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1065
Review :::::
..
.
:;
.
;,: ..
.
.
.
#{149}:
:,
#{149}...
.
‘
Lyme Disease
and Radiologic
Jack
W. Rahn2’3
P. Lawson1
Lyme disease
and Daniel
typically
with a pathognomonic ingitislike early
symptoms
stage,
cardiac,
begins
in the spring
or summer
skin lesion and associated [1]. If the patient neurologic,
or
is not treated
months,
during
this
manifesta-
tions may occur weeks to months later [2]. Although the clinical picture of Lyme disease is extremely variable, the diagnosis can be made in most cases by recognizing the typical patterns of organ involvement and associated immunologic abnormalities [3].
Lyme disease is a tick-transmitted, spirochetal, infectious disease with multisystem inflammatory manifestations. It was first identified as a distinct entity in the United States in 1975 [4], but a similar illness, tick-borne meningopolyradiculitis, had been recognized in Europe decades earlier [5]. Although the precise incidence is unclear, Lyme disease is the most com-
monly reported vector-transmitted disease in the States; cases have been reported from 43 of the particularly from the Northeast, the upper Midwest, Northern California coast. In fact, Lyme disease has distribution; it has been detected on all continents Antarctica
[6]. The causative
organism,
Borrella
United states, and the a global except
burgdorferi,
is transmitted dammini, three-host
by the nymph stage of infected ticks (!xodes Ixodes pacificus, or Ixodes ricinus). These ticks are organisms;
in successive
life stages,
a tick
may
parasitize and infect a number of different animals, including mice, raccoons, and several other small mammals, in addition to the deer, which is the preferred host and breeding around for the adult ticks. By 1988, 5000 cases of Lyme disease were being reported in the
United
States
each
year,
but it is estimated
that
:
:
.
Findings
flulike or men-
musculoskeletal
..
the
.
3 Present
address:
Department
of Medicine,
Medical
May 1992 036i-803X/92/i585-1065
College
of Georgia,
0 American
Augusta, Roentgen
#{149}
,
,.
in Lyme Arthritis
actual incidence of the disease may be five to 10 times higher. The incidence appears to be increasing rapidly in some areas, presumably associated with urban development encroaching on the ticks’ natural habitat. In certain areas of Westchester County, NY, for example, it is estimated tick nymphs are infected; that in the infected tick can be found in every 2 sq in some urbanized areas, one infected
that 25% of the deerwooded areas, one yd (1 .6 m2); and that tick can be found in
every 4 sq yd (3.2 m2) [7]. Public awareness and anxiety also have increased dramatically. In 1989,’each of two commercial reference laboratories in the northeastern United States performed more than 100,000 serologic tests for Lyme disease
[8].
Clinical
Features
In most
patients,
the first evidence
of Lyme
disease
is the
appearance of the pathognomonic skin lesion, erythema chronicum migrans (ECM), at the site of a tick bite. The tick itself is no larger than a pinhead. ECM is an expanding, erythematous macular lesion with a sharply demarcated outer border and, frequently, partial clearing centrally. Although the lesions can occur anywhere on the body, they most frequently are found on the lower extremities and in the groin and axillae, sites preferred
by the ticks
thattransmit
the infection. A lesion the causative from material
can be up to 50 cm in diameter. B. burgdorferi, organism, has been identified in and cultured from
ECM
lesions.
The interval between the tick bite and the appearance of ECM varies from several days to a month. However, only a
Received January 31 , 1990: accepted December 4, 1991. I Department of Diagnostic Imaging, Yale University School of Medicine, 333 Cedar St. , New Haven, CT 0651 0. Address 2 Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510.
AJR 158:1065-1069,
.
Article
GA 30912. Ray Society
reprint requests to J. P. Lawson.
LAWSON
1066
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minority of patients with skin lesions recall a bite, and approximately one third of patients do not have this unique cutaneous marker of the early stage of Lyme disease. Neverthe-
less, ECM remains the best clinical marker of Lyme disease and often provides a definitive indication of the date of onset of the disease. Other signs and symptoms commonly associated with the early stage of Lyme disease include fever, chills, myalgias, arthralgias, headache, stiff neck, and exhaustion. Nonspecific laboratory findings include mild leukocytosis, increased sedimentation rate, and minimally increased serum
levels of transaminases. The most useful laboratory marker, however, is an increase in total serum 1gM, which occurs in 33% of patients during the early stage, particularly those with systemic
signs
and
symptoms
and
ECM.
A persistent
in-
crease in total 1gM in untreated patients is a predictor of risk for later manifestations of Lyme disease [9]. Specific antibodies against B. burgdorferi usually are not detectable with conventional enzyme-linked immunosorbent assays or immunofluorescence tests until 3-6 weeks after the onset of disease, so serologic tests are not generally helpful for early diagnosis [1 0]. Furthermore, these assays cannot distinguish between persons with active infection and persons with previous exposure without persistence of infection. The diagnosis of Lyme disease cannot be made on the basis of serologic results alone in the absence of appropriate clinical features. Several weeks to a few months after the onset, most untreated patients have signs and symptoms of disseminated Lyme disease. In general, the sequence of organ involvement is predictable, but it can vary. Many patients do not seek treatment until late in the disease; therefore, initial clinical presentation with carditis, meningoencephalitis, or Lyme arthritis is not uncommon. Lyme carditis typically occurs 4 weeks after the onset of the disease.
