This process leads to an overproduction of proinflammatory cytokines, resulting in hemophagocytosis, tissue infiltration, and life threatening endorgan damage 1. Macrophage activation syndrome as part of systemic juvenile. Hyperferritinemia is associated with a multitude of clinical conditions and with worse prognosis in critically ill patients. Macrophage activation syndrome mas is a potentially lifethreatening complication of rheumatic disorders, which is encountered most frequently in systemic juvenile idiopathic arthritis sjia and in its adult equivalent, adultonset stills disease aosd. A panel of 28 experts was first asked to classify 428 patient profiles as having or not. Histiocytic glomerulopathy associated with macrophage. This is reminiscent of cytokine release syndrome crsinduced ards and secondary hemophagocytic lymphohistiocytosis shlh observed in patients withsars cov and merscov as well as in leukemia patients receiving engineered t cell therapy.
Evidencebased diagnosis and treatment of macrophage. We report the first observation of this association in africa, south of the sahara, and we discuss the diagnosis and therapeutic challenge. In rheumatology, it occurs most frequently in patients with systemic juvenile idiopathic arthritis sjia and systemic lupus erythematosus. Under the stimulation of bacterial, viral or fungal infection and certain medicines, t cells are activated and may directly. Macrophage activation syndrome in patients with systemic. Macrophage activation syndrome mas is an acute episode of overwhelming inflammation characterized by activation and expansion of t lymphocytes and hemophagocytic macrophages. 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. 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 recent decades, an uncommon phenomenon of macrophage activation syndrome mas or hemophagocytic syndrome hs is increasingly reported in patients with severe dengue. Macrophage activation syndrome, glomerulonephritis. A rare case of macrophage activation syndrome presenting as. Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis.
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. To the best of our knowledge, this is the first case reported in literature for a constellation of mas, glomerulonephritis, pericarditis, and retinal vasculitis as initial presentation of sle. 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, a form of hemophagocytic lymphohistiocytosis, which is a systemic inflammatory process involving the expansion, activation, and overproduction of hemophagocytic macrophages and t lymphocytes with cytokine release. In addition, mas has been described in association with systemic lupus erythematosus sle, kawasaki disease, and adult. Learn about the signs, causes and treatment of mas. Activation syndrome an overview sciencedirect topics. Application of ms score in macrophage activation syndrome. Although mas has been reported in association with almost any rheumatic disease, it is by far most common in systemic juvenile idiopathic arthritis. Macrophage activation syndrome as part of systemic. Macrophage activation syndrome induced by infections and medications. Macrophage activation syndrome mas is a clinical disorder associated with systemic symptoms caused by overwhelming inflammation caused by immune dysregulation often in the setting of rheumatologic disease with marked increases in circulating cytokines.
The pathological mechanisms of mas are not fully understood. Tocilizumab modifies clinical and laboratory features of. Frontiers the immunology of macrophage activation syndrome. 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. Ferritin and scd163, hence, could be charted and noted as important markers for monitoring dengue disease progression.
A diagnosis of macrophage activation syndrome complicating primary sjogrens syndrome was selected with a probability of 97. In adults, macrophage activation syndrome develops due to the complication of stills disease. Mas manifests as fever, liver dysfunction, pancytopenia, central nervous system disturbance, hyperferritinemia, hemophagocytosis, and coagulopathy. Macrophage activation syndrome in adults with rheumatic disease. In summary, two distinct markers of macrophage activation syndrome were investigated in dengue patients. The infant presented with cerebral irritability, pain, tachypnoea and vomiting for 10 days. Macrophage activation syndrome mas is a lifethreatening hyperinflammatory syndrome characterised by excessive activation and proliferation of t lymphocytes and macrophages and a consequent massive production of cytokines, or cytokine storm. It belongs to the hemophagocytic lymphohistiocytosis group of diseases. Macrophage activation syndrome mas is a lifethreatening condition, and it is a subset of hemophagocytic lymphohistiocytosis hlh. Mas is a severe, potentially fatal disease characterized by severe systemic inflammation. Flares of the underlying disease or infection are most. Macrophage activation syndrome mas is a potentially lifethreatening complication of rheumatic disorders, particularly systemic juvenile idiopathic arthritis. Hyperferritinemia and increased serum scd163 are shown in the study to be consistent with severe manifestations of dengue. The evolution was favorable under a treatment including etoposide vp16.
