Erythema migrans

The last months of spring, summer and warm fall are the season of activity of many insects, including ixodid ticks. Accordingly, this is also the time of peak incidence of infections carried by such ticks. The most common such infection is considered to be lyme borreliosis, or tick-borne boreliosis, or Lyme disease. A typical sign of this pathology is erythema migrans, a skin manifestation of the disease that occurs in the area of the bite of an infected tick. The pathogen penetrates into the human skin with the salivary fluid of the insect. The infection is diagnosed and treated in an infectious disease department using antibiotics and symptomatic therapy. [1]

Epidemiology

Erythema migrans is an infectious skin lesion that occurs mainly after the bite of a borreliosis-carrying insect. The infection spreads very rapidly, so the erythema tends to enlarge rapidly.

The disease develops regardless of a person's age, race, or gender. Most cases occur in people between the ages of 21 and 60.

The most common site of development of erythema migrans is the upper and lower torso, head, and upper extremities.

Migratory erythema is the initial stage of borreliosis, which is endemic in the United States, Australia, European countries and Siberia. In the vast majority of cases, the disease is registered during the warm season.

The first description of erythema migrans was made more than a century ago by the physician Afzelius, and somewhat later by Dr. Lipschutz. However, the essence of the disease was clarified only relatively recently - in 70-80 years of the XX century, when the causative agent was isolated and the infection borreliosis was described. To date, erythema migrans is practically associated with this infection and is considered a kind of indicator of Lyme disease (the second name of borreliosis).

Causes of the erythema migrans

The most common causative agent of erythema migrans is a spirochete of the genus Borrelia, which is directly related to ixodes ticks. Together with the salivary secretion of the insect during a bite, the spirochete enters human tissues. Characteristic signs develop on the skin in the affected area.

From the zone of penetration with lymph and blood flow, the infection spreads to internal organs, joints, lymph nodes, nervous system. The dead spirochetes release an endotoxic substance into the tissues, which entails a number of immunopathologic processes.

In general, we can name two basic (most common) causes for the development of erythema migrans, and they are all due to mite attack:

• bite of an infected tick Ixodes dammini or pacificus;
• Lone star tick bite, or Amblyomma americanum.

A tick can "suckle" on a person's skin while walking in a park or forest. These insects can live in the grass, on bushes and trees, as well as carried on birds, rodents and other animals. Carriers of infection are quite widespread: in our country, they can be found almost everywhere, especially in the summer season. [2]

Risk factors

The main risk group for the development of erythema migrans can be described as workers of forestry organizations, hunters and fishermen, people who work on dacha plots, in gardens and vegetable gardens, as well as those who regularly visit forest plantations to collect berries and wild herbs.

Both tourists and ordinary vacationers who like to spend their free time closer to nature can suffer from tick bites and the development of erythema migrans. Specialists do not advise to visit areas of possible insect habitat without special necessity, and especially in the period from May to July. If you still have to go to the forest, it is desirable to choose the beaten paths, without plunging into the thickets. By the way, ticks are more noticeable on light-colored items of clothing.

Immune defense of a person is of great importance in the development of erythema migrans. Against the background of strong immunity, erythema is often not manifested: however, this does not mean that the entry of the causative agent of borreliosis into the tissues will not entail infection and further development of the infectious-inflammatory process. [3]

Pathogenesis

The infectious agent of erythema migrans is most often the gram-negative bacterium Borrelia spirochete, which is carried by infected ticks.

Usually in nature, these insects live in forest parks, on the banks of rivers and lakes, near mass grass and flower plantations. A person is able to become infected through a bite: it is from this place on the skin that the development of erythema migrans begins. It does not matter how quickly the tick is removed from the body: the infection enters the body immediately at the moment of the bite, together with the salivary secretion of the insect.

During the attack, the mite bites the skin, breaking its integrity. Some of the pathogen settles directly in the wound, the rest of it spreads with the bloodstream and lymph flow throughout the body, lingering in the lymph nodes.

Erythema migrans is considered an unequivocal and typical sign of the onset of borreliosis, or Lyme disease. Widening of the clinical picture with the onset of multiorgan involvement is noted approximately four weeks after the onset of erythema. However, approximately 30% of patients with borreliosis do not show erythema migrans. Specialists attribute this to individual peculiarities of human immunity, as well as the volume of infiltrated infection and virulence of bacteria.

