Treatment of Ollier's disease (dyschondroplasia) in South Korea

No other infectious disease raises as many questions as tick-borne borreliosis. The reasons for this are the diversity of the clinical picture of the disease, different opinions of specialists regarding the diagnosis and treatment of this disease, and low awareness of the population about this disease. In this review, we will try to provide the most objective information about this disease, as far as possible at present. This review is based mainly on data from European experts (EUCALB).

What is borreliosis (Lyme disease)

Lyme disease (tick-borne systemic borreliosis, Lyme borreliosis) is a transmissible, natural focal disease characterized by damage to the skin, joints, nervous system, heart, often taking a chronic, relapsing course. Among infectious diseases transmitted by ticks, Lyme disease (LD) is the most common. The name of the disease comes from the name of the small town of Old Lyme in Connecticut (USA), where in the mid-1970s a number of cases of arthritis after tick bites were described. In Europe, Borrelia infection had already been known for a long time under various names (erythema migrans, Bannwart syndrome), but the pathogen was isolated only in 1982.

Pathogens

The causative agents of Lyme disease are several species of human pathogenic borrelia - Borrelia burgdorferi, Borrelia garinii and Borrelia afzelii. Borrelia are microaerophiles and, like other gram-negative spirochetes, are extremely demanding on cultivation conditions. Infections caused by Borrelia burgdorferi most often present with arthritis (especially in North America, where it is the only causative agent of borreliosis), while B. garinii is more likely to cause neurological disorders and B. afzelii is more likely to cause chronic skin diseases. All three pathogens cause erythema migrans.

Epidemiology

The natural hosts of Borrelia in nature are wild animals (rodents, birds, deer), which feed ticks of the genus Ixodes - carriers of Borrelia. During blood sucking, borrelia enter the tick's intestines, where they multiply and are excreted in feces. Despite the high level of infection of ticks, the possibility of infection through a bite is not always realized, because borrelia are contained in the salivary glands in small quantities or are absent altogether.

In natural foci, the circulation of the pathogen occurs as follows: ticks → wild animals → ticks. It is possible that domestic animals - goats, sheep, cows - may be involved in the epidemiological chain. The likelihood of other carriers of Borrelia, such as horse flies, is being studied. A person becomes infected with Lyme disease in natural foci. Natural foci of Lyme disease are found mainly in forest landscapes of the temperate climate zone. In recent years, it has been established that the area of ​​distribution of tick-borne borreliosis coincides with tick-borne encephalitis, and the disease is registered throughout the Russian Federation. However, the incidence of Lyme disease is 2-4 times higher than tick-borne encephalitis, and it occupies one of the first places among natural focal zoonoses. Tick-borne borreliosis is widespread in Europe, Asia, and America. In Russia, borreliosis is widespread in the forest and forest-steppe zones from Kaliningrad to Sakhalin. In European Russia, borreliosis is the most common tick-borne infection.

The risk of getting borreliosis after a tick bite is much higher than tick-borne encephalitis. Natural foci of tick-borne borreliosis coincide with the range of ixodid ticks. The incidence of borreliosis is seasonal and coincides with the activity of ticks. The first patients with tick bites are usually registered in March-April. The latter, in the presence of warm weather, are recorded even in October. Peak activity occurs in May-June. The percentage of ticks infected with borreliosis differs in different regions. A tick can simultaneously be infected with Borrelia, tick-borne encephalitis virus and other pathogens. Therefore, the development of a mixed infection is possible.

Transmission of the infection occurs transmissibly through a tick bite (inoculation), although the possibility of infection cannot be ruled out when tick feces come into contact with the skin, followed by rubbing them in when scratching (contamination). In case of a tick rupture, due to improper removal? the pathogen may enter the wound. The nutritional route of infection through consumption of raw goat or cow milk is discussed.

The main risk groups are workers of forestry farms, timber industry enterprises, hunters, foresters and residents of forested areas.

