CASE #1: Tick bite
The tick was identified as Ixodes daminii (deer tick), but no parasites where found in its mouth. Lyme disease (LD), the most common tick-borne illness in the United States, is a systemic infection caused by the spirochete Borrelia burgdorferi. The spirochete is introduced into the skin by the bite of infected Ixodes black-legged ticks, primarily of the Ixodes scapularis species. Approximately 20,000 cases of LD are reported annually, with a yearly incidence rate of 8.2 per 100,000 persons and with higher prevalence in northeastern and north-central states.1 Most cases occur in children aged 5 to 14 years and adults aged 55 to 70 years.1 Furthermore, most disease cases result from the bites of infected Ixodes nymphs, as their small size allows them to subtly infect their targets.
Clinically, LD is diagnosed in three distinct stages. First, in the early-localized infection stage, which occurs several days to weeks after infection, multiple erythema migrans lesions (≥5 cm) appear in a bull’s-eye pattern. The erythema migrans starts as a red papule at the site of the bite but gradually spreads to an annular lesion with red borders and partial central clearing. Patients may experience flulike symptoms, muscle and joint aches, and fatigue. The incubation period from infection to onset of the erythema migrans rash is approximately seven to 14 days but can be as short as one day and as long as 30 days.
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Second, in the early-disseminated infection stage, which occurs within a few days to weeks after infection, the spirochete spreads hematogenously to different sites, and patients may develop multiple erythema migrans lesions. Patients can present with such symptoms as facial-nerve palsy, fatigue, lymphadenopathy, muscle and joint pain, and meningitis. Cardiovascular symptoms are less common but may include atrioventricular blockage and carditis.
Third, in the late-disseminated infection stage, which occurs months or years postinfection, patients may develop acrodermatitis chronica atrophicans, chronic polyneuropathy, or encephalopathy. More common is asymmetric oligoarticular arthritis, which develops in about 60% of untreated patients at a mean of six months from the onset of disease. In addition, patients with the alloantigen HLA-DR4 have a high risk of developing chronic arthritis involving intermittent pain of one or more large joints (particularly of the knees).
The differential diagnosis of LD, specifically the rash of the erythema migrans localized stage, includes tinea corporis, nummular eczema, and granuloma annulare. However, the differential diagnosis becomes complex as the infection disseminates and affects the musculoskeletal system, nervous system (CNS), or heart. Carditis may be confused with endocarditis, and facial nerve palsy may be diagnosed as idiopathic Bell’s palsy, central nervous system tumor, or acute rheumatic fever. Meningitis may be misdiagnosed as other meningitis infections (viral, leptospiral, tuberculosis, bacterial, and subacute).
The diagnosis of LD is made by both clinical and serologic evaluation, primarily favoring such indirect methods as assays over direct techniques involving polymerase chain reaction (PCR) and culture. Two direct detection methods of biopsy specimens involve PCR, which is used to amplify genomic DNA of B. burgdorferi in skin, blood, cerebrospinal fluid (CSF), and synovial fluid, and culturing of B. burgdorferi samples enriched in special bacteriologic media for up to 12 weeks. These direct methods are unreliable, however, due to several limitations. Culturing is labor-intensive and time-consuming and is only sensitive to skin samples from patients with erythema migrans. Although PCR offers very rapid results, it lacks satisfactory sensitivity, particularly in PCR determinations of CSF from LD patients with neuroborreliosis. Overall, neither process provides any information about dissemination of the infection to other organs.
Serologic testing is the more common and corroborative laboratory standard for LD. Because serologic tests alone can yield false-positives and false-negatives, the CDC recommends a two-step process using the enzyme-linked immunosorbent assay (ELISA) or indirect fluorescent antibody (IFA) tests to detect anti-B. burgdorferi-specific antibodies, followed by confirmation using Western immunoblotting.2 The use of recombinant antigens, particularly VlsE lipoprotein of B. burgdorferi and the C6 peptide, which reproduces the invariable region 6 of VlsE, offers excellent specificity in ELISA testing. Anti-B. burgdorferi-specific antibodies are usually detected within two to four weeks after onset of symptoms. Next, the Western blot, which increases specificity, is normally interpreted using standardized criteria requiring at least two to three bands for a positive immunoglobulin (Ig) M Western blot and five of 10 bands for a positive IgG Western blot.2
The duration and type of LD treatment depends on the stage and severity of infection. Early, localized erythemas should be treated with oral antibiotic therapies. The first line of treatment consists of doxycycline (100 mg twice per day) and amoxicillin (500 mg t.i.d.) for approximately two to three weeks.3 Second-choice treatment includes azithromycin (500 mg daily) and cefuroxime (500 mg b.i.d.). Doxycycline in particular has been shown to have the most effective penetration into the CSF, which is important in light of the potential for the spirochetes to spread to the CNS in erythema migrans patients. Third-line treatments include oral macrolides, but these are less effective than the b-lactams and tetracyclines.
If neurologic impairments or atrioventricular heart block develop in later stages of LD, IV therapy may used. The primary option is ceftriaxone (2,000 mg daily), and the secondary options include cefotaxime (2,000 mg at eight-hour intervals) and penicillin G (five million IU at six-hour intervals). Each therapy should be administered for at least four weeks. Drugs that are not recommended for treatment include erythromycin, roxithromycin, clarithromycin, and cephalexin.
Overall, it is important for patients and clinicians to recognize that LD can be prevented through several lifestyle adjustments. Advise patients to avoid ticks by wearing protective clothing, avoiding brushy habitats, applying insect repellent, and inspecting themselves daily. However, if the patient does contract the disease in its initial stages (i.e., erythema migrans), early treatment of LD has an incredible success rate and prevents the development of complicated subsequent-stage symptoms.
The patient’s Lyme antibody test came back negative, and a blood smear showed no evidence of babesiosis. The patient was in good health at the follow-up exam three months later, and a serum Lyme antibody test was nonreactive.
