AJR 2005; 184:1904-1909
© American Roentgen Ray Society
MRI Features of Lyme Arthritis in Children
Kirsten Ecklund1,
Sigella Vargas1,
David Zurakowski2 and
Robert P. Sundel3
1 Department of Radiology, Children's Hospital, 300 Longwood Ave., Boston, MA
02115.
2 Departments of Orthopaedics and Biostatistics, Children's Hospital, Harvard
Medical School, Boston, MA 02115.
3 Rheumatology Program, Division of Immunology and the Department of Pediatrics,
Children's Hospital, Harvard Medical School, Boston, MA 02115.
Received June 30, 2004;
accepted after revision September 13, 2004.
Address correspondence to K. Ecklund
(kirsten.ecklund{at}childrens.harvard.edu).
Abstract
OBJECTIVE. Oligoarthritis is the most common manifestation of late
Lyme disease in children. Considerable overlap can occur in the clinical
presentation of Lyme arthritis and acute septic arthritis. Early
differentiation is critical, given the disparate therapeutic implications;
Lyme arthritis is treated with outpatient oral antibiotics, while septic
arthritis requires hospitalization, IV antibiotics, and, often, surgical
drainage. We wanted to identify MRI features that may distinguish Lyme
arthritis from septic arthritis in children.
MATERIALS AND METHODS. Knee MR images in 11 children with Lyme
arthritis and 7 with septic arthritis, with a mean age 10.6 years old and 11.7
years old, respectively, were reviewed by a radiologist blinded to the final
diagnosis. Joint effusion size, synovial thickness, adenopathy, subcutaneous,
marrow, and muscle edema on MRI; and clinical parameters including age, sex,
fever, WBC, erythrocyte sedimentation rate, C-reactive protein, and joint
fluid WBC in the two patient groups were compared using univariate and
multivariate analyses.
RESULTS. Subcutaneous edema was seen in all septic arthritis
patients but in only one of 11 patients with Lyme arthritis (p <
0.01). Myositis and adenopathy were present in all Lyme arthritis patients and
two of seven patients with septic arthritis (both p < 0.01). No
significant difference was present in synovial thickness, marrow edema, or
joint fluid size. There were no statistically significant differences in the
clinical parameters assessed.
CONCLUSION. Our results identified three MRI features, specifically,
myositis, adenopathy, and lack of subcutaneous edema, that strongly suggest
the diagnosis of Lyme arthritis rather than septic arthritis in children with
acute inflammation of the knee. Awareness of these characteristic MRI features
may avoid unnecessary invasive procedures and cost.
Introduction
Lyme disease, caused by infection with the spirochete Borrelia
burgdorferi, is the most common vector-borne illness in the United
States. The annual number of cases reported to the Centers for Disease Control
and Prevention has increased steadily since surveillance was initiated in
1982. In the year 2002 alone, 23,763 new cases of Lyme disease were reported
in the U.S. [1]. The disease
has striking seasonal and geographic predilections. Nearly 80% of cases are
reported between May and August. Most cases occur in New England, the
Mid-Atlantic states, and, to a lesser extent, the Midwest. The highest
reported incidence occurs in children 5-9 years old
[2].
Lyme disease is divided into early and late phases, with early infection
characterized by constitutional symptoms and the hallmark rash, erythema
migrans. Fewer than half of patients present with early-phase symptoms, and
even fewer recall a tick bite. In contrast to adults, who typically develop
neurologic symptoms in the late phase of Lyme disease, children more often
present with oligoarticular arthritis, especially involving the knee
[3].
Timely diagnosis of Lyme arthritis is difficult. No rapid laboratory test
reliably identifies serologic markers of borellial infection, and there is
considerable overlap in the clinical, laboratory, and radiographic
presentation of children with Lyme arthritis and those with other acute
arthritides. In fact, Lyme arthritis is diagnosed on initial presentation in
fewer than 20% of children [4].
Yet early differentiation from septic arthritis is particularly important
because of the disparate therapeutic implications of each diagnosis. Treatment
for septic arthritis involves hospitalization, joint aspiration, a lengthy
course of IV antibiotics, and, often, surgical drainage. In contrast, initial
therapy for Lyme arthritis is a 4-week course of oral doxycycline or
amoxicillin [3].
Even when Lyme is suspected, the diagnosis can be delayed pending the
results of serologic analysis. Formal diagnosis of Lyme disease is dependent
on visualization of antibodies to the causative spirochete by serum enzyme
immunoassay (EIA), followed by Western immunoblot confirmation, which can take
up to a week [5]. The purpose
of this study was to determine whether unique MRI characteristics of Lyme
arthritis in children may differentiate the disease from septic arthritis.
