What is Lyme Disease?
Lyme borreliosis (synonyms: Lyme disease, Lyme borreliosis, ixodic tick-borne borreliosis.) Currently, Lyme disease is considered as a natural focal, infectious, polysystemic disease with a complex pathogenesis involving a complex of immune-mediated reactions.
Various clinical manifestations of Lyme disease have long been known and described as independent diseases or as syndromes of unclear etiology: chronic migrating erythema, Erythema Afcelius, tick-borne erythema, acrodermatitis, chronic atrophic acrodermatitis, lymphodenosis of the skin, serous meningitis, radiculoneuroses, and lymphocytes, cytodermatitis, lymphodenosis of the skin, serous meningitis, lymphocytosis, lymphocytes, cytodermatitis, chronic lymphodenosis of the skin, serous meningitis, lymphocytosis, lymphocytes, systroma ), chronic arthritis, etc. In 1981, the spirochetotic etiology of these manifestations was established, after which it was already possible to speak about diseased and how nosological form with different clinical manifestations.
Lyme disease was first described in 1975 as a local outbreak of arthritis in Lyme, Connecticut (USA); develops after a bite of ixodic ticks infected with borrelia. In subsequent years, as a result of research, it turned out that the geographical spectrum of the spread of this infection is much wider. The disease is found not only in North America, but also in many countries in Europe and Asia. Tick-borne Lyme borreliosis is also widespread in Russia. BL in our country was first serologically verified in 1985, in 1991 included in the official list of nosological forms available in Russia. Much work on the study of this infection and the dissemination of accumulated experience was carried out under the direction of EI Korenberg at the Republican Center for the Study of Borreliosis (Research Institute of Microbiology named after NF Gamalei of the Russian Academy of Medical Sciences).
Causes of Lyme Disease
The family Spirochaetaceae, a genus of Borrelia, includes a significant number of pathogens of humans and animals. In 1984, R. Johnson described a new species of borrelia – Borrelia bitrgdorferi, which got its name in honor of the American microbiologist W. Burgdorfer, who first isolated Borrelia from ixodic ticks in 1981. The connection of an outbreak of arthritis in the town of Lyme with isolated borrelia has been proven.
The spirochete Borrelia burgdorferi resembles in its form a corkscrew-twisted spiral consisting of an axial filament around which the cytoplasm is located, its length is from 11 to 25 μm and its width is 0.18-0.25 μm; sizes vary in different hosts and under cultivation. Curls are uneven, with vital observation they make slow rotational movements. Both right-handed and levogyrate forms were found (the pathogenetic significance is unknown so far). In terms of morphology, these spirochetes are more similar to treponemas, but larger than them. They have groups of surface antigens Osp A, Osp B and Osp C, which determine the difference between individual strains. Belong to gram-negative bacteria. Aniline dyes are stained more intensely than treponema, and slightly weaker than other borrelia. Like other Borrelia, they are cultivated in Kelly’s modified medium (BSK-K5 selective medium).
Until very recently, it was believed that the only causative agent of Lyme disease is Borrelia burgdoiferi. However, some differences in the protein composition of isolates of Borrelia from different natural foci allowed initially to suggest that Lyme borreliosis is etiologically heterogeneous.
Currently, more than 10 genomic groups belonging to the Borrelia burgdorferi sensu lato complex, are unevenly distributed around the globe. The groups B. burgdorferi sensu stricto, V. garinii, V. garinii (type NT29), B. afielii, B. valaisiana (group VS116), V. lusitaniae (group PotiB2), B. japonica, B. tanukii and B. turdae, and in America – Borrelia burgdorferi s. s., B. andersonii (group DN127), 21038, CA55 and 25015. As regards the B-japonica found in Japan, it seems to be non-pathogenic for humans. It should be noted that today the pathogenic potential of the group VS116 (V. valaisiana) is also unknown. The results of studies and clinical observations in recent years suggest that the nature of organ lesions in a patient may depend on the type of borrelia. Thus, data on the existence of an association between V. garinii and neurological manifestations, B. burgdorferi s. s. and Lyme arthritis, V. afielii and chronic atrophic dermatitis. Consequently, the observed differences in the clinical picture of the course of Lyme disease in patients at different points of the nosoareal of this infection may be based on the genetic heterogeneity of the B. complex. Burgdorferi sensu lato. Considering all these facts, at present, the term “Lyme disease” is commonly meant to mean a whole group of etiologically independent ixodic tick-borne borreliosis.
