Treating TAFRO Syndrome: A Case Study of Castleman Disease Kidney Complications

Introduction: TAFRO syndrome, a rare variant of idiopathic multicentric Castleman disease, presents with Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis on bone marrow biopsy, and Organomegaly (TAFRO). This case details successful treatment of a young male with siltuximab, steroids and eculizumab. Case Description: A previously healthy 19-year-old male presented to an outside hospital with respiratory symptoms. Imaging exposed pleural and pericardial effusions requiring drainage, antibiotics, antifungals, and steroids. At that time, he had Cr 1.3 mg/dL, low-grade proteinuria, and negative serologic workup for glomerulonephritis (GN). He presented 3 weeks later with worsening fatigue, edema, nausea, vomiting and diarrhea with Cr 2.5 mg/dL and thrombocytopenia. Renal function rapidly declined, requiring dialysis. Renal biopsy showed features of thrombotic microangiopathy (TMA). He was transferred for higher level of care. Another extensive GN and infectious workup was negative. Imaging showed lymphadenopathy and splenomegaly. Initial lymph node biopsy was inconclusive. Bone marrow biopsy was negative. Patient continued to deteriorate despite steroids to treat suspected Castleman’s disease. A second renal biopsy again showed TMA. Eculizumab was started with improvement in renal function, but not thrombocytopenia. A second lymph node biopsy confirmed a plasma cell variant of Castleman’s disease diagnosing TAFRO. He was started on siltuximab and thrombocytopenia improved after 6 doses. Renal function improved, dialysis was weaned off, and eculizumab was stopped after Castleman’s disease was controlled. Discussion: TAFRO syndrome involves systemic inflammation and is a subtype of multicentric Castleman’s disease (MCD). Lymph node biopsy findings in MCD are crucial for TAFRO diagnosis. Thrombocytopenia, always found in TAFRO, is not always present in MCD. The renal pathology in TAFRO is unclear, but TAFRO may trigger the complement cascade, leading to TMA. Eculizumab can be stopped once TAFRO is controlled. As in other complement mediated diseases, Eculizumab can also be weaned off once the triggering disease is controlled. Further research is needed to understand renal involvement, optimal treatment, and long-term outcomes in TAFRO.