Diagnosing haemophagocytic syndrome

Abstract

Haemophagocytic syndrome, or haemophagocytic lymphohistiocytosis (HLH), is a hyperinflammatory disorder characterised by uncontrolled activation of the immune system. It can result from mutations in multiple genes involved in cytotoxicity or occur secondary to a range of infections, malignancies or autoimmune rheumatic diseases. In the latter case, it is also known as macrophage activation syndrome (MAS). Characteristic features are persistent fever, hepatosplenomegaly, petechial/purpuric rash, progressive cytopenias, coagulopathy, transaminitis, raised C reactive protein, falling erythrocyte sedimentation rate, hypertriglyceridaemia, hypofibrinogenaemia and extreme hyperferritinaemia often associated with multi-organ impairment. Distinguishing HLH from systemic sepsis can present a major challenge. Criteria for diagnosis and classification of HLH and MAS are available and a serum ferritin >10 000 µg/L is strongly supportive of HLH. Without early recognition and appropriate treatment, HLH is almost universally fatal. However, with prompt referral and advancements in treatment over the past two decades, outcomes have greatly improved.

H-ferritin and proinflammatory cytokines are increased in the bone marrow of patients affected by macrophage activation syndrome

“…These results suggest potentially new biomarkers evaluating severity of the MAS clinical picture, possibly improving outcome in these patients [37,38]. In fact, diagnosis and appropriate treatments may be delayed, due to non-specific findings in the early phases of disease, thus new biomarkers may improve the management of this life-threating syndrome [39][40][41][42]. Although a rigorous process of validation is needed, the use of novel biomarkers in these patients may help physicians, thus improving diagnosis with early recognition and prompt therapy as well as predicting response to treatment and outcome, as suggested in other rheumatic diseases [43][44][45][46][47].…”

Macrophage activation syndrome in adult systemic lupus erythematosus: report of seven adult cases from a single Italian rheumatology center

“…M acrophage activation syndrome (MAS) is a severe and life-threatening disease, characterized by uncontrolled activation of the immune system with proliferation of T cells and well-differentiated non-neoplastic macrophages, which exhibit hemophagocytic activity (1). This massive systemic inflammatory response is associated with cytopenia, liver dysfunction, coagulopathy and extreme hyperferritinemia.…”

“…MAS has been reported in association with almost any rheumatologic disorders, but the most common associations are, by far, with systemic juvenile idiopathic arthritis, adult-onset Still disease, and systemic lupus erythematosus (SLE) (1). MAS occurring in patients with SLE and other autoimmune diseases can be separated into two Adult SLE-associated MAS ORIGINAL PAPER different entities: cases associated with an active infection, often as a complication of immunosuppressive therapy, and cases specifically associated with activity of the underlying disease (at its onset, or during a flare) (1). Data on SLE-associated MAS are still limited.…”

“…This massive systemic inflammatory response is associated with cytopenia, liver dysfunction, coagulopathy and extreme hyperferritinemia. It is classified in: 1) primary (or familial) hemophagocytic lymphohistiocytosis (HLH), a constellation of rare autosomal recessive disorders associated with various abnormalities in the cytolytic pathway; 2) secondary MAS, triggered by conditions affecting immune homeostasis, such as infections, malignancies, and autoimmune disorders (1). MAS has been reported in association with almost any rheumatologic disorders, but the most common associations are, by far, with systemic juvenile idiopathic arthritis, adult-onset Still disease, and systemic lupus erythematosus (SLE) (1).…”

“…It is classified in: 1) primary (or familial) hemophagocytic lymphohistiocytosis (HLH), a constellation of rare autosomal recessive disorders associated with various abnormalities in the cytolytic pathway; 2) secondary MAS, triggered by conditions affecting immune homeostasis, such as infections, malignancies, and autoimmune disorders (1). MAS has been reported in association with almost any rheumatologic disorders, but the most common associations are, by far, with systemic juvenile idiopathic arthritis, adult-onset Still disease, and systemic lupus erythematosus (SLE) (1). MAS occurring in patients with SLE and other autoimmune diseases can be separated into two Adult SLE-associated MAS ORIGINAL PAPER different entities: cases associated with an active infection, often as a complication of immunosuppressive therapy, and cases specifically associated with activity of the underlying disease (at its onset, or during a flare) (1).…”