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Lyme Disease: Differential Diagnoses & Workup
Updated: Apr 17, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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Differential Diagnoses
Other Problems to Be Considered
Myositis
Workup
Laboratory Studies
The following laboratory tests are indicated in Lyme disease:
- CBC count: WBC count can be normal or elevated.
- Erythrocyte sedimentation rate usually is elevated.
- Serum glutamic-oxaloacetic transaminase (SGOT) may be elevated.
- C3 and C4 generally are normal or slightly elevated.
- Antinuclear antibody (ANA) and rheumatoid factor test results are negative.
- Microscopic hematuria and mild proteinuria also have been described.
- Joint fluid in patients with arthritis may have 25,000-125,000 WBCs/mcL, often with a polymorphonuclear predominance.
- Cerebrospinal fluid (CSF) in patients with meningitis often reveals a mild pleocytosis (<1000 cells/mcL) with lymphocyte predominance.
- Diagnosis is made clinically in the early stages of disease by the presence of erythema migrans (EM) rash.
- Culturing B burgdorferi is impractical; the organism is difficult to culture and requires an invasive procedure, such as biopsy or lumbar puncture, to obtain adequate samples.
- Serology is the standard of diagnosis in later stages of the disease.
- Reported specificity of Lyme serology is only 90-95%. Therefore, the positive predictive value of the test is highly dependent on the prevalence of disease. Lyme serology should not be performed in children with nonspecific symptoms without history of tick exposure or from nonendemic areas.
- Antibodies are known to persist for many years despite eradication of the infection. Diagnosis of repeat infection or evidence of cure can be difficult based on serology alone.
- Serology should include a two-step process. The first step is to perform an enzyme-linked immunosorbent assay (ELISA) or immunofluorescent assay (IFA). The second step, performed if the ELISA or IFA result is positive, is a Western blot analysis against specific antigens. This step is not interpretable in the absence of a positive ELISA or IFA result. Most assays require immunoglobulin against at least 3 specific proteins (for immunoglobulin M [IgM]) or 5 specific proteins (for immunoglobulin G [IgG]) for results to be considered positive. Lyme serology should be performed by a reference laboratory. Patients with early Lyme disease who are treated with antibiotics may never develop positive titer results.
- Early disease: Only one third of patients have a positive titer result; therefore, clinicians rely on the presence of the rash to make the diagnosis. For patients without an EM rash but in whom Lyme disease is suspected, serial titers eventually can be used to confirm the diagnosis.
- Early disseminated disease: Ninety percent of patients have a positive titer result.
- Late disease: All patients have a positive titer result.
- With the exception of synovial fluid, polymerase chain reaction (PCR) testing is not recommended because of unacceptable low sensitivity, especially from the CSF (does have high specificity if test is positive).
- CSF titers to B burgdorferi should not be used for diagnosis of Lyme meningitis but may have value in patients who have recurrent infection or for following serial markers in patients with persistent symptoms. CSF titers should be performed and interpreted at a reference laboratory.
Procedures
- Lumbar puncture: Whether all patients with cranioneuropathy require lumbar puncture before treatment is controversial. Occasionally Lyme disease presents as pseudotumor cerebri; an opening pressure is essential for diagnosis.
- Currently, in most patients with isolated Bell palsy and no associated signs of aseptic meningitis, most physicians do not perform a lumbar puncture. For most other patients with cranioneuropathies and suspected Lyme disease, a lumbar puncture should be performed, particularly in patients who live in an endemic area and present during peak Lyme disease season or with headache; CSF pleocytosis leads to treatment as indicated for CNS Lyme disease.
- Obtain a CT scan or MRI before the lumbar puncture if increased intracranial pressure or mass lesion is suspected. Occasionally, Lyme disease presents as pseudotumor with frank papilledema; imaging should be done prior to lumbar puncture in these cases.
- Joint aspiration for diagnostic reasons is unnecessary if only Lyme disease is suspected (and not septic arthritis or another etiology of effusion).
More on Lyme Disease |
| Overview: Lyme Disease |
 Differential Diagnoses & Workup: Lyme Disease |
| Treatment & Medication: Lyme Disease |
| Follow-up: Lyme Disease |
| Multimedia: Lyme Disease |
| References |
| Further Reading |
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References
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Halperin JJ. Nervous system lyme disease: diagnosis and treatment. Rev Neurol Dis. Winter 2009;6(1):4-12. [Medline].
