Heavy chain disease

Introduction to heavy chain disease Heavy chain disease (HCD) is a malignant tumor of lymphoplasmacytic cells. It is characterized by the malignant proliferation of monoclonal lymphoblast cells, which synthesizes and secretes a large number of monoclonal immunoglobulins with structurally incomplete molecular structure. The chain is composed without the light chain. basic knowledge The proportion of illness: 0.001% Susceptible people: no specific population Mode of infection: non-infectious Complications: renal failure, fracture

Cause of heavy chain disease

(1) Causes of the disease

The specific cause is still unclear. It is known that this group of diseases is caused by the mutation of B lymphocytes, which makes the function of synthesizing immunoglobulin disorder, so that only HC is produced or defective HC is produced, and light chain (LC) and HC can not form a complete immunoglobulin, a large number of non-immune HC in the plasma, the pathogenesis of renal damage may be similar to the pathogenesis of primary amyloidosis or light chain deposition disease.

1. heavy chain disease This disease is about 1/4 of patients with heavy chain disease complicated by autoimmune diseases, rheumatoid arthritis is the most common, followed by autoimmune hemolytic anemia, Sjogren's syndrome, systemic erythema Lupus, vasculitis, idiopathic thrombocytopenic purpura and myasthenia gravis, etc., autoimmune diseases can promote the progression of the disease, suggesting that chronic antigen stimulation may be related to the pathogenesis of the disease, a small number of patients may have tuberculosis and History of chronic cholecystitis, or years of high gamma globulinemia before diagnosis of this disease.

2. heavy chain disease This disease is the most common type of heavy chain disease, parasitic, bacterial, viral and other areas of intestinal infection are the predilection areas of this disease, indicating that its cause is related to infection, in addition, the disease may be Related to genetic factors, tumor viruses may also play a certain pathogenic role. The former affects genes, resulting in inconsistency between IgA heavy and light chains. Cytogenetics found that there are 14q32 and 9p11 complex translocations in alpha heavy chain disease.

3. The majority of patients with -heavy chain disease have a history of chronic lymphocytic leukemia or non-Hodgkin's lymphoma.

(two) pathogenesis

The pathogenesis of renal damage may be similar to the pathogenesis of renal damage in primary amyloidosis or light chain deposition disease. Due to mutation and abnormal proliferation of plasma cells, synthetic dysfunction, only the heavy chain or defective of immunoglobulin The heavy chain cannot form a complete immunoglobulin molecule with the light chain, resulting in a large number of free immunological heavy chains in the serum and urine, called heavy chain disease.

Heavy chain disease prevention

The disease is a malignant disease, and the condition often develops irreversible. The purpose of prevention is to delay the development of the disease and prolong the survival of the patient. The main measures are active anti-infective treatment, strengthen support for symptomatic treatment, especially for those with renal failure. Patients with end-stage renal failure require dialysis or kidney transplantation.

Heavy chain disease complications Complications, renal failure, fracture

Infection, renal failure, and pathological fractures are the main complications of this disease. Early treatment should be actively treated to prevent it.

1. heavy chain disease This disease is about 1/4 of patients with heavy chain disease complicated by autoimmune diseases, rheumatoid arthritis is the most common, followed by autoimmune hemolytic anemia, Sjogren's syndrome, systemic erythema Lupus, vasculitis, idiopathic thrombocytopenic purpura and myasthenia gravis.

2. The stage of alpha heavy chain disease can evolve into reticulocyte sarcoma or immunoblastic sarcoma.

3. A small number of patients with heavy chain disease may have amyloidosis, pathological fractures and lymphoma-like lesions.

