Pathogenesis of lyme disease. After inoculation in the skin, B burgdorferi replicates within the dermis producing EM and spreads hematogenously to other organs. The organism has tropism for the skin, joints, heart and CNS. A rise in immunoglobulin M (IgM) is detected within 2-3 weeks after the onset of infection; an increase in IgG and IgA is established after 2-3 months of infection. Host genetic factors may determine the likelihood of tissue damage; for example, patients with human leukocyte antigens DR4 and DR2 may be more susceptible to chronic arthritis.