September 2000, Volume 50, Issue 9

Case Reports

Intravenous Immunoglobin G Therapy in Evans Syndrome

Shahina Qureshi  ( Children Hospital. Pakistan Institute of Medical Sciences, Islamabad. )
S. Zaman  ( Children Hospital. Pakistan Institute of Medical Sciences, Islamabad. )
Javed lqbal  ( Children Hospital. Pakistan Institute of Medical Sciences, Islamabad. )

The combination of coombs positive auto immune hemolytic anaemia and immune thrombocytopen ic purpura was first described by Evans in 19511. It is rare in childhood, with usually no underlying etiology2. The clinical course is chronic and relapsing. Treatment with corticostero ids, immunosuppressive agents and splenectomy is generally unsatisfactory. Successful treatment with high dose intravenous immunoglobulin G was first reported in 19853 We tried this forni of therapy in our patient with chronic AIHA arid ITP with good results.

Case Report

An eleven years old boy was admitted to Childrens Hospital with a history of pallor, vomiting and bruises for four days. There ws no intake of any drug or infection prior to this illness. He had several episodes of pallor and bruising since the age of five years, requiring hospitalizations and transfusions. Last admission was in Childrens Hospital, four months prior to this episode. He was treated with corticosteroids. blood and platelet transfusions, for three weeks. There was some improvement and lie was discharged in stable condition.
Physical examination on admission revealed a pale child in no distress. Temperature was 100.4°F. Pulse 125/min, blood pressure 110/70mm Hg. Weight was 26Kg. He had jaundice, purpura and ecchymosis on the extremities. Liver was palpable 3.5 ems below the right costal margin, spleen 4.0 ems below the left costal margin and there was no lymphadenopathy or ascites.
Laboratory studies revealed a hemoglobin of 4.5 Gms/dl, leukocyte count 10,500/mm with a normal differential count. Reticulocyte count was 40%, Platelet count 45,000/cmm, Total serum bilirubin 4.0 mg/dl, Direct bilirubin 1.0 mg/dl. Liver function tests normal, hepatitis B surface antigen negative and ESR 80 mm 1st hour. Peripheral smear showed hypochrornic macrocytic red cells with many target cells. Bone marrow examination showed a hyperce l lular marrow with erythro id hyperplasia.
Hemoglobin electrophoresis was normal. G-6-PD negative and Antinuclear antibodies were not detected. Serum lgG was increased to 30.4 g/1. Serum IgA and 1gM were normal. Platelet associated immunoglobulins and anti platelet antibodies could not be determined. Direct Coonibs test was positive.
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He was transfused packed red blood cells and platelets. Oral prednisolone 2.0 mg/kg/d was started. He continued to show reticulocytosis and thrombocytopenia. As there was no response. prednisolone was tapered after fourteen days and discontinued in three weeks. Intravenous Immunoglobulin G was given in a dose of 400 mg/kg/d on day 21st for four days. Platelet count increased and after two days. On day 25 platelet count was 169,000/cmm and Reticulocyte count decreased to 2.5%. He was discharged and followed in the out patient clinic. Five months later, his hemoglobin was 11.2 gms/dl, platelet count 250.000/cmmm, and reticulocyte count 1.5%.

