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. Loading slideshow in 5 seconds macrophage activation syndrome powerpoint presentation. Rheumaknowledgy macrophage activation syndrome mas. 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. The resources below provide information about treatment options for this condition. Secondary hlh due to autoimmune disease is known as macrophage activation syndrome mas. Standardized diagnostic and treatment guidelines for mas in sjia are currently lacking. Jul 30, 2014 the stimulation of m1 macrophage activation andor the prevention of m2 macrophage activation have the potential to provide protection against a myriad of fungal infections, including c. 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 severe, potentially fatal condition associated with excessive activation of macrophages and t cells leading to an overwhelming inflammatory reaction.
It belongs to the hemophagocytic lymphohistiocytosis group of diseases. There are four uncommon medical conditions characterized by high levels of ferritin, namely the macrophage activation syndrome. For language access assistance, contact the ncats public information officer. Mas is a severe, potentially fatal disease characterized by severe systemic inflammation. 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. The existing terminology for shlh is confusing, leading to a growing call for a unified nomenclature across specialties. Macrophage activation syndrome mas is a lifethreatening condition. Background to evaluate the impact of macrophage activation syndrome mas on clinical features in patients with kikuchifujimoto disease kfd and to compare the features of mas in kfd with those of adultonset stills disease aosd and systemic lupus erythematosus sle. 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. 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. A diagnosis of macrophage activation syndrome mas was made.
Anakinra 100 mg subcutaneously daily was initiated, along with pulse methylprednisolone 1 gday for 3 days, then prednisone 25 mg twice daily. Jul 29, 2017 persistent activation of macrophages leads to massive increase in proinflammatory cytokines. Macrophage activation syndrome mas is a serious, potentially fatal complication of rheumatic diseases caused by excessive activation and expansion of t lymphocytes and macrophages that exhibit hemophagocytic activity 14. A rare case of macrophage activation syndrome presenting as the.
Activation and uncontrolled proliferation of lymphocytes and welldifferentiated macrophages cause widespread haemophagocytosis and cytokine overproduction. Haemophagocytic lymphohistiocytosis in adult critical care. Macrophage activation syndrome treatment, symptoms, life. Hyperferritinemia is associated with a multitude of clinical conditions and with worse prognosis in critically ill patients. Macrophage activation syndrome 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. Laboratory abnormalities of mas include pancytopenia, hyperferritinemia, hypertriglyceridemia and elevated serum transaminases. Over the last few years, accumulating data have implicated a role for ferritin as a signaling molecule and direct mediator of the immune system.
It occurs most commonly with systemiconset juvenile idiopathic arthritis sojia. Mas is currently classified among the secondary or acquired forms of haemophagocytic lymphohistiocytosis shlh. Figure 1 bone marrow biopsy with abundant cellbound haemosiderin and focal haemophagocytosis with cellular debris identified in macrophage cytoplasm arrows. Macrophage activation syndrome treated with anakinra the. Macrophage activation syndrome in the era of biologic therapy. Association of macrophage activating syndrome with. We report the case of a 71yearold japanese woman with adultonset stills disease aosd in whom macrophage activation syndrome mas developed despite therapy with oral highdose prednisolone and intravenous methylprednisolone pulse therapy twice. Macrophage activation syndrome mas is an episode of overwhelming inflammation that occurs most commonly in children with systemic juvenile idiopathic arthritis. List of macrophage activation syndrome medications 1. Haemophagocytic lymphohistiocytosis hlh is an aberrant hyperinflammatory, hyperferritinemic immune response syndrome driven by macrophages and cytotoxic t cells.
Macrophages, the sentinels of innate immunity, take residence in nearly every tissue and display marked heterogeneity in their cell surface markers, location, and function. 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. 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. Persistent activation of macrophages leads to massive increase in proinflammatory cytokines. Mas is a lifethreatening complication of rheumatic disorders, including sjia, adultonset stills disease aosd and lupus. Macrophage activation syndrome mas is a potentially fatal complication of rheumatic disease, most notably systemic juvenile idiopathic arthritis. Control of macrophage activation and function by ppars.
