Allen Steere and Arthur Weinstein treat chronic bad-knee-Lyme with long term antibiotics

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Subject: Allen Steere and Arthur Weinstein treat chronic bad-knee-Lyme
with long term antibiotics

Date: Oct 13, 2007 11:07 AM

(Read it carefully- this article does not say what the title says. The
drugs are
antibiotics.)


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(R)
(antibiotic) or sulfasalazine
(antibiotic)," 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(R), 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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