Patient's question:
Checked for hemophagocytic lymphohistiocytosis last Tuesday and currently in the fever stage, vomiting everything I eat.Doctor's answer:
Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic lymphocytosis, is classified as type II histiocytosis and includes familial and secondary types. Familial hemophagocytic lymphohistiocytosis (FHLH) is a rare autosomal dominant genetic disorder. Infants are typically born healthy but may suddenly develop high fever, jaundice, bleeding, and hepatosplenomegaly between 6 months and 1 year of age, with convulsions occurring in a minority of cases. Approximately 50% of cases have a positive family history, and the clinical course is often fatal. Untreated patients have a median survival of 2 months. It is caused by a genetic defect on chromosome 10, and it is usually considered FHLH in individuals under 2 years of age. Secondary HLH can be categorized as infection-related or tumor-related. Historically, it was believed that infection-related HLH was primarily caused by viral infections such as cytomegalovirus, herpes simplex virus, varicella-zoster virus, influenza virus, and human parvovirus B19. However, it is now recognized that the disease can also be caused by enteric Gram-negative bacteria, Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus, Brucella, fungi, and Leishmania donovani. Tumor-related HLH occurs in patients with hematologic or non-hematologic malignant diseases, resulting from increased susceptibility to infections due to the malignancy itself and immunosuppression caused by chemotherapy or radiation therapy. Systemic lupus erythematosus and children with congenital immunodeficiencies can also develop this condition. The most significant pathological feature of HLH is the benign proliferation of histiocytes accompanied by hemophagocytosis, commonly observed in lymphatic sinuses and medullary cords of lymph nodes, liver sinusoids, portal veins, red pulp of the spleen, and bone marrow. During the acute phase, the disease may resemble leukemia, malignant histiocytosis, or infectious mononucleosis. Moreover, not all cases will show hemophagocytic cells on the first bone marrow aspiration, and multiple site aspirations may be required for diagnosis. The treatment and prognosis of HLH depend on the disease type. Current treatments primarily include: (1) intravenous immunoglobulin (IVIG), corticosteroids, or high-dose methylprednisolone pulse therapy; (2) specific T-cell activation inhibitors like cytotoxic T-lymphocyte-associated protein 4 (cytA) or combined with granulocyte colony-stimulating factor (G-CSF); (3) chemotherapy to reduce or inhibit lymphokine supply; and (4) hematopoietic stem cell transplantation or plasma exchange after chemotherapy. In 1994, the International Histiocytosis Society recommended the HIM-94 protocol: chemotherapy combined with immunotherapy (etoposide + corticosteroids + cytA) + methotrexate intrathecal injection.Treatment Recommendations:
a. Chemotherapy: Commonly used cytotoxic drugs include vinblastine or vincristine in combination with corticosteroids. Repeated plasma exchange or the combination of VP16 or VM26 with corticosteroids may also be used. Some cases have achieved good results with VP16, corticosteroids, intrathecal methotrexate (MTX), and cranial irradiation. Others advocate low-dose maintenance therapy with the aforementioned drugs during remission.
b. Immunotherapy: Cyclosporine A has shown satisfactory effects in treating familial HLH. Similarly, antithymocyte globulin (ATG) can also induce remission.
c. Hematopoietic stem cell transplantation: Although the above chemotherapies can induce remission, with some cases lasting for 9 years, they do not provide a definitive cure for familial HLH. Fisher et al. (1986) first reported successfully treating familial HLH with bone marrow transplantation. At the 2000 International Pediatric Hematology and Oncology Conference in Shanghai, Japanese scholar Imashuk reported on five cases of EBV-induced HLH treated with hematopoietic stem cell transplantation, followed by cyclosporine A and VP16, significantly improving the prognosis of the disease.