Wiskott-Aldrich Syndrome 

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

Overview

Background

Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by the clinical triad of microthrombocytopenia, eczema, and recurrent infections. Wiskott-Aldrich syndrome is named after two physicians who originally described the condition. In 1937, Alfred Wiskott, a German pediatrician, first described three brothers who had chronic bloody diarrhea, eczema, and recurrent ear infections. All three brothers died before the age of 2 years from bleeding or infection. Later, in 1954, Robert Aldrich, an American pediatrician, reported a Dutch kindred of boys who all died of similar clinical symptoms described by Wiskott, clearly demonstrating an X-linked mode of inheritance. Forty years later, the gene responsible for WAS was identified on the short arm of the X chromosome (Xp11.22-p11.23) by linkage analysis.

The gene product, Wiskott-Aldrich Syndrome Protein (WASp) is a 502 amino acid protein expressed within the cytoplasm of non-erythroid hematopoietic cells. More than 300 unique mutations in the WAS gene have been identified. The most common mutations are missense mutations, followed by nonsense, splice-site, and short deletion mutations. Of note, the original family described by Wiskott was confirmed to have a deletion of two nucleotides (AC73-74del) of the WAS gene. Depending on the mutations within the WASp gene product, there is wide variability of clinical disease. In one study of 154 patients with WAS, only 30% had the classic presentation with thrombocytopenia, small platelets, eczema, and immunodeficiency; 84% had clinical signs and symptoms of thrombocytopenia, 80% had eczema, 20% had only hematologic abnormalities, and 5% had only infectious manifestations.[1] Autoimmune disease is common and occurs in up to 40–70% of patients. There is also a significantly increased risk of lymphoreticular malignancy (10–20%), such as lymphoma, leukemia, and myelodysplasia.

In general, WAS gene mutations that cause absent protein expression result in classic WAS. Reduced WASp protein expression results in X-linked thrombocytopenia. WASp activating gain-of-function mutations result in X-linked neutropenia.

Eczematous lesions in Wiskott-Aldrich syndrome. Th Eczematous lesions in Wiskott-Aldrich syndrome. The lesion is essentially indistinguishable from that of atopic dermatitis except for the presence of purpura and petechiae.

Pathophysiology

WAS results from an X-linked genetic defect in the Wiskott-Aldrich syndrome protein (WASp). The gene resides on Xp11.22-23, and its expression is limited to cells of non-erythroid hematopoietic lineage.[2] The exact function of WASp is not fully elucidated, but it seems to function as a bridge between signaling and movement of the actin filaments in the cytoskeleton. Researchers identified many different mutations[3] that interfere with the protein binding to Cdc42 and Rac GTPases, among other binding partners, most of which are involved in regulation of the actin cytoskeleton of lymphocytes.[2] This ultrastructural component of cellular architecture is involved fundamentally in intracellular and cell substrate interactions and signaling via its role in cell morphology and movement. The actin cytoskeleton is responsible for cellular functions such as growth, endocytosis, exocytosis, and cytokinesis.

Researchers propose several models of actin assembly; this topic is an extremely active area of cell biology research.[4] Actin filament growth occurs by rapid monomer addition (polymerization) to the barbed leading end of a nucleated site. Nucleation, the rate-limiting step, is stimulated by a complex of actin-related protein Arp2/3 and WASp. Cdc42 GTPase also interacts with WASp to increase this nucleation. Next, gelsolin (activated by Ca++) severs actin filaments to create barbed ends, but then must be uncapped from the filament by phosphatidylinositol 4,5-bisphosphonate and Rac to proceed with polymerization. WASp also interacts with Rac and, thus, is involved in regulation of this process at multiple interrelated sites.

WAS neutrophils have been reported to manifest abnormal NAD(P)H autofluorescence, indicating defective intracellular energy flux. Presumably, WASp mutations interfere with the proper signaling and growth of cells of the hematopoietic lineage, resulting in the platelet and immune defects observed clinically, although the exact mechanisms and defective pathways remain largely unknown.

