Not All Erythema Migrans Lesions Are Lyme Disease

Accepted Manuscript Not All Erythema Migrans Lesions are Lyme Disease Jerome Goddard, Ph.D. PII:

S0002-9343(16)30907-X

DOI:

10.1016/j.amjmed.2016.08.020

Reference:

AJM 13686

To appear in:

The American Journal of Medicine

Received Date: 8 August 2016 Revised Date:

15 August 2016

Accepted Date: 15 August 2016

Please cite this article as: Goddard J, Not All Erythema Migrans Lesions are Lyme Disease, The American Journal of Medicine (2016), doi: 10.1016/j.amjmed.2016.08.020. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Brief Observation

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Not All Erythema Migrans Lesions are Lyme Disease

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Jerome Goddard, Ph.D.

Department of Biochemistry, Molecular Biology, Entomology, and Plant Pathology, Mississippi State University, Starkville, MS [email protected] 662-325-2085

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Funding: None. No grant funding was received for this study/manuscript, nor was any money received from pharmaceutical companies for preparation of it. Conflicts of interest: The author has no conflicts of interest to disclose. The author had all access to the data and wrote the manuscript in its entirety.

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Running head: Not all Erythema Migrans Lesions are Lyme

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Key words: Lyme disease; Erythema migrans; STARI; tick bites; rash

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Abstract

Background

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Lyme disease is the number one arthropod-transmitted disease in the U.S., and one of the diagnostic criteria for the illness is development of an erythematous bull’s eye rash around a tick bite which may expand over time, hence the term erythema migrans. However, there are other

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erythema migrans-like rashes such as those from a condition known as southern tick-associated rash illness. This paper describes a patient with an erythema migrans-like lesion similar to that

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associated with Lyme disease, resulting from a bite by a nymphal stage lone star tick, Amblyomma americanum. Methods

A tick removed from the center of an erythema migrans-like lesion in a patient was identified to species and then submitted to the Centers for Disease Control and Prevention for

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testing for the agent of Lyme disease, Borrelai burgdorferi. The patient was evaluated by an internist seven weeks later. After another three weeks, the patient’s blood was tested

Results

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serologically for Lyme disease by American Esoteric Laboratories, Memphis, TN.

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Both the tick and human blood sample from this patient were negative for evidence of Lyme disease. Clinically, other than the erythema migrans-like lesion, the patient displayed no signs or symptoms consistent with Lyme disease. Conclusions

This case presents clinical, serological, and molecular evidence that erythema migrans lesions may occur after tick bites in patients and that these lesions may not be due to infection with the agent of Lyme disease. 2

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Lyme disease is the most common vector-borne disease in the United States, with case numbers that could easily exceed 100,000 per year, depending on how one calculates

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incidence.1,2 Most cases occur in the northeastern and north-central U.S., although there are reports of Lyme disease in the southern U.S. which are considered controversial.3-6 Although the Centers for Disease Control and Prevention often labels southern Lyme disease-like illnesses as

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“southern tick-associated rash illness,” many physicians persist in diagnosing such lesions

resulting from tick bites as the erythema migrans lesion of Lyme disease.5 Diagnosis of Lyme

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disease is generally based upon clinical presentation which can be more or less accurately confirmed (depends on who you ask) by a two-step procedure: a sensitive enzyme-linked immunosorbent assay followed by immunoblot (IgM and IgG) if reactive. It should be noted that there are a number of tests for Lyme disease which are unreliable and not recommended.7 This paper presents data, both from the patient and the tick, in a case of erythema migrans after tick

Methods

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bite, which was clearly not Lyme disease.

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After performing field research two days earlier, the author found and removed an attached tick from his waistline on April 2, 2016 and placed it in 70% ethanol. Upon

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development of a 9 cm diameter palpable, itchy, erythematous rash 3 days later (Figure 1), the tick was retrieved, identified as a male lone star tick, Amblyomma americanum, using a standard tick identification guide,8 and submitted to the Centers for Disease Control and Prevention for testing1 for presence of Borrelia burgdorferi, the causative agent of Lyme disease. The erythema migrans lesion which developed at the tick bite continued to expand until the 14th day, reaching a size of 14 x 10 cm, subsequently fading over the next week or so. No clinical signs or symptoms 1

This tick was submitted as part of an ongoing research project on field-collected ticks and Lyme disease in Mississippi.

