Autoimmune lymphoproliferative syndrome is a hereditary pathological condition. Belongs to the category of heterogeneous. There are two modes of inheritance: autosomal dominant and recessive. In rare cases, the cause is somatic mutations. Lymphoproliferative syndrome may be acquired.
History and Facts
The original x-linked lymphoproliferative syndrome in boys was officially recognized and formalized in science in 1967 for the first time. Since 1976, it has been classified as a primary immunodeficiency. The attention of scientists to the pathological condition has been riveted since the last decades of the last century. Even then, it was revealed that abnormal lymphocytic apoptosis becomes the basis for the development of the disease.
Revealing the features of autoimmune lymphoproliferative syndrome, scientists have found that all patients are characterized by abnormal expression of fasl membrane receptors, CD95. It is this nuance that determines the genetically explainable abilitycells to die. A pathological condition develops in the case of a gene mutation that affects apoptosis.
Biology and anatomy: how does it work?
In autoimmune lymphoproliferative syndrome in a child, CD95 expression is localized in T, B cells. Apoptosis does not proceed correctly, due to which cells accumulate. Hyperplasia is diagnosed in the chronic form of lymph tissues. Most clearly, the pathological process is noticeable in the lymph nodes, spleen. The liver is severely affected. The main percentage of cellular structures disturbed due to pathological processes are T, CD4, CD8 cells. Scientists suggest that these structures, before being affected by the wrong processes, may be active adult CTLs, which, due to a genetic reason, have lost the ability to express coreceptors. At the same time, cellular structures are transformed into polyclonal ones and receive the expression of other elements. This leads to an overproduction of IL-10, cells that stimulate autoimmunity.
In medical propaedeutics, lymphoproliferative syndrome is usually divided into several varieties. For classification, the features of the genetic differences of a particular case are taken into account. Gene mutations can affect the eighth and tenth caspases, CD95, CD178. At the same time, it should be noted that there is no generally accepted official classification of cases into groups.
Features of manifestation
Symptoms of the disease are extremely varied. Usually x-linked lymphoproliferative syndrome is detected in the first years of life,somewhat less often - at an older age (up to fifteen). The key symptom is the proliferation of lymphoid tissue, which provokes splenomegaly, lymphadenopathy. The phenomena are inherent in the chronic nature of the course. At the same time, the patient suffers from manifestations of an autoimmune imbalance. Analyzes help to identify autoimmune cytopenia. It is possible in the form of neutro-, thrombocytopenia, anemia. Somewhat less often, cytopenia appears before the proliferation of lymphoid tissues.
X-linked lymphoproliferative syndrome provokes disturbances in the work of the hematopoietic, circulatory systems. As a rule, hepatitis of an autoimmune nature is fixed. Many suffer from eczema, glomerulonephritis. Patients are characterized by uveitis, thyroiditis. Approximately 1 in 10 develop B-cell lymphoma over time.
Clinical manifestations
Lymphoproliferative syndrome in children has a number of typical features. The most striking is lymphoproliferation. The process is characterized by a benign character, the pathological condition is chronic. Usually formed already in early childhood, sometimes it is established in one-year-old babies. The condition persists for six months or more. At the same time, persistent proliferation of lymph nodes of the peripheral lymphatic system is observed. To make a diagnosis, it is necessary to identify such processes in three groups of nodes or more. The knots are dense, not soldered to nearby tissues. For many, tests help detect hepatosplenomegaly.
X-linked lymphoproliferative syndrome in boys manifests itself as autoimmune symptoms. The classic variant is anemia,Neutro-, thrombocytopenia. Possible vasculitis. There are frequent cases of arthritis, hepatitis. Patients are prone to uveitis, glomerulonephritis, thyroiditis. Some other autoimmune diseases are possible.
Pay attention
Lymphoproliferative syndrome is associated with a high probability of developing a malignant formation. The process localization area is unpredictable. Incorrectly proceeding apoptosis, the work of which is associated with the activity of Fas receptors, leads to a decrease in control over the processes of tissue growth. The ability to survive in cells that have undergone pathological transformation is growing. Normally, this gene is a factor that inhibits the development of tumor components.
More often the disease is accompanied by the formation of type B, T lymphomas. In addition, there is a high probability of cancerous processes in the mammary gland, intestinal tract, and respiratory organs. Myelo-lymphoproliferative syndrome with a high degree of probability can provoke lymphogranulomatosis.