Recently published research demonstrates that the Cdc42-WASp interaction is necessary for certain chemoattractant-induced T-cell chemotaxis.[5] Further studies have now demonstrated abnormal migration and motility in multiple key cellular components of the immune system (specifically, dendritic cells and neutrophils, as well as both B and T lymphocytes).[6, 7] With regard to WASp-deficient neutrophil adhesion and migration abnormalities, this may be caused by profound defects in clustering beta-2 integrins.[8] Also of note, CD43 (a major T-cell sialoglycoprotein) is located on microvilli; disruption of WASp regulation of cytoskeletal structure may be the cause of the CD43 defects often observed in patients with WAS.[9] WASp may also have a role in transcriptional signaling and regulation of NK cells, independent of its functions in cytoskeletal actin polymerization.[10]

Studies of genotype-phenotype correlation in WAS and closely related conditions, with detailed analyses of WASp expression, have led to our understanding of the 3 distinct WAS phenotypes: 1) classic WAS triad of microthrombocytopenia, recurrent infections, and eczema; 2) the milder X-linked thrombocytopenia variant; and 3) congenital X-linked neutropenia without any of the clinical findings chracteristic of WAS. Absent WASp protein expression results in classic WAS. Mutated WASp protein expression causes X-linked thrombocytopenia. Missense mutations at the Cdc42-binding site results in X-linked neutropenia.[11, 12, 13]

Extensive study is also underway to further identify and characterize important WASp-associated proteins, such as WASp-interacting protein (WIP)[14, 15, 16, 17, 18] and several Wiskott-Aldrich syndrome proteins verprolin homologous (WAVE).[19, 20, 21] New research suggests that N-WASp (neural Wiskott-Aldrich syndrome protein), a ubiquitously expressed homologue of WASp, may have some redundancy with WASp itself.[22]

Epidemiology

Frequency

United States

The incidence of classic WAS phenotype has been estimated at 1 and 10 in 1 million cases per live birth. Overall, WAS accounts for about 3% of all primary immunodeficiency disorders.

International

A study from Switzerland reported the incidence of WAS is 4.1 cases per 1 million live births. The same study also examined the prevalence of WAS in several national registries (ie, Italy, Japan, Switzerland, Sweden) and found that this condition occurred in 2-8.8% of patients with primary immunodeficiencies, although this statistic is subject to ascertainment bias.[23] A similar range has been documented in a national registry in Ireland, as well.[24]

Mortality/Morbidity

Median survival has increased from 8 months (patients born before 1935) to longer than 6 years (patients born after 1964).[25] In one case series, 94 surviving patients ranged in age from 1-35 years, with a median of 11 years; the average age of patients who died was 8 years.[1]

The cause of death is largely infections or bleeding, but, in one series, 12% of patients developed malignancies, primarily B-cell lymphomas, and leukemia. In that series, the relative risk of malignancy was more than 100-fold that of normal and the risk increased with age.[25] Another study showed similar results, with the reported cause of death among patients who did not receive bone marrow transplants being infection (44%), bleeding (23%), or malignancy (26%).[1]

With aggressive care (eg, splenectomy), longer survival is possible.[26, 27] Bone marrow transplant can be curative.[26] Survival rates after stem cell transplant have continued to increase, particularly after more recent emphasis on performing these procedures as soon as possible after diagnosis.[28, 29]

Outcomes of hematopoietic cell transplantation have especially improved since 2000.[30]  From the most recent series of transplanted patients, overall survival from HSCT was approximately 90%.

Race-, sex-, and age-related characteristics

One large series of 301 confirmed and probable cases of WAS from 149 families reported that 8 families were black and 4 families were Chicano. Of the 40 families whose ancestry was traced outside North America, 38 emigrated from Europe.[25]

WAS is an X-linked recessive genetic disorder. The abnormal gene is relatively rare, and untreated individuals often do not survive childhood.

WAS occurs almost exclusively in males, although it is also reported in females. One report of WAS in an 8-year-old girl found a WASp gene mutation on her paternal X chromosome associated with nonrandom inactivation of her maternal X chromosome.[31] Other closely related genetic abnormalities (such as WIP deficiency) have also been reported in females, with clinical features similar to WAS.[32]

WAS is a severe congenital immunodeficiency; therefore, it occurs primarily in children. However, 2 large case series reported patients in their fourth decade of life.[25, 1]

Prognosis

Long-term prognosis was poor in the past. Prior to use of stem cell transplantation, few patients survived beyond their teens and most succumbed to compications of bleeding, infection, or malignancy.[33] Median survival in a cohort of patients born after 1964 was 6.5 years, althought survival rates have continued to increase over time.[25]

With aggressive care, prognosis has substantially improved. One study projects median survival of 25 years for patients who undergo splenectomy, and even longer for patients who undergo successful bone marrow transplant.[26] Success rates of all categories of stem cell transplantation (HLA-identical, matched/related, matched/unrelated, umbilical cord blood) have continued to climb over time.[28, 29, 30] From the most recent series of transplanted patients, overall survivial from HSCT was approximately 90%.

Patient Education

Educate patients about the function of their platelets and their immune system and about signs and symptoms that require prompt medical attention, including those seen with infections, bleeding, and malignancy.

