eMedicine Specialties > Pediatrics: General Medicine > Allergy & Immunology
Wiskott-Aldrich Syndrome: Treatment & Medication
Updated: Feb 3, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Stem cell reconstitution is now first choice therapy for Wiskott-Aldrich syndrome (WAS) and should be performed as soon as the diagnosis is confirmed in order to prevent life-threatening infections.20 Potential sources for CD34+ stem cells include bone marrow, cord blood, and CD34+ peripheral cells mobilized by granulocyte colony-stimulating factor (G-CSF) treatment of the donor. The success of the transplantation is associated with many factors including the recipient's age, donor selection, the conditioning regimen, and the extent of reconstitution.
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.21 In utero transplantation is not an option because of the need for pretransplant immunosuppression.
Gene therapy is expected to become available in the future because studies in mice are promising. One study successfully transferred the WASP gene into hematopoietic stem cells, using the WASP –containing lentiviral vector, combined with nonlethal irradiation.22 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.1 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.23 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.
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.
Consultations
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.
Diet
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.
Activity
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.
Medication
Otitis media is treated with conventional first-line antibiotics (eg, amoxicillin, amoxicillin/clavulanate, cefuroxime axetil). Intramuscular injection of antibiotics is avoided because of the risk of excessive bleeding. The duration of antibiotic therapy should follow conventional recommendations for the specific infection being treated.
Most medical care is provided on an outpatient basis with the caveat that episodes of bacteremia and sepsis present higher risks for patients with Wiskott-Aldrich syndrome (WAS), and signs and symptoms may be subtle because of an inadequate inflammatory response resulting from phagocytic and humoral immune defects.
Administration of tetanus and diphtheria toxoids and the acellular pertussis and conjugated Hib and pneumococcal vaccines is essential and usually results in a protective, although subnormal, antibody response. The attenuated varicella vaccine has been administered without complication. Live measles and poliovirus vaccines are contraindicated. Influenza and hepatitis vaccines should be safe, but experience in administering them to patients with Wiskott-Aldrich syndrome is limited.
IVIG has been administered to selected patients with frequent bacterial infections.
Some patients may benefit from conventional inhaler therapies for reactive airway disease.
Replacement therapy with intravenous immunoglobulin in patients with primary immune deficienciesThe consensus among clinical immunologists is that a dose of intravenous immunoglobulin (IVIG) of 400-600 mg/kg/mo or a dose that maintains trough serum immunoglobulin G (IgG) levels greater than 500 mg/dL is desirable. Patients with meningoencephalitis require much higher doses (1 g/kg) and perhaps intrathecal therapy. Measurement of preinfusion (trough) serum IgG levels every 3 months until a steady state is achieved and then every 6 months if the patient is stable may be helpful in adjusting the dose of IVIG to achieve adequate serum levels. For persons who have a high catabolism of infused IgG, more frequent infusions (eg, every 2-3 wk) of smaller doses may maintain the serum level in the reference range. The rate of elimination of IgG may be higher during a period of active infection; measuring serum IgG levels and adjusting to higher dosages or shorter intervals may be required.
For replacement therapy for patients with primary immune deficiency, all brands of IVIG are probably equivalent, although differences in viral inactivation processes are noted (eg, solvent detergent versus pasteurization and liquid versus lyophilized). The choice of brands may depend on the hospital or home care formulary and the local availability and cost. The dose, manufacturer, and lot number should be recorded for each infusion in order to review for adverse events or other consequences.
Recording all side effects that occur during the infusion is crucial. Monitoring liver and renal function test results periodically, approximately 3-4 times yearly, is also recommended. The US Food and Drug Administration (FDA) recommends that for patients at risk for renal failure (eg, preexisting renal insufficiency, diabetes, volume depletion, sepsis, paraproteinemia, age >65 y, use of nephrotoxic drugs), recommended doses should not be exceeded and infusion rates and concentrations should be the minimum levels that are practicable.
The initial treatment should be administered under the close supervision of experienced personnel. The risk of adverse reactions in the initial treatments is high, especially in patients with infections and those who form immune complexes. In patients with active infection, infusion rates may need to be slower and the dose halved (ie, 200-300 mg/kg), with the remaining dose administered the next day to achieve a full dose. Treatment should not be discontinued. After achieving reference range serum IgG levels, adverse reactions are uncommon unless patients have active infections.
