Cytomegalovirus reactivation exacerbated thrombocytopenia and haemolysis in a patient with systemic lupus erythematosus

Abstract

To the editor, Immunosuppressive therapy, including high-dose corticosteroids and other immunosuppressive agents, has markedly improved systemic lupus erythematosus (SLE) patient survival. However, these patients are deemed at increased risk for opportunistic infection because of impaired immunity due to immunosuppressive therapy. We encountered a patient with diVuse lupus nephritis complicated with severe thrombocytopenia and haemolytic anaemia, whose haematological manifestations might have been related to cytomegalovirus (CMV) reactivation. A 23-year-old Japanese man was hospitalized because of urinary abnormalities. Two months prior to admission, proteinuria and haematuria had been detected on a routine health examination. On admission, physical Wndings were unremarkable; however, laboratory testing revealed active nephritic urinary sediments with marked urinary protein excretion (2.6 g per day), low serum complement [C3 (24 mg/dl) and C4 (6 mg/dl)] values, and high titre of antidouble-stranded DNA (ds-DNA) antibody (63.1 IU/ml; reference range < 20). Renal biopsy revealed diVuse mesangial proliferation and capillary wall thickening on light microscopy, “full-house” pattern on immunoXuorescence microscopy, and mesangial/subendothelial electron-dense deposits on electron microscopy. During hospitalization, constitutional manifestations (i.e., fever and general myalgia), arthritis, and lymphopenia developed; thus, we diagnosed him to have SLE associated with diVuse lupus nephritis [International Society of Nephrology (ISN), Class IV]. Intravenous methyl prednisolone (0.5 g, three consecutive days) once every 2 weeks and oral corticosteroid (prednisolone, 55 mg per day) was started. This treatment improved his immunological abnormalities (i.e., hypocomplementaemia and elevated anti-ds-DNA antibody levels); however, his renal function deteriorated and serum creatinine levels were elevated to around 3.0 mg/dl with nephrotic-range proteinuria. On the 60th hospital day, gross haematuria, systemic petechia, melena, and epistaxis suddenly developed. He was afebrile, and physical examination was unremarkable except the bleeding tendency; however, laboratory data revealed marked thrombocytopenia (9,000/ l). Peripheral blood smear showed no morphological abnormalities. Coagulation screening results and serum transaminases were normal, but a haptoglobin level was undetectable. Bone marrow aspiration test showed a normal level and morphology of megakaryocytes, an active erythroid system, and no signs of haemophagocytosis. Abdominal computed tomography revealed no remarkable abnormalities. Platelet-associated IgG (157 ng/10 cells; reference range 5.0–25.0 ng/10 cells) was positive, but direct Coombs’ test, anti-granulocyte antibody, anti-cardiolipin-IgM/IgG antibodies, anti2 glycoprotein I antibody, cryoglobulin, and plasma activity of von Willebrand factorcleaving protease (69.5%) showed negative or normal results. Evaluation for bacterial infection, including blood and urine cultures, yielded negative results. Anti-parvovirus B 19 IgM antibody and Epstein–Barr (EB) virus plasma viremia were also negative, but peripheral blood CMV antigenaemia assay showed an equivocal result (5/34,000 peripheral blood leukocytes) [1]. Platelets transfusion for the marked bleeding symptoms was initiated. Intravenous methyl prednisolone (1.0 g per day, three consecutive days) followed by oral corticosteroid (prednisolone, 55 mg per T. Sugimoto (&) · M. Aoyama · N. Takeda · M. Sakaguchi · Y. Nishio · T. Uzu · A. Kashiwagi Department of Internal Medicine, Shiga University of Medical Science, Seta, Otsu, Shiga 520-2192, Japan e-mail: toshiro@belle.shiga-med.ac.jp