It is relatively
uncommon,
however,
affecting
fewer than 10% of persons with untreated Lyme disease. The syndrome is transient; it resolves within a few days in most patients
even without
specific
antibiotic
therapy.
The neurologic manifestations of Lyme disease are variable and may occur anytime from a few days after the onset of the disease to years later. In the United States, in 10-1 5% of persons not treated during the early stage of the disease, neurologic signs develop within the first few months of illness.
These include, litis, sensory
in various
combinations,
meningitis,
AND
RAHN
AJR:158,
articular
May 1992
pain for as long as 6 years after ECM, without
joint swelling or other clinical signs mation. Migratory musculoskeletal
having
and symptoms of inflampain is a common rheu-
matic complaint in persons suspected of having Lyme disease; the certainty with which this complaint can be attributed to Lyme disease is not always clear, however. In Connecticut, approximately 50% of persons with ECM who are not treated eventually have at least one attack of arthritis. The mean latency period from onset of disease to occurrence of arthritis is 6 months. The typical patient with Lyme arthritis has intermittent
bouts
of inflammation
of one or a few large joints.
The predilection is for involvement of the knees (80% of patients). Other areas involved include the shoulders, elbows, ankles, hips, wrists, small bones of the extremities, and the temporomandibular joints. Involvement of the temporomandibular
joint
is a diagnostically
helpful
feature
because
such
involvement is rarely an early feature of other chronic arthritic disorders. The duration of these attacks of arthritis varies from several
hours
to a few weeks;
chronic
synovitis
develops
in only a minority of such patients. Approximately 90% of patients in whom chronic arthritis develops have DR4 or DR2 HLA alloantigens; these antigens are present in only 25% of patients in whom acute arthritis develops. The attacks are characterized clinically by short duration, swelling out of proportion to pain, and massive effusions; often 1 00 ml or more of joint fluid can be aspirated from the knee of a patient with acute Lyme arthritis. Joint fluid shows signs of inflammation; the number of leukocytes, which are mostly polymorphonuclear cells, is in the range of 20 x i0 cells/mm3. B. burgdorferi has been detected in joint fluid and synovial biopsy samples
[1 1]. Synovial involvement in Lyme arthritis is similar histologically to that associated with rheumatoid arthritis: synovial hyperplasia, synovial infiltration by lymphocytes, and vascular proliferation. The Lyme synovial lesion is unique, however, because perivascular tissues contain antigens of B. burgdorferi, which can be detected by staining with monoclonal antibodies [12]. The natural history of Lyme arthritis is variable. Episodes of inflammation, migratory pains, or chronic synovitis can recur intermittently for years. However, 10-20% of untreated patients with Lyme arthritis achieve spontaneous long-term remission yearly.
encepha-
and motor
radiculoneuritis, and cranial neuritis. Lyme meningitis and encephalitis seem to be caused by direct borrelial infection of the CNS, and generally appropriate antibiotic therapy is rapidly effective. However, spirochetes have never been cultured from the nerves of patients who have the
peripheral nervous system manifestations of Lyme disease, and antibiotic therapy is not as effective in these cases as it is in the CNS syndromes. Lyme arthritis, the manifestation that in the United States led to the recognition of Lyme disease as a distinct illness, actually occurs late in the course of the disease for most patients. Migratory arthralgias and myalgias occur commonly early in the disease, often accompanied by ECM, but frank arthritis is rare in the first weeks of illness. In the past, some untreated patients have had migratory muscle, joint, or peri-
Radiologic
Abnormalities
in Lyme
Arthritis
Since the disorder was first identified in 1976, more than 200 cases of Lyme arthritis have been studied at the Lyme disease clinic of Yale University School of Medicine. However, only 26 of the patients have had arthritic changes of sufficient duration and severity to merit radiologic examination [13]. Unfortunately the limited number of studies obtained in this small number of patients does not allow a clear description of the development and progression of the radiologic changes in this disease. Consequently, the abnormalities that have been detected represent only a qualitative assessment of the
radiologic findings Lyme arthritis.
that may be noted in patients
with severe
AJR:158,
LYME
May 1992
DISEASE
AND
LYME
both
1067
ARTHRITIS
normal
plicae
and
ribbonlike
bands
of hypertrophied
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synovium within the distended fluid-filled joint (Fig. 3). A number of patients with warm and swollen joints radiologic evidence diffuse periarticular of musculotendinous
have
not only of joint effusions but also of soft-tissue swelling associated with loss planes (Fig. 1). This finding is frequently
associated with edema of the infrapatellar fat pad and has been detected only when joint fluid or synovial thickening was present. Many patients with radiologic have multiple areas of irregular,
patellar shown
fat pad, suggesting
Fig. 1.-13-year-old boy with Lyme disease who had intermittent softtissue swelling and effusion of right knee for several months. Radiograph shows extensive soft-tissue swelling, a large effusion, areas of mottled density
Involving
infrapatellar
fat pad, and osteoporosis.