With the new generation of IVIG products, adverse effects are much reduced. Adverse effects include tachycardia, chest tightness, back pain, arthralgia, myalgia, hypertension or hypotension, headache, pruritus, rash, and low-grade fever. More serious reactions are dyspnea, nausea, vomiting, circulatory collapse, and loss of consciousness. Patients with more profound immunodeficiency or patients with active infections have more severe reactions.
Anticomplementary activity of IgG aggregates in the IVIG and the formation of immune complexes are thought to be related to the adverse reactions. The formation of oligomeric or polymeric IgG complexes that interact with Fc receptors and trigger the release of inflammatory mediators is another cause. Most adverse reactions are rate related. Slowing the infusion rate or discontinuing therapy until symptoms subside may diminish the reaction. Pretreatment with ibuprofen (5-10 mg/kg every 6-8 h), acetaminophen (15 mg/kg per dose), diphenhydramine (1 mg/kg per dose), and/or hydrocortisone (6 mg/kg per dose, maximum 100 mg) 1 hour before the infusion may prevent adverse reactions. In some patients with a history of severe adverse effects, analgesics and antihistamines may be repeated.
Acute renal failure is a rare but significant complication of IVIG treatment. Reports suggest that IVIG products using sucrose as a stabilizer may be associated with a greater risk for this renal complication. Acute tubular necrosis, vacuolar degeneration, and osmotic nephrosis are suggestive of osmotic injury to the proximal renal tubules. The infusion rate for sucrose-containing IVIG should not exceed 3 mg sucrose per kg/min. Risk factors for this adverse reaction include preexisting renal insufficiency, diabetes mellitus, dehydration, age older than 65 years, sepsis, paraproteinemia, and concomitant use of nephrotoxic agents. For patients at increased risk, monitoring BUN and creatinine levels before starting the treatment and prior to each infusion is necessary. If renal function deteriorates, the product should be discontinued.
Immunoglobulin E (IgE) antibodies to immunoglobulin A (IgA) have been reported to cause severe transfusion reactions in IgA-deficient patients. A few reports suggest true anaphylaxis in patients with selective IgA deficiency and common variable immunodeficiency who developed IgE antibodies to IgA after treatment with immunoglobulin. However, in actual experience this is very rare. In addition, this is not a problem for patients with X-linked agammaglobulinemia (XLA) (Bruton disease) or severe combined immunodeficiency (SCID). Exercise caution in patients with IgA deficiency (<7 mg/dL) who need IVIG because of IgG subclass deficiencies. IVIG preparations with very low concentrations of contaminating IgA are advised (see the Table below).
Immune Globulin, Intravenous24,25,26,27
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Table
| Brand(Manufacturer) | Manufacturing Process | pH | Additives* | Parenteral Form and Final Concentrations | IgA Content mcg/mL |
| Carimune NF (CSL Behring) | Kistler-Nitschmann fractionation; pH 4 incubation, nanofiltration | 6.4-6.8 | 6% solution: 10% sucrose, <20 mg NaCl/g protein | Lyophilized powder 3%, 6%, 9%, 12% | Trace |
| Flebogamma (Grifols USA) | Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization | 5.1-6 | Sucrose free, contains 5% D-sorbitol | Liquid 5% | <50 |
| Gammagard Liquid 10% (Baxter Bioscience) | Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation | 4.6-5.1 | 0.25M glycine | Ready-for-use Liquid 10% | 37 |
