http://www.nytimes.com/2001/07/10/health/10LYME.html
July 10, 2001
Certainty and
Uncertainty in Treatment of Lyme Disease
By PHILIP J. HILTS
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study
to be reported on Thursday in The New England Journal of Medicine is fueling a
running disagreement among medical researchers over the unresolved issues in
Lyme disease, a tick-borne illness that is endemic in much of the Northeast and
in other pockets around the nation.
The study, by Dr. Mark S. Klempner of Boston University Medical Center,
showed that prolonged treatment with antibiotics was no more effective than
placebos among those with persistent Lyme disease symptoms.
Citing its importance to patients and doctors, the journal posted the study,
along with two others and an editorial, on its Web site (www.nejm.com) a month
before the scheduled publication date. The question is, Why do a few patients
who appear to have been treated successfully for Lyme disease have symptoms
that come back strongly later?
Both sides agree that antibiotics work in 90 percent of patients and that
the disease never recurs in those patients, at least not from that tick bite.
But among the other patients, symptoms either persist or come back after the
standard treatment. Do the symptoms recur because the bacteria have been hiding
out in the body, only to emerge again later? Or could the Lyme bacteria, even
though they were wiped out by treatment, have brought on a secondary disease, a
Lyme autoimmune disorder, in which the body's immune system attacks its own cells
as if they were the Lyme disease organism?
Because the patients in Dr. Klempner's study were given a new round of
antibiotics, the bacteria should have been killed, and the patients' symptoms
should have gone away. Since that did not happen, proponents of the autoimmune
theory say, the Klempner study is good evidence for their position.
But critics say more answers are needed. Some doctors have been treating
persistent Lyme disease with much heavier doses of antibiotics than the
Klempner study used, and they believe that has helped. So, they say, the issue
will not be resolved until the heavier doses are tested in experiments.
One patient group, the Lyme Disease Foundation, based in Hartford, has sided
with heavy antibiotic use until the questions have been resolved.
Dr. Anthony Lionetti, who works in a New Jersey clinic and is associated
with the foundation, said that some patients suffered persistent infection that
needed to be treated but that the bacterium might not always show up in tests.
He said he sometimes asked patients to take as many as 10 tests before
accepting that a patient with symptoms did not have a persistent bacterial
infection.
One complicating issue is that among patients who have recurrent Lyme
symptoms, at least two distinct groups seem to have emerged.
One group's symptoms are centered on arthritis symptoms like pain and
swelling, usually in the knees. A second group has nervous system symptoms like
memory loss, confusion, fatigue, muscle weakness and numbness or tingling.
The two sides in the dispute tend to accept the arthritis symptoms as an
autoimmune reaction. The dispute is centered on the other patients.
"We really believe these patients are in pain," Dr. Klempner said
in a telephone interview, "and what is needed now is to find out what the
cause is, if it is not persistent infection."
But Dr. Brian A. Fallon, a psychiatrist at Columbia University and director
of the Lyme Disease Program at the New York Psychiatric Institute in Manhattan,
said that despite the Klempner study, which he described as important and
illuminating, it was too soon to give up the "persistent infection"
hypothesis.
Dr. Fallon is beginning to recruit patients who complain of chronic Lyme
disease and have neurological and cognitive impairments for a study financed by
the National Institutes of Health. They will be treated with 10 weeks of
intravenous antibiotics in hopes of killing off any bacteria that may be hiding
in the brain or other tissues.
Dr. Phillip Baker, chief of the Lyme disease program at the National
Institute of Allergy and Infectious Diseases, said researchers there were also
planning a study to look into whether the constellation of symptoms called
chronic Lyme disease might actually be an autoimmune disorder. That study will
look to see if the body's defenses attack its own tissues in the same way they
attack the bacteria.
Within two or three years, the researchers say, they hope to have some
useful, and maybe even decisive, information from this research.
Meanwhile, as the tick season begins, here are questions and answers about
Lyme disease.
Q. What is Lyme disease?
A. Lyme disease is a bacterial infection caused by Borrelia burgdorferi, a
spiral- shaped bacterium, or spirochete. But it is not passed from person to
person; rather, its carrier is a tiny arachnid, the so-called deer tick (in the
Ixodes ricinus group). In the eastern United States, this tick feeds on the
blood of white-tailed deer, white-footed mice and other mammals, which commonly
carry the Lyme bacterium in their blood, though it does not make them sick.
When an infected tick bites a person and begins feeding, it can transmit the
bacteria.
