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Tick-Borne Diseases, Lyme: Differential Diagnoses & Workup

Author: Jonathan A Edlow, MD, Associate Professor of Medicine, Department of Emergency Medicine, Harvard Medical School; Vice Chairman, Department of Emergency Medicine, Beth Israel Deaconess Medical Center
Contributor Information and Disclosures

Updated: Aug 26, 2009

Differential Diagnoses

Babesiosis
Pericarditis and Cardiac Tamponade
Bell Palsy
Tick-Borne Diseases, Colorado
Bites, Insects
Tick-Borne Diseases, Ehrlichiosis
Heart Block, Second Degree
Tick-Borne Diseases, Introduction
Heart Block, Third Degree
Tick-Borne Diseases, Q Fever
Meningitis
Tick-Borne Diseases, Relapsing Fever
Myocarditis
Tick-Borne Diseases, Rocky Mountain Spotted Fever
Pediatrics, Headache
Tick-Borne Diseases, Tularemia
Pediatrics, Meningitis and Encephalitis

Workup

Laboratory Studies

  • Laboratory testing depends entirely on the presenting problem of the patients.13 Evaluation of the CBC, erythrocyte sedimentation rate, and liver function generally is unnecessary, and serologic tests can be misleading if performed in the wrong setting.
    • The patient with solitary, typical EM requires no laboratory testing whatsoever. Expected results for the CBC and erythrocyte sedimentation rate are likely normal. At this stage of illness, serologic testing is unnecessary because the pretest probability of Lyme disease is high, and the sensitivity of the serologic test is low (during the first several weeks).
    • Leukopenia or thrombocytopenia suggests co-infection with Ehrlichia or Babesia species.
    • Elevation of at least one liver function test result is reported to occur in 40% of patients with Lyme disease. This finding also is common in ehrlichiosis.
  • Culture of B burgdorferi
    • Because of the organism's fastidious growth requirements, culture has not been a useful test in the past; however, this situation is improving. Its usefulness depends on the specimen being cultured. Nevertheless, in routine practice, borrelial cultures are often unavailable.13
    • In the skin, where findings are most likely to be positive, culturing is least likely to be clinically useful, except in cases of atypical rash.
    • In other body fluids (eg, blood, synovial fluid, CSF), the yield is lower. However, recent data suggest that if a high volume (9 mL) of plasma is used, approximately 44% of patients with EM are determined to be spirochetemic at presentation.

Imaging Studies

  • Imaging studies are almost never indicated in patients with Lyme disease who present with early syndromes. Patients with some clinical syndromes may require imaging studies, depending on the specifics of the case. For example, a patient with fever and severe back pain, with signs of radiculopathy, might require spine imaging.

Other Tests

  • Serologic testing for Lyme disease is complex. Rational ordering and interpretation of these test results requires some understanding of the basic underlying principles and performance characteristics of the test.
  • Most importantly, the most commonly performed test measures antibodies to various proteins of the spirochete, some of which are very specific for the organism and others of which are nonspecific. The test results do not rule in or rule out Lyme disease; however, the results make a clinical diagnosis of Lyme disease more (or less) likely.
  • The CDC recommends a 2-step procedure consisting of a screening enzyme-linked immunoassay (ELISA) (or immunofluorescent assay [IFA]) and a confirmatory Western blot for specimens that have positive or equivocal results with the ELISA. Furthermore, in patients with a high likelihood of having Lyme disease (eg, classic EM in an endemic area), no serologic test should be ordered. Conversely, in a patient with a low pretest likelihood of having Lyme disease (eg, someone with vague symptoms where the test is being used as a screening test), testing is also not recommended because in such a population, the number of false-positive results greatly outnumbers the true positive results.
  • Numerous conditions (eg, viral and bacterial infections, inflammatory diseases, neoplasms) can cause false-positive ELISA results. Also, a small percentage of the healthy population has positive test results with ELISA testing. For these reasons, confirmatory Western blot testing is recommended.
  • Timing is extremely important. Seroconversion may take several weeks in patients infected with the spirochete, so early seronegativity is to be expected.
  • Even occasional patients with facial nerve palsy or carditis (ie, early disseminated disease) may be seronegative on presentation. However, testing is recommended in these individuals. Furthermore, early or partial treatment with antibiotics may blunt or abrogate the subsequent serologic response. Some patients with late disease are seronegative, but significant controversy exists regarding the frequency of late seronegativity. Most authorities suggest that this phenomenon is rare.
  • On the other hand, patients with prior Lyme disease may have persistently positive results. Also, vaccinated patients will have a positive ELISA result (although Western blot results should be negative). Lack of attention to the details of the test result and the reliability of the laboratory performing the test might lead the physician to an erroneous conclusion about the cause for a given patient's symptoms.
  • Patients may remain seropositive for long periods; therefore, serologic test results cannot be used as a proof or test of cure. Also, if a patient with past Lyme disease who remains seropositive comes in with new symptoms, care should be taken to not necessarily ascribe these new symptoms to Lyme disease.
  • The emergency physician must remember 2 important concepts. First, a negative Lyme test result does not indicate the absence of disease, nor does a positive result indicate the presence of disease. Second, a positive result is not required for someone with clear-cut EM; these early-presenting patients frequently have negative results, and they should be treated for EM empirically.
  • In the last few years, research on newer serologic tests—specifically the C6 peptide and the VlsE—is promising. These test results may well turn positive earlier and revert to negative after successful treatment. In July 2008, investigators published a prospective comparison between the standard 2-tier testing and an IgG of the VlsE of the C6 peptide. They found that both tests were sensitive, but the 2-tier testing had slightly better specificity.14 The current CDC recommended 2-tier testing remains the preferred method in routine practice, and serological testing is still not recommended for patients with erythema migrans.