| Gamunex (Talecris Biotherapeutics) | Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation | 4-4.5 | Contains no sugar, contains glycine | Liquid 10% | 46 |
| Iveegam EN (Baxter Bioscience) | Cohn-Oncley fraction II/III; ultrafiltration; pasteurization | 6.4-7.2 | 5% solution: 5% glucose, 0.3% NaCl | Lyophilized powder 5% | <10 |
| Polygam S/D Gammagard S/D (Baxter Bioscience for the American Red Cross) | Cohn-Oncley cold ethanol fractionation, followed by ultracentrafiltration and ion exchange chromatography; solvent detergent treated | 6.4-7.2 | 5% solution: 0.3% albumin, 2.25% glycine, 2% glucose | Lyophilized powder 5%, 10% | <1.6 (5% solution) |
| Octagam (Octapharma USA) | Cohn-Oncley fraction II/III; ultrafiltration; low pH incubation; S/D treatment pasteurization | 5.1-6 | 10% maltose | Liquid 5% | 200 |
| Panglobulin (Swiss Red Cross for the American Red Cross) | Kistler-Nitschmann fractionation; pH 4, trace pepsin, nanofiltration | 6.6 | Per gram of IgG: 1.67 g sucrose, <20 mg NaCl | Lyophilized powder 3%, 6%, 9%, 12% | 720 |
| Privigen Liquid 10% (CSL Behring) | Cold ethanol fractionation, octanoic acid fractionation, and anion exchange chromatography; pH 4 incubation and depth filtration | 4.6-5 | L-proline (~250 mmol/L) as stabilizer; trace sodium; does not contain carbohydrate stabilizers (eg, sucrose, maltose) | Ready-for-use liquid 10% | <25 |
| Brand(Manufacturer) | Manufacturing Process | pH | Additives* | Parenteral Form and Final Concentrations | IgA Content mcg/mL |
| Carimune NF (CSL Behring) | Kistler-Nitschmann fractionation; pH 4 incubation, nanofiltration | 6.4-6.8 | 6% solution: 10% sucrose, <20 mg NaCl/g protein | Lyophilized powder 3%, 6%, 9%, 12% | Trace |
| Flebogamma (Grifols USA) | Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization | 5.1-6 | Sucrose free, contains 5% D-sorbitol | Liquid 5% | <50 |
| Gammagard Liquid 10% (Baxter Bioscience) | Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation | 4.6-5.1 | 0.25M glycine | Ready-for-use Liquid 10% | 37 |
| Gamunex (Talecris Biotherapeutics) | Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation | 4-4.5 | Contains no sugar, contains glycine | Liquid 10% | 46 |
| Iveegam EN (Baxter Bioscience) | Cohn-Oncley fraction II/III; ultrafiltration; pasteurization | 6.4-7.2 | 5% solution: 5% glucose, 0.3% NaCl | Lyophilized powder 5% | <10 |
| Polygam S/D Gammagard S/D (Baxter Bioscience for the American Red Cross) | Cohn-Oncley cold ethanol fractionation, followed by ultracentrafiltration and ion exchange chromatography; solvent detergent treated | 6.4-7.2 | 5% solution: 0.3% albumin, 2.25% glycine, 2% glucose | Lyophilized powder 5%, 10% | <1.6 (5% solution) |
| Octagam (Octapharma USA) | Cohn-Oncley fraction II/III; ultrafiltration; low pH incubation; S/D treatment pasteurization | 5.1-6 | 10% maltose | Liquid 5% | 200 |
| Panglobulin (Swiss Red Cross for the American Red Cross) | Kistler-Nitschmann fractionation; pH 4, trace pepsin, nanofiltration | 6.6 | Per gram of IgG: 1.67 g sucrose, <20 mg NaCl | Lyophilized powder 3%, 6%, 9%, 12% | 720 |
| Privigen Liquid 10% (CSL Behring) | Cold ethanol fractionation, octanoic acid fractionation, and anion exchange chromatography; pH 4 incubation and depth filtration | 4.6-5 | L-proline (~250 mmol/L) as stabilizer; trace sodium; does not contain carbohydrate stabilizers (eg, sucrose, maltose) | Ready-for-use liquid 10% | <25 |
*IVIG products containing sucrose are more often associated with renal dysfunction, acute renal failure, and osmotic nephrosis, particularly with preexisting risk factors (eg, history of renal insufficiency, diabetes mellitus, age >65 y, dehydration, sepsis, paraproteinemia, nephrotoxic drugs).
