If these three symptoms occur, you need to be highly alert to hemophagocytic syndrome!

Author: Wang Zhao, Chief Physician, Beijing Friendship Hospital, Capital Medical University

Reviewer: Zhi Xiuyi, Chief Physician, Xuanwu Hospital, Capital Medical University

When people hear the name hemophagocytic syndrome, they understand the literal meaning, which is that the blood cells are being swallowed and eaten.

This is indeed the case, because at the beginning, it was discovered that macrophages can phagocytose blood cells, leading to a decrease in blood cells, so the disease was named hemophagocytic syndrome. However, in 2004, its formal international name was changed to hemophagocytic lymphohistiocytosis.

Why did we change the name? Because we realize that the more important cause of this disease is the life-threatening inflammatory factor storm. This inflammatory factor is mainly secreted by the abnormal activation and proliferation of lymphocytes, monocytes and macrophages. It has a negative regulation on the bone marrow, inhibits the growth and proliferation of bone marrow hematopoietic cells, and leads to a decrease in blood cells.

Of course, excessive activation of macrophages will engulf some normal blood cells and even hematopoietic stem and progenitor cells, which is also one of the reasons for blood cell reduction.

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Many ordinary people believe that benign diseases are generally not a big problem, and malignant diseases are life-threatening. In fact, this is not the case. In essence, hemophagocytic syndrome is not a malignant disease, but it is often more dangerous than malignant diseases and causes death more quickly.

According to the cause, hemophagocytic syndrome can be divided into primary hemophagocytic syndrome and secondary hemophagocytic syndrome.

Primary hemophagocytic syndrome has a clear genetic defect, which eventually leads to the onset of the disease. Such patients often have a family history and generally require allogeneic hematopoietic stem cell transplantation.

Secondary hemophagocytic syndrome is often caused by patients who have undergone genetic and functional testing, and no clear primary hemophagocytic syndrome gene defect has been found according to current standards. It usually has clear causes, such as secondary to infection factors, tumor factors, rheumatic immune disease factors, organ transplantation or some metabolic diseases, and some drug-induced hemophagocytic syndrome, so there are many causes.

The direct cause of death of patients with tumor-induced hemophagocytic syndrome is often the tumor-induced inflammatory factor storm, which leads to organ failure and death.

There is some controversy internationally on how to suspect or consider hemophagocytic syndrome at an early stage, but generally speaking, there are three mainstream views:

The first point is fever of unknown cause. This means that the patient has a persistent fever, but it is difficult to explain this persistent and uncontrollable fever with a certain cause, such as fungal infection, bacterial infection or rheumatism.

The second point is unexplained hepatosplenomegaly or impaired liver function. There is no hepatitis, no drug-induced damage, and no other reasons to explain this liver function damage and hepatosplenomegaly.

The third point is unexplained blood cell reduction, which means that two or more blood cell lines have decreased, but the patient has undergone many tests such as bone marrow puncture, and the cause of the blood cell reduction cannot be clearly found.

Figure 2 Original copyright image, no permission to reprint

When these three points are met, hemophagocytic syndrome should be considered. At this time, various specific tests should be completed as soon as possible, such as serum ferritin detection, soluble CD25, NK cell activity, etc. After a clear diagnosis, treatment can be started as soon as possible.

Early diagnosis and early treatment are the most important aspects to cure or improve the efficacy of hemophagocytic syndrome.

Hemophagocytic syndrome is an interdisciplinary disease.

The investigation found that 1/3 or 1/4 of the patients first visited the liver disease department because of fever and abnormal liver function. After examination, they found a decrease in blood cells and suspected hemophagocytic syndrome, so they went to the hematology department for treatment.

But for the final treatment, hematology is more suitable. Why? Because many patients need transplantation, cytotoxic drugs and chemotherapy drugs, and hematology has more experience in this area.

However, there are some patients with hemophagocytic syndrome associated with rheumatism. These patients may only need to be treated in the rheumatology department. This is because hemophagocytic syndrome associated with rheumatism is treated with hormone shock therapy in the early stages, and cytotoxic drugs are considered only if the effect is not good.

There are also some pregnancy-related hemophagocytic syndromes, which are very dangerous. If diagnosed and treated in time, both mother and child can be safe. However, if the diagnosis and treatment are not timely, both the child and the mother will be in danger of death.

Therefore, it is an interdisciplinary disease, not only related to hematology and pediatrics, but also to infectious diseases, ICU, hepatology, rheumatology and immunology, and even obstetrics and gynecology.