Update On Lyme Disease

Interview with Experts

Leonard Sigal, MD
Director of Rheumatology
Robert Wood Johnson Medical School , New Brunswick, NJ

  1. How Is Lyme Disease Diagnosed?
  2. Use of the Laboratory in Lyme Disease
  3. Detecting a Spider Bite vs. a Tick Bite
  4. How to Prevent Lyme Disease
  5. Lyme Arthritis vs Rheumatoid Arthritis vs Reactive Arthritis
  6. Oral Treatment of Lyme Disease
  7. Other Tick-borne Diseases

How Is Lyme Disease Diagnosed?

The diagnosis of Lyme disease is made the way that one makes any diagnosis: complete history, physical examination, and laboratory tests. However, lab tests can be overused in this problem. Lyme disease causes objective findings in patients. Objective findings may include:

  • erythema migrans - an expanding red rash, usually painless; the "classic bull's-eye" rash of Lyme disease is seen in about one-third of all patients with a rash, or other rashes;
  • Viral Syndrome-like illness, such as fever, headache, chills, and aching muscles;
  • arthritis (inflamed swollen joints) and arthralgias (aching joints);
  • myalgias (aching muscles), and other soft tissue problems (such as inflammation of tendons and bursae);
  • heart disease, manifest as mild carditis (inflammation) or a slowed heart rhythm caused by improper conduction of electrical signals through the heart;
  • lymphocytic meningitis (inflammation of the membrane surrounding the brain);
  • facial nerve palsy (Bell's palsy), or other nerve paralyses;
  • peripheral neuropathy, ranging from a tingling to a burning in fingers, hands, and feet;
  • cognitive dysfunction, such as poor concentration, forgetfulness, and memory loss.

All of these things can be objectified, if not by physical examination, then by the judicious use of laboratory tests, which could include analysis of synovial fluid (the fluid in joints) and spinal fluid analysis, as well as neuropsychological testing to identify people with true cognitive dysfunction, electrocardiogram and other heart studies.

Both patient and physician need to be objective. The patient needs a physician who is not biased toward making the diagnosis of Lyme disease even before the encounter, one who does not walk into the clinical encounter saying, "How am I going to find (or invent) the diagnosis of Lyme disease here?" The proper approach is "How am I going to figure out what is going on with my patient and make that patient feel better?" If testing for Lyme disease can help eliminate it from consideration and allay the patient's concerns, then testing may be useful. However, physicians make a diagnosis based on history, physical examination and the judicious use of laboratory tests. The laboratory is by far the least important of those three factors. One should never make a diagnosis of Lyme disease based solely on the results of laboratory if the patient has no historical or physical features suggesting Lyme disease.

Use of the Laboratory in Lyme Disease

There are only a few laboratory tests that are available for confirming Lyme disease. I prefer to use the term "confirmatory test" rather than "diagnostic test", because you don't make the diagnosis of Lyme disease based on blood tests or any other tests. You consider Lyme disease, come up with what you consider the pre-testing likelihood of the disease, and then you test and interpret the testing in the clinical setting.

The initial screening blood test is ELISA, which stands for enzyme-linked immunosorbent assay. Your blood is placed in little wells coated with the Borrelia organism that cause Lyme disease. If your blood has antibodies to the organism, these antibodies will attach to the Borrelia proteins on the well wall. However, because even in normal people some blood antibodies may loosely attach to the Borrelia proteins, the results from normal people are not totally negative. So every laboratory must establish an accurate "normal" range for the population in its area - and that can be a delicate process fraught with problems. ELISA is by definition a high sensitivity, relatively low specificity assay. That means it is designed to pick up everybody who might be infected but in so doing, it also picks up as positive some normal people; so there is a risk of false positives. A positive or an equivocal ELISA alone does not mean you have Lyme disease. It should be confirmed by Western blot test.

