Case Presentation: A 43-year-old African-American female with a history of multiple sclerosis complicated by paraplegia, neurogenic bladder, and seizures presented to the hospital with a syncopal episode and was found to have a hemoglobin of 2.9 (12.0 to 16.0 gm/dL) with red blood cell count RBC 0.96 (4.00 – 5.20×10^6/uL), lactate dehydrogenase 639 (<201 U/L), reticulocyte count 4.2% (0.5-1.5%), haptoglobin <30 (30-195 mg/dL) and direct antiglbulin test (DAT) showing Ant-IgG positive and Complement C3 negative. Bone marrow biopsy showed trilineage hematopoiesis with no blasts. Autoimmune hemolytic anemia (AIHA) was suspected and patient was treated with blood transfusion and methylprednisolone with recovery of hemoglobin. Several months later, she presented with bleeding gums and purpura in her oropharynx. She was found to be thrombocytopenic to 10,000 (normal 150,000-450,000 / uL of blood). Disseminated intravascular coagulation (DIC) labs including fibrinogen and D-dimer were normal. Peripheral smear did not show any pseudothrombocytopenia or schistocytes. Septic work-up was negative. There was no splenomegaly on ultrasound. She was treated for immune thrombocytopenia (ITP) with steroids, intravenous immunoglobulin (IVIG) with improvement of platelets to 30,000 on the day of discharge. Platelet counts increased to 80,000 (4 weeks) to 154,000 (7 weeks) with continued steroid treatment. She then underwent 4 weeks of rituximab infusions for complete recovery of platelet count to 255,000 at the end of therapy.
Discussion: Multiple sclerosis (MS) is an autoimmune condition affecting the central nervous system that can progressively debilitate patients leading to profound neurologic dysfunction, fatigue, pain, and depression. Hematologic manifestations, however, are less well described. There are a few studies indicating that anemia in MS correlated with worsening disease course, but neutropenia, anemia, and thrombocytopenia are not common laboratory findings. Evans syndrome (ES) is a very rare disease characterized by autoimmune hemolytic anemia, usually warm, as well as immune thrombocytopenia. ES is usually associated with autoimmune conditions, but its characteristics are not well elucidated due to very few cases in the adult literature. We present here the first case of adult MS associated with development of ES. It is critical to understand that hematologic abnormalities, although rare, must be treated seriously in young women with MS.
Conclusions: As primary ES is a diagnosis of exclusion, it is important to consider similar diseases such as hemolytic uremic syndrome, thrombotic thrombocytopenic purpura (deficit of ADAMTS 13), Kasabach Merritt disease, and paroxysmal nocturnal hemogloburia. Secondary ES in the literature have strong association with autoimmune pathophysiology, such as lupus, lymphoproliferative syndrome, autoimmune hepatitis, and chronic leukemia. The case described here is typical of reported clinical courses of ES, as it is a heterogenous chronic disease with spontaneous remissions and exacerbations, as seen by the nine month delay in symptoms. However, this is the first report of multiple sclerosis associated Evans Syndrome. Our patient responded well to steroids, IVIG, and rituximab. Other second line treatments include cyclosporine, cyclophosphamide, and even hematopoietic stem cell transplantation. ES should also always be on the differential when the above lab abnormalities occur in MS patients.