Changes
The most
frequently
is joint effusion the knee;
detected
abnormality
(Fig. 1). The most commonly
unilateral
involvement
occurs
more
in Lyme
affected
arthritis
joint is
frequently
than
bilateral involvement. Effusions of more than 1 00 ml may occur, and it is not uncommon for the amount of fluid to be greater than is anticipated from the patient’s moderate discomfort. Arthrography may show irregular filling defects (shown surgically to be due to gelatinous chips of proteinaceous coagulum) and, frequently, a large posterior and inferior extension of the joint space (Fig. 2), similar to the giant synovial extensions associated with rheumatoid arthritis. MR imaging may show the large joint effusion and, in addition,
Fig. 2.-28-year-oldwoman with Lyme who had heat and swelling in right knee for 9 months. Double-contrast arthrogram shows contrast material and air (arrows) in an inferomedial extension of joint.
disease
of synovium
Enthesopathic involved joints
fluid into the fat pad
changes may be noted. Tendons may be thickened. This thickening
with loss of definition
frequently,
loss
of definition
soft-tissue
of the tendon
of adjacent
swelling
margins
soft-tissue
may be present.
around may be
and,
planes.
Not surpris-
ingly, the quadriceps tendon and the patellar ligament are the structures most frequently involved. Calcification or ossification may be detected in entheses (Fig. 4). Again, the entheses around the knee joint are the most commonly involved sites.
New bone formation in the insertion of the joint capsule also has been detected (Fig. SC). These enthesopathic changes have been shown in those patients with Lyme disease who have the most dramatic joint swelling. Diffuse tenderness and swelling of a muscle or group of muscles may occur. The swelling can be detected on plain films and, more satisfactorily, on CT scans. On CT scans, the involved muscle groups have normal attenuation (Fig. 6A). Increased uptake of gallium-67 has been shown in the af-
fected muscle groups of patients
shows prominent effusion and ribbonlike folds of hypertrophied synovium. Large effusion had displaced meniscus anterioriy (white arrow). Frondlike extensions (black arrows) of synovium and synovial fluid
fat pad.
and synovial
associated
Fig. 3.-17-year-old boy with Lyme disease who had swelling of his left knee for 7 months. Sagittal T2weighted MR image (i500/80)through medial condyle
extend into infrapatellar
has
of the fat and frondlike
3).
Generalized Soft-Tissue
edema (Fig. 1). MR imaging
that this is due to both edema
extensions (Fig.
evidence of joint fluid also mottled density in the infra-
with Lyme disease (Fig. 6B).
Fig. 4.-39-year-old
woman
with Lyme disease
who had arthritis in left knee for 1 1 months. Radiograph shows multiple calcific densities in insertion of quadriceps tendon. (Reprinted with permission from Lawson and Steere (13J.)
LAWSON
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1068
AND
RAHN
AJA:158,
Fig. 5.-61-year-old man with Lyme disease who had arthritis in both hips and shoulders for 2 years. A, Radiograph of right hip shows loss of articular cartilage, erosions of articular cartilage, and subarticular “cysts.” B, RadIograph of left shoulder shows calcification (arrows) in articular cartilage of humeral head. (Reprinted with permission from Lawson [13].) C, Radiograph of right shoulder shows cartilage loss, erosions of articular cortex, and subarticular cysts. Note pooriy defined new bone
attachments
May 1992
and Steere (arrows)
at
of joint capsule.
Fig. 6.-42-year-old
man with Lyme disease
who had muscle pain months. A, CT scan through
diffuse
enlargement
in left
shows diffuse increased
None of the patients with muscle been examined by MR imaging.
Cartilaginous
tenderness
or swelling
have
Changes
Loss of articular cartilage occurs in approximately 25% of patients who have chronic Lyme arthritis. This is seen most often in the kneejoint but also may be detected in the shoulder
and hip joints. The loss of cartilage is uniform and symmetrical and does not appear to involve the weight-bearing areas (Figs. 5A and 5C). Chondrocalcinosis may occur. This finding ciated with severe previous joint involvement.
has been asso-
The finding be fine, delicate, linear calcification of articular cartilage 5B) or more extensive calcification of fibrocartilage (Fig. all instances, no other cause for the chondrocalcinosis be established.
may (Fig. 7). In could
Osseous
middle
of abductor
des (arrows). B, Posterior scintigram injection of 5 mCi (185 in region muscles. left side.
thigh
for
of thigh
several shows
group of mus-
obtained MBq) of
48 hr after TGa-citrate
uptake of radionuclide
of left gluteal, upper, and mid thigh Note cervical and axillary uptake on
Changes
Periarticular erosions, presumably associated with synovial hypertrophy, may be seen on radiographs (Fig. 8). In addition, erosions of articular cortex, suggesting an origin in inflammatory cartilage, may be detected (Figs. 5A and SC). These changes have been observed most often in the larger joints.
However,
this may simply
reflect the joint distribution
of the
changes associated with chronic arthritis. Osteoporosis may occur and may vary from mild to severe. It is usually juxtaarticular and most pronounced immediately adjacent to the articular cortex. The most pronounced osteoporosis has been detected in the youngest patients. Proliferative formation of new bone may be detected, usually as formation of osteophytes. However, less well defined new bone may be seen at the joint margins. This is thought to represent a proliferative enthesopathy at the site of capsular or ligamentous attachments (Fig. SC).
..,3.
of these changes, radiographs have not been obtained in these patients. Both the clinical picture and the radiologic changes of Lyme arthritis may be similar to those of pauciarticular juvenile arthritis. However, in contrast to juvenile arthritis, in Lyme disease, antinuclear antibodies are rarely found, and iridocyclitis has not been detected. Prolonged monoarticular involvement without other signs and symptoms is unusual in Lyme disease, and when a patient has such involvement, Lyme disease must be distinguished from a
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..,
slowly I Fig. 7.-49-year-old man with Lyme disease who had intermittent clinically active arthritis in right knee for a total of 2 years. Radiograph of knee shows streaky calcification in both medial and lateral menisci.