The infectious agent penetrates into the tissues, and in the deepest layers - thanks to the lymphatic vessels. An inflammatory process with an allergic component develops. Exudative, proliferative processes occur with the participation of cells of the protective and reticulo-endothelial system, lymphocytes and macrophages. The pathogen is bound, as it is perceived by structures as a foreign agent. At the same time, cell proliferation is stimulated, the tissue damage in the bite area heals.

Directly migrating erythema is a consequence of excessive reaction of the cutaneous vascular network, inhibition of blood circulation and increased plasma pressure on capillary vessels. As a result, a certain amount of plasma is released into the dermis, edema begins, and a spot protruding above healthy skin develops. Further to the dermis there is a migration of T-lymphocytes of the vascular system: they exercise control over the "uninvited guests" and destroy the remaining pathogen. Erythema originates from the central zone of the bite. In the area of the original lesion, the inflammatory response subsides, and the borders continue to enlarge at the expense of T-lymphocytes and cellular structures of the dermis. Migratory erythema tends to increase centrifugally.

Symptoms of the erythema migrans

A reddish papule forms on the skin at the bitten site and increases in diameter ("spreads") daily. This enlargement may last from one to several weeks. The diametric size of the spot often exceeds 50 mm. As the papule enlarges, the central part of the erythema becomes pale.

A similar reaction occurs in the area of the bite: most often the upper torso, buttocks, and extremities are affected. The borders of the spot are usually flattened, without signs of peeling. Pathology is almost never found on the plantar and palm surfaces.

Chronic erythema migrans is a type of infectious dermatosis caused by borrelia that have entered the tissues after a tick bite. Some victims, in addition to erythema migrans, have more serious manifestations of the disease, in particular, meningitis.

The bite area is usually a purplish-reddish spot, which makes itself known after a certain period of time after the lesion. The pathologic element rapidly expands and acquires an oval, semicircular or ring-shaped form. The average size of the spot is 50-150 mm. As a rule, a person is bitten by only one insect, so the spot is usually single.

Subjective sensations are mostly absent, there are no complaints against the background of skin redness. After some time, erythema migrans gradually disappears, often leaving behind a peculiar trace in the form of a pigmented spot, which also flattens and lightens over time.

Individual patients may complain of tingling, mild itching, and a general state of discomfort. If complications join, the clinical picture expands and is supplemented with new relevant symptoms. [4]

First signs

Tick-borne erythema migrans usually appears 3-30 days after the tick bite. However, in some cases, the incubation period can last up to 90 days.

The erythema area has the appearance of a pinkish or reddish spot with a papule in the area of the insect bite. The formation has a small convexity, the outline is constantly increasing and changing. When you touch it, you can feel a slight warmth. As it increases, the central zone becomes lighter, the erythema acquires the appearance of a ring. The initial stage in individual patients may be accompanied by a slight itching, aching discomfort.

Other background symptoms may include:

• sleep disturbances;
• a slight rise in temperature;
• weakness, a constant feeling of fatigue;
• head pain, lightheadedness.

Stages

Erythema migrans in Lyme disease has 3 stages:

• localized early;
• disseminated early;
• late.

Between the early and late stages, there is usually a lapse of time without obvious symptomatic manifestations.

Let's break down each of the stages separately.

1. Erythema migrans in borreliosis is a basic early symptom and is found in most patients. The beginning of its development is the appearance of a reddish spot like a papule in the area of tick-bite skin. The sign appears about a month after the bite, but it can appear earlier - even on the third or fourth day. It is important that not all patients know that they have been attacked by an insect: many do not realize it and therefore at first do not pay attention to the redness. Over time, the reddened area "spreads", a zone of lucency is formed between the central and peripheral parts. The center is sometimes thickened. If untreated, erythema migrans usually resolves within about one month.
2. The disseminated early stage shows signs of spread of the pathogen throughout the body. After completion of the first stage and disappearance of the erythema migrans, which has not been properly treated, numerous ring-shaped secondary elements appear on the skin, without a compacted central part. Additionally, neuromyalgia and flu-like signs (general discomfort, stiffness of the occipital muscles, and fever) appear. Such symptoms sometimes last for several weeks. Due to the nonspecificity of the clinical picture, the disease is often misdiagnosed, so the treatment is prescribed incorrectly. In some patients, in addition to the above symptoms, there are lumbar pain, dyspepsia, sore throat, enlargement of the spleen and lymph nodes. The clinical picture of the second stage of erythema migrans is often unstable and changes quickly, but the constant signs are general ill health and loss of strength, which last for quite a long time - more than a month. In some patients there is a fibromyalgic syndrome characterized by widespread pain, fatigue. Immediately signs of erythema migrans on the skin are able to reappear, but in a lighter variation. Neurological disorders join (about 15% of cases), preceding the development of arthritis. Most often such disorders are represented by lymphocytic meningitis, cranial neuritis, radiculoneuropathies. Myocardial disorders (myopericarditis, atrioventricular blockages) are noted in less than 10% of cases.
3. If there is no further treatment, the erythema migrans and infectious lesions progress to the next, late stage, which develops several months or even years after the tick-borne lesion. Most patients develop arthritis, and the joints become swollen and painful. The formation and even rupture of Baker's cysts is possible. Among the common signs of the disease are general discomfort, weakness, a slight increase in temperature. In the further absence of therapy, atrophy develops in the form of chronic acrodermatitis, polyneuropathy, encephalopathy.