Advise patients to appropriately restrict activities, depending on the severity of thrombocytopenia (eg, protective headgear may be indicated).

Teach patients excellent general skin care and moisturization to manage eczema.

Refer women known to be carriers for WAS for genetic counseling, and advise them that prenatal diagnosis is available.

For patient education resources, see the Skin, Hair, and Nails Center, as well as Eczema.

The Immune Deficiency Foundation (http://primaryimmune.org/) is a valuable educational resource for patients and families with primary immunodeficiency (PI) such as Wiskcott-Aldrich syndrome. There is a wealth of online educational publications and resources available to help patients and families understand and manage their condition.

The Jeffrey Modell Foundation (http://www.info4pi.org/) is another valuable online educational resource for patients and families with primary immunodeficiency. The foundation is “devoted to early and precise diagnosis, meaningful treatments, and ultimately, cures - through clinical and basic research, physician education, patient support, advocacy, public awareness and newborn screening.”

 

Presentation

History

Male infants typically present in the first year of life with severe persistent thrombocytopenia, eczema, recurrent sinopulmonary infections, and opportunistic infections. Pronounced bleeding after circumcision is an early diagnostic sign to watch out for. The most consistent laboratory finding at the time of diagnosis is thrombocytopenia and small platelets. Therefore, any male with microthrombocytopenia should be evaluated for WASp expression and WAS gene mutation. Depending on the mutations within the WASp gene product, there is wide variability of clinical disease at presentation. In one study of 154 patients with WAS, only 30% had the classic presentation with thrombocytopenia, small platelets, eczema, and immunodeficiency; 84% had clinical signs and symptoms of thrombocytopenia, 80% had eczema, 20% had only hematologic abnormalities, and 5% had only infectious manifestations.[1] Autoimmune disease is common and occurs in up to 40–70% of patients. One review of 55 patients with WAS from a single hospital in France, over a course of 20 years, found autoimmune or inflammatory conditions in 70% of patients, most commonly autoimmune hemolytic anemia (see Donath-Landsteiner Hemolytic Anemia and Cold Agglutinin Disease).[34] There is also a significantly increased risk of malignancy in WAS (10–20%), especially with B-cell lymphoma. Patients with autoimmune disease were significantly more likely to develop malignancy.[1]

Male infants with WAS usually present with bleeding, commonly bloody diarrhea, excessive bleeding after circumcision, purpura, or unusual bruising.

One series of 154 patients found petechiae or purpura in 78%, serious gastrointestinal bleeding (hematemesis or melena) in 28%, epistaxis in 16%, and intracranial bleeding in 2% of patients.[1]

Recurrent sinopulmonary infection with encapsulated organisms occur frequently and include otitis media (64%), pneumonia (25%0, sepsis (7%), and meningitis (4%).

Opportunistic infections with Pneumocystis jirovecii can occur.

Patients with WAS can also develop severe and disseminated viral infections, including herpes simplex (6%) and varicella (3%).

Atopic symptoms are frequently present, and eczema develops in 80% of these patients.[1] Severe eczema requires aggressive therapy. The eczema may improve as the patient gets older, although serious complications such as secondary infection (eg, cellulitis, abscess) or erythroderma can occur.[35]

Cutaneou infections are common and may require systemic antibiotics.

Autoimmune disease is common and occurs in up to 40–70% of patients.

Physical

Watch for signs of bleeding, infection, malignancy, and atopy during the physical examination.

  • Patients' general appearance and vital signs are important. Follow height and weight over time to monitor appropriate development.

  • Examine the skin for any evidence of eczema, purpura (eg, thrombocytopenia), or superficial or deep infections (eg, impetigo, cellulitis, furuncles, abscesses).

  • During head and neck examinations, note any abnormalities of the tympanic membranes (eg, otitis media) or sinuses and mucous membranes (eg, sinonasal infections, pharyngitis, thrush).

  • Auscultate lungs carefully to check for wheezing (eg, asthma) and rales or rhonchi (eg, pulmonary infection such as bronchitis or pneumonia).

  • Investigate for a possible malignancy if adenopathy or hepatosplenomegaly is present.

  • Neurological examination is particularly relevant if meningitis, central nervous system lymphoma,[36] or intracranial bleeding or infection is considered.

