The term macrophage activation syndrome mas identifies a severe and potentially fatal complication of sjia, and, more rarely of other rheumatic diseases. 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 revealing systemic lupus. Mas is a severe systemic inflammatory reaction characterised by uncontrolled activation and. The inflammation can be in any organ system including the bone marrow, liver, and spleen. Standardized diagnostic and treatment guidelines for mas in sjia are currently lacking. While hlh and mas have numerous etiologies, sarcoidosis should be considered as a potential underlying diagnosis, and prompt treatment. The figure illustrates several mechanisms underlying macrophage polarization and shows the fee dback regulation between m1 and m2 signal pathways. Pdf intravenous immunoglobulin treatment for macrophage. A diagnosis of macrophage activation syndrome mas was made. Within 48 hours of anakinra treatment, blood count increased and fever abated. Macrophage activation syndrome mas, also known as secondary hemophagocytic.
Hyperferritinemia is associated with a multitude of clinical conditions and with worse prognosis in critically ill patients. Macrophage activation definition of macrophage activation. 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 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.
List of macrophage activation syndrome medications 1. 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. 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. Sobi investigator initiated clinical trial of anakinrato treat mas case of. 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, also known as secondary hemophagocytic lymphohistiocytosis, is mediated by cytokine overproduction from excessive activation of t lymphocytes and macrophages.
Measurement of the serum ferritin level may assist in the diagnosis and may be a useful indicator of disease. Macrophage activation syndrome kill or be killed randy q. Macrophage activation syndrome is thought to be caused by excessive activation and proliferation of t lymphocytes and macrophages. 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. Macrophage activation syndrome is described as a clinical syndrome of hyperinflammation resulting in an uncontrolled and ineffective immune response in the context of an autoinflammatory or rheumatic disease. Macrophage activation syndrome mas, or secondary hemophagocytic. Hemophagocytic syndrome, hemophagocytic lymphohistiocytosis hlh, histiocytic erythrophagocytosis. Macrophage activation syndrome mas is a lifethreatening complication of rheumatic diseases, requiring immediate and appropriate treatment. Prognosis depends on the severity of neurologic manifestations. Autoimmuneassociated hemophagocytic syndromemacrophage.
Encouraging findings from small studies involving treatment of sjia with drugs. Evidencebased diagnosis and treatment of macrophage. 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. Macrophage activation syndrome in a child with systemic onset. Mas share similarities in clinical features and laboratory abnormalities with primary and secondary heamophagocytic lymphohystiocytosis hlh. 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. Review macrophage polarization in inflammatory diseases. Macrophage activation syndrome is a serious complication of rheumatic disease, thought to be caused by excessive activation of macrophages and lymphocytes. Those include the activation of stat1 mediated by ifn. Macrophage activation syndrome secondary to underlying. This study aimed to evaluate the demographic, clinical, laboratory properties of patients with macrophage activation syndrome and treatment outcomes. Macrophage activation syndrome genetic and rare diseases. Jan 17, 2017 macrophage activation syndrome mas is a severe complication of rheumatic disease in childhood, particularly in systemic juvenile idiopathic arthritis sjia.
Rheumaknowledgy macrophage activation syndrome mas. Successful tocilizumab therapy for macrophage activation. Macrophage activation syndrome treatment, symptoms, life. Macrophage activation syndrome is considered as a rare syndrome. The array of processes that upregulate macrophage activity. Macrophage activation syndrome mas is a serious, potentially fatal complication of rheumatic diseases, which is seen most frequently in systemic juvenile idiopathic arthritis sjia and in. The pathogenesis of macrophage activation syndrome.
Although the reported mortality rates for mas reach 20%, the clinical presentation of macrophage activation syndrome mas is generally acute and occasionally dramatic. It is often considered a type of secondary hemophagocytic lymphohistiocytosis hlh and results from overactivation of t lymphocytes and macrophages. Soon afterward, her fever ceased and high levels of both ferritin and creactive. Treatment of macrophage activation syndrome mas with. Combining all definite and potential mas cases from the three cohorts.
In recent decades, an uncommon phenomenon of macrophage activation syndrome mas or hemophagocytic syndrome hs is increasingly reported in patients with severe dengue. It is characterised by pancytopenia, liver dysfunction, coagulopathy and neurological symptoms. We present a dermatomyositis patient with mas, caused by hypercytokinemia. Macrophage activation syndrome is a severe, potentially lifethreatening, complication of several chronic rheumatic diseases of childhood. There are four uncommon medical conditions characterized by high levels of ferritin, namely the macrophage activation syndrome. Objectives the aim of our study is to report unrecognized mas manifestation as an initial symptom of sle and describe both clinical and immunological. Pdf background macrophage activation syndrome mas is a severe complication of rheumatic disease in childhood, particularly in systemic juvenile. The macrophage activation syndrome mas in its secondary form is known to complicate rheumatic diseases as systemic lupus erythematous sle but rarely realizes a form of revelation.
