What are the causes of hemophagocytic syndrome?

Hemophagocytic syndrome is a very harmful disease that has tremendous adverse effects on the body. This is mainly because the human serum contains inhibitory substances that inhibit the proliferation of hematopoietic progenitor cells, thereby leading to a continuous decrease in beneficial cells in the bone marrow. Hemophagocytic syndrome mostly occurs in infants and young children, and has a strong familial inheritance. This disease has many symptoms, including fever, sweating, hepatosplenomegaly, etc. in the early stages.

1. Causes of Hemophagocytic Syndrome

1. Increase of hemophagocytic cells, accelerating the destruction of blood cells;

2. The presence of inhibitory substances for the proliferation of hematopoietic progenitor cells in the serum, and the progressive decrease in granulocyte and erythroid precursor cells and megakaryocytes in the bone marrow are attributed to the production of inhibitory monokines and lymphokines, such as γ-interferon, tumor necrosis factor (TNF) and interleukin-1, as well as the production of hematopoietic growth inhibitory factor.

2. Etiology and clinical manifestations of hemophagocytic syndrome

Familial hemophagocytic syndrome

The age of onset is generally early, with 70% occurring within 1 year of age. The disease may even occur before birth, with clinical manifestations present at birth. Most cases occur in infancy, but some cases may develop as late as 8 years old. Adult-onset disease does not rule out familial hemophagocytic syndrome.

The age of onset is similar within the same family. Symptoms and signs are diverse. In the early stages, they are mostly fever, liver and spleen enlargement. Some also have rash, lymphadenopathy and neurological symptoms. The fever persists and may subside on its own; the liver and spleen are obviously enlarged and progressive; the rash is non-characteristic and often transient, and is often accompanied by high fever; about half of the patients have enlarged lymph nodes, and some have giant lymph nodes. Symptoms of the central nervous system generally appear in the late stage of the disease, but may also occur in the early stage, manifested as increased excitability, fullness of the anterior fontanelle, neck stiffness, increased or decreased muscle tone, convulsions, etc. There may also be paralysis of the VI or VII cranial nerves, ataxia, hemiplegia or complete paralysis, blindness, impaired consciousness, increased intracranial pressure, etc. Pulmonary symptoms are mostly caused by infiltration of pulmonary lymphocytes and macrophages, but they are difficult to distinguish from infection.

Secondary hemophagocytic syndrome

1. Infection-associated hemophagocytic syndrome (IAHS)

A strong immune response caused by severe infection, lymphohistiocytic hyperplasia accompanied by phagocytosis of hemocytes. This disease often occurs in immunocompromised people. Those caused by viral infections are called virus-associated hemophagocytic syndrome (VAH), but other microbial infections, such as bacteria, fungi, rickettsia, protozoa, etc., can also cause hemophagocytic syndrome. Its clinical manifestations include the common manifestations of hemophagocytic syndrome (as described above) and evidence of infection. Bone marrow examination showed lymphohistiocytic hyperplasia, and phagocytosis of red blood cells, platelets and nucleated cells.

2. Tumor-associated hemophagocytic syndrome

This disease is divided into two categories: one is the hemophagocytic syndrome associated with acute lymphoblastic leukemia (ALL), which may be accompanied by hemophagocytic syndrome with or without infection before or during treatment. In addition to acute lymphoblastic leukemia, secondary hemophagocytic syndrome often occurs in mediastinal seminoma.

The second type is lymphoma-related hemophagocytic syndrome. Lymphoma is often subclinical and has no symptoms of lymphoma, so it is often misdiagnosed as infection-related hemophagocytic syndrome, especially Epstein-Barr virus-related lymphoma.