Lyme disease (lyme borreliosis)

Lyme disease (ticked borreliosis, systemic tick-borne borreliosis, Lyme borreliosis) is an inflammatory disease caused by spirochetes and transmitted by ticks; it is characterized by early skin lesions and chronic migratory erythema (CME), after which, weeks and months after infection, pathological changes in the nervous system, heart, and joints may develop. Diagnosis of Lyme disease is initially clinical, but detection of antibody titers during illness and recovery may be used. Treatment of Lyme disease is with antibiotics such as doxycycline or, in severe cases, ceftriaxone.

ICD-10 codes

• A69.2. Lyme disease. Erythema chronicum migrans due to Borrelia burgdorferi.
• L90.4. Acrodermatitis chronica atrophica.
• M01.2. Arthritis in Lyme disease.

What causes Lyme disease?

Lyme disease (Lyme borreliosis) was identified in 1975, when a number of cases were reported in the Old Lyme area, Connecticut. Since then, it has been encountered in 49 states in the United States, especially in the form of focal outbreaks on the northeastern coast from Massachusetts to Maryland, in Wisconsin, Minnesota, California, and Oregon. It is also known in Europe and is found in the former Soviet Union, China, and Japan. People usually become ill in the summer or early fall, regardless of gender and age, although most cases affect children and young people living in wooded areas.

Lyme borreliosis is transmitted by Ixodes scapularis, a deer tick. In the United States, the natural reservoir of infection is mainly white-footed mice, which are the primary reservoir and preferred host for tick nymphs and larvae. Deer are hosts for adult ticks, but do not carry borrelia. Other mammals (such as dogs) may be accidental hosts and may develop Lyme disease. In Europe, sheep are hosts, but they never become ill.

B. burgdorferi enter the skin at the site of the tick bite. After an incubation period of 3 to 32 days, they disseminate in the skin around the bite via lymphatics (regional lymphadenopathy) or via the bloodstream to other organs and skin areas. The relatively low number of organisms in tissues suggests that most clinical manifestations of the disease are related to the host immune response rather than to the damaging role of the organisms.

What are the symptoms of Lyme disease?

Lyme disease has three stages: early localized, early disseminated, and late. The early and late stages are usually separated by an asymptomatic period.

Chronic migratory erythema (CME) is the most important clinical feature of Lyme disease, which begins in 75% of patients with the appearance of a red spot or papule, usually on the proximal parts of the extremities or on the trunk (especially on the thighs, buttocks, and armpits), between the 30th and 32nd days after the tick bite. This formation enlarges (up to 50 cm in diameter), often becoming pale in the center. In half of the cases, many similar skin lesions appear soon after the first spot, but they are smaller and without central induration. Cultivation of biopsy material from these secondary lesions may be positive and indicate dissemination of the infection. Chronic migratory erythema usually lasts for several weeks; during the recovery period, a rash may quickly pass. Mucosal changes are not observed.

Symptoms of early disseminated Lyme disease begin several days to weeks after the initial lesions, as the bacteria spread throughout the body. CME is most often accompanied by (sometimes preceded by several days) a flu-like symptom complex that includes weakness, malaise, chills, fever, headache, neck stiffness, myalgias, and arthralgias. Because symptoms of Lyme disease are often nonspecific, the diagnosis is not always made; a high index of suspicion is necessary. Frank's arthritis is rare at this stage. Less common are back pain, nausea and vomiting, sore or scratchy throat, lymphadenopathy, and enlarged spleen. Most symptoms come and go, except for weakness and malaise, which last for weeks. Some patients develop symptoms of fibromyalgia. Less severe lesions may appear in the same places before an attack of arthritis. Severe neurological impairment develops in approximately 15% of patients within a few weeks or months of CME (often before arthritis).

Neurological symptoms of Lyme disease develop in approximately 15% of patients, over weeks to months against the background of erythema migrans. They usually last for several months and disappear without a trace. The most frequently observed - individually and in various combinations - are lymphocytic meningitis (pleocytosis in the CSF about 100/mcl), meningoencephalitis, cranial nerve neuritis (especially Bell's palsy, sometimes bilateral), sensory or motor radiculoneuropathy.

Myocardial dysfunction is observed in 8% of patients several weeks after the onset of chronic migratory erythema. It consists of symptoms of atrioventricular block with variable severity (grade 1, Wenckebach block, grade 3), less often myopericarditis with a decrease in the left ventricular ejection fraction and cardiomegaly.

In untreated patients, the late stage begins months to years after the onset of the disease. Arthritis occurs in about 60% of patients with chronic erythema migrans within a few weeks or months after its onset, but sometimes later - up to 2 years. Intermittent swelling and pain in some large joints, especially the knee, usually recur over several years. Swelling is more pronounced than pain; the joint is hot, sometimes reddened. Baker's cysts may form and rupture. Symptoms of Lyme disease such as weakness, malaise, and mild fever that accompany chronic erythema migrans may precede or accompany exacerbations of arthritis. Chronic arthritis of the knee (more than 6 months) develops in 10% of patients. Other late (years later) consequences include chronic atrophic acrodermatitis, which responds to antibiotic therapy, and chronic neurological disorders such as polyneuropathy, encephalopathy, memory impairment, and sleep disorders.

How is Lyme disease diagnosed?

Isolation of the pathogen from tissues or body fluids is rare; they must be used to diagnose other pathogens. Detection of antibody titers during the acute stage of the disease and during convalescence is of diagnostic value. A positive titer should be confirmed by Western blot. However, seroconversion may be late (>4 weeks) or sometimes absent. A positive IgG antibody titer may indicate previous infection. PCR testing of CSF and synovial fluid is often positive when these structures are involved. The diagnosis depends on the results of both tests and the presence of typical clinical data. Classic erythema is indicative of Lyme disease if other data are present (recent tick bite, stay in an endemic area, typical systemic symptoms).