Awareness of such findings could avoid delay in diagnosis and unnecessary
invasive interventions.
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Fig. 1. —16-year-old boy with bacterial arthritis of left knee.
Sagittal intermediate-weighted fat-suppressed MR image shows large joint
effusion with maximal distention of suprapatellar bursa.
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Fig. 2. —12-year-old boy with septic arthritis of right knee. Maximum
synovial thickness measures 4.11 mm along anterior aspect of suprapatellar
bursa on this sagittal T1-weighted postcontrast MR image with fat
suppression.
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Materials and Methods
A review of radiology and rheumatology department databases from a large
New England children's hospital between 1997 and 2004 revealed 11 children who
underwent MRI of the knee and ultimately were diagnosed with Lyme arthritis,
and seven children similarly imaged who were found to have bacterial septic
arthritis. All patients were imaged within 48 hr of their presentation with
acute inflammatory arthritis of the knee. The Lyme group consisted of seven
boys and four girls with an age range of 2.4-16.7 years; mean, 10.6 ±
4.5 (SD) years. In the septic arthritis group, there were three boys and four
girls with an age range of 1.2-17.6 years; mean, 11.7 ± 6.6 years. The
requirement for the diagnosis of Lyme arthritis was a positive serologic EIA
with Western immunoblot confirmation. Septic arthritis was confirmed by joint
fluid culture, either by percutaneous aspirate or operative drainage. Joint
fluid was aspirated percutaneously within 24 hr before MRI in seven of 11
children with Lyme arthritis and four of seven with septic arthritis. One
patient from each group underwent arthroscopic drainage of the knee before
MRI.
MRI was performed on a 1.5-T MR scanner using a standard extremity coil
with the following sequences: axial and sagittal fast spin-echo inversion
recovery or T2-weighted spin-echo with fat suppression, sagittal
intermediate-weighted spin-echo, and coronal T1-weighted spin-echo. All but
two patients also had sagittal T1-weighted images with fat suppression
obtained after the IV administration of gadopentetate dimeglumine (Magnevist,
Berlex). Images were viewed on the radiology department's Fuji Synapse PAC
system (Fujifilm Medical Systems). An experienced pediatric radiologist
blinded to the final diagnosis reviewed the MRI examinations.
MR images were reviewed for size of joint effusion; presence of marrow,
muscle, and subcutaneous edema; synovial thickness; synovial enhancement; and
presence of popliteal lymph nodes. The amount of joint fluid was considered
small if the suprapatellar bursa was mildly distended, moderate if extension
into the posterior recesses of the joint was present, and large if maximal
distention of the suprapatellar bursa was present
(Fig. 1). Subcutaneous edema
was considered present only if it was generalized rather than focal, which
could be related to recent joint aspiration. Maximum synovial thickness was
measured along the anterior aspect of the suprapatellar bursa on the sagittal
postcontrast images using the standard PAC system measurement tool
(Fig. 2).
The patients' clinical records were reviewed for the following data at the
time of presentation and MRI: age, sex, presence of fever, serum WBC, serum
erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), joint fluid
WBC, and Lyme titer results. Institutional review board approval was obtained
for review of the MR images and clinical and laboratory records of the 18
patients.
Statistical Analysis
Univariate and multivariate analyses were performed to identify differences
in clinical and MRI variables between patients with Lyme arthritis and those
with septic arthritis. All continuous variables were tested for normality to
determine the most appropriate statistical tests. CRP and joint fluid WBC were
evaluated as median values and ranges with groups compared using the
nonparametric Mann-Whitney U test. All other continuous variables,
including age, serum WBC, ESR, and synovial thickness, were presented in terms
of the mean ± SD and compared using the Student's t test.
Categoric data, including sex; fever; presence of marrow, muscle, and
subcutaneous edema; and hemarthrosis were compared using Fisher's exact test
for binomial proportions. Joint effusion size was assessed using the
chi-square test with Yates correction. Multiple logistic regression with the
backward stepwise procedure was applied to identify which variables were
independently associated with differentiation of Lyme disease and septic
arthritis using the likelihood ratio test to determine significance
[6]. Data analysis was
conducted using the Statistical Package for the Social Sciences (version 12.0,
SPSS). Two-tailed values of p < 0.05 were considered statistically
significant.
Results
The comparison of the clinical variables between the patients with Lyme
arthritis and those with septic arthritis is shown in
Table 1. No significant
differences in age, sex, serum WBC, ESR, or CRP were present between the
patients with Lyme disease and those with septic arthritis. Although fever was
more common in children with septic arthritis, the difference was not
statistically significant. Similarly, there was no significant difference in
the median joint fluid WBC between the two groups, although all patients with
a joint fluid WBC higher than 70,000 cells/µL had septic arthritis.
