Infection with Borrelia burgdorferi have a range of clinical presentations, depending on the length of time after the infection, the organs/systems affected, and host factors, such as the vulnerability of the immune system and immunogenetic factors. Clinical presentations can generally be divided into three stages, early localised Lyme borreliosis, early disseminated and late disseminated Lyme borreliosis. Lyme borreliosis mainly affects skin, joints and the neurological system, with typical manifestations such as detailed below. Some symptoms might not be specific (such as fatigue or pain) and may occur in other conditions. Therefore, a differential diagnosis should always be investigated as well. Some patients present with later manifestations without having experienced, or noticed, early stage symptoms. The diagnosis of Lyme borreliosis must be made in the light of the clinical history and physical findings, exposure risk history and laboratory evidence.
Early, localised Lyme borreliosis.
Erythema migrans (EM)
Erythema migrans, the characteristic painless rash spreading from the site of a tick bite, typically starts about three to thirty days after the tick bite and is the direct result of the spirochaete migrating through the skin. It is present in approximately 60-80% of cases of early Lyme borreliosis. Lesions that start earlier could be due to a local reaction to the tick bite (Figure 1) or an acute bacterial infection, such as streptococcus or staphylococcus.
The EM rash can become relatively large – up to 75 centimeters (30 inches) in diameter (Figure 2) – sometimes with gradual clearing of the erythema (redness) from the centre, so that the skin returns to its normal appearance. This phenomenon has given rise to the term “bulls-eye rash” (Figure 3).
Some rashes may be very faint, with little or no swelling or raising of the advancing edge (Figure 4), and may be easily missed, especially if the person has dark skin or the bite is in an inconspicuous site.
There is recent evidence that infections with B. afzelii result in annular EM whereas infections with B. garinii produce more homogenous EM (i.e. without central clearing) (Figure 5), and these tend to develop more rapidly.
The patient may also experience other symptoms, including a mild ‘flu-like’ illness (excluding rhinitis, coughing or sore throat) and swelling of the lymph nodes (glands) of the area affected by the rash. If these symptoms are severe or accompanied by marked arthralgia (joint pains), myalgia (muscle pains), headache or neck stiffness, it is likely that there has been some secondary spreading of the infection to other parts of the body, or that another diagnosis might be associated.
Early disseminated Lyme borreliosis
The organism can spread through the bloodstream and lymphatics to other tissues, which may include other parts of the skin, nervous system, musculoskeletal system and heart. The targeting of any of these systems can cause a wide variation of clinical features presenting from a few weeks to over 6 months after the initial infection.
Clinical features of this stage may include:
- Cutaneous manifestations:
- Multiple erythema migrans (same characteristics as solitary erythema migrans, but not centered by the tick-bite and rather at distance of the tick-bite over the body, Figure 7)
- Borrelial lymphocytoma
Borrelial lymphocytoma is an uncommon form of early, localised Lyme borreliosis, which is usually seen on the earlobe (especially in children), nipple or scrotum appearing as an intense bluish-red localised painless patch of skin (Figure 6). The patient may not recall a tick-bite but will have a history of recent exposure to ticks. Microscopic examination shows a very dense infiltrate of lymphocytes.
Neurological manifestations:
- radiculitis (hyperalgesia, with awakenings, unilateral) +/- associated with meningitis (meningo-radiculitis);
- Facial palsy (Figure 8);
- Other cranial nerve palsies;
- Aseptic (viral-type) meningitis;
- Mild encephalitis;
- Peripheral neuritis.
Rheumatological manifestations: arthritis (large joints, more often one knee, unilateral, always asymmetrical)
The knee is the most commonly affected joint (Figure 9). Direct infection of the joint has been implicated through spirochaete culture and DNA detection in joint fluid. However, the scarcity of spirochaetes in the synovial membrane and the difficulty of cultivation from the synovial fluid suggest that a reactive pathogenesis may be at work. A small percentage of patients show inflammation of tendons and enthesitis (the point where tendons attach to the bone). The condition usually “burns out” after several years but may leave some residual joint damage in severe cases. It is thought that some patients, particularly those with treatment-resistant arthritis, may also have a genetic predisposition to Lyme arthritis, as it has been seen more frequently in people with HLA-DR2 or DR4 phenotypes – suggesting an immunogenetic factor in pathogenesis.
More rarely: Carditis with conduction defects (usually partial heart block), and uveitis.
Late Lyme borreliosis
Progression to this stage is uncommon but may occur in patients who were not treated or inadequately treated at an earlier stage. Symptoms present several years after the initial infection and may involve the joints (Lyme arthritis), skin (acrodermatitis chronica atrophicans) or, rarely, chronic neurological syndromes.
Acrodermatitis chronica atrophicans (ACA)
ACA is an unusual progressive fibrosing skin lesion, which is probably the most common manifestation of late Lyme borreliosis in Europe. It usually occurs in the lower limbs of elderly people, starting with a bluish discolouration of the skin with oedema, followed by gradual epidermal atrophy, the skin developing a thin shiny, papery appearance (Figure 10). The condition is due to the effect of continuing active infection. Live spirochaetes have been isolated from skin biopsy specimens of patients with ACA as long as ten years after initial infection. ACA may also occur in young people and a case involving all 4 limbs of an 11-year-old was reported recently (Brzonova et al., 2002).
Chronic encephalomyelitis
Lyme encephalomyelitis is rare. It should not be diagnosed in the absence of laboratory evidence of B. burgdorferi infection. The clinical manifestations associate encephalitis manifestations (cephalalgia, psychomotor slowing etc.) and myelitis manifestations (dysautonomic disorders etc.).
Post-Treatment Lyme Borreliosis Syndrome
Patients with post-Lyme borreliosis syndrome show symptoms such as musculoskeletal pain, neurocognitive symptoms and/or fatigue, similar to chronic fatigue syndrome or fibromyalgia, which persist more than 6 months after a well-administered antibiotic therapy according to guidelines.
These symptoms may have severe repercussions on quality of life.
There is rarely evidence for the presence of spirochaetes in these cases and it is thought to be partly due to pro-inflammatory imbalance.
A multi-authored international review of ‘chronic’ Lyme borreliosis (N Engl J Med 357;14, 2007) concluded that despite strong advocacy by some physicians and patient groups, the “assumption that chronic, subjective symptoms are caused by persistent infection with B. burgdorferi is not supported by carefully conducted laboratory studies or by controlled treatment trials. Chronic Lyme disease, which is equated with chronic B. burgdorferi infection, is a misnomer, and the use of prolonged, dangerous, and expensive antibiotic treatments for it is not warranted”. This conclusion is still valid (Halperin, 2015 Infect Drug Resist. 8:119-28).
Symptomatic therapy is generally recommended as well as physical rehabilitation and cognitive behavioral therapy.
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