Case Presentation: A 38-year-old man without stable housing presented with severe anasarca, a diffuse rash, cytopenias, and acute kidney injury. He had recently trekked the Appalachian Trail. On admission, he was febrile at 38.5°C and tachycardic at 118 beats per minute. He was profoundly edematous, with tense ascites and bilateral pleural effusions on imaging. Laboratory evaluation showed thrombocytopenia of 58 K/µL, anemia with hemoglobin of 8.9 g/dL, elevated C-reactive protein, hypoalbuminemia, and creatinine of 3.1 mg/dL.CT imaging of the abdomen and pelvis revealed large-volume ascites and retroperitoneal lymphadenopathy initially interpreted as reactive. Differential diagnoses included cirrhosis, thrombotic microangiopathy, glomerulonephritis, and systemic infection. Diagnostic paracentesis showed high SAAG, high protein ascites without evidence of infection or malignancy, making cirrhosis and peritoneal malignancy less likely and raising concern for a systemic inflammatory or capillary leak process.His course was complicated by worsening renal failure and hypoxic respiratory failure from volume overload, requiring ICU transfer and hemodialysis. Blood cultures later grew Staphylococcus species, and broad-spectrum antibiotics were started. Despite appropriate therapy and improved respiratory status, his anasarca worsened, inflammatory markers remained elevated, and thrombocytopenia persisted, while hepatic enzymes remained relatively normal. Autoimmune and hematologic evaluations were unrevealing.Reconsideration of these discordant findings, together with the earlier retroperitoneal lymphadenopathy, raised concern for a lymphoproliferative or cytokine-mediated process. After multidisciplinary discussion and stabilization, an excisional lymph node biopsy was performed. Histopathology demonstrated atrophic germinal centers with vascular proliferation and interfollicular plasmacytosis, confirming idiopathic multicentric Castleman disease with TAFRO features. Treatment with tocilizumab, rituximab, and corticosteroids led to gradual diuresis, improved inflammatory markers, and recovery of renal function with dialysis independence.
Discussion: TAFRO syndrome is a rare cytokine-driven inflammatory disorder that causes massive anasarca, cytopenias, organomegaly, and multiorgan dysfunction. Its presentation often resembles sepsis, macrophage activation syndrome, autoimmune disease, or malignancy, which contributes to delayed recognition. Distinguishing clues include thrombocytopenia out of proportion to systemic inflammation, preserved hepatic enzymes despite large-volume ascites, and persistent inflammatory elevation without an infectious source. High protein, high SAAG ascites can support a non-cirrhotic inflammatory process.
Conclusions: This case underscores the importance of revisiting early diagnostic information when a patient’s clinical course diverges from expectations. Integration of evolving laboratory and imaging data led to timely biopsy and disease-directed treatment. Hospitalists, through continuous assessment and coordination, are well positioned to identify such diagnostic inflection points in complex multisystem illness.