Procedures

  • Because the spirochete can enter the CSF early in the course of infection and because the finding of meningitis (defined here as abnormal CSF in the setting of active Lyme disease) changes the treatment, many physicians have a low threshold for performing a lumbar puncture (LP) in patients with EM and any CNS symptoms or in patients with isolated seventh nerve palsy due to Lyme disease. They do this with the notion that an elevated protein level or pleocytosis mandates parenteral therapy.
  • A 2008 study randomized 118 European patients with CNS lyme to 2 weeks of oral doxycycline versus parenteral ceftriaxone therapy.15 They found that clinical outcomes were the same in both groups, indicating that an LP may not be necessary if the purpose is to decide on route of therapy. Because of the differences in causative borrelial species, it is not clear if this finding is relevant to North American patients.
  • In addition, a lumbar puncture ought to be performed if Lyme meningitis is in the differential diagnosis.
  • Occasional patients with Lyme disease–related heart block will require temporary cardiac pacing. The indications for cardiac pacing are the same as for any other patient with varying degrees of heart block. Permanent wires are very rarely needed.

More on Tick-Borne Diseases, Lyme

Overview: Tick-Borne Diseases, Lyme
Differential Diagnoses & Workup: Tick-Borne Diseases, Lyme
Treatment & Medication: Tick-Borne Diseases, Lyme
Follow-up: Tick-Borne Diseases, Lyme
Multimedia: Tick-Borne Diseases, Lyme
References
Further Reading
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References

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Keywords

tick-borne disease, Lyme disease, tick bite, Borrelia burgdorferi, Ixodes, vector-borne disease, juvenile arthritis, B burgdorferi, spirochete, tick-borne pathogens, myalgias, arthralgias, flulike illness, borrelial lymphocytoma

acrodermatitis chronicum atrophicans, lymphocytic meningitis, facial weakness, Bell palsy, borrelial facial palsy, lymphocytic pleocytosis, Bannwarth syndrome, chronic encephalopathy, syncope, heart block, complete heart block, lyme pericarditis, lyme myocarditis, lyme myopericarditis, myositis, tendonitis, bursitis, synovitis, conjunctivitis, keratitis, iritis, erythematous papule, erythematous macule, polycranial neuropathy

meningoradiculitis, lyme encephalopathy, peripheral axonal neuropathy, tamponade, congestive heart failure, monoarthritis, oligoarthritis, retinal hemorrhages, retinal exudates, papilledema, pseudotumor cerebral-like syndrome, splenomegaly, hepatomegaly, regional lymphadenopathy, , white matterencephalitis, HLA-DR4 antigen

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Contributor Information and Disclosures

Author

Jonathan A Edlow, MD, Associate Professor of Medicine, Department of Emergency Medicine, Harvard Medical School; Vice Chairman, Department of Emergency Medicine, Beth Israel Deaconess Medical Center
Jonathan A Edlow, MD is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

Dan Danzl, MD, Chair, Department of Emergency Medicine, Professor, University of Louisville Hospital
Dan Danzl, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Kentucky Medical Association, Society for Academic Emergency Medicine, and Wilderness Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Jon Mark Hirshon, MD, MPH, Associate Professor, Department of Emergency Medicine, University of Maryland School of Medicine
Jon Mark Hirshon, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Public Health Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Rick Kulkarni, MD, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: WebMD Salary Employment

 
 
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