping DMARD therapy at the time of surgery lowered
the risk of subsequent prosthesis infection (HR 0.65, 95%
CI 0.09 – 4.95), but this was statistically not significant.
There were 3 prosthesis infections in 38 patients who were
Table 2. Characteristics of 657 surgeries in 462 patients
with rheumatoid arthritis*
Characteristic
Type of surgery
Primary
Revision
Joint replaced
Primary THA
Revision THA
Primary TKA
Revision TKA
Perioperative systemic prophylactic
antibiotics
Antibiotic impregnated cement used
Steinbrocker functional classification at
time of surgery
Class 1 (patient normally active)
Class 2 (patient able to maintain
occupation but less active)
Class 3 (unable to maintain occupation)
Class 4 (largely or wholly incapacitated)
Unknown
Value
402 (61.2)
255 (38.8)
164 (25.0)
164 (25.0)
238 (36.2)
91 (13.8)
656 (99.9)
209 (31.8)
6 (1.0)
265 (40.3)
258 (39.3)
121 (18.4)
7 (1.0)
* Values are the number (percentage). THA ⫽ total hip arthroplasty;
TKA ⫽ total knee arthroplasty.
Risk Factors of Prosthetic Joint Infection in RA Patients
Table 3. Characteristics of 23 infections following 657
surgeries among 462 patients with rheumatoid arthritis*
Characteristic
Time from surgery to infection, years
Mean ⫾ SD
Median (interquartile range)
Joint replaced
Primary THA
Revision THA
Primary TKA
Revision TKA
Type of surgery
Primary
Revision
Infection site
Hip
Knee
Prosthesis age at time of infection
diagnosis
ⱕ30 days
31–365 days
ⱖ366 days
No. of revisions of the index joint
0
1
2
3
4
Prior prosthetic joint infection in index
joint
Surgery performed on infected joint
No surgery
Debridement only
Removal only
Removal and reimplantation
Organism
Staphylococci
Streptococci
Gram-negative bacilli
Other
Value
1.1 ⫾ 1.53
0.3 (0.1–0.8)
2 (8.7)
10 (43.5)
6 (26.1)
5 (22.7)
8 (34.8)
15 (65.2)
12 (52.2)
11 (47.8)
8 (34.8)
6 (26.1)
9 (39.1)
8 (34.8)
6 (26.1)
6 (26.1)
1 (4.3)
2 (8.7)
7 (30.4)
3 (13.0)
4 (17.4)
10 (43.5)
6 (26.1)
15 (65.2)
4 (17.4)
2 (8.7)
5 (22.7)
* Values are the number (percentage) unless otherwise indicated.
THA ⫽ total hip arthroplasty; TKA ⫽ total knee arthroplasty.
treated with anti-TNF agents at the time of surgery as
compared with no infection in 12 patients who stopped
their anti-TNF therapy prior to surgery. This difference
was not statistically significant. Perioperative corticosteroid use was not associated with an increased risk of
prosthesis infections.
Is RA an independent risk factor for prosthesis infection? Each of the 462 patients with RA was matched to a
patient with OA according to age, sex, site of surgery, and
type of arthroplasty (primary versus revision). Characteristics of both cohorts are shown in Table 5. Compared with
patients with OA, those with RA had a higher prevalence
of comorbidities and impaired physical functioning. Patients in both cohorts were censored at last followup or
second surgery for these analyses. The mean ⫾ SD followup time was 3.1 ⫾ 2.4 years for patients with RA and
3.8 ⫾ 2.6 years for patients with OA, corresponding to
1,427 and 1,760 person-years of followup, respectively.
1717
During followup, a total of 15 patients with RA (4.2% at
5 years) and 4 patients with OA (1.4% at 5 years) developed a prosthesis infection (log rank P ⫽ 0.005). The
higher risk in patients with RA was statistically significant
(HR 4.08, 95% CI 1.35–12.33), even after adjusting for
previous infection in the index joint (HR 3.74, 95% CI
1.23–11.33). Age, sex, functional class, and comorbidity
were not significant predictors of infection.
When restricting the analysis to infections diagnosed
within the first year after surgery, 10 patients with RA
(2.3% at 1 year) and 1 patient with OA developed an
infection. Again, the excess risk for patients with RA was
statistically significant (odds ratio 10.30, 95% CI 1.31–
80.26).
DISCUSSION
Although advances in preventive strategies have contributed to a decline in prosthetic joint infection following
total joint replacements, this serious complication was
observed in 4.2% of total hip or knee replacements in RA
patients by 5 years after the surgery. This estimate of risk
for hip and knee prosthesis infections is consistent with
previous studies. Fitzgerald et al reported a deep infection
after hip replacement in 3.1% of 223 RA patients (17).
