Background: Symptomatic reinfections with Borrelia burgdorferi sensu lato occur, but their clinical and microbiologic characteristics are insufficiently defined. It, therefore, remains unclear whether having had a primary infection influences the presentation or course of reinfection.
Methods: We compared the clinical and microbiologic findings in patients with primary infection versus reinfection, with each episode presenting with erythema migrans (EM). The analysis included a cohort of patients diagnosed with EM between 1990 and 2014 at an outpatient clinic in Slovenia.
Results: A total of 11,169 patients with EM were included, comprising 635 reinfections and 10,534 primary infections. Patients with reinfection were older (56 vs 48 years; p < 0.001), less frequently had multiple EM lesions (4.4% vs 7.3%; p = 0.022), and less often reported local symptoms at the EM site (42.5% vs 53.6%; p < 0.001). Reinfected patients were less often Borrelia IgM seropositive (35.0% vs 43.6%; p = 0.028) and more often IgG seropositive (63.0% vs 52.8%; p = 0.011). The rate of Borrelia isolation from EM skin lesions, however, was similar in both groups (53%). Reinfections were more frequent in immunocompromised than in immunocompetent patients (6.8% vs 2.4%; p < 0.001).
Conclusions: Compared with primary infection, EM due to reinfection shows distinct clinical and serologic features and is less often disseminated. The increased frequency of reinfection among immunocompromised patients supports a role of host immunity in protection against Borrelia reinfection.
Trial registration: NCT06835075.
Keywords: Borrelia burgdorferi sensu lato; Cohort study; Erythema migrans; Lyme borreliosis; Reinfection.
© 2026. The Author(s).