Jan 08, 2019 cutaneous vasculopathy, generalized lipodystrophy, metabolic abnormalities, hematologic manifestations including macrophage activation syndrome, and osteoporosis also may be encountered. Typically, patients become acutely ill with the sudden onset of nonremitting high fever. Hemophagocytic lymphohistiocytosis hlh and macrophage activation syndrome mas are clinically related lifethreatening immune dysregulatory processes characterized by fever, systemic inflammation, organomegaly, coagulopathy, and hematologic cytopenias. Macrophage activation syndrome mas aboutkidshealth. It is characterized by expansion and activation of t lymphocytes and hemophagocytic macrophages, and bears great similarity to hemophagocytic lymphohistiocytosis hlh. Macrophage activation syndrome is a serious complication of rheumatic disease, thought to be caused by excessive activation of macrophages and lymphocytes. In addition, mas has been described in association with systemic lupus erythematosus sle, kawasaki disease, and adultonset stills disease.
Coronavirus infection results in monocyte, macrophage, and dendritic cell activation. Autoimmuneassociated hemophagocytic syndromemacrophage. It infrequently occurs in systemic lupus erythematosus sle, and it is extremely rare to be the first presentation of sle. The pathological mechanisms of mas are not fully understood. Evidencebased diagnosis and treatment of macrophage. Macrophage activation syndrome mas is a severe and potentially life. Ppt macrophage activation syndrome powerpoint presentation. Jdm, macrophage activation syndrome, and pharmacologic immunosuppression in a. One possible hypothesis for uncontrolled expansion of t cells is a defect in cytolytic function. Soon afterward, her fever ceased and high levels of both ferritin and creactive protein. Clinical features acute presentation sudden onset of nonremitting fever profound. Secondary hlh reported to occur in patients with systemic lupus erythematosus sle, steel disease, polyarteritisnodosa pan, mixed connective tissue disease, pulmonary sarcoidosis and. Successful tocilizumab therapy for macrophage activation. Hemophagocytic lymphohistiocytosis and macrophage activation.
Autoimmuneassociated hemophagocytic syndromemacrophage activation syndrome 95 intravenous immunoglobulin ivig, which may be sufficient to control hyperinflammation. Macrophage activation syndrome as an initial presentation of. There are similarities in genetic background, pathogenesis, and clinical and laboratory features with primary hlh phlh. 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. The main manifestations of mas include fever, hepatosplenomegaly, lymphadenopathy, severe cytopenias. Grom, in textbook of pediatric rheumatology seventh edition, 2016.
Genetic and rare diseases information center gard po box 8126, gaithersburg, md 208988126 tollfree. 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. We describe findings in mouse models of secondary hlh, comparing them with. Cytokine release syndrome in severe covid19 science.
Hemophagocytic syndrome, hemophagocytic lymphohistiocytosis hlh, histiocytic erythrophagocytosis. Macrophage activating syndrome mas or secondary hemophagocytic lymphohistocytosis hlh is a lifethreatening disease that follows lymphoma, viral infections and some auto immune disorders. Mist attenuates macrophage inflammatory response and uptake of modified ldl lowdensity lipoprotein. If you have problems viewing pdf files, download the latest version of adobe reader. Macrophage activation syndrome is a severe, potentially lifethreatening, complication of several chronic rheumatic diseases of childhood. Macrophage activation syndrome macrophage activation syndrome mas is a severe and. The clinical presentation of macrophage activation syndrome mas is generally acute and occasionally dramatic. Within 48 hours of anakinra treatment, blood count increased and fever abated. Nov 21, 2018 the clinical presentation of macrophage activation syndrome mas is generally acute and occasionally dramatic. Macrophage activation syndrome is characterized by pancytopenia, liver insufficiency, coagulopathy, and neurologic symptoms and is. Macrophage activation syndrome an overview sciencedirect.
Macrophage activation syndrome powerpoint ppt presentation. A free powerpoint ppt presentation displayed as a flash slide show on id. Evaluation of macrophage activation syndrome in hospitalised. Macrophage activation syndrome mas is a potentially fatal complication of rheumatic diseases.
In mas, this excessive cellular activation and expansion leads to a hyperinflammatory state associated with three cardinal features. This bone marrow biopsy figure 1 shows haemophagocytosis consistent with macrophage activation syndrome mas secondary to previously undiagnosed systemic lupus erythematosus sle. The mechanism leading to expansion of activated macrophages is not clear. Application of ms score in macrophage activation syndrome.
