Lyme Disease or Lyme Borreliosis

Introduction

This monograph on Lyme disease, known more accurately as Lyme borreliosis, was prepared by a group of Belgian experts and was subsequently reviewed for accuracy by several specialized committees.

What is Lyme borreliosis and how is it contracted?

Borrelia burgdorferi, the etiologic agent of Lyme disease, is transmitted to humans via the bite of infected ticks. Ticks can bite humans throughout much of their lifecycle (larval, nymph, or adult stage) but seem to most frequently transmit Borrelia during the nymph stage. Nymphs are smaller (less than 2 mm in diameter) than adult ticks and thus more often go undetected; they are more active in summer and early autumn.

What are some of the risk factors for contracting Lyme disease?

Taking part in out-of-door activities increases the risk of being infected by B. burgdorferi. The risk of transmission is also affected by various other factors, including the length of time a tick remains attached to the body of the host (transmission is most likely when a tick is attached for 24-48 hours); the density of ticks in the area; the percentage of ticks carrying B. burgdorferi (in Europe, an average of 14%; however, there is significant regional variation); weather conditions; the types of vegetation in the area; and the nature of the host’s outdoor activities.

What general precautions should be observed in order to avoid contracting Lyme borreliosis?

Experts generally recommend the following precautions for individuals participating in out-of-door activities, particularly during the summer and early autumn:

• Wear clothing that fully covers the body;
• Use insect repellent
• Inspect the body for ticks
• Remove any ticks from the skin as soon as possible;
• Treat outdoor gear with permethrin as needed

What are characteristic tick bite symptoms?

Within two days of being bitten by a tick, victims typically develop an itchy, poorly-defined skin rash less than 5 cm in diameter. This reaction is not a sign of borreliosis, but rather a standard inflammatory or hypersensitivity reaction to the tick bite. The lesion should fade naturally after two or three days; as a general rule, patients are advised to monitor the area for changes.

A rash that persists longer than 4-5 days may be a sign of borreliosis; patients should recognize, though, that such lesions may likewise be due to a variety of other (non-borreliosis) bacterial infections resulting from the bite or from removal of the tick.

It is important to note that a substantial proportion of individuals exposed to B. burgdorferi will never develop clinical manifestations of borreliosis. However, even in the absence of symptoms, exposure to B. burgdorferi prompts the production of antibodies specific to the bacteria: this explains why such antibodies have been detected in a substantial number of asymptomatic patients.

What are the clinical manifestations of Lyme borreliosis?

Lyme borreliosis is associated with a variety of symptoms, grouped below into three classes:

1. Cutaneous manifestations:
   
   • Skin rashes (erythema migrans) start at the site of the tick bite and gradually expand outward, sometimes reaching diameters of 30 cm. Such lesions often occur in the armpits, knees, groin, perineum, back, and buttocks, as well as on the head, and in some cases are associated with local pain. Other accompanying symptoms may include muscle and joint pain, low-grade fever, fatigue, and adenopathy. The lesions frequently last no longer than a month and fade on their own, without medical intervention.
   • “Secondary” cutaneous lesions (multiple erythema migrans) are typically smaller than the primary lesion and frequently appear days or weeks – if not months or years – after the initial tick bite. They fade naturally over time and are associated with various nonspecific symptoms, among them muscle or joint pain, low-grade fever, fatigue, and adenopathy. These secondary lesions result from dissemination of the bacteria throughout the body: B. burgdorferi may spread via the bloodstream to the nervous system, joints, and heart. Other organs (e.g., the eyes and liver) may also be affected, though this is highly atypical.
   • In rare instances, patients may develop lymphocytoma, a benign lesion that generally manifests 1-6 months after a bite. Lymphocytomas present as small, purplish-red nodules and are most frequently found on the earlobe. In the event of an equivocal diagnosis, a biopsy may be required.
     
     
2. Extra-cutaneous manifestations:
   
   • Neurological damage may manifest as headaches or as paralysis; in such cases, paralysis is often accompanied by neuropathic pain that is more pronounced at night. Damage to the cranial nerves may result in paralysis of the facial muscles, abdominal wall, or lower extremities (paresis). In children, paralysis often takes the form of acute facial nerve palsy.
   • Cardiac manifestations are rare and typically involve spontaneously-resolving conduction disturbances (reduced heart rate). More serious cardiac disorders may also occur, but are rare.
     
   • Lyme arthritis most commonly affects the knees; this late-onset inflammatory reaction emerges months, if not years, after the initial tick bite.
     
     
3. Additional symptoms (less common):
   
   • Acrodermatitis chronica atrophicans chiefly affects women and is characterized by cutaneous lesions that may not appear until 10 years after the initial tick bite. The condition may be accompanied by other symptoms, among them arthritis, dislocation of hand and foot joints, and Achilles tendinitis
   • If early-stage Lyme disease is left untreated, patients may develop late Lyme neuroborreliosis, which involves gradual damage (developing over more than six months) to the brain or spinal cord. Signs of neuroborreliosis include numbness in the legs, ataxia, paralysis of the extremities, and hearing loss.
     
