Sex and Gender Impact Lyme Disease Immunopathology, Diagnosis and Treatment

Lyme disease is an emerging tick-borne disease that is increasingly prevalent across temperate regions of North America and Eurasia. Investigators from the Centers for Disease Control and Prevention (CDC) recently estimated that there are approximately 300,000 cases annually in the United States. Lyme disease presents with several different clinical phenotypes, largely dependent on the stage of the infection and the presence or absence of prior antibiotic treatment. Compared to other infectious and chronic diseases where sex differences are more pronounced, differences in the number of CDC-reported cases of Lyme disease by sex are unremarkable. Although the prevalence of early Lyme disease appears to be relatively equal by sex, late Lyme disease with objective neurologic or rheumatologic findings appears to be more common in males than females. In contrast, subjective syndromes of more tenuous and complex origin such as post-treatment Lyme disease syndrome (PTLDS) and chronic Lyme disease (CLD) appear to be more commonly reported in females than males. Several factors could contribute to these observed differences in clinical presentation between the sexes. While social and behavioral risk factors may play an important role, this chapter will focus on underlying differences in the immune response between males and females following infection, which could affect bacterial clearance, development of autoimmune-like responses, and seroconversion on two-tier antibody tests. In the four decades of research since the discovery of the Lyme spirochete, much remains unknown regarding sex- and gender-based differences in the epidemiology, clinical presentation, and immunologic response to this infection.