Symptoms of heavy chain disease Common symptoms Dyspnea, osteolytic damage, intestinal perforation, lymph node enlargement, hepatosplenomegaly, renal failure, skin itching, pleural effusion

1. heavy chain disease (Selingman disease) The age of onset of this disease is relatively mild, and the clinical symptoms can be classified into two types: intestinal type and lung type. The most common clinical manifestation is the intestinal type which is characterized by severe malabsorption syndrome. The disease is progressive, with intermittent diarrhea in the early stage, and later manifested as persistent diarrhea, accompanied by abdominal pain, steatorrhea, late weight loss, dehydration, intestinal obstruction, intestinal perforation, ascites, abdominal mass, fever, rare, liver and spleen Most of the lymph nodes are not swollen. It is rare that the lungs are characterized by repeated respiratory infections, and there may be pleural effusion and mediastinal lymphadenopathy.

Intestinal type (also known as immunoproliferative small bowel disease, IPSID) often manifests as progressive malabsorption syndrome with intractable diarrhea, weight loss, dehydration and hypokalemia and hypocalcemia, some patients may have abdominal pain or mental retardation, intestinal meal Examination showed that the small intestine mucosa thickened, rough, narrow or dilated lumen, most patients with lesions confined to the lamina propria of the small intestine, involving the rectum, stomach, and even disseminated to the bone marrow and the posterior nasal cavity, the disease generally does not invade the liver, spleen and surrounding Lymph nodes.

Lung type is rare, old age and children have reported, the main symptoms are dyspnea, but without cough, cough and fever, lung X-ray showed a point-like shadow, resembling alveolar fibrosis, mediastinal lymph nodes can also be swollen, Half of the patients have skin itching, early benign hyperplasia, and later can evolve into reticulocyte sarcoma or immunoblastic sarcoma.

2. heavy chain disease (Frankin disease) heavy chain disease is the earliest discovered heavy chain disease, its clinical features are the blood and urine of the patient can detect the monoclonal heavy chain, due to the clinical and pathological manifestations of the disease The variation is large, and some people divide the disease into three categories:

1 disseminated lymphoproliferative lesions;

2 local lymphoproliferative lesions;

3 no obvious lymphoproliferative lesions, the clinical manifestations of this disease are:

(1) swollen lymph nodes: more common in the neck, armpits, can also be seen in the clavicle, submandibular and groin, the disease can be advanced in the superficial lymph nodes, swollen lymph nodes, no adhesion, no tenderness A small number of patients may only have deep lymphadenopathy, and the lymph nodes of the pharyngeal lymphatic ring may cause upper eyelids, edema and edema, resulting in difficulty in breathing.

(2) Hepatosplenomegaly: 50%, 60% of cases can be seen liver or spleen enlargement.

(3) Other symptoms: manifested as fever, skin damage of subcutaneous nodules, 1/3 cases may be associated with autoimmune diseases such as SLE, rheumatoid arthritis, hemolytic anemia, etc., also showing thyroid, parotid and other parts Extramedullary plasmacytoma.

3. The clinical manifestations of heavy chain disease may have fever, anemia, hepatosplenomegaly, and a few may have bone marrow destruction and pathological fracture.

4. Heavy chain disease has multiple myeloma, characterized by renal failure, osteolytic damage in the skull, and abnormal plasma cells in the bone marrow.

Inspection of heavy chain disease

1. Peripheral blood alpha heavy chain disease, heavy chain disease often has mild to moderate anemia, gamma heavy chain disease in almost all cases have mild or moderate anemia, some have severe anemia, some cases can see leukopenia and neutropenia The classification shows atypical lymphocytes, plasma cells and eosinophils, and 15% to 25% of cases can have thrombocytopenia at the same time.

