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Autoimmune Lymphoproliferative Syndrome Medication

  • Author: Luke M Webb, MD; Chief Editor: Harumi Jyonouchi, MD  more...
 
Updated: Aug 15, 2014
 

Medication Summary

Agents used to treat autoimmune lymphoproliferative syndrome (ALPS) include immunosuppressants and immune globulins.

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Immunosuppressant Agents

Class Summary

Initial therapy for autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP) includes corticosteroids. In refractory autoimmune cytopenias necessitating long-term steroid therapy, mycophenolate mofetil has been shown to be an effective steroid-sparing agent.

Prednisone

 

Prednisone

Prednisone is useful for treating inflammatory and allergic reactions; it may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte (PMN) activity. It is the drug of choice for all adult patients with platelet counts below 50,000/µL. Asymptomatic patients with platelet counts higher than 20,000/µL or patients with counts of 30,000-50,000/µL with only minor purpura may not need therapy; withholding medical therapy may be appropriate for asymptomatic patients, regardless of platelet count.

Methylprednisolone (Solu-Medrol, Depo-Medrol, A-Methapred)

 

Methylprednisolone decreases inflammation by suppressing migration of PMNs and reversing increased permeability. It is used as the alternative glucocorticoid of choice for all patients with severe life-threatening bleeding or children with platelet counts below 30,000/µL. Careful observation without medical treatment may be appropriate in some asymptomatic children.

Mycophenolate (CellCept, Myfortic)

 

Mycophenolate inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. It inhibits antibody production. Two formulations are available; they are not interchangeable. The original formulation, mycophenolate mofetil (CellCept) is a prodrug that, once hydrolyzed in vivo, releases the active moiety, mycophenolic acid. A newer formulation, mycophenolic acid (Myfortic), is an enteric-coated product that delivers the active moiety.

Prednisolone (Orapred, Pediapred, Millipred)

 

Corticosteroids act as potent inhibitors of inflammation. They may cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to their modification of the immune response of the body. Alternative corticosteroids may be used in equivalent dosage. It is used in all patients with severe life-threatening bleeding or children with platelet counts below 30,000/µL. Careful observation without medical treatment may be appropriate in some asymptomatic children.

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Immune Globulin

Class Summary

High-dose (1-2 g/kg IV) immune globulin may be considered for concomitant use with pulse-dose corticosteroids in those with severe AIHA.

Immune globulin intravenous (Carimune, Octagam, Gammaplex, Gammagard Liquid, Privigen)

 

Immune globulin intravenous is given as a temporary measure to increase platelets. It neutralize circulating myelin antibodies through anti-idiotypic antibodies; down-regulates proinflammatory cytokines, including interferon gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells while augmenting suppressor T cells; blocks the complement cascade; promotes remyelination; and may increase immunoglobulin G (IgG) in cerebrospinal fluid (10% of cases).

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Contributor Information and Disclosures
Author

Luke M Webb, MD Staff Physician, Department of Allergy and Immunology, Evans Army Community Hospital

Luke M Webb, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology

Disclosure: Nothing to disclose.

Coauthor(s)

David J Schwartz, MD Staff Physician, Department of Allergy and Immunology, Eisenhower Army Medical Center

David J Schwartz, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Allergy, Asthma and Immunology

Disclosure: Nothing to disclose.

V Koneti Rao, MD FRCPA, Staff Clinician, Lymphocyte Clinical Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health

V Koneti Rao, MD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter's University Hospital

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Pediatric Research, Society for Mucosal Immunology

Disclosure: Nothing to disclose.

Acknowledgements

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Acknowledgments

The authors acknowledge Drs Kip Hartman and Margaret Merino of the Pediatric Hematology and Oncology Department at the Walter Reed Army Medical Center for the use of their clinical expertise and patient photographs in this article. In addition, the authors thank Dr Scott Whitworth of the Department of Radiology at Walter Reed Army Medical Center for his assistance with positron emission tomography (PET) imaging. Finally, the authors also express thanks to the patients and parents who granted permission to use these photographs.

This research was supported by the Intramural Research Program of the National Institutes of Health. The views expressed in this article are those of the authors and do not reflect the official policy of the Department of Army, Department of Defense, or the US Government.

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Examples of an autoimmune lymphoproliferative syndrome (ALPS) in a patient with grade IV (visible) lymphadenopathy.
Autoimmune lymphoproliferative syndrome (ALPS) and ALPS-related disorders classification:
Primary and accessory diagnostic criteria for autoimmune lymphoproliferative syndrome (ALPS).
A patient with autoimmune lymphoproliferative syndrome (ALPS) who developed pneumococcal sepsis, a serious complication secondary to neutropenia and asplenia. Note the patient's cochlear implant; he has neurosensory hearing loss from prior episode of pneumococcal meningitis.
Positron emission tomography (PET) superimposed over a CT scan from a patient with autoimmune lymphoproliferative syndrome (ALPS). Note the massive cervical adenopathy. PET scans may be used as a screening tool in patients with autoimmune lymphoproliferative syndrome to decrease the number of lymph node biopsies used in screening for malignancy.
The extrinsic pathway of apoptosis. Mutations have been identified in each of the genes coding for Fas, Fas-ligand (FasL), caspase-8, and caspase-10. This figure was previously published in Rao VK, Straus SE. Autoimmune Lymphoproliferative Syndrome. Clinical Hematology. 58;759. 2006: Elsevier.
Suggested treatment algorithm for patients with autoimmune lymphoproliferative syndrome (ALPS). This schematic diagram is included only as a suggested guideline for managing children with autoimmune lymphoproliferative syndrome–associated autoimmune multilineage cytopenias. Use of granulocyte-colony stimulating factor (G-CSF) may be warranted for severe neutropenia associated with systemic infections. Similarly, use of other chemotherapeutic and immunosuppressive agents (eg, vincristine, methotrexate, mercaptopurine, azathioprine, cyclosporine, hydroxychloroquine, tacrolimus, sirolimus) besides mycophenolate mofetil (MMF) should be considered as a steroid-sparing measure or while avoiding or postponing surgical splenectomy at the discretion of the treating clinicians based on the circumstances of a specific patient.
 
 
 
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