Early in the immune response your body makes antibodies called IgM; later, these antibodies are replaced by IgG antibodies (although in some cases, the IgM antibodies may persist for months or even years.) Western blot is done to detect both IgM and IgG antibodies. IgM criteria apply in early infection. IgG criteria apply in later disease. So if somebody comes in within the first 6 to 10 weeks OF Lyme disease, one would expect to see IgM reactivity. If somebody comes in with a diagnosis of Lyme disease that supposedly started a few months to a year or more ago, one would expect to see IgG criteria satisfied.

Serologic reactivity (the results of your blood in the specific test) can persist for quite a while, so, in general, a person who is treated and then cured should not be retested. The only circumstance in which we retest is when somebody comes in with worsening of complaints or new complaints. As an example: If somebody is treated for erythema migrans and does well, but 6 months later comes in with an arthritis that we think is Lyme disease, then we may retest to compare. In that circumstance, I would expect to see the ELISA being higher and the Western blot would give an even stronger indication of infection. So there the laboratory can help the physician confirm what the clinical impression. But to retest patients who are asymptomatic to see if they need more antibiotics is wrong. The person is cured - leave them alone. There is no reason to retest.

One can look for antibodies in joint and spinal fluids in patients with Lyme arthritis or Lyme neurologic disease. One laboratory (Imugen, in Norwood, MA) does a very good job in this kind of testing and we recommend such samples be sent there.

Other tests are also available:

PCR (polymerase chain reaction) which amplifies the genetic material (DNA) of the organism can be done on joint fluid or tissue, spinal fluid and blood. The problem with PCR is that there are a lot of false positives. It is a very sensitive assay that can pick up contaminants along the way. But, of more importance, the Borrelia organism doesn't persist in the fluid phase system that long. So, shortly after infection, the organism will no longer circulate in the blood, will not be found in the synovial or spinal fluid. So, doing PCR is not necessarily a high yield test.

One can grow Borrelia burgdorferi directly from blood or tissue; this is done by a few scientists around the United States. In general, this is not available and some of the tests are not confirmed.

- The Lyme Urinary Antigen Test (LUAT) is not a test that we use, and I think is a test that should not be used. It is of no proven value in the diagnosis and management of Lyme disease. It frequently produces false positive results and thus encourages the false diagnosis of Lyme disease.

Detecting a Spider Bite vs. a Tick Bite

It is important to distinguish between tick bites and other bites. The brown recluse spider in the Northeast does indeed try to hide. It backs into its own little corner, its own niche. Brown recluse spiders are found in that corner of your garage that you haven't explored for about four years and the old woodshed that you haven't opened up for a long time or in piles of wood that you haven't disturbed for quite a while. When you disturb such an area, the brown recluse spider will try to hide, and if it can't, it will bite you in defense. So the areas where people are bitten are their hands or feet when they accidentally enter that sort of danger zone for the brown recluse spider.

Those are not typical places to have erythema migrans. Erythema migrans is typically in the armpit, groin, behind the knee, around the waistline and chest, where the tick typically bites.

Further, the brown recluse spider bite hurts a lot, and it hurts relatively quickly. So you will have somebody in a lot of pain; in fact sometimes they have necrosis (tissue death) at the center of the brown recluse spider bite, whereas the erythema migrans rash is usually asymptomatic. (If there are symptoms from a tick bite, it is mild itching or burning, and it evolves over the course of a couple of days, not immediately upon exposure.)

With attention to detail, one can differentiate between spider bites and tick bites reasonably well.

How to Prevent Lyme Disease

Knowing where there is Lyme disease is the best way to prevent Lyme disease. Most Lyme disease is acquired around the house, on your own property. Ticks do not survive on sunlit lawns for too long. They dry out relatively quickly. They survive in the leaf clutter at the bottom of the forest. So, if you live in an area immediately above the forest, clean up the leaf clutter at the edge of the forest. Replace it with wood chips. Wood chips dry out very nicely, so if you want to apply a chemical that kills ticks, that is where you apply it.

You really have no need to "blanket bomb" your back yard, because ticks do not survive in the bright sun. But they are surviving in the leaf clutter and the brush at the edge of the forest. Clean that out, replace it with wood chips, and take the kids toys and such away from that area. If the kids play in the middle of the lawn, they are less likely to get Lyme disease.

