Macrophage activation syndrome mas is a phenomenon characterized by cytopenia, organ dysfunction, and coagulopathy associated with an inappropriate activation of macrophages. A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. In clinically similar primary hlh, the uncontrolled proliferation of t cells and macrophages has been linked to decreased natural killer nk cell and cytotoxic t cell function, often due to mutations in the gene encoding perforin. It remains a rare pathology, with a guarded prognosis, characterized by clinical and biological signs that are not very specific and whose association helps invoke the diagnosis. Macrophage activation syndrome, a rare complication of. Discussion hemophagocytic syndromehemophagocytic lymphohistiocytosishlh it is a rare ds. Standardized diagnostic and treatment guidelines for mas in sjia are currently lacking. In fact, sjia can be viewed as an autoinflammatory disease rather than an autoimmune disease. Macrophage activation syndrome as onset of systemic lupus. Interleukin1 blockade with highdose anakinra in patients.
As of march 12, 2020, coronavirus disease 2019 covid19 has been confirmed in 125 048 people worldwide, carrying a mortality of approximately 37%,1 compared with a mortality rate of less than 1% from influenza. Macrophage activation marker soluble cd163 associated with. Macrophage activation syndrome mas is a lifethreatening condition. Furthermore, with several animal models, they demonstrate that il18 is not just a biomarker but rather a driver of inflammation and potential therapeutic target in some patients. Macrophage activation syndrome mas is a lifethreatening complication of sjia marked by sudden onset of nonremitting high fever, profound depression in all three blood cell lines i. Sep 24, 2015 macrophage activation syndrome mas is a potentially lifethreatening complication of rheumatic diseases such as systemic juvenile idiopathic arthritis sjia and systemic lupus erythematosus. In adults, macrophage activation syndrome develops due to the complication of stills disease. To identify criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis sjia, the diagnostic sensitivity and specificity of the clinical and laboratory. Macrophage activation syndrome mas is a severe and potentially life. The inflammation can be in any organ system including the bone marrow, liver, and spleen. Macrophages are a type of immune cell in the body that eats infectious organisms and damaged cells.
One possible hypothesis for uncontrolled expansion of t cells is a defect in cytolytic function. The heterogeneity is further illustrated by description of cases with spiking fever, exanthema associated with this typical cytokine pattern, and nk cell dysfunction but without arthritis. Laboratory features sjia presentation mas presentation. Hlh can occur as a familial or sporadic disorder, and it can be triggered by a variety of. Specifically, it is a secondary hyperinflammatory condition involving uncontrolled immune activation caused by excessive proliferation of macrophages and lymphocytes and is considered a secondary form of haemophagocytic lymphohistiocytosis hlh. However, its pathogenesis is still poorly understood and has many similarities with that of the other forms of hemophagocytic lymphohistiocytosis hlh. Macrophage activation syndrome clinical presentation. Laboratory abnormalities of mas include pancytopenia, hyperferritinemia, hypertriglyceridemia and elevated. Macrophage activation syndrome mas is a rare but lifethreatening systemic inflammatory complication, usually arising from superimposed viral infections or flares of underlying rheumatological conditions. The mechanism leading to expansion of activated macrophages is not clear. Macrophage activation syndrome mas is a severe, potentially lifethreatening complication of autoimmune diseases. The clinical presentation of mas is generally acute and can be dramatic. Aug 31, 2018 macrophage activation syndrome mas is a lifethreatening condition, and it is a subset of hemophagocytic lymphohistiocytosis hlh. The main clinical manifestations include cytopenias, liver dysfunction.
Macrophage activation syndrome is a condition in which the bodys immune system activates excessively, leading to tissue and organ damage. Macrophage activation syndrome mas is an acute episode of overwhelming inflammation characterized by activation and expansion of t lymphocytes and hemophagocytic macrophages. In addition, mas has been described in association with systemic lupus erythematosus sle, kawasaki disease, and adultonset stills disease. Sometimes mas can be the mode of initial presentation adding to the diagnostic complexity. Learn about the signs, causes and treatment of mas. Macrophage activation syndrome mas mas is present in up to 50% of children with systemic juvenile idiopathic arthritis sjia in a subclinical or overt 10% form. How is macrophage activation syndrome mas complicating. Macrophage activation syndrome mas is an intriguing and potentially lifethreatening condition 1, 2, clinically characterized by nonremitting fever, hepatosplenomegaly, lymphadenopathy, encephalopathy, coagulopathy and even multi organ failure in severe cases. Macrophage activation syndrome is a serious complication of rheumatic disease, thought to be caused by excessive activation of macrophages and lymphocytes. Macrophage activation syndrome, an important differential. Ab0286 14 cases study of macrophage activation syndrome.
