Lyme disease: causes, symptoms, diagnosis, treatment, and prognosis

Lyme disease, also known as Lyme borreliosis, is a zoonosis caused by Borrelia burgdorferi transmitted by ticks, and is characterized by systemic lesions.


Causes

The pathogen is Borrelia burgdorferi. Borrelia burgdorferi is a 10 - 40μm long, 0.2 - 0.3μm wide, unicellular, loosely coiled, left-handed spirochete, with 3 – 7, loose, irregular spirals, with slightly pointed ends. The pathogen can move with many ways such as twist and rotation. The bacteria are negative in Gram stain, reddish blue in Giemsa stain or Wright stain, bluish purple to light purple in Eosin Thiazin stain, and well stained in silver stain. The outer membrane and 7 - 12 flagella can be seen in electron microscopy. The flagellum is located between the outer membrane and the protoplasm, so it is also called endoflagellum. Under microaerobic conditions, the bacteria can grow slowly in the BSK-II (Barbour Stoenner Killy-II) culture medium at 30°C - 34°C, and can be seen under in dark field microscopy in 2 - 5 weeks.

The bacteria are highly resistant to moisture and low temperatures, but can be inactivated by heat, dryness, and general disinfectants.

Epidemiology

Source of infection

Some wild and domesticated animals are the host of the bacteria, and rodents are the main source of infection.

Route of transmission

The transmitter is ticks.

Pathogenesis

The pathogen Borrelia burgdorferi is transmitted by the tick bites, and humans and animals may be infected. However, the disease may not occur in individuals bitten by infected ticks. After tick bites, Borrelia burgdorferi invades the skin and propagates locally, mostly spreading on the localized skin, thus forming erythema migrans (EM). Within few days to several weeks, the spirochetes enter the lymph nodes through the lymphatic vessels, or are disseminated to various organs through the blood. Subsequently, human body produces IgG and IgM antibodies against the flagellin of Borrelia burgdorferi, and then induces the body's specific immune response. The formation of the circulating immune complex (CAC) causes vascular damage, leading to lesions in the myocardium, retina, muscles, bones, synovium, spleen, liver, meninges, and brain. The lesions evolve into severe chronic disease in about 10% of patients, with poor therapeutic effects.


Signs and Symptoms

The incubation period is 3 - 32 days. At the end of the incubation period or before and after the onset of erythema migrans (EM), most patients present with influenza-like symptoms, such as meningeal irritation, sore muscles and joints, and localized or generalized swollen lymph nodes.

Erythema migrans is a clinical mark of Lyme disease, occurs 3 - 32 days after tick bites, and can be seen in more than 90% of patients, mostly on the proximal extremities and trunk, particularly thighs, groin, and armpits. There is initially an erythema or papule at the site bitten by a tick, peripherally expanding to about 3 - 68cm, usually 15cm. The central lesions partially subside, and the outer edges are red. The skin lesions are generally flat and without scales. Sometimes, there are redness, induration, blisters, or necrosis in the center, with burning sensation, occasionally with pain and pruritus. The skin lesions spontaneously subside 2 - 3 weeks, occasionally leaving scars or pigmentation.

Figure 1 erythema migrans after tick bites

Skin lesions are often accompanied by influenza-like symptoms, such as indisposition, fatigue, headache, fever, chills, myalgia, and joint pain. If there is no erythema migrans, there may be missed diagnosis.

Nervous abnormalities occur few weeks to several months after erythema migrans, usually prior to arthritis, in about 15% of patients, and can last for several months but usually recover completely. The most common conditions are lymphocytic meningitis, meningoencephalitis, cranial neuritis, and sensorimotor neuropathy, and they can occur alone or in combination.

The heart may be involved several weeks after erythema migrans in approximately 8% of patients. The main manifestation is atrioventricular block, and there are myopericarditis, thorcalgia, decreased ejection fraction, and enlarged heart in few patients.

Arthritis occurs few months, occasionally up to 2 years, after erythema migrans, in approximately 60% of patients. Intermittent swelling and pain may occur in the large joints, especially the knee joint, and can typically persist for several years. There are swelling rather than pain in the affected joints, and there are often fever, but redness is rare. Popliteal cysts can occur or rupture. Discomfort, fatigue, and low grade fever may be followed by or accompanied by arthritis. Chronic arthritis occurs in about 10% of patients, and there is not remission in ≥6 months.

Histopathology

There are infiltrations of lymphocytes, plasma cells, and eosinophils, and spirochetes can be seen in Warthin-Starry stain.


Diagnosis

On the basis of a history of tick bites, clinical presentations, pathogen isolated, and specific antibody, this disease can be diagnosed.


Treatment

The treatment regimen for erythema migrans is doxycycline 100mg orally twice daily for 10 days, extending to 20 days as needed, not for children and pregnant women; or amoxicillin 500mg 4 times a day in adults, 50mg/(kg.d) in children, for 10 days. For those who are allergic to the above-mentioned medications, erythromycin 250mg 4 times daily for 10 days can be considered. Clarithromycin or azithromycin can also be used as appropriate.

The treatment regimen in the late stage is doxycycline 100mg twice daily or amoxicillin 500mg 3 times a day orally for 1 - 2 months.

The treatment regimen for pregnant patients is amoxicillin 500mg 3 times a day for 21 days in the early stage, and penicillin G 20,000,000 U/day intravenously in divided doses for 10 - 14 days in the late stage.


Prognosis

With early diagnosis and prompt treatment, there are generally good prognosis. Most patients heal in 12 - 18 months. Occasionally, arthritis may be recurrent. Post-treatment Lyme disease syndrome may occur in some patients. If there are severe damage of central nervous system, sequelae or deformities may be present.