Because the disease depends on the deer, mice, ticks and bacteria, it is
limited geographically to the areas where all three live. Eight states, from
Maryland north to Massachusetts, account for about 90 percent of this country's
reported cases. Other pockets are in Minnesota, Wisconsin and Northern
California. In these areas the ticks and the bacteria may be slightly different.
About 16,000 cases of Lyme disease are reported each year to the federal
Centers for Disease Control and Prevention, making it the most common disease
carried by insects or arachnids. The agency also says the true number of cases
is almost certainly far higher.
Q. How do the ticks infect people?
A. About three-quarters of the people who get the disease never spot the tiny
ticks, which tend to hide in the hair, groin and armpits and at the back of the
knees.
But people who do spot the ticks have a good chance of
avoiding the disease. Only about 1 percent of deer ticks are actually infected,
and the infections are most often transmitted by the nymph-stage ticks that are
most common from May to September and peak in June and July. July 10, 2001
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Ticks are slow feeders, so if they are spotted
and removed within 72 hours after they make contact, Lyme disease can usually
be avoided.
Q. How can people avoid being infected?
A. The ticks live in wooded areas or shady grasslands, often hiding under leaf
debris. The best way to avoid them in affected areas is to stay to the center
of paths and to wear long pants tucked into socks, long- sleeve shirts and
boots. Chemicals can be sprayed on clothing and skin to help repel the ticks.
And people should check themselves regularly for ticks.
Q. How is Lyme disease diagnosed?
A. About three-quarters of the cases are diagnosed by the symptoms that show up
after the tick bite, often but not always beginning with a characteristic
bull's-eye rash, an area with a red center and an outer red ring. Blacks
develop the same rash as whites, though it is harder to detect on darker skin.
The size of the rash typically increases from half an inch to several inches
across, and it may get much larger. Accompanying or following the rash may be
other symptoms like fever, stiff neck, headache, body aches and fatigue.
These initial symptoms occur within the first few weeks of infection. Later,
other symptoms may appear. A common one is Lyme arthritis, which can bring on
pain, redness and swelling in the joints, particularly the knees. The arthritis
can last from a few days to a few months, but if the Lyme infection goes
untreated the arthritis may become a chronic problem.
Other late-onset symptoms include severe headaches, temporary paralysis of
some facial muscles (Bell's palsy), numbness of the limbs and poor
coordination. Some patients report mental problems like memory loss or
inability to concentrate.
Doctors diagnose Lyme disease based on symptoms and patient history, but
they can also use blood tests to spot antibodies to the Lyme bacteria or tests
that spot the genetic material of the bacterium if it is present. Sometimes,
however, the disease is present when tests are negative, or tests are positive
when the disease is absent.
The lack of a clear-cut diagnostic test is a
major problem. Researchers at the National Institutes of Health and elsewhere
are developing new tests.
Q. What are the treatments and the prognosis?
A. If left untreated, 60 percent of people with the disease develop
intermittent attacks of joint swelling and pain. On the other hand, some people
have such mild cases that they may never know they have had Lyme disease. In a
few cases, untreated disease can lead to severe, chronic and disabling illness,
according to the Centers for Disease Control. In any event, taking antibiotics
for 14 to 21 days cures more than 90 percent of the patients. Most of the rest
are cured after a second course.
Q. Once you have had Lyme disease, can you get it again?
A. Yes, getting the disease once does not protect you from getting it again.
You can be reinfected repeatedly.
Q. What is happening with people who continue to suffer symptoms?
A. Some patients show up with strong symptoms long after treatment. In some
cases, when the bacteria can be spotted in the body, another treatment with
antibiotics may work. If the bacteria are not spotted by tests, doctors have
differing advice about what to do.
Most doctors who treat Lyme disease believe that continuing symptoms are not
caused by the presence of the bacteria themselves. It may be, they say, that
before the Lyme bacteria were eradicated from the body, they caused some damage
that led to recurring symptoms. For example, the bacteria may set off a
reaction that leads the body to attack its own tissues instead of attacking the
bacteria.
Or, they say, patients are suffering from symptoms of some other condition
unrelated to tick bites.
Some researchers have suspected that the re-emergence of the disease comes
because the bacteria remain hidden in the body and emerge later. They say
people who continue to suffer symptoms must be treated with long-term courses
of antibiotics.
The Klempner study challenged this view. It found that extended treatment
with antibiotics did not help people who believed they had persistent Lyme
infection, a finding that suggested that their symptoms were unrelated to the
bacteria. But believers in the long-term Lyme theory criticized the design of
the study. Meanwhile, other research is under way.
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