Macrophage activation syndrome is a severe, potentially life-threatening, complication of several chronic rheumatic diseases of childhood. It occurs most commonly with
systemic-onset juvenile idiopathic arthritis (SoJIA). In addition, MAS has been described in association with
systemic lupus erythematosus (SLE),
Kawasaki disease
Kawasaki disease is a syndrome of unknown cause that results in a fever and mainly affects children under 5 years of age. It is a form of vasculitis, where blood vessels become inflamed throughout the body. The fever typically lasts for more th ...
, and
adult-onset Still's disease
Adult-onset Still's disease (AOSD) is a form of Still's disease, a rare systemic autoinflammatory disease characterized by the classic triad of fevers, joint pain, and a distinctive salmon-colored bumpy rash. The disease is considered a diagno ...
. It is thought to be closely related and pathophysiologically very similar to reactive (secondary)
hemophagocytic lymphohistiocytosis
Hemophagocytic lymphohistiocytosis (HLH), 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. It is a ...
(HLH).
The incidence of MAS is unknown as there is a wide spectrum of clinical manifestations, and episodes may remain unrecognized.
Signs and symptoms
The hallmark clinical and laboratory features include high fever,
hepatosplenomegaly
Hepatosplenomegaly (commonly abbreviated HSM) is the simultaneous enlargement of both the liver (hepatomegaly) and the spleen (splenomegaly). Hepatosplenomegaly can occur as the result of acute viral hepatitis, infectious mononucleosis, and his ...
,
lymphadenopathy,
pancytopenia
Pancytopenia is a medical condition in which there is significant reduction in the number of almost all blood cells (red blood cells, white blood cells, platelets, monocytes, lymphocytes, etc.).
If only two parameters from the complete blood coun ...
,
liver dysfunction
Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.
Signs and symptoms
Some of the s ...
,
disseminated intravascular coagulation,
hypofibrinogenemia,
hyperferritinemia, and
hypertriglyceridemia
Hypertriglyceridemia is the presence of high amounts of triglycerides in the blood. Triglycerides are the most abundant fatty molecule in most organisms. Hypertriglyceridemia occurs in various physiologic conditions and in various diseases, and ...
. Despite marked systemic inflammation, the
erythrocyte sedimentation rate
The erythrocyte sedimentation rate (ESR or sed rate) is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. It is a common hematology test, and is a non-specific measure of ...
(ESR) is paradoxically depressed, caused by low
fibrinogen
Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood cl ...
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.
Cause
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
Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony-stimulating factor 2 (CSF2), is a monomeric glycoprotein secreted by macrophages, T cells, mast cells, natural killer cells, endothelial cells and fibroblasts tha ...
. The underlying causative event is unclear, and is the subject of ongoing research. In many cases of MAS, a decreased
natural killer cell (NK-cell) function is found.
Diagnosis
A febrile patient with known or suspected SoJIA must be considered for macrophage activation if:
* Ferritin >684 ng/ml
and any 2 of the following:
* Hemoglobin <90g/L (in infants <4 weeks: <100g/L)
* Platelets <100 x 109/L
* Neutrophils <1.0 x 109/L
* Fasting triglycerides ≥3.0 mmol/L (i.e., ≥ 265 mg/dl)
* Fibrinogen ≤1.5 g/L
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
Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
, and
cyclosporine
Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease ...
. In refractory cases treatment regimens are used similar to that in HLH.
Anakinra
Anakinra, sold under the brand name Kineret, is a biopharmaceutical medication used to treat rheumatoid arthritis, cryopyrin-associated periodic syndromes, familial Mediterranean fever, and Still's disease. It is a recombinant and slightly modif ...
is also effective.
See also
*
Cytokine release syndrome
References
External links
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, SNOMED CT = 430478003
Macrophage Activation Syndrome MedScape
Rheumatology
Syndromes