Forms

Erythema is an abnormal reddening of the skin, or reddish rashes caused by increased blood flow to the capillaries - and not in all cases the problem is due to the entry of Borrelia spirochetes into the tissues. Erythema migrans is categorized into several varieties, and each has its own specific signs and causes.

• Darier's erythema migrans is a rare and poorly understood disease. It manifests itself against the background of symptoms of exacerbation of latent viral infection provoked by Epstein-Barr virus. The pathogenesis of this type of erythema is still unclear.
• Migrating erythema nodosum is a specific type of inflammatory process in adipose tissue (panniculitis), which is characterized by the appearance of palpable painful subcutaneous nodules of a reddish or purple-red hue, more often in the lower legs. Pathology occurs as a result of provoking systemic disease with streptococcal infection, enterocolitis and sarcoidosis.
• Necrolytic erythema migrans is provoked by the development of glucagonoma, which arises from the α-cells of the pancreas in patients with diabetes mellitus. Pathology is manifested by a cyclic erythematous rash with superficial blisters at the edges, accompanied by a sensation of itching or burning. Histological examination determines necrosis of the upper epidermal layers with swelling and necrotized keratinocytes.
• Erythema migrans Afzelius Lipschutz is the most common type of pathology, which is the initial stage in the development of tick-borreliosis (Lyme disease).
• Gammel's erythema migrans is a specific skin rash, itchy, streaky, garland-like, which occurs against the background of oncologic processes in the body. Erythema has the appearance of hundreds of ring-shaped elements resembling urticaria, but scattered all over the torso. Often the spot is similar to a tree cut or tiger skin. The main feature of the disease is a rapid change of outlines, which fully justifies the name of migratory (changeable) redness.

Complications and consequences

Erythema migrans most often resolves about a month after onset (sometimes after several months). Transient flaking, pigmented spots remain on the skin. For some time, the patient will experience mild itching, numbness, and decreased sensitivity to pain.

If erythema migrans is not treated or treated incorrectly, the pathology transforms into a chronic form: the growing inflammatory process contributes to the development of atrophic and degenerative disorders - primarily in the nervous system. Patients begin to have problems with sleep, attention and memory deteriorate, there is emotional lability, a constant feeling of anxiety. Since such reactions are a consequence of demyelination of nerve fibers, the patient progresses encephalomyelitis, encephalopathy with epileptic-like seizures develops. Cranial nerves (optic, vestibulocochlear) may be affected. Such pathological symptoms as tinnitus, dizziness, decreased visual acuity, distortion of visual perception. With further damage to the spinal cord, sensitivity is disturbed and numbness occurs in any of the vertebral compartments.

Diagnostics of the erythema migrans

The diagnosis of erythema migrans is made by an infectious disease doctor, taking into account the information obtained from examining and interviewing the patient. In most cases, visual examination is sufficient to make a diagnosis, especially in the case of a proven tick bite. At an early stage, laboratory diagnosis is not so informative, as erythema migrans is detected before positive results of serologic tests appear. [5]

To confirm the infectious nature of the disease, blood tests (antibodies to Borrelia, enzyme-linked immunosorbent assay or ELISA) are performed. The study is considered positive if the following indicators are detected:

• IgM to Borrelia is 1:64 or more;
• IgG to Borrelia is 1:128 or more.

Such studies are not always indicative, so they are performed several times, with a certain time interval.