The carriers of Borrelia are ticks of the genus Ixodes, in our country and Europe - I. ricinus and I. persulcatus, in America - I. pacificus and I. scapularis. The life cycle of these ticks (larva - nymph - adult) lasts an average of three years. Ticks become infected from numerous rodents, as well as hares, hedgehogs, birds, etc. Ticks live in grasses, ferns and low shrubs.

Possible complications

Quite often, complications accompanying the disease are characterized by the transformation of chondromatous nodes into malignant or benign tumors. With prolonged or improper treatment, shortening of the limb is possible, and curvature of the spinal column is also likely, which is characterized by increasing pain and tissue swelling.

The early development of a tumor-like neoplasm in the phalanges can provoke ugly deformities of the fingers. When the disease develops in early childhood, the risk of serious consequences for the patient is high.

Often in adolescence, Ollier's disease is accompanied by the formation of bone chondrosarcoma, which requires only surgical intervention

Pathogenesis

Clinical symptoms that appear at different stages of the disease are caused by a combination of immunopathological reactions and the presence of the pathogen and its antigens in the tissues. Penetrating into the human body, borrelia at the site of introduction cause the formation of a primary affect - papules, tick-borne erythema, then hematogenously enter various organs and tissues, where they are adsorbed on cells, interacting most actively with galactocerebrosides of neuroglial membranes. Perivascular infiltrates appear, consisting of lymphocytes, macrophages, plasma cells, and diffuse infiltration of damaged tissues by these elements. Borrelia and the resulting immune complexes lead to the development of vasculitis and vascular occlusion. Borrelia are capable of persisting in tissues for a long time, up to several years, especially in the absence of treatment, which is associated with a chronic relapsing course of the disease.

In the later stages of the disease, borrelia, playing the role of a trigger, provoke the development of immunopathological processes that are of great importance for the pathogenesis of neuroborreliosis and chronic arthritis. Among this kind of patients, the most common are those with the HLA-DR2 and HLA-DR4 genotypes. Already in the early stages of the disease, specific antibodies are produced, the titer of which increases over the course of the disease. The immune response is most pronounced in the later stages, especially when joints are affected. With effective therapy and recovery, antibody levels normalize. Their long-term persistence or appearance in high titers in later stages indicates the persistence of the pathogen even in the absence of clinical manifestations.

Forecast

According to research, most often by puberty, cartilage tissue is replaced by bone tissue (perhaps this is why cases of the disease are extremely rare in adults). However, in young children the prognosis is less rosy: the deformation, although slowly, progresses. This is precisely why Ollier's disease is dangerous.

The disease manifests itself so individually in each case that it is difficult to clearly assess the overall prognosis. With numerous lesions it is more favorable than in the case of localized single changes. Single deformities lead to shortening of one of the limbs and, consequently, to their asymmetry, especially when it comes to small children. And this can no longer be corrected. Also, with the early development of tumors, the risk of various finger deformities increases.

Borreliosis infection

The incubation period ranges from 2 to 30 days, with an average of 14 days. The infection may be asymptomatic, but may also have a different clinical picture of the disease. The infection is divided into three stages, but in principle these are different clinical pictures of the disease. The division of the disease into stages is arbitrary, and clinical manifestations of all stages of the disease in one patient are not necessary. In some cases, the first stage may be absent, in others - the second or third. Sometimes the disease manifests itself only in the chronic stage, so the general practitioner should remember that patients with arthritis, polyneuropathy, encephalomyelitis and other syndromes characteristic of Lyme disease must be examined to exclude borreliosis.

Stage 1: Early local infection

It is characterized by the development at the site of introduction of the pathogen of a primary affect in the form of chronic migratory erythema of Afzelius-Lipschütz, which is a single (sometimes several) rounded red spot at the site of the bite, which over the course of several weeks, gradually growing centrifugally, reaches 15-20 cm or more in diameter .

