Case Presentation: Case 1: A 25-year-old female was transferred to our hospital with fever and systemic inflammation refractory to prednisolone treatment. Two weeks prior to the transfer, she was admitted to another hospital on account of fever, thrombocytopenia, elevated alkaline phosphatase level and hepatonephromegaly on CT scan. No peripheral edema, pleural effusion, ascites or lymphadenopathy were noted. Bone marrow biopsy revealed increased number of megakaryocytes and diminished levels of hemophagocytosis. She was treated with 30 mg/day of prednisolone, which turned out to be ineffective in managing her symptoms. After the transfer, she was treated with methylprednisolone pulse therapy based on the diagnosis of hemophagocytic syndrome due to viral infection. Her symptoms subsided, and she was discharged home on 10mg/day of prednisolone. Ten days after discharge, she was readmitted to our hospital due to recurrent fever and systemic inflammation. At that time, a small left cervical lymphadenopathy（1.0 cm in diameter) was noted. The result of cervical lymph node biopsy was consistent with TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis, organomegaly) syndrome. Her symptoms resolved after addition of cyclosporine 6 mg/kg/day.
Case 2: A 66-year-old male was admitted to our hospital with fever, systemic inflammation, thrombocytopenia and elevated alkaline phosphatase level. He was first diagnosed with TAFRO syndrome two years prior to admission and followed up with prednisolone. Upon admission, there were pleural effusion, ascites and paraaortic lymphadenopathy on CT scan. He was treated with 40 mg/day of intravenous dexamethasone for three days and 3 mg/day of cyclosporine. Additionally, he was treated with bortezomib considering his presentation as a variant of multicentric Castleman disease (MCD). He was discharged on prednisolone 10 mg and cyclosporine 3 mg/day.
Discussion: TAFRO syndrome, which was first described in 2010, is a systemic inflammatory disorder characterized by thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R) and organomegaly (O). TAFRO syndrome was first described as a variant of MCD, characterized by polyclonal hypergammaglobulinemia, multiple lymphadenopathy and a chronic clinical course. However, it is currently considered as a distinct clinical entity with hypo- to normogammaglobulinemia, thrombocytopenia, elevated alkaline phosphatase and acute to subacute disease progression. Because it is diagnosed with combinations of clinical conditions, it may still be heterogeneous. Cyclosporine is a key drug for patients with moderate symptoms. In patients with severe symptoms, the treatment strategy is planned based on their conditions. In our cases, the first patient had no pleural effusion or ascites. Her lymphadenopathy was almost insignificant with respect to size. On the contrary, the second patient demonstrated apparent fluid retention and lymphadenopathy, which resembled MCD. Although cyclosporine seems to be an essential drug, we need to consider additional agents in patients with fatal symptoms based on the pathophysiology.
Conclusions: Our cases illustrate the need to recognize TAFRO syndrome as a differential diagnosis in patients with fever, systemic inflammation, thrombocytopenia, and elevated alkaline phosphatase. Since it is still a heterogeneous entity, the treatment strategy should be based on the clinical presentation and underlying pathophysiology of the individual patient.