ties. Early antibiotic therapy may also cause false-negative test results, and cases of seronegative Lyme disease have been reported.93

False-positive results may also occur as a result of crossreaction between B. burgdorferi and other spirochetes, such as T. pallidum. Cross-reactivity between a Lyme immunofluorescence assay test and an FTA-ABS test is reported in 11– 54% of patients.94–96 In a study by Hunter and coworkers,97 22% of patients with Lyme disease had a reactive FTA-ABS test at a dilution of 1 : 5, but all of these samples were negative at a dilution of 1 : 10. Nevertheless, the rapid plasma reagin test and the microhemagglutination–T. pallidum test are usually negative in patients with Lyme disease.94 Falsepositive results have also been reported in many autoimmune disorders, Rocky Mountain Spotted Fever, infectious mononucleosis, and neurologic disorders.96,98–100 Importantly, in most areas of the United States the prevalence of Lyme disease is low. Even with a sensitivity and a specificity of 90%, the predictive value of a positive ELISA for Lyme disease is probably less than 20% in patients with a clinical picture atypical for the disease.

A fourfold increase in serial anti-B. burgdorferi IgM antibody levels in patients with a clinical history compatible with Lyme disease remains the most specific laboratory indicator, but this increase is not often documented by serial tests. Western blot analysis and PCR101,102 are increasingly used for the diagnosis.

Recommendations for laboratory screening for Lyme disease include obtaining an ELISA using both an IgMspecific and IgG-specific antiimmunoglobulin or a poly­ valent antiimmunoglobulin.98 Persistence of the specific IgM response throughout infection is an unusual feature of the antibody response seen in some patients with Lyme disease, and may be secondary to an impairment in the helper T-cell function needed to switch from IgM to IgG production.103 All positive or equivocal results by ELISA should be confirmed by Western blotting.104,105 Because the clinical appearances of Lyme disease and syphilis are similar, a rapid plasma reagin test and an FTA-ABS test should be performed on all patients tested for Lyme disease, and infectious mononucleosis should also be considered as a possible cause of false-positive results. Finally, the importance of pursuing a history of tick bites, residence in or travel to areas with endemic Lyme disease, rash, chronic joint complaints, or facial nerve palsy cannot be overemphasized.

The literature is now replete with articles stressing the overdiagnosis of Lyme disease.104–106In cases of ocular inflammation without a clinical history of tick bite, characteristic rash, arthritis, or neurologic complaints, the likelihood is extremely low that Lyme disease is the cause of the inflammation. In such cases, serologic testing is probably not indicated.107,108 Cases of uveitis in endemic areas with suspicious nonocular symptoms should be evaluated with ELISA. As mentioned earlier, positive ELISA results should be confirmed with Western blotting, and in certain cases ocular samples may be obtained for PCR, cytologic study, or culture.109,110 More recently, PCR has been used to help diagnose ocular Lyme disease.110a

Prognosis

From 10% to 40% of patients with untreated erythema chronicum migrans progress to stage 2 Lyme disease; 3–10%

Spirochetes

Table 10-7  Treatment of lyme disease

EARLY INFECTION

Adults

Doxycycline 100 mg PO bid × 14–21 days OR

Amoxicillin 500 mg PO tid × 14–21 days

If penicillin allergic use cefuroxime axetil 500 mg PO bid

Children

Amoxicillin 50 mg/kg/day divided into three doses (maximum 500 mg/ dose)

SEVERE UVEITIS OR NEUROLOGIC ABNORMALITIES OR ARTHRITIS

Ceftriaxone 2 g/day IV × 14–21 days

of patients experience chronic arthritis, acrodermatitis chronica atrophicans, or neurologic disease. Once it occurs, arthritis does not always respond to antibiotic therapy. Similarly, it is not known whether neurologic involvement is prevented by oral antibiotic therapy for early Lyme disease.

Treatment

Recommendations for the treatment of Lyme disease were reviewed by the Infectious Diseases Society of America104 and can be found in Table 10-7. Patients with mild ocular disease may respond well to oral antibiotics, but in cases of more severe ocular manifestations, such as posterior uveitis, intravenous antibiotic therapy with ceftriaxone is probably the treatment of choice, if prolonged treatment is required. Some data suggest that prior treatment with corticosteroids may predispose the patient to antibiotic failure; therefore, the use of topical corticosteroids should be limited to patients with anterior segment inflammation who are also being treated with antibiotics.77,111 Topical corticosteroids are also used to treat Lyme keratitis.60 If the suspicion for Lyme disease is high a therapeutic trial of antibiotics seems warranted, even in seronegative patients. Finally, chemoprophylaxis and vaccine development continue to be pursued despite early disappointments.89

Relapsing fever

Etiology and Epidemiology

Relapsing fever is an acute infectious disease caused by spirochetes of the genus Borrelia and characterized by recurrent bouts of fever separated by relatively asymptomatic periods.112,113 Relapsing fever is divided into two epidemiologic types: epidemic, or louse-borne, and endemic, or tickborne (Box 10-4). Epidemic relapsing fever is transmitted from person to person by the human body louse Pediculus humanus, which has previously ingested blood infected with Borrelia recurrentis.114 Infection occurs when the hemolymph from infected body lice contaminates abraded or even normal skin, usually from scratching, when lice are crushed and come into contact with previously excoriated bites. The epidemic form of relapsing fever is found in parts of Africa, South America, and China where crowding, poor sanitation, and famine foster louse infestation.112

Endemic relapsing fever was first documented in the United States in 1915 after five persons contracted the disease in Bear Creek Canyon, Colorado.115 This form of the disease is caused by at least 15 species of Borrelia, and the tick vectors have now been identified as several species of the genus Ornithodorus with a rodent reservoir.112,116

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