Evans syndrome (ES) is a rare autoimmune disorder of unknown etiology. It is characterized by the occurrence of two or more hematologic immune cytopenias, most often immune thrombocytopenia and autoimmune hemolytic anemia (AIHA). In this study we present a rare case of a 9-year-old girl, who was diagnosed with secondary ES associated with active systemic lupus erythematosus (SLE).
On November 16th, 2018, a 9-year old girl, presented for the first time with recent onset of gum bleeding and decreased level of consciousness for two weeks. On examination, she was conscious but not oriented, unable to walk, showed scanty hair with oral and gum bleeding, and had multiple bruises and massive hepatosplenomegaly. No parental consanguinity, and no similar history in the family was noted. She had low platelet count (1×103 /μL), with high mean platelet volume (19 fl), anemia (HB 5.5 g/dL), with normal white blood cell count, positive direct Coombs test, and hemolysis with no malignant cells on a peripheral blood smear. Bone marrow evaluation showed hypercellularity, and increased number of megakaryocytes, with no other significant abnormalities. Her flowcytometry study was normal. Brain computed tomography (CT) revealed left subdural hematoma with elements of old brain atrophy (Photo 1), with significant dilatation of ventricular system. Chest X-ray showed mild right pleural effusion. Abdominal ultrasonography showed hepatosplenomegaly with no focal lesions, and mild-to-moderate ascites. Both antinuclear antibody and anti-phospholipid antibody tests showed positive results and C3 was low. Hepatitis and human immunodeficiency virus (HIV) serology were negative.Autoimmune lymphoproliferative syndrome gene sequence analysis was negative. The patient was diagnosed with SLE, after she fulfilled the American Rheumatology Association criteria, associated with Evans syndrome. Any planned surgery was postponed until thrombocytopenia correction, and their aim was to increase the platelet count to a level of above 100.The patient received packed red blood cells (RBCs) and platelets several times. To control her condition, several medications were tried. These medications included intravenous immunoglobulin (1 gm/kg) for two successive days, prednisolone (2 mg/kg/day); however, no improvement was observed after 10 days. Therefore, all of these medications were replaced with methylprednisolone pulse therapy (30 mg/kg for three days), with one dose of anti-D (75 mcg/kg IV). Our next choice was mycophenolate mofetil, which was stopped after finishing the course of five weeks, but the patient did not show any improvement. Moreover, platelets failed to respond to four doses of Rituximab (370 mg/m2/dose) for four weeks and to two cycles of high dose of dexamethasone 20mg/m2 for 4 days every 4 weeks. On 12/29/2018, chloroquine (4 mg/kg/day) was administered for two weeks in conjunction with cyclosporine (4 mg/kg/day). Splenectomy was an option but was not performed because her platelet levels never recovered. Her anemia started to improve on 1/9/2019 with combination of prednisolone and cyclosporine and Coombs test results were negative. On 1/23/2019, the patient was started on Eltrombopag, in a dose-escalated manner starting with 25 mg/kg/day up to 75 mg/kg/day in addition to corticosteroids. One week later, her platelet counts markedly improved (Photo 2). No major side effects were reported. On 2/12/2019, the patient underwent left side burr-hole evacuation of subdural hematoma, but her consciousness was never regained. She was maintained in intensive care unit and ventilated, but she developed multiple postoperative complication, including sepsis with high inflammatory markers and spiking fever. Her platelet count was continuously high, so the dose of Eltrombopag was decreased to 50 mg/kg/day to just keep the level between 50 and 100. Despite all of therapeutic interventions, she passed away one month later, on 3/13/2019, due to respiratory failure.
The incidence of ES is quite rare, especially in children. Eltrombopag is a safe and effective drug for management of refractory thrombocytopenia in cases of ES associated with SLE.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.