In an autoimmune disease, the patient is prone to urticaria, vasculitis. Some have a slow development of the body.
Clarification of the diagnosis
Lymphoproliferative syndrome is diagnosed if a non-cancerous lymphadenopathy is established. Possible splenomegaly. The diagnosis is made with a combination of these two phenomena or the presence of any of them, if the duration of the development of the condition is six months or more. If a diagnosis is suspected, the patient should be referred for testing. In vitroestablish a failure of mediated lymphocyte apoptosis, specify the concentration of cellular structures CD4, CD8 T: if the content is more than 1%, we can talk about a pathological condition.
In lymphoproliferative syndrome, genetic studies show the presence of gene mutations. In autoimmune disease, a number of specific markers are possible that are inherent in the individual case. There are several known that are currently used as auxiliary in differential diagnosis. Lymphoproliferative syndrome may indicate itself as markers of the activity of T-type cell structures, an increase in the concentration of CD5 + B cells. Some are diagnosed with an increase in the content of IL-10, hypergammaglobulinemia. Histological analysis allows you to see the follicular proliferation of lymphoid tissue in the nodes, white pulp.
Features of the case
The following is a form of the disease that is not associated with a violation of genetics during the development of the embryo. The following applies to the acquired form of the disease.
Lymphoproliferative syndrome is a symptom complex that can accompany not only lymphocytic leukemia, which proceeds according to a typical scenario, but also more rare forms of a pathological condition. Sometimes it is installed with hairy cell leukemia, lymphatic, as a complication of which is cytolysis. It is known that a complex of symptoms can develop against the background of drug therapy, radiation, and the influence of chemical components. Much attention in modern medicine attractspost-transplant lymphoproliferative syndrome, which significantly worsens the prognosis of a person who has undergone surgery. In the development of a syndrome that is not inherited, the influence of retroviruses is most powerful.
Nuances and prevalence
Medical statistics show that the predominant percentage of patients with lymphoproliferative syndrome are people over the age of fifty. Occasionally, the disease is detected in those under 25, but such cases are rare. Among males, the frequency of occurrence is on average twice as high as among women. Based on the course, they speak of a benign form, splenomegalic, tumor, prone to rapid progress, affecting the bone marrow, abdominal cavity. There is also a prolymphocytic type.
When the lymphoproliferative syndrome is just beginning to develop, internal diseases do not bother, the person feels satisfactory, there are no active complaints. Some note weakness, a tendency to catch colds. The sweat glands function somewhat more actively than the norm. The disease at this stage can be detected as part of a preventive examination or at a random examination. The main signs are abnormally large lymph nodes, lymphocytosis, increased concentration of leukocytes in the circulatory system.
Specific symptoms
When the disease tends to increase the lymph nodes in the neck, in the armpit. Somewhat later, when the disease takes on a developed form, an increase in other groups is noted. The sizes vary greatly, as does the consistency: some look like loose dough, when examined by paindo not respond, do not merge with each other or with the skin. For such areas, the formation of ulcers or suppuration is uncharacteristic.
When the disease takes on a developed form, the manifestations become pronounced, the patient feels weak, the ability to work sharply decreases. The patient's sweat glands are active, he loses weight, suffers from fever. Lymph nodes are significantly enlarged, which attracts attention during the initial examination.
Examination of the patient: a complex of manifestations
When examining a patient, lymphoproliferative syndrome can be suspected if lymphadenopathy is clearly diagnosed. In many patients, the transformation of individual areas of the skin is visible: an infiltrate appears, non-specific lesions are detected. If a person has previously suffered from skin diseases, they become aggravated due to the described syndrome. Many are concerned about exfoliative erythroderma. Against the background of the syndrome, the development of herpes, urticaria, dermatitis is possible.
To clarify the condition, it is necessary to refer the patient to CT, ultrasound. The lymphoproliferative syndrome is indicated by the growth of lymph nodes in the sternum, abdominal cavity, while the condition is not always accompanied by manifestations of compression. The patient's spleen and liver are larger than normal. The study of the mucous membranes of the digestive tract allows you to notice leukemic infiltration. Additional manifestations are ulcers in the stomach, intestinal tract, bleeding in this area. There is a possibility of malabsorption syndrome.
Status Progress
Whenlymphoproliferative syndrome may involve the respiratory system in pathological processes. Leukemic infiltration can affect both the upper and lower airways. The patient coughs, shortness of breath is disturbed, expectoration of sputum with bloody inclusions is possible. Sometimes pleurisy is established.