Subarticular “cysts,” particularly involving the knees and shoulder joints, may be detected. The cysts are usually small and multiple and may become confluent. Thin sclerotic margins are typical (Figs. SA and 5C).
The constellation
of osseous
and cartilaginous
changes
found in the 26 patients with the most severe chronic Lyme arthritis suggested an inflammatory arthritis in 44%, a degenerative arthritis in 28%, and an arthritis with features of both processes in 28%. The changes may be age related. The median age of the patients with probable inflammatory arthritis was 29.5 years; the median age of the other two groups
was 47 and 48.5 years, respectively. Lyme disease has both from several other rheumatic migratory polyarthritis and
similarities with and differences disorders. As in rheumatic fever, carditis may be features of the
early stage of Lyme disease. large
joint
effusions,
are less marked
which
However, are seen
in rheumatic
the osteoporosis later
fever.
in Lyme
Furthermore,
and
disease,
valvular
involvement and the changes of Jaccoud (post-rheumatic fever) arthropathy have not been detected in Lyme disease. Although unusual, symmetrical polyarthritis, suggestive of rheumatoid arthritis, has been noted in Lyme disease. In these patients, who have not had rheumatoid factor, joint involvement has been intermittent. Because of the transient nature
progressive
infection.
In adults,
the asymmetrical
and
intermittent involvement of large joints, particularly the knee; the soft-tissue swelling; and the tendon changes all suggest Reiter’s syndrome. In contrast to Reiter’s syndrome, in Lyme arthritis, involvement of the joints of the feet is rare, and conjunctivitis, urethritis, mucocutaneous lesions, and involvement of the axial skeleton have not been detected.
Recommendations
for Diagnosis
of Lyme
Arthritis
Inflammatory changes in one or more large joints is the most common radiologic manifestation of Lyme arthritis; the knee is the joint most often involved. The disease can usually
be diagnosed
on the basis of the typical
clinical
features,
namely, a history of the characteristic rash (ECM) or a flulike illness that occurs during the summer. Unfortunately, a history of tick bite is usually not obtainable. In those patients who initially seek treatment because of arthritis, the clinical picture may suggest rheumatic fever, pauciarticular juvenile arthritis (in children), or Reiter’s syndrome (in adults). Serologic tests
are generally
not helpful in the diagnosis
early in the disease
but typically are positive at the time of later manifestations. Antibiotics are usually effective therapy for this potentially chronic disease. Thus, it is essential that in endemic areas, clinicians and radiologists be aware of both the usual and the less common manifestations of Lyme disease.
REFERENCES 1 . Steere AC, Bartenhagen NH, Craft JE. et al. The early clinical manifestations of Lyme disease. Ann Intern Med 1983:99 : 76-82 2. Steere AC, Malawista SE, Hardin JA, Ruddy S. Askenase PW, Andiman WA. Erythema chronicum migrans and Lyme arthritis. Ann Intern Med
1977:36:685-698 3. Steere AC, Schoen AT, Taylor E. The clinical evolution of Lyme arthritis. Ann Intern Med 1987:107:725-731 4. Steere AC, Malawista SE, Snydman DR. et al. Lyme arthritis: an epidemic of oligo-articular arthritis in children and adults in three Connecticut communities. Arthritis Rheum 1977:20:7-17 5. Bannworth A. Zur klinik und pathogenese der “chronischen lymphozytaren Meningitis.” Arch Psychiatr Nervenkr 1944:1 17: 161 -1 85 6. Tsai TF, Bailey AE, Moore PS, Phil M. National surveillance of Lyme disease, 1987-1988. Conn Med 1989:53:324-326 7. Daniels TJ, Falco AC. The Lyme disease invasion. Nat Hist 1989;98:4-10 8. Schwartz BS, Goldstein MD, Aibeiro JMC, Schuize TL, Shahied SI. Antibody testing in Lyme disease. JAMA 1989:262:3431-3434 9. Steere AC, Hardin JA, Ruddy S. Mummaw JG, Malawista SE. Lyme arthritis. Arthritis Rheum 1979:22:471-483 10. Shrestha M. Grodzicki AL, Steere AC. Diagnosing early Lyme disease. Am J Med 1985:78:235-239 1 1 . Snydman DR. Schenkein DP. Berardi VP. Lastavica CC. Pariser KM. Borrelia burgdorferi in joint fluid in chronic Lyme arthritis. Ann Intern Med
1986;104:798-800 Fig. 8-30-year-old thritis
for a total
man with Lyme disease of
I 1 months.
Radiograph
who had intermittent shows
erosion
posterosuperior margin of tibia. Fullness in suprapatellar to hypertrophied synovium and proteinaceous coagulum.
(arrow)
arin
pouch was due
1 2. Steere AC, Duray PH, Burcher EC. Spirochetal antigens and lymphoid cell surface markers in Lyme synovitis. Arthritis Rheum 1988:31 :487-495 1 3. Lawson JP, Steere AC. Lyme arthritis: radiologic findings. Radiology 1985:154:37-43
1065
Review :::::
..
.
:;
.
;,: ..
.
.
.
