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As traditionally described, the first symptom associated with LD is a dermal reaction at the site of the tick bite called Erythema Migrans (EM). The appearance of EM after transmission of Bb is broad but generally averages 7 to 10 days, and can present as early as 2 or 3 days after the tick is recognized (50). It is commonly stated that 60% to 80% of Americans with LD experience this initial cutaneous lesion, characterized as an erythematous target shaped rash, which should measure at least 5 cm in width to qualify as EM or bulls eye rash (see below). In fact, this percentage is clearly an overestimate, as a majority of patients do not recall a rash, certainly not a classic bull’s eye form with central clearing. Recent reports confirm that in most cases the dermatologic presentation is an amorphous flat, expanding rash rather than the target or bulls eye shape (51). As mentioned previously, an allergic reaction can occur due to the saliva injected by the tick but should not be easily confused with EM. The salivary reaction is typically small, usually less than1 cm, and generally disappears one day after the bite.
Erythema migrans, on the other hand, is a gradually expanding lesion, frequently taking the target or bulls eye form, which develops 7-10 days after the bite and can last for days to weeks (52). The characteristics of size, expansion, and chronicity of the rash are more important and consistent features with LD than the morphology of the rash. It has been noted that unusual, multiple simultaneous EM lesions can occur. Whether this represents a condition compatible with disseminated EM or, perhaps less likely, represents multiple simultaneous Bb bites, is not clear (53). We have had several patients describe and document this feature of the illness. Our record for disseminated Bb target lesions is 50 or so EM lesions noted at one time, reported by a female podiatrist who resides in the countryside just a few miles south of Charlotte, NC.
A little recognized fact about the EM rash is that it can recur, usually in the original site, with or without antibiotic therapy. We estimate that between 5-10% of patients demonstrate this phenomenon during their illness. Other patients remark that they have migratory rashes of moderate duration from time to time that remain unexplained. It is more common, in our experience, to observe the presence of recurrent EM after the onset of antimicrobial therapy. We note that some patients erupt with rash repeatedly while on antibiotic therapy, often in different areas. Eventually this dissipates as the patient improves on antibiotic therapy. Pressure points may play a role in the appearance of the rash, but gravitational influence does not appear to play a role in terms of the site of eruption, i.e. as one would see in a vasculitis-like presentation characteristic of most drug reactions. The first appearance of rash has been reported as late as 6 months into therapy (personal observation). This has led to obvious diagnostic challenges when one is on antibiotic therapy and has to consider a drug reaction. However, we have come to recognize that the LD rash on treatment presents as flat or occasionally raised coalescent islands of erythema, in contrast to the classic generalized morbilliform rash caused by a drug reaction. When confronted with this clinical picture, the Jemsek Specialty Clinic views this as a positive indication of therapeutic benefit, probably representing a dermal form of the “Herxheimer reaction”, and so we generally proceed cautiously on with antibiotic therapy, usually with eventual resolution of the rash.
In the initial infection stage, or acute illness, a variety of flu like symptoms may occur a few days after the appearance of the rash. Specific symptoms may include fever, malaise, fatigue, joint pain, muscle pain, lymphadenopathy, and not uncommonly encephalopathy, or altered mental status, with or without headache. We believe that, consistent with the conventional doctrine, most cases of LD respond to relatively short courses of antibiotics. However, we prefer to treat at higher than usual doses for up to four weeks instead of 7 to 10 days, in the hope that we may prevent a few cases from going on to develop neuroborreliosis (see discussion below). We believe the benefit to risk ratio with this approach is extremely high. Unfortunately, given the lack of consensus on diagnosis of LD and issues on the validity of a persistent form of this infection, the clinical trials needed to confirm the value of our approach cannot easily be performed at this time. Nonetheless the Clinic has interviewed numerous individuals who present to us with a history of relapsing into a persistent set of symptoms after having been administered the standard 7 to 10 days of therapy for presumptive LD.
As was mentioned above, in many cases the symptoms of LD present in the absence of EM or any typical expanding rash. Occasionally this can be explained by the fact that the rash has occurred in the scalp, hairline, or in a posterior location where it may not have been easily visible. In persons of color, the obvious difficulties in identifying a rash undoubtedly hold true here as well. In cases without rash, one may also wish to consider Ehrlichiosis, which has been increasingly referred to as “spotless fever”(54,55,56).