Lyme Disease Diagnosis and Treatment: A Q&A with David J. Herman, MD, FACP

Internal Medicine World Report Editor-in-Chief Simon Douglas Murray, MD, consulted with David J. Herman, MD, FACP, Senior Partner at ID Care, the largest network of infectious disease specialists in New Jersey, on the treatment of Lyme disease and other tick-borne infections.

Despite the fact that Lyme disease is relatively common, there still seems to be a great deal of confusion about its diagnosis, treatment, and prognosis. Practicing physicians in the Northeast see many cases of suspected Lyme disease and are often not clear about the actual diagnosis.What tools are available for diagnosing Lyme disease beyond a good history and physical exam? Specifically, what is the value of Western blot testing, and are there any other tests of value?

The recommended testing for Lyme disease is to screen with an antibody test using the enzyme-linked immunosorbent assay (ELISA) method. If the result is positive or equivocal, then perform a confirmatory test with a Western blot. Both forms of testing should be performed by a laboratory that has been accredited by the College of American Pathologists (CAP).

Lyme disease testing should only be performed if all of the following criteria are met: (1) The patient resides or has traveled to an area endemic for Lyme disease; (2) the patient has risk factors for exposure to ticks; and (3) the patient has symptoms compatible with early disseminated Lyme disease or late-stage Lyme disease, including meningitis, arthritis, carditis, or cranial nerve palsy. The testing should not be ordered on asymptomatic patients living in an endemic area or those with nonspecific symptoms.

The serologic tests are not very sensitive in very early Lyme disease infection, as there are many false negative tests in the first few weeks following infection. Therefore, patients who present with an erythema migrans rash do not need serologic testing; instead, those patients should just be treated.

The Western blot is not intended to be used as a screening test. Rather, it should be used as a confirmatory test, since it is more specific than the ELISA test, and thus produces fewer false positive results. Nonetheless, neither of these serologic tests should be ordered on synovial fluid.

Although neither of these serologic tests should be ordered on synovial fluid, the polymerase chain reaction (PCR) test may be useful to help confirm the diagnosis of Lyme disease on synovial fluid, and perhaps on cerebrospinal fluid (CSF). However, it should not be ordered if the serum tests are negative, because a positive PCR test on synovial fluid or CSF in the setting of a negative serum antibody test likely represents a false positive result.

PCR testing is most useful in a patient with a positive Lyme disease antibody with a confirmatory Western blot and a joint effusion that recurs after treatment. If the PCR test on the synovial fluid is positive after treatment, it suggests the possibility of ongoing infection, instead of immunologic reasons for the recurrent joint effusion.

What are the stages of Lyme disease and what is the best treatment based upon stage?

Lyme disease may be divided into 3 stages: (1) Early localized disease, such as erythema migrans rash; (2) early disseminated disease, such as Lyme carditis, meningitis, and cranial nerve palsies; and (3) late-stage disease, such as Lyme arthritis and Lyme encephalopathy.

The recommended treatment for early localized disease is twice-daily oral doxycycline 100 mg for 10-21 days or thrice-daily oral amoxicillin 500 mg for 14-21 days. Although other antibiotics such as azithromycin, clarithromycin, and cefuroxime axetil have been used, none are more effective than doxycycline or amoxicillin, and some are much more expensive. In fact, some trials have shown azithromycin to be less effective than amoxicillin.

The recommended therapy for early disseminated Lyme disease without meningitis is twice-daily doxycycline 100 mg for 21 days. In patients who are unable to take doxycycline, amoxicillin may be used.

Other recommended therapies for early disseminated and late-stage Lyme disease are as follows:

• Lyme meningitis: Daily intravenous (IV) ceftriaxone 2 grams for 14-28 days.
• Lyme arthritis: Twice-daily doxycycline 100 mg or thrice-daily amoxicillin 500 mg for 30 days.
• Lyme encephalopathy: Daily ceftriaxone 2 grams for 28 days.
• Lyme carditis First-degree atrioventricular (AV) block with PR interval <0.3 seconds: Twice-daily doxycycline 100 mg for 14-21 days First-degree AV block with PR interval >0.3 seconds, or a second- or third-degree AV block: IV ceftriaxone for 14 -21 days, although there is no data to show that it is superior to oral doxycycline.

What is the role of IV therapy in the treatment of Lyme disease?

IV therapy is only used for central nervous system Lyme disease, Lyme carditis with a PR interval >0.3 seconds, or for proven Lyme arthritis that is unresponsive to oral antibiotics. There is no data to support IV antibiotic therapy in excess of 30 days.

There is a great deal of hysteria surrounding Lyme disease. Many patients are frightened the disease is easily missed by doctors and will go on to become very serious and life-threatening. I had a patient who went as far as replacing all the grass in the yard with Astroturf before allowing the children play outside. In the summer months, patients are exposed to deer ticks on a daily basis. At the same time, I don't see hospitals and offices filled with people with crippling arthritis and neuropsychiatric symptoms attributable to Lyme disease.Is it possible that only a minority of patients will develop long-term complications, even if left untreated?

The best data I can find on this subject revolves around the diagnosis of Lyme arthritis. In the late 1970s, before the cause of Lyme disease and the role of antibiotics were known, the natural history of Lyme arthritis was described in a cohort of 55 patients followed prospectively from the onset of the disease with erythema migrans through later manifestations of the disease. Months after the onset of infection, about 60% of the untreated patients developed joint swelling and pain.

