Allen Steere and Arthur Weinstein treat chronic knee Lyme with long term antibiotics
Peenies, Peenies, Peenies, My Name is Chuck and I love McSweenies'
http://www.ciaomed.org/articles.cfm?articleID=1012
NSAIDs/DMARDs Can Thwart Antibiotic-Refractory Lyme Arthritis
October 25, 2006
by Denise Mann Kleinman
BOSTON, Mass-A new report highlights effective postantibiotic
strategies for treating antibiotic-refractory Lyme arthritis and helps
to identify risk factors for this rare, but vexing condition.
Lyme arthritis patients with proliferative synovitis following a 1-
month course of oral antibiotics may benefit from 2 grams a day of
intravenous ceftriaxone for an additional month, and if their
polymerase chain reaction (PCR) tests are still positive, retreatment
with one course of oral antibiotics can be effective, write Allen C.
Steere, MD, and Sherilyn M. Angelis, MD, of Massachusetts General
Hospital, in Boston, in Arthritis & Rheumatism.1
"Although chronic Lyme arthritis may cause functional disability with
erosion of cartilage and bone, it eventually resolves in all
patients." -Allen C. Steere, MD and Sherilyn M. Angelis, MD, of
Massachusetts General Hospital.
Patients with a negative PCR test, however, may benefit from
nonsteroidal anti-inflammatory drugs (NSAIDs) or hydroxyquinolone. If
the arthritis persists for longer than 1 year, arthroscopic
synovectomy is an option.
"Although chronic Lyme arthritis may cause functional disability with
erosion of cartilage and bone, it eventually resolves in all
patients," they conclude.
They compared characteristics and treatments among 117 Lyme arthritis
patients, including 67 with signs of antibiotic-resistant arthritis
(defined as persistent joint swelling for 3 or more months after the
start of at least 4 weeks of IV antibiotic therapy or at least 8 weeks
of oral antibiotic therapy or both).
After antibiotic therapy, patients received nonsteroidal
antinflammatory drugs (NSAIDs) or intraarticular steroids, and if the
arthritis persisted for two years, they underwent arthroscopic
synovectomy (strategy 1). Strategy 2 added disease modifying
antirheumatic drugs (DMARDs), namely hydroxychloroquine, for patients
with negative PCR tests and persistent arthritis. If synovitis
persisted, researchers tried methotrexate (MTX) or infliximab, when it
became available.
Most patients treated with either strategy received NSAIDs or one or
two injections of intraarticular steroids. The overall rate of
arthritis resolution was similar in both groups and the longest
duration of arthritis was about 3.5 years. Specifically, all patients
treated by strategy 1 showed resolution of their arthritis within 14
months after the start of antibiotic therapy, while arthritis
persisted for about 9 months after the start of antibiotic therapy
among those treated with by strategy 2.
When it comes to antibiotic use, longer is not necessarily better, the
researchers point out. Several of the patients received oral
antibiotics for 6 months to 1 year or IV antibiotics for 6 to 8 weeks,
but the elongated treatment regimens had no bearing on joint swelling.
In addition, the longer the course of the antibiotics, the greater the
risk of adverse events, including IV line sepsis.
Risk Factors for Antibiotic-Refractory Lyme Arthritis
Risk factors for antibiotic-refractory arthritis include specific HLA-
DRB1 alleles, greater immune reactivity with an epitope of Borrelia
burgdorferi outer-surface protein A (OspA) and, potentially, treatment
with intraarticular steroids prior to antibiotic therapy, according to
the new report.
"Intraarticular corticosteroids given prior to antibiotics may be a
risk factor for persistent Lyme arthritis and, in animal models, are
associated with higher spirochetal burdens and longer persistence or
spirochetal DNA," they write. "Thus intraarticular corticosteroids
should not be given prior to antibiotic therapy and we now rarely use
them in the postantibiotic period."
