Lyme disease

Introduction to Lyme disease Lymedisease is a natural epidemic disease caused by Borrelia burgdorferi, also known as Lymeborreliosis. The early stage of the disease is often characterized by chronic migratory erythema. The clinical manifestations are mainly multiple systems such as skin, heart, nerves and joints, and multiple organ damage. In 1975, the disease was concentrated in children in the town of Lyme, Connecticut, USA. basic knowledge The proportion of illness: 0.002% Susceptible people: no specific population Mode of transmission: insect vector transmission Complications: ataxia, acute pericarditis, myocarditis

Cause of Lyme disease

Pathogenic bacteria infection (50%):

The pathogen of Lyme disease was first confirmed by Burgdorferi and Barbour in 1982 as a new species of Borrelia, called B. Burgdorferi, or Borrelia burgdorferi. Borrelia burgdorferi is a single-cell loosely coiled L-coil, 10 to 40 m long, 0.2 to 0.3 m wide, with 3 to 7 loose and irregular spirals, and slightly pointed at both ends. The longest and narrowest diameter of the body.

Pathogenesis:

Borrelia burgdorferi is mainly found in the midgut diverticulum of the sputum. When biting a person, it can flow from the sacral gland in the parotid gland or the midgut to the suction cavity, then invade the microvascular of the human skin and flow through the blood to the whole body. Organ tissues, however, the pathogen causes a short period of bacteremia, and the amount of spirochetes in the blood is not much, but it can cause damage to so many organs and multiple systems. The pathogenic mechanism may be the result of multi-factor synthesis. It was found that the spirochete has two kinds of adhesions, namely, DbpA (decorin binding protein A) and DbpB, which binds the spirochete to the collagen-associated extracellular matrix proteoglycan of the skin and other organ tissue cells by the adhesin. In the presence of lesions, there are lipopolysaccharide (LPS) components in the cell wall of Borrelia burgdorferi, which have endotoxin-like biological activities; and their outer membrane surface proteins Osp A, Osp B, Osp C have important pathogenicity and invasiveness. In turn, spirochetes can induce host cells to release cytokines, which can aggravate the inflammation of diseased tissues.

A few days after the spirochete enters the skin, it causes the primary skin primary damage in the first phase. There are plasma cells and lymphocytes infiltrated in the superficial and deep blood vessels of the damaged skin, which is characterized by chronic migratory erythema (ECM), spirochete. The LPS component can cause systemic symptoms and hepatosplenomegaly. ECM tissue sections can be seen with epithelial thickening, mild keratinization with mononuclear cell infiltration, epidermal edema, no suppurative and granulomatous reactions, when spirochetes After the blood circulation infects various tissues and organs, it enters the second stage (distributed diseased stage), and the central nervous system (especially the cranial nerve) and the heart-damaged lesions are around the blood vessels of the cerebral cortex and the cranial nerves, especially the facial nerves. Ocular nerves and nerves, mononuclear cell infiltration in heart tissue, etc., the disease lasts for more than a few months, then enter the third phase (continuous infection period), mainly joints, skin lesions and advanced nerve damage, visible joint hyperplasia Erosive synovitis with vascular hyperplasia, synovial hypertrophy, fibrin deposition, monocyte infiltration, bone and cartilage also have varying degrees of erosive destruction, skin atrophy Decolorization or collagen fiber bundle thickening, tightly arranged, similar to scleroderma lesions and atrophic dermatitis, the nervous system is mainly progressive encephalomyelitis and axonal demyelinating lesions, lymphocytes infiltration around the blood vessels, blood vessel wall Thickening, collagen fiber proliferation.

Lyme disease prevention

1. Management of infectious sources: The affected areas should mobilize the masses to take comprehensive measures, including rodent control, and treat infected livestock and pets.

2. Cut off the transmission route: It is mainly to eliminate hard sputum. It should be combined with the patriotic health movement to eradicate weeds in the epidemic areas and transform the environment. When field operations are carried out, drugs can be sprayed around the ground to kill hard cockroaches.

