, A man in his 60s with a history of dyslipidemia presented with month-long fever (38 °C), diarrhea, abdominal pain, and anorexia. Physical examination showed stable vital signs, mild abdominal tenderness, and generalized anasarca without dehydration. The patient exhibited no arthralgia, skin rash, neuropathy, or lymphadenopathy. Imaging demonstrated pericardial effusion, pleural effusion, ascites, and hepatosplenomegaly (Fig. 1).
Laboratory evaluation revealed severe thrombocytopenia (platelet count, 8,000/μL), impaired renal function (creatinine, 3.26 mg/dL), and elevated inflammatory markers (C-reactive protein, 14.56 mg/dL). Urinalysis demonstrated hematuria (red blood cell, 50–99/high power field) and proteinuria (1.13 g/gCr). Urinary electrolytes were markedly decreased (Na, <20 mEq/L; Cl, <20 mEq/L), indicating significant fluid retention. Comprehensive serologic testing, including complement levels, gamma globulin, antinuclear antibodies, and M-protein, yielded normal or negative results. Bone marrow examination showed no evidence of hemophagocytosis, hematopoietic abnormalities, or malignancy.
Initial broad-spectrum antimicrobial therapy proved ineffective, and despite multiple platelet transfusions, the patient’s condition deteriorated. Given the clinical constellation and elevated serum vascular endothelial growth factor (VEGF; 426 pg/mL) and interleukin 6 (IL-6; 21.9 pg/mL) levels, we suspected TAFRO syndrome. Treatment was initiated with prednisolone 40 mg daily. Renal biopsy revealed mesangiolysis, endothelial cell swelling with marked subendothelial space expansion, and glomerular basement membrane double contours (Fig. 2A). Immunofluorescence microscopy showed no significant immune deposits. Electron microscopy revealed pathognomonic striped noncrystalline deposits within the expanded subendothelial space (Fig. 2B).
Following corticosteroid therapy, the patient’s symptoms improved substantially, with renal function recovering to a creatinine level of 0.8–0.9 mg/dL and proteinuria decreasing to 0.18 g/gCr.
This study was approved by the Institutional Review Board of the Tohoku Medical and Pharmaceutical University Hospital (No. 2023-4-005). It was conducted in accordance with the Declaration of Helsinki of the World Medical Association. We obtained informed consent from the patient for publication of this report in accordance with the journal’s patient consent policy.
TAFRO syndrome represents a distinct clinicopathological entity characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. The renal manifestations exhibit characteristic pathological features of glomerular microangiopathy (GMA), with electron microscopy revealing distinctive striped noncrystalline deposits within the expanded subendothelial space.
The pathogenesis involves mesangial cell dysfunction, leading to altered glomerular hemodynamics. Specifically, mesangial cell injury results in compromised inward traction forces, facilitating the accumulation of plasma components adjacent to the endothelium, ultimately culminating in endothelial cell alterations and subendothelial edema. The marked reduction in urinary sodium excretion, despite euvolemia, suggests primary sodium retention mechanisms.
The IL-6/VEGF axis plays a crucial role in disease manifestation. Elevated IL-6 levels trigger enhanced VEGF production, resulting in decreased salt excretion and increased vascular permeability, thereby explaining the characteristic anasarca.
While TAFRO syndrome shares certain clinical features with idiopathic multicentric Castleman disease (iMCD), their renal manifestations are distinctly different. In contrast to iMCD, which presents with various glomerular pathologies, TAFRO syndrome consistently demonstrates GMA without immune complex deposition.
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