Case Presentation: A 21M with a PMHx of juvenile rheumatoid arthritis on chronic prednisone and Ilaris presented with fevers and diarrhea. He was seen by his rheumatologist on morning of presentation for his monthly Ilaris injection, who sent him in when he was found to be hypotensive and febrile in the office. Patient endorsed a two day history of diarrhea and two episodes of non-bilious, non-bloody vomiting. Vital signs on admission were significant for fever to 100.4, tachycardia, and hypotension unresponsive to IV fluids. Physical examination revealed mild tenderness to palpation in the lower abdominal quadrants bilaterally. Laboratory studies revealed microcytic anemia, thrombocytopenia, leukocytosis, hyponatremia, elevated lactate, and transaminitis. A chest X-ray was clear and a CT abdomen revealed mild splenomegaly. He was started on vancomycin and zosyn for presumed sepsis. Patient became hypothermic to 92.9F the day after admission with an increasing serum lactate. The patient’s infectious workup including UA, hepatitis panel, EBV, CMV, mononucleosis, c. difficile, stool ova and parasite, blood cultures, and urine cultures were all negative. Patient’s anemia workup was significant for serum ferritin of 143,373 and an LDH of 648. Antibiotics were discontinued and he was started on high dose IV Decadron and fludrocortisone, resulting in marked clinical improvement. A bone marrow biopsy revealed hemoerythrophagocytosis, consistent with a diagnosis of macrophage activation syndrome. He completed six days of IV therapy and was discharged to home on oral Decadron and fludrocortisone with plan for rheumatologic follow-up.
Discussion: Macrophage activation syndrome (MAS) is a rare, but life-threatening complication of systemic juvenile idiopathic rheumatoid arthritis (SoJIA). Symptoms are caused by an overwhelming inflammatory response due to T cell and macrophage activation, resulting in sudden onset of fevers and hypotension. The diagnosis is often delayed due to its similar presentation to SIRS and sepsis, resulting in a mortality rate as high as 22%. Currently, there are no definitive diagnostic criteria for MAS. The syndrome is characterized by an acute onset of systemic signs of illness including fevers, hypotension, lymphadenopathy, and hepatosplenomegaly. Laboratory features include pancytopenia, coagulopathy, hyponatremia, hypertriglyceridemia, hyperferritinemia, abnormal liver function tests, and a paradoxical decrease in ESR. Elevated serum ferritin may be particularly suggestive of MAS, since ferritin has been found to be secreted by activated macrophages and released by tissues when damaged by activated macrophages. A definitive diagnosis requires a bone marrow biopsy which shows macrophage hemophagocytosis. The etiology of MAS is not well understood, but can potentially be triggered by flares in existing SoJIA, viral or bacterial illnesses, or new medications. Early detection and treatment is crucial for patients with MAS. Approximately 50% of patients will respond with high-dose IV corticosteroids for 3-10 days, followed by transition to oral prednisone. Cyclosporin is second-line treatment.
Conclusions: Here we report a rare case of MAS in a patient with history of SoJIA presenting with fevers and hypotension. There are no definitive diagnostic criteria for MAS, but it often resembles sepsis, which can cause a delay in diagnosis and therefore increased morbidity and mortality. If appropriately identified, patients often respond favorably to IV steroids.