#{149}:
:,
#{149}...
.
‘
Lyme Disease
and Radiologic
Jack
W. Rahn2’3
P. Lawson1
Lyme disease
and Daniel
typically
with a pathognomonic ingitislike early
symptoms
stage,
cardiac,
begins
in the spring
or summer
skin lesion and associated [1]. If the patient neurologic,
or
is not treated
months,
during
this
manifesta-
tions may occur weeks to months later [2]. Although the clinical picture of Lyme disease is extremely variable, the diagnosis can be made in most cases by recognizing the typical patterns of organ involvement and associated immunologic abnormalities [3].
Lyme disease is a tick-transmitted, spirochetal, infectious disease with multisystem inflammatory manifestations. It was first identified as a distinct entity in the United States in 1975 [4], but a similar illness, tick-borne meningopolyradiculitis, had been recognized in Europe decades earlier [5]. Although the precise incidence is unclear, Lyme disease is the most com-
monly reported vector-transmitted disease in the States; cases have been reported from 43 of the particularly from the Northeast, the upper Midwest, Northern California coast. In fact, Lyme disease has distribution; it has been detected on all continents Antarctica
[6]. The causative
organism,
Borrella
United states, and the a global except
burgdorferi,
is transmitted dammini, three-host
by the nymph stage of infected ticks (!xodes Ixodes pacificus, or Ixodes ricinus). These ticks are organisms;
in successive
life stages,
a tick
may
parasitize and infect a number of different animals, including mice, raccoons, and several other small mammals, in addition to the deer, which is the preferred host and breeding around for the adult ticks. By 1988, 5000 cases of Lyme disease were being reported in the
United
States
each
year,
but it is estimated
that
:
:
.
Findings
flulike or men-
musculoskeletal
..
the
.
3 Present
address:
Department
of Medicine,
Medical
May 1992 036i-803X/92/i585-1065
College
of Georgia,
0 American
Augusta, Roentgen
#{149}
,
,.
in Lyme Arthritis
actual incidence of the disease may be five to 10 times higher. The incidence appears to be increasing rapidly in some areas, presumably associated with urban development encroaching on the ticks’ natural habitat. In certain areas of Westchester County, NY, for example, it is estimated tick nymphs are infected; that in the infected tick can be found in every 2 sq in some urbanized areas, one infected
that 25% of the deerwooded areas, one yd (1 .6 m2); and that tick can be found in
every 4 sq yd (3.2 m2) [7]. Public awareness and anxiety also have increased dramatically. In 1989,’each of two commercial reference laboratories in the northeastern United States performed more than 100,000 serologic tests for Lyme disease
[8].
Clinical
Features
In most
patients,
the first evidence
of Lyme
disease
is the
appearance of the pathognomonic skin lesion, erythema chronicum migrans (ECM), at the site of a tick bite. The tick itself is no larger than a pinhead. ECM is an expanding, erythematous macular lesion with a sharply demarcated outer border and, frequently, partial clearing centrally. Although the lesions can occur anywhere on the body, they most frequently are found on the lower extremities and in the groin and axillae, sites preferred
by the ticks
thattransmit
the infection. A lesion the causative from material
can be up to 50 cm in diameter. B. burgdorferi, organism, has been identified in and cultured from
ECM
lesions.
The interval between the tick bite and the appearance of ECM varies from several days to a month. However, only a
Received January 31 , 1990: accepted December 4, 1991. I Department of Diagnostic Imaging, Yale University School of Medicine, 333 Cedar St. , New Haven, CT 0651 0. Address 2 Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510.
AJR 158:1065-1069,
.
Article
GA 30912. Ray Society
reprint requests to J. P. Lawson.
LAWSON
1066
Downloaded from www.ajronline.org by 117.244.25.240 on 11/12/15 from IP address 117.244.25.240. Copyright ARRS. For personal use only; all rights reserved
minority of patients with skin lesions recall a bite, and approximately one third of patients do not have this unique cutaneous marker of the early stage of Lyme disease. Neverthe-
less, ECM remains the best clinical marker of Lyme disease and often provides a definitive indication of the date of onset of the disease. Other signs and symptoms commonly associated with the early stage of Lyme disease include fever, chills, myalgias, arthralgias, headache, stiff neck, and exhaustion. Nonspecific laboratory findings include mild leukocytosis, increased sedimentation rate, and minimally increased serum
levels of transaminases. The most useful laboratory marker, however, is an increase in total serum 1gM, which occurs in 33% of patients during the early stage, particularly those with systemic
signs
and
symptoms
and
ECM.
A persistent
in-
crease in total 1gM in untreated patients is a predictor of risk for later manifestations of Lyme disease [9]. Specific antibodies against B. burgdorferi usually are not detectable with conventional enzyme-linked immunosorbent assays or immunofluorescence tests until 3-6 weeks after the onset of disease, so serologic tests are not generally helpful for early diagnosis [1 0]. Furthermore, these assays cannot distinguish between persons with active infection and persons with previous exposure without persistence of infection. The diagnosis of Lyme disease cannot be made on the basis of serologic results alone in the absence of appropriate clinical features. Several weeks to a few months after the onset, most untreated patients have signs and symptoms of disseminated Lyme disease. In general, the sequence of organ involvement is predictable, but it can vary. Many patients do not seek treatment until late in the disease; therefore, initial clinical presentation with carditis, meningoencephalitis, or Lyme arthritis is not uncommon. Lyme carditis typically occurs 4 weeks after the onset of the disease.