3. Personal protection: Avoid sitting and lying on the grass during the season of the disease. When working in the wild area, you should tighten the cuffs, neckline and trousers to prevent the hard cock from entering the body. If you find a bite, It can be prevented by removing it early (within 24 hours) and using antibiotics.

Recently, recombinant OspA subunit vaccine has been applied in foreign countries. It has been confirmed to be effective and safe by crowd test. The first dose and the 12th month after the first dose injection are boosted once, and the country develops Lyme disease according to the popular genotype. The vaccine has also been launched.

Lyme disease complications Complications, ataxia, acute pericarditis, myocarditis

1. When the nervous system is damaged, it may be complicated by meningitis, encephalitis, cranial neuritis, exercise and sensory neuritis, chorea, cerebellar ataxia, and myelitis.

2. Acute myocardial pericarditis can occur when the heart is extensively affected.

3. Joints sometimes damage the cartilage and bone, which can make the joints crippled. When the large joints are involved, there are vasospasm formation and bone and cartilage erosion.

4. There are also occlusive endarteritis, rare chronic neuropathy and transverse myelitis, diffuse sensory axonal neuropathy and CNS myelin loss, etc. Some patients can develop iris Inflammation, or even total ophthalmia, leads to loss of vision.

Symptoms of Lyme disease Common symptoms Itching joint pain, papules, joint swelling, diarrhea, abdominal pain, splenomegaly, myalgia, fatigue, meningeal irritation

The incubation period is 3 to 32 days. Most patients have "flu"-like symptoms at the end of the incubation period or before and after ECM. Meningeal irritation and muscle and joint pain, localized or systemic lymphadenopathy usually refer to early manifestations of ECM and related symptoms. One stage; several weeks to months after the emergence of nerves, abnormal heart, musculoskeletal symptoms or periodic joint damage, known as the second phase; months to years after the performance of chronic skin, nervous system, joint involvement, known as the third Period, however, there are obvious individual differences in clinical manifestations. Lighter cases are subclinical infections or only one system is damaged. Some may have multiple organs, such as skin, nervous system, joints, heart, etc., any system. Involvement can be temporary, recurrent and chronic, and the clinical characteristics of different regions can be different. In the United States, arthritis is more common, while in Europe, neurological changes are more common.

Early performance

Migratory erythema (EM) is a clinically characteristic syndrome of Lyme disease. It is found in more than 90% of cases, initially as an erythema or papule, which appeared in the original feeding place (usually long), reddening area When gradually expanding to about 15cm (range 3 ~ 68cm), the common part of the center subsides, the outer edge is red, generally flat, without scales, sometimes the center is red, induration, and even blisters or necrosis, the situation may be different, such as possible For polycyclic damage, thighs, groin and axillary fossa are good sites, damage to the fever, but often no pain, easy to miss, routine histological examination for non-specific changes: mononuclear infiltration in the dermis is thick, epidermis There is no abnormality outside the bite.

Skin damage ECM is the most common, the incidence rate is about 90%, occurs in the thigh, armpit, groin and other parts, starting with a red rash or pimples. After 3 to 32 days (average 7 to 9 days), the rash gradually enlarges to form a piece. Large round skin lesions with sharp outer edges (generally flat, even bulging), and the center is degenerative, so it looks like a red ring or a few new circular red circles in the skin lesion. In the early stage of skin lesions, there is dense erythema, hard change, herpes, necrosis, often burning sensation, occasional pain, itching, skin lesions expanding day by day, diameter up to 6 ~ 68cm (average 16cm), generally 2 to 3 weeks of skin lesions Retreat on your own, leaving scars and pigmentation.

Skin involvement is often accompanied by flu-like symptoms: violation, fatigue, headache, fever and chills, myalgia, joint pain and so on.

