Lyme Disease Executive Summary
Widespread variation in testing, diagnosis and treatment still exists
despite current literature-based evidence.
Scope and focus of guideline
To aid the clinician to appropriately diagnose and treat Lyme disease. The
guideline offers the practitioner solid evidence to explain the rationale for
treatment plans to patients.
Pediatric and adult primary care practitioners.
Key clinical points
- The most common reason for Lyme treatment failure is incorrect
diagnosis. As many as 75% of patients seen for presumed Lyme disease or
Lyme treatment failure actually have fibromyalgia.
- Lyme disease is a clinical diagnosis. The presence of an erythema
migrans rash makes the diagnosis of Lyme disease without any need to do blood
testing. Adequate travel history is imperative.
- Lyme test positivity does not equal Lyme disease. In the setting
of a patient who presents without a tick bite and without a rash, a low
positive Lyme ELISA test, such as 1.01 to 1.10 with a cut-off of 0.99, is much
more likely to represent a false positive rather than a true positive test.
The limitations of laboratory studies including high false positive rates must
- Serial Lyme titers do not give any useful clinical information for
follow-up. Persistent Lyme seropositivity in a patient who has been cured
is common and should not cause any alarm or result in treatment.
- A three week course of oral antibiotics will cure the vast majority of
cases. There are very few definitive indications for IV antibiotics in
Lyme disease. Persistent symptoms following successful treatment can occur on
an immunologic basis, which may explain the concept of Lyme associated
fibromyalgia. Usually this presentation does not require IV treatment.
- Bell's Palsy, even in a non-edemic area, should trigger a Lyme serology.
Key clinical strategies
- Taking a complete and careful history is essential.
- Do not order ELISA unless indicated by pretest likelihood of disease.
- Treat with PO antibiotics unless specific indications for IV, i.e., CNS
disease or PO treatment failure.
Level of evidence
Expert opinion and consensus.
Guideline initially authored by Allen Smiley, MD, William Teubl, MD,
Richard Brown, MD, Anna Simpson, MD, John Donhowe, MD, Jean Collins, Betty
Diorio, Carol DeLaMarter and revised by Alan Gross, MD, Jeffrey Stein, MD,
Paul Lemanski, MD, Jeffrey Palmer, MD, Bonnie Richardson, MD, Steven Luger, MD
Guideline For Diagnosis Of Lyme
Annotations for Lyme Diagnostic
- Any set of signs or symptoms the practitioner feels is consistent with
Lyme such as rash, viral syndrome, arthritis, arthralgias, myalgias,
neuropathy, etc. Symptoms presenting in isolation need a careful consideration
of the differential diagnosis.
- Symptoms suggesting need for immediate treatment include: (1) an Erythema
Chronicum Migrans (ECM) rash, (2) viral syndrome after a tick bite (especially
between June and September), (3) Bells Palsy in an endemic area, or (4) a tick
bite in a pregnant woman. There is no benefit to testing in this setting. An
ECM rash is defined as a slowly enlarging rash that develops 3 to 30 days
after a tick bite. Circling the rash with a pen mark may be helpful. A viral
syndrome is defined as flushing, documented increased temperature, chills,
etc. with arthralgias or myalgias in the absence of gastroenteritis or a URI.
- Current recommendations for treatment are:
- Amoxicillin 500 mg PO TID or
- Doxycycline 100 mg PO BID (in adults or children >9 years old)
- For PCN allergic patients less than 9 years old: Ceftin 500 mg BID
All regimes are given for a total of three weeks. Summer viral syndrome may
be Ehrlichiosis and practitioners may choose to use Doxycycline 100 mg BID for
three weeks with sunscreen as first line treatment in this setting for either
adults or children. At least two deaths have been reported from Ehrlichiosis
treated with Amoxicillin alone.
- The knee is the most common site, but any large joint arthritis needs to
include Lyme in a differential diagnosis.
- Arthrocentesis may be indicated to rule out a septic joint.
- An inflammatory effusion is an effusion with a white blood cell count of
>2000 that had a sterile culture.
- Differential diagnosis would include either a septic joint or some other
joint problem that has a low grade inflammatory component (e.g., mechanical).
- Bells Palsy could be a presentation of Lyme disease even in nonendemic
areas. However many cases of Bells Palsy under these circumstances will not be
due to Lyme. Hence serologic testing is recommended to help sort out etiology.