In areas endemic for Lyme disease, many patients present to physicians for similar symptoms of the disease but without evidence of erythema migrans. In such individuals, an elevated IgG titer against a normal IgM titer may indicate a past infection but not an acute or chronic infection. Such cases can lead to prolonged and unnecessary antibiotic therapy if misinterpreted.

Instrumental diagnostics includes microscopy of various biomaterials: blood, cerebrospinal fluid, lymph, intra-articular fluid, tissue biopsy specimens, etc. Culture tests are relatively rare, since germination of borreliosis cultures is a rather labor-intensive and time-consuming process.

If there is no rash in the form of erythema migrans, it becomes more difficult to make a correct diagnosis.

Differential diagnosis

Depending on the clinical manifestations, erythema migrans often has to be distinguished from other diseases:

• acute respiratory infection;
• pink shingles;
• erythematous type swelling;
• allergic process in response to an insect bite.

In South American states and the Atlantic coast, Amblyomma americanum insect bites can cause a rash similar to erythema migrans accompanied by nonspecific systemic signs. However, the development of borreliosis in this situation is out of the question.

Treatment of the erythema migrans

Patients with a moderate or complicated course of erythema migrans are admitted to the Infectious Diseases Department for inpatient treatment. Mild cases may be treated as outpatients.

To neutralize the infectious agent of the disease, antibiotics of the tetracycline group or semi-synthetic penicillins are used (injections and internal administration of medications). In chronic erythema migrans, it is appropriate to use cephalosporin drugs of the latest generation (in particular, Ceftriaxone). [6]

It is obligatory to conduct and symptomatic therapy:

• detoxification treatment, correction of acid-base balance (administration of glucose-salt solutions);
• Antiedema treatment (administration of diuretics in the form of Furosemide, Reogluman).

To optimize capillary blood circulation in tissues prescribe:

• Cardiovascular drugs (Cavinton, Trental, Instenon);
• antioxidants (tocopherol, ascorbic acid, Actovegin);
• nootropic drugs, B-group vitamins;
• painkillers and anti-inflammatory drugs (Indomethacin, Paracetamol, Meloxicam);
• agents optimizing neuromuscular processes (Proserin, Distigmine).

Treatment is prolonged, prescribed by a doctor on an individual basis.

Prevention

The basic methods of preventing erythema migrans are the same as those for preventing infection with borreliosis.

It is necessary to pay attention to the proper selection of clothing when going to work or resting outdoors, walking in the park or forest belt. It is obligatory to use headgear, whether it is a hat, panama or scarf. Clothing is better to choose light colors, with long sleeves. Optimally, if the cuffs in the area of the hands and shins will be dense, on the elastic band. Shoes should be closed.

On clothing and exposed parts of the body (excluding the face) it is recommended to apply special repellents - external preparations that repel insects, including ticks.

When you return home - after a walk, rest, or after a work shift - you should carefully inspect your clothes, body, and hair for ticks.

It is also necessary to know the basic rules for removing the insect, if it does penetrate the body. The tick should be tightly grasped at the level of its penetration into the skin, using clean tweezers, or just clean fingers to hold the insect at a right angle, twist it and pull it out. The area of the bite should be treated with an antiseptic solution (for example, any alcohol lotion, vodka, etc.). It is desirable to put the tick in a clean jar and take it to the nearest sanitary-epidemiologic station (SES) to assess the likelihood of infection. If there is no possibility to examine the insect, it is burned.

The resulting wound is regularly inspected and body temperature is measured for four weeks. This is necessary in order to timely detect the first signs of pathology. Appeal to a doctor should become mandatory if the affected area is found to have such symptoms:

• redness with brightly marked outlines, with a diametric size of 30 mm or more;
• pain in the head, dizziness of unknown origin;
• lumbar pain;
• an increase in temperature over 37.4°C.

Some experts recommend prophylactic administration of antibiotics (penicillin, tetracycline series, cephalosporins) after a tick bite:

• within five days if antibiotic therapy was started from the first day of the bite;
• within 14 days if it has been three days or more since the bite.

Self-administration of antibiotics is unacceptable: medication is prescribed by an infectious disease doctor based on suspicions and symptoms.

Forecast

The prognosis for life is favorable. However, if untreated, the disease can become chronic, with further damage to the nervous system, joints, with impaired ability to work and disability. In many cases, patients have to limit their professional activity, if it is accompanied by excessive loads on the affected organs.

The modern approach to the treatment of erythema migrans always assumes a complex effect: it is under such conditions we can talk about the greatest effectiveness and favorable prognosis for patients.