Revelance of Serum Antibody Responses After Antibiotic Therapy for EM
Clinical Relevance of Different IgG and IgM Serum Antibody Responses to Borrelia burgdorferi After Antibiotic Therapy for Erythema Migrans
Glatz M, Golestani M, Kerl H, Müllegger RR
Arch Dermatol. 2006;142:862-888
Approximately 75% of patients infected with the Lyme disease (LD) pathogen Borrelia burgdorferi present with erythema migrans, a figurate erythema that classically presents with 1 or more "bull's-eye" lesions. Systemic symptoms of LD include malaise, fever, arthralgias, and headache, and LD can lead to late-stage cardiac, rheumatologic, and cardiac complications, especially when untreated. The utility of serologic testing to confirm the diagnosis of LD has been controversial, with most clinicians taking a "treat if clinically consistent with Lyme" approach, especially in Lyme-endemic areas. Whether serum antibody levels to B burgdorferi provide useful information regarding the therapeutic response to antibiotic therapy remains to be determined.
In a retrospective European study, Glatz and colleagues addressed this important question by investigating the immunologic response of 113 patients with erythema migrans (EM) during a mean follow-up period of at least 1 year after standard antibiotic therapy. The study population consisted of 113 patients meeting the following criteria:
clinically diagnosed EM (88% solitary EM; 12% multiple EM lesions);
treatment with a standard antibiotic regimen for at least 2 weeks (68% treated with tetracyclines, 32% treated with beta-lactam antibiotics);
clinical follow-up available for at least 1 year after treatment;
serum samples available for anti-B burgdorferi IgG and IgM analysis (pretreatment and posttreatment samples, with the last sample drawn at least 1 year after therapy); and
clinical information including patient demographics, size and number of EM lesions, presence or absence of extracutaneous symptoms, and type/duration of therapy.
Most patients (88%) had solitary EM lesions, and only 32% presented with extracutaneous manifestations of LD, including fever, arthralgias, fatigue, and/or headache. Patients were excluded from the study if they possessed variables that could influence the development of anti-B burgdorferi antibodies (eg, prior history of LD, antibiotic therapy prior to the first antibody titer, autoimmune diseases).
Investigators found that the patients with EM met 1 of 3 antibody profiles:
persistence of a positive antibody titer throughout the observation period; 11% of patients had persistent positive IgM titers and 12% of patients had persistent IgG titers;
persistently negative antibody titer; 56% had persistent negative IgG titers and 42% had persistent negative IgM titers; and
a positive pretreatment antibody titer that converted to negative during the follow-up period; 30% reverted from positive to negative IgG titers and 43% reverted from positive to negative IgM titers.
Patients with EM that was present for a longer duration prior to treatment and patients with larger-diameter EM lesions were more likely to have persistently positive IgG titers. In contrast, serologic markers did not correlate with treatment type or duration, presence of extracutaneous manifestations of LD, or clinical course.
This retrospective Austrian study confirms prior reports that the persistence of positive anti-Borrelia IgG titers correlates with the duration of EM before therapy. In addition, Glatz and colleagues found that larger EM lesions were more likely to yield a persistent positive IgG response; however, the presence of multiple EM lesions or extracutaneous manifestations of LD appeared to have no impact on immune response. These findings make sense, because early antibiotic therapy may limit the exposure time of the host's immune system to B burgdorferi antigens.
Although no correlations were found between host antibody response and short-term clinical outcome, long-term ramifications are intriguing. Are individuals with persistent anti-Borrelia antibody titers more likely to develop autoimmune sequelae associated with LD? If so, early treatment of EM and LD may reduce the incidence of complications such as chronic arthralgias and fatigue. Does the presence of a persistent IgG titer correlate with chronic infection and a worse prognosis (a possibility not supported by the current study)? Conversely, are patients who receive early antibiotic therapy less immune to future B burgdorferi infection? Finally, one should not assume that results from this European study can be simply applied to cases of LD in the United States, because geographic differences in both pathogen and disease course have been described.