As the erythema grows, its central part undergoes regression; in its area a mark (in the form of a reddish dot) from a tick bite can be clearly visible. Most often the lesion is localized on the torso, limbs, but can also be on the face. As it grows, the marginal border of the erythema can rupture, turning into a garland-like strip that sometimes passes through the chest, neck, and face of the patient. Erythema at the site of a tick bite is the main clinical sign of Lyme disease. Erythema is usually hot to the touch, painful, often accompanied by itching and burning, its shape is round or oval, less often - irregular. Erythema can persist for a long time (months), sometimes disappears without treatment after 2-3 weeks, in some cases faster (after 2-3 days). Against the background of etiotropic therapy, it quickly regresses and by the 7-10th day it completely disappears, without a trace or leaving behind pigmentation and peeling.

A crust or scar remains at the site of the tick bite. In a number of patients, “daughter” erythema occurs not only at the site of the tick bite, but also on other areas of the skin, due to the hematogenous spread of Borrelia. Compared to the primary lesion, they are smaller in size and do not have traces of a tick bite and an induration zone in the center. Erythema can occur without fever and without intoxication, being the only symptom of Lyme disease, but in 30-60% of cases it may be absent. Patients often experience an intoxication syndrome: headache, chills, nausea, fever from low-grade to 40˚C, myalgia and arthralgia, severe weakness, fatigue, drowsiness. Regional lymphadenitis and stiffness of the neck muscles are often detected at the site of the tick bite. Of the general toxic symptoms, the most constant are weakness and drowsiness. At the 1st stage of the disease, antibodies to Borrelia may often not be detected, but their study is necessary to prevent later complications of the disease.

Stage 2. Early disseminated borreliosis

Stage 2 of the disease, caused by lymphogenous and hematogenous dissemination of the pathogen and developing from the 2nd to the 21st week of the disease (usually in the 4-5th week), is characterized by lesions of the nervous system (serous meningitis, neuritis of the cranial nerves, radiculoneuritis) , cardiovascular system (myocarditis, pericarditis, conduction disorders (especially atrioventricular block). A flu-like syndrome often occurs (headache, fever, weakness, myalgia). Skin lesions at this stage may have the character of secondary ring-shaped elements with a diameter of 1-5 cm, erythematous rash on the palms of the type of capillaritis, urticarial rashes, as well as benign lymphocytoma of the skin of Spiegler.

Mild symptoms of meningeal irritation may appear early, when erythema still persists, and pronounced neurological symptoms are more often observed several weeks after the onset of the disease, when erythema - a marker of tick-borne borreliosis - has already disappeared. Serous meningitis is accompanied by headache of varying intensity, nausea, vomiting, photophobia, soreness of the eyeballs, stiff neck, and other symptoms of irritation of the meninges are less common.

In 1/3 of patients, moderate symptoms of encephalitis are found in the form of sleep disturbances, decreased attention, memory disorders, increased excitability, emotional disorders, etc. Neuritis of the cranial nerves occurs in more than half of the patients. The VII pair of cranial nerves is most often affected, often with paresis of the facial muscles, numbness and tingling of the affected half of the face, pain in the ear or lower jaw, without clear disturbances of sensitivity. The oculomotor, visual, auditory, and rarely the IX-X pairs of cranial nerves may also be affected. Damage to peripheral nerves is also observed. Radicular sensitivity disorders occur in the cervical, thoracic, and lumbar spine. One of the typical neurological disorders is Bannwart syndrome, which includes serous meningitis and damage to the spinal nerve roots with a predominant localization in the cervicothoracic spine.

Neurological disorders usually disappear completely after 1 month, but can recur and become chronic. Damage to the nervous system may be the only manifestation of Lyme disease when general infectious syndrome and erythema are absent. In the 5th week, approximately 8% of patients experience cardiac disorders: pain, discomfort in the heart area, interruptions in heart contractions. The ECG shows atrioventricular block of varying degrees and diffuse damage to the heart muscle. Myocarditis and pericarditis may develop. The duration of cardiac symptoms ranges from several days to 6 weeks. Throughout the entire period, weakness and migrating pain in the bones, muscles, and joints persist.

Stage 3. Late chronic borreliosis

Stage 3 of the disease is characterized by joint damage. It begins 2 months or later from the onset of the disease, sometimes after 1-2 years. Large joints are usually affected, especially the knees, often with unilateral localization. In some cases, symmetrical polyarthritis develops. Arthritis, as a rule, recurs over several years and becomes chronic with destruction of bones and cartilage. At a late stage of the disease, persistence of the pathogen in the patient’s body leads to a chronic course of the disease.

