Wiskott-Aldrich Syndrome Medication
- Author: Donald A Dibbern Jr, MD; Chief Editor: Michael A Kaliner, MD more...
Medication Summary
WAS is treated with a variety of therapeutic agents from several different categories, including antibiotics, antivirals, antifungals, chemotherapeutic agents, immunoglobulins, and corticosteroids. Agents are selected based on the patient's clinical presentation and response. When treating infections, if possible, identify the suspected pathogen before selecting antibiotic, antiviral, and/or antifungal agents. Antibiotics are indicated to treat bacterial infections and for prophylaxis in patients who have had a splenectomy. Antiviral and antifungal agents are indicated to treat viral and fungal infections, respectively. Chemotherapeutic agents are indicated to treat lymphoreticular and/or hematologic malignancies, but are also used as ablative agents, with or without total-body irradiation, prior to bone marrow transplantation. Immunoglobulins and systemic corticosteroids are indicated to treat thrombocytopenia. Use topical steroids to treat eczema.
Corticosteroids
Class Summary
Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Prednisone (Sterapred)
Immunosuppressant for treating autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Used to treat thrombocytopenia. Many different steroid treatment regimens are used to treat thrombocytopenia. Consider using other corticosteroids at equivalent doses (eg, prednisolone, methylprednisolone).
Methylprednisolone (Medrol, Solu-Medrol)
Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability. Used to treat thrombocytopenia. Many different steroid treatment regimens are used to treat thrombocytopenia. Consider using other corticosteroids at equivalent doses (eg, dexamethasone, prednisolone).
Fluocinolone (Synalar)
High-potency topical corticosteroid that inhibits cell proliferation. Immunosuppressive, antiproliferative, and anti-inflammatory. Used to treat eczema. Use lowest effective potency and dose. Consider using equivalent doses of other topical corticosteroid preparations (eg, hydrocortisone, mometasone). Topical steroids are preferred, but for rapid control of severe disease, consider a brief burst of moderate-dose PO steroids.
Immunoglobulins
Class Summary
Provide functional immunoglobulins in patients whose ability to respond to bacterial antigens is abnormal and may inhibit platelet sequestration by the reticuloendothelial system.
Immune globulin (Gammagard, Gamunex, Iveegam EN, Privigen)
Used to treat thrombocytopenia; also may be indicated if serum IgG level is low or patient cannot produce functional antibody responses (eg, to polysaccharide antigens). See Hypogammaglobulinemia for dosing.
Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol. Dec 1999;93(3):190-7. [Medline].
Sullivan KE, Mullen CA, Blaese RM, Winkelstein JA. A multiinstitutional survey of the Wiskott-Aldrich syndrome. J Pediatr. Dec 1994;125(6 Pt 1):876-85. [Medline].
Snapper SB, Rosen FS. The Wiskott-Aldrich syndrome protein (WASP): roles in signaling and cytoskeletal organization. Annu Rev Immunol. 1999;17:905-29. [Medline].
Kwan SP, Hagemann TL, Radtke BE, et al. Identification of mutations in the Wiskott-Aldrich syndrome gene and characterization of a polymorphic dinucleotide repeat at DXS6940, adjacent to the disease gene. Proc Natl Acad Sci U S A. May 9 1995;92(10):4706-10. [Medline].
Yin HL, Stull JT. Proteins that regulate dynamic actin remodeling in response to membrane signaling minireview series. J Biol Chem. Nov 12 1999;274(46):32529-30. [Medline].
Haddad E, Zugaza JL, Louache F, et al. The interaction between Cdc42 and WASP is required for SDF-1-induced T- lymphocyte chemotaxis. Blood. Jan 1 2001;97(1):33-8. [Medline].
Snapper SB, Meelu P, Nguyen D, et al. WASP deficiency leads to global defects of directed leukocyte migration in vitro and in vivo. J Leukoc Biol. Mar 17 2005;Epub:[Medline].
Westerberg L, Larsson M, Hardy SJ, et al. Wiskott-Aldrich syndrome protein deficiency leads to reduced B-cell adhesion, migration, and homing, and a delayed humoral immune response. Blood. Feb 1 2005;105(3):1144-52.
