If the confirmatory test for Lyme (Lyme disease) is negative, do I still treat?

From the Guidelines

Treatment for Lyme disease is generally not recommended if the confirmatory test is negative, unless there are strong clinical signs and symptoms suggesting Lyme disease despite the negative test. If you have a negative confirmatory test (typically Western blot) following a positive screening test (ELISA), this usually indicates that the initial screening was a false positive. However, in some cases where Lyme disease is strongly suspected based on symptoms, tick exposure history, and presence in an endemic area, a physician might consider treatment despite negative tests, as suggested by the clinical practice guidelines by the Infectious Diseases Society of America 1.

Considerations for Treatment

• The decision to treat should be based on clinical judgment, taking into account the patient's symptoms, medical history, and risk factors for Lyme disease.
• The standard treatment would be doxycycline 100mg twice daily for 10-21 days (depending on manifestations), or alternatives like amoxicillin 500mg three times daily or cefuroxime 500mg twice daily for patients who cannot take doxycycline, as recommended by the guidelines 1.
• It is essential to note that serologic tests may be negative early in the disease or if antibiotics were started before antibody development, which may lead to false-negative results.
• If you're concerned about possible Lyme disease despite negative testing, consult with an infectious disease specialist who can evaluate your specific situation and symptoms, as they can provide guidance on the best course of action.

Clinical Practice Guidelines

• The clinical practice guidelines by the Infectious Diseases Society of America 1 recommend clinical diagnosis rather than laboratory testing for patients with potential tick exposure in a Lyme disease endemic area who have one or more skin lesions compatible with erythema migrans.
• The guidelines also suggest antibody testing performed on an acute-phase serum sample (followed by a convalescent-phase serum sample if the initial result is negative) rather than currently available direct detection methods such as polymerase chain reaction (PCR) or culture performed on blood or skin samples 1.
• For patients with Lyme arthritis, the guidelines recommend treatment with antimicrobial agents administered orally, such as doxycycline, amoxicillin, or cefuroxime axetil, for 28 days 1.

From the Research

Treatment of Lyme Disease

• The treatment of Lyme disease typically involves the use of antibiotics, such as doxycycline or amoxicillin, to prevent the progression of the disease to its later stages 2, 3.
• A 14-day course of amoxicillin has been shown to be effective in resolving the erythema migrans skin lesion and preventing the development of objective neurologic, cardiac, or rheumatologic manifestations 4.
• A network meta-analysis of 31 randomized controlled trials found that oral amoxicillin, oral azithromycin, injectable ceftriaxone, and injectable cefotaxime were effective for treating Lyme disease, while cefuroxime and penicillin were safe for treating the disease 5.

Confirmatory Testing

• A negative confirmatory test for Lyme disease does not necessarily rule out the possibility of infection, as the test may not be sensitive enough to detect the disease in its early stages 3.
• The diagnosis of Lyme disease is typically based on clinical findings, such as the presence of erythema migrans, and a history of a possible or confirmed tick bite 2, 3.
• Serological tests may not be useful in the early stages of the infection, and a negative test result should not be used to exclude the diagnosis of Lyme disease 3.

Treatment Decision

• The decision to treat Lyme disease should be based on clinical judgment and the presence of symptoms, rather than solely on the results of confirmatory testing 2, 3.
• Treatment with antibiotics should be initiated as soon as possible after the diagnosis of Lyme disease is made, to prevent the progression of the disease to its later stages 2, 3.
• The choice of antibiotic and the duration of treatment will depend on the stage and severity of the disease, as well as the patient's medical history and other factors 2, 5, 3.