     

Lyme borreliosis and pregnancy: Lyme borreliosis is not transmitted from mother to fetus; indeed, the disease is not transmissible between humans. Though previous publications have raised concerns about Lyme borreliosis and pregnancy outcomes, these fears appear to be unfounded: there is no clear link between the disease and premature delivery, fetal death, or birth defects.

In some instances, individuals with a documented history of Lyme disease who received appropriate treatment at the onset of their illness have nonetheless reported the persistence (longer than 6 months) of nonspecific symptoms. These include fatigue; recurrent, migratory musculoskeletal pain; impaired memory and/or concentration; and migraines. This condition is sometimes described as post-Lyme disease treatment syndrome, a diagnosis not without controversy: indeed, the scientific community continues to debate whether the syndrome actually exists. Opponents argue, for instance, that some patients with a history of Lyme borreliosis may actually have been misdiagnosed (i.e., not all patients who report such symptoms may have had the disease in the first place); they also point out that there is no evidence that borreliosis patients are more likely to experience these symptoms relative to the general population.

What are the most effective therapies for the various forms of Lyme borreliosis?

Regardless of specific symptoms, all Lyme borreliosis patients should receive targeted antibiotic therapy. Principal components of these antibiotic regimens include doxycycline or a combination of ceftriaxone and penicillin derivatives. The emergence of antibiotic-resistant Borrelia species has not yet been reported. Among patients who display no clinical symptoms of borreliosis, the presence of specific anti-B. burgdorferi antibodies in the bloodstream may be due either to a prior Borrelia infection or to cross-reaction between antibodies (i.e., a false positive result). In such cases, no treatment should be administered, thus avoiding unnecessary exposure to antibiotics.

If, in spite of appropriate antibiotic therapy, the patient does not experience significant improvement in health or does not recover fully (the most common concern), the diagnosis must be reevaluated. A prolonged course of treatment or extended antibiotic regimen is not indicated, as the efficacy of such measures has not been demonstrated; rather, they seem likely to unnecessarily expose the patient to additional antibiotics.

Pregnant women ought also to be treated with appropriate antibiotics.

Lyme-related arthritis that lasts more than two months after a full course of treatment is known as antibiotic-refractory Lyme arthritis and is rarely observed in Europe. In such cases, antibiotics ought to be avoided, while non-steroidal anti-inflammatory drugs and corticosteroids are generally beneficial.

Should tick bite victims routinely receive antibiotics?

At present, Belgian specialists discourage antibiotic prophylaxis in response to tick bites. However, individuals who know or suspect that they have been bitten should arrange to have the bite monitored by a clinician over the following month. Health professionals should examine the area around the bite for emergence of erythema migrans, the most common symptom of borreliosis.

How are different forms of Lyme borreliosis diagnosed?

Diagnosis of Lyme disease is either clinical (based on presentation of specific symptoms) or serological (based on blood tests). Serology is the method of choice and in most instances is the only available diagnostic option. Prompt diagnosis of borreliosis also requires that physicians be able to recognize and distinguish between the various manifestations of the disease, as discussed above.

Diagnostic tests can be grouped into several overarching categories, including:

• I. Immunologic testing for IgG antibodies specific to B. burgdorferi. If antibodies are detected, a second and more specific test is required in order to confirm the results.
• II. Analysis of cerebrospinal fluid from a lumbar puncture. If antibodies have been detected in the blood or if neuroborreliosis is suspected, analysis should include tests for antibody production.

Other laboratory tests for Lyme borreliosis are available but have not yet been approved for use. Of these, one of the most promising is a PCR-based assay for detection of bacterial DNA, though this technique only exhibits sufficient sensitivity in patients suffering cutaneous or joint-based symptoms.

It should be noted that serological tests for B. burgdorferi are not effective in the absence of specific clinical symptoms, such as pain or persistent fatigue.

Detection of B. burgdorferi-specific antibodies in the absence of clinical symptoms/a discernible tick bite: how to proceed?

Detection of specific antibodies (IgG, IgM) associated with Lyme borreliosis is not indicative of active disease unless the patient also presents with some of the symptoms described above. This can be explained as follows: antibodies specific to Lyme borreliosis persist in the blood for a significant period of time, even among patients who have received appropriate treatment with antibiotics. Thus, a positive immunologic test in an asymptomatic patient is never considered sufficient grounds for antibiotic therapy.

Is it possible to be re-infected by B. burgdorferi?

Patients should recognize that B. burgdorferi IgG antibodies have poor neutralizing capabilities; the presence of these antibodies is thus not sufficient to prevent reinfection. Such reinfections generally manifest as erythema migrans.

Lyme borreliosis in Belgium: what data are available?

Cases of Lyme borreliosis have been observed throughout Belgium, though the incidence varies from region to region and from one year to the next. For instance, the disease is rarely reported along the Belgian coast but is more prevalent in other regions. Infection rates are slightly higher among males, perhaps because men are more likely to take part in out-of-door professional or leisure activities.

The number of borreliosis cases in Belgium has remained stable over the past 10 years, as determined by three separate investigations. On average, 1000 Lyme disease patients were hospitalized each year from 1999 to 2010 (the last year for which data are available). An increase in hospitalizations was noted at the beginning of the decade; this uptick likely reflects the increasing sophistication and wider availability of diagnostic tests for Lyme borreliosis