Zhang H, Schaff UY, Green CE, Chen H, Sarantos MR, Hu Y. Impaired integrin-dependent function in Wiskott-Aldrich syndrome protein-deficient murine and human neutrophils. Immunity. Aug 2006;25(2):285-95. [Medline].
Remold-O'Donnell E, Rosen FS. Sialophorin (CD43) and the Wiskott-Aldrich syndrome. Immunodefic Rev. 1990;2(2):151-74. [Medline].
Huang W, Ochs HD, Dupont B, et al. The Wiskott-Aldrich syndrome protein regulates nuclear translocation of NFAT2 and NF-kappaB (RelA) independently of its role in filamentous actin polymerization and actin cytoskeletal rearrangement. J Immunol. Mar 1 2005;174(5):2602-11. [Medline].
Ochs HD, Notarangelo LD. Structure and function of the Wiskott-Aldrich syndrome protein. Curr Opin Hematol. Jul 2005;12(4):284-91. [Medline].
Notarangelo LD, Notarangelo LD, Ochs HD. WASP and the phenotypic range associated with deficiency. Curr Opin Allergy Clin Immunol. Dec 2005;5(6):485-90. [Medline].
Ochs HD, Thrasher AJ. The Wiskott-Aldrich syndrome. J Allergy Clin Immunol. Apr 2006;117(4):725-38; quiz 739. [Medline].
Anton IM, Jones GE. WIP: a multifunctional protein involved in actin cytoskeleton regulation. Eur J Cell Biol. Apr 2006;85(3-4):295-304. [Medline].
de la Fuente MA, Sasahara Y, Calamito M, et al. WIP is a chaperone for Wiskott-Aldrich syndrome protein (WASP). Proc Natl Acad Sci U S A. Jan 16 2007;104(3):926-31. [Medline].
Konno A, Kirby M, Anderson SA, Schwartzberg PL, Candotti F. The expression of Wiskott-Aldrich syndrome protein (WASP) is dependent on WASP-interacting protein (WIP). Int Immunol. Feb 2007;19(2):185-92. [Medline].
Calle Y, Anton IM, Thrasher AJ, Jones GE. WASP and WIP regulate podosomes in migrating leukocytes. J Microsc. Sep 2008;231(3):494-505. [Medline].
Ramesh N, Geha R. Recent advances in the biology of WASP and WIP. Immunol Res. Nov 19 2008;[Medline].
Soderling SH, Scott JD. WAVE signalling: from biochemistry to biology. Biochem Soc Trans. Feb 2006;34(Pt 1):73-6. [Medline].
Takenawa T, Suetsugu S. The WASP-WAVE protein network: connecting the membrane to the cytoskeleton. Nat Rev Mol Cell Biol. Jan 2007;8(1):37-48. [Medline].
Westerberg LS, Dahlberg C, Baptista M, et al. Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for peripheral B cell development and function. Blood. Mar 12 2012;[Medline].
Perry GS 3d, Spector BD, Schuman LM, et al. The Wiskott-Aldrich syndrome in the United States and Canada (1892- 1979). J Pediatr. Jul 1980;97(1):72-8. [Medline].
Ryser O, Morell A, Hitzig WH. Primary immunodeficiencies in Switzerland: first report of the national registry in adults and children. J Clin Immunol. Nov 1988;8(6):479-85. [Medline].
Abuzakouk M, Feighery C. Primary Immunodeficiency Disorders in the Republic of Ireland: First Report of the National Registry in Children and Adults. J Clin Immunol. Jan 2005;25(1):73-77. [Medline].
Mullen CA, Anderson KD, Blaese RM. Splenectomy and/or bone marrow transplantation in the management of the Wiskott-Aldrich syndrome: long-term follow-up of 62 cases. Blood. Nov 15 1993;82(10):2961-6. [Medline].
Syrigos KN, Makrilia N, Neidhart J, et al. Prolonged survival after splenectomy in Wiskott-Aldrich syndrome: a case report. Ital J Pediatr. Sep 10 2011;37:42. [Medline]. [Full Text].
Kobayashi R, Ariga T, Nonoyama S, Kanegane H, Tsuchiya S, Morio T. Outcome in patients with Wiskott-Aldrich syndrome following stem cell transplantation: an analysis of 57 patients in Japan. Br J Haematol. Nov 2006;135(3):362-6. [Medline].