2. In a few cases of Coomb's test, there may be autoimmune hemolytic anemia with positive Coomb's test.

3. Serum protein examination The serum protein electrophoresis of -heavy chain disease showed an abnormally wide band between 2 and regions. Immunoelectrophoresis showed abnormal protein reacted with anti- heavy chain antiserum, but not with light resistance. Chain serum reaction, heavy chain disease mostly belongs to 1 subtype. Because this disease can not synthesize light chain, urine-peripherin is negative, and serum protein electrophoresis of heavy chain disease is most common in the 1 or 2 region. Electrophoresis shows that abnormal proteins can react with specific anti- heavy chain antiserum, but not with kappa or lambda light chain. heavy chain protein can be divided into 4 subtypes: the most common is 1, followed by 3, It is rare to be 4 and 2. The serum protein electrophoresis of heavy chain disease shows a single plant peak between 2 or . The immunoelectrophoresis shows a fast-moving double-arc curve and reacts with anti- chain serum. Light chain serum does not react. In most cases, the protein in this week can be detected in the urine, mostly in the type. The serum protein electrophoresis of heavy chain disease can be seen in a narrow band between and , which is considered to be the heavy chain of four. Poly, alpha, gamma, and heavy chain diseases can have low egg leukemia and normal immune cells The protein is falling.

4. Bone marrow examination of -heavy chain disease, 60% of cases may have plasma cells, lymphocytes or plasmacytoid lymphocytes, heavy chain disease bone marrow examination with lymphocytosis, accompanied by increased plasma cells, and Most plasma cells have vacuoles.

5. Other examinations of erythrocyte sedimentation rate, alpha heavy chain disease often have low potassium, low sodium and hypomagnesemia.

6. X-ray and endoscopy examination of alpha heavy chain disease: X-ray barium meal examination can be seen duodenum, jejunal mucosal fold hypertrophy and pseudopolyposis formation, may have stenosis or filling need to be defective, liquid level, abdominal CT can show peritoneum Post-lymph node enlargement, fiber endoscopic biopsy has a great diagnostic value for -heavy chain disease. Five basic forms can be seen under endoscopy: invasive, nodular, ulcer, mosaic, simple mucosal fold thickening, above Type 5 can be presented alone or in combination, with the most characteristic of infiltration type. Pathological biopsy can have three manifestations: mature plasma cells and lymphoplasmacytic cells infiltrating the lamina propria, villi atrophy and not fixed; atypical plasma cells or Lymphocytes and/or atypical immunoblast-like cells penetrate at least submucosally; conform to immunoblastic lymphoma or form discrete ulcerative tumors or extensively infiltrate, invading the entire layer of the intestinal wall.

7. Chromosome examination The common chromosomal abnormalities of -heavy chain disease have gene rearrangement in 14q32, and chromosomal abnormalities of -heavy chain disease may manifest as karyotype abnormalities, aneuploidy and complex chromosomal abnormalities.

8. Pathological examination of lymph node pathology of heavy chain disease showed that 38% showed different tissue types of non-Hodgkin's lymphoma, 36% had lymphoplasmacytic hyperplasia, and 11% were plasmacytoma.

Alpha heavy chain disease most often affects the small intestine and is divided into three phases according to its pathological changes:

(1) Stage A: manifested as infiltration of mature plasma cells in the lamina propria of the intestinal mucosa, partial villus atrophy, involvement of the mesentery and retroperitoneal lymph nodes.

(2) Phase B: Atypical plasma cells or atypical immune cells are infiltrated into the submucosa, and the villus structure disappears.

(3) Stage C: It is characterized by obvious immune cell lymphoma in the small intestine and mesenteric lymph nodes, forming a scattered ulcer-type tumor that can penetrate the intestinal wall.

According to the antigenicity of heavy chain structure, it is divided into IgA heavy chain disease ( heavy chain disease), heavy chain disease ( heavy chain disease), IgM ( heavy chain disease), IgD heavy chain disease ( heavy chain disease).

9. According to the condition, do ECG, B-ultrasound, liver and kidney function, electrolytes, gastrointestinaloscopy and other examinations.

Diagnosis and identification of heavy chain disease

diagnosis

1. The endoscopic and biopsy of the duodenum and jejunum of heavy chain disease is the first choice for the diagnosis of this disease. The diagnosis depends on serum immunofixation electrophoresis. The serum protein electrophoresis can be seen between the 2 and regions. In the zone, serum immunoelectrophoresis showed reaction with anti- heavy chain antiserum, but not with anti-light chain serum.

