Two Cases of Refractory Thrombocytopenia in Systemic Lupus Erythematosus that Responded to Intravenous Low-Dose Cyclophosphamide
A 24-yr-old woman had been diagnosed with SLE according to the presence of antinuclear antibody (ANA) and anti-ds DNA, pancytopenia, and arthritis in June 2010. At the time of diagnosis, she had an ANA titer of 1:640, mixed type; an anti-ds DNA level of 571.3 AU (ELISA, positive, ≥ 92.6 AU); a white blood cell (WBC) count of 560/µL (neutrophils, 82.6%; lymphocytes, 2.6%); a platelet count of 65,000/µL; and a hemoglobin concentration of 6.7 g/dL. The erythrocyte sedimentation rate (ESR) was 2 mm/h, and the C-reactive protein (CRP) concentration was 4.80 mg/L. Complements 3 and 4 were decreased to 22.1 mg/dL (normal: 90-180 mg/dL) and 5.65 mg/dL (normal: 10-40 mg/dL), respectively. We performed a bone marrow biopsy that showed no abnormal findings. Concluding that the leucopenia and thrombocytopenia were hematological manifestations associated with SLE, we started administration of prednisolone (1 mg/kg/day) and AZA (25 mg/day). The thrombocytopenia improved, with an increased platelet count above 100,000/µL, and the dose of prednisolone was tapered to 15 mg/day. However, she was admitted with fever, pleuritic chest pain, and pancytopenia, including severe thrombocytopenia, 6 months later. Laboratory results on admission showed that WBC and platelet counts were 2,250/µL (neutrophils, 86.3%; lymphocytes, 7.6%) and 10,000/µL, respectively. The hemoglobin concentration was 6.7 g/dL, and the corrected reticulocyte percentage was 1.04%. The ESR was 39 mm/hr, and the CRP concentration was 33.02 mg/L. Complements 3 and 4 were reduced to 36.4 and 9.1 mg/dL, respectively, while the anti-ds DNA level had increased, from 497.3 to 548.3 AU (ELISA). Computed tomography of the chest and abdomen revealed pericardial and bilateral pleural effusion, but not splenomegaly. To rule out other diseases, including hemophagocytic syndrome and aplastic anemia, we performed a bone marrow biopsy. The results showed normal cellularity and abundant megakaryocytes, suggesting severe thrombocytopenia in SLE. She received pulsed intravenous methylprednisolone (1,000 mg/day) for 3 days, followed by oral prednisolone (1 mg/kg/day) and intravenous immunoglobulin (5 g/day) for 5 days. The anemia, leucopenia, and serositis were markedly improved, but the platelet count was still 11,000/µL after finishing pulsed methylprednisolone therapy. Next day after pulsed methylprednisolone therapy, she began low-dose IV CYC therapy (500 mg/day, biweekly). Her platelet count increased to 50,000/µL on day 11 after the first CYC infusion, and a stable platelet count above 100,000/µL was maintained with no CYC complications. She completed six cycles of low-dose IV CYC therapy over 3 months and could decrease the dose of prednisolone. She maintained on low-dose prednisolone (10 mg/day) and 50 mg of AZA, and her platelet count was remained above 150,000/µL after 12 months ().