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macrophage activation syndrome

Etiology: - complication of rheumatoid disease - systemic juvenile idiopathic arthritis - adult-onset Still disease - systemic lupus erythematosus - Kawasaki disease - viral infections (influenza, Herpes simplex, & EBV) Pathology: - hepatosplenomegaly - hepatic insufficiency - coagulopathy - neurologic disorder - activation & uncontrolled proliferation of T-cells & well-differentiated macrophages, leading to widespread hemophagocytosis & cytokine overproduction - decreased NK-cell cytolytic function resulting from decreased perforin gene (PRF1) expression - expansion of cytotoxic T lymphocytes that produce macrophage- activating cytokines, including IFN-gamma - alternative pathway of macrophage differentiation - elevated IL-18 in serum Laboratory: - complete blood count: pancytopenia - liver function tests - serum transaminases may be moderate elevated - serum ferritin: very elevated [4] - prothrombin time, INR often prolonged - aPTT often prolonged - D-dimer: fibrin degradation products often present - plasma fibrinogen: hypofibrinogenemia - serum triglycerides: hypertriglyceridemia - IL-18 in serum elevated Complications: - may be rapidly fatal (8-60%) [4] Management: - parenteral administration of high doses of corticosteroids - high-dose intravenous immunoglobulins, cyclophosphamide, plasma exchange, & etoposide has been used with conflicting results - cyclosporine A may be useful in corticosteroid-resistant disease - stem cell transplantation provides only long-term disease-free survival - consults: - rheumatology - hematology/oncology - infectious disease

Specific

hemophagocytic lymphohistiocytosis; hemophagocytic syndrome

General

leukocyte disorder syndrome

References

  1. Ravelli A et al eMedicine: Macrophage Activation Syndrome http://emedicine.medscape.com/article/1380671-overview
  2. Ravelli A Macrophage activation syndrome. Curr Opin Rheumatol. 2002 Sep;14(5):548-52. PMID: 12192253
  3. Sawhney S et al Macrophage activation syndrome: a potentially fatal complication of rheumatic disorders Arch Dis Child 2001;85:421-426 PMID: 11668110 http://adc.bmj.com/content/85/5/421.abstract
  4. Cho J, Jong SC, Ng SB et al A Woman With Fever and Lymphadenopathy. JAMA. 2018;319(24):2552-2553. PMID: 29946706 https://jamanetwork.com/journals/jama/fullarticle/2685964