2. The diagnosis of heavy chain disease depends on serum, urine immunoelectrophoresis, and serum immunoelectrophoresis. A heterogeneous abnormal M protein appears between and . This protein can immunoprecipitate with anti- heavy chain and anti-Fc antiserum. It cannot react with anti-Fab, anti-Fd, anti-kappa, anti- serum.

3. Heavy chain disease Where there are clinically abnormal proliferation of lymphoplasmacytic cells and obvious vacuoles in the plasma cytoplasm of the bone marrow, hematuria immunoelectrophoresis is required. If the urine-peripherin is positive, serum protein is electrophoresed in the 2 region or Single-factor peaks appear between and , and serum immunoelectrophoresis shows a fast-moving double-arc curve, which can be diagnosed by reacting with anti- chain serum and not reacting with anti-light chain serum.

4. Heavy chain disease serum protein electrophoresis showed a small narrow band between 2 and . Serum immunoelectrophoresis showed chain and lack of light chain.

Differential diagnosis

1. Malignant lymphoma Malignant lymphoma is mostly elevated by multiple peak immunoglobulins, and lymph node pathology can confirm the diagnosis.

2. Multiple myeloma multiple myeloma clinically has bone pain, osteolytic damage, renal dysfunction, bone marrow is mainly malignant plasma cell proliferation, serum M protein is mainly IgG, IgA, IgD or light chain see.

3. Primary macroglobulinemia Primary macroglobulinemia serum IgM is significantly elevated, abnormal lymphocytes, plasma cells, lymphoplasmacytic cells and infiltration in the bone marrow and lymph nodes, can Identification with heavy chain disease.

4. Immunoproliferative small intestinal disease (IPSID) The epidemiology of intestinal type -HCD and IPSID, involving organs, clinical manifestations, pathological examinations and treatments are similar, the diagnosis of IPSID reported in the literature only Relying on small bowel biopsy, regardless of whether -HCD protein is found in serum, it is reported that -HCD protein is present in the serum of about 65% of IPSID patients. This part of the patient is -HCD. In recent years, IPSID is considered to be a mucosa-associated A special form of lymphoma (MALT).

5. Chronic lymphocytic leukemia mainly needs to be differentiated from -HCD and -HCD, because anemia, lymph node and hepatosplenomegaly are their common clinical manifestations, and -HCD can also be associated with slow-leaching, the following Points help to identify the two.

(1) The patients with chronic bleed were characterized by a significant increase in peripheral blood and mature lymphocytes of the bone marrow, whereas in HCD patients, only lymphocytes or plasma cells were slightly elevated.

(2) In the lymph node pathology, the structure of the slow lymph node was replaced by a large amount of mature lymphocyte infiltration, and the latter lymph node structure showed many chronic inflammation changes.

(3) Although M protein is present in the serum of some patients with CLL, most of them are intact monoclonal immunoglobulins, while the M protein of HCD patients is a monoclonal free incomplete heavy chain.

(4) For patients with blood and no M protein found in the urine, sometimes lymph node or bone marrow pathological immunohistochemistry is the fundamental means to identify them.

6. Intestinal tuberculosis is mainly differentiated from intestinal type -HCD. Clinically, chronic diarrhea, malabsorption, progressive consumption, fever, anemia and increased erythrocyte sedimentation rate are common in both, and intestinal tuberculosis patients can also express bone marrow plasma cells. Increased sex, serum, urine and small intestinal fluid M protein identification is the key to identify the two, fiber endoscopy and small bowel biopsy is also the fundamental means of differential diagnosis of the two, if necessary, the clonal identification of bone marrow plasma cells also help identify, in addition, Intestinal tuberculosis patients generally have no proteinuria, serum polyclonal immunoglobulin concentration is often increased, while intestinal type -HCD patients with proteinuria are common, serum polyclonal immunoglobulin concentration is often reduced.

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