List of macrophage activation syndrome medications 1. Recent findings in hemophagocytic lymphohistiocytosis, a disease that is clinically similar to mas, highlight the possible. The pathological mechanisms of mas are not fully understood. Macrophage activation syndrome is characterized by pancytopenia, liver insufficiency. Aug 22, 20 over the last few years, accumulating data have implicated a role for ferritin as a signaling molecule and direct mediator of the immune system. Chart and diagram slides for powerpoint beautifully designed chart and diagram s for powerpoint with visually stunning graphics and animation effects. Macrophage activation syndrome mas is the term used to describe a potentially lifethreatening complication of systemic inflammatory disorders, which occurs most commonly in systemic juvenile idiopathic arthritis jia and in its adult equivalent, adultonset stills disease 14, although its occurrence in patients. It most frequently affects infants from birth to 18 months of age, but the disease is also observed in children and adults of all ages. It is characterize by an uncontrolled activation and proliferation of t lymphocytes and macrophages. Current focus has been on the development of novel therapeutics, including antivirals and vaccines. Recent findings in hemophagocytic lymphohistiocytosis, a disease that. Mas is a severe, potentially fatal disease characterized by severe systemic inflammation. There are four uncommon medical conditions characterized by high levels of ferritin, namely the macrophage activation syndrome.
Macrophage activation syndrome complicating rheumatic. Systemic lupus erythematosus sle has myriad manifestations that can affect any organ system in the body. Macrophage activation syndrome angelo ravelli, md macrophage activation syndrome mas is a serious complication of childhood systemic inflammatory disorders that is thought to be caused by excessive activation and proliferation of t lymphocytes and macrophages. For language access assistance, contact the ncats public information officer. Classical versus alternative macrophage activation. Background macrophage activation syndrome mas is a severe, potentially lifethreatening syndrome.
The condition is considered part of secondary hemophagocytic lymphohistiocytoses hlh. We describe findings in mouse models of secondary hlh, comparing them with. The main manifestations of mas include fever, hepatosplenomegaly, lymphadenopathy, severe cytopenias. Macrophage activation syndrome is characterized by pancytopenia, liver insufficiency, coagulopathy, and neurologic symptoms and is. Macrophage activation syndrome is a rare and potentially fatal disease, to be considered in patients with a sirs like clinical presentation. Macrophage activation syndrome mas is a lifethreatening complication of rheumatic disease that, for unknown reasons, occurs much more frequently in individuals with systemic juvenile idiopathic arthritis sjia and in those with adultonset still disease. Macrophage activation syndrome mas is a lifethreatening condition, and it is a subset of hemophagocytic lymphohistiocytosis hlh. Ppt hemophagocytic lymphohistiocytosis hlh powerpoint. The management of patients with these disorders is discussed separately. Characterized by benign proliferation of the mature histiocyte. Macrophage activation syndrome an overview sciencedirect. The treatment of macrophage activation syndrome mas is traditionally based on the parenteral administration of high doses of corticosteroids. Macrophage activation syndrome mas or hemophagocytic lymphohistiocytosis hlh is a life. Macrophage activation syndrome mas is a severe and potentially lethal complication of several inflammatory diseases but seems particularly linked to systemic juvenile idiopathic arthritis sjia.
Pediatric macrophage activation syndrome, recognizing the tip of the. Although macrophage disorders are usually a consequence of a decrease in function, an increase in macrophage activity can also have adverse consequences for individuals. It is often considered a type of secondary hemophagocytic lymphohistiocytosis hlh and results from overactivation of t lymphocytes and macrophages leading to a cytokine storm. A diagnosis of macrophage activation syndrome mas was made. Review macrophage activation syndrome as part of systemic juvenile idiopathic arthritis. There are similarities in genetic background, pathogenesis, and clinical and laboratory features with primary hlh phlh. Macrophage activation syndrome is a rare but serious complication that usually occurs within the first few months after show more results learn how uptodate can help you. Pdf why the immune mechanisms of pulmonary intravascular. Macrophage activation syndrome as part of systemic. Mas is currently classified among the secondary or acquired forms of haemophagocytic lymphohistiocytosis shlh. Macrophage activation syndrome in sjia alexei grom.
May 23, 2016 macrophage activation syndrome mas is a disorder whereby the immune system generates very high levels of substances cytokines that promote inflammation to the extent dysfunction occurs in multiple organ systems which if unchecked, is frequently fatal to the affected individual. It is characterized by benign proliferation of mature histiocytes and uncontrolled phagocytosis of the platelet, erythrocytes, lymphocytes and their hematopoieti. Macrophage activation syndrome is a severe, potentially lifethreatening, complication of several chronic rheumatic diseases of childhood. Excessive activation and proliferation of t lymphocytes and tissue macrophages histiocytes. In clinically similar primary hlh, the uncontrolled proliferation of t cells and macrophages has been linked to decreased natural killer nk. Macrophage activation syndrome mas is a clinical syndrome caused by excessive activation and proliferation of well differentiated macrophages. Part patients were analysed the polymorphisms of perforin a91v ncbi.