The comparison of MRI findings between the patients with Lyme arthritis and
those with septic arthritis is shown in
Table 2. All of the children
had joint effusions. All 16 patients who received IV contrast showed synovial
enhancement. No difference was present in synovial thickness between the two
groups of children. Two patients with Lyme arthritis did not have postcontrast
imaging. A mild amount of marrow edema was present in two children with septic
arthritis but none with Lyme arthritis. All 11 children with Lyme arthritis
had edema within the adjacent muscles, especially within the popliteus
(Fig. 3), while associated
myositis was seen in only two of the seven children with septic arthritis.
Similarly, popliteal adenopathy was seen in all patients with Lyme arthritis
(Fig. 4), but in just two
patients with septic arthritis. Subcutaneous edema was present in all patients
with septic arthritis (Fig. 5). Only one child with Lyme arthritis showed subcutaneous edema at MRI, and that
examination was obtained 24 hr after surgical drainage. There was no
significant difference in the presence of subcutaneous edema between the
children who underwent preimaging arthrocentesis and those who did not.
Hemarthrosis was seen in two children with Lyme arthritis and none with septic
arthritis. Popliteal cysts were present in three patients with Lyme arthritis
and none with septic arthritis.
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Fig. 3. —9-year-old boy with Lyme arthritis of knee. Sagittal
T2-weighted fat-suppressed MR image shows joint effusion, synovial thickening,
and high-signal-intensity fluid within popliteus muscle
(arrow).
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Fig. 5. —4-year-old girl with septic arthritis of left knee. Sagittal
intermediate-weighted fat-suppressed MR image reveals joint effusion, synovial
thickening, and extensive high-signal-intensity edema within subcutaneous
tissues (arrow).
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Based on univariate analysis, three MRI variables were significantly
different between patients with Lyme disease and those with septic arthritis.
The findings of muscle edema, subcutaneous edema, and popliteal
lymphadenopathy showed statistical significance (all p < 0.01).
None of the other imaging variables were significantly different between the
two study groups (all p > 0.05). Multiple logistic regression
analysis confirmed that the best independent predictor of Lyme arthritis
versus septic arthritis was the lack of subcutaneous edema on MRI with a
likelihood ratio test of 10.89, p < 0.001. This implies that
independently of all of the other variables evaluated in this study, patients
who were found to have subcutaneous edema on MR images were significantly more
likely to have septic arthritis compared with Lyme disease. The final logistic
regression model indicated that irrespective of the other variables, when
subcutaneous edema was absent in the patient groups evaluated, the estimated
probability that a patient had Lyme disease was greater than 99% and the
probability of septic arthritis was less than 1%.
Discussion
Lyme disease in children is occurring with increasing frequency in endemic
regions in the United States. The highest reported incidence occurs in
children ages 5-9 years old
[7]. Oligoarthritis is the most
common manifestation of late phase Lyme disease in children and usually
involves the knee, although the hip, ankle, elbow, and wrist are other common
sites [8]. Initial reports
claimed that more than half of children had a history of the characteristic
erythema migrans rash. More recently, however, it has been recognized that
fewer than 20% of children with Lyme arthritis ever had erythema migrans. With
the increasing recognition of this and other clinical and laboratory
similarities between Lyme arthritis and acute bacterial arthritis, more groups
are reporting diagnostic uncertainty when children present with an acute
inflammatory monoarthritis
[9].
Articular involvement due to B. burgdorferi may develop from 2
weeks to 2 years after infection or onset of systemic symptoms, making
attribution to Lyme disease difficult. Patients usually present with fever,
limp, joint pain, and elevated acute phase reactants, all of which are also
seen in children with acute septic arthritis. Radiographs reveal joint
effusion in both groups. Our finding that clinical and laboratory parameters,
including serum WBC, ESR, CRP, or joint fluid WBC, cannot distinguish between
Lyme and septic arthritis are consistent with earlier reports
[9]. MRI may be requested in
children with acute infectious arthritis to assess severity or to exclude
associated osteomyelitis. Our results identified three MRI features,
specifically myositis, lymphadenopathy, and lack of subcutaneous edema, that
help differentiate Lyme arthritis from septic arthritis of the knee in
children (Figs. 6A,
6B, and
6C).
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Fig. 6A. —12.5-year-old girl with Lyme arthritis of right knee.
Sagittal T2-weighted fat-suppressed image shows joint effusion, synovial
thickening, and high-signal-intensity masslike lesion posteriorly
(arrow).
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Fig. 6B. —12.5-year-old girl with Lyme arthritis of right knee.