Mar 24, 2016 macrophage activation syndrome mas is a potentially fatal complication of rheumatic disease, most notably systemic juvenile idiopathic arthritis. The following list of medications are in some way related to, or used in the treatment of this. The condition is considered part of secondary hemophagocytic lymphohistiocytoses hlh. Rituximab therapy in refractory macrophage activation. The main manifestations of mas include fever, hepatosplenomegaly, lymphadenopathy, severe cytopenias, serious liver disease, and disseminated. Treatment of macrophage activation syndrome mas with. In adults, macrophage activation syndrome develops due to the complication of stills disease. 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. Twelve novel long noncoding rnas are dysregulated in macrophages from highfat dietfed obese mice. Macrophage activation syndrome mas is a lifethreatening complication of rheumatic disease that. Charecterised by activation and proliferation of t lymphocytes and macrophages that. We read with great interest the recent article by saper et al 1 describing high mortality of systemic juvenile idiopathic arthritis sjia patients affected by parenchymal lung disease ld. Classical versus alternative macrophage activation.
Hemophagocytic lymphohistiocytosis, also known as haemophagocytic lymphohistiocytosis british spelling, and hemophagocytic or haemophagocytic syndrome, is an uncommon hematologic disorder seen more often in children than in adults. The inflammation can be in any organ system including the bone marrow, liver, and spleen. Macrophage activation syndrome is characterized by pancytopenia, liver insufficiency. Macrophage activation syndrome mas is a severe complication of rheumatic disease in childhood, particularly in systemic juvenile idiopathic arthritis sjia. Introduction life threatning disorder of chronic rheumatological conditions like systemic onset juvenile rheumatoid arthritis, sle, adult onset stills disease, kawasakis disease. 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. The clinical presentation of mas is generally acute and can be dramatic. Macrophage activation syndrome mas is a lifethreatening complication of rheumatic. 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. Macrophage activation syndrome page 2 of 7 the rheumatologist. Macrophage activation syndrome mas is a severe, potentially lifethreatening complication of childhood systemic inflammatory disorders. Jdm, macrophage activation syndrome, and pharmacologic immunosuppression in a 15yearold girl.
Ld with sjia has also been associated with macrophage activation syndrome mas. It is a lifethreatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages, characterised by. Macrophage activation syndrome as onset of systemic lupus. Sir, macrophage activation syndrome mas is a lifethreatening condition characterised by high fever, pancytopenia, liver insufficiency and coagulopathy. 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 a lifethreatening. In addition, mas has been described in association with systemic lupus erythematosus sle, kawasaki disease, and adult. Macrophage activation syndrome linkedin slideshare. Macrophage activation syndrome genetic and rare diseases. Il6 release then instigates an amplification cascade that results in cis signaling with t h 17 differentiation, among other lymphocytic changes, and trans signaling in many cell types, such as endothelial cells. Macrophage activation syndrome mas is a potentially fatal condition. Macrophage activation syndrome in sjia alexei grom. We describe findings in mouse models of secondary hlh, comparing them with models of p. 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.
Hemophagocytic syndrome, hemophagocytic lymphohistiocytosis hlh, histiocytic erythrophagocytosis icd9 code. It is characterize by an uncontrolled activation and proliferation of t lymphocytes and macrophages. Charecterised by activation and proliferation of t lymphocytes and macrophages that infiltrate organs. Macrophage activation syndrome in systemic juvenile. The stimulation of m1 macrophage activation andor the prevention of m2 macrophage activation have the potential to provide protection against a myriad of fungal infections, including c. Cutaneous vasculopathy, generalized lipodystrophy, metabolic abnormalities, hematologic manifestations including macrophage activation syndrome, and osteoporosis also may be encountered. Macrophage activation syndrome in the era of biologic. Macrophageactivation syndrome is a severe, potentially lifethreatening, complication of several chronic rheumatic diseases of childhood.
Macrophage activation syndrome in sjia alexei grom slideshare. Macrophageexpressed long noncoding rna macrophage inflammationsuppressing transcript mist is downregulated in mouse adipose tissue macrophages on dietinduced obesity. Macrophage activation syndrome as an initial presentation. Drugs used to treat macrophage activation syndrome. 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. It is rare as the first manifestation of systemic lupus erythematosus sle. 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.