Discussion

In 1951 Evans and Co-workers described the association of thrombocytopenia with a Coombs positive hemolytic anemia. This combination was later reported in a number of disorders including systemic lupus erythmatosis4,2 dermatornyositis5 scleroderma4 leukemia2 liver cirrhosis, infectious mononucleosis6, Castlemans disease7, Guillain-Barre syndrome and insulin dependant diabetes mellitus.
In patients with AIHA thrombocytopenia and leucopenia occur relatively frequently1,2,8-10 as compared to patients with ITP in which only a few had acute hemolytic anemia2. Evans syndrome is characterized by this combination in the absence of an overt cause. Quantitative serum immunoglobulin abnormalities and lymphoid hyperplasia suggest that it may be an immune deficiency disorder11, The presence of granulocytotoxic and lymphocytotoxic antibodies in the sera of these patients also suggest an autoimmune process. Like in ITP, there may be a history of an antecedent febrile illness2.
The treatment of children with chronic autoimmune hemolytic anemia has not been very successful. Corticosteroids often result in improvement, but relapses are common and maintenance steroid therapy seems necessary in the majority of effected children9. Immunosuppressive agents have also been used, either alone or in combination with corticosteroids2. Splenectorny often provides sustained remission in 70% of patients with chronic ITP and 50% of those with chronic AIHA9,12, but it seldom results in prolonged remission in Evans syndrome2. Many recent observations have shown that intravenous immunoglobin G therapy is useful in the management of acute and chronic ITP12-14. As AIHA and ITP are considered to have common pathophysiological mechanisms so treatment of Evans syndrome with intravenous immunoglobulin G seems logical. However the total dose of  lgG required to obtain a complete response has been higher than in comparable patients with ITP or autoimmune neutropenia14,15. Although the mechanism of the immunoglobulin effect is not completely known, several possibilities have been considered in ITP. Reticuloendothelial system I-c receptor blockade, decrease in autoantibody synthesis, protection of platelets, have been cited2,12,16.
Our report apparently is one of the few successful experiences of intravenous immunoglobin G in the control of AIHA. Though expensive it has fewer side effects than other modes of treatment. The optimal therapy for Evans syndrome however, still remains undefined11,17.

References

1. Evans RS, Takahashi K, Duane RT. el at. Primauy thrombocytopenic purpuraand acquired hemolytic anemia. Arch. Int. Med., 1951;87:48.
2.  Pui Cl-I, Williams J, Wang W. Evans syndrome in childhood. J. Pediatr.. 1 980;97:754.
3. Hideaki Oda, Akihito Honda. High dose intravenous immunoglobulin G infusion in refractory autoimmune hemolytic anemia (Evans syndrome). J. Pediatr., l985;107:744.
4. Miller BA, Beardsky DS. Aulloimmune pancytopenia of childhood associated with multisystem disease manifestation. J. Pediatr., l983;l07:877,
5. Hay EM, Makris M, Wintield J, et at, Evans syndrome associated with dermatomyositis. Ann. Rh. Dis., 1990;49:793.
6. Clark RH, Korbitz BC, Clive WAS. Infectious mononucleosis complicated by hetnolytie anemia and thrombocytopenic purpura. Wisconsin Med .J., 1971;70:181.
7. Marsh JH, Co1burn DS, Donovan V. et al. Systemic Castleman’s disease in association with Evans syndrome and vitiligo. Med. Pediatr. Oncol,,1990;18:169.
8. Ztibanska B, Lawkowicz W, Gorska B, et al. Autoimmunc heinolytic anaemia in children. Br. J, Haematol., 1976;34:511.
9. Habibi B, Homberg JC, Schaison G, et al. Auto immune heinolytic anaemia in children. A review of 50 cases. Am. J. Med., 1974;56:61.
10. Buchanan GR, Boxer LA, Nathan DG. The acute and chronic nature of idiopathic immune hemolytic anaemia in childhood. J. Pediatr., 1976;88:780.
11. Wang W, Herrod H, Pui Ch, et al. Immunoregulatory abnormalities in Evans syndrome. Am. J Hernatol., 1983:15:38).
12. Simons SM. Main CA, Yaish HM, et al. ITP in children. J. Pediatr., 1975:87:16.
13. Imbach P. Barandun S. DApuzzon, et al. High dose immunoglobulin G. for lip in childhood. Lancet, 1981;I :1128.
14. Bussel JB, Kimberly RP. Schulma I, et al. Intravenous gammaglobulin treatment of chronic ITP. Blood, 1983:62:480.
15. Blanchette VS, Kirby MA, Turner C. Role of intravenous immunoglobulin 0 in autoimmune hematologic disorder. Seminars in Haematol. 1992;29:72,
16. Bussel JB, Hilgartner MW. The use and mechanism of action of iminunoglobulin G in the treatment of immune hematologic disorders. Br. J Haematol., 1 984;56: 1.
17. Mathew P, Chen 0, Wand W. Evans syndrome: Results of a national study. Pediatr. Hematol. Oncol., 1997;19:433.

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