Lyme Disease



Lyme Disease


Anne R. Bass

Steven K. Magid





KEY POINTS



  • Lyme disease is caused by the spirochete Borrelia burgdorferi.


  • In endemic areas, B. burgdorferi is transmitted by the bite of an Ixodes tick. This generally occurs in the late spring or early summer.


  • Early Lyme disease is characterized by the rash, erythema migrans (EM). Early dissemination of B. burgdorferi can result in fever, headache, myalgias, disseminated skin lesions, cranial neuropathy, radiculitis, meningitis, carditis, and/or arthritis. Manifestations of late, untreated Lyme disease include monoarthritis or oligoarthritis, peripheral neuropathy, or encephalopathy.


  • Early Lyme disease is diagnosed clinically. There is generally no role for serologic testing in this setting.


  • In late Lyme disease, serologic testing is virtually always positive.



  • Lyme disease should never be diagnosed based on a positive serology alone. The diagnosis of late Lyme disease can be made when symptoms specific for Lyme disease are present, and serology is positive.


  • The most common cause of “seronegative Lyme disease” is misdiagnosis.


  • A positive result for Lyme disease on enzyme-linked immunosorbent assay (ELISA) must be confirmed by Western blot test before using it to confirm a diagnosis of Lyme disease.


  • Lyme disease is treatable with antibiotics.


  • A small number of patients with a history of Lyme disease continue to have symptoms after completing a full course of intravenous antibiotics. Studies have shown that additional antibiotic treatment does not relieve these symptoms.

Lyme disease was first detected in the United States in 1977, when clusters of an illness, first thought to be juvenile idiopathic arthritis, were noted in three small communities in Connecticut. Although the earliest cases of Lyme disease were thought to have occurred 25 years ago in Cape Cod and in Connecticut, the spirochete has been identified in ticks collected more than 50 years ago.

Lyme disease is now the most common vector-borne illness in the United States. Although it is most prevalent in the Northeast Coast of the United States, the disease is also seen in Wisconsin and Minnesota, some West Coast states, and in Europe.


ETIOPATHOGENESIS


I. SPIROCHETE

Lyme disease is caused by the spirochete Borrelia burgdorferi. The B. burgdorferi that is found in the United States belongs to the subspecies B. burgdorferi sensu stricto, whereas in Europe, B. burgdorferi garinii and B. burgdorferi afzelii predominate. This may account for some of the differences in the clinical presentation of Lyme disease that is found in Europe from that found in the United States.



  • More than 30 B. burgdorferi proteins have been identified. There are three major outer surface proteins (Osp): Osp A (30 kDa), Osp B (34 kDa), and Osp C (23 kDa). Strain-specific differences in Osp C influence the ability of B. burgdorferi to disseminate from the skin.


  • There is also a 41-kDa flagellar (Fla) antigen that is shared by other spirochetes. Basic membrane protein A (Bmp A) (39 kDa) appears to be highly specific for B. burgdorferi. In contrast, the 58-, 60-, 66-, and 72-kDa antigens are heat shock proteins, which are widely conserved in all cells and have strong homology with other organisms.


II. VECTOR

B. burgdorferi is transmitted by ticks of the Ixodes family. On the East Coast of the United States, Ixodes scapularis is the most important vector. In the western United States, I. pacificus is responsible. I. ricinus is the main vector in western and central Europe, and I. persulcatus is found in eastern Russia, China, and Japan.



  • The life cycle of I. scapularis spans 2 years and includes three stages of development: larva, nymph, and adult. Ticks eat once at each stage of life and can acquire B. burgdorferi during the process of eating. There is no vertical transmission from adult tick to larva.


  • In the endemic areas of the Northeast, 30% to 50% of nymphal and adult ticks may be infected with B. burgdorferi. In the north central United States, infection rates of 10% to 20% are reported, while on the Pacific Coast the rate of tick infection is approximately 1% to 2%.


