Autoimmune lymphoproliferative syndrome is a hereditary pathological condition. Belongs to the category of heterogeneous. There are two mechanisms of inheritance: autosomal dominant and recessive. In rare cases, the cause is somatic mutations. Lymphoproliferative syndrome may be acquired.
History and Facts
For the first time, the initial x-linked lymphoproliferative syndrome of boys was officially recognized and formalized in science in 1967. Since 1976 he has been ranked as primary immunodeficiency. The attention of scientists to the pathological condition has been riveted since the last decades of the last century. Already then it was revealed that the basis for the development of the disease is irregular lymphocytic apoptosis.
Revealing the features of autoimmune lymphoproliferative syndrome, scientists found that all patients are characterized by improper expression of membrane receptors fasl, CD95. It is this nuance that determines the genetically explained ability of cells to die. A pathological condition develops in the case of a gene mutation that affects apoptosis.
Biology and anatomy: how does everything happen?
In autoimmune lymphoproliferative syndrome in a child, the expression of CD95 is localized in T and B. cells. Apoptosis does not proceed correctly, due to which cells accumulate. Hyperplasia in the chronic form of lymph tissue is diagnosed. The most clearly pathological process is noticeable in the lymph nodes, spleen. The liver suffers significantly. The main percentage of cell structures that are disturbed due to pathological processes are “T”, CD4, and CD8 cells. Scientists suggest that these structures, before the influence of incorrect processes on them, can be active adult CTLs, which, due to a genetic reason, have lost the ability to express coreceptors. At the same time, cellular structures degenerate into polyclonal ones and obtain expression of other elements. This leads to excessive production of IL-10, cells that stimulate autoimmunity.
In medical propaedeutics, lymphoproliferative syndrome is usually divided into several varieties. For classification, take into account the features of the genetic differences of a particular case. Gene mutations can affect the eighth and tenth caspases, CD95, CD178. At the same time, it is worth noting that there is no universally recognized official classification of cases into groups.
Features of manifestation
Symptoms of the disease are extremely diverse. Typically, x-linked lymphoproliferative syndrome is detected in the first years of life, somewhat less often at an older age (up to the age of fifteen). The key symptom is proliferation of lymphoid tissue, provoking 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. Tests can detect autoimmune cytopenia. It is possible in the form of neutro, thrombocytopenia, anemia. Cytopenia appears less frequently before proliferation of lymphoid tissues.
X-linked lymphoproliferative syndrome provokes disturbances in the work of the blood-forming, circulatory systems. As a rule, hepatitis of an autoimmune nature is fixed. Many suffer from eczema, glomerulonephritis. Patients are characterized by uveitis, thyroiditis. About one in ten eventually develops lymphoma from type B cells.
Clinical manifestations
Lymphoproliferative syndrome in children has a number of typical signs. The most striking is lymphoproliferation. The process is inherent in a benign nature, the pathological condition is chronic. It is usually formed already in early childhood, sometimes it is established in one-year-old babies. The condition persists for six months or more. However, there is a persistent proliferation of lymph nodes in the peripheral lymphatic system. To make a diagnosis, it is necessary to identify such processes in three groups of nodes or more. The nodes are dense, with nearby tissues not soldered. In many, tests help identify hepatosplenomegaly.
X-linked lymphoproliferative syndrome in boys manifests itself as autoimmune signs. The classic option is anemia, neutro, thrombocytopenia. Possible vasculitis. Cases of arthritis and hepatitis are frequent. Patients are prone to uveitis, glomerulonephritis, thyroiditis. Some other autoimmune diseases are possible.
Note!
Lymphoproliferative syndrome is associated with a high probability of developing malignant formation. The process localization area is unpredictable. Improperly occurring 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 survive a pathological transformation is growing. Normally, this gene is a factor that inhibits the development of the components of tumors.
More often, the disease is accompanied by the formation of type B, T lymphomas. In addition, there is a high probability of cancer processes in the mammary gland, intestinal tract, and respiratory organs. Myelo-lymphoproliferative syndrome with a high degree of probability can provoke lymphogranulomatosis.
With an autoimmune disease, the patient is prone to urticaria, vasculitis. Some have slower development of the body.
Diagnosis
Lymphoproliferative syndrome is diagnosed if non-malignant lymphadenopathy is established. Splenomegaly is possible. The diagnosis is made by 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 analysis. In laboratory conditions, a failure of mediated lymphocytic apoptosis is established, the concentration of the cellular structures CD4, CD8 T is specified: with a content of more than 1%, one can speak of a pathological condition.
In lymphoproliferative syndrome, genetic studies show the presence of gene mutations. With autoimmune disease, a number of specific markers inherent in an individual case are possible. There are several known, currently used as auxiliary in differential diagnosis. Lymphoproliferative syndrome can indicate itself as markers of the activity of cell structures of type “T”, an increase in the concentration of CD5 + B cells. Some people are diagnosed with an increase in the content of IL-10, hypergammaglobulinemia. Histological analysis allows you to see the follicular growth of lymphoid tissue in the nodes, white pulp.
Case features
Next, a form of the disease that is not associated with a violation of genetics during the development of the embryo is considered. The following applies to the acquired form of the disease.