In the absence of a rash, the diagnosis is difficult because other symptoms of Lyme disease may not be expressed. The previously disseminated phase may imitate juvenile RA in children, reactive arthritis, atypical RA in adults. These diseases can be excluded in the absence of morning stiffness, subcutaneous nodules, iridocyclitis, mucosal lesions, rheumatoid factor, antinuclear antibodies. Lyme disease, manifested by a musculoskeletal, flu-like syndrome in the summer, may resemble ehrlichiosis, tick-borne rickettsiosis. The absence of leukopenia, thrombocytopenia, elevated transaminases and inclusion of bodies in neutrophils allow us to determine Lyme disease. In some cases, namely, with migratory polyarthritis with ECG changes (prolongation of the PQ interval) or chorea (as a manifestation of meningoencephalitis), the differential diagnosis includes acute rheumatic fever. Heart murmurs are rarely heard in Lyme disease and there is no evidence of a previous streptococcal infection.

In the late stage, the axial skeleton is not involved, unlike spondyloarthropathy with peripheral joint involvement. Lyme disease can cause Bell's palsy, fibromyalgia, chronic fatigue syndrome, and can mimic lymphocytic meningitis, peripheral neuropathies, and similar CNS syndromes.

In endemic areas, many patients with arthralgia, chronic fatigue, difficulty concentrating, or other disturbances may be suspected of having Lyme disease. Despite the absence of a history of erythema or other symptoms of early localized or disseminated disease, these patients are indeed ill. In such patients, a rising IgG antibody titer indicates past exposure but not persistent infection, and this often leads to prolonged and futile antibiotic therapy.

How is Lyme disease treated?

Antibacterial treatment of Lyme disease is effective at all stages of the disease, but is most effective in the early stages. In the later stages, antibiotics can eradicate bacteria in most patients, but some patients continue to have persistent arthritis symptoms. Lyme disease in children is treated similarly, but doxycycline should be avoided in children under 8 years of age; pediatric doses are based on body weight. The duration of treatment has not been determined in clinical trials, and literature data are inconsistent.

Antibiotic Treatment of Lyme Disease in Adults

Early Lyme disease

• Amoxicillin 500 mg 3 times daily orally for 10-21 days or 1 g orally every 8 hours (some experts recommend adding probenecid 500 mg orally 3 times daily; this is not necessary if amoxicillin is prescribed according to the latest regimen)
• Doxycycline orally 2 times a day for 10-21 days
• Cefuroxime axetil 500 mg orally 2 times a day for 10-21 days
• Azithromycin, 500 mg orally once a day for 7 days (less effective than other regimens)

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Neurological symptoms

• Bell's palsy (no other neurological manifestations)
• Doxycycline as for early disease Meningitis (with or without radicular neuropathy or encephalitis)
• Ceftriaxone 2.0 g IV once a day for 14-28 days
• Benzylpenicillin 5 million units intravenously every 6 hours for 14-28 days
• Doxycycline 100 mg orally 2 times a day for 14-28 days
• Chloramphenicol 500 mg orally or intravenously 4 times a day for 14-28 days

In case of heart damage

• Ceftriaxone 2 g IV once a day for 14-28 days
• Penicillin G 20 million units intravenously once a day for 14-28 days
• Doxycycline 100 mg orally 2 times a day for 21 days (for moderate carditis with first-degree heart block - PQ less than 30 sec, normal ventricular function)
• Amoxicillin 500 mg orally 3 times a day or 1 g orally every 8 hours for 21 days (for moderate carditis with first-degree heart block - PQ less than 30 sec, normal ventricular function)

Arthritis

• Amoxicillin 500 mg PO 4 times daily or 1 g PO every 8 hours and probenecid 500 mg PO 4 times daily for 30 days (if no neurological involvement)
• Doxycycline 100 mg orally 2 times a day for 30 days (if there are no neurological lesions)
• Ceftriaxone 2.0 g IV once a day for 14-28 days
• Penicillin G 20 million units intravenously once a day for 14-28 days

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Chronic atrophic acrodermatitis

• Amoxicillin 1 g orally once a day for 30 days
• Doxycycline 100 mg orally 2 times a day for 30 days (if there are no neurological lesions)

1. Pregnant women may receive amoxicillin 500 mg/kg 3 times daily for 21 days. No treatment is required for pregnant women who are seropositive but asymptomatic.
2. Without neurological, cardiac, or joint involvement. For early Lyme disease limited to erythema simplex migrans, 10 days is sufficient. The optimal duration of therapy is unknown. There are no controlled clinical trials longer than 4 weeks for any neurological manifestations of Lyme disease.

Symptomatic treatment of Lyme disease is based on the use of NSAIDs. Complete heart block may require an artificial pacemaker. If there is significant effusion in the knee joint, fluid is aspirated from it; the use of crutches is recommended. If antibiotic therapy is ineffective in knee arthritis, arthroscopic synovectomy may give good results.

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How to prevent Lyme disease?

Lyme disease can be prevented by avoiding tick bites in endemic areas. The deer tick nymphs that infect humans are very small and difficult to see. Once on the skin, the tick feeds on blood for several days. B. burgdorferi is transmitted when the tick remains at the bite site for more than 36 hours, making it extremely important to find and remove it.

A single oral dose of doxycycline 200 mg reduces the risk of developing Lyme disease, but many clinicians do not recommend this treatment or reserve it for patients with known tick infestations. If a bite is known to have occurred, the patient should be instructed to monitor the bite site and to seek medical attention if a rash develops; it is much more difficult to decide what to do with a patient who has no known history of a bite.

The vaccines are ineffective and have therefore been withdrawn from sale.