Chronic Lyme disease occurs with alternating remissions and relapses, sometimes becoming continuously relapsing. The most common syndrome is arthritis. Changes typical of chronic inflammation develop: osteoporosis, thinning and loss of cartilage, and less commonly, degenerative changes. Often there is a skin lesion in the form of benign lymphocytoma, which is a dense, edematous, bright crimson infiltrate (or nodule), slightly painful on palpation, located on the earlobe or around the nipple of the mammary gland and lasting from several days to months and even years .

Another lesion typical of the late stage is chronic atrophic acrodermatitis: cyanotic-red spots on the extensor surfaces of the extremities, tending to peripheral growth, fusion, and periodic inflammation. Gradually, the skin at the site of the spots atrophies and takes on the appearance of tissue paper. The process develops over several months and years. The neurological manifestations of chronic Lyme disease, neuroborreliosis, consist of progressive chronic encephalomyelitis and polyneuropathies. Encephalomyelitis is similar to multiple sclerosis. Mental disorders are observed - memory, sleep, speech disorders. Polyneuropathies are accompanied by impaired sensitivity, distal paresthesia, radicular pain, etc. The protracted and chronic course of the disease sometimes leads to partial or complete loss of ability to work.

Symptoms of the disease

In order not to miss signs of the disease, parents should be wary if their child:

• some areas of the limb/limbs are delayed in development;
• asymmetry and shortening are noted in them;
• lameness is observed;
• there is a pelvic distortion;
• there are curvatures of the joints of the valgus or varus type.

All these factors make it possible to assume that the child has Ollier disease.

The disease does not always appear immediately at birth, but already at the age of 1-4 years you can notice that the child’s legs or arms are growing more slowly than expected. This is the main symptom of the disease that cannot be ignored. Otherwise, the baby is developing normally, despite the fact that he was diagnosed with Ollier disease.

Dyschondroplasia most often affects one limb, however, cases of damage to both are not uncommon. If the disease affects the legs, the child will be short due to their shortening. Bone growth is especially severely delayed if the pathological process began very early. The deformities are painful and progress slowly. The limb affected by the disease becomes shorter, thicker, the gait changes, and lameness is observed. Varus or valgus deformity of the knee (less commonly, the proximal end of the thigh or foot), and scoliosis of the spine may be observed. Muscle atrophy is not present in this disease.

The phalanges, metatarsals and, in some cases, metacarpal bones undergo major changes. They are shortened, widened, awkward and contain many cartilaginous enlightenments.

People suffering from Ollier disease are susceptible to fractures because their bone tissue does not develop properly as a result of the disease. However, fractures most often heal without problems.

Diagnostics

Early diagnosis is based on clinical and epidemiological data. With the classic picture of erythema migrans, the diagnosis is made based on clinical signs; the diagnosis is registered even in the absence of laboratory confirmation and data on a tick bite. In other cases, the diagnosis is confirmed by laboratory methods. Culture, detection of pathogen antigen and histological examination of the skin are not sensitive and specific enough; histological examination is, in addition, invasive. Therefore, the diagnosis is confirmed mainly by serological methods - the detection of specific antibodies to the pathogen in the blood.

PCR testing for the presence of genetic material of the pathogen is ineffective in this case. IgG antibodies can be detected 1-3 weeks after infection; the maximum amount of IgG antibodies is synthesized 1.5-3 months after infection. IgG antibodies are often not detected in the early, localized stage of the disease or with early antimicrobial therapy. IgG antibodies circulate in the blood for a long time (from several months to several years), even after successful antimicrobial therapy and cure of the infection. Immunity against Borrelia is not sterile. People who have been ill may become infected again after a few years. False-positive results of determining IgG antibodies to Borrelia may be due to the presence in the blood of specific antibodies for diseases caused by spirochetes (syphilis, relapsing fever); a low level of IgG antibodies is possible in infectious mononucleosis, hepatitis B, rheumatic diseases (SLE), periodontal diseases, in 5-15% of healthy individuals from the epidemic zone.