Nigrovic LE, Thompson AD, Fine AM, Kimia A. Clinical predictors of Lyme disease among children with a peripheral facial palsy at an emergency department in a Lyme disease-endemic area. Pediatrics. Nov 2008;122(5):e1080-5. [Medline].
Halperin JJ, Shapiro ED, Logigian E, Belman AL, Dotevall L, Wormser GP. Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. Jul 3 2007;69(1):91-102. [Medline].
The ILADS Working Group. Evidence-based guidelines for the management of Lyme disease. Expert Rev Anti Infect Ther. 2004;2(1 Suppl):S1-13.
Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. Nov 1 2006;43(9):1089-134. [Medline].
Afzelius A. Erythema chronicum migrans. Acta Derm Venereol. 1921;2:120-125.
Avery RA, Frank G, Glutting JJ, Eppes SC. Prediction of Lyme meningitis in children from a Lyme disease-endemic region: a logistic-regression model using history, physical, and laboratory findings. Pediatrics. Jan 2006;117(1):e1-7. [Medline].
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Cook SP, Macartney KK, Rose CD, Hunt PG, Eppes SC, Reilly JS. Lyme disease and seventh nerve paralysis in children. Am J Otolaryngol. Sep-Oct 1997;18(5):320-3. [Medline].
Edlow JA. Lyme disease and related tick-borne illnesses. Ann Emerg Med. Jun 1999;33(6):680-93. [Medline].
Gerber MA, Zemel LS, Shapiro ED. Lyme arthritis in children: clinical epidemiology and long-term outcomes. Pediatrics. Oct 1998;102(4 Pt 1):905-8. [Medline].
Halsey NA, Abramson JS, Chesney PJ. American Academy of Pediatrics. Committee on Infecious Diseases. Prevention of Lyme disease. Pediatrics. Jan 2000;105(1 Pt 1):142-7. [Medline].
Kaplan RF, Trevino RP, Johnson GM, et al. Cognitive function in post-treatment Lyme disease: do additional antibiotics help?. Neurology. Jun 24 2003;60(12):1916-22. [Medline].
Krupp LB, Hyman LG, Grimson R, et al. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology. Jun 24 2003;60(12):1923-30. [Medline].
Masuzawa T. Terrestrial distribution of the Lyme borreliosis agent Borrelia burgdorferi sensu lato in East Asia. Jpn J Infect Dis. Dec 2004;57(6):229-35. [Medline].
Moses JM, Riseberg RS, Mansbach JM. Lyme disease presenting with persistent headache. Pediatrics. Dec 2003;112(6 Pt 1):e477-9. [Medline].
Nadelman RB, Nowakowski J, Fish D, et al. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med. Jul 12 2001;345(2):79-84. [Medline].
Seltzer EG, Shapiro ED, Gerber MA. Long-term outcomes of lyme disease. JAMA. Jun 21 2000;283(23):3068-9. [Medline].
Shapiro ED. Lyme disease. Pediatr Rev. May 1998;19(5):147-54. [Medline].
Steere AC. Lyme borreliosis in 2005, 30 years after initial observations in Lyme Connecticut. Wien Klin Wochenschr. Nov 2006;118(21-22):625-33. [Medline].
Steere AC. Lyme disease. N Engl J Med. Jul 12 2001;345(2):115-25. [Medline].
Vázquez M, Sparrow SS, Shapiro ED. Long-term neuropsychologic and health outcomes of children with facial nerve palsy attributable to Lyme disease. Pediatrics. Aug 2003;112(2):e93-7. [Medline].
Further Reading
- Practice parameter: treatment of nervous system Lyme disease (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology
- Evidence-based guidelines for the management of Lyme disease
- Infectious Diseases Society of America practice guidelines for clinical assessment, treatment and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis
Keywords
lyme borreliosis, Borrelia burgdorferi, B burgdorferi, Ixodes scapularis, deer tick, tickbite, tick bite, tick-borne illness, Lyme arthritis, Lyme disease, Lyme meningitis, Ixodid ticks, erythema migrans, EM, aseptic meningitis, cranioneuropathies, Bell palsy, encephalitis, carditis, rash, treatment, diagnosis, skin rash, meningismus