Causes

WAS is caused by various mutations in the gene coding for the WASp. This mutation is expressed in hematopoietic cells (eg, lymphocytes) and impairs the normal function of WASp in actin polymerization.[2] A strong phenotype-genotype correlation has been described.[37] Absent WASp protein expression results in classic WAS. Mutated WASp protein expression causes X-linked thrombocytopenia. Missense mutations at the Cdc42-binding site results in X-linked neutropenia.[11, 12, 13]

The WASp gene is located on the Xp11.22-23 region of the X chromosome and is inherited in a sex-linked fashion. A male child of a female carrier has a 50% chance of being affected; a female child has a 50% chance of being a carrier.[38]

Complications

Complications from 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]

Malignancy, especially lymphoreticular, occur in 10–20% of WAS patients

 

DDx

 

Workup

Laboratory Studies

Obtain a complete blood cell count with manual differential, lymphocyte and plately enumeration, and peripheral blood smear. The most consistent finding at diagnosis is thrombocytopenia and small platelets. Lymphopenia is also characteristic for classic WAS during childhood.

Screen for WASp mutations with flow cytometery with anti-WASp antibody.

Patients with mutated WASp expression may be missed with flow cytometery, therefore direct Sanger sequencing of patient DNA is essential for confirming the diagnosis in patients with abnormal protein expression.

Measure quantitative serum immunoglobulin levels of all other classes (ie, immunoglobulin A [IgA], immunoglobulin G [IgG], immunoglobulin E [IgE]).

In classic WAS, IgM levels are low and IgG levels are relatively normal, but IgA and IgE levels may be elevated.

Test humoral immune function by measuring the patient's ability to develop antibody responses to standard polysaccharide and protein antigen vaccines (eg, pneumococcal vaccine, tetanus toxoid), using preimmunization and postimmunization antibody titers.

Measure cellular immune function by examining lymphocyte proliferative responses to mitogens, alloantigen, and recall antigens and the patient's ability to react to anergy battery skin testing with delayed-type (type IV) hypersensitivity responses. The latter skin test antigens typically consist of candidal, mumps, trichophyton, and tetanus toxoid antigens.

In WAS, defects in a patient's response to polysaccharide vaccination and anergy are common. Responses to protein antigens and lymphocyte proliferation may also be impaired.[1]

Enumeration of T- and B-cell subsets by flow cytometry may be helpful.

This test provides quantitative and morphologic information about cellular elements of the immune system and information about platelet numbers and morphology. T-cell deficiency may occur, although B-cell number is usually preserved (albeit with possibly significantly altered phenotypic expression). Thrombocytopenia and small platelets are present in patients with this disorder.[1, 40] Patients with WAS may have unstable sialoglycoprotein CD43 (sialophorin) on the surface of lymphocytes[9] . One study of 154 patients with WAS revealed lymphopenia in 22% and low CD8+ T-cell counts in 61%.[1]

Consider genetic testing for carrier status. Prenatal diagnosis via amniocentesis or chorionic villus sampling is possible.[41]

Patients may require other tests based on clinical presentation. Serious disorders (eg, bleeding, infection, malignancy) form part of this syndrome.

Imaging Studies

If pneumonia is considered, obtain a chest radiograph.

Use computed tomography to evaluate for splenomegaly, help rule out malignancy, help rule out intracranial bleeding, evaluate sinus infection, and/or evaluate for pulmonary infections.

Procedures

Consider obtaining a bone marrow biopsy to assist diagnosis in complex cases or to evaluate for hematologic malignancy. However, patients generally do not require bone marrow biopsy. If performed, megakaryocytes usually appear normal.[40]

If meningitis is considered, a lumbar puncture may be necessary.

Recurrent otitis media may require tympanostomy tube placement.

Histologic Findings

Platelets in patients with WAS are small, with a decreased diameter and volume. One study of platelets in patients with WAS found an average diameter of 1.82 micrometer (normal = 2.23 micrometer)[42] , and another study found a mean volume of 3.8-5 fL, compared with 7.1-10.5 fL in individuals without WAS.[40]

 

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/m2) 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]

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]

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.

Diet

Patients do not require dietary restrictions.

Activity

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

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]

Prevention

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

 

Medication

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.

 

Follow-up

Further Outpatient Care

Patients must receive close pediatric or medical follow-up, specialized allergy and immunology care, and, often, hematology or oncology care.

Further Inpatient Care

Patients with severe infections, bleeding, or malignancies may require hospitalization for intravenous antibiotics, for monitoring and/or transfusions, or for oncologic care, respectively.

Inpatient & Outpatient Medications

Patients with WAS often need antibiotics for recurrent infections, either in an inpatient or outpatient setting. Patients who had a splenectomy usually require daily prophylactic antibiotics.[26, 58]

Transfer

Patients may need evaluation, and sometimes transfer, to a referral center with expertise in pediatric immunodeficiencies.

Deterrence/Prevention

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