It is relatively
uncommon,
however,
affecting
fewer than 10% of persons with untreated Lyme disease. The syndrome is transient; it resolves within a few days in most patients
even without
specific
antibiotic
therapy.
The neurologic manifestations of Lyme disease are variable and may occur anytime from a few days after the onset of the disease to years later. In the United States, in 10-1 5% of persons not treated during the early stage of the disease, neurologic signs develop within the first few months of illness.
These include, litis, sensory
in various
combinations,
meningitis,
AND
RAHN
AJR:158,
articular
May 1992
pain for as long as 6 years after ECM, without
joint swelling or other clinical signs mation. Migratory musculoskeletal
having
and symptoms of inflampain is a common rheu-
matic complaint in persons suspected of having Lyme disease; the certainty with which this complaint can be attributed to Lyme disease is not always clear, however. In Connecticut, approximately 50% of persons with ECM who are not treated eventually have at least one attack of arthritis. The mean latency period from onset of disease to occurrence of arthritis is 6 months. The typical patient with Lyme arthritis has intermittent
bouts
of inflammation
of one or a few large joints.
The predilection is for involvement of the knees (80% of patients). Other areas involved include the shoulders, elbows, ankles, hips, wrists, small bones of the extremities, and the temporomandibular joints. Involvement of the temporomandibular
joint
is a diagnostically
helpful
feature
because
such
involvement is rarely an early feature of other chronic arthritic disorders. The duration of these attacks of arthritis varies from several
hours
to a few weeks;
chronic
synovitis
develops
in only a minority of such patients. Approximately 90% of patients in whom chronic arthritis develops have DR4 or DR2 HLA alloantigens; these antigens are present in only 25% of patients in whom acute arthritis develops. The attacks are characterized clinically by short duration, swelling out of proportion to pain, and massive effusions; often 1 00 ml or more of joint fluid can be aspirated from the knee of a patient with acute Lyme arthritis. Joint fluid shows signs of inflammation; the number of leukocytes, which are mostly polymorphonuclear cells, is in the range of 20 x i0 cells/mm3. B. burgdorferi has been detected in joint fluid and synovial biopsy samples
[1 1]. Synovial involvement in Lyme arthritis is similar histologically to that associated with rheumatoid arthritis: synovial hyperplasia, synovial infiltration by lymphocytes, and vascular proliferation. The Lyme synovial lesion is unique, however, because perivascular tissues contain antigens of B. burgdorferi, which can be detected by staining with monoclonal antibodies [12]. The natural history of Lyme arthritis is variable. Episodes of inflammation, migratory pains, or chronic synovitis can recur intermittently for years. However, 10-20% of untreated patients with Lyme arthritis achieve spontaneous long-term remission yearly.
encepha-
and motor
radiculoneuritis, and cranial neuritis. Lyme meningitis and encephalitis seem to be caused by direct borrelial infection of the CNS, and generally appropriate antibiotic therapy is rapidly effective. However, spirochetes have never been cultured from the nerves of patients who have the
peripheral nervous system manifestations of Lyme disease, and antibiotic therapy is not as effective in these cases as it is in the CNS syndromes. Lyme arthritis, the manifestation that in the United States led to the recognition of Lyme disease as a distinct illness, actually occurs late in the course of the disease for most patients. Migratory arthralgias and myalgias occur commonly early in the disease, often accompanied by ECM, but frank arthritis is rare in the first weeks of illness. In the past, some untreated patients have had migratory muscle, joint, or peri-
Radiologic
Abnormalities
in Lyme
Arthritis
Since the disorder was first identified in 1976, more than 200 cases of Lyme arthritis have been studied at the Lyme disease clinic of Yale University School of Medicine. However, only 26 of the patients have had arthritic changes of sufficient duration and severity to merit radiologic examination [13]. Unfortunately the limited number of studies obtained in this small number of patients does not allow a clear description of the development and progression of the radiologic changes in this disease. Consequently, the abnormalities that have been detected represent only a qualitative assessment of the
radiologic findings Lyme arthritis.
that may be noted in patients
with severe
AJR:158,
LYME
May 1992
DISEASE
AND
LYME
both
1067
ARTHRITIS
normal
plicae
and
ribbonlike
bands
of hypertrophied
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synovium within the distended fluid-filled joint (Fig. 3). A number of patients with warm and swollen joints radiologic evidence diffuse periarticular of musculotendinous
have
not only of joint effusions but also of soft-tissue swelling associated with loss planes (Fig. 1). This finding is frequently
associated with edema of the infrapatellar fat pad and has been detected only when joint fluid or synovial thickening was present. Many patients with radiologic have multiple areas of irregular,
patellar shown
fat pad, suggesting
Fig. 1.-13-year-old boy with Lyme disease who had intermittent softtissue swelling and effusion of right knee for several months. Radiograph shows extensive soft-tissue swelling, a large effusion, areas of mottled density
Involving
infrapatellar
fat pad, and osteoporosis.