Antibiotics
Amoxicillin, amoxicillin/clavulanate, and cefuroxime axetil are the PO drugs of choice for the common extracellular bacteria that cause sinopulmonary infections. Ceftriaxone administered intravenously is the first-line antibiotic for suspected bacteremia or sepsis and for pneumonia. It covers penicillin-resistant pneumococci. Intramuscular administration is avoided because of bleeding caused by thrombocytopenia. Nafcillin is chosen for invasive S aureus. Vancomycin is needed for penicillin-allergic patients and for treatment of methicillin-resistant S aureus. Vancomycin-resistant S aureus, GISA, may require fluoroquinolones, linezolid or Synercid.
Prophylactic antibiotics for patients with splenectomies are penicillin or amoxicillin; a macrolide can be used for penicillin-allergic patients.
Amoxicillin (Trimox, Amoxil, Biomox)
Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.
Adult
500 mg PO tid
Prophylactic dose: 250 mg PO bid
Pediatric
60-120 mg/kg/d PO divided bid/tid
Prophylactic dose: 125-250 mg PO bid
Reduces the efficacy of PO contraceptives
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in renal impairment; may enhance chance of candidiasis
Amoxicillin/clavulanate (Augmentin)
Drug combination treats bacteria resistant to beta-lactam antibiotics.
For children >3 mo, base dosing protocol on amoxicillin content. Because of different amoxicillin–clavulanic acid ratios in 250-mg tab (250/125) vs 250-mg tab (250/62.5), do not use 250-mg tab until child weighs >40 kg.
Adult
875 mg PO bid
Pediatric
<40 kilograms: 50 mg/kg/d PO divided bid
>40 kilograms: Administer as in adults
Coadministration with warfarin or heparin increases risk of bleeding
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in renal impairment; may enhance chance of candidiasis
Cefuroxime axetil (Ceftin)
Second-generation cephalosporin maintains gram-positive activity that first-generation cephalosporins have. Adds activity against Proteus mirabilis, H influenzae, E coli, K pneumoniae, and Moraxella catarrhalis.
Adult
500 mg PO bid
Pediatric
30 mg/kg/d PO divided bid; not to exceed 1 g/d
Disulfiramlike reactions may occur when alcohol is consumed within 72 h after taking cefuroxime; may increase hypoprothrombinemic effects of anticoagulants; may increase nephrotoxicity in patient receiving potent diuretics such as loop diuretics; coadministration with aminoglycosides increase nephrotoxic potential
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Administer half dose if CrCl is 10-30 mL/min and one quarter dose if <10 mL/min
Ceftriaxone (Rocephin)
Third-generation cephalosporin with broad-spectrum activity; efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins.
Adult
2 g IV q12h
Pediatric
100 mg/kg/d IV divided q12h
Probenecid may increase ceftriaxone levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in renal impairment; caution in breastfeeding women, patients <2 mo, and allergy to penicillin
Vancomycin (Lyphocin, Vancocin, Vancoled)
Potent antibiotic directed against gram-positive organisms and active against Enterococcus species. Indicated for patients who cannot receive or who have not responded to penicillins and cephalosporins or who have infections with resistant staphylococci.
To avoid toxicity, current recommendation is to assay vancomycin trough levels after third dose drawn 0.5 h before next dosing. Use creatinine clearance to adjust dose in patients with renal impairment.
Adult
500 mg IV q6h
Pediatric
60 mg/kg/d IV divided q6h
Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; when taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal failure and neutropenia; red man syndrome is caused by too rapid IV infusion (dose administered over a few min) but is rare when dose is administered as 2-h administration or as PO or IP administration; red man syndrome is not an allergic reaction
Nafcillin
DOC for acute pneumonia and deep-seated abscesses caused by S aureus.
Adult
1.5 g IV q4h
Pediatric
200 mg/kg/d IV divided q4h
Associated with warfarin resistance when administered concurrently; effects may decrease with bacteriostatic action of tetracycline derivatives
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dosage for renal compromise
Bronchodilators, inhaled
These agents are used to relieve bronchoconstriction and decrease the inflammatory response in the respiratory tree. Both pulmonary and nasal inhalers may be needed. Children 4 years and older may use inhalers effectively. Inhaler use is hampered in young children and others unable to understand the technique of administration and in older individuals unable to achieve a forceful inhalation. Adding a spacer is customary to improve coordination in children. Steroid inhalation is followed by rinsing the mouth to avoid thrush, and a spacer is highly recommended for use with steroid pressurized metered dose inhalers for all patients.
