Wiskott-Aldrich Syndrome Treatment & Management

Updated: Aug 24, 2017
  • Author: Peter N Huynh, MD; Chief Editor: Michael A Kaliner, MD  more...
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Treatment

Medical Care

Patients require vigilant general medical or pediatric care. Promptly and aggressively treat infections and bleeding. General treatment strategies includes use of antibiotics, intravenous immunoglobulin (IVIG) therapy, splenectomy in special cases, gene therapy, and early hematopoietic stem cell transplantation (HSCT). Immunomodulatory agents such as rituximab may serve a role in associated autoimmunity. 

  • Patients with WAS mutations and lymphopenia are candidates for Pneumocystis Jerovici prophylaxis (Cotrimazole 20 mg/kg/day).
  • Give intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SQIG) (500 mg/kg) every 3-4 weeks for patients with classic WAS. Gammaglobulin replacement may be considered for patients with the milder variant of X-linked thrombocytopenia and for those with recurrent infection.
  • Additional prophylactic antibiotic therapy such as azithromycin (10 mg/kg/day three times a week) may be considered if infections continue despite immunoglobulin infusions.
  • Acyclovir may be considered for chronic herpes virus infection.
  • Post-exposure to chicken pox may be treated with IVIG, which contains high anti-varicella antibody titers.
  • Eczema may be severe. Manage the eczema aggressively, with careful attention to skin care, emollient use, and appropriate topical steroid therapy. [35]
  • Cutaneous infections are common and may require systemic antibiotics.
  • Patients with severe thrombocytopenia may require high dose intravenous immunoglobulin (2 gm/kg/day) and/or corticosteroids (2 mg/kg/day).
  • Patients with severe bleeding may require platelet and/or red blood cell transfusions. All blood products should be irradiated. Non-irradiated blood contains T lymphocytes, which could lead to fatal graft-versus-host disease.
  • Autoimmune disease is common and occurs in up to 40–70% of patients. Autoimmune cytopenias can be difficult to treat, but may respond to rituximab (4 weekly doses of 375 mg/m 2) combined with prednisolone (2 mg/kg/day).  
  • Surveillance for malignancy is an important aspect of care.
  • Killed vaccines may be given, however, responses may be insufficient due to underlying immune dysfunction.
  • Live attenuated vaccines are contraindicated.

Stem cell transplantation

The standard of care for infants with classical WAS is early hematopoietic stem cell transplantation (HSCT) prior to the development of complications from infection, bleeding and autoimmune disease. 

Donor histocompatibility has been an important determinant of survival after bone marrow transplant for WAS. A survival rate of 80% was observed in patients who received HLA-identical transplants, but a survival rate of only 23% was observed in patients who received mismatched (haploidentical) transplants. [43] A later study of outcome of bone marrow transplant in patients with WAS examined 170 patients and found a 70% 5-year survival rate for all patients who received transplants. This included a 5-year survival rate of 87% with HLA-identical sibling donors, 52% with other related donors, and 71% with unrelated donors. [44]

However, continued improvement in graft success and survival rates has progressed over time, with rates now generally near 70-80% in case series from 1990-2005 in Italy [29] and 1985-2004 in Japan. [28] The most recent series now show much improved outcomes, even in the setting of HLA mismatch. [30] When a matched sibling donor is unavailable, umbilical cord blood stem cell transplantation has been used. [45]

Increased attention has been given to pretransplant reduced-intensity conditioning regimens, in comparison to myeloablative conditioning, with regard to posttransplant mixed chimerism and the possibility of increased autoimmunity. [46]

If bone marrow transplantation is successful, hematologic and immunologic defects are corrected and eczema resolves. [26, 47]

Gene therapy

Gene therapy trials (phase I/II studies to start in Europe) to reconstitute WASp expression in autologous hematopoietic stem cells have been planned. [48, 49] Mouse models for this process to date have used a modified lentiviral (HIV-1 derived) vector. [49, 50, 51, 52] Proof of principle for gene therapy in WAS has been reported. [53, 54, 55]  

A 2015 study of 7 patients with severe Wiskott-Aldrich syndrome who were infused with gene-corrected autologous hematopoietic stem cells demonstrated the feasibility of the use of gene therapy in these patients. One patient died, but the remaining 6 all showed decreased susceptibility to infections and 5 patients exhibited improved autoimmunity. [56]

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Surgical Care

Patients may require splenectomy to help control thrombocytopenia [57] , although this intervention may increase the already elevated risk of infection from encapsulated organisms (eg, pneumococcal sepsis). Studies demonstrate that most patients who had a splenectomy achieve normal platelet counts, and their rates of serious bleeding decrease 5- to 6-fold. [1, 26, 58]

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Consultations

Refer patients to an allergist/clinical immunologist and/or pediatric hematologist to exclude other comorbid immune defects and to ensure accurate diagnosis.

Patients with associated thrombocytopenia, bleeding, and malignancies may require consultation with a hematologist or oncologist to assist with management.

Patients with refractory infections may require consultation with an infectious diseases specialist.

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Diet

Patients do not require dietary restrictions.

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Activity

Patients with thrombocytopenia must take precautions to prevent bleeding (eg, fall precautions, protective headgear, no contact sports).

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Complications

Complications for infection, bleeding, autoimmune disease, and malignancy characterize WAS.

Autoimmune and rheumatologic conditions may also occur. [39] One study found these conditions in 40% of patients, and often multiple conditions coexisted in the same patient. Patients with autoimmune disease were significantly more likely to develop malignancy. [1] Another review of 55 patients with WAS from a single hospital in France, over 20 years, found autoimmune or inflammatory conditions in 72%, most commonly autoimmune hemolytic anemia (see Donath-Landsteiner Hemolytic Anemia and Cold Agglutinin Disease), among multiple other conditions. [34]

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Prevention

Genetic testing and prenatal diagnosis are options that may contribute to decreased occurrence of this condition.

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