Changes
The most
frequently
is joint effusion the knee;
detected
abnormality
(Fig. 1). The most commonly
unilateral
involvement
occurs
more
in Lyme
affected
arthritis
joint is
frequently
than
bilateral involvement. Effusions of more than 1 00 ml may occur, and it is not uncommon for the amount of fluid to be greater than is anticipated from the patient’s moderate discomfort. Arthrography may show irregular filling defects (shown surgically to be due to gelatinous chips of proteinaceous coagulum) and, frequently, a large posterior and inferior extension of the joint space (Fig. 2), similar to the giant synovial extensions associated with rheumatoid arthritis. MR imaging may show the large joint effusion and, in addition,
Fig. 2.-28-year-oldwoman with Lyme who had heat and swelling in right knee for 9 months. Double-contrast arthrogram shows contrast material and air (arrows) in an inferomedial extension of joint.
disease
of synovium
Enthesopathic involved joints
fluid into the fat pad
changes may be noted. Tendons may be thickened. This thickening
with loss of definition
frequently,
loss
of definition
soft-tissue
of the tendon
of adjacent
swelling
margins
soft-tissue
may be present.
around may be
and,
planes.
Not surpris-
ingly, the quadriceps tendon and the patellar ligament are the structures most frequently involved. Calcification or ossification may be detected in entheses (Fig. 4). Again, the entheses around the knee joint are the most commonly involved sites.
New bone formation in the insertion of the joint capsule also has been detected (Fig. SC). These enthesopathic changes have been shown in those patients with Lyme disease who have the most dramatic joint swelling. Diffuse tenderness and swelling of a muscle or group of muscles may occur. The swelling can be detected on plain films and, more satisfactorily, on CT scans. On CT scans, the involved muscle groups have normal attenuation (Fig. 6A). Increased uptake of gallium-67 has been shown in the af-
fected muscle groups of patients
shows prominent effusion and ribbonlike folds of hypertrophied synovium. Large effusion had displaced meniscus anterioriy (white arrow). Frondlike extensions (black arrows) of synovium and synovial fluid
fat pad.
and synovial
associated
Fig. 3.-17-year-old boy with Lyme disease who had swelling of his left knee for 7 months. Sagittal T2weighted MR image (i500/80)through medial condyle
extend into infrapatellar
has
of the fat and frondlike
3).
Generalized Soft-Tissue
edema (Fig. 1). MR imaging
that this is due to both edema
extensions (Fig.
evidence of joint fluid also mottled density in the infra-
with Lyme disease (Fig. 6B).
Fig. 4.-39-year-old
woman
with Lyme disease
who had arthritis in left knee for 1 1 months. Radiograph shows multiple calcific densities in insertion of quadriceps tendon. (Reprinted with permission from Lawson and Steere (13J.)
LAWSON
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1068
AND
RAHN
AJA:158,
Fig. 5.-61-year-old man with Lyme disease who had arthritis in both hips and shoulders for 2 years. A, Radiograph of right hip shows loss of articular cartilage, erosions of articular cartilage, and subarticular “cysts.” B, RadIograph of left shoulder shows calcification (arrows) in articular cartilage of humeral head. (Reprinted with permission from Lawson [13].) C, Radiograph of right shoulder shows cartilage loss, erosions of articular cortex, and subarticular cysts. Note pooriy defined new bone
attachments
May 1992
and Steere (arrows)
at
of joint capsule.
Fig. 6.-42-year-old
man with Lyme disease
who had muscle pain months. A, CT scan through
diffuse
enlargement
in left
shows diffuse increased
None of the patients with muscle been examined by MR imaging.
Cartilaginous
tenderness
or swelling
have
Changes
Loss of articular cartilage occurs in approximately 25% of patients who have chronic Lyme arthritis. This is seen most often in the kneejoint but also may be detected in the shoulder
and hip joints. The loss of cartilage is uniform and symmetrical and does not appear to involve the weight-bearing areas (Figs. 5A and 5C). Chondrocalcinosis may occur. This finding ciated with severe previous joint involvement.
has been asso-
The finding be fine, delicate, linear calcification of articular cartilage 5B) or more extensive calcification of fibrocartilage (Fig. all instances, no other cause for the chondrocalcinosis be established.
may (Fig. 7). In could
Osseous
middle
of abductor
des (arrows). B, Posterior scintigram injection of 5 mCi (185 in region muscles. left side.
thigh
for
of thigh
several shows
group of mus-
obtained MBq) of
48 hr after TGa-citrate
uptake of radionuclide
of left gluteal, upper, and mid thigh Note cervical and axillary uptake on
Changes
Periarticular erosions, presumably associated with synovial hypertrophy, may be seen on radiographs (Fig. 8). In addition, erosions of articular cortex, suggesting an origin in inflammatory cartilage, may be detected (Figs. 5A and SC). These changes have been observed most often in the larger joints.
However,
this may simply
reflect the joint distribution
of the
changes associated with chronic arthritis. Osteoporosis may occur and may vary from mild to severe. It is usually juxtaarticular and most pronounced immediately adjacent to the articular cortex. The most pronounced osteoporosis has been detected in the youngest patients. Proliferative formation of new bone may be detected, usually as formation of osteophytes. However, less well defined new bone may be seen at the joint margins. This is thought to represent a proliferative enthesopathy at the site of capsular or ligamentous attachments (Fig. SC).