Pathogenesis during Lyme Disease
At the stage of accumulation of knowledge about borreliosis, given the generality of epidemiology, the similarity of pathogenesis and clinical manifestations, it is quite acceptable to unite them under the common name “Ixodic tick-borne borreliosis” or “Lyme disease”, paying tribute to the first described tick-borne ixodic borreliosis.
Natural foci of Lyme disease are confined mainly to the glued landscapes of the temperate climate zone. In the USA, the main carriers are pasture mites fxodes scapularis (the old species name /. Dammini), and are of less importance. pacificus, in the Eurasian part of its nozareareal, are two common ixodid ticks: taiga (/. persulcatus) and forest (/. ricinus). In Russia, the taiga tick is of paramount epidemiological and epizootological importance; as a carrier, more effective than /. ricinus. Tick larvae more often parasitize on small rodents, nymphs and mature individuals – on many vertebrates, mainly forest animals. A certain epidemiological role belongs to dogs. The natural infection of ticks with borrelia in endemic foci reaches 60%. The possibility of symbiosis of several species of borrelia in one tick has been proved. The simultaneous infection of ixodic ticks with tick-borne encephalitis and Lyme disease causative agents determines the existence of conjugate natural foci of these two infections, which creates prerequisites for the simultaneous infection of people and the development of mixed infection. Human infection occurs in a transmissible manner. The pathogen is inoculated when a tick bites with its saliva. It is not excluded, but a different route of infection, for example, alimentary (like tick-borne encephalitis) has not been definitively proven. Transplacental transfer of borrelia during pregnancy from the mother to the fetus is possible, which can be explained by a rather high percentage of patients of preschool and primary school age. Human susceptibility to borrelia is very high, and possibly absolute. No infection is transmitted from a patient to a healthy person. For primary infections, spring-summer seasonality is characteristic, due to the period of activity of ticks (from April to October). Infection occurs during a visit to the forest, in a number of cities – in forest parks within the city limits. In terms of incidence, this infection is in our country one of the first places among all natural focal zoonoses.
When infected, a complex of inflammatory-allergic skin changes usually develops at the site of tick infestation, manifested as a specific erythema characteristic of Lyme disease. The local persistence of the pathogen for a certain period of time determines the characteristics of the clinical picture — relatively satisfactory state of health, mild general intoxication syndrome, the absence of other manifestations characteristic of Lyme disease, the lateness of the immune response.
With the progression of the disease (or in patients without a local phase immediately) in the pathogenesis of the symptom complexes, the hematogenous, possibly lymphogenous pathway of borrelia from the site of introduction to the internal organs, joints, lymphatic formations matters; perineural, and subsequently rostral, with involvement of the meninges in the inflammatory process. When the pathogen enters the various organs and tissues, an active irritation of the immune system occurs, which leads to a generalized and local humoral and cellular hyperimmune response. At this stage of the disease, the production of IgM antibodies and then IgG occurs in response to the appearance of the flagella flagellate antigen of Borrelia with a mass of 41 kD. An important immuno-genome in pathogenesis is the surface proteins Osp C, which are characteristic mainly for European strains. In the case of disease progression (absence or insufficient treatment), the spectrum of antibodies to spirochete antigens (to polypeptides from 16 to 93 kD) expands, which leads to a long-term production of IgM and IgG. The number of circulating immune complexes increases. Immune complexes can also be formed in the affected tissues, which activate the main factors of inflammation – the generation of leucotactic stimuli and phagocytosis. A characteristic feature is the presence of lymphoplasmic infiltrates found in the skin, subcutaneous tissue, lymph nodes, spleen, brain, peripheral ganglia. The cellular immune response is formed as the disease progresses, with the highest reactivity of mononuclear cells manifested in the tissues of the “targets”. The level of T-helperovi T-suppressors, the index of stimulation of blood lymphocytes increases. It has been established that the degree of change in the cellular element of the immune system depends on the severity of the course of the disease.
The leading role in the pathogenesis of arthritis is borne by liposaccharides that are part of borrelia, which stimulate the secretion of interleukin-1 by monocyte-macrophage cells, some T-lymphocytes, B-lymphocytes, etc. that is, it activates inflammation in the joints, which leads to bone resorption, destruction of cartilage, stimulates the formation of pannus.
