Vol. 18, No. 19
THE JOHNS HOPKINS MICROBIOLOGY NEWSLETTER
Monday, May 24, 1999
A 24 year-old female medical student presented to her student health clinic with a two day history of "a large red patch" on her right thigh accompanied by occasional numbness in her right leg and foot. Over the past six hours, she had also developed right inguinal lymphadenopathy. The patient reported no chills or fever. She had gone home to the Connecticut shoreline area to visit her family five days ago. She did not spend any time outdoors but the family does have two outdoor cats whom she was in contact with. The past medical history was unremarkable. The family history was remarkable for her father having Lyme disease two years ago. On physical exam, the patient was afebrile. There was a 6 x 4 cm warm, annular erythematous rash on the patient’s right upper thigh which was consistent with erythema chronicum migrans. Enlarged and tender lymph nodes were present in the right groin. The remainder of the physical exam was unremarkable. The patient was sent home on a three week course of doxycycline for presumptive Lyme disease (LD). Initial results of a LD ELISA and western blot were negative for IgM and IgG. A repeat LD ELISA ten days later was positive for IgM, confirmed by western blot.
Lyme Disease
Background
Lyme disease was first described by Steere and colleagues at Yale University in 1977 as "Lyme arthritis", following an epidemic of arthritis occurring in residents from a small Connecticut town called Old Lyme. Steere noted that the arthritic symptoms had almost always been preceded by a distinctive rash, an erythematous papule that developed into a rapidly expanding annular lesion. This rash resembled a lesion that had been reported in Europe since the 1920’s called "erythema chronicum migrans". In 1982, Burgdorfer and colleagues isolated a spirochete from the suspected tick vector and this new species of Borrelia was subsequently named Borrelia burgdorferi in his honor. Cases of LD have been reported worldwide, within the entire northern hemisphere. Two other species have been found in Europe and Asia: B. garinii and B. afzelii. Atypical strains of B. burgdorferi have also been isolated along the eastern seaboard, some of which lack the outer surface protein "OspA" which is often used in diagnostic reagents. LD is now the most common vector-borne disease in the United States. In the East and North Central regions of the United States, the vector is usually Ixodes scapularis (dammini) whereas in the Northwest the vector is Ixodes pacificus. The life cycle of the ticks consists of three stages and a life span of two years. The most effective stage for transmission is the nymph, which is prevalent in late spring and early summer.
Clinical Presentation
The clinical manifestations of LD occur in three stages. Stage one follows the initial tick bite and is associated with the erythema chronicum migrans (ECM) lesion. Some studies have shown that over 90% of patients develop this rash and 50% have systemic symptoms, including lymphadenopathy. The second stage results from spirochetemia and presents most often as acute arthritis and/or meningitis. Other cutaneous lesions, infection of the eye, hepatitis, meningitis, and myocarditis may also occur. The third stage is the chronic phase of the disease and is characterized by other chronic skin lesions, neurologic symptoms and arthritis. Vertical transmission during pregnancy is exceedingly rare. No documented cases of transfusion-related infection have been reported.
Diagnosis
Lyme disease may be diagnosed based on the presence of the ECM lesion, since this is specific for LD. Diagnosis may also be made from culturing citrated blood, although this takes 2-3 weeks. Biopsy specimens of ECM will show spirochetes on silver stain in up to 40% of cases, but further identification is necessary to confirm the diagnosis. Immunofluorescence and ELISA serologic techniques are used most commonly. Antibody may be absent early but is usually present after several weeks. IgM titers may remain elevated throughout the course of illness and even years later, so the presence of IgM cannot be used to diagnose acute infection. It is recommended that blood specimens be collected at the time of presentation and again after 8-14 days in order to document seroconversion. Positive results should be confirmed with both IgM and IgG immunoblots. Cross-reactivity in assays for B. burgdorferi may occur in patients with other borrelial infections, treponemal infections, HIV, EBV, and rickettsial infections. Current recognition of antigenic diversity among different strains of B. burgdorferi may lead to regionalized, more sensitive tests in the future.
Treatment
The initial therapy for LD was penicillin or tetracycline, but treatment failures with both antibiotics have been reported. Ceftriaxone, erythromycin, and doxycycline have also been used successfully. Despite therapy, some studies have shown that long-term patient prognosis includes an increased risk of impaired musculoskeletal function and verbal memory. The FDA has recently approved a recombinant OspA vaccine that has shown a moderate degree of efficacy in prevention of Lyme disease.
References
1. Centers For Disease Control and Prevention: Lyme disease–United States, 1994. MMWR 44: 459-462, 1995.
2. Koneman EW et al: Diagnostic Microbiology, fifth ed. Lippincott, Philadelphia, pp 964-971, 1997.
3. Magnarelli LA: Current status of laboratory diagnosis for Lyme disease. Am J Med 98: 10s-12s, 1995.
4. Steere AC: Lyme disease. N Engl J Med 321: 586-596, 1989.
Example of a classic erythema chronicum migrans Adult female Ixodes scapularis
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