|Year : 2015 | Volume
| Issue : 1 | Page : 91-93
Diagnostic dilemma in Evans syndrome
Harish Chandra1, Smita Chandra1, Anita Sharma2
1 Department of Pathology, Medicine, Himalayan Institute of Medical Sciences, Doiwala, Dehradun, Uttarakhand, India
2 Department of Medicine, Himalayan Institute of Medical Sciences, Doiwala, Dehradun, Uttarakhand, India
|Date of Web Publication||13-Apr-2015|
Dr. Harish Chandra
Department of Pathology, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Doiwala, Dehradun - 248 140, Uttarakhand
Source of Support: None, Conflict of Interest: None
Evans syndrome, a complex uncommon disease, poses a great diagnostic dilemma due to its variable presentation. The present case of 26-year-old Indian female faced similar difficulty as it was not diagnosed initially when it presented with thrombocytopenia and was treated by platelet concentrate transfusion and steroids. However, the patient showed repeated episodes of remissions and exacerbations without any substantial improvement and later at a tertiary care center it was diagnosed as Evans' Syndrome after direct antiglobulin test and relevant investigations to rule out other causes. This case stresses on the importance of direct antiglobulin test in every patient presenting with autoimmune thrombocytopenia to rule out autoimmune hemolytic anemia and thus excluding this syndrome.
Keywords: Autoimmune hemolytic anemia, Evans syndrome, thrombocytopenia
|How to cite this article:|
Chandra H, Chandra S, Sharma A. Diagnostic dilemma in Evans syndrome. Arch Med Health Sci 2015;3:91-3
| Introduction|| |
Evans syndrome, an uncommonly diagnosed complex condition, is a combination or sequence of autoimmune thrombocytopenia (AITP) and autoimmune hemolytic anemia (AIHA) which is secondary to no known clinical condition. , A generalized immune dysregulation, both cellular and humoral has been found to be associated with Evans' syndrome. , It is basically a diagnosis of exclusion and confounding factors such as infections, malignancies and rheumatologic diseases should be ruled out. This syndrome shows a variable complicated clinical course with remissions, exacerbations and association with significant morbidity and mortality.  This feature itself lays the importance of early diagnosis of Evans' syndrome when it is presenting as a combination or as an isolated episode of AIHA or AITP. It is in this view that a patient presenting with AITP should undergo a direct antiglobulin (Coombs) test at the time of diagnosis or during follow-up, especially if there is anemia.
| Case Report|| |
A 26-year-old Indian female, an Indian hailing from the Himalayan region presented with history of episodic recurrent jaundice, headache, pallor, fatigue, purpura, and petiche all over the body for about 20 days. Previously she had similar episodes for last 1 year for which she had consulted locally. She had received steroids and platelet concentrate transfusion but there were recurrent episodes of exacerbations and she was referred to the present tertiary care centre for further investigations. There was no history of prolonged fever or any other drug intake. On examination, the patient had no splenomegaly but there was bilateral axillary lymphadenopathy. Lab studies showed hemoglobin 45 gm/L, total leukocyte count 2.5 × 10 9 /L, differential leukocyte count - polymorphs 38%, lymphocytes 52%, monocytes 7%, eosinophils 3%, platelet count 24 × 10 9 /L and erythrocyte sedimentation rate (Westergren method) was 72 mm fall in first hour. Corrected reticulocyte count was 4%. On peripheral blood examination the smear showed marked agglutination of red blood cells along with fair number of spherocytes and few nucleated red blood cells. Direct antiglobulin (Coombs) test was advised and was found to be positive. There was decreased levels of immunoglobulin (Turbox ® , Orion diagnostica) and Enzyme linked immunosorbent assay (ELISA) for Human Immunodeficiency Virus (HIV I and II) was found to be non-reactive. Malarial antigen test was also negative. Chest X-Ray was unremarkable and abdominal ultrasonography was normal. Urine examination was within normal limits and showed no hemoglobinurea and hemosiderinurea. Test for Lupus antibody, antinuclear antibody (ANA) and rheumatoid factor was also negative. Anti- Ds DNA was not done initially but in the follow-up it was found to be negative. Ham's test for paroxysmal nocturnal hemoglobinurea was negative. Bone marrow aspirate examination showed normoblastic erythroid hyperplasia with increased number of megakaryocytes and its many immature forms. No infiltrative process or parasite was evident on bone marrow examination. Fine needle aspiration cytology of axillary lymph node showed reactive hyperplasia.