The delayed immune response associated with relatively late and mild borrelemia, the development of autoimmune reactions and the possibility of intracellular persistence of the pathogen are among the main causes of chronic infection.
Symptoms of Lyme Disease
The course of Lyme disease is divided into early and late periods. In the early period, stage I of the local infection is isolated, when the pathogen enters the skin after tick sucking, and stage II – dissemination of borrelia to various organs (characterized by a wide range of clinical manifestations resulting from spirochetes in different organs and tissues). The late period (stage III) is determined by the persistence of infection in any organ or tissue (unlike stage II, it is manifested by the primary lesion of any one organ or system). The division into stages is rather arbitrary and applies only to the disease as a whole. Sometimes staging may not be observed at all, in some cases only stage I may be present, and sometimes the disease debuts with one of the later syndromes. In the early period, it is advisable to isolate the erythemal and non-erythemal forms of the disease. Firstly, it is important in diagnosing the disease, secondly, the clinical picture has its own characteristics depending on the presence or absence of erythema at the site of the tick bite and, finally, shows the features of the relationship between macro and microorganism. At the stage of dissemination of the pathogen, differing in the polymorphism of clinical manifestations, it is still possible to identify the prevailing group of symptoms that determine the clinical course: febrile, neuritic, meningeal, cardiac, mixed. The selection of the course variant and the severity of the clinical syndrome help to determine the severity of the pathological process: mild, moderate, severe and extremely severe (rare) forms.
The incubation period ranges from 1 to 20 days (usually 7-10), the reliability of which depends on the accuracy of establishing the fact of tick suction. Up to 30% of patients do not remember or deny the history of this vector bite. The disease usually begins subacutely with the appearance of pain, itching, swelling and redness at the point of suction of the flare. Patients complain of mild headache, general weakness, malaise, nausea, feeling of tightness and loss of sensitivity in the area of the pincer bite. At the same time, a characteristic erythema of the skin appears (up to 70% of patients). Body temperature often rises to 38 ° C, sometimes accompanied by chills. The febrile period lasts 2-7 days, after a decrease in body temperature, subfebrile temperature is sometimes observed for several days.
Migrating erythema – the main clinical marker of the disease – appears after 3-32 days (an average of 7) in the form of a red macula or papule at the site of a tick bite. The area of redness around the bite area expands, separating from the unaffected skin with a bright red border; In the center of the lesion, the intensity of changes is less pronounced. Dimensions of erythema can be from a few centimeters to tens (3-70 cm), but the severity of the disease is not related to their size. Intense erythema is sometimes observed at the site of the initial lesion, vesicles and necrosis (primary affect) appear. The intensity of the color spreading skin lesions is uniform throughout; within the outer boundary several red rings may appear, the central part of which turns pale with time. In place of the former erythema often increased pigmentation and peeling of the skin. In some patients, the manifestations of the disease are limited to skin lesions at the site of a pincer bite and mild general symptoms, in some patients, apparently, hematogenous and lymphogenous borrelia can spread to other skin areas, secondary erythema occurs, but unlike the main one there is no primary affect. There may be other skin symptoms: a rash on the face, urticaria, transient punctate and small ring-like rashes, conjunctivitis. In some patients, the developed erythema is similar to erysipelas, and the presence of primary affect and regional lymphadenitis is similar to the manifestations of tick-borne typhus and tularemia. Skin symptoms are often accompanied by headache, neck stiffness, fever, chills, migrating muscle and bone pain, arthralgia, severe weakness and fatigue. Less common is generalized lymphadenopathy, sore throat, dry cough, conjunctivitis, testicular edema. The first symptoms of the disease usually subside and completely disappear within a few days (weeks) even without treatment.
Stage II is associated with the dissemination of Borrelia from the primary lesion to various organs. In non-erythematous forms, the disease often manifests with manifestations of the disease characteristic of this stage and is more severe than in patients with erythema.
