Prospective Evaluation of the Frequency and Severity of Symptoms in Lyme Disease Patients With Erythema Migrans Compared With Matched Controls at Baseline, 6 Months, and 12 Months.

BACKGROUND: Erythema migrans is the most common clinical manifestation of Lyme disease. Despite antibiotic therapy, typically at least 10% of adult patients with erythema migrans experience persistence of at least 1 subjective symptom for ≥6 months (posttreatment Lyme disease symptoms [PTLDS]). METHODS: This study was designed to determine whether the frequency and severity (based on a visual analogue scale) of 12 particular symptoms in patients with erythema migrans (n = 52) differed from matched control subjects (n = 104) followed prospectively for 12 months. RESULTS: At baseline, patients with Lyme disease were more likely than controls to have at least 1 symptom (P = .006). Among symptomatic subjects, Lyme disease patients had a higher mean number of symptoms (P < .001) and a higher mean total symptom severity score (P < .001). At both 6 and 12 months, however, there were no significant differences for these variables and no significant differences in the frequency or severity of any of the 12 individual symptoms assessed. However, 10 patients were clinically assessed as having possible PTLDS. CONCLUSIONS: Patients with erythema migrans were more likely than matched control subjects to be symptomatic at baseline with a greater symptom severity score, but this was not found at ≥6 months. Use of symptom survey data alone, however, was less likely to identify patients with possible PTLDS compared with individual clinical assessments. Because it is very challenging to be certain that the presence of long-term symptoms in a particular patient is correctly attributable to having had Lyme disease, an objective biomarker would be highly desirable.

Patients with Erythema Migrans: Characterizing the Impact of Initiation of Antibiotic Therapy Prior to Study Enrollment.

Erythema migrans is the most common clinical manifestation of Lyme disease, with concomitant subjective symptoms occurring in ∼65% of cases in the United States. We evaluated the impact of having been started on antibiotic treatment before study enrollment on 12 particular symptoms for 38 subjects with erythema migrans versus 52 untreated subjects. There were no significant differences in the frequency of having at least one symptom or in the symptom severity score on study entry. However, the frequency of having at least one symptom was significantly greater for those who had received <7 days of antibiotic treatment than for those who had been treated for ≥7 days (23/24 [95.8%] versus 8/14 [57.1%], P = 0.006). In addition, the percentage of subjects who were males was significantly lower among the group on treatment than among the untreated study subjects (13/38 [34.2%] versus 34/52 [65.4%], P = 0.005). In conclusion, based on these findings, combining untreated and treated groups of patients with erythema migrans for research study analyses may have limitations and, depending on the study objectives, might not be preferred. Additional studies are warranted to better understand the day-to-day impact of antibiotic treatment on the presence, type, and severity of symptoms in patients with early Lyme disease.

Evaluation of selected variables to determine if any had predictive value for, or correlated with, residual symptoms at approximately 12 months after diagnosis and treatment of early Lyme disease.

Subjective symptoms may persist after antibiotic treatment of patients with erythema migrans. Selected baseline variables were evaluated to determine if any correlated with symptom persistence to 12 months (PTLDS). Tingling or an abnormal skin sensation were reported by 5 (71.4%) of the 7 PTLDS cases at the baseline visit versus 4 (13.3%) of the 30 initially symptomatic subjects without PTLDS (P= 0.005). The frequency of having a total score of ≥17, when the Beck Depression Inventory score was added to the number of pain sites that the subject reported at the baseline visit, also showed a significant difference: 71.4% versus 10%, P= 0.002. All but 1 of the 7 subjects with possible PTLDS had either a total score of at least 17 on these 2 measures combined or had a score of ≥2 on the stress event questionnaire used. Clinical investigations should be conducted to validate these findings with other patient cohorts.