New Strategies Make Sense
"Antibiotic-refractory Lyme arthritis is a very uncommon feature
overall in Lyme disease, since it occurs in about 10% of patients with
Lyme arthritis and Lyme arthritis is no longer very common (relative
to how common Lyme disease is) since it can be prevented by
appropriate treatment of Lyme disease in its early stages," explained
Arthur Weinstein, MD, a professor of medicine at Georgetown
University Medical Center in Washington, DC.
"Lyme arthritis, even with appropriate antibiotic therapy, often takes
some months to resolve so I believe Dr. Steere's recommendation to
wait for 1 to 2 months after the second course of antibiotics is
appropriately conservative," he told CIAOMed.
"My approach in the past has had elements of both strategy 1 and 2 and
is similar to his current recommendations," he said. "If a patient
does not respond to a 1-month course of oral doxycycline and persists
with inflammatory synovitis, I give another 1-month course of therapy-
generally intravenous ceftriaxone and not oral doxycycline," he said.
"Most patients gradually improve after this, and even if there is some
joint swelling, aspiration reveals only mildly or noninflammatory
fluid."
"Patients who have persistent or recurrent inflammatory synovitis with
negative PCR receive anti-inflammatory therapy (NSAIDs, intraarticular
corticosteroids), and if it persists, they will receive a course of
Plaquenil® or sulfasalazine," he said.
"I have not gone on to give stronger DMARD therapy at this juncture,
but rather go to arthroscopic synovectomy," Dr. Weinstein said. "I
have given MTX only in those few patients for whom synovectomy did not
lead to a durable remission, [and] I have not seen significant joint
damage (cartilage/bone erosion) in these patients, but have not
routinely done magnetic resonance imaging (MRI)."
"Slow Resolution" Arthritis, a Better Descriptive Term?
"We don't see very much Lyme arthritis, and most people who get
treated are cured, so emphasizing refractory Lyme arthritis is doing
somewhat of a disservice," said Raymond Dattwyler, MD, professor of
medicine and microbiology, chief of immunology, and chief of a new
division of allergy, immunology and rheumatology at New York Medical
College in Valhalla.
Dr. Dattwytler prefers the term 'slow-resolution arthritis' as most of
these patients do get better. "Even in referral centers, the incidence
of slow resolution is really uncommon," he said. In the new report,
refractory could be as little as 4months after being on an
antibiotic. "I always tell patients to 'be patient' and if someone is
resolving slowly, it's okay."
When it comes to treatment after antibiotics, "I think we need to
weigh the risks and benefits of therapy," he said. "NSAIDS and
intraarticular steroids are OK, but if we start to use MTX or
Remicade®, what do we gain if everyone is getting better anyway?"
Aggrecanase 1 Plays Causal Role in Lyme Arthritis
Related research sheds light on how infection with Borrelia
burgdorferi results in Lyme arthritis. B burgdorferi infection induces
aggrecanase 1 or ADAMTS-4 in human chondrocyte cell cultures, mice
with arthritism and patients with Lyme arthritis, but Aggrecanase 2 or
ADAMTS-5 does not, according to a report in Arthritis & Rheumatism. 2
In vitro and ex vivo studies show that ADAMTS-4 is processed and found
in its most active form within the joint. The researchers suspect that
ADAMTS-4 cleaves aggrecan and exposes the joints' collagen matrix,
allowing it to be processed by matrix metalloproteinases (MMPs) and
resulting in cartilage degradation and destruction. Aggrecanases, not
MMPs, seem to mediate the cleavage of aggrecan, according to bovine
cartilage explants of this disease.
The "use of selective aggrecanase inhibitors may impart cartilage
protection by preventing aggrecan degradation without some of the
negative responses associated with more broad-spectrum MMP
inhibitors," the study authors conclude.
References
1. Steere AC, Angelis SM. Therapy for Lyme arthritis: Strategies
for the treatment of antibiotic-refractory arthritis. Arthritis Rheum.
2006;54:3079-3086.
2. Behera AK, Hildebrand E, Szafranski J, et al. Role of
aggrecanase 1 in Lyme arthritis. Arthritis Rheum. 2006;54:3319-3329.
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