Wilson et al (8) observed a prosthesis infection in 2.2% of
2,076 knee replacements. However, a direct comparison is
hampered due to nonreporting of a mean followup and
losses to followup in these trials.
Elbow, finger, and shoulder arthroplasties were not ac-
Table 4. Univariate analysis of potential predictors of
prosthetic joint infection in 462 patients with
rheumatoid arthritis*
Risk factor
Age (per 10-year increase)
Revision arthroplasty
Male sex
Disease duration, years
⬍10
10–20
20–30
⬎30
TKA vs. THA
DMARD therapy withheld
Corticosteroid use
Operative time (per 60-minute
increase)
Functional class (Steinbrocker)
1 and 2
3
4
Comorbidities
Extraarticular disease manifestations
Previous infection at index joint
Previous infection at any joint
Hazard ratio
(95% CI)
0.86 (0.61–1.22)
2.99 (1.02–8.75)
1.31 (0.42–4.12)
1.0
0.18 (0.02–1.59)
0.89 (0.24–3.32)
1.05 (0.28–3.91)
0.91 (0.33–2.50)
0.65 (0.09–4.95)
1.28 (0.46–3.60)
11.36 (1.02–1.81)
1.0
1.30 (0.40–4.27)
1.87 (0.50–6.96)
1.03 (0.33–3.24)
1.01 (0.36–2.78)
5.49 (1.87–16.14)
4.18 (1.43–12.25)
* 95% CI ⫽ 95% confidence interval; TKA ⫽ total knee arthroplasty; THA ⫽ total hip arthroplasty; DMARD ⫽ disease-modifying
antirheumatic drug.
1718
Bongartz et al
Table 5. Characteristics of 462 patients with OA and 462 patients with RA*
Characteristic
OA patients
RA patients
Female sex
Age at first Mayo surgery, years
Mean ⫾ SD
Median (IQR)
Length of followup, years
Mean ⫾ SD
Median (IQR)
Joint replaced
Primary THA
Revision THA
Primary TKA
Revision TKA
Type of surgery
Primary
Revision
Surgery on knee
Functional class
Class 1
Class 2
Class 3
Class 4
Unknown
At least 1 comorbidity
Previous prosthetic infection in
index joint
338 (73.2)
363 (78.6)
67.2 ⫾ 10.8
67.8 (59.9–76.0)
63.6 ⫾ 13.3
66.2 (55.1–73.8)
P
0.06
⬍ 0.001
–
3.8 ⫾ 2.6
3.3 (1.8–5.7)
3.1 ⫾ 2.4
2.4 (1.1–5.0)
126 (27.3)
112 (24.2)
163 (35.3)
61 (13.2)
117 (25.3)
122 (26.4)
158 (34.2)
65 (14.1)
289 (62.6)
173 (37.4)
224 (48.5)
275 (59.5)
187 (40.5)
223 (48.3)
6 (1.3)
338 (73.2)
108 (23.4)
8 (1.7)
2 (0.4)
383 (83.0)
24 (5.2)
4 (0.9)
183 (39.6)
184 (39.6)
86 (18.6)
6 (1.3)
337 (73.0)
43 (9.3)
0.81
0.34
0.95
⬍ 0.0001
⬍ 0.001
0.02
* Values are the number (percentage) unless otherwise indicated. OA ⫽ osteoarthritis; RA ⫽ rheumatoid
arthritis; IQR ⫽ interquartile range; THA ⫽ total hip arthroplasty; TKA ⫽ total knee arthroplasty.
counted for in our analysis and would contribute an additional life-time risk for prosthetic joint infection in patients with RA.
Previous studies of the frequency, risk factors, and other
aspects of prosthetic joint infection in patients with RA
have been derived from data that relied on an RA diagnosis
not confirmed by a rheumatologist (7–18). It has been
demonstrated that the accuracy of such a diagnosis is low
and the agreement between database and medical record
diagnosis is poor (31). To prevent misclassification of patients as having RA when in fact they do not, we applied
ACR classification criteria to each patient at medical
record and electronic chart review.
Our experience is consistent with the previously observed poor performance of electronic database diagnosis
of RA: 31% of patients who were listed as having RA in the
total joint registry did not meet ACR criteria for the diagnosis of this disease. This high rate of misclassification
represents a serious threat to any estimate derived from an
RA cohort that uses the database diagnosis as the sole
source of diagnostic classification.
Although we did not systematically explore the reasons
for the high rate of misclassification in our database, it
appears unlikely that this discrepancy was due to a low
accuracy of ACR criteria when applied during retrospective chart review. All records were reviewed by experienced rheumatologists who were able to assign an alternative diagnosis to the majority of misclassified patients.
Revision arthroplasty has been identified previously as a
predictor of prosthetic joint infection in mixed cohorts
(including patients with OA and RA) (7,11,17). This observation underlines the importance of adjusting for revision arthroplasty when comparing the frequency of infectious complications between cohorts that have a different
distribution of prosthetic joint revisions.
