A 33 year-old Hispanic male without significant history presented with an unremitting fever for 5 days, associated with myalgais, fatigue, night sweats, and a rash. Upon admission, he was tachycardic, hypotensive and febrile at 103F. Physical exam revealed a diffuse non-blanching, maculo-papular rash, sparing the face, palms and soles. Labs revealed pancytopenia, transaminitis, elevated ferritin, and low fibrinogen. He was started on empiric antibiotics. Blood cultures were drawn and returned negative, yet he continued to spike fevers. On the 4th day, he suffered acute respiratory distress syndrome (ARDS), was intubated and transferred to the intensive care unit (ICU), where he continued to deteriorate.
Given the clinical picture of persistent fever, pancytopenia, transaminitis, low fibrinogen and elevated ferritin, Macrophage Activation Syndrome was considered, based on recent classification criteria. He was started on high-dose methylprednisolone. He rapidly recovered, was extubated within 24 hours and discharged later that week.
Discussion:
Macrophage Activation Syndrome (MAS) is a rare but life-threatening systemic inflammatory complication, arising from viral infections, rheumatological conditions, malignancies, and immunological deficiencies. It is characterized by an uncontrolled immune response, involving the expansion of T-Cells, Macrophages, and the hypersecretion of pro-inflammatory cytokines.
The pathophysiology of this disease is not fully understood, and the diagnostic criteria have been hotly debated. This year, an international panel of experts just released new guidelines for the diagnosis of MAS. The 2016 criteria offers greater sensitivity, specificity, and laboratory guidelines. Our case provides support for these new guidelines, and is possibly the first published after their release. The classic finding of hemophagocytic macorphages on biopsy is neither sensitive nor specific. Diagnosis is made by a suspicious clinical presentation, with fever and hyperferritinemia, along with two of the following: thrombocytopenia, triglyceridemia, hypofibrinoginemia or transaminitis. First line treatment is methyprednisolone, with the addition of cyclosporin in refractory cases.
Conclusions:
MAS is a rare condition with a debated definition, and a mortality rate of up to 30%. As a result, it remains a diagnostic menace. This case supports the new 2016 guidelines and confirms methylprednisolone as a first-line treatment. Furthermore, it provides another data point in the investigation of this perplexing and dangerous phenomenon.