Lyme disease and Relapse-Reinfection versus Relapse

Erythema migrans.

Lyme disease is the most common tick-borne infection in the United States and Europe. Clues to differentiating reinfection from relapse of Lyme disease

During both the initial infection and subsequent episodes, the majority of patients with Lyme disease manifest the distinctive skin lesion erythema migrans. In untreated patients, erythema migrans resolves spontaneously within a median of about twenty eight days, but relapse may occur within a longer period, usually within a year or so of the appearance of the initial lesion. After treatment with presently recommended antibiotic regimens, however, persistence, progression, or recurrence of the skin lesion or the development of objective extra cutaneous manifestations of Lyme disease is exceedingly rare.

Relapse has been well-documented (on the basis of recovery of B. burgdorferi by culture) only in patients treated with antibiotics like cephalexin also known to have poor activity in vitro against this microorganism, although some patients treated with certain macrolides also appear to experience relapse clinically. Thus, the development of a new erythema migrans lesion in a person with a prior history of Lyme disease who was treated with recommended regimens is prima facie evidence for reinfection.

Clinical features that suggest reinfection rather than relapse include the development of an erythema migrans lesion at a site different from that of the original lesion and the presence of a punctum in the lesion. A punctum is a small raised or depressed point near the center of a primary erythema migrans lesion, representing the site from which the tick detached. In the United States, repeat episodes of erythema migrans due to reinfection almost always develop in a subsequent transmission season during the late spring or summer (R.B.N., unpublished data) at the time when nymphal stage (i.e., the stage that is the principal vector for Lyme disease) scapular’s or Ixodes pacificus ticks are most abundant. In Eurasia, reinfection, usually transmitted by nymphal Ixodes ricinus or adult Ixodes persulcatus, is also expected to occur mostly during the late spring or summer. In contrast, cases of relapse of preexisting infection would not necessarily be expected to occur in a seasonal pattern and would be likely to arise within a few weeks to several months after the initial episode.

Lyme disease and Relapse-Differentiating reinfection from relapse

Limited data are available regarding the clinical manifestations of second episodes of erythema migrans in patients with Lyme disease who have reinfection. A recent report described twenty eight patients from Block Island, Rhode Island, who had repeated episodes of erythema migrans and were believed to have been re-infected with B. burgdorferi (five additional persons had only “flu-like illnesses” as either their first or second episode of infection but were considered to have Lyme disease on the basis of seroconversion). None of the patients had clinical evidence of immunodeficiency. Persons with reinfection were equally distributed by sex; however, 6 (86%) of 7 persons who experienced a third episode of Lyme disease were female. This finding is difficult to explain but is consistent with the observations in a recent Swedish study, in which the investigators found that twenty seven of thirty one re-infected persons were women aged 44 years old.

Lyme disease and Relapse-Analysis

As one would predict, nearly all cases of recurrent infection in the Block Island study occurred during the late spring or summer. The number and severity of symptoms were similar in the first and second episodes and appeared to be less severe during the third episode, although these findings were not statistically significant. Surprisingly, all patients with recurrent Lyme disease did not seek medical attention sooner than did those who had only a single episode. That was very interesting.

A preliminary report summarized findings for eleven men and another eleven women with who each experienced two episodes of erythema migrans and were seen at our institution; the episodes occurred a mean (±SD) of 3.25 ± 2.65 years apart. A prior tick bite at the site of erythema migrans was recalled with similar frequency in patients who experienced first and second episodes. Patient symptoms (including fever), diameter of erythema migrans, abnormal findings on physical examination, and laboratory results (complete blood count, transaminase levels, and erythrocyte sedimentation rate) during second episodes were similar to those during first episodes. These findings were also similar to those for contemporaneous control subjects who experienced single episodes of erythema migrans. This study obviously had insufficient power to detect relatively small differences.

In this study, patients were >2 times as likely to have multiple erythema migrans skin lesions (a marker of hematogenous dissemination of B. burgdorferi infection) during their first episode of Lyme disease than during their second episode (7 [32%] patients during the first episode vs. 3 [14%] patients during the second episode; P = .15). Although this finding could be a chance event, alternatively, it could be related to the development of partial host immunity, leading to protection from hematogenous dissemination after reinfection