A 48-year-old Japanese man with a 2-month history of general fatigue developed right back pain and edema. He was admitted to a local hospital because of a high level of serum C-reactive protein (CRP) (28.9 mg/dL) and hypoalbuminemia (1.7 g/dL). Soon after admission, he developed a high fever, difficulty of breathing, and oliguria. A computed tomography (CT) scan showed right adrenal hemorrhaging and bilateral thickening of the Gerota's fascia. After treatment with antibiotics and intravenous hydrocortisone, he was referred to our hospital. At that time, the platelet (PLT) count was 61,000 /muL, serum albumin (Alb) 1.5 g/dL, creatinine (Cr) 1.16 mg/dL, estimated glomerular filtration rate (eGFR) 54.3 mL/min/1.73 m2, Na 131 mEq/L, CRP 38.6 mg/dL, IgG4 44.1 mg/dL, and PCT 8.09 ng/mL (normal range, <0.5). Anti-cardiolipin (CL) antibodies, anti-CL/beta2-glycoptotein 1 (beta2GP1) antibodies, lupus anticoagulants, myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA), and proteinase 3 anti-neutrophil cytoplasmic antibodies (PR3-ANCA) were negative. Urine culture and repeated blood cultures were negative. A CT scan showed bilateral pleural effusion, hepatosplenomegaly, right adrenal hemorrhaging, and systemic lymphadenopathy (Fig. 1A-C). He was treated with antibiotics, intravenous steroids, Alb infusion, and diuretics. His symptoms gradually improved. One month later, he was referred to our department for further examinations.
At the presentation, his body temperature was 36.7C. A physical examination showed cervical lymph node swelling and edema. A urinalysis showed hematuria (50-99 red blood cells/high power field) without proteinuria. His white blood cell (WBC) count was 14,800 /muL, hemoglobin (Hb) 9.8 g/dL, PLT count 36,000 /muL, activated partial thromboplastin time (APTT) 29.5 sec, prothrombin time-international normalized ratio (PT-INR) 1.23, fibrinogen (Fib) 305.0 mg/dL, fibrinogen degradation product (FDP) 28.0 mug/mL, and D-dimer 12.52 mug/mL. Serum total protein (TP) was 5.1 g/dL, Alb 2.6 g/dL, blood urea nitrogen (BUN) 20.0 mg/dL, Cr 0.42 mg/dL, aspartate transaminase (AST) 89 U/L, alanine transaminase (ALT) 132 U/L, alkaline phosphatase (ALP) 684 U/L, lactate dehydrogenase (LDH) 226 U/L, gamma-glutamyl transpeptidase (gamma-GTP) 412 U/L, total bilirubin (T. Bil) l.4 mg/dL, Na 139 mEq/L, K 2.5 mEq/L, and Cl 89 mEq/L. Serum CRP was 0.85 mg/dL, antinuclear antibodies (ANA) <20, IgG 1,301 mg/dL, IgA 162 mg/dL, IgM 41 mg/dL, C3 118 mg/dL, C4 27 mg/dL, CH50 60 U/mL, and IL-6 3.8 pg/mL (normal range, <4.0). Serum and urinary protein electrophoresis showed no monoclonal paraproteins. Blood culture and urine culture were negative. There was no evidence of infections caused by hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), HIV, human T-lymphotropic virus (HTLV)-1, toxoplasma, Aspergillus species, or Mycobacterium tuberculosis.
A cervical lymph node biopsy showed atrophic germinal centers with reactive interfollicular plasma cell proliferation (Fig. 2A and B). Immunostaining for CD21 showed follicular dendritic cell proliferation (Fig. 2C). Bone marrow aspiration and a bone marrow biopsy revealed normocellular bone marrow with mild fibrosis without atypical cells (Fig. 2D). On the basis of these pathological findings and symptoms (thrombocytopenia, anasarca, fever, reticulin fibrosis/renal dysfunction, and organomegaly), he was diagnosed with TAFRO syndrome.
On day 22 after admission to our department, oral prednisolone (PSL: 50 mg/day) therapy was started instead of intravenous steroids, and the dose of PSL was gradually reduced to 30 mg/day. On day 46 after admission, a CT scan showed that the pleural and abdominal fluids had disappeared, the adrenal hematoma had improved, and systemic lymphadenopathy was diminished. His PCT level had decreased to 0.56 ng/mL. He was discharged on day 67. At that time, the PLT count was 260,000 /muL, serum Alb 4.2 g/dL, Cr 0.51 mg/dL, and CRP 0.11 mg/dL.