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. 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. Hlh is termed macrophage activation syndrome mas when associated with rheumatic disease where it is best characterized in systemic jia. Treatment of macrophage activation syndrome mas with. Review macrophage activation syndrome as part of systemic juvenile idiopathic arthritis.
Current focus has been on the development of novel therapeutics, including antivirals and vaccines. It is often considered a type of secondary hemophagocytic lymphohistiocytosis hlh and results from overactivation of t lymphocytes and. 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. Macrophage activation syndrome mas is a lifethreatening condition caused by excessive activation and proliferation of t lymphocytes and haemophagocytic macrophages. Pathogenesis of macrophage activation syndrome and. Macrophage activation syndrome page 2 of 7 the rheumatologist. Mas falls under the umbrella group of diseases known as of hemophagocytic lymphohistiocytosis hlh or hemophagocytic syndrome hps. 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. Macrophage activation syndromeassociated markers in. 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. Mas is severe inflammation of the immune system and is a very serious condition. To identify macrophage activation syndrome mas in patients with systemic juvenile idiopathic arthritis sjia undergoing tocilizumab tcz treatment, and to confirm laboratory marker changes and responses to treatment in patients with mas receiving tcz.
Macrophage activation syndrome mas is a rare manifestation of systemic lupus erythematosus sle with potentially lifethreatening consequences. Although macrophage disorders are usually a consequence of a decrease in function, an increase in macrophage activity can also have adverse consequences for individuals. Macrophage activation syndrome mas itself is a rare, potentially lifethreatening complication of a rheumatic disease, mostly seen in juvenile idiopathic arthritis. Hemophagocytic syndrome, hemophagocytic lymphohistiocytosis hlh, histiocytic erythrophagocytosis icd9 code. It infrequently occurs in systemic lupus erythematosus sle, and it is extremely rare to be the first presentation of sle. Macrophage activation syndrome hematologyoncology clinics. 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. Macrophage activation syndrome mas is a severe, potentially fatal condition associated with excessive activation and expansion of macrophages and t cells, leading to an overwhelming inflammatory reaction.
Highdose anakinra as treatment for macrophage activation. There are four uncommon medical conditions characterized by high levels of ferritin, namely the. The study group consisted of pediatric mas patients due to sjia or aids, followed up in the. Macrophage activation syndrome, a rare complication of. Macrophage activation syndrome affects the immune system and causes inflammation. Macrophage activation syndrome mas is a serious complication of childhood systemic inflammatory disorders that is thought to be caused by excessive.
Pdf macrophage activation syndrome rakshita aggarwal. Standardized diagnostic and treatment guidelines for. 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. Macrophage activation syndrome mas is a rare complication of childhood with rheumatic disease. Macrophage activation syndrome mas is a pathological systemic inflammatory reaction that is often fatal and underdiagnosed. Macrophage activation syndrome mas is a severe condition due to a hyperinflammatory response resulting from exaggerated activation and proliferation of nonmalignant macrophages. It is associated with multiple rheumatic diseases, such as rheumatoid arthritis. Macrophage activation syndrome mas is a rare form of haemophagocytic lymphohistiocytosis hlh associated with rheumatologic conditions. Macrophage activation syndrome is characterized by pancytopenia, liver insufficiency. 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. Macrophage activation syndrome mas aboutkidshealth. Hemophagocytic lymphohistiocytosis hlh is an aggressive and lifethreatening syndrome of excessive immune activation. Macrophage activation syndrome mas occurs as a severe lifethreatening complication of several chronic rheumatic diseases. Laboratory abnormalities of mas include pancytopenia.