Albuterol (Proventil HFA, Ventolin HFA)
Relaxes bronchial smooth muscle by action on beta2-receptors with little effect on cardiac muscle contractility.
Adult
Inhalant: 2 inhalations (90 mcg/inhalation) q4-6h; not to exceed 12 inhalations per d
Nebulizer: Dilute 0.5-1 mL (2.5-5 mg) of 0.5% inhalation sol in 1-2.5 mL of sterile NS or water and administer via nebulizer q4-6h
Pediatric
<12 years (inhalant): 1-2 inhalations qid with tube spacer
>12 years (inhalant): Administer as in adults
<5 years (nebulizer): Dilute 0.25-0.5 mL (1.25-2.5 mg) of 0.5% inhalation sol in 1-2.5 mL of NS and administer q4-6h in equally divided doses
>5 years (nebulizer): Administer as in adults
Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by albuterol; cardiovascular effects may increase with MAOIs, inhaled anesthetics, tricyclic antidepressants, and sympathomimetic agents
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders
Salmeterol (Serevent Diskus)
By relaxing the smooth muscle fibers of the bronchioles it can relieve bronchospasms. Effect may also facilitate expectoration.
Adult
Diskus powder inhalant: 1 inhalation (50 mcg) bid, administered at least 12 h apart (50 mcg per actuation)
Pediatric
<4 years: Not established
>4 years: Administer as in adults
Concomitant use of beta-blockers may decrease bronchodilating and vasodilating effects of beta agonists such as salmeterol; concurrent administration with methyldopa may increase pressor response; coadministration with oxytocic drugs may result in severe hypotension; ECG changes and hypokalemia resulting from diuretics may worsen when coadministered with salmeterol
Documented hypersensitivity; angina; tachycardia; cardiac arrhythmias associated with tachycardia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Not indicated to treat acute symptoms
Beclomethasone (QVAR)
Inhibits bronchoconstriction mechanisms and produces direct smooth muscle relaxation. May decrease number and activity of inflammatory cells, in turn decreasing airway hyperresponsiveness.
Some patients may require higher doses of inhaled beclomethasone. Available as 40-mcg and 80-mcg per inhalation.
Adult
40-80 mcg inhaled bid; not to exceed 320 mcg bid
Pediatric
<5 years: Not established
5-11 years: 40 mcg inhaled bid initially; may increase and adjust with strict physician supervision
>12 years: Administer as in adults
Coadministration with ketoconazole may increase plasma levels, but this effect does not appear to be clinically significant
Documented hypersensitivity; bronchospasm; status asthmaticus; other types of acute episodes of asthma
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Suppression of the HPA or linear growth or Cushing syndrome may occur; caution with untreated systemic infections, ocular herpes simplex, or respiratory tuberculosis; rinse mouth after use to reduce likelihood of PO candidiasis; use with spacer
Fluticasone (Flovent HFA)
Has extremely potent vasoconstrictive and anti-inflammatory activity. Has a weak hypothalamic-pituitary-adrenocortical axis inhibitory potency when applied topically.
Some patients may require higher doses of inhaled fluticasone.
Adult
44 mcg per actuation, 2-6 inhalations per d; alternatively, 110 mcg per actuation, 2 inhalations per d
Pediatric
Administer as in adults
Drugs metabolized by CYP3A4 isoenzyme (eg, ketoconazole) might increase fluticasone concentrations
Documented hypersensitivity; viral, fungal, and bacterial skin infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Suppression of HPA or linear growth or Cushing syndrome may occur; caution with untreated systemic infections, ocular herpes simplex, or respiratory tuberculosis; rinse mouth after use to reduce likelihood of PO candidiasis; use with spacer
Hyperimmune globulins
A limited number of immunoglobulin preparations have been developed to provide prophylaxis against specific microorganisms. For primary immunodeficiency diseases including Wiskott-Aldrich syndrome, VZIG has proven efficacy to prevent primary varicella when administered within 48-72 hours postexposure. It may modify varicella when administered up to 96 hours later.