Ppt macrophage activation syndrome powerpoint presentation. Macrophage activation syndrome mas is the term used to describe a potentially lifethreatening complication of rheumatic diseases, which is seen most frequently in systemic juvenile idiopathic arthritis sjia and in its adult equivalent, adultonset stills disease,, although it is encountered with increasing frequency in systemic lupus erythematosus of either childhood. Mas is severe inflammation of the immune system and is a very serious condition. Snp rs359472 using special primers by polymerase chain reaction pcr. See treatment and prognosis of hemophagocytic lymphohistiocytosis. Data regarding the clinical course, management and outcome of adults with mas is limited.
Macrophage activation syndrome mas is a serious, potentially lifethreatening complication of rheumatic disorders, which is seen most commonly in systemic juvenile idiopathic arthritis sjia. The clinical features and diagnosis of hlh and a related disorder, the macrophage activation syndrome mas, will be discussed here. Another term for this form of hlh is reactive hemophagocytic syndrome. Nov 21, 2018 the clinical presentation of macrophage activation syndrome mas is generally acute and occasionally dramatic. Hypercytokinemia accompanied by severe clinical disease seen in evd is reminiscent of what has been described for macrophage activation syndrome mas and hemophago. A panel of 28 experts was first asked to classify 428 patient profiles as having or not. Macrophage activation syndrome mas is a potentially fatal complication of rheumatic diseases. Macrophage activation syndrome mas is a severe complication of rheumatic disease in childhood, particularly in systemic juvenile idiopathic arthritis sjia. Clinical features of macrophage activation syndrome as the. Macrophage activation syndrome in systemic juvenile. Macrophage activation syndrome mas, also called secondary hemophagocytic lymphohistiocytosis hlh is characterized hematologic manifestations of systemic lupus erythematosus view in chinese thrombotic microangiopathy, caps, severe infections, hemophagocytic lymphohistiocytosis macrophage activation syndrome hlhmas, and severe drug. Macrophage activation syndrome mas is a disease of uncontrolled lymphocyte and macrophage proliferation and activation, which has various triggers, including autoimmune disorder, viral infection, and malignancy. The clinical features include a persistent highgrade fever, hepatosplenomegaly, lymphadenopathy, hemorrhagic manifestations, and a sepsislike condition.
Pathogenesis of macrophage activation syndrome and potential. Clinical analysis of macrophage activation syndrome in. Macrophage activation syndrome mas is most common in sjia, and it has been reported that the frequency of marked mas is 10%, but it is known that the frequency of mas, which is not reflected in clinical practice, reaches up to 3040%. Typically, patients become acutely ill with the sudden onset of nonremitting high fever. It occurs most commonly with systemiconset juvenile idiopathic arthritis sojia. In addition to macrophages, dendritic cells likely play a critical role in antigen presentation to cytolytic lymphocytes, as well as contributing to. We report a case of macrophage activation syndrome presenting as pyrexia of unknown origin. In individuals with macrophage activation syndrome mas, the immune system is uncontrolled and works in overdrive, leading to too much inflammation in the entire body. Macrophage activation syndrome mas is a lifethreatening complication of rheumatic. Grom, in textbook of pediatric rheumatology seventh edition, 2016.
Treatment of macrophage activation syndrome mas with. Our new crystalgraphics chart and diagram slides for powerpoint is a collection of over impressively designed datadriven chart and editable diagram s guaranteed to impress any audience. Download fulltext pdf download fulltext pdf why the immune mechanisms of pulmonary intravascular coagulopathy in covid19 pneumonia are distinct from macrophage activation syndrome with. Macrophage activation syndrome treatment, symptoms, life. Macrophage activation syndrome mas in a recently released. Evidencebased diagnosis and treatment of macrophage. May 22, 2012 macrophage activation syndrome mas belongs to secondary hemophagocytic lymphohistiocytosis hlh syndrome. Macrophage activation syndrome mas is a severe, potentially fatal condition caused by excessive activation and expansion of macrophages and t cells, leading to an overwhelming inflammatory reaction. Hyperferritinemia is associated with a multitude of clinical conditions and with worse prognosis in critically ill patients. Clinical and laboratory features of mas include sustained fever.
