CAUSES and clinical manifestations of Lyme disease.
Lyme disease (LD) is a tickborne infection caused by a spiral bacteria (spirochaete). As this spirochaete is a Borrelia species, the illness is also known as Lyme borreliosis (LB).
Mothers of children in Lyme, Connecticut, US, were concerned that local children diagnosed with juvenile rheumatoid arthritis had also reported unusual skin lesions following tick bite.
In 1981, Burgdorfer and Barbour isolated the causative spirochaete (Borrelia burgdorferi) from Ixodes dammini ticks (now called I. scapularis). This first detection was followed by discovery of other Borrelia strains from European LB patients. Since then, many Borrelia species related to the original isolate have been described and are grouped under the banner of Borrelia burgdorferi sensu lato (sl) genospecies group (Table 2).
The main organism that causes LB in northeastern US is B. burgdorferi sensu stricto (ss).
Within each Borrelia species, there is variation in animal reservoir host specificity (favoured animal reservoir in the wild) as well as variation in human pathogenicity (ability to cause illness).
Additionally, some species are strongly associated with tissue tropism and disease manifestations (e.g. B. garinii with neurological manifestations, B. afzelii with skin manifestations, typical Lyme arthritis is more common in North America, due to B. burgdorferi ss).
Standard classification of clinical manifestations of LB are presented in Table 1.
While stages of illness appear separate, there may be overlap, e.g. stage I erythema migrans (EM) lesion may still be present when stage II manifestations occur.
The ‘hallmark’ skin lesion of LB is EM. It can appear at the tick-bite site, but it can also appear elsewhere and be multiple. It may be a short-lived lesion or a chronic skin lesion (erythema chronicum migrans). The lesion may vary in size from a few centimetres to a very large lesion that involves a large part of the body surface, having expanded from the original lesion site.
Neither a history of tick bite nor EM is required for the diagnosis of LB as neither tick bite nor EM is reported in 30—40% and 10—25% of cases respectively in endemic areas. These percentages may vary in different endemic areas often reflecting the prevalence of different species in those areas. Initial presentation with stage II or stage III manifestations can present diagnostic difficulties, as the differential diagnosis may be wide (e.g. aseptic meningitis, facial nerve palsy, arthritis, etc).
A history of potential exposure in an endemic area may not be elicited or volunteered but should be sought. Diagnostic tests will be discussed in a subsequent article.
Clinical manifestations of LB are confounded by both the protean manifestations of the illness as well by the possibility of co-infection with other tickborne pathogens including Anaplasma, Babesia, Bartonella, Ehrlichia, Rickettsia, tickborne viruses and even other Borrelia species not classified as being in the B. burgdorferi sl group. The incidence of co-infection in any endemic area depends on the prevalence of infection of ticks (to which humans are exposed) with these pathogens.
Multiple tick bites can cause infection with multiple pathogens, but a single tick bite can also cause infection with multiple pathogens if that tick is infected with multiple pathogens.
Complicating matters further is the likelihood a tick is infected with multiple strains of LB-associated Borrelia (e.g. different species or strains with different pathogenicity). A recent publication noted the role of Borrelia miyamotoi infection and illness in persons in northeastern US LB-endemic areas. This Borrelia is a member of the relapsing fever Borrelia group (RFB), indicating that Borrelia infection with LB and relapsing fever can both occur in Lyme-endemic areas.
Currently, conventional thinking is that LB is endemic only in the northern hemisphere, although B. garinii has been detected in wildlife and ticks in the southern hemisphere.
Borreliosis is a general description of infection caused by Borrelia species, of which one subset is LB. There is an expanding range of Borrelia species associated with both LB and RFB.
It is likely therefore that new endemic areas will be described for these infections. The situation in Australia will be reviewed in a subsequent article.
Standard classification of clinical manifestations of Lyme disease
- Stage I – Skin, usually mild constitutional Erythema (chronicum) migrans (e.g. 2–30 days)
- Stage II – Skin, central nervous system (CNS), cardiac multiple EM, aseptic meningitis, nerve roots and nerve pain, heart problems (e.g. weeks to months)
- Stage III – Joints, CNS/peripheral nervous system, skin, arthritis (1/>1 joints) US (80% if untreated) (days/weeks) encephalomyelitis, peripheral neuropathy (months/years) acrodermatitis chronica atrophicans (years)
Borrelia burgdorferi sensu lato species globally*
B. afzelii, B. bavariensis, B. garinii, B. japonica, B. lusitaniae, B. sinica, B. spielmanii, B. tanukii, B. turdi, B. valaisiana, B. yangtze
B. americana, B. andersonii, B. californiensis
Both Old and New World
B. burgdorferi ss, B. bissettii, B. carolinensis, B. kurtenbachii
*Distribution may change with further study (Rudenko et al). Species in bold have been associated with human infection. Others have not been isolated from humans.
Rudenko N et al. doi:10.1016/j.ttbdis.2011.04.002
Krause PJ et al. doi:10.1056/NEJMc1215469
Borrelia burgdorferi sensu lato species globally*