Methotrexate-Associated Lymphoproliferative Disorders

Introduction to methotrexate-associated lymphoproliferative disorders Methotrexate-associated lymphoproliferative disease refers to the long-term use of the immunosuppressant methotrexate (MTX) in individuals (autoimmune diseases such as rheumatoid arthritis, psoriasis and dermatomyositis) Lymphoid tissue proliferation or lymphoma. basic knowledge The proportion of illness: 0.00035% Susceptible people: no special people Mode of infection: non-infectious Complications: lymphoma

Methotrexate-related causes of lymphoproliferative disorders

Cause:

Nearly two-thirds of patients have spontaneous or partial remission after discontinuation of MTX, suggesting that the disease is closely related to MTX, but epidemiological investigations show that 85% of the cases are found in patients with rheumatoid arthritis (RA). In patients with RA who are treated with MTX, the estimated risk of lymphoma is 2 to 20 times higher than that of the normal population, so whether or not MTX itself increases the risk of developing lymphoma is still controversial.

Although tumor cell EBV is positive in about 50% of cases, a case-control study showed that the positive rate of EBV in patients with RA-associated lymphoma was not higher than that in patients without lymphoma, suggesting that lymphoma occurs in RA patients. Immunosuppression is not related, therefore, the pathogenesis of this disease needs further study.

Methotrexate-related lymphoproliferative disease prevention

There is no effective preventive measure for this disease. Early detection and early diagnosis are the key to the prevention and treatment of this disease.

Methotrexate-related complications of lymphoproliferative disorders Complications lymphoma

1. Explosive infectious mononucleosis associated with virus-associated hematophagocytic syndrome (VAHS) accounts for 58%, the most common. It happened between 5 and 17 years old. It is characterized by a large proliferation of CD8+ T cells, EBV-infected B cells and macrophages and infiltration in various organs of the body, resulting in fulminant hepatitis and poor myeloproliferative. Other affected tissues have extensive white matter necrosis of the spleen, infiltration of mononuclear cells around the cerebrovascular, mild mononuclear myocarditis, mild interstitial nephritis and thymocyte deficiency and endothelial cell necrosis. Liver failure is a common cause of death. VAHS occurs in 90% of FIM boys and nearly half of XLP children. Tissue cell infiltration, which is extensively engulfed by red blood cells and nuclear debris, is characteristic of VAHS, and most die within 1 month after EBV infection.

2. The abnormality of gamma globulin accounts for 31%. This type is more common. After EBV infection, there are often different degrees of low IgG and IgM. Necrosis, calcification, and loss can occur in lymphoid tissues (lymph nodes, spleen white matter, thymus, bone marrow).

3. Lymphoid malignancies account for 30%. Lymphoma always occurs outside the lymph nodes, most often invading the intestinal ileocecal zone, with less involvement in the central nervous system, liver and kidneys. Pathology is usually Burkitt type, a few are Hodgkin's lymphoma; most are B-celled, and a few are T-cell.

4. Aplastic anemia accounts for 3%. A small number of children develop simple aplastic anemia (complete blood cell anemia or pure red blood cell aplastic anemia) after EBV infection, and their pathogenesis is poorly known.

5. Lymphomatoid granuloma in the blood vessels and lungs accounted for 3%. Development of lymphangiitis caused by aneurysm or arterial wall dilatation damage. It can be expressed as lung T cells and central nervous system lymphomatoid granuloma. Lymphocyte proliferation is primarily a result of CD4+ T cell activation and may be unrelated to EBV infection.

Methotrexate-related symptoms of lymphoproliferative disorders Common symptoms Subcutaneous nodular persistent pain

40% of cases involve extranodal tissues, including the gastrointestinal tract, skin, lungs, kidneys, and soft tissues. In each tissue type, the extranodal involvement rate is different: diffuse B-cell lymphoma (DLBCL) is 50%, Hodgkin's lymph The tumor (HL) was 20%, the follicular lymphoma was 40%, the lymphoplasmacytic lymphoma or atypical lymphoplasmacytic infiltration was 100%, and other clinical manifestations of the same type of lymphoma unrelated to MTX were indistinguishable.

Examination of methotrexate-associated lymphoproliferative disorders

Cell morphology and histopathology, the most common tissue type in the reported cases is DLBCL, accounting for 35%, other tissue types including HL (25%), HL-like lymphoproliferative disease LPD (8%), follicles Lymphoma (10%), BL (4%), peripheral T-cell lymphoma (4%), in addition, about 14% of cases showed pleomorphic small lymphocytes or lymphoplasmacytic infiltration.

In cellular immunology, the cellular immunophenotype of this disease is essentially the same type of lymphoma as MTX. HL-like LPD tumor cells are CD20 and CD30, but CD15-, whereas HL tumor cells are CD15.

Cellular and molecular genetics, the same type of lymphoma that is not associated with MTX.

Diagnosis and identification of methotrexate-associated lymphoproliferative diseases

A long history of drug use of methotrexate, with the corresponding symptoms and histological examination, can be diagnosed.

Mainly identified with lymphoma, the main point of identification is through cellular immunology.

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