Sagittal T1-weighted postcontrast fat-suppressed MR image at the same level as
A confirms that posterior lesion is distended popliteal cyst with
thickened, enhancing synovium peripherally (arrow).
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Fig. 6C. —12.5-year-old girl with Lyme arthritis of right knee.
Sagittal T1-weighted postcontrast fat-suppressed MR image just medial to
B shows associated lymphadenopathy (white arrows) and myositis
(black arrow).
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All inflammatory arthritides result in synovial hyperemia. It is not
surprising that joint effusion, synovial hypertrophy, and enhancement were
seen in both groups of patients, with no significant difference in synovial
thickness. In contrast, myositis and lymphadenopathy were seen in all of the
children with Lyme arthritis but in only two with septic arthritis. Lyme
myositis has been reported
[10], so this finding may
represent a fundamental difference in the tissue tropism of borellial and
bacterial causes of arthritis. Conversely, edema within the subcutaneous
tissues was seen in all patients with septic arthritis and in only one child
with Lyme. Similar proportions of patients with Lyme arthritis (64%) and
septic arthritis (57%) underwent percutaneous joint aspiration before MRI. The
effect of this procedure on the MRI findings is likely negligible with the
exception of insignificant foci of subcutaneous edema related to needle
insertion. Arthroscopy, on the other hand, is more invasive and likely
complicates the MRI appearance of the joint, increasing the soft-tissue
swelling and synovial enhancement. The one patient with Lyme arthritis who
exhibited subcutaneous edema was also the only patient in that group who had
undergone preimaging arthroscopy, likely accounting for the finding. Overlying
cellulitis is much more common in bacterial septic arthritis, which may
account for the increased incidence of superficial edema in those patients.
Marrow edema, a hallmark of osteomyelitis, was rare in both groups, as would
be expected.
In addition, the MR images of two patients with Lyme arthritis revealed
hemarthrosis. This feature of Lyme arthritis has been described
[11] and may be the result of
subclinical trauma to the hyperemic synovium. Although not seen in our series,
hemarthrosis has also been reported in septic arthritis and probably cannot be
used as a distinguishing feature.
One recent study of Lyme arthritis in children stated that MRI was not
useful in the diagnostic evaluation
[9]. However, only two of 10
patients in that study underwent MRI and no control patients with bacterial
septic arthritis were used for comparison. Differences between our conclusions
and those of that study may be related to the small number of MR images that
they evaluated.
The results of this study are limited by its retrospective nature and the
small sample size. This is in part because patients thought to have septic
arthritis are not routinely referred for MRI on acute presentation at our
institution. MRI is most often requested when there is lack of clinical
improvement after joint aspiration and antibiotic therapy. It is interesting
to note that eight of the 18 total patients underwent MRI in the last year of
the 6-year study period. This coincides with the time of our initial
observation that associated soft-tissue findings might help differentiate Lyme
from septic arthritis. It is likely that the increase in referrals for MRI
relates to increased awareness of these findings on the part of referring
physicians.
Our study was confined to a comparison of the MRI findings of Lyme
arthritis with those of acute septic arthritis in children. We did not
evaluate other common inflammatory monoarthridites, such as juvenile
rheumatoid arthritis (JRA). JRA is somewhat less likely to be confused
clinically with acute infectious arthritis. Some children with Lyme arthritis,
however, come to medical attention in the chronic phase of their illness, when
the disease is more likely to be confused with JRA. It will be important for
future studies to compare the MRI features of Lyme arthritis with those of
JRA.
Despite the small number of patients, we identified three MRI features in
children with acute onset of arthritis of the knee—myositis,
lymphadenopathy, and lack of subcutaneous edema—that are more suggestive
of Lyme than septic arthritis. In geographic regions where Lyme disease is
endemic, MRI may play an important role in the diagnosis and management of
children with acute arthritis. This should not be interpreted as a
recommendation for MRI in all children presenting with acute arthritis, but
rather as a report that MRI can offer additional information in those cases
where clinical and laboratory data are inconclusive for septic arthritis. If
myositis, lymphadenopathy, and especially lack of subcutaneous edema are
identified, Lyme disease should be suggested. However, caution should be used
when MRI is performed after operative drainage procedures that may alter the
findings, especially with respect to subcutaneous edema. Since our initial
recognition of the soft-tissue features accompanying Lyme arthritis, we have
found that the radiologist is often the first to suggest the diagnosis.
Confirmation of our findings would allow educational efforts to be directed
toward disseminating these MRI manifestations of Lyme arthritis among other
caregivers responsible for the diagnosis and treatment of children with acute
arthritis, including emergency department physicians, orthopedists, and
rheumatologists.
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Abstract
Introduction
