Pediatric Wiskott-Aldrich Syndrome Treatment & Management

Updated: Apr 28, 2021
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Harumi Jyonouchi, MD  more...
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Medical Care

The Wiskott-Aldrich syndrome (WAS) disease severity is variable, although somewhat predictable from genotype. [5] Accordingly, treatment strategies range from conservative to early definitive intervention.

Optimally, donor cells should match the patient at all 6 major histocompatibility (MHC) sites because an incomplete match carries a higher risk for complications (particularly graft versus host disease [GVHD]) in Wiskott-Aldrich syndrome compared with patients with most other primary immunodeficiency diseases. Matched-related bone marrow transplantation from a sibling has been successful in almost 90% of patients with Wiskott-Aldrich syndrome, with full T-cell, B-cell, and platelet engraftment.

Because a patient with Wiskott-Aldrich syndrome has some degree of cell-mediated immunity, the patient must receive a preparative regime of immunosuppressive therapy, typically cyclophosphamide, busulfan, and, possibly, total body irradiation, to allow donor cells to engraft. Recently, fludarabine-based myeloablative conditioning regimens have been developed with promising results of good engraftment and low treatment-related toxicities. [42] In utero transplantation is not an option because of the need for pretransplant immunosuppression.

Gene therapy is becoming available. [43] In mice, one study successfully transferred the WASP gene into hematopoietic stem cells, using the WASP –containing lentiviral vector, combined with nonlethal irradiation. [44] Another murine study showed that the WASp transgene expression can be successfully maintained long-term in recipients and that it is associated with a significant repair of migratory defects. [7] Phase I and II clinical studies are starting soon in several European countries to assess the safety and efficacy of this lentiviral vector in Wiskott-Aldrich syndrome and early results are promising. [45, 43, 46] Although the WASP gene is cloned, its exact identity and function are not fully understood, leading to concern that overexpression of WASP could cause clinical illness.

Management of infection includes antibiotics and possibly intravenous immunoglobulin G (IVIG). The decision to use prophylactic antibiotics and/or IVIG is made case-by-case, based on incidence and severity of infection in the individual patient. Postsplenectomy, prophylactic antibiotics are mandatory, although the patients who undergo splenectomy remain at considerable risk for overwhelming sepsis despite of prophylaxis. Immunizations are mandatory with conjugated polysaccharide Hib and pneumococcal vaccines and with the unconjugated meningococcal vaccines.

Postexposure prophylaxis for varicella is indicated. Varicella-zoster immune globulin is administered within 48 hours if possible, although it may be effective until 96 hours postexposure. Beyond that time, acyclovir is recommended during the incubation period. Patients with severe eczema are at risk for both disseminated varicella-zoster infection and eczema herpeticum. The appropriate treatment for both is oral acyclovir.

Manage acute bleeding with platelet transfusions and packed erythrocytes. All blood products should be leukocyte-free and screened to avoid transmission of cytomegalovirus (CMV), in addition to regular screening for human immunodeficiency virus (HIV) and hepatitis viruses. Minimizing exposure to allogeneic cells in the patient for whom stem cell reconstitution is planned is important because such exposure increases graft rejection rates. Platelets have a shorter survival in Wiskott-Aldrich syndrome than in healthy individuals. Recurrent episodes of significant bleeding have been managed by splenectomy when immune reconstitution was not an option. Splenectomy is a controversial procedure because it increases the risk of infection with encapsulated organisms.

Treat eczema with conventional topical moisturizing creams and topical steroids. Milk and other potential food allergens may be eliminated from the diet on a trial basis to observe for improvement. Eczema often waxes and wanes with no apparent trigger, although some patients seem to improve during antibiotic therapy. Allergic rhinitis and asthma are treated in the same manner as in an immunocompetent individual. Eczema herpeticum is treated with oral acyclovir.

Manage autoimmune hemolytic anemia (AIHA) and other autoimmune disorders as in immunocompetent individuals. Interestingly, high-dose IVIG is unlikely to have benefit in AIHA or immune thrombocytopenia. Romiplostim may be useful in treating thrombocytopenia in children with Wiskott-Aldrich syndrome. [47]

For more information, see Dermatologic Manifestations of Wiskott-Aldrich Syndrome and Wiskott-Aldrich Syndrome.


Surgical Care

Surgical intervention is likely to be necessary for complications of bleeding. If subdural hematoma formation occurs, the neurosurgeon must work closely with the clinical immunologist and the blood bank for an optimal outcome. Bleeding after any minor trauma may require surgical evacuation of hematomas or intervention to halt blood loss. Platelet and erythrocyte transfusions must be available immediately and maintained during and after surgery. Consider blood products cautiously when stem cell therapy is planned. Splenectomy is an option for patients in whom severe thrombocytopenia and frequent bleeding coexist and for whom stem cell reconstitution is not considered. However, splenectomy creates an additional risk for overwhelming fatal sepsis and leaves the patient at continued risk for the complication of malignancy.



A hematologist and an oncologist are the most common consultations needed when AIHA, immune neutropenia, or lymphoreticular malignancies develop. Support from blood banking can be critical when active bleeding occurs. Bone marrow transplantation teams now are an obligatory component of Wiskott-Aldrich syndrome management. Because the outcome of stem cell reconstitution is best in children younger than 2 years, early consultation is essential.

Unlike other primary immunodeficiencies, unusual infections are relatively rare in Wiskott-Aldrich syndrome. Autoimmune disorders that require consultation include arthritis (usually transient) and renal compromise.



Offer most patients a normal nutritious diet. In the presence of significant eczema, the physician may try eliminating common foods associated with allergy; although milk is the most likely culprit, nuts, eggs, and legumes may also be at fault.



Encourage normal levels of physical activities, with the notable exception of sports that risk CNS trauma because of the presence of thrombocytopenia. Toddlers should wear helmets, although this is difficult to enforce. Most patients can attend school or work under normal circumstances. Advise patients to avoid exposure to varicella.



Families carrying known mutations in the WASP gene should have prenatal diagnosis using mutation analysis. Identifying an affected infant in utero allows consideration of caesarian delivery to avoid bleeding at birth. Most importantly, prenatal diagnosis allows consideration of early stem cell reconstitution and identification of a donor as early as possible.

A critical point to remember is that platelet count alone does not establish the diagnosis of Wiskott-Aldrich syndrome in all infants; mean platelet volume (MPV) must be assessed. Immune functions may not show a classic pattern, making input from a clinical immunologist essential for accurate identification. In some cases, only determination of DNA mutational analysis allows discrimination among Wiskott-Aldrich syndrome, the more minor disorder of X-linked thrombocytopenia, and a non–Wiskott-Aldrich syndrome diagnosis.