In the laboratories of the CityLab Association this study is - 45-20-109 - Antibodies to Borrelia IgG (Lyme disease, borreliosis)

Material for research: blood serum.

Collection of material for research: blood is taken into a vacuum tube without preservatives.

Preparation for the study: no special preparation is required.

The study is carried out using the enzyme immunoassay method (ELISA)

Units of measurement: qualitative result.

Interpretation of results

A positive test result indicates a current or past infection. This can sometimes lead to incorrect assessment of the study results if the clinical picture of the disease is atypical.

A negative test result can occur in the absence of infection, when the study is carried out in the early stages of the disease or in the long term after an infection. It must be remembered that the absence of antibodies does not exclude early infection, but does exclude chronic borreliosis.

If a questionable result is obtained, the test must be repeated after 10-14 days.

In principle, the need for treatment cannot be determined based on serological studies alone and the effectiveness of therapy cannot be assessed. These problems must be resolved individually, taking into account clinical data.

Provoking factors for the development of the disease

The disease can occur in equal proportions in men and women. Most often, dyschondroplasia is first discovered in childhood. In severe forms of the disease, small bones are involved in the inflammatory process. The only area where the disease is not localized is the skull. The disease is extremely rare, occurring in 10 cases out of 1000.

To date, the etiology of this disease has not been fully studied, however, there are hypotheses that explain the development of the pathological process by an autosomal dominant type of genetic transmission. In this case, changes occur at the stage of embryonic formation of the fetus.

Similar in symptoms to Ollier's disease are Proteus syndrome (the development of benign neoplasms in different areas of the body) and Maffucci syndrome (characterized, in addition to benign tumors in skeletal tissue and cartilage, by the formation of vascular hemangiomas).

Proteus syndrome is a congenital disorder that is extremely rare and causes abnormally rapid bone growth and tumors.

It is important to note that the area of ​​cartilage tissue grows as we grow older, which leads to even greater deformation of the bone tissue. In some cases, chondrosarcomas (malignant neoplasms) and chondromas (benign tumors) are noted.

Treatment

Patients with moderate Lyme disease are subject to mandatory hospitalization in an infectious diseases hospital at all stages of the disease. Patients with a mild course of the disease (tick-borne erythema, in the absence of fever and intoxication) can be treated at home. Antibiotics are used as etiotropic drugs, the choice of which, dose and duration of use depend on the stage of the disease, the prevailing clinical syndrome and severity. All those bitten by ticks and who have recovered from Lyme disease are subject to clinical observation for 2 years.

Clinical examination is carried out by an infectious disease specialist or a general practitioner. Patients and persons after a tick bite should be examined clinically and serologically after 3, 6, 12 months and 2 years. According to indications, consultations with a cardiologist, rheumatologist, neurologist are prescribed, an ECG test is performed, a blood test for CRP, rheumatoid factor. Pregnant women bitten by ticks deserve special attention. Due to the lack of specific prophylaxis and the known teratogenic effect of Borrelia in the early stages of pregnancy, it is advisable to decide on an individual basis for maintaining pregnancy.

If late manifestations of borreliosis occur, patients are treated in specialized hospitals (rheumatology, neurology, cardiology) according to clinical indications. Convalescents of borreliosis with residual effects are observed by specialists, depending on the damage to one or another system (neurologist, cardiologist, rheumatologist).

Classification of chronic myeloproliferative diseases

The following types of HMPP are distinguished:

• chronic myeloid leukemia (CML);
• neutrophilic leukemia;
• eosinophilic leukemia;
• CMPD polycythemia vera;
• essential thrombocythemia;
• idiopathic myelofibrosis;
• unclassified CMPD (when the development and clinical signs do not correspond to any of the above forms of the disease).

All CMPD is characterized by the absence of dysplastic changes in the bone marrow and blood cells in the initial stages of the disease.