In the epidemic area of Lyme disease, if the above syndrome occurs in the summer, even if there is no EM, it should be treated. Some patients have signs of meningeal irritation or mild encephalopathy, such as paroxysmal severe headache and neck pain, tough or oppressive, but This period generally lasts only for a few hours. There is no increase in the number of CSF cells, and there is no objective symptom of neurological deficit. Except for fatigue and lethargy, which are often recurrent, other early syndromes are generally intermittent and variable, such as patients. There are meningitis-like episodes for several days, and after several days of improvement, there are migratory bone and muscle pains, spread to the joints (generally not swelling), tendons, burs, muscles and bones. The pain often only affects one or two places, each pain It can last from several hours to several days. There are different symptoms (or no EM) in the days before EM. After the skin damage disappears, it can still last for several months (especially fatigue and lethargy).

2. Later performance

(1) manifestations of the nervous system: the onset of disease for several weeks to several months, mainly refers to the substantial damage of the nervous system, excluding the "meningitis"-like performance at the initial stage of the pathology, the incidence rate is 11% to 15%, including meningitis, brain Inflammation, cranial neuritis, exercise and sensory neuritis are the most common, chorea can also occur, cerebellar ataxia, myelitis, most of which manifest as extensive involvement of the nervous system, lesions can overlap, and a few manifestations of localized nervous system involvement, Such as facial nerve spasm, Bell-like paralysis can also occur alone, usually the nervous system appears in the 2 to 4 weeks after ECM, can also be developed from early meningitis symptoms to chronic meningitis, patients with meningitis symptoms, at this time CSF may have Lymphocytosis (about 100/mm3), diffuse slow waves are sometimes seen on the EEG, but neck stiffness is rare (unless extreme neck flexion); Kernig's sign and Brudzinski's sign are absent, no ECM, nervous system symptoms often Prior to joint symptoms, neurological syndrome usually lasts for several months, but generally recovers completely (see late neurological complications).

(2) cardiac manifestations: also within weeks to months of onset, about 8% of cases of heart involvement, mostly adult males, with atrioventricular block most common, especially for grade I or II degree atrioventricular block Most patients have more extensive heart involvement, such as ECG changes in acute myocardial pericarditis, radionuclide scans showing mild left ventricular dysfunction, and occasionally enlarged heart. A few patients may have atrial fibrillation, and heart damage is generally mild. Unexplained damage to the heart valve, short duration, cardiac involvement often transient (7 days to 6 weeks), but can relapse.

(3) joint performance: shortly after onset for several weeks, up to 2 years, about 60% of cases with obvious arthritis, usually appear within 6 months, the early can appear with ECM, late can be followed It occurs in 14 months, usually starting from one or a few joints (unilateral, asymmetrical), initially migratory, involving multiple joints, most commonly seen in the knee, followed by shoulders, elbows, ankles, Hip and temporomandibular joints, occasional finger joints, usually manifested as intermittent joints of asymmetrical joint swelling and pain, mainly in large joints (especially knees), involving one or two joints each time, knee joint When affected, the swelling is often more painful, often fever, but rarely red; Baker cysts may occur, and early rupture, but both large and small joints can be affected, a small number of patients with symmetric polyarthritis, arthritis usually lasts Weeks to months, often experience recurrence for several years, and then gradually decrease with time, the rest of the joints show pain during exercise, initial joint symptoms generally last for a week, some up to 6 months, joints during recurrence Symptoms last for a short time, sometimes damaging Cartilage and bone erosion, joint can disability.

Some patients may have tendon, tendon sheath, muscle or bone migration pain in the early stage of the disease, which lasts for several hours to several days. When the active joint is involved, the patient often feels tired, but fever and other systemic symptoms are not yet in this period. Commonly, the number of white blood cells in joint fluid varies from 500 to 110,000/mm3, with an average of about 25,000/mm3. It is mainly composed of multinucleated cells, with a total protein content of 3-8 g/dl, and C3 and C4 levels are generally > 1/3 of serum. Glucose levels > 2/3, rheumatoid factor and antinuclear antibodies were negative.

