Overview.
Hemophagocytic syndrome, also known as phagocytic lymphoid tissue hyperplasia syndrome, is a group of disorders characterized by excessive inflammatory responses due to genetic or acquired immune deficiencies. It is not a simple disease per se, but a clinical condition.
Etiology and pathogenesis.
When the immune system of the body is stimulated by a certain antigen, tissue cells, natural killer cells, and killer T lymphocytes are activated and interact with each other to produce large amounts of inflammatory and chemotherapeutic factors. The activated phagocytes in human body are a double-edged sword, on the one hand, they can engulf invading bacteria and aging cells in the body like cleaners and remove harmful substances in the body, and play a protective role in the body, and this immune response can be terminated by the organism in time; on the other hand, in patients with impaired immune function, the inflammatory response is overactive and cannot be terminated in time, and the phagocytes On the other hand, in patients with impaired immune function, the inflammatory response is overactive and cannot be terminated in time, and phagocytes will devour the useful cells of the body regardless of the enemy, causing damage to multiple organs throughout the body. Phagocytic syndromes are divided into two categories: primary (familial) and secondary (acquired).
Clinical manifestations and laboratory tests.
Typical clinical manifestations include fever, hepatosplenomegaly and hematocrit. Other rare ones include lymph node enlargement, rash, jaundice, edema, and central nervous system symptoms. Laboratory tests include hypertriglyceridemia, hypofibrinogenemia, abnormal liver function, elevated transferrin, elevated transaminases, hyponatremia, elevated protein in the cerebrospinal fluid, and moderate lymphocytosis. Histopathology reveals widespread accumulation of lymphocytes, macrophages, and sometimes phagocytes in the liver, spleen, enlarged lymph nodes, bone marrow, and cerebrospinal fluid.
Diagnosis and differential diagnosis.
Early clinical manifestations are non-specific and lack characteristic examination indices, making it easy to misdiagnose and miss the diagnosis.The diagnostic criteria for HPS proposed in 1991 were suggested by the Histocyte Society based on clinical manifestations, laboratory and histopathological manifestations.The revised diagnostic guidelines in 2004 built on the original 5 guiding principles.
1, fever.
2. splenomegaly.
3, hemocytopenia with lineage 2 or 3 reduction in peripheral blood.
4, hypertriglyceridemia or hypofibrinogenemia.
5, the bone marrow, spleen or lymph nodes found phagocytosis phenomenon based on the addition of three other criteria
6, reduced or complete absence of NK cell activity.
7, hypoferritinemia.
8, elevated levels of soluble interleukin receptors. The diagnosis is made by having 5 or more of the above 8 items.
Many of the early clinical manifestations and cytology of HPS may not match, but as the disease progresses, typical clinical features may appear one after another. Therefore, patients with persistent high fever, enlarged liver, spleen and lymph nodes, and reduced peripheral blood two or three lines should be alerted to the possibility of HPS. The main diseases that need to be differentiated from this disease are acute leukemia and malignant histiocytosis, which can be identified by bone marrow aspiration and flow cytology.
Treatment.
HPS is a fatal disease, whether primary or secondary, and if not intervened in a timely manner is prone to progression to multiorgan functional impairment with a high mortality rate. treatment of HPS should involve early identification of the underlying cause and prompt administration of appropriate therapy. If the cause is infectious, intensive anti-infective or gammaglobulin therapy should be administered depending on the possible pathogen (bacteria, virus, fungus, etc.). Initial treatment may include corticosteroids to control excessive inflammatory response, and early initiation of etoposide containing therapy may be considered if clinical symptoms are progressively worse. HLH-94 and its revised protocol HLH-2004 is based on dexamethasone, cyclosporine, and etoposide as the main therapeutic agents, with a total treatment duration of 40 weeks. Hematopoietic stem cell transplantation is considered to be the only treatment currently available to achieve long-term remission or even cure in patients with HPS. For patients with definite diagnosis of HPS, if there is an HLA-matched donor, HSCT is recommended as soon as possible after achieving complete remission. For secondary patients with effective initial treatment, transplantation can be suspended and should be performed as soon as the disease is prolonged, relapses or treatment is ineffective.
Prognosis.
HPS has aggressive symptoms, high mortality rate, poor prognosis and very low survival rate before the application of chemotherapeutic drugs and immunosuppressive therapy. The prognosis of HLH is related to the primary disease, and the presence of CNS involvement and persistent reduced NK cell activity predicts a poor prognosis.