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Clin Infect Dis. 2020 Jan 23. pii: ciz1215. doi: 10.1093/cid/ciz1215. [Epub ahead of print]

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.

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Division, of Infectious Diseases, Department of Medicine, New York Medical College, Valhalla, New York, USA.
Division of Internal Medicine, Department of Medicine, New York Medical College, Valhalla, New York, USA.
Department of Pediatrics, Yale University, New Haven, Connecticut, USA.
Department of Epidemiology of Microbial Diseases, Yale University, New Haven, Connecticut, USA.
Baystate Medical Center, Springfield, Massachusetts, USA.



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]).


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.


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.


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.


Borrelia burgdorferi ; Lyme disease; PTLDS; outcome; posttreatment symptoms


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