Thus, the case at the time of presentation showed the features of autoimmune hemolytic anemia, autoimmune thrombocytopenia and neutropenia with no evidence of infection, malignancy or any other obvious underlying etiology. However, there were decreased levels of serum immunoglobulin.
Patient was given injection methyl prednisone 500 mg intravenously for 3 days and then was switched to gradually tapering dose of oral prednisone starting from 1 mg/kg/day. She responded dramatically and was discharged with a strict advice of constant follow up. At discharge she was advised maintenance dose of 0.5 mg/kg/day of oral prednisone. She was also told about the chronic nature of the condition, which included periods of remission and exacerbation. After 1 month, during her first follow-up, there was marked improvement in symptoms and her baseline hematological parameters were within normal limits. The patient is presently on constant follow up.
| Discussion|| |
Evans' syndrome, a rare and wide spectrum autoimmune disorder, can present as an isolated episode or a combination of AIHA and AITP.  If sequential, it usually presents initially with AIHA followed by AITP. However, in other series by Sureyya Savasan et al, all the patients initially presented with thrombocytopenia and two patients out of total eleven had hemolytic anemia at presentation.  The usual reported age is in the first decade and affects boys more than girls. However, in adults, women are more commonly affected.  The present case is of a female presented at a later age group with a combination of AIHA and AITP with nutropenia. This may be due to that the disease was undiagnosed until the later presentation of cytopenia. This fact itself lays the importance of early diagnosis of Evans' syndrome to prevent the morbidity and mortality of the patient. The case of thrombocytopenia should be subjected to direct Coombs test to exclude AIHA and thus to rule out possibility of Evans' syndrome.
The basic pathology is suggested by the role of non-cross-reacting autoantibody against red cells and platelets. This syndrome may be associated with other immune deregulations characterized by abnormal serum immunoglobulin, primary immunodeficiency, collagen vascular diseases and autoimmune lymphoproliferative syndrome (ALPS).  The present case also showed decreased levels of serum immunoglobulin suggesting an associated immune deregulation. As Evans syndrome is a diagnosis of exclusion so other confounding factors such as malignancies, infections and rheumatologic disorders have to be ruled out by performing different tests such as ELISA for HIV I and II, malarial antigen, urine examination, ultrasonography, chest X-ray, Lupus antibody, antinuclear antibody and Ham's test. Sasidharan et al. have proposed that hematological manifestations are common presentation of SLE and may be missed if index of suspicion is low and therefore have proposed major and minor criteria for diagnosis of SLE which include ANA and Anti- Ds DNA.  However, in the present case ANA and Anti- Ds DNA were negative. Bone marrow examination is very essential if the patient is presenting with pancytopenia to exclude infiltrative process or an aplastic marrow. The bone marrow examination in this pateint showed marked normoblastic erythroid hyperplasia and increased megakaryocytes with no infiltrative process indicating that there are certain antibodies directed against red cells and platelets causing their destruction in circulation. The clinical course is complicated and associated with poor outcome in patients with Evans' syndrome as compared to patients having isolated episodes of AIHA or AITP. Initial treatment is with gluco-corticosteroids or intravenous immunoglobulin and surgical splenectomy in few cases. , The risk of complications is major and associated with hemorrhage even leading to death. A strict constant follow-up is very essential along with the education of the patient regarding the chronic nature of this condition.
| Conclusion|| |
Evans' Syndrome although a rare disorder should definitely be considered in cases presenting with AIHA or AITP occurring simultaneously or in follow up after excluding the causes of known etiology. An isolated presentation of thrombocytopenia should always be subjected to direct Coombs test to rule out AIHA. The acute episodes can be effectively controlled by prednisone therapy. The risk of complications is major and associated with hemorrhage and even leading to death. The early diagnosis, a constant follow-up and the knowledge of variable complicated presentation of this syndrome is very essential due to remissions, exacerbations, and association with significant morbidity and mortality.
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