macroglobulinemia
Introduction
Introduction to macroglobulinemia The abnormal increase of IgM in the blood is macroglobulinemia. The disease is divided into primary and secondary, and the cause of primary macroglobulinemia is unknown, also known as Walsh macroglobulinemia. There are primary and secondary points in this disease. The unexplained increase in monoclonal lgM is called primary macroglobulinemia (Waldenstrom macroglobulinemia), and monoclonal or polyclonal lgM secondary to other diseases. The increase is called secondary macroglobulinemia. The clinical manifestations of primary macroglobulinemia are age-related, anemia, bleeding tendency, and high-viscosity syndrome. The diagnosis is based on the presence of large amounts of monoclonal lgM in the blood and lymphoid plasma cell infiltration in the bone marrow. The disease is a chronic process, chemotherapy is not recommended without clinical symptoms, and chemotherapy is used for progressive disease. basic knowledge The proportion of illness: 0.005% Susceptible people: no specific population Mode of infection: non-infectious Complications: anemia, lymphoma, leukemia
Cause
Cause of macroglobulinemia
Genetic factors (40%):
Macroglobulinemia accounts for about 2% of all hematological tumors and is a rare disease. The incidence of Caucasians is higher, while African descent only accounts for 5% of all patients with macroglobulinemia. There are a large number of reports on familial diseases, including macroglobulinemia and other generations of B lymphoproliferative disorders, and genetic factors are important. Study and observation of 181 patients with macroglobulinemia, about 20% of their first-degree family members have macroglobulinemia or other B-cell diseases, and healthy relatives are also susceptible to other immune diseases, with low gamma globulin blood. Symptoms, hypergammaglobulinemia (especially polyclonal lgM), produce autoantibodies (especially for the thyroid), and increase the number of active B cells. Whether it is related to environmental factors is not certain.
Infection (35%):
Chronic antigenic stimulation caused by autoimmune diseases or special occupational exposures is not clearly associated with macroglobulinemia. Whether it is related to viral infection remains to be determined. There is still debate about the correlation between HCV, HHV-8 and macroglobulinemia.
Pathogenesis
Although a number of studies in genetics have a limited number of cases, it has also been shown that there are many chromosome numbers or structural abnormalities in patients with macroglobulinemia.
The common number of abnormalities are 17, 18, 19, 20, 21, 22, X and Y chromosome deletions, and the increase in the number of chromosomes 3, 4, and 12 has also been reported. There is a 6q21-22 deletion in 40-90% of patients with macroglobulinemia, especially in patients with a family history. This region may contain several tumor suppressor genes, of which BLIMP-1 is a major regulatory gene involved in lymphoplasmacytic differentiation.
However, macroglobulinemia does not have the recombination of the lgH switch gene, and this finding can be used to identify macroglobulinemia and lgM myeloma with lgH switch recombination as the main feature. Macroglobulinemia Bone marrow clonal B cells are differentiated from small lymphocytes with a large amount of immunoglobulin deposits on the surface to lymphoplasma cells, and then to clones of mature plasma cells containing immunoglobulins in the cytoplasm. .
Sometimes, clonal B cells can be detected in peripheral blood B lymphocytes, and the number thereof is increased in patients with drug resistance or disease progression. These clonal blood cells have a special ability to automatically differentiate into plasma cells when cultured in vitro.
Prevention
Macroglobulinemia prevention
The treatment of this disease is based on the severity of the patient's condition, and different treatments are given at different times. If the patient is asymptomatic, he or she can remain stable for many years without treatment, and only close follow-up is required. Early symptomatic treatment of patients with own disease is a necessary means to reduce mortality and prolong survival.
Complication
Macroglobulinemia complications Complications anemia lymphoma leukemia
The main complications were disease progression, anemia, hemorrhage, infection, and some patients died of acute myeloid leukemia due to the development of diffuse large cell lymphoma (Richter syndrome).
