Pure red cell aplasia (PRCA) is a group of disorders characterized by impaired bone marrow hematopoiesis of the pure red lineage and reduced peripheral blood reticulocytes and mature red blood cells (with essentially normal white blood cells and platelets). Congenital PRCA is also known as Diamond-Blackfan anemia (DBA). I. Etiology and pathogenesis Various factors, such as viruses, thymomas, drugs, lymphoproliferative disorders and autoimmune diseases, cause a decrease in the number of cells in various stages of the red lineage due to disorders of the red lineage progenitor cells. In some patients, the disease is primary and no clear cause can be found. It is generally believed that the disease is caused by abnormal immunity through B lymphocytes or/and T lymphocytes, which produce autoantibodies against erythropoietin (Epo), the Epo receptor. It has been demonstrated that plasma from PRCA patients injected into experimental animals inhibits bone marrow red lineage hematopoiesis from its IgG fraction, which inhibits the growth of self and normal red lineage progenitor cells (BFU-E, CFU-E) in a dose-dependent manner, but has no significant effect on the growth of self and normal granulocyte-monocyte progenitor cells (CFU-GM). Electron microscopy revealed that this inhibitory factor was directly attached to the primitive erythrocyte membrane. PRCA is closely related to lymphoproliferative diseases such as thymoma and chronic lymphocytic leukemia. About 20% to 50% of PRCA patients have thymoma, and about 6% have chronic lymphocytic leukemia and autoimmune diseases. Clinical treatment of PRCA with thymectomy, immunosuppressive or killing drugs for T lymphocytes is effective, and it is also thought that T lymphocyte-mediated immune damage to the red lineage hematopoiesis also plays an important role in the pathogenesis of some PRCAs. In addition, γδ T cells have been found to clonally proliferate in the thymus of patients with PRCA and cause an increased proportion of Th2 cells, and NK cells may be associated with the development of some PRCA. The most common infectious factor is microvirus B19, a DNA virus with specific tropism and high affinity for BFU-E and CFU-E, which takes erythrocyte globoside as its receptor. Microvirus B19 invades erythroid progenitor cells and proliferates rapidly, inducing “apoptosis” of BFU-E and CFU-E. “like death. This is commonly seen in cases of immune deficiency or suppression, such as AIDS, or after the application of immunosuppressive drugs or radiotherapy. EBV infection causing PRCA has also been reported. Drugs associated with the development of PRCA, such as isoniazid, chloramphenicol and α-methyldopa, can produce direct toxic effects on BFU-E and CFU-E, and of course no methyldopa can also induce the production of IgG and circulating immune complexes to inhibit erythropoiesis. Some DBAs are associated with mutations in the ribosomal protein (RP) gene, which regulates cell growth, so RP deficiency leads to impaired protein synthesis in many tissues, especially in tissues with high proliferative activity. The following have been identified: RPS19, RPS24, RPS17, RPL5, RPL11, RPL35a. Since many patients with DBA show only erythroid hematopoietic involvement (only partially in embryonic developmental organs), this is not consistent with the presumption that mutations in the RP gene have a general effect. The presence of RPS19 mutations in DBA suggests that RPS19 is involved in early primitive erythroid development, and the introduction of the RPS19 gene into the hematopoietic progenitors of patients with RPS19-deficient DBA results in an exponential increase in the number of BFU-E and CFU-E. Clinical manifestations Common anemia symptoms, such as pale face, weakness, palpitations, shortness of breath after activity, etc. Long-term severe anemia is likely to be complicated by anemic heart disease. Some patients have thymoma, but it is not easily detected by physical examination alone, but often by chest X-ray or chest CT. Complications with other diseases have primary manifestations, such as lymphoproliferative diseases with lymph nodes and splenomegaly. About 10%-25% of patients with DBA have a family history, while the rest are sporadic. 