Signs indicating a possible damage to the lining of the brain may appear early, when the erythema of the skin is still present, but at this time they are usually not accompanied by the syndrome of inflammatory changes in cerebrospinal fluid. In the course of several weeks (rarely before 10–12 days) or months from the onset of the disease, 15% of patients show obvious signs of damage to the nervous system. During this period, it is advisable to isolate the syndromes of serous meningitis, meningo-encephalitis and syndromes of the peripheral nervous system: sensory, mainly algic syndrome in the form of myalgia, neuralgia, plexalgia, radiculoalgne; amyotrophic syndrome due to limited segmental radiculoneuritis, isolated neuritis of the facial nerve, mononeuritis, regional to the site of tick infestation, common polyradiculoneuritis (Bannwart syndrome), myelitis; sometimes it is possible to isolate the paralytic syndrome of the peripheral nervous system, but, as a rule, it is not isolated.
In the course of several weeks from the moment of infection, signs of heart damage may appear. Most often it is atrioventricular block (1 or II degree, sometimes complete), intraventricular conduction disturbances, and rhythm disturbances. In some cases, more diffuse lesions of the heart develop, including myopericarditis, dilated myocardiopathy or pancarditis. At this stage, transient pains in the bones, muscles, tendons, and periarticular bags are noted. As a rule, swelling and other obvious signs of joint inflammation at this stage of the disease do not exist. The symptomatology is observed some weeks, there can be relapses.
In stage III, in terms from several months to several years from the onset of the disease, late manifestations of Lyme disease may appear. Recurrent oligoarthritis of large joints is typical, but small joints may also be affected. Biopsy of the synovial membrane reveals fibrin deposits, villous hypertrophy, vascular proliferation, and marked plasma cell and lymphocytic infiltration. The number of leukocytes in synovial fluid ranges from 500 to 000 in 1 mm. Most of them are segmented. Often there is an increased protein content (from 3 to 8 g / l) and glucose. Lime arthritis is similar to reactive arthritis in its course. Over time, changes typical for chronic inflammation are noted in the joints: osteoporosis, thinning and loss of cartilage, cortical and marginal Uzuras, and sometimes degenerative changes: subarticular sclerosis, osteophytosis.
Late lesions of the nervous system are manifested by chronic encephalomyelitis, spastic paraparesis, ataxia, erased memory disorders, chronic axonal radiculopathy, dementia. Often there is polyneuropathy with radicular pain or distal parasthesia. Patients noted headache, fatigue, hearing loss. In children, there is a slowdown in growth and sexual development. Skin lesions in stage III manifest as widespread dermatitis, atrophic acrodermatitis, and scleroderma-like changes.
Complications of Lyme borreliosis are very rare and often manifest as residual effects.
Diagnosing Lyme Disease
The diagnosis of Lyme disease is complicated especially in the late period due to pronounced clinical polymorphism and the frequent absence of typical manifestations of the disease. Diagnosis is based primarily on the clinical picture, epidemiological data and is confirmed by the results of serological research. Clinical diagnosis can be considered reliable only in cases where a history of migrating erythema – a clinical marker of the disease. Borrelia cultures from a sick person stand out with difficulty. Serological methods are widely used to confirm the diagnosis. In our country, indirect immunofluorescence (n-REEF) and enzyme-labeled antibodies (ELISA) are used to detect antibodies to borrelia. However, there are seronegative variants of the disease. Often false-positive results are observed with syphilis. About possible infection can be judged by the detection of Borrelia in preparations of the intestine of a sucking tick using dark-field microscopy. In the affected organs and tissues, borrelia can be detected by electron microscopy, special silver staining, and monoclonal anti-borreliosis antibodies. A promising method is chain polymerization (polimerase chain reaction – PCR), the use of which allows one to confirm the diagnosis with a small number of microbial bodies in the body.
Peripheral blood changes in Lyme disease are non-specific and mainly reflect the degree of inflammatory changes in the organs.
The differential diagnosis is carried out with tick-borne encephalitis, a group of serous meningitis and meningoencephalitis, reactive and rheumatoid arthritis, acute rheumatism, neuritis, radiculo-neuritis, heart diseases with conduction and rhythm disorders, myocarditis, dermatitis of various etiology.
Lyme Disease Treatment
Treatment of Lyme disease includes a complex of therapeutic measures, in which etiotropic therapy plays the leading role. Drugs are prescribed orally or parenterally, depending on the clinical picture and the period of the disease.