Is it advisable to treat patients prophylactically for tick bites?

It is generally not advisable to treat patients prophylactically for tick bites. Many patients do not know what bit them. Even if they knew it was a tick, they may not know what type.

However, if the patient was bitten by a deer tick, and if the tick fed for >36 hours, and if the treatment can be started within 72 hours of the tick bite, then a single dose of doxycycline 200 mg has been shown to decrease the occurrence of Lyme disease from 0.4% in the doxycycline treated patients to 3.2% in the placebo treated patients. But if a known tick bite occurred and the patient is observed for signs and symptoms, then treatment may be initiated at that time with an approximate 90% cure rate from a 14-day course of doxycycline or amoxicillin.

Is there any value in analyzing the ticks that patients are exposed to? Over the years, patients have brought me specimens of ticks pulled from their skin, but I do not find this particularly helpful, other than to identify the ticks as deer ticks.

Although laboratories are available that can identify ticks and determine if the ticks carry the Lyme disease bacteria, such testing is not very useful. If the tick tests positive, it does not tell you whether the tick transmitted the disease to the human, and if the tick tests negative, it will give the patient a false sense of security because the person may have suffered other unrecognized tick bites and still be infected.

One approach I have employed when treating patients who have a suspected deer tick imbedded in their skin is to withhold antibiotic treatment until symptoms develop, and then if they don't develop in a matter of a few weeks, I bring the patients back for an ELISA and Western blot test.How soon after exposure to a tick bite can we expect the antibody tests to become positive, and how long will they remain positive?

After erythema migrans, immunoglobulin M (IgM) antibodies become positive within 1—2 weeks, while immunoglobulin G (IgG) antibodies become positive within 2–6 weeks. The antibody and Western blot tests may remain positive for months to years even after successful treatment.

I have read a recommendation to give a single dose of doxycycline while waiting for symptoms to develop or a positive test. Is this rational?

As I mentioned before, a one-time dose of doxycycline may be administered in certain circumstances to prevent the occurrence of Lyme disease. Once it is initiated, one would not expect symptoms to occur.

It is important to note that one study indicated that in an area with a high incidence of Lyme disease, at least 40 patients would need to be treated to prevent one case of Lyme disease. In areas without a high incidence of Lyme disease, many more patients would have to be treated to prevent one case of Lyme disease.

What is chronic Lyme disease and how is it diagnosed? I am unaware of any blood test that may aid in the diagnosis, but are there diagnostic criteria for making one? How is it different than post-Lyme treatment symptoms?

The post-Lyme disease syndrome refers to nonspecific complaints that persist for months after the treatment of Lyme disease in some patients. There is no data to support that these symptoms are secondary to active infection, and there is also no data to support that further courses of antibiotics will hasten the resolution of these symptoms, which have sometimes been attributed to “chronic Lyme disease.”

Clinical trials have discovered other explanations for some of these symptoms, such as fibromyalgia, depression, chronic fatigue syndrome, and obstructive sleep apnea (OSA) in some patients. However, Lyme disease is not a diagnosis of exclusion, so it should not be assumed that lack of another diagnosis proves that active Lyme disease infection provides an explanation for the symptoms.

What happened to the Lyme disease vaccine?

Though some patients claimed adverse reactions to the vaccine, those symptoms were not seen in the clinical trials, which included more than 10,000 patients. The vaccine’s manufacturer, GlaxoSmithKline, only cited poor sales as the reason for withdrawing it from the market.

In addition to Lyme disease, what are other important tick-borne illnesses that internists should consider?

The other important tick borne illnesses are babesiosis and anaplasmosis, which was previously termed Human Granulocytic Ehrlichiosis. These 2 infections are transmitted by the same tick that carries Lyme disease. Similar to Lyme disease, anaplasmosis is treated with doxycycline, though babesiosis is treated with other antibiotics.

Human Monocytic Ehrlichiosis is transmitted by a different tick, as is Rocky Mountain spotted fever, which is rarely seen in New Jersey.

Bartonella has been cited as a tick-borne illness, so numerous molecular surveys to detect Bartonella DNA in ticks have been conducted. However, there is little evidence that Bartonella species can replicate within ticks, and there is no definitive evidence of transmission by a tick to a vertebrate host.

Looking at Lyme disease and what you have learned about it over the past 20 years, what are your biggest frustrations with primary care physicians’ approach to the diagnosis and treatment? What are the pitfalls and best practices?

My biggest frustration about the diagnosis and treatment of Lyme disease is the misinterpretation of laboratory tests by some physicians. The IgM antibody and IgM Western blot should only be used to diagnose Lyme disease in a patient whose symptoms have been present for less than one month, because the IgM tests are notoriously inaccurate in patients whose symptoms have been present for more than one month.

I frequently see patients with joint complaints present for months or years with only positive IgM antibodies and negative IgG antibodies. Such an antibody response is not consistent with late-stage Lyme disease. Many of these patients receive weeks or months of antibiotics without improvement. A patient with this pattern of test results does not have Lyme arthritis, and should not be treated as such.

A positive Lyme disease IgM test result with a negative IgG test result in a patient with symptoms that are present for months or years signifies a false positive test, so in that case, other diagnoses should be pursued.