Early Lyme Disease: Solving the Subtle Clinical Clues in an Elderly Patient

Authors: 

Brooke E. Salzman, MD, and James Studdiford, MD, FACP

Citation: 

Pages 20 - 25

Case Presentation
A 63-year-old woman presented in June complaining of a 1-week history of malaise, headache, generalized body aches, and low-grade fever of 101 degrees F. She denied any upper respiratory, gastrointestinal, or other associated symptoms. Physical examination was generally unremarkable with the exception of a slightly raised, 8 x 6–cm, irregular, ovoid patch with spotty areas of mildly intense-to-faded erythema found on her right anterior thigh (Figure 1). A central papule was noted, consistent with a punctum from a recent tick or insect bite (Figure 2). When the lesion was pointed out to the patient, she remembered that it had been present for several days. She described the skin lesion as mildly pruritic, slightly tender, and slowly expanding. On further questioning, the patient recalled removing a small insect from her leg—possibly a tick—the week before while gardening. Her house borders a large city park in Pennsylvania, and deer sightings are frequent.

Discussion
The rash depicted represents primary erythema migrans (EM), a dermatologic manifestation of early Lyme disease (LD). The differential diagnosis includes tinea corporis, pityriasis rosea, granuloma annulare, urticaria, eczematoid dermatitis, insect bite, cellulitis, and allergic contact dermatitis.

In the United States, LD is caused by the spirochete Borrelia burgdorferi, which is transmitted through the bite of the Ixodes scapularis tick. LD is associated with a variety of signs and symptoms that may reflect different stages of infection. The stages include early localized (stage 1), early disseminated (stage 2), and late chronic (stage 3). Most patients (70-80%) develop the early localized form of LD, which is characterized by the presence of EM and flu-like symptoms.1 Primary EM occurs at the site of a tick bite and typically presents as a slowly expanding erythematous patch. EM lesions may have central clearing, classically described as a bull’s eye or target-like appearance. However, more commonly, EM lesions are homogenously erythematous and lack central clearing (Table I).2 EM lesions typically expand to 5 cm or more in diameter, and tend to be mildly tender or pruritic.

Various atypical EM lesions have been reported, including lesions with vesicles, erythematous papules, central edema, ulceration, purpura, lymphangitic streaking, alopecia, and desquamation.2,3 Variation in EM appearance may be the result of variations in host response, inoculum size, or differences in borrelia species.2,3 In the elderly population, atypical and often subdued presentations of cutaneous diseases are common, as there is decreased dermal vascularity and cellularity in aging skin, as well as a decline in immune responsiveness with aging.4,5 Such factors may have influenced the faded appearance of EM in the patient described above.

EM lesions typically develop 7-10 days after a tick bite, with a reported range of 1 to 32 days.2 Lesions that occur while the Ixodes tick is still attached or develop within 48 hours of tick detachment are likely to be local hypersensitivity reactions to the tick bite, and not EM.6 Early LD is usually accompanied by nonspecific, flu-like symptoms including myalgias, arthralgias, fatigue, headache, neck stiffness, and sometimes fever. Upper respiratory tract and gastrointestinal symptoms are typically absent.1 Most cases of early LD occur during the late spring and summer, peaking in June and July.7 This timeframe correlates with the nymphal stage of the life cycle of the Ixodes tick, which accounts for the large majority of LD transmission.7

Analysis of data reported to the Centers for Disease Control and Prevention (CDC) from 2001 and 2002 indicate that most cases of LD in the United States occur in northeastern, mid-Atlantic, and north-central states.7 Twelve states (Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Wisconsin) account for 95% of cases reported nationally.7 Figure 3 demonstrates the endemicity of LD in these particular areas of the country. Ages of patients with LD range from less than 1 to 101 years, and follow a bimodal distribution, with incidence peaking among children ages 5-14 years and adults ages 50-59 years.7

The diagnosis of early LD is generally a clinical one, based primarily on clinical findings, including the presence of EM and a history of tick exposure in an endemic area. Routine use of serological tests in patients with EM is not recommended because of the high rate of false-negative results in the acute phase (the first 2 weeks of infection). In particular, individuals residing in an area of high endemicity who have EM confer a high pretest probability of LD. These patients should be diagnosed and treated for LD without further testing.7,8 Cases in which serologic testing may provide valuable information include patients with clinical findings suggestive of later-stage disseminated LD or patients with prolonged constitutional symptoms (> 2 weeks) suggestive of early LD without EM.8,9 When testing is indicated, both acute-phase and convalescent-phase (2 weeks after the acute phase) serum samples should be tested using a two-tiered assay recommended by the CDC. With the two-tiered assay, a positive or indeterminate screening test (ie, enzyme-linked immunosorbent assay [ELISA]) is followed by a more specific confirmation test (ie, Western blot).

Effective oral treatments for early-stage LD include doxycycline, amoxicillin, and cefuroxime for a 14-21–day course6,8,10 (Table II6,8). Signs and symptoms usually resolve within 3 weeks after treatment.2 Without treatment, EM resolves spontaneously within a median of approximately 4 weeks.6 However, hematogenous spread of the spirochete to extracutaneous sites may result in significant clinical sequelae involving the skin, joints, nervous system, and heart. About 60% of patients with EM who are not treated will go on to develop arthritis, most frequently involving the knee.11 Other possible clinical manifestations of early disseminated LD include secondary annular skin lesions, meningitis, cranial neuropathy, radiculoneuritis, atrioventricular nodal block, myocarditis, migratory musculoskeletal pain in joints, bursae, tendon, muscle, or bone, and, rarely, eye manifestations.12Outcome of the Case Patient
A clinical diagnosis of EM consistent with early-stageLD was made, and the patient was treated with doxycycline 100 mg twice daily for 14 days. No further blood tests were obtained. The patient experienced a brief flare in her symptoms 12 hours after initiation of antimicrobial therapy, consistent with a Jarisch-Herxheimer reaction. The latter can occur in up to 15% of treated patients.13 Thereafter, the patient made a complete recovery.

Measures recommended to reduce the risk of future infection with LD include avoiding tick-infested areas, wearing protective clothing, using tick repellents,checking the entire body for ticks daily, and promptly removing attached ticks before transmission of the infection can occur.8The authors report no relevant financial relationships.Dr. Salzman is Clinical Assistant Professor, Division of Geriatric Medicine, and Dr. Studdiford is Clinical Associate Professor, Department of Family and Community Medicine, Jefferson Medical College, Philadelphia, PA.References
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2. Smith RP, Schoen RT, Rahn DW, et al. Clinical characteristics and treatment outcome of early Lyme disease in patients with microbiologically confirmed erythema migrans. Ann Intern Med 2002;136:421-428.

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4. Aging and the skin. In: Beers MH, Berkow, eds. The Merck Manual of Geriatrics. 3rd ed. Whitehouse Station, NJ: Merck Research Laboratories, division of Merck & Co., Inc; 2000:1231-1327.

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7. Centers for Disease Control and Prevention, Lyme Disease---United States, 2001-2002. Available at:
http:www.cdc.gov/mmwr/preview/mmwrhtml/mm5317a4.htm. Accessed March 7, 2007.

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11. Steere AC, Schoen RT, Taylor E. The clinical evolution of Lyme arthritis. Ann Intern Med 1987;107:725-731.

12. Steere AC, Coburn J, Glickstein L. The emergence of Lyme disease. J Clin Invest 2004;113:1093-1101.

13. Nadelman RB, Luger SW, Frank E, et al. Comparison of cefuroxime axetil and doxycycline in the treatment of early Lyme disease. Ann Intern Med 1992;117:273-280.