Consistent with earlier findings (13), our study identified previous prosthetic joint infection of the replaced
joint as a strong risk factor for a subsequent infection after
implantation of a new prosthesis. Of 24 patients with RA
who had a previous prosthetic joint infection and underwent revision arthroplasty, 7 (29.2%) experienced a subsequent prosthetic joint infection. In all of these patients,
multiple methods such as indium scan, intraoperative histology/gram stain, and/or joint aspirations with culture
were used to confirm clearance of the previous infection
prior to implantation of new hardware.
Reimplantation procedures after removal of an infected
prosthesis carry a considerable risk of reinfection. In a
study of 160 patients with RA, a reinfection risk of 21%
and 39% for 2-stage exchange and resection arthroplasty,
respectively, has been reported (32). A reinfection risk of
9 –14% was observed in a mixed cohort of patients who
underwent second-stage reimplantation after a first infection (33).
The high rate of infection in the replaced prosthetic joint
raises the question of whether these reinfections are due to
persistence of bacteria in the replaced joint and a low
sensitivity of the diagnostic methods used to identify their
presence prior to reimplantation, or if the previous infec-
Risk Factors of Prosthetic Joint Infection in RA Patients
tion is simply an indicator of a host with higher infection
susceptibility.
Patients in our study who had a previous prosthetic joint
infection and then subsequent replacement of joints other
than a previously infected joint had a risk of another
infection of only 3.5%, as compared with 29.2% after
revision of the previously infected joint. This finding suggests that these infections are due to undetected persistence of bacteria and not to a general susceptibility to
infections.
Our evaluation of potential predictors of prosthetic joint
infections after hip or knee replacement in patients with
RA also included examination of perioperative DMARD
treatment. Although we found a lower risk of subsequent
prosthesis infections in patients who stopped their
DMARD therapy prior to surgery, our results were statistically not significant. To avoid dilution of a potentially
increased risk with immunosuppression, we excluded
agents that are of lower immunosuppressive potency (hydroxychloroquine and sulfasalazine) and focused our analysis on methotrexate, azathioprine, leflunomide, and biologic response modifiers, including anti-TNF agents and
anakinra. This strategy did not change our estimate of risk.
Our comparison between patients with RA and OA
showed a significantly higher rate of infections in those
with RA after accounting for age, sex, surgery site, and
surgery type by matching. Although several studies support this finding (7,8,10,11,13,14,17), others did not detect
an association between RA and increased risk of prosthesis
infection (9,14,16,18). However, none of these studies
made an attempt to verify a database diagnosis of RA
through application of ACR criteria by a rheumatologist,
some did not apply formal statistical tests (12,15,17), and
only a few adjusted for some potential confounders
(7,14,16 –18) or offered data on completeness of followup
(7,17,18).
Although our 2 cohorts were matched according to several potential confounders such as age, sex, site of surgery,
and type of surgery, we cannot exclude residual confounding when comparing the incidence of prosthetic joint infections between patients with RA and those with OA. For
example, insurance and socioeconomic status were not
abstracted during chart review and may act as unmeasured
confounders.
In conclusion, we are able to provide an estimate for the
incidence of prosthesis infections after hip and knee arthroplasty in a modern cohort of patients with RA. The
identification of patients with RA as being at significantly
higher risk of prosthetic joint infections emphasizes the
importance of utilizing all possible pre- and postoperative
prophylactic measures in this high-risk group. Especially
in the setting of a revision arthroplasty or a preceding
infection, physicians should maintain a high index of suspicion for postoperative infections.
Our results are based on a methodologic approach that
fulfills several major criteria of methodologic quality in
cohort studies: exposure definition (RA versus OA) according to validated criteria, minimal loss to followup,
strict definition of outcomes (prosthetic joint infection),
and accounting for important confounders by a conclusive
1719
matching algorithm contribute to the methodologic robustness of this study.
AUTHOR CONTRIBUTIONS
Dr. Bongartz had full access to all of the data in the study and
takes responsibility for the integrity of the data and the accuracy
of the data analysis.
Study design. Bongartz, Osmon, Bamlet, Hanssen, Matteson.
Acquisition of data. Bongartz, Halligan, Bamlet, Matteson.
Analysis and interpretation of data. Bongartz, Osmon, Reinalda,
Bamlet, Crowson, Hanssen, Matteson.
Manuscript preparation. Bongartz, Osmon, Reinalda, Bamlet,
Hanssen, Matteson.
Statistical analysis. Bongartz, Reinalda, Bamlet, Crowson.
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hip, incidence, patients, joint, knee, factors, tota, prosthetic, arthritis, infectious, replacement, risk, rheumatoid
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