Lymphoproliferative syndrome is a symptom complex that can accompany not only lymphocytic leukemia proceeding according to the standard scenario, but also more rare forms of the pathological condition. Sometimes it is prescribed for 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, the influence of chemical components. Much attention in modern medicine is attracted by post-transplant lymphoproliferative syndrome, which significantly worsens the prognosis of a person who underwent surgery. In the development of a syndrome that is not inherited, the influence of retroviruses is most pronounced.
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 the age of 25, but such cases are rare. Among males, the incidence rate is on average twice as high as in women. Based on the course, they speak of a benign form, splenomegaly, tumorous, prone to rapid progress, affecting the bone marrow, abdominal cavity. There is also a pro-lymphocytic 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 colds. Sweat glands function somewhat more actively than normal. 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, an increase in the concentration of leukocytes in the circulatory system.
Specific Symptoms
When the disease is prone to an increase in lymph nodes in the neck, in the axillary fossa. A little later, when the disease takes on an expanded form, an increase in other groups is noted. The sizes vary greatly, as does the consistency: some are similar to loose dough, do not respond to pain when examined, do not merge with each other or with skin integuments. For such sites, 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 has active sweat glands, he loses weight, suffers from heat. 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 certain areas of the skin is visible: there is an infiltrate, non-specific affected areas are detected. If a person has previously suffered from skin diseases, they are exacerbated by the syndrome described. Many are concerned about exfoliative erythroderma. Against the background of the syndrome, the development of herpes, urticaria, dermitis 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 has more than normal spleen, liver. A study of the mucous membranes of the digestive tract makes it possible 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
With lymphoproliferative syndrome, the respiratory system may be involved in pathological processes. Leukemic infiltration can affect both the upper sections and the lower airways. The patient coughs, shortness of breath is disturbing, expectoration of sputum with bloody inclusions is possible. Sometimes pleurisy is established.
In some cases, the described syndrome provokes an infiltration of the renal parenchyma. This condition rarely manifests itself as typical symptoms. Perhaps the spread of infiltrate to the central nervous system, which leads to meningitis, some forms of encephalitis and paralysis of the nervous structures, can cause coma. When the infiltrate spreads to the corpora cavernosa, the patient suffers from a prolonged and pain-provoking erection, in medicine called priapism.
Laboratory tests
If you suspect a lymphoproliferative syndrome, the patient is sent for a blood test. This condition is accompanied by an increase in the concentration of lymphocytes, white blood cells. Anemia is possible.
Laboratory tests help diagnose a patient's hematoma, proteinuria. An analysis of biochemistry clarifies hypogammaglobulinemia. In a small percentage of cases, patients establish hypoalbuminemia. Hepatocytic cytolysis indicates hyperfermentemia.
An immunological study indicates an increase in concentration in the spleen, circulatory system of lymphocytes, a malfunction in the balance of lymphocyte helpers and suppressors. At the same time, the concentration of IgG, IgA, IgM decreases (for the last two changes are especially pronounced). Immunophenotyping is the basis to conclude 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 chromosome 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 health condition is rapidly deteriorating, the liver and spleen, lymph nodes are rapidly increasing. Cytostatics are indispensable for leukemic infiltration of the central nervous system fibers, as well as if processes affect organs outside the hematopoietic system. The condition indicates severe pain and malfunctioning of the systems and organs.
If the number of leukocytes in the circulatory system is steadily and rapidly growing, chlorobutin, spirobromine are indicated. A good reaction of the body allows you to get prosidin, cyclophosphamide. Sometimes doctors recommend staying on papentsil. If there are specific indications for this, polychemotherapy may be prescribed. As part of this course, cytostatic agents that affect the body in different ways are combined.
Activities and methods: how to help the patient?
With an increase in the leukocyte count to a level of 200 * 10 by 9 / L, lymphocytapheresis is recommended. If individual lymph nodes increase dramatically and strongly, such processes are detected in the spleen, if lymphadenopathy passes into a systemic generalized form, radiation treatment is prescribed. When the spleen grows, which is not 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 with a disease accompanied by severe splenomegaly, certain forms of leukocytosis, leukemia. Splenectomy is indispensable for granulocyte, erythro-, thrombocytopenia, autoimmune type anemia, 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 preceded this pathological condition, glucocorticoids are prescribed as the main course of therapy. These drugs help with the chronic subleukemic course of lymphocytic leukemia, accompanied by a strong proliferation of the liver, spleen, and lymph nodes. Glucocorticoids are used if the patient does not tolerate cytostatic drugs, it is not possible to apply radiation, or the pathological condition is resistant to such therapeutic approaches.
Important Nuances
Hormonal drugs are indispensable if cytotoxic drugs 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. The most commonly used drugs are a wide spectrum of effectiveness. Macrolides, aminoglycosides have proven themselves well. You can use semisynthetic agents from the penicillin series, cephalosporin, immunoglobulin.
Myeloproliferative syndrome
This pathological condition is often considered in the framework of 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 blood production. The syndrome combines several diseases - leukemia, myelofibrosis, thrombocytosis, polycythemia. Myelodysplastic syndrome is also considered here.