Case Presentation: A 29-year-old female with a past medical history of microcytic anemia and recently-diagnosed AOSD presented with 2 weeks of progressive dyspnea. On her preceding hospital admission, her AOSD was diagnosed and clinical suspicion for MAS was initially mounted. At that time, she demonstrated polyarthralgia, pruritic rash, high-grade fevers, hepatosplenomegaly, diffuse lymphadenopathy, neutrophilic leukocytosis, elevated aspartate aminotransferase, hypertriglyceridemia, profoundly elevated ferritin, and elevated soluble CD25. Infectious, autoimmune, and malignant workups were negative. A lymph node biopsy revealed nonspecific paracortical hyperplasia with many immunoblasts and a bone marrow biopsy was free of hemophagocytosis. Following clinical improvement, the patient was discharged on anakinra and prednisone. 14 days later she re-presented with rapidly progressing dyspnea. On this admission, the patient continued to meet clinical criteria for both AOSD and MAS but newly demonstrated pancytopenia and heart failure with an ejection fraction of 25-30%. In addition to continuing glucocorticoids and anakinra, the patient underwent repeat bone marrow biopsy, which newly demonstrated hemophagocytosis. She was started on etoposide and goal-directed medical therapy for systolic heart failure with which she ultimately experienced clinical improvement of her pancytopenia and heart failure symptoms. She was discharged to outpatient hematologist and rheumatologist follow up.
Discussion: This case demonstrates the significant clinical overlap of AOSD and MAS. The patient satisfied both the Yamaguchi criteria for AOSD and the HScore threshold for sHLH (i.e. MAS in this patient) on both hospital admissions. Her subsequent pancytopenia only strengthened her clinical diagnosis of MAS. Both disease processes have been associated with autoinflammatory myocarditis, but this patient’s systolic dysfunction only began to clinically improve after initiation of etoposide for MAS. While bone marrow histopathology can supplement diagnostic evaluations for MAS, it is neither sensitive nor specific and should not singularly influence clinical decision-making. Both of these disease processes demonstrate hypercytokinemia, but MAS is also marked by cytolytic dysfunction and histiocytic proliferation. Unsurprisingly, glucocorticoids and cytokine-directed therapies like anakinra have been successfully used as first- and second-line agents for both diseases but, in cases of refractory or severe MAS, etoposide is considered the specific therapeutic choice.
Conclusions: MAS is a potentially lethal manifestation of AOSD and other rheumatic diseases. Furthermore, it remains a clinical diagnosis. If a patient persistently meets inclusionary and exclusionary clinical criteria for MAS or develops multi-organ dysfunction in their setting, graduation to MAS-specific therapy should be considered regardless of clinical symmetry with underlying rheumatic disease or negative histopathologic findings.