eMedicine Specialties > Pediatrics: General Medicine > Hematology

Evans Syndrome: Treatment & Medication

Author: Prasad Mathew, MBBS, DCh, Director, Hemostasis and Hematology Program, Professor of Pediatrics, University of New Mexico
Contributor Information and Disclosures

Updated: Nov 19, 2009

Treatment

Medical Care

  • The management of Evans syndrome is challenging. Although almost all patients require therapy at some time during the course of the disease, the search for a consistent, effective, and nontoxic therapy continues. Medical therapy continues to be the mainstay. Response to therapy varies even within the same individual, and the disease is characterized by periods of remission and exacerbation. No randomized trials have been conducted in patients with Evans syndrome, and the evidence for treatment is based on case reports, case series, and retrospective studies.
  • Prednisone therapy, the most commonly used first-line therapy, often effectively controls acute episodes, although relapses may be frequent when patients are weaned off prednisone.
  • Intravenous immunoglobulin (IVIG) may help patients who depend on steroids.19,20
  • Other therapies effective in small series include danazol, cyclosporine, azathioprine, cyclophosphamide, and vincristine.
  • Recently, rituximab (a chimeric human/mouse monoclonal antibody which targets CD20 on B lymphocytes) has been used in the management of refractory patients.21,22,23,24,25,26  Responses have varied. Norton and Roberts recently reviewed the use of rituximab in 18 patients (aged 0.3-65 y).27 The results were encouraging, with sustained complete remission of as long as 17 months. In a recent pediatric prospective series by Rao et al, 2 patients with Evans syndrome were treated with rituximab; one had a partial response, and one had no response.26 Complications associated with rituximab in these studies have been minimal; the most common is infusion-associated reaction.
  • In an acute setting, blood transfusions and/or platelet transfusions may be required to alleviate symptoms, although their use should be minimized.
  • Additional therapies include splenectomy, alemtuzumab administration, and hematopoietic stem cell transplantation.
    • The role of splenectomy is not clearly established, but it may improve blood counts and reduce steroid dependence; relapses are common and, in most cases, occur within 1-2 months postsplenectomy.
    • Children with Evans syndrome appear to have a higher risk of postsplenectomy sepsis, especially children with pancytopenia.
    • Autologous and allogeneic stem cell transplantation have been used in a small number of patients (14 patients aged 5-52 y), with mixed results.28
    • Alemtuzumab is a humanized IgG monoclonal antibody specific for the CD52 antigen present on T cells and B cells. Willis et al reported its use in 3 patients with Evans syndrome; although a response was seen in 2 patients, both relapsed in 3 months.29

Surgical Care

Consider splenectomy in refractory cases.

  • Splenectomy may improve CBC counts and decrease the steroid requirement, although relapses are common.
  • According to a national survey, splenectomy provided a reported duration of response that ranged from 1 week to 5 years; however, the median response duration was just one month.10
  • The risk of infection after splenectomy appears to be increased in children with pancytopenia.

Consultations

  • Pediatric hematologist
  • Pediatric oncologist
  • Rheumatologist
  • Immunologist

Diet

  • Dietary restrictions are not usually required.
  • Patients receiving steroid therapy should have some restrictions on their salt, sugar, and fluid intake to prevent excessive fluid retention.

Activity

  • Restrict activities based on patient tolerance and the degree of anemia and bruising.

Medication

Prednisone (eg, 1-2 mg/kg dose, usually divided twice or three times daily) often effectively controls acute episodes of Evans syndrome. Although some patients are successfully weaned off steroids, relapses may occur when prednisone is tapered or stopped. Use an alternate-day steroid therapy, if possible.

Patients with persistent immune cytopenia and those who require prolonged or high doses of steroids may benefit from intravenous immunoglobulin (IVIG), at doses such as 1-2 g/kg/d for 1-2 days. Their thrombocytopenia is more likely than their hemolysis to respond. Long-term control of thrombocytopenia is reportedly achieved with interval doses of IVIG.

Other therapies reported in a national survey by Mathew et al included immunomodulating agents (eg, cyclosporine, danazol, azathioprine, cyclophosphamide, vincristine).10 Plasmapheresis was performed in 3 patients. One patient had transient responses, at best, to receiving the immunosuppressive agent tacrolimus (Prograf, FK506), protein A-Sepharose column plasmapheresis, whole blood exchange transfusion, and total nodal irradiation. Another patient showed some response to treatment with a combination of Rh D immunoglobulin (anti-D), methotrexate, prednisone, and folic acid (responses to these agents varied).

One pilot study showed that a multiagent approach may be effective in patients with Evans syndrome30 . Transfusions of RBCs and platelets were also used as adjuncts to treatment.