Symptom
Symptoms of macroglobulinemia common symptoms bleeding tendency weight loss fatigue chronic renal insufficiency lymph node enlargement blood viscosity increased thrombocytopenia visual impairment
For elderly patients, there are anemia, hemorrhage, hyperviscosity, renal insufficiency, etc., in addition to common fatigue, weakness, weight loss and other symptoms.
More common in men, with an average age of 63 years. Common symptoms are fatigue, weakness, weight loss, episodes of bleeding and high viscosity syndrome.
Physical examination revealed lymphadenopathy, hepatosplenomegaly, purpura and mucosal hemorrhage, peripheral sensory neuropathy, and Raynaud's phenomenon.
Anemia is the most common clinical manifestation, with 80% of patients having anemia at the time of diagnosis. The causes of anemia are various, including hematopoietic function inhibition, red blood cell destruction acceleration, and blood loss.
Hemorrhage often manifests as nasal, oral mucosal hemorrhage, skin purpura, and visceral or cerebral hemorrhage in the advanced stage. Hemorrhage is caused by the combination of monoclonal lgM with various coagulation factors or covering the surface of platelets, affecting the function of blood coagulation factors and platelets.
Hyperviscosity syndrome occurs when serum viscosity is above 4 times normal. Common symptoms include headache, visual impairment, abnormal mental state such as confusion or dementia, and changes in consciousness can progress to coma, ataxia or nystagmus.
Congestive heart failure.
Ophthalmoscopy examines retinal vein-sausal changes, retinal hemorrhage, and papilledema.
Changes in the nervous system can have peripheral neuropathy and localized central nervous system damage. Peripheral neuropathy is the most common, limb sensation and dyskinesia are symmetrical, sensory dysfunction is often more important than dyskinesia, lower extremity symptoms often appear first, and often heavier than upper limbs. The incidence of renal insufficiency in this disease is significantly lower than that of multiple myeloma, and this-week proteinuria is also rare.
Examine
Examination of macroglobulinemia
The disease needs to be checked as follows:
Blood routine examination, bone marrow routine examination, cytochemical staining, serum immunological examination, erythrocyte sedimentation rate, urine examination, renal function examination, cryoglobulin examination, tissue biopsy.
Laboratory examination: elevated serum lgM (usually >30mg/ml), 75% of cases of monoclonal lgM have light chain, normal or reduced immunoglobulin in serum, most patients with elevated serum viscosity, but only 20 % had high viscous syndrome, 80% of patients had normal cells with normal pigmented anemia, and most patients had no significant reduction in white blood cell and platelet counts at the time of diagnosis. Tumor B cells are monoclonal and express B cell surface antigens (such as CD19, CD20, CD24), and tumor B cells also express CD5, CD10 (CALLA), CD11b, CD9.
Bone marrow biopsy is common: lymphocytes, plasmacytoid lymphocytes or plasma cells infiltrate. Prolonged thrombin time, prothrombin time and activated partial thromboplastin time can be extended. Although proteinuria is common this week, only 3% of patients exceed 1g/24h, which is of little significance. About 60% of patients with macroglobulinemia have elevated b2-microglobulin (3 mg/l).
Diagnosis
Diagnosis and diagnosis of macroglobulinemia
Diagnostic criteria
Clinical manifestation
(1) Elderly patients with unexplained anemia and bleeding tendency.
(2) Central and/or peripheral nervous system symptoms.
(3) Visual impairment.
(4) Renault phenomenon.
(5) Liver, spleen, and swollen lymph nodes.
2. Laboratory examination
(1) The monoclonal IgM in serum is >30/L.
(2) There may be anemia, white blood cells and thrombocytopenia, and a small number of atypical plasma cells may appear in the periphery.
(3) Lymphoid plasma cell infiltration in the bone marrow, liver, spleen and lymph nodes.
(4) Increased blood viscosity.
(5) Fundus hemorrhage or varicose veins.
For some heavier cases, it should be differentiated from multiple myeloma, chronic lymphocyte blood disease and lymphoma.