About 10% of arthritis patients with large joint involvement can become chronic damage, vasospasm formation and bone and cartilage erosion, synovial biopsy similar to rheumatoid arthritis, fibrin deposition, villus hypertrophy, vascular hyperplasia, a large number of single Infiltration of nucleated cells, occlusive endarteritis can also be seen, and spirochetes can be seen. It has been pointed out that Borrelia burgdorferi can induce cytokines in monocytes (such as interleukin-1, tumor necrosis factor-, interleukin- 6), the concentration of inflammatory cytokines in synovial fluid increased, in a patient with chronic Lyme arthritis, the synovial membrane produced in tissue culture produced a large amount of collagenase and prostaglandin E2, showing the joints of Lyme disease The number of cells in the fluid, immune reactants (except rheumatoid factor), synovial tissue changes, the amount of enzyme released by the synovial membrane and the resulting destruction of bone and cartilage may be similar to rheumatoid arthritis.

(4) Others: Other late changes associated with this infection, as well as a skin lesion, known as chronic atrophic dermatitis in Europe, but still rare in the United States, it is a purplish invasive plaque Or nodules, more common in the extension, eventually atrophy, late rare chronic neuropathy and transverse myelitis (transverse myelitis), diffuse sensory axonal neuropathy and CNS myelin loss, mild memory impairment Mild emotional changes and chronic fatigue are also common.

About 10% of patients have hepatitis-like symptoms and signs in the early stage. A few patients have diffuse abdominal pain, diarrhea, splenomegaly, periorbital edema and testicular swelling and pain. Some patients may develop iritis or even total ophthalmia and cause vision loss. .

The disease can still cause congenital infection through mother-to-child transmission. It has been reported that the pregnant woman has not been treated with antibiotics within 3 months. After 35 weeks of delivery, the baby died of congenital heart disease within 1 week. The baby was found to have spleen and kidney at autopsy. There are 19 cases of Lyme disease in the bone marrow, and there are 19 cases of Lyme disease in pregnancy, 5 cases of infants and fingers (toes), central blindness, stillbirth, premature delivery, early maturity and so on.

The diagnosis of Lyme disease depends on a comprehensive analysis of epidemiological data, clinical manifestations and laboratory findings:

1. Epidemiological data: I have been to an infected area in the past few days to several months, or have a history of bites;

2. Clinical manifestations: early typical skin lesions, that is, ECM, and later affected by the heart, nerves, joints, etc.;

3. Laboratory tests: pathogens are isolated from infected tissues or body fluids, or specific antibodies are detected.

Lyme disease check

Blood picture

Peripheral blood is mostly in the normal range, occasionally leukocytosis with nuclear left shift phenomenon, erythrocyte sedimentation rate often increases.

2. Pathogen examination

(1) Finding pathogens directly or by staining: taking the skin, synovial membrane, lymph nodes and other tissues of the patient and cerebrospinal fluid, and examining the Borrelia burgdorferi with dark-field microscopy or silver staining, the pathogenic diagnosis can be quickly made, but the detection rate is low. .

(2) Pathogen isolation: pathogens were isolated from patients' skin, lymph nodes, blood, cerebrospinal fluid, joint synovial fluid, skin lavage fluid, etc., wherein the skin positive rate was higher (86%), and the separation methods were:

1 The sample was inoculated into a 6 ml BSK-II medium tube, and cultured at 33 ° C for 1 time/week.

2 Inoculate the specimen in golden hamster (body weight 50 g), 1 ~ 1.5ml / only, 7 ~ 14 days after inoculation, aseptically dissected, spleen and kidney tissue, and inoculated in BSK-II medium .

