Macrophage activation syndromeis a severe, potentially life-threatening, complication of several chronic rheumatic diseases of childhood. It occurs most commonly withsystemic-onset juvenile idiopathic arthritis(SoJIA). In addition, MAS has been described in association withsystemic lupus erythematosus(SLE),Kawasaki disease,andadult-onset Still's disease.It is thought to be closely related and pathophysiologically very similar to reactive (secondary)hemophagocytic lymphohistiocytosis(HLH).[1]The incidence of MAS is unknown as there is a wide spectrum of clinical manifestations, and episodes may remain unrecognized.
| Macrophage activation syndrome | |
|---|---|
| Other names | MAS |
| Specialty | Rheumatology |
Signs and symptoms
editThe hallmark clinical and laboratory features include high fever,hepatosplenomegaly,lymphadenopathy,pancytopenia,liver dysfunction,disseminated intravascular coagulation,hypofibrinogenemia,hyperferritinemia,andhypertriglyceridemia.Despite marked systemic inflammation, theerythrocyte sedimentation rate(ESR) is paradoxically depressed, caused by lowfibrinogenlevels. 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 showshemophagocytosis.
Cause
editIn many cases a trigger is identified, often a viral infection, or a medication.[2]There is uncontrolled activation and proliferation of macrophages, and T lymphocytes, with a marked increase in circulating cytokines, such asIFN-gamma, andGM-CSF.The underlying causative event is unclear, and is the subject of ongoing research. In many cases of MAS, a decreasednatural killer cell(NK-cell) function is found.
Diagnosis
editA 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[3]
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. [4]
Treatment
editThe best treatment for MAS has not been firmly established. Most commonly used treatments include high-doseglucocorticoids,andcyclosporine.In refractory cases treatment regimens are used similar to that in HLH.
See also
editReferences
edit- ^Grom AA, Mellins ED (September 2010)."Macrophage activation syndrome: advances towards understanding pathogenesis".Curr Opin Rheumatol.22(5): 561–6.doi:10.1097/01.bor.0000381996.69261.71.PMC4443835.PMID20517154.
- ^Agarwal S (2011). "A rare trigger for macrophage activation syndrome".Rheumatology International.31(3): 405–7.doi:10.1007/s00296-009-1204-0.PMID19834709.S2CID8454417.
- ^"Macrophage Activation Syndrome".
- ^Badugu, Srinivasarao (2010). "MACROPHAGE ACTIVATIONS SYNDROME, AN IMPORTANT DIFFERENTIAL DIAGNOSIS FOR SEPTIC SHOCK".Critical Care Medicine.38.
- ^Halyabar, Olha; Chang, Margaret H.; Schoettler, Michelle L.; Schwartz, Marc A.; Baris, Ezgi H.; Benson, Leslie A.; Biggs, Catherine M.; Gorman, Mark; Lehmann, Leslie; Lo, Mindy S.; Nigrovic, Peter A.; Platt, Craig D.; Priebe, Gregory P.; Rowe, Jared; Sundel, Robert P. (2019-02-14)."Calm in the midst of cytokine storm: a collaborative approach to the diagnosis and treatment of hemophagocytic lymphohistiocytosis and macrophage activation syndrome".Pediatric Rheumatology.17(1): 7.doi:10.1186/s12969-019-0309-6.ISSN1546-0096.PMC6376762.PMID30764840.
External links
edit- Macrophage Activation Syndrome,MedScape