Ms. B is a 28-year-old woman who was generally healthy until 1 month ago. She is an RN and avid outdoor enthusiast who enjoys camping, hiking, and canoeing. Six weeks ago, she took a 2-week hiking and camping trip on a portion of the Appalachian Trail in New England. She reports feeling flu-like symptoms (muscle aches, headache, and fatigue) approximately 1 week after returning from her trip. She presents today with a rash on her torso and continued malaise.

Upon exam, Ms. B has some difficulty ambulating in the exam room and getting on to the exam table. Her vital signs are stable and her oxygen saturation is 98% on room air. The patient reports that she has gone back to work since returning from her trip, but has no energy after her shift and spends the weekends sleeping. Her friends and family members are concerned that she does not seem to have her usual level of energy and enthusiasm. Ms. B's physical exam is normal with the exception of a red rash on her upper posterior thorax. It is warm but painless to palpation. It is circular, red around the edges, with central clearing, and the innermost portion is dark red and indurated. The lesion measures 3 inches (7.62 cm) in diameter. Ms. B denies itching or drainage from the rash. She does not recall an insect bite, trauma, or irritation at the site.

After completing Ms. B's history and physical exam, the NP ordered several tests to assist in the differential diagnosis: a complete blood cell (CBC) count, complete metabolic profile (CMP), thyroid-stimulating hormone (TSH), and enzyme-linked immunosorbent assay (ELISA) with reflex Western blot. Ms. B was treated empirically with doxycycline 100 mg twice a day for 14 days1 and asked to return to the office in 2 weeks to review the results.

Lyme disease

Lyme disease is the most frequently reported vector-borne illness.2 It is a multisystem inflammatory disease caused by the tick-borne Gram-negative spirochete Borrelia burg dorferi.3 The blacklegged tick (also known as the deer tick) is responsible for transmitting Lyme disease.

In addition to Lyme disease, ticks are significant carriers of several other diseases such as Rocky Mountain spotted fever and tularemia. Ticks are extremely small and often the initial bite goes unnoticed. They embed their heads under the skin to obtain blood from the host and then enlarge as they fill with blood. As they enlarge, they release toxins and/or transmit microorganisms. Following a tick bite, spirochetes spread via the bloodstream to various joints, the heart, the nervous system, and distant skin sites over a period of days to weeks.

Symptoms of Lyme disease occur in three stages. First, a localized infection occurs soon after the tick bite with erythema migrans (bull's eye rash), fever, fatigue, arthralgia, and myalgia (see Erythema migrans). After the initial infection, there is disseminated disease with occasional secondary erythema migrans, arthralgia, depression, neuritis, and/or cardiovascular symptoms. Late, persistent Lyme disease can continue for years with arthritis, encephalopathy, and/or polyneuropathy.1 Accurate diagnosis of the disease and appropriate treatment and follow-up with an infectious-disease specialist are essential to avoid secondary and/or late persistent Lyme disease.

Lyme disease testing

The diagnosis of Lyme disease can be made on the clinical presentation and history of tick bite or probable exposure. However, most clinicians prefer to supplement this information with diagnostic testing. The lab diagnosis of Lyme disease is rarely based on a culture of the offending organism Borrelia burgdorferi. There are few of these organisms in clinical specimens of patients who have been infected, and the Lyme spirochetes require specialized media for growth with prolonged incubation time.4

Serologic tests are the most sensitive and specific tests used to aid in the diagnosis of Lyme disease. The ELISA is 89% sensitive and 72% specific for detecting Lyme disease.5 It determines titers of specific IgM and specific IgG antibodies to the Borrelia burgdorferi spirochete. Levels of IgM antibody peak during the third to the sixth week after initial infection and then gradually decline. Titers of specific IgG antibodies are generally low during the third to the sixth week after spirochete infection, reach maximum levels in 4 to 6 months, and may remain elevated for years after exposures.5 False-positive ELISA test results may occur in patients with rheumatoid arthritis, or with other spirochete infections such as tick borne relapsing fever, leptospirosis, or syphilis.4,5

Because of the relatively low sensitivity and specificity of the ELISA test and numerous false positives, testing for Lyme disease is a two-step process in most labs. It is recommended that positive ELISA results be confirmed by a Western blot specific Lyme disease test.6,7

In Lyme disease, Western blot analysis detects serum antibodies to specific antigens of Borrelia burgdorferi. It is reported as a qualitative yes or no result. According to CDC guidelines, a positive IgG blot is defined as the presence of antibodies that react with at least five out of ten specific proteins. A positive IgM blot is defined as the presence of anti bodies that react with at least two out of three specific proteins.7 Western blot analysis is typically performed on serum, but it may also be performed on cerebrospinal fluid. In patients with suspected Lyme disease (due to exposure and classic symptoms) and a negative initial Western blot, the Western blot should be repeated.5

Polymerase chain reaction (PCR) may be tested in serum, joint aspiration, or cerebrospinal fluid. However, it should be noted that the positive predictive value of PCR can be very low. These tests are typically only conducted by experts in Lyme disease diagnosis and treatment.4

Conclusion

Ms. B returned to the clinic after 2 weeks to review her test results. She reported that her rash was resolved, but other constitutional symptoms were worse. She was missing several days of work per week and concerned about her health and job security. Ms. B was informed that her CBC, CMP, and TSH were normal. However, her ELISA and Western blot results were positive for Lyme disease. Ms. B was referred to a local infectious disease expert for further testing and Lyme disease treatment.

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