Anakinra 100 mg subcutaneously daily was initiated, along with pulse methylprednisolone 1 gday for 3 days, then prednisone 25 mg twice daily. Within 48 hours of anakinra treatment, blood count increased and fever abated. We describe findings in mouse models of secondary hlh, comparing them with models of p. In addition, mas has been described in association with systemic lupus erythematosus sle, kawasaki disease, and adult. Genetic and rare diseases information center gard po box 8126, gaithersburg, md 208988126 tollfree. Macrophage activation syndrome page 2 of 7 the rheumatologist. In pediatric rheumatology, the term macrophage activation syndrome mas refers to a condition caused by excessive activation and expansion of t lymphocytes and macrophagic histiocytes that exhibit hemophagocytic activity.
A bone marrow biopsy often provides pathologic evidence of mas. It is characterized by an uncontrolled immune response, involving the expansion of tcells, macrophages, and the hypersecretion of proinflammatory cytokines. Based on the clinical presentation and investigations the differential diagnosis must now include macrophage activation syndrome mas cause unknown but a number of triggers such as infection ebv, bacterial, parasitic and fungal and certain types of medication have been identified. Macrophage activation syndrome mas aboutkidshealth. Macrophage activation syndrome genetic and rare diseases. Macrophage activation syndrome mas occurs as a severe lifethreatening complication of. Macrophage activation syndrome mas is a lifethreatening complication of rheumatologic diseases. Macrophage activation syndrome treated with anakinra the. In rheumatology, it occurs most frequently in patients with systemic juvenile idiopathic arthritis sjia and systemic lupus erythematosus. Apart from these inflammatory disorders, different autoinflammatory dysfunctions like kawasaki disease, systemic lupus erythematosus, and periodic fever syndromes can trigger the onset of adult and childhood macrophage activation syndrome. Mas manifests as fever, liver dysfunction, pancytopenia, central nervous system disturbance, hyperferritinemia. In this issue of blood, weiss et al and girardguyonvarch et al demonstrate the ability of free plasma interleukin18 il18 to distinguish macrophage activation syndrome mas from other inflammatory disorders. Introduction hemophagocytic syndrome is a rare disorder of the mononuclear phagocytic system.
Pdf background macrophage activation syndrome mas is a severe complication of rheumatic. We describe two cases of mas in association with systemic onset. Hemophagocytic syndrome, hemophagocytic lymphohistiocytosis hlh, histiocytic erythrophagocytosis. Macrophage activation syndrome mas is a rare, but potentially lifethreatening complication of systemic lupus erythematosus sle. Macrophage activation syndrome affects the immune system and causes inflammation. The term mas designates a clinicopathologic entity that occurs in different hemophagocytic syndromes hss. It belongs to the hemophagocytic lymphohistiocytosis group of diseases. Synonymous with secondary hemophagocytic lymphohistiocytosis, macrophage activation syndrome mas is a term used by rheumatologists to describe a potentially lifethreatening complication of systemic inflammatory disorders, most commonly systemic juvenile idiopathic arthritis sjia and systemic lupus erythematosus sle. A free powerpoint ppt presentation displayed as a flash slide show on id. Nov 21, 2018 macrophage activation syndrome is characterized by a highly stimulated but ineffective immune response. Macrophage activation syndrome case study immunopaedia. While specific but insensitive for identifying mas, strict usage of hlh2004 criteria may delay diagnosis in patients with a less severe initial presentation 5. Rheumaknowledgy macrophage activation syndrome mas.
Macrophage activation syndrome mas is a serious complication of childhood systemic inflammatory disorders that is thought to be caused by excessive activation and proliferation of t lymphocytes and macrophages. Jul 17, 2014 because macrophage activation is involved in the outcome of many diseases, including metabolic diseases, allergic disorders such as airway hyperreactivity, autoimmune diseases, cancer, and bacterial, parasitic, fungal, and viral infections, we need to establish a common language for describing the properties of the macrophages under. Macrophage activation syndrome mas is a potentially lifethreatening complication of sjia as well as sometimes complicating other rheumatologic conditions, such as juvenile systemic lupus erythematosus thought to result from immune activation of pathogenic t cells and hemophagocytic macrophages. Activation syndrome an overview sciencedirect topics. Persistent activation of macrophages leads to massive increase in proinflammatory cytokines. Macrophage activation syndrome mas is a potentially fatal condition. Defining criteria for macrophage activation syndrome, a. Hemophagocytic lymphohistiocytosis hlh is an aggressive and lifethreatening syndrome of excessive immune activation. Macrophageactivation syndrome is a severe, potentially lifethreatening, complication of several chronic rheumatic diseases of childhood. If you have problems viewing pdf files, download the latest version of adobe reader. Hlh is not a single disease but is a hyperinflammatory syndrome that can occur in. Pathogenesis of macrophage activation syndrome and. Demographics, clinical data, treatment, and outcomes were analyzed. Typically, patients become acutely ill with the sudden onset of nonremitting high fever, profound depression in all 3 blood cell lines ie, leukopenia, anemia, and thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and elevated serum liver enzyme levels.
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