  • White-footed mice (plus the occasional bird, small mammal, or human) are the preferred host for larval and nymphal ticks, and serve as a reservoir for B. burgdorferi. Adult ticks feed on deer by attaching to its body (hence the term “deer tick”) or, rarely, by attaching to humans.


  • B. burgdorferi, acquired by larva, can be passed on to humans when those larvae become nymphs, and feed again. Nymphs feed during the late spring and
    early summer, which accounts for the peak time of onset of early Lyme disease. The small size (1 mm) of the nymphs, and the light clothing worn by humans at this time of year contribute to the ease of disease transmission. Although adult ticks can also transmit B. burgdorferi when they feed in the fall, their large size makes them easy to see and remove before transmission of disease can occur. In practice, human contact of B. burgdorferi from the bite of an adult deer tick is rare.


III. TRANSMISSION

B. burgdorferi are present in low numbers in the midgut of the tick, where they express Osp A. When the tick attaches and feeds on a host, the spirochete multiplies, but remains in the gut of the tick for at least 15 hours. After 48 hours, when the temperature in the gut reaches 37°C, the spirochete disseminates to the salivary glands of the tick from where it can be transmitted to the host (Osp C is up-regulated and Osp A is down-regulated at this time). The implication of this is that the risk of disease transmission is low if a tick has been attached for less than 36 hours (i.e., is not engorged with blood).


IV. INFECTIOUS OR REACTIVE DISEASE?

Polymerase chain reaction (PCR) testing, culture, and staining of human tissues and tissues of experimental animals suggest that B. burgdorferi is present at sites of pathology, albeit in small numbers. This, and the response of the disease to antibiotics, suggest that it is an infectious, rather than a “reactive” process.

Nonetheless, host factors play a role in disease expression, and a subset of patients with the human leukocyte antigen (HLA)-DR4 haplotype may develop an antibiotic-resistant chronic arthritis, which may be reactive in nature. It has been hypothesized that cross-reactivity between Borrelia Osp A, and the human leukocyte antigen, leukocyte function antigen-1 (LFA-1), may lead to autoimmunity in these immunologically susceptible hosts.


V. IMMUNITY

Prior infection with B. burgdorferi results in serologic immunity, but in most cases does not seem to confer protection from repeated infection.


PREVALENCE

The incidence of Lyme disease has been increasing in the northeastern United States over the last 25 years. This is likely due to the replacement of farmland by suburbs, and an associated increase in forestation. Forested areas, adjacent to “meadows” (lawns) serve as ideal habitats for white-footed mice, and deer. After 1982, more than 157,000 cases of Lyme disease have been reported in the United States and 23,763 cases were reported in 2002 to the various Centers for Disease Control and Prevention.



  • The overall incidence in the United States is approximately 7/100,000 individuals/year, but in endemic areas it may be as high as 1 to 3/100 individuals.


  • As of 2001, cases of Lyme disease have been reported in all states except Montana. Eight states (Connecticut, Rhode Island, Massachusetts, New York, New Jersey, Pennsylvania, Maryland, and Wisconsin) accounted for 90% (15,385) of the 17,029 cases reported. New York State and Connecticut reported 45% (7,680) of all cases.


  • Cases of Lyme disease have been reported from most European countries, in addition to Russia, China, Japan, and Australia. Lyme disease occurs in all age groups, but is seen most often in children aged 0 to 14 years, and in adults aged 30 to 49 years.


CLINICAL MANIFESTATIONS

The clinical manifestations are as follows (Table 47-1):


I. EARLY LOCALIZED DISEASE (STAGE 1)

Erythema migrans (EM), the characteristic rash of Lyme disease, develops in 80% of patients, 3 to 32 days (mean 7 days) after transmission of B. burgdorferi through the bite of an infected tick. Only one-third of patients will remember a tick bite.

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Jul 29, 2016 | Posted by in RHEUMATOLOGY | Comments Off on Lyme Disease

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