In addition to the above types, in modern oncology there is a separate group with myeloid dysplasia, which occupies an intermediate position between CMPD and myelodysplastic syndrome.

Classification of CMPD with myelodysplasia:

• myelomonocytic chronic leukemia;
• myelomonocytic chronic juvenile leukemia;
• chronic atypical myeloid leukemia;
• unclassified CMPD with myelodysplasia (when the development and clinical signs do not correspond to any of the above forms of the disease).

Prevention

There is no prophylactic vaccine to prevent borreliosis. The best prevention is protection against tick bites. Prevention consists of observing individual protection measures against tick attacks and raising awareness among the general public. Proper tick removal is of great importance for preventing infection. If the tick has attached itself, it needs to be removed quickly. Borrelia live in the intestines of the tick and do not immediately enter the bloodstream. The longer the tick was on the body, the higher the risk of borreliosis.

The question of the benefits of preventing borreliosis after a tick bite with antibiotics is controversial. Prescribing antibiotics in the first days after a bite can reduce the risk of illness. But they should only be prescribed by a doctor. If a bite occurs, you should immediately seek medical help.

Due to the lack of specific prevention measures, identifying patients based on early clinical signs and mandatory antibiotic therapy according to a rational regimen are of particular importance to avoid severe late complications.

Who is susceptible to the disease

Chondromatosis of the bones was previously thought to be rare. But now, when X-ray examination is carried out quite widely, it turned out that it cannot be called a rarity. If 20 years ago 30 cases were described, now there are twice as many.

It is usually impossible to determine the exact onset if regular dynamic X-ray examinations have not been carried out since birth, especially in early childhood and intrauterine development, when, in fact, Ollier’s disease occurs. By the way, this disease is detected in girls almost twice as often as in boys.

Used Books

1. Ofitserov V.I. Lyme borreliosis and its diagnosis. News "Vector-Best" N 2 (28). June 2003.
2. Coyle PK: Neurologic Lyme disease update. 12th International Conference on Lyme Disease and Other Spirochetal and Tick-Borne Disorders, New York, NY, 1999.
3. Coyle PK, Schutzer SE, Deng Z., et al: Detection of Bb-specific antigen in antibody-negative cerebrospinal fluid in neurologic Lyme disease. Neurology 45:2010-2015, 1995.
4. Coyle PK, Deng Z, Schutzer SE, et al: Detection of Bb antigens in cerebrospinal fluid. Neurology 43:1093-97, 1993.
5. Elliott DJ, Eppes SC, Klein JD Teratogen update: Lyme disease. Teratology. 2001
6. Fallon BA, Das S, Plutchok JJ, et al: Functional brain imaging and neuropsychological testing in Lyme Disease. Clin Infectious Disease 25(s):57-63, 1997.
7. Heertum RV: Functional brain imaging in the diagnosis of chronic CNS Lyme disease. 12th International Conference on Lyme Disease and Other Spirochetal and Tick-Borne Disorders, New York, NY, 1999.
8. Jonathan A., Edlow MD, Bull's Eye: Unraveling the Medical Mystery of Lyme Disease, Yale University Press, 2003
9. Logigian EL, Johnson KA, Kijewski MF, et al: Reversible cerebral hypoperfusion in Lyme encephalopathy. Neurology 49:1661-1670, 1997.
10. Practice Guidelines for the Treatment of Lyme Disease. Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1089-1134
11. Prevention of Lyme disease. American Academy of Pediatrics. Committee on Infectious Diseases. Pediatrics. 2000 Jan;105(1 Pt 1):142-7.
12. Sood, SK Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme disease. Clin Infect Dis. 2002 Jul 19; 35:451-464.
13. Steere AC, Coburn J., Glickstein L. The emergence of Lyme disease. J Clin Invest. 2004 Apr 15; 113(8): 1093-1101.
14. Tietz Clinical guide to laboratory tests. 4th ed. Ed. Wu ANB- USA, WB Sounders Company, 2006, 1798 p.
15. Treatment of Lyme Disease. The Medical Letter, Inc. Volume 47 (Issue 1209) May 23, 2005.