Pai SY, DeMartiis D, Forino C, Cavagnini S, Lanfranchi A, Giliani S. Stem cell transplantation for the Wiskott-Aldrich syndrome: a single-center experience confirms efficacy of matched unrelated donor transplantation. Bone Marrow Transplant. Nov 2006;38(10):671-9. [Medline].
Shin CR, Kim MO, Li D, et al. Outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome. Bone Marrow Transplant. Mar 19 2012;[Medline].
Parolini O, Ressmann G, Haas OA, et al. X-linked Wiskott-Aldrich syndrome in a girl. N Engl J Med. Jan 29 1998;338(5):291-5. [Medline].
Lanzi G, Moratto D, Vairo D, et al. A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP. J Exp Med. Jan 16 2012;209(1):29-34. [Medline]. [Full Text].
Peacocke M, Siminovitch KA. Wiskott-Aldrich syndrome: new molecular and biochemical insights. J Am Acad Dermatol. Oct 1992;27(4):507-19. [Medline].
Ochs HD. Mutations of the Wiskott-Aldrich Syndrome Protein affect protein expression and dictate the clinical phenotypes. Immunol Res. Dec 11 2008;[Medline].
Schwaber J, Rosen FS. X chromosome linked immunodeficiency. Immunodefic Rev. 1990;2(3):233-51. [Medline].
Ochs HD, Slichter SJ, Harker LA, et al. The Wiskott-Aldrich syndrome: studies of lymphocytes, granulocytes, and platelets. Blood. Feb 1980;55(2):243-52. [Medline].
Schwartz M, Mibashan RS, Nicolaides KH, et al. First-trimester diagnosis of Wiskott-Aldrich syndrome by DNA markers [letter]. Lancet. Dec 9 1989;2(8676):1405. [Medline].
Kenney DM. Wiskott-Aldrich syndrome and related X-linked thrombocytopenia. Curr Opin Pediatr. 1990;2:931-4.
Buckley RH. Advances in the correction of immunodeficiency by bone marrow transplantation. Pediatr Ann. May 1987;16(5):412-3, 416-21. [Medline].
Filipovich AH, Stone JV, Tomany SC, et al. Impact of donor type on outcome of bone marrow transplantation for Wiskott-Aldrich syndrome: collaborative study of the International Bone Marrow Transplant Registry and the National Marrow Donor Program. Blood. Mar 15 2001;97(6):1598-603. [Medline].
Knutsen AP, Steffen M, Wassmer K, et al. Umbilical cord blood transplantation in Wiskott Aldrich syndrome. J Pediatr. May 2003;142(5):519-23. [Medline].
Ochs HD, Filipovich AH, Veys P, Cowan MJ, Kapoor N. Wiskott-Aldrich syndrome: diagnosis, clinical and laboratory manifestations, and treatment. Biol Blood Marrow Transplant. Jan 2008;15(1 Suppl):84-90. [Medline].
Parkman R, Rappeport J, Geha R, et al. Complete correction of the Wiskott-Aldrich syndrome by allogeneic bone-marrow transplantation. N Engl J Med. Apr 27 1978;298(17):921-7. [Medline].
Boztug K, Dewey RA, Klein C. Development of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome. Curr Opin Mol Ther. Oct 2006;8(5):390-5. [Medline].
Galy A, Roncarolo MG, Thrasher AJ. Development of lentiviral gene therapy for Wiskott Aldrich syndrome. Expert Opin Biol Ther. Feb 2008;8(2):181-90. [Medline].
Frecha C, Toscano MG, Costa C, Saez-Lara MJ, Cosset FL, Verhoeyen E. Improved lentiviral vectors for Wiskott-Aldrich syndrome gene therapy mimic endogenous expression profiles throughout haematopoiesis. Gene Ther. Jun 2008;15(12):930-41. [Medline].
Marangoni F, Bosticardo M, Charrier S, Draghici E, Locci M, Scaramuzza S, et al. Evidence for Long-term Efficacy and Safety of Gene Therapy for Wiskott-Aldrich Syndrome in Preclinical Models. Mol Ther. Mar 3 2009;[Medline].
Scaramuzza S, Biasco L, Ripamonti A, et al. Preclinical Safety and Efficacy of Human CD34(+) Cells Transduced With Lentiviral Vector for the Treatment of Wiskott-Aldrich Syndrome. Mol Ther. Feb 28 2012;[Medline].