There is no literature to support approaching endemic and nonendemic Bells
Palsy differently; this recommendation is based on physician consensus. If
Lyme serology is positive, a lumbar puncture should be performed.
- See testing guideline for further details.
- The literature uses 48 hours fairly consistently as a cutoff when
evaluating the likelihood of infection being transmitted. If no bite was ever
noted by the patient, the answer to this question is no and the user should
proceed to box 13. If a bite is remembered by the patient but the duration is
unknown, the practitioner will likely want to assume it had been on for >
48 hours, especially if the bite occurred in an endemic area.
- Arthralgias, myalgias, headaches or fatigue are recognized as common minor
symptoms that raise the question of Lyme disease. These symptoms are termed
minor not because of low morbidity but because they are not highly predictive
of Lyme disease.
- A tick bite can be observed for one month for an ECM rash or a viral
syndrome. The development of symptoms would then allow for reentry into the
guideline for reevaluation.
- Same as #11.
- Endemic areas in the East include Fire Island, Block Island, Cape Cod,
Nantucket, Martha's Vineyard, the Jersey Shore to Maryland, and parts of
Connecticut, Massachusetts, New York State, Rhode Island, and Maine. The
Pacific coast and upper midwest states are also considered endemic.
Practitioners should check with local public health departments for more
current information in their areas.
- See testing guideline for further details.
- This point in the guideline represents the differential diagnosis of a
patient with non-specific symptoms that caused the consideration of Lyme
disease but without the following: ECM, viral syndrome, Bells Palsy, large
joint effusion, tick bite > 48 hours, arthralgias, myalgias or headache.
The likelihood of Lyme in this setting is very low, and the chief complaint
should be scrutinized and the differential diagnosis generated around that
- Either treating or testing is justifiable at this juncture. If empiric
treatment is chosen, only oral therapy is warranted. If the practitioner feels
IV treatment needs consideration, testing and/or referral is strongly
encouraged. If empiric testing is chosen, follow-up Lyme testing is of unclear
benefit, so clinical endpoints should be defined by the practitioner in
advance of treatment. Lastly, the literature suggests that the placebo
response to antibiotics in the setting of possible Lyme disease is as high as
Annotations for Lyme Testing and Treatment
- The Elisa test currently being used has a sensitivity of 94% and a
specificity of 97%. Lyme titers may be falsely positive in patients with
mononucleosis, periodontal disease, connective tissue disease and other less
- Positive Elisa? No comment.
- It is estimated that the likelihood of Lyme disease at this point is about
1%. The main differential to consider is fibromyalgia. A referral to
rheumatology or neurology is considered reasonable at this point. Frankly
asking the patient if he or she is willing to accept a diagnosis other than
Lyme disease may be of value. This will help identify patients who are
convinced they have Lyme disease. Discussing why a patient feels that way and
their fears might be more appropriate than focusing on the technical aspects
of the disease alone.
- If a non-Lyme diagnosis reasonable, treating the patient for the diagnosis
is the obvious next step. If treatment has failed, the practitioner could
re-enter the guideline at this point and proceed to box 5.
- An early test could be falsely negative. Although literature is limited, 6
weeks is a rational interval for retesting to allow for seroconversion.
- Positive Elisa? No comment.
- At this point the likelihood of Lyme is quite low. However, the
limitations of testing and the high anxiety of some patients will lead some
practitioners to opt to treat. Empiric treatment is considered far more
reasonable than recurrent testing because of the increasing risk for a false
positive result (especially high at this point because of the low pretest
probability). Should the practitioner opt for treatment, the patient should
understand the risks (mainly reaction to antibiotics) and benefits (hard to
define; placebo effects may be as high as 35%). Empiric treatment should
consist of a single course of oral medication. If symptoms persist after
treatment, consultation should be considered.
- The Western blot is very specific if a positive test is defined as 5 out
of 10 reactive IgG bands. This step will eliminate most false positives. The
IgM Western Blot is in a state of flux; review by a national consensus panel
is needed before making any recommendations concerning interpretation.
Practitioners are encouraged to rely on IgG values and to seek phone
consultation with Dr. Allen Smiley, rheumatologist with expertise in
Lyme Disease in the Hudson Valley Region (Phone # 914/471-2800 or
- Positive Western Blot? No comment.