Varicella-zoster immune globulin (VariZIG)
Contains IgG varicella-zoster antibodies. Provides passive immunization to exposed individuals at high risk of complications from varicella. Administration recommended within 48 h postexposure but may be efficacious up to 96 h postexposure. The US product VZIG was discontinued by the manufacturer. An investigational product (VariZIG) is currently available via IND (contact FFF Enterprises at 800-843-7477).
Adult
625 U IM; not to exceed 2.5 mL per injection site
Pediatric
<10 kilograms: 125 U IM
10-20 kilograms: 250 U IM
20-30 kilograms: 375 U IM
30-40 kilograms: 500 U IM
>40 kilograms: 625 U IM
Interferes with active immunization with live viruses; however, MMR and OPV are contraindicated for WAS patients
Documented hypersensitivity; thrombocytopenia is a relative contraindication so that platelet transfusions might need to be considered in selected WAS patients in whom the platelet count is <50,000/µL or active bleeding is present
Pregnancy
Precautions
Must provide prolonged pressure at the IM injection site to optimize hemostasis; do not inject IV; may cause pain, redness, or swelling at injection site
Immunizations
Vaccines that contain viral components (not live viruses) should be administered to patients with Wiskott-Aldrich syndrome because a protective antibody response is often obtained. Injection technique is critical because of the risk of bleeding and hematoma at the injection site. Live virus vaccines are contraindicated with the possible exception of varicella-zoster virus. For current Advisory Committee on Immunization Practices (ACIP) recommended immunizations schedule for immunocompromised individuals, see the Centers for Disease Control and Prevention (CDC) guidelines.28,29
Vaccines
Diphtheria and tetanus toxoids (DT or Td), acellular pertussis, conjugated HIB, conjugated pneumococcal vaccine, unconjugated meningococcal A and C, hepatitis B (HBV), and influenza. CDC/AAP recommendations undergo continuing reevaluation.
Adult
Each vaccine is administered in 0.5-mL doses IM at separate sites
Td is the adult dosage q10y
Conjugated HIB and pneumococcal may require 2 doses
HBV schedule is 1 mo later for second dose, 6 mo later for third dose
Pediatric
Each vaccine is administered in 0.5-mL doses IM at separate sites
DPT is the pediatric dosage; pertussis is administered until age 7 y; initial immune response requires a series of 3 administered 4-6 wks apart
HIB, pneumococcal, and HBV schedules are same as adult
Influenza initially requires 2 doses 1 mo apart before age 9 y; for ages 6 mo to 3 years, the dose is 0.25 mL
None reported
Documented hypersensitivity; patients with WAS should receive no live virus vaccines
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Prolonged pressure at the injection site to stop bleeding is mandatory
More on Wiskott-Aldrich Syndrome |
| Overview: Wiskott-Aldrich Syndrome |
| Differential Diagnoses & Workup: Wiskott-Aldrich Syndrome |
 Treatment & Medication: Wiskott-Aldrich Syndrome |
| Follow-up: Wiskott-Aldrich Syndrome |
| Multimedia: Wiskott-Aldrich Syndrome |
| References |
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References
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Further Reading
Keywords
Wiskott-Aldrich syndrome, WAS, Wiskott-Aldrich-Huntley syndrome, eczema-thrombocytopenia syndrome, eczema-thrombocytopenia-diarrhea syndrome, eczema-thrombocytopenia immunodeficiency syndrome, X-linked thrombocytopenia, intermittent thrombocytopenia, neutropenia, lymphomas, leukemia, atopic dermatitis, otitis media, pneumonia, sepsis, meningitis, reactive airway disease, allergic rhinitis, Haemophilus influenzae type B, Hib, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, varicella-zoster virus, herpes simplex virus, autoimmune hemolytic anemia, AIHA, arthritis, nephritis, immune thrombocytopenia, non-Hodgkin lymphoma, impetigo, cellulitis, furuncles, abscesses, eczema herpeticum, molluscum, sinonasal infections, pharyngitis, thrush