1/3 of patients have autosomal dominant inheritance and the rest have autosomal recessive inheritance. The majority of patients with DBA develop anemia in the neonatal period or infancy, basically within the first year of life, while the white blood cells and platelets are normal. Leukocytopenia, thrombocytopenia, and even complete thrombocytopenia may occur later in the course of the disease. Laboratory tests Orthocytic orthochromic anemia with reduced or absent reticulocytes, normal leukocytes and platelets, normal leukocyte classification, and no pathological hematopoiesis. The bone marrow is well proliferated, but the red lineage is significantly reduced or absent, other systems are generally normal. Some PRCA may have increased gamma globulin, heterophilic antibodies and autoantibodies. Serum iron and serum ferritin are increased, and iron saturation is increased, but iron utilization is low. DBA can detect mutations in the ribosomal protein gene. those with RPS19 mutations often have increased levels of erythrocyte adenosine deaminase, and the presence of RPS19 mutations can be inferred from this index. Diagnosis and differential diagnosis Anemia symptoms and signs, orthocytic orthochromic anemia, reduced reticulocyte count, normal white blood cells and platelets; poorly proliferating bone marrow red lineage, normal granulocyte system and megakaryocyte system are generally diagnostic of the disease. A decrease in BFU-E and CFU-E colonies in cell culture can help diagnose the disease. DBA should be diagnosed based on the following criteria: the presence of lymphoproliferative diseases such as thymoma, CLL, and autoimmune diseases, as well as the history of infections and medications that may trigger the disease. The diagnosis of DBA is based on the following criteria: (1) the presence of orthocytic (or macrocytic) orthochromic anemia in infancy (less than 2 years old); (2) reduced reticulocyte count; (3) marked reduction or lack of bone marrow erythropoietic precursor cells (<< span="">5% of nucleated cells); and (4) normal chromosomal fragility test. PRCA should be distinguished from acute hematopoietic arrest induced by other causes or sudden onset of “remitting crisis” with hemolysis as the underlying disease. It often resolves spontaneously after infection control. Other congenital disorders such as Fanconi anemia, Pearson syndrome and chondro-hair dysplasia syndrome with physical development also need to be differentiated from DBA. V. Treatment 1. Supportive treatment. Severe anemia transfusion of red blood cells, evaluation of body iron load, attention to iron removal treatment. 2. Remove the cause of the disease. Discontinue suspected drugs. Thymoma should be removed as soon as possible, the remission rate can be 25%~50% after surgery. However, thymectomy is not recommended for PRCA without thymoma. Microvirus B19 infection should be treated with timely antiviral or high-dose intravenous immunoglobulin. 3. Immunosuppressive therapy. Adrenocorticotropic hormone is the first-line treatment for PRCA, and the starting dose of prednisone is 1-2 mg/kg?d. The remission rate is about 50%, but the number of persistent patients is small. Most of them require maintenance therapy or change of regimen due to relapse. If continuous use of prednisone for 4-6 months is still ineffective or requires high-dose maintenance, a switch or addition of other immunosuppressive drugs should be considered. Cyclosporine alone or in combination with anti-human thymocyte immunoglobulin has an efficacy of about 50-80%. Cytotoxic immunosuppressive therapies such as cyclophosphamide, azathioprine, and 6-mercaptopurine should be used with caution because of their toxic side effects. High-dose intravenous immunoglobulin inhibits B and T lymphocyte function and blocks Fc receptors in the monocyte macrophage system through feedback immunomodulatory effects. Immunoglobulin also has an anti-infective effect and can be used in patients with microvirus B19 infection. DBA treatment for children with prednisone starts at 60 mg/m2/d, and elevated reticulocytes and hemoglobin are seen after 1 to 2 weeks for those who are effective. The dose is usually reduced when the hemoglobin level reaches 100g/L. If there is no response to the hormone for 3~4 weeks, it is considered an ineffective case and the treatment drug or program is changed promptly. About 60-70% of DBA is effective to glucocorticoids, but the efficiency of RPS19 mutant is only 40% more, and it is more likely to develop transfusion dependence and need allogeneic hematopoietic stem cell transplantation. 4. Allogeneic hematopoietic stem cell transplantation is the only way to cure DBA. Transfusion-dependent DBA should be transplanted early, and HLA-matched sibling donors are preferred. Prognosis The prognosis of secondary PRCA depends on the primary disease, most of which are effective against immunosuppression and have a long survival. However, patients with DBA are prone to complications of multiple malignancies, with AML and MDS being the most common, and once they occur, the prognosis is poor.