If you live in an area where there are deer wandering in and out of your yard, then you have some degree of risk. If there are white-footed field mice wandering around in your property, then you are at some risk. Some would say that having a bird feeder represents a risk, because birds are notoriously sloppy eaters and the mice will come along and get the stuff that is on the ground.

A stone wall on one's property, e.g., an old colonial stone wall that used to serve as a boundary marker, is also a "condominium" for mice. Mice like living in the cracks between the rocks- that is where there are going to be mice, and mice carry ticks. So, if you have those areas around you, you might want to spray in the immediate area around the old stone wall. You might want to clean up some of the leaf clutter around your property and put down some wood chips at the edge of your property.

Most importantly, at the end of every day, do a tick check. Get to know your freckles, especially get to know freckles that are moving!! What people don't seem to remember is that ticks take 24 hours or longer to settle down. The only way that the tick can spread the organism into you is having already taken its blood meal. That gives you an additional 24 to 36 hours. A tick must be on board for two days in order to deposit the organism into you.

So when your children go out to play, at the end of every day, do a tick check. Give them a shower and use a washcloth. Do not over-do it and abrade them down to the point of bleeding, but a tick that is not attached yet will be knocked off by a reasonably applied washcloth.

If the tick is attached and it is not engorged with blood that it has sucked, the likelihood of getting Lyme disease is less than 1%. Get a very thin set of tweezers, apply as close to the skin surface as possible, and pull gently but firmly and remove the tick. Clean up the skin, leave it alone, and keep an eye on the person. If an erythema (redness) develops -- not a dime-sized erythema that may be a reaction to the tick saliva -- a red area develops and expands and expands and persists for more than two or three days, or other symptoms develop, then there is a possibility of Lyme disease, and a physician visit is warranted.

Lyme Arthritis vs Rheumatoid Arthritis vs Reactive Arthritis

In Lyme arthritis, the classic pattern is an inflammatory joint disease of the knee, chronically. The knee is swollen, red, and stiff, though not very painful. The knee can be so swollen that patients can't pull their knee in. There is a big effusion (fluid in the knee joint) and when it is aspirated (the fluid removed with a needle), the fluid re-accumulates rapidly. You can take 80 cc out of a Lyme-diseased knee, and three days later, there is 135 cc. The re-accumulation is very rapid, much like reactive arthritis. There are times when one confuses reactive arthritis with Lyme arthritis.

The way the diagnosis of Lyme arthritis is made is first from a full history, to exclude the other features of reactive arthritis and to include risk factors such as residence. If there was a prior diagnosis of Lyme disease, one can then go ahead and do blood tests, ELISA and Western blot or do Western blot on the synovial (joint) fluid. One can look for concentration of antibodies within the synovial fluid compared with the serum. If one finds a high level of antibodies against the organism in the synovial fluid, then I think one can make the diagnosis of Lyme disease/Lyme arthritis with confidence.

The treatment for that is oral antibiotics for four to six weeks. If people do not respond, then the next step would be intravenous antibiotics, using ceftriaxone or cefotaxime for four weeks. The durations are not well established on the basis of double blind placebo controlled studies.

I have seen two patients with a bilaterally symmetric inflammatory joint disease affecting the small joints in the hand, looking like rheumatoid arthritis, who, in fact, had Lyme arthritis. It is not a common pattern, and I think that one is reasonably assured that if one sees what looks like rheumatoid arthritis, it probably is rheumatoid arthritis. Lyme disease patients do not usually have positive findings on blood tests used to diagnose rheumatoid arthritis; that is, they are usually negative for ANA and rheumatoid factor. The sedimentation rates (a measure of inflammation) are typically not all that high in Lyme arthritis. If one sees somebody with bilaterally symmetric inflammatory joint disease and an ELISA that is positive and a Western blot that is negative and a rheumatoid factor at 1:160, I think that is rheumatoid arthritis.