Of the oral drugs, preference is given to tetracycline antibiotics. Drugs prescribed in the first period of the disease in the presence of erythema at the site of tick suction, fever and symptoms of general intoxication in the absence of signs of damage to the nervous system, heart, joints. Assign tetracycline 0.5 g 4 times a day or doxycycline (Vibramitsin) – 0.1 g 2 times a day, the course of treatment is 10 days. Children up to 8 years old are prescribed amoxicillin (amoksil, flemoksin) orally 30-40 mg / (kg x day) in 3 doses or parenterally 50-100 mg / (kg x day) in 4 injections. You can not reduce a single dose of the drug and reduce the multiplicity of medication, as to obtain a therapeutic effect, it is necessary to constantly maintain a sufficient bacteriostatic concentration of the antibiotic in the patient’s body.
When identifying patients with signs of damage to the nervous system, heart, joints (in patients with acute and subacute), it is not advisable to prescribe tetracycline drugs, since some patients after the course of treatment have relapses, late complications, the disease has become chronic. Penicillin or ceftriaxone is usually used to detect neurological, cardiac and articular lesions. In contrast to the recommended schemes of penicillin therapy, we specified a single dose of the drug, the frequency of its introduction and the duration of the course of treatment. Benzylpenicillin (penicillin G) is administered 500 thousand U intramuscularly 8 times a day (with an interval strictly after 3 hours). Course duration 14 days. Patients with clinical signs of meningitis (meningoencephalitis) receive a single dose of penicillin up to 2-3 million units depending on body weight and decrease to 500 thousand U. after normalization of CSF. Multiple administration of penicillin is maintained at a constant bactericidal concentration in the blood and affected tissues. A similar scheme of penicillin therapy has been tested and successfully used in the treatment of syphilis, the pathogenesis of which is largely similar to the pathogenesis of Lyme disease. So, there is a similar mechanism of early lesion of the central nervous system in these infections, common features of immunological processes and similarity of pathogens of both infections.
Currently, the most effective drug for the treatment of Lyme disease is ceftriaxone (longacef, rocephin), in a daily dose of 1-2 g. The course lasts 14-21 days.
In the chronic course of the disease, treatment with penicillin follows the same pattern for 28 days. It seems promising to use the antibiotics of the penicillin series of prolonged action – extensillin (retarpen) in single doses of 2.4 million IU once a week for 3 weeks.
In chronic course with isolated skin lesions, positive results can be obtained from the treatment of tetracycline antibiotics.
In cases of mixed infections (Lyme disease and tick-borne encephalitis), anti-tick gamma globulin is used along with antibiotics.
Preventive treatment of a tick affected by a borrelia-infected tick (the contents of the intestine and tick hemolymph are examined using dark-field microscopy) is performed with tetracycline 0.5 g 4 times a day for 5 days. Also for this purpose, the Department of Infectious Diseases of the Military Medical Academy with a good result uses retarpen (extensillin) at a dose of 2.4 million IU intramuscularly once, doxycycline 0.1 g 2 times a day for 10 days, amoxiclav 0.375 g 4 times a day within 5 days. The treatment is carried out no later than the 5th day from the moment of the bite. The risk of disease is reduced to 80%.
Along with antibiotic therapy, pathogenetic treatment is used. It depends on the clinical manifestations and severity. So, with high fever, severe intoxication, parenteral detoxification solutions are prescribed, with meningitis – dehydration agents, with neuritis of the cranial and peripheral nerves, arthralgias and arthritis – physiotherapy treatment. Patients with signs of heart damage are prescribed panangin or asparkam, 0.5 g 3 times a day, Riboxin, 0.2 g 4 times a day. In cases of detection of immunodeficiency prescribed thymalin 10-30 mg per day for 10-15 days. In patients with signs of autoimmune manifestations, for example, often recurrent arthritis, delagil is prescribed 0.25 g. Once a day in combination with non-steroidal anti-inflammatory drugs (indomethacin, metindol, brufen, etc.). The course of treatment is 1-2 months.
The prognosis for Lyme disease is favorable. When late started or inadequate etiotropic therapy, the disease progresses, often turns into a relapsing and chronic course. Disability and in some cases disability due to persistent residual effects. Those who have been ill are subject to dynamic medical observation during the year (examination of an infectious disease specialist, general practitioner, neuropathologist, setting up an indirect immunofluorescence reaction every 3 months), after which it is concluded that infection is absent or chronic.
Lyme Disease Prevention
Specific prevention of Lyme disease is currently not developed. Non-specific prophylaxis measures are similar to those in tick-borne encephalitis. A very effective way to prevent infection is to prevent ticks from sticking (use of protective clothing and scaring agents).