One of the newer agents that has been tried in refractory Evans syndrome is rituximab. However, recent reports suggest that it is being used as a second-line therapy. Rituximab is approved for the treatment of relapsed and refractory B-cell non-Hodgkin lymphoma. Binding of rituximab to cells expressing CD20 results in cell death by means of a combination of mechanisms, including antibody-dependent cell cytotoxicity, complement activation and apoptosis. Hence, it has been used in the treatment of various autoimmune disorders mediated by autoantibodies.

Galor et al reported the successful use of rituximab in a patient with Evans syndrome.21 Mantadakis et al reported its successful use in a patient with long-lasting Evans syndrome refractory to standard treatments; the patient responded well to Rituximab and then responded again when relapse occurred 7 months later.22 In contrast, Grossi et al treated 2 patients with rituximab without success.31 In fact, the patients had a worsening of their anemia. Zecca et al described the weekly use of rituximab in 5 children with Evans syndrome, all of whom were successfully treated.23 In a retrospective review of patients at the Mayo Clinic, Shanafelt reported responses in one of the cytopenias among 3 patients with Evans syndrome, but not both.24

Glucocorticoids

Initial therapy for Evans syndrome. Elicits anti-inflammatory properties and cause profound and varied metabolic effects. They modify the immune response of the body to diverse stimuli.


Prednisone (Deltasone, Meticorten, Orasone, Sterapred)

Commonly used steroid medication that interferes with macrophage Fc gamma and C3b receptors responsible for destruction of red cells and platelets; may work by decreasing abnormal IgG antibody production that may be responsible for destruction of the cells; can increase vascular stability and ameliorate endothelial abnormalities associated with thrombocytopenia; also helps decrease clearance of opsonized platelets.

Adult

Up to 60-80 mg/d PO divided bid/tid (or equivalent IV form)

Pediatric

1-2 mg/kg/d PO divided bid/tid (or equivalent IV form)

Coadministration with estrogens may decrease prednisone clearance; concurrent digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, or rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Documented hypersensitivity; serious infections (excluding meningitis and septic shock), fungal or varicella infections

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Administer with meals to decrease GI upset; early onset adverse effects include glucose intolerance, hypertension, agitation, indigestion; long-term use, usually more than a month, may cause growth retardation, osteoporosis, pseudotumor cerebri, cataracts, hypertension, fluid retention, psychosis, acne, and cushingoid facies; abrupt discontinuation of glucocorticoids may cause adrenal crisis

Immune Globulin

This is a purified preparation of gamma globulin. It is derived from large pools of human plasma and is composed of 4 subclasses of antibodies, approximating the distribution of human serum.


Immune globulin intravenous (Carimune NF, Gammar-P, Gammagard, Iveegam EN)

Neutralizes circulating myelin antibodies through antiidiotypic antibodies; down regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade; promotes remyelination; may increase CSF IgG (10%).

Adult

1-2 g/kg/d IV for 1-2 d

Pediatric

Administer as in adults

May cause live virus vaccines (eg, MMR) to not replicate successfully, thus, decreasing immune response

Documented hypersensitivity; anti-IgE/IgG antibodies

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Acquire low IgA-titer product for IgA deficient patients; slowly increase infusion rate to prevent infusion related adverse effects (eg, hypotension, fever); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-5 d postinfusion to 30 d)
Increases risk of renal tubular necrosis in elderly patients and in patients with diabetes, volume depletion, and preexisting kidney disease; laboratory test result changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia

More on Evans Syndrome

Overview: Evans Syndrome
Differential Diagnoses & Workup: Evans Syndrome
Treatment & Medication: Evans Syndrome
Follow-up: Evans Syndrome
References
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References

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Further Reading

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Keywords

Evans syndrome, ES, autoimmune hemolytic anemia, AIHA, idiopathic thrombocytopenia, ITP, Evans syndrome, autoimmune lymphoproliferative syndrome, ALPS, common variable immunodeficiency, IgA deficiency, diabetes mellitus, Hodgkin disease, Celiac disease, treatment, diagnosis, symptoms

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Contributor Information and Disclosures

Author

Prasad Mathew, MBBS, DCh, Director, Hemostasis and Hematology Program, Professor of Pediatrics, University of New Mexico
Prasad Mathew, MBBS, DCh is a member of the following medical societies: American Society of Hematology
Disclosure: Nothing to disclose.

Medical Editor

Gary R Jones, MD, Associate Medical Director, Clinical Development, Berlex Laboratories
Gary R Jones, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Gary D Crouch, MD, Program Director of Pediatric Hematology-Oncology Fellowship, Department of Pediatrics, Associate Professor, Uniformed Services University of the Health Sciences
Gary D Crouch, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Hematology
Disclosure: Nothing to disclose.

CME Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD, King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine
Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

 
 
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