(3) PCR technology: According to the unique 5S23SrRNA gene structure of Borrelia burgdorferi, the primers were designed to detect Lyme disease spirochete DNA (Bb-DNA) such as blood, urine, cerebrospinal fluid and skin samples, and the sensitivity level was up to 2 ×10-4Pg (1 Bb contains about 2×10-3 pg DNA), and the genotype of the infected strain can be measured at the same time.

3. Serological testing

At present, the serum test for the detection of specific antibodies against Lyme disease, the diagnostic reagents and detection procedures are still lack of standardization, there are certain false negatives and false positives; the false negatives of antibody detection are also found within 3 to 4 weeks after infection. The window period or patients who have been treated with antibiotics must therefore be interpreted in conjunction with the patient's clinical presentation.

(1) Indirect immunofluorescence (IFA) test: It can detect specific antibodies of blood or cerebrospinal fluid, in which IgM antibody is 1:64 positive, mostly occurs 2 to 4 weeks after EM occurs, peaks at 6-8 weeks, large Most patients fall to normal levels within 4 to 6 months. Most of the IgG antibodies begin to rise within 6-8 weeks after the disease, and reach a peak in 4 to 6 months. They are maintained for several months or years, and the serum anti-B31 is often used in China. American standard strain) IFA IgG antibody 1:128 or double serum antibody titer increased more than 4 times as a basis for diagnosis.

(2) Enzyme-linked immunosorbent assay (ELISA): domestically applied ultrasonic treatment and dextran chromatography purification of anti-detection specific antibodies, the sensitivity and specificity are better than IFA.

(3) Western blot: The sensitivity and specificity of this method are better than IFA and ELISA. It can be confirmed by ELISA and the result is suspicious.

4. Blood and body fluid other tests

The total amount of serum cryoprecipitated globulin is often increased by more than 100 mg / L (normal value is <80 mg / L), serum immunoglobulin and complement have increased to varying degrees, accompanied by myocardial or liver involvement can have ALT and AST increased, the nervous system affected, cerebrospinal fluid leukocytes can increase, mainly lymphocytes, sugar and protein changes little, but the immunoglobulin slightly increased.

Histopathology: Infiltration of mixed cells around the blood vessels and interstitial cells, visible lymphocytes, plasma cells and eosinophils, Walthin-Starry staining showed spirochetes in the upper part of the dermis.

Diagnosis and diagnosis of Lyme disease

Differential diagnosis

1. Rheumatism: The disease has fever, ring erythema, arthritis and heart involvement, etc., can be based on serum hemolytic streptococcus antibodies, including anti-streptolysin "O", anti-streptokinase, anti-hyaluronidase and anti-hyper Increased M protein antibodies, C-reactive protein and pathogen examination can help identify.

2. Rheumatoid arthritis: The disease is a chronic autoimmune disease with symmetrical polyarthritis. It starts from the facet joint and later involves the large joint. The serum rheumatoid factor and anti-rheumatic synergistic antigen antibody (anti-RANA antibody) are positive. The joint cavity puncture fluid can find rheumatoid cells (regocyte) and X-ray examination, etc., and can generally be identified.

3. Rat bite heat: The disease is caused by small snails and bacillus streptococci, fever, rash, migratory joint pain, myocarditis and central nervous system symptoms are easily confused with Lyme disease, according to typical ECM , serology and pathogen examinations are identified.

4. Ascariasis: The characteristics of skin eschar and ulcers in the bite of larvae, plaque and lymphadenopathy are different from EM. Serum exo-fibrillation (OXk) and indirect immunofluorescence assay specific antibodies can help diagnose.

5. Syphilis: Both have skin, heart, nerve and joint lesions, and because of the common antigenicity between Borrelia and Treponema pallidum, syphilis patients may also have cross-reactive antibodies against Lyme disease spirochetes. However, a negative result of the syphilis blood stasis test contributes to the difference between Lyme disease and syphilis.

Others need to be differentiated from skin diseases of viral encephalitis, neuritis and fungal infections.

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