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consistent with Lyme disease were noted. However, on May 24, 2016, the author visited his internal medicine physician for consultation about the erythema migrans lesion and a Lyme disease serology was ordered (American Esoteric Laboratories, Memphis, TN).

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Discussion

Although the lesion described here closely resembled those reported in Lyme disease patients (Figure 2), the tick in this case was reported as negative for B. burgdorferi by the

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Centers for Disease Control, and serological analysis of the patient’s blood also turned out

negative (<0.01). There was at least two months between the time of tick bite and the blood test,

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allowing ample time for development of antibodies. Consequently, the diagnosis for this erythema migrans-like lesion was southern tick-associated rash illness – a rash resulting from patient exposure to salivary proteins upon tick feeding. Amblyomma americanum has been shown previously to produce skin lesions,9,10 even erythematous halos.11,12 Further, experiments

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in our lab with human volunteers have demonstrated development of moderate to severe pruritic, vesicular lesions after bites by this tick.10 Conclusions

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This case presents clinical, serological, and molecular evidence that erythema migrans lesions may occur after tick bite in patients living in areas where the lone star tick occurs, and

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that these lesions may not be due to infection with the agent of Lyme disease. Physicians should be aware that this tick species – Amblyomma americanum – is not a vector of the agent of Lyme disease, and patients bitten by A. americanum may develop Lyme-like lesions which might be reported to state health departments as Lyme disease.5 In addition, many such patients are treated presumptively for Lyme disease, often with only tenuous support for the diagnosis.4

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References

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7. 8.

9. 10. 11.

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4. 5.

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Bonnefoy X, Kampen H, Sweeney K. Public Health Significance of Urban Pests. World Health Organization Europe, Copenhagen, 569 pp.; 2008. Hinckley AF, Connally NP, Meek JI, et al. Lyme disease testing by large commercial laboratories in the United States. Clin. Infect. Dis. 2014;59:676-681. Barbour A. Does Lyme disease occur in the south? A survey of emerging tick-borne infections in the region. Am. J. Med. Sci. 1996;311:34-40. Dennis DT. Rash decisions: Lyme disease or not? Clin. Infect. Dis. 2005;41:966-968. Goddard J, Varela-Stokes A, Finley RW. Lyme-disease-like illnesses in the South. J. Mississippi State Med. Assoc. 2012;53(3):68-72. Philipp MT, Masters E, Wormser GP, Hogrefe W, Martin D. Serologic evaluation of patients from Missouri with erythema migrans-like skin lesions with the C6 Lyme test. Clin. Vaccine Immunol. 2006;13(10):1170-1171. CDC. Caution regarding testing for Lyme disease. CDC, MMWR, 54: 125; 2005. Strickland RK, Gerrish RR, Hourrigan JL, Schubert GO. Ticks of veterinary importance. USDA, APHIS, Agri. Hndbk. No. 485, U.S. Department of Agriculture, Washington, D.C., 122 pp.; 1976. Fisher EJ, Mo J, Lucky AW. Multiple pruritic papules from lone star tcik larvae bites. Arch. Dermatol. 2006;142:491-494. Goddard J, Portugal JS. Cutaneous lesions due to bites by larval Amblyomma americanum. JAMA Dermatol. 2015;151:1373-1375. Patterson JW, Fitzwater JE, VConnell J. Localized tick bite reaction. Cutis. 1979;24:168172. Masters E, Granter S, Durway P, Cordes P. Physician-diagnosed erythema migrans-like rashes following lone star tick bites. Arch. Dermatol. 1998;134:955-960.

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FIGURE LEGENDS

Figure 1. Erythema migrans lesion following tick bite: day 3 (top), and day 10 (bottom). The tick was attached in the center of the lesion. Figure 2. Erythema migrans lesion in a case of Lyme disease (Photo courtesy Centers for Disease Control).

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Clinical Significance

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One criterion for diagnosis of Lyme disease is development of an erythema migrans lesion surrounding a tick bite.


Presence of an erythema migrans lesion may be due to other conditions or etiologies.

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Lyme disease, especially in the southern U.S.

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Physicians should be aware that not all erythema migrans lesions are indicative of