..,3.
of these changes, radiographs have not been obtained in these patients. Both the clinical picture and the radiologic changes of Lyme arthritis may be similar to those of pauciarticular juvenile arthritis. However, in contrast to juvenile arthritis, in Lyme disease, antinuclear antibodies are rarely found, and iridocyclitis has not been detected. Prolonged monoarticular involvement without other signs and symptoms is unusual in Lyme disease, and when a patient has such involvement, Lyme disease must be distinguished from a
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..,
slowly I Fig. 7.-49-year-old man with Lyme disease who had intermittent clinically active arthritis in right knee for a total of 2 years. Radiograph of knee shows streaky calcification in both medial and lateral menisci.
Subarticular “cysts,” particularly involving the knees and shoulder joints, may be detected. The cysts are usually small and multiple and may become confluent. Thin sclerotic margins are typical (Figs. SA and 5C).
The constellation
of osseous
and cartilaginous
changes
found in the 26 patients with the most severe chronic Lyme arthritis suggested an inflammatory arthritis in 44%, a degenerative arthritis in 28%, and an arthritis with features of both processes in 28%. The changes may be age related. The median age of the patients with probable inflammatory arthritis was 29.5 years; the median age of the other two groups
was 47 and 48.5 years, respectively. Lyme disease has both from several other rheumatic migratory polyarthritis and
similarities with and differences disorders. As in rheumatic fever, carditis may be features of the
early stage of Lyme disease. large
joint
effusions,
are less marked
which
However, are seen
in rheumatic
the osteoporosis later
fever.
in Lyme
Furthermore,
and
disease,
valvular
involvement and the changes of Jaccoud (post-rheumatic fever) arthropathy have not been detected in Lyme disease. Although unusual, symmetrical polyarthritis, suggestive of rheumatoid arthritis, has been noted in Lyme disease. In these patients, who have not had rheumatoid factor, joint involvement has been intermittent. Because of the transient nature
progressive
infection.
In adults,
the asymmetrical
and
intermittent involvement of large joints, particularly the knee; the soft-tissue swelling; and the tendon changes all suggest Reiter’s syndrome. In contrast to Reiter’s syndrome, in Lyme arthritis, involvement of the joints of the feet is rare, and conjunctivitis, urethritis, mucocutaneous lesions, and involvement of the axial skeleton have not been detected.
Recommendations
for Diagnosis
of Lyme
Arthritis
Inflammatory changes in one or more large joints is the most common radiologic manifestation of Lyme arthritis; the knee is the joint most often involved. The disease can usually
be diagnosed
on the basis of the typical
clinical
features,
namely, a history of the characteristic rash (ECM) or a flulike illness that occurs during the summer. Unfortunately, a history of tick bite is usually not obtainable. In those patients who initially seek treatment because of arthritis, the clinical picture may suggest rheumatic fever, pauciarticular juvenile arthritis (in children), or Reiter’s syndrome (in adults). Serologic tests
are generally
not helpful in the diagnosis
early in the disease
but typically are positive at the time of later manifestations. Antibiotics are usually effective therapy for this potentially chronic disease. Thus, it is essential that in endemic areas, clinicians and radiologists be aware of both the usual and the less common manifestations of Lyme disease.
REFERENCES 1 . Steere AC, Bartenhagen NH, Craft JE. et al. The early clinical manifestations of Lyme disease. Ann Intern Med 1983:99 : 76-82 2. Steere AC, Malawista SE, Hardin JA, Ruddy S. Askenase PW, Andiman WA. Erythema chronicum migrans and Lyme arthritis. Ann Intern Med
1977:36:685-698 3. Steere AC, Schoen AT, Taylor E. The clinical evolution of Lyme arthritis. Ann Intern Med 1987:107:725-731 4. Steere AC, Malawista SE, Snydman DR. et al. Lyme arthritis: an epidemic of oligo-articular arthritis in children and adults in three Connecticut communities. Arthritis Rheum 1977:20:7-17 5. Bannworth A. Zur klinik und pathogenese der “chronischen lymphozytaren Meningitis.” Arch Psychiatr Nervenkr 1944:1 17: 161 -1 85 6. Tsai TF, Bailey AE, Moore PS, Phil M. National surveillance of Lyme disease, 1987-1988. Conn Med 1989:53:324-326 7. Daniels TJ, Falco AC. The Lyme disease invasion. Nat Hist 1989;98:4-10 8. Schwartz BS, Goldstein MD, Aibeiro JMC, Schuize TL, Shahied SI. Antibody testing in Lyme disease. JAMA 1989:262:3431-3434 9. Steere AC, Hardin JA, Ruddy S. Mummaw JG, Malawista SE. Lyme arthritis. Arthritis Rheum 1979:22:471-483 10. Shrestha M. Grodzicki AL, Steere AC. Diagnosing early Lyme disease. Am J Med 1985:78:235-239 1 1 . Snydman DR. Schenkein DP. Berardi VP. Lastavica CC. Pariser KM. Borrelia burgdorferi in joint fluid in chronic Lyme arthritis. Ann Intern Med
1986;104:798-800 Fig. 8-30-year-old thritis
for a total
man with Lyme disease of
I 1 months.
Radiograph
who had intermittent shows
erosion
posterosuperior margin of tibia. Fullness in suprapatellar to hypertrophied synovium and proteinaceous coagulum.
(arrow)
arin
pouch was due
1 2. Steere AC, Duray PH, Burcher EC. Spirochetal antigens and lymphoid cell surface markers in Lyme synovitis. Arthritis Rheum 1988:31 :487-495 1 3. Lawson JP, Steere AC. Lyme arthritis: radiologic findings. Radiology 1985:154:37-43
