Case Presentation
A 45-year-old man was transferred to our hospital for the evaluation of renal dysfunction and anasarca. After the first dose of the COVID-19 mRNA vaccine (Moderna), he developed fever and macrohematuria for 3 to 4 days and developed edema and abdominal distension from the day after the first COVID-19 mRNA vaccination. Six days after vaccination, his symptom was persisted and he was detected renal dysfunction (eGFR 39.2 mL/min/1.73 m2, serum Creatinine 1.59 mg/dL), elevated C-reactive protein value (22.4 mg/dL), and proteinuria.
On admission to our hospital, the patient was 171.0 cm tall and weighed 80.0 kg (weight gain of 7 kg in 1 week), with a blood pressure of 142/73 mmHg, pulse rate of 60 /min, and body temperature of 37.3 degree. He complained of epigastric pain, dyspnea, and bilateral pitting edema of the lower extremities. Oxygen saturation was 92% in room air. Electrocardiography was normal, and echocardiogram revealed normal left ventricular systolic function. Laboratory data revealed elevated levels of C-reactive protein (22.6 mg/dL) and renal dysfunction (eGFR 49 ml/min/1.73 m2). The platelet count was 9.1 × 10³ /μL (Table 1). The PCR test results for COVID-19 were negative.
Bilateral pleural effusions and a slight accumulation of ascites were detected on computed tomography (CT) (Figure 1). There was no abnormal uptake on gallium scintigraphy. Levels of IL-6 and VEGF in pleural effusion and ascites were significantly elevated (Table 2).
Bone marrow biopsy showed hyperplastic and increased megakaryocytes, and reticular fiber hyperplasia was partially observed by silver staining.
We performed renal biopsy for the definitive diagnosis of renal injuries. Light microscopy showed diffuse hypercellularity with thrombotic microangiopathy (TMA) lesions of the glomeruli. There was diffuse and global endothelial cell enlargement due to cytoplasmic swelling, with a large number of inflammatory cells (Figure 2a). The partial dissolution of the mesangial matrix (mesangiolysis) is also shown (Figure 2b). Endothelial cell swelling occluding the capillary lumen with loss of fenestrations and expansion of the subendothelial space was observed by electron microscopy (Figure 2d,2e). Immunoperoxidase staining for CD34 and CD68 was positive (Figure 2f,2g). Immunofluorescence analysis revealed negative staining for IgG, IgA, IgM, C3, and C1q.
Overall, this patient fulfilled three major categories (thrombocytopenia, anasarca, and systemic inflammation) and three minor categories (renal insufficiency, organomegaly, and myelofibrosis). Thus, the patient was diagnosed with TAFRO syndrome. After second high-dose steroid pulse therapy with 500 mg methylprednisolone for 3 days, followed by prednisolone 40 mg/day, anasarca, systematic inflammation and renal injuries were improved (C-reactive protein <0.1 mg/dL, eGFR 67 ml/min/1.73 m2). The platelet count increased to the normal range on the 31st day of admission. Eleven months after discharge, the patient had never relapsed under PSL treatment (5 mg/day).