In some cases, the described syndrome provokes infiltration of the renal parenchyma. This condition rarely manifests itself as a typical symptomatology. It is possible that the infiltrate spreads to the central nervous system, which leads to meningitis, some forms of encephalitis and paralysis of nerve structures, and can cause coma. When the infiltrate spreads to the cavernous bodies, the patient suffers from a prolonged and painful erection, in medicine called priapism.
Lab tests
If a patient is suspected of having a lymphoproliferative syndrome, the patient is sent for a blood test. This condition is accompanied by an increase in the concentration of lymphocytes, leukocytes. Possible anemia.
Laboratory tests help diagnose hemato-, proteinuria in a patient. Biochemistry analysis clarifies hypogammaglobulinemia. In a small percentage of cases, patients have hypoalbuminemia. Hepatocyte cytolysis indicates hyperenzymemia.
An immunological study indicates an increase in the concentration in the spleen, the circulatory system of lymphocytes, a failure in the balance of helpers and suppressors from among lymphocytes. At the same time, the concentration of IgG, IgA, IgM decreases (for the last two, the changes are especially pronounced). Immunophenotyping - the basisconclude that leukemic cell structures are CD 5, 19, 20, 23 from the class of B-lymphocytes. The results of cytogenetic analysis in 65% of cases indicate chromosomal abnormalities.
What to do?
With lymphoproliferative syndrome, the patient is shown compliance with the treatment regimen developed by the doctor - the program is selected individually. The patient is prescribed cytotoxic drugs. This is especially true if the state of he alth is rapidly deteriorating, the liver and spleen, lymph nodes are rapidly increasing. Cytostatics are indispensable for leukemic infiltration of CNS fibers, as well as if the processes affect organs outside the hematopoietic system. The condition indicates itself with severe pain and failure of the functionality of systems and organs.
If the number of leukocytes in the circulatory system is growing steadily and rapidly, chlorbutin, spirobromine are indicated. A good reaction of the body allows you to get prospidin, cyclophosphamide. Sometimes doctors recommend stopping at pafencil. If there are specific indications for this, polychemotherapy may be prescribed. Within the framework of such a course, cytostatic agents that affect the body in different ways are combined with each other.
Activities and methods: how to help the patient?
With an increase in the content of leukocytes to the level of 20010 by 9 / l, lymphocytapheresis is recommended. If individual lymph nodes increase sharply and strongly, such processes are detected in the spleen, if lymphadenopathy passes into a systemic generalized form, radiation treatment is prescribed. With enlargement of the spleen,corrected by medications and radiation, the patient is recommended splenectomy. It must be passed if heart attacks of this organ are frequent, as well as in case of a disease accompanied by severe splenomegaly, certain forms of leukocytosis, leukemia. Splenectomy is indispensable for granulocyto-, erythro-, thrombocytopenia, anemia of the autoimmune type, thrombocytopenia, which cannot be regulated by glucocorticoids.
If hormonal compounds show a pronounced effect in thrombocytopenia, if hemolytic anemia is established, and chronic lymphocytic leukemia was a precursor for this pathological condition, glucocorticoids are prescribed as the main course of therapy. These drugs help with chronic subleukemic course of lymphocytic leukemia, accompanied by a strong proliferation of the liver, spleen, and lymph nodes. Glucocorticoids are used if the patient is intolerant of cytotoxic drugs, radiation is not feasible, or the condition is resistant to such therapeutic approaches.
Important nuances
Hormonal agents are indispensable if cytostatic agents have caused cytopenia, hemorrhagic syndrome. They are used as part of polychemotherapy, combining the main course and prednisone.
The described pathological condition is characterized by complications of an infectious nature. With this development of the situation, the patient is shown a course of antibiotics. Most often, drugs with a broad spectrum of effectiveness are used. Well provenmacrolides, aminoglycosides. You can use semi-synthetic agents from the penicillin series, cephalosporin, immunoglobulin.
Myeloproliferative syndrome
This pathological condition is often considered in the educational program along with the one described above. The term is used to denote a pathology in which myeloid cells are actively produced. The cause of the phenomenon is the malfunction of the stem cells of the system responsible for the production of blood. The syndrome combines several diseases - leukemia, myelofibrosis, thrombocytosis, polycythemia. Myelodysplastic syndrome is also commonly referred to here.
