Applied Evidence

Beyond the bull's eye: Recognizing Lyme disease

J Fam Pract. 2016 June;65(6):373-379

From The Journal of Family Practice | 2016;65(6):373-379.

References

1. Centers for Disease Control and Prevention. Lyme disease data. Available at: http://www.cdc.gov/lyme/stats. Accessed April 19, 2016.

2. Lantos PM, Nigrovic LE, Auwaerter PG, et al. Geographic expansion of Lyme disease in the Southeastern United States, 2000-2014. Open Forum Infect Dis. 2015;2:ofv143.

3. Gerstenblith TA, Stern TA. Lyme disease: a review of its epidemiology, evaluation and treatment. Psychosomatics. 2014;55:421-429.

4. Wright WF, Riedel DJ, Talwani R, et al. Diagnosis and management of Lyme disease. Am Fam Physician. 2012;85:1086-1093.

5. Marques AR. Lyme disease: a review. Curr Allergy Asthma Rep. 2010;10:13-20.

6. Borchers AT, Keen CL, Huntley AC, et al. Lyme disease: a rigorous review of diagnostic criteria and treatment. J Autoimmun. 2015;57:82-115.

7. Shapiro ED. Clinical practice. Lyme disease. N Engl J Med. 2014;370:1724-1731.

8. Cook MJ. Lyme borreliosis: a review of the data on transmission time after tick attachment. Int J Gen Med. 2014;8:1-8.

9. Tibbles CD, Edlow JA. Does this patient have erythema migrans? JAMA. 2007;29:2617-2627.

10. 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 Disease Society of America. Clin Infect Dis. 2006;43:1089-1134.

11. Khalil S, Padala SK, Hui CC, et al. Lyme carditis in the fast lane: from alternating bundle branch block to asystole in 12 hours. Conn Med. 2015;79:517-520.

12. Sigal LH. Early disseminated Lyme disease: cardiac manifestations. Am J Med. 1995;98:25S-28S.

13. Blaut-Jurkowska J, Jurkowski M. [Post-Lyme disease syndrome.] Pol Merkur Lekarski. 2016;40:129-133.

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The Western blot is interpreted using standardized criteria requiring at least 2 of 3 bands for a positive IgM diagnosis and 5 of 10 bands for a positive IgG diagnosis. Antibodies against Borrelia species are slow to develop. IgM generally is undetectable for the first one to 2 weeks after infection, and IgG often does not emerge for 4 to 6 weeks.

With patients who are seronegative at presentation, but for whom there is strong suspicion of Borrelia infection, it is advisable to obtain evidence of seroconversion, preferably within 8 to 14 days after presentation. Early antibiotic treatment may prevent the development of seropositivity.^1,3-7,14

Past or newly acquired infection? IgM and IgG produced in response to B burgdorferi may persist for years following antimicrobial therapy, which makes it impossible to distinguish between past and newly acquired infections based on seropositivity alone. These persistently elevated levels are not an indication of ineffective treatment or chronic infection. Therefore, it is not recommended to repeat serologic testing for documentation of treatment effectiveness or cure.

Since no serologic test has sufficient specificity to be used alone, efforts are being made to develop testing that detects antibodies against the 26-mer peptide from the sixth invariant region (C6) of the VlsE lipoprotein (C6VlsE). In 2007, the US Food and Drug Administration (FDA) approved a C6 ELISA for first-tier testing; unfortunately, it still has the problem of cross-reactivity with other spirochetal and viral pathogens. The C6 ELISA may one day be approved as a single-tier test.^4-7,14

Culture. The isolation of Borrelia species by culture is not routinely performed because it is expensive and requires special media and laboratory expertise, as well as a prolonged period of observation (6 to 12 weeks). Furthermore, this technique lacks sensitivity with samples taken from anywhere other than the rash site of patients with EM, in whom there is little need for laboratory diagnosis. Culture of cerebrospinal fluid has a positive yield of less than 10%,⁵ and it is extremely rare to isolate the spirochete from joint fluid. Therefore, negative results do not exclude a diagnosis of disease.^4,5,14

The CDC recommends against cultures, immunofluorescence staining, and cell sorting of cell wall-deficient or cystic forms of B burgdorferi.¹

Polymerase-chain reaction (PCR). This test is used to amplify genomic DNA of B burgdorferi and is most useful in patients with Lyme arthritis because of a high rate of DNA detection in synovial fluid samples (60% to 85%).⁵ In skin biopsies from EM lesions, PCR sensitivity can range from 25% to 90%.⁵ The PCR test is also used in cases of diagnostic uncertainty, but is generally performed only for research purposes. Negative findings do not exclude diagnosis of the disease.^5,6,14

Urine antigen test. This test has a high false-positive rate and is generally not recommended.^1,5