Macrophage-activation syndrome (MAS) is a severe, potentially life-threatening, complication of several chronic rheumatic diseases of childhood. It occurs most commonly with systemic-onset juvenile idiopathic arthritis

Juvenile idiopathic arthritis

Juvenile idiopathic arthritis is the most common form of persistent arthritis in children. JIA is a subset of arthritis seen in childhood, which may be transient and...

 (SoJIA), which is also known as Still's disease

Still's disease

Still's disease can refer to:* Juvenile idiopathic arthritis* Adult-onset Still's disease...

. In addition, MAS has been described in association with systemic lupus erythematosus

Systemic lupus erythematosus

Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...

 (SLE), Kawasaki disease

Kawasaki disease

Kawasaki disease , also known as Kawasaki syndrome, lymph node syndrome and mucocutaneous lymph node syndrome, is an autoimmune disease in which the medium-sized blood vessels throughout the body become inflamed. It is largely seen in children under five years of age...

, and adult-onset Still's disease. It is thought to be closely related and pathophysiologically very similar to reactive (secondary) hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis , also known as hemophagocytic syndrome, is an uncommon hematologic disorder that, typically, clinically manifests as fever, hepatosplenomegaly, lymphadenopathy, jaundice and rash, with laboratory findings of lymphocytosis and histiocytosis, and the pathologic...

 (HLH). The incidence of MAS is unknown as there is a wide spectrum of clinical manifestations, and episodes may remain unrecognized.

Clinical and laboratory findings

The hallmark clinical and laboratory features include high fever, hepatosplenomegaly

Hepatosplenomegaly

Hepatosplenomegaly is the simultaneous enlargement of both the liver and the spleen . Hepatosplenomegaly can occur as the result of acute viral hepatitis or infectious mononucleosis, or it can be the sign of a serious and life threatening lysosomal storage disease...

, lymphadenopathy

Lymphadenopathy

Lymphadenopathy is a term meaning "disease of the lymph nodes." It is, however, almost synonymously used with "swollen/enlarged lymph nodes". It could be due to infection, auto-immune disease, or malignancy....

, pancytopenia

Pancytopenia

Pancytopenia is a medical condition in which there is a reduction in the number of red and white blood cells, as well as platelets.If only two parameters from the full blood count are low, the term bicytopenia can be used...

, liver dysfunction, disseminated intravascular coagulation

Disseminated intravascular coagulation

Disseminated intravascular coagulation , also known as disseminated intravascular coagulopathy or consumptive coagulopathy, is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside the blood...

, hypofibrinogenemia, hyperferritinemia, and hypertriglyceridemia

Hypertriglyceridemia

In medicine, hypertriglyceridemia denotes high blood levels of triglycerides, the most abundant fatty molecule in most organisms. It has been associated with atherosclerosis, even in the absence of hypercholesterolemia . It can also lead to pancreatitis in excessive concentrations In medicine,...

. Despite marked systemic inflammation, the erythrocyte sedimentation rate

Erythrocyte sedimentation rate

The erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...

 (ESR) is paradoxically depressed, caused by low fibrinogen

Fibrinogen

Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...

 levels. The low ESR helps to distinguish the disorder from a flare of the underlying rheumatic disorder, in which case the ESR is usually elevated. A bone marrow biopsy or aspirate usually shows hemophagocytosis

Hemophagocytosis

Hemophagocytosis is phagocytosis by histiocytes of erythrocytes, leukocytes, platelets, and their precursors in bone marrow and other tissues.It is part of the presentation of hemophagocytic lymphohistiocytosis....

.

Etiology and pathophysiology

In many cases a trigger is identified, often a viral infection, or a medication. There is uncontrolled activation and proliferation of macrophages, and T lymphocytes, with a marked increase in circulating cytokines, such as IFN-gamma, and GM-CSF. The underlying causative event is unclear, and is the subject of ongoing research. In many cases of MAS, a decreased natural killer cell

Natural killer cell

Natural killer cells are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses...

 (NK-cell) function is found.

Diagnosis

The diagnosis relies on the findings outlined above. In addition, other specific markers of macrophage activation (e.g. soluble CD163), and lymphocyte activation (e.g. soluble IL-2 receptor) can be helpful. NK cell function analysis may show depressed NK function, or, flow cytometry may show a depressed NK cell population.

Treatment

The best treatment for MAS has not been firmly established. Most commonly used treatments include high-dose glucocorticoids, and cyclosporine. In refractory cases treatment regimens are used similar to that in HLH.

External links

• Macrophage Activation Syndrome, MedScape