Development and initial validation of the ms score for. A case of macrophage activation syndrome complicating severe. Macrophage activation syndrome as onset of systemic lupus. Flares of the underlying disease or infection are most common triggers of mas. 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 mas is an unusual, hyperinflammatory response to a rheumatologic stimulus characterized by hyperferritinemia, pancytopenia, thermal dysregulation and multiorgan. A rare case of macrophage activation syndrome presenting. Macrophage activation syndrome treatment, symptoms, life. Feb 17, 2016 in recent decades, an uncommon phenomenon of macrophage activation syndrome mas or hemophagocytic syndrome hs is increasingly reported in patients with severe dengue. We read with great interest the article by minoia et al which named development and initial validation of the macrophage activation syndrome massystemic juvenile idiopathic arthritis sjia ms score for diagnosis of mas in sjia. Haemophagocytic lymphohistiocytosis hlh is an underrecognized hyperinflammatory condition with a high mortality, characterized by inappropriate survival of histiocytes and cytotoxic t cells ctls, leading to a cytokine storm, haemophagocytosis and multiorgan damage. This syndrome has been reported as a complication of many rheumatic diseases, most commonly in. 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. He did not fulfil any of the classic diagnostic criteria for kd.
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. Hlh can occur as a familial or sporadic disorder, and it can be triggered by a variety of. 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. This can occur in the setting of a number of different immune. In this context, cytokine storm is often called macrophage activation syndrome mas, a reference to activated macrophages often seen on tissue biopsy, despite lack of evidence that these cells cause the syndrome although they do, at least under some circumstances, produce inflammatory cytokines 15. Cureus macrophage activation syndrome secondary to. Hemophagocytosis was reported in dengue with multiorgan complications 12, observed in severe dengue involving both children and adults 15 and associated with.
The inflammation can be in any organ system including the bone marrow, liver, and spleen. The clinical presentation of macrophage activation syndrome mas is generally acute and occasionally dramatic. Mas is a lifethreatening complication of rheumatic disorders, including sjia, adultonset stills disease aosd and lupus. Macrophage activation syndrome is a rare entity, rarely reported during primary sjogrens syndrome.
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. Macrophage activation syndrome mas is a serious, potentially lifethreatening, hyperinflammatory condition, which belongs to the spectrum of hemophagocytic lymphohistiocytosis hlh and can complicate several immunologic and rheumatic disorders. It infrequently occurs in systemic lupus erythematosus sle, and it is. In japan, 394 patients with sjia were registered in an allpatient registry surveillance of tcz as of january 15, 2012. Mas is considered a secondary or acquired form of haemophagocytic lymphohistiocytosis hlh and is usually associated. The study group consisted of pediatric mas patients due to. Macrophage activation syndrome mas is a severe, potentially lifethreatening complication of rheumatic diseases, which is clinically characterized by fever, hepatosplenomegaly, lymphadenopathy, profound depression of all three blood cell lines, deranged liver function, intravascular coagulation, and central nervous system dysfunction. Recent findings in hemophagocytic lymphohistiocytosis, a disease that. A case of macrophage activation syndrome complicating. Dec 03, 2015 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. Nov 21, 2018 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. Pericardial effusion on echocardiography in addition to severe dilatation of the coronary arteries in combination with leucocytosis. Macrophage activation syndrome is a severe, potentially lifethreatening, complication of several chronic rheumatic diseases of childhood.
Mas is characterized by a dysfunctional immune response that is similar. Macrophage activation syndrome mas is a clinical syndrome caused by excessive activation and proliferation of well differentiated macrophages. Macrophage activation syndrome mas is a potentially fatal condition. There are four uncommon medical conditions characterized by high levels of ferritin, namely the macrophage activation syndrome. Hemophagocytic lymphohistocytosis hlh is characterized by fulminant cytokine storm leading to multiple organ dysfunction and high mortality. Pdf background macrophage activation syndrome mas is a severe complication of rheumatic disease in childhood, particularly in systemic juvenile. Clinical and laboratory features of mas include sustained fever. Clinical features and correct diagnosis of macrophage activation syndrome.
Macrophage activation syndrome an overview sciencedirect. Anakinra treatment in macrophage activation syndrome. A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. Over the last few years, accumulating data have implicated a role for ferritin as a signaling molecule and direct mediator of the immune system. In japan, 394 patients with sjia were registered in an allpatient registry. It occurs most commonly with systemiconset juvenile idiopathic arthritis sojia.
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