Galy A, Thrasher AJ. Gene therapy for the Wiskott-Aldrich syndrome. Curr Opin Allergy Clin Immunol. Dec 2011;11(6):545-50. [Medline].
Astrakhan A, Sather BD, Ryu BY, et al. Ubiquitous high-level gene expression in hematopoietic lineages provides effective lentiviral gene therapy of murine Wiskott-Aldrich Syndrome. Blood. Mar 19 2012;[Medline].
Litzman J, Jones A, Hann I, et al. Intravenous immunoglobulin, splenectomy, and antibiotic prophylaxis in Wiskott-Aldrich syndrome. Arch Dis Child. Nov 1996;75(5):436-9. [Medline].
Lum LG, Tubergen DG, Corash L, Blaese RM. Splenectomy in the management of the thrombocytopenia of the Wiskott-Aldrich syndrome. N Engl J Med. Apr 17 1980;302(16):892-6. [Medline].
Akman IO, Ostrov BE, Neudorf S. Autoimmune manifestations of the Wiskott-Aldrich syndrome. Semin Arthritis Rheum. Feb 1998;27(4):218-25. [Medline].
Dupuis-Girod S, Medioni J, Haddad E, et al. Autoimmunity in Wiskott-Aldrich syndrome: risk factors, clinical features, and outcome in a single-center cohort of 55 patients. Pediatrics. May 2003;111(5 Pt 1):e622-7. [Medline].
Buckley RH. Primary Immunodeficiency Diseases. In: Middleton E Jr, Reed CE, Ellis EF, Adkinson NF Jr, Yunginger JW, Busse WW, eds. Allergy: Principles and Practice. Vol 2. 5th ed. St. Louis, Mo: Mosby-Year Book; 1998:713-34.
Winkelstein JA, Fearon E. Carrier detection of the X-linked primary immunodeficiency diseases using X-chromosome inactivation analysis. J Allergy Clin Immunol. Jun 1990;85(6):1090-7. [Medline].
Conley ME, Saragoussi D, Notarangelo L, et al. An international study examining therapeutic options used in treatment of Wiskott-Aldrich syndrome. Clin Immunol. Dec 2003;109(3):272-7. [Medline].
Friedrich W, Schutz C, Schulz A, Benninghoff U, Honig M. Results and long-term outcome in 39 patients with Wiskott-Aldrich syndrome transplanted from HLA-matched and -mismatched donors. Immunol Res. Oct 10 2008;[Medline].
Grabenstein JD. Immune Globulin Intravenous (Human). In: ImmunoFacts: Vaccines & Immunologic Drugs. Conshohocken, Pa: Wolters Kluwer Health (Facts and Comparisons); 1999:212-24b.
Guill MF, Brown DA, Ochs HD, et al. IgM deficiency: clinical spectrum and immunologic assessment. Ann Allergy. Jun 1989;62(6):547-52. [Medline].
Hobbs JR, Milner RD, Watt PJ. Gamma-M deficiency predisposing to meningococcal septicaemia. Br Med J. Dec 9 1967;4(579):583-6. [Medline].
National Institutes of Health Consensus Conference. Intravenous immunoglobulin. Prevention and treatment of disease. JAMA. Dec 26 1990;264(24):3189-93. [Medline].
Park JY, Shcherbina A, Rosen FS, et al. Phenotypic perturbation of B cells in the Wiskott-Aldrich syndrome. Clin Exp Immunol. Feb 2005;139(2):297-305. [Medline].
Sorensen RU, Tomford JW, Gyves MT, et al. Use of intravenous immune globulin in pregnant women with common variable hypogammaglobulinemia. Am J Med. Mar 30 1984;76(3A):73-7. [Medline].
Taha S, Kindzelskii AL, Petty HR. Neutrophils Metabolic Oscillations in Wiskott-Aldrich Syndrome. J Allergy Clin Immunol. 2000;105 (part 1 of 2):S217.
Yocum MW, Strong DM, Chusid MJ, Lakin JD. Selective immunoglobulin M (IgM) deficiency in two immunodeficient adults with recurrent staphylococcal pyoderma. Am J Med. Apr 1976;60(4):486-94. [Medline].