Oral Treatment of Lyme Disease

Lyme disease, with early manifestation that includes mild carditis and erythema migrans -- should be treated with oral antibiotics. And the oral antibiotic of choice would be amoxicillin or doxycycline. The two are equivalent. There is some concern about doxycycline in pregnant women and in children under the age of 8. Nonetheless, those are the drugs of choice. Other drugs have been tested, but no drug is superior. Doxycycline has the added advantage of also treating another tick-borne infection occasionally seen in the same areas as Lyme disease: human granulocytic ehrlichiosis.

Duration of therapy is still not fully established and may depend on disease manifestation. Anything between two and four weeks seems to work. Some communities use four weeks because of the degree of anxiety, but two weeks seems to be more than adequate. For people with arthritis, we typically treat for six weeks, although that is not well established. For people with meningitis or severe carditis, we use two weeks of intravenous therapy and that would be ceftriaxone 2 grams a day or cefotaxime 3 grams twice a day. Those are the adult doses; the pediatric doses are based on weight of the child. Those drugs for two weeks are effective in the treatment of Lyme meningitis or Lyme central nervous system disease. If somebody has not responded to oral antibiotics, or if somebody has evidence of central nervous system disease aside from meningitis, we typically treat for four weeks. We don't know what the optimum duration is, but what we have noticed over the course of the years is that that duration does work.

Note that in patients with Lyme arthritis, and especially in patients with central nervous system Lyme disease, the time to ultimate resolution may be measured in months and even years. So a person with cognitive dysfunction, memory and concentration difficulty, who is treated with intravenous antibiotics, is cautioned that a response may not be obvious over the course of the first couple of weeks or even months. Physicians do interim cognitive testing in order to demonstrate to the patient that there is improvement. But it has taken 18 months in some to see a really good response when cognitive and behavioral changes have been the manifestation of Lyme disease.

Other Tick-borne Diseases

Lyme disease is a diagnosable and treatable phenomenon. However, there are two fellow travelers worthy of mention: ehrlichiosis and babesiosis. They are both here in the Northeast, well described in New Jersey, New York, and Connecticut; they are both spread by the same tick.

Both of these syndromes differ from Lyme disease in that they commonly cause high fevers. In Lyme disease with erythema migrans one would expect fever to be 101, in a child maybe 102. If somebody tells you that they had a rash and then they had a 102 or 103 or higher fever, I would be very concerned about the possibility of one of the other infections in combination with Lyme disease - two infections spread by the same tick bite, presumably. These other infections can also cause thrombocytopenia (a condition in which there is an abnormally low number of platelets in the circulating blood) and neutropenia (the presence of abnormally low numbers of neutrophils in the circulating blood) - neither of which occurs in Lyme disease. Both ehrlichiosis and babesiosis can also cause liver function test abnormalities and you typically don't see that in Lyme disease either. So if the rest of the laboratory tests also suggest that this is a more severe disease, a person may have Lyme disease and human granulocytic ehrlichiosis, which is similar to Rocky Mountain Spotted Fever.

Alternatively, someone can come in with "Lyme disease" but no erythema migrans; but if they were very ill with high fevers, they might have those other two tick-borne infections. And those can be diagnosed on the basis of examination of a thick smear of blood looking for the Babesia parasite within red blood cells or the Ehrlichia organism within the white blood cells called granulocytes. There are blood tests that can be done that are reasonably good for the Babesia human granulocytic ehrlichiosis. In some cases, a patient may seem very ill and have a fever, but may recover in a few days. They may have had a viral infection.

If the person continues to be ill, in spite of the fact that tests are initially negative, another test should be done a few weeks later. There are no chronic Ehrlichia or Babesia syndromes. These infections are usually handled very nicely by normal people, and, in fact, the infections may cause minimal if any symptoms and clear on their own. On the other hand, people with immune deficiency syndromes, the very young and the very old, and people who have had their spleens removed are predisposed to developing severe Babesia and Ehrlichia infections, and they can rarely be fatal in those populations. (Addendum: In population studies in endemic areas, most cases of Ehrlichia and of Babesia are asymptomatic, i.e. there are a lot of people who are seropositive for one or both of these organisms but who never had a syndrome compatible with acute infection).

From an interview with Dr. Leonard Sigal by Dr. Stephen A. Paget

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