- Lyme disease can cause heart block of any grade. The treatment of 3rd
degree AV block requires IV antibiotics and cardiac consultation to evaluate
the need for temporary pacing. Lower degrees of block can be treated with an
oral course of medication along with careful follow-up.
- See #11.
- The key issue at this point is to determine whether to treat the patient
with PO or IV medication. It is generally agreed among our expert consultants,
and in the most recent literature, that CNS Lyme and Lyme arthritis that has
failed PO therapy are indications for IV treatment. Lyme arthritis is
relatively easy to identify, but most Lyme arthritis will respond to PO
medication so failures will be rare.
The major dilemma is determining the
presence or absence of CNS disease. The presence of the following in CSF would
be adequate to establish the diagnosis of CNS Lyme:
1. Pleocytosis plus or minus increased protein
2. Positive CNS
Elisa or PCR to Lyme
It is recognized that many practitioners do not perform spinal taps and
that spinal taps can be falsely negative. Furthermore, memory loss and
fatigue, possible manifestations of CNS disease, are nonspecific and difficult
to objectify. A guideline to help the practitioner at this juncture is too
complex and uncertain.
Should practitioners opt to treat, it should be
remembered that follow-up testing after treatment with antibiotics is
generally uninterpretable. Careful attention to the clinical symptoms marked
for improvement with treatment is important and will likely be the only basis
for determining efficacy.
- The most recent practice among centers treating Lyme disease is to use
four weeks of Ceftriaxone instead of two weeks (2 gm OD in adults and 50-75
mg/kg OD in children).
The following articles were used as a reference by the Lyme Disease
1. "Empiric Parenteral Antibiotic Treatment of Patients with Fibromyalgia and
Fatigue and a Positive Serologic Result for Lyme Disease: A Cost Effective
Analysis," Robert W. Lightfoot, Jr. et al (1993, American College of Physicians,
Comment: Even in endemic areas, the incidence of false positive
serologic tests in patients with myalgia or fatigue exceeds true positives by a
ratio of 4:1.
2. "The Use of Serologic Tests for Lyme Disease in a Prepaid Health Plan in
California," Catherine Lay, MS et al (JAMA 2/9/94-Vol. 271, No. 6)
Over a three month period, 117 patients out of Kaiser Permanente HMO site had
Lyme blood tests done. Only one was positive. Only 19% of the tests were
performed because physicians suspected Lyme Disease in the patients.
3. "Appropriateness of Parenteral Antibiotic Treatment for Patients with
Presumed Lyme Disease," Benjamin J. Lefft, MD et al (1993 American College of
Physicians p. 518)
Comment: In patients whose only evidence for Lyme Disease
is a positive immunologic test, the risk for empiric antibiotic treatment
outweighs the benefits.
4. "Lyme Disease: Clinical Update for Physicians," Prepared by American Lyme
Disease Foundation, Inc. (Fall 1993)
5. "Management of Lyme Disease Refractory to Antibiotic Therapy," Leonard H.
Siegel, MD (Rheumatology Clinics of North America, Vol. 21, No. 1, 2/95, p.
Comment: This review article by Dr. Siegel discusses the use and misuse
of lab tests and other everyday issues. This is a key review article if one was
going to limit their reading material.
6. "Lyme Disease," R.F. Meenan, MD (1994 Yearbook of Rheumatology published
by Mosby p. 217)
Comment: This introduces the article by Dr. Dressler in the
journal of Infectious Disease that sets the framework for the criteria for the
interpretation of the Western blot test.
7. "The Overdiagnosis of Lyme Disease," Allen C. Steere, MD et al (JAMA,
4/14/93-Vol. 269, No. 14, p. 1812)
Comment: In this study, the most common
reason for lack of response to antibiotics was misdiagnosis.
8. "Summary of the First 100 Patients Seen at a Lyme Disease Referral
Center," Leonard H. Siegel, MD (American Journal of Medicine, 6/1990, Vol. 88,
Comment: Out of the first hundred patients referred to the Robert
Woods Johnson Lyme referral clinics, only 37 of the 100 patients met the
criteria for Lyme Disease; 25 out of these 100 are diagnosed as a fibromyalgia.
This was the first known association between the two