Macrophage activation syndrome mas is a severe complication of rheumatic disease in childhood, particularly in systemic juvenile idiopathic arthritis sjia. Evaluation of macrophage activation syndrome associated with. Recent findings in hemophagocytic lymphohistiocytosis, a disease that. Macrophage activation syndrome triggered by coeliac disease. Macrophage activation syndrome mas is a potentially fatal condition. 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. 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. The pathological mechanisms of mas are not fully understood. Mas is a lifethreatening condition associated with high mortality rates.
Mas is a severe, potentially fatal disease characterized by severe systemic inflammation. Mas is currently classified among the secondary or acquired forms of haemophagocytic lymphohistiocytosis shlh. Macrophageactivation syndrome is a severe, potentially lifethreatening, complication of several chronic rheumatic diseases of childhood. Although the clinical features of mas have been well documented, early diagnosis can be difficult. Macrophage activation syndrome case study immunopaedia. Mar 15, 2012 macrophage activation syndrome mas is a serious, potentially fatal complication of rheumatic diseases, which is seen most frequently in systemic juvenile idiopathic arthritis sjia and in its. Macrophage activation syndrome mas, a form of secondary hemophagocytic lymphohistiocytosis, is a frequently fatal complication of a variety of pediatric inflammatory disorders. Macrophage activation syndrome mas is address correspondence to dr wulffraat. It is characterize by an uncontrolled activation and proliferation of t lymphocytes and macrophages. Defining criteria for macrophage activation syndrome, a.
Current associations of macrophage activation syndrome with autoimmune disease most notably include a host of rheumatological conditions and inflammatory. It occurs most commonly with systemiconset juvenile idiopathic arthritis sojia. Over the last few years, accumulating data have implicated a role for ferritin as a signaling molecule and direct mediator of the immune system. Macrophage activation syndrome mas refers to acute overwhelming. It belongs to the hemophagocytic lymphohistiocytosis group of diseases. Successful treatment of macrophage activation syndrome in a. There are four uncommon medical conditions characterized by high levels of ferritin, namely the macrophage activation syndrome mas, adult onset stills disease aosd, catastrophic antiphospholipid syndrome caps and septic shock, that share a similar clinical and laboratory features, and also respond to similar treatments, suggesting a common pathogenic. Macrophage activation syndrome mas is a potentially lifethreatening complication of rheumatic diseases such as systemic juvenile idiopathic arthritis sjia and systemic lupus erythematosus. Macrophage activation syndromeassociated markers in severe.
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. The probable evolution towards a fatal multivisceral failure in the absence of proper diagnosis and management makes it. The main manifestations of mas include fever, hepatosplenomegaly, lymphadenopathy, severe cytopenias, serious liver disease, and disseminated. 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. Macrophage activation syndrome in the era of biologic therapy. Macrophage activation syndrome as onset of systemic lupus.
Anakinra 100 mg subcutaneously daily was initiated, along with pulse methylprednisolone 1 gday for 3 days, then prednisone 25 mg twice daily. Macrophage activation syndrome mas and hemophagocytic lymphohistiocytosis hlh are incompletely understood conditions associated with uncontrolled and ineffective immune activation. 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. Cytokines mediate most of the neurological symptoms. 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. In addition, mas has been described in association with systemic lupus erythematosus sle, kawasaki disease, and adult. If you have problems viewing pdf files, download the latest version of adobe reader. Hlh is termed macrophage activation syndrome mas when associated with rheumatic disease where it is best characterized in systemic jia. Type 2 has mutations in rab27a and haemophagocytic syndrome, with abnormal tcell and macrophage activation.
Macrophage activation syndrome mas aboutkidshealth. Collectively these genetic lesions likely combine with states of chronic. Dec 01, 2010 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. Both conditions have high mortality rates, particularly when untreated 14. For language access assistance, contact the ncats public information officer. However, yet now 100 cases of macrophage activation syndrome is mentioned in medical literature. The treatment strategy for mas is usually based on the parenteral. Macrophage activation syndrome page 2 of 7 the rheumatologist.
Autoimmuneassociated hemophagocytic syndromemacrophage activation syndrome 95 intravenous immunoglobulin ivig, which may be sufficient to control hyperinflammation. Hemophagocytosis was reported in dengue with multiorgan complications 12, observed in severe dengue involving both children and adults 15 and associated with. Macrophage activation syndrome treated with anakinra the. Macrophage activation syndrome is one of the rare causes of puo. Excessive activation and proliferation of t lymphocytes and tissue macrophages histiocytes. Macrophage activation syndrome mas pediatric focus. There are four uncommon medical conditions characterized by high levels of ferritin, namely the macrophage activation syndrome mas, adult onset stills disease aosd, catastrophic antiphospholipid syndrome caps and septic shock, that share a similar clinical and laboratory features, and also respond to similar treatments, suggesting a common pathogenic mechanism. 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 an overview sciencedirect. Sep 17, 2014 the macrophage activation syndrome mas in its secondary form is known to complicate rheumatic diseases as systemic lupus erythematous sle but rarely realizes a form of revelation. Macrophage activation syndrome in systemic juvenile. Injury, surgery or other stressors physical or emotional can trigger systemic flares of fever and macrophage activation syndrome maslike symptoms that can persist for weeks.
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