He was only 21 years old, just in the days of youth, but now he was lying in the intensive care unit, with various tubes and instruments attached to his body, depressed, shortness of breath, and subcutaneous bleeding spots everywhere in his body. The grief-stricken mother could not understand how, although her son had a rheumatic disease called polymyositis two years ago, but after treatment has been controlled and stable, to the hospital to check the indicators are also normal; just because a month ago and the usual fever, and then has been high fever does not go away, a lot of injections are useless, slowly became this way, the local hospital can not do anything, had to be transferred to the The local hospital could not do anything, so we had to transfer to a big hospital in the provincial capital. The local hospital did nothing, so he had to be transferred to a large hospital in the provincial capital. This investigation was remarkable, as many internal organs were severely damaged: liver failure, pneumonia, pleural effusion, extremely low platelets, skin and mucous membrane bleeding. During the discussion, a doctor reminded the local hospital that a bone marrow aspiration had been performed before the patient was transferred to the hospital, and when he called, he found “phagocytosis” in the bone marrow. Hearing this result, everyone’s heart felt a chill, so the young man had a rare but very dangerous complication of rheumatic immune disease – macrophage activation syndrome, or MAS! What is this MAS demon that has left the local hospital helpless and the doctors in the provincial hospital puzzled? Macrophage activation syndrome (MAS) is a rare but serious rheumatic complication characterized by excessive macrophage activation and a non-malignant proliferation of lymphocytes and histiocytes resulting in a “cytokine storm” as the basis for its pathogenesis, with progressive exacerbation and potentially life-threatening conditions. It is most common in systemic juvenile idiopathic arthritis, followed by systemic lupus erythematosus (SLE) and adult Still’s disease (AOSD), then rheumatoid arthritis, polymyositis, etc. How do we understand the concept of “macrophage hyperactivation” and “non-malignant proliferation of lymphocytes and histiocytes”? The human immune system and cells are activated by endogenous or exogenous stimuli and produce a large number of cytokines to initiate the immune process to clear the threat to the body. This immune process is regulated, and when the immune response is completed this process has to be negatively regulated, that is, suppressed back, when a natural killer cell is needed to clear the already activated immune cells such as lymphocytes and histiocytes. However, in patients with MAS, there is a problem with the body’s own inhibitory function, for example, due to a genetic defect, the activated immune function is out of control, and the activated immune cells secrete a large number of cytokines, which further activate the immune cells, and the cycle continues, just like the “cascade reaction” in the nuclear reaction “A cascade reaction is uncontrollable. Macrophages are another extremely important part of this reaction, not only secreting cytokines themselves, but also migrating to various tissues and organs by their own activation plus tissue cells, directly causing damage to various organs. For example, when macrophages migrate to the bone marrow to engulf hematopoietic cells, they will cause a decrease in white blood cells, red blood cells and platelets, and the bone marrow aspiration picture shows macrophages engulfing blood cells, which is the so-called “hematophagy”. In the two pictures below, the large cell is the uncontrolled macrophage, which can be seen greedily devouring other blood cells. Patients with MAS usually have an acute or even explosive onset of the disease, clinically showing damage to multiple organs and systems, or even multiple organ failure within a short period of time, with a death rate of 20%-60%. Fever is the most important manifestation of MAS, liver, spleen and lymph node enlargement appear; central nervous system dysfunction may include drowsiness, irritability, disorientation, headache, convulsion, coma; coagulation disorder and bleeding tendency may be manifested as purpura, mucosal bleeding, digestive tract bleeding, heart, lung and kidney damage are seen in heavy cases. Blood tests may reveal a decrease in blood cell trisomy; abnormal liver function, such as elevated transaminases and bilirubin; abnormal coagulation; elevated triglycerides, lactate dehydrogenase, serum ferritin, etc. There is still no good clinical standard for the diagnosis of MAS, and the most used criteria are those proposed by the International Society for Hemophagocytic Histiocytosis (HlH) in 2004: fever; splenomegaly; hematocrit (affecting 2 or more lines), Hb≤90g/L, PLT<100, neutrophils<1.0; hypertriglyceridemia (TG>2.0mmol/L after fasting) 2.0 mmol/L) and hypofibrinogenemia (≤1.5 g/L); phagocytosis in bone marrow, spleen or lymph nodes, while excluding tumor infiltration; decreased or absent cytotoxic activity of NK cells; hyperserotoninemia (≥500 μg/L); and increased soluble CD25 (IL-2Rα chain ≥2400 U/L). MAS can be diagnosed by meeting 5 of the above 8 criteria. For the treatment of MAS, glucocorticoids are still the first choice, cyclosporine and VP-16 are the most used immunosuppressive agents, and gammaglobulin shock therapy is helpful. In recent years, with the application of biologics in rheumatic immune diseases, many biologics have also been tried in MAS, such as antagonizing cytokines like TNF, IL-1, IL-6, etc. Some efficacy has been achieved, but at the same time, there are also cases of inducing MAS or aggravating the disease after use, so the real mechanism of action of cytokine antagonists in MAS is actually not very clear. Returning to our young patient at the beginning, unfortunately, although the doctors diagnosed the patient quickly within hours of his admission and transferred him to the intensive care unit for very aggressive treatment with high doses of hormones and gammaglobulin shock, they were unable to save his young life and he was killed by the disease in just one week! So vigilance, early detection of MAS tendency and appropriate treatment are the keys to improve the prognosis; but obviously there is still a lot to go.