Macrophage activation syndrome (MAS), first named in 1993, is a subcategory of hemophagocytic lymphohistiocytosis (HLH), characterized by prolonged fever, hepatosplenomegaly, pancytopenia, liver dysfunction, and most notably hyperferritinemia. MAS, in particular, is the term used to describe secondary HLH, or HLH caused by rheumatologic conditions. Secondary HLH can also be associated with other systemic autoimmune diseases, underlying malignancy, infection, or medications and can be a life-threatening complication. MAS is characterized by unwarranted proliferation and stimulation of T cells and benign macrophages leading to an excessive inflammatory state with hypersecretion of cytokines. This, in turn, leads to phagocytosis of normal blood cells and injury to the organs containing these macrophages (liver, spleen, bone marrow, lymph nodes). With regard to rheumatologic conditions, MAS is most often seen associated with juvenile idiopathic arthritis (incidence of 7-13%) while it is much less commonly seen in systemic lupus erythematosus (SLE) with an incidence of 0.9-4.6%. The etiology is unknown, although there are hypotheses.
A 53 year old female with SLE complicated by lupus nephritis and lupus anticoagulant initially presented with a syncopal episode. While walking out of the rheumatologist office, she felt faint and had an assisted fall to the floor with transient loss of consciousness. The patient reported approximately 1-2 months of decreased oral intake, weight loss, daily fevers to 102-103°F, lightheadedness, dry cough, and 1 week of rash on her upper chest. During this time, her rheumatologist adjusted her SLE medications, attributing her symptoms to a SLE flare. Work up during this admission (labs listed in Table 1) ruled out sepsis as a source of fever. It was determined that her symptoms and lab abnormalities were likely secondary to a lupus flare given her fever, rash, constitutional symptoms, and pancytopenia in the setting of SLE that was difficult to control. Early macrophage activation syndrome (MAS) was also on the differential given the elevated ferritin level. Her symptoms improved with pulse dose steroids and resuming mycophenolate mofetil for immunosuppression. The plan was to change this to cyclosporine as an outpatient to prevent MAS.
Before switching to cyclosporine however, the patient was readmitted for recurrent fevers, fatigue, diarrhea, and worsening lab abnormalities. On admission, her physical exam was significant for fever to 102.4°F, tachycardia, and dry mucus membranes. Labs are shown in Table 2. The most remarkable finding was a ferritin of 11,741 which was a significant increase from 4,542 during her last admission. The patient underwent a bone marrow biopsy, which demonstrated increased macrophages with hemophagocytic activity, confirming a diagnosis of MAS.
McGhee, MD, Amy
"Persistent Fever and Pancytopenia: Lupus Flare vs Macrophage Activation Syndrome,"
The Medicine Forum: Vol. 16, Article 11.
Available at: https://jdc.jefferson.edu/tmf/vol16/iss1/11