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Severe Combined Immunodeficiency: Treatment & Medication
Updated: Dec 8, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
The only cure for severe combined immunodeficiency (SCID) is bone marrow transplantation. HLA-identical donor bone marrow transplantation is optimal, followed by HLA-matched unrelated donor transplantation. HLA-mismatched related donor transplantation is an alternative and can often be successful if an HLA-matched donor cannot be identified.
- This approach is successful if the disease is diagnosed within their first 3 months of life.
- Neither pretransplantation chemoablation nor GVHD prophylaxis is required for successful engraftment with an identical donor; however, pretransplantation myeloablation is necessary in nonidentical HLA-matched donors.
- All blood products must receive 25-Gy irradiation to prevent fatal GVHD. Advances in gene therapy should lead to the correction of single genetic defects in lymphocytes.
- No live vaccines, such as the BCG vaccine, should be administered to patients with SCID prior to bone marrow transplantation.
- Several gene therapy clinical trials based on gene transfer to hematopoietic cells have been performed, but these approaches still require further development before becoming routine protocols.2,3
Consultations
- Consultation with an internal medicine specialist and an infectious disease specialist is important in the management and prevention of infection.
- A hematologist and/or an oncologist should be consulted for bone marrow transplantation.
Medication
Severe combined immunodeficiency (SCID) is best managed with stem cell replacement to reconstitute a functional immune system. For disorders caused by a single-gene defect, gene replacement in stem cells may offer a better prognosis. Without an effective immune system, patients with SCID have a poor prognosis, and management requires preventive prophylaxis of infections due to common pathogens and vigilant monitoring of potential infections. Immediate treatment upon the diagnosis of new infections is critical. Patients with known enzyme deficiency, such as ADA deficiency, may receive enzyme replacement. Also, intravenous immunoglobulin (IVIG) may help prevent symptoms of common infectious disorders.
Intravenous immunoglobulin
IVIG can be used to restore antibody levels until the B-cell system is restored with transplantation. However, long-term use fails to change the terminal course of SCID.
Immune globulin intravenous (Gamimune, Gammagard, Sandoglobulin)
Human serum fraction that contains gamma globulin antibodies. The therapeutic function is passive immunization to prevent infection.
Adult
100-800 mg/kg/mo IV; trough levels >500 mg/dL are beneficial
Pediatric
Administer as in adults
May interfere with the normal immune response to some live vaccines, including measles, mumps, and rubella virus vaccines
Documented hypersensitivity to immune globulins or additives (maltose, thimerosal, glycine, polyethylene glycol, albumin); selective IgA deficiency
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
Check serum IgA level before use (use an IgA-depleted product, eg, Gammagard S/D); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-30 d postinfusion); increases risk of renal tubular necrosis in elderly patients and in patients with diabetes, volume depletion, or preexisting kidney disease; infusion may elevate antiviral or antibacterial antibody titers for 1 mo and/or cause apparent hyponatremia and 6-fold increase in ESR for 2-3 wk
Antibiotics
Antibiotics are used in the primary treatment and prophylaxis of PCP pneumonia.
Trimethoprim/sulfamethoxazole (Septra DS, Bactrim DS, Cotrim DS)
Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Antibacterial activity of TMP-SMZ affects common urinary tract pathogens, except Pseudomonas aeruginosa. Each 5 mL vial for IV administration contains 80 mg of trimethoprim and 400 mg of sulfamethoxazole. Each 5 mL vial must be added to 125 mL of 5% dextrose in water. Please consult the hospital pharmacist when preparing this medication.
Adult
PCP infections: 15 mg/kg/d IV divided q6h for 21 d, based on trimethoprim; give infusion over 60-90 min and administer within 6 h of mixing; switch to oral medication after clinical status improves
Example of dosing calculation: A 70-kg adult would require 1050 mg trimethoprim IV q24h (14 vials/24h), which would be 3.5 vials mixed in 437.5 mL of 5% dextrose in water to be given IV q6h
Pediatric
10-20 mg TMP/kg/d PO/IV divided tid/qid for 14 d (for IV administration see information above)
May increase PT with warfarin (perform coagulation tests and adjust dose); coadministration with dapsone may increase blood levels of both; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly patients; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine
Documented hypersensitivity; megaloblastic anemia (due to folate deficiency); porphyria; patients aged <2 mo
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
Discontinue at first appearance of skin rash or adverse reaction; frequently obtain CBC counts; discontinue if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, give 5-15 mg/d leucovorin); caution in folate deficiency (eg, those with chronic alcoholism or malabsorption syndrome, elderly patients, those receiving anticonvulsant therapy); hemolysis may occur in G-6-PD deficiency; patients with AIDS may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation
Enzyme replacement
These agents are used in patients with ADA deficiency and SCID who benefit from bone marrow transplantation.
Pegademase (Adagen)
Provides enough ADA activity in the bloodstream to eliminate toxic effect of both deoxyadenosine and adenosine that may result in the immune deficiency. ADA deficiency can be treated with a weekly intramuscular injection of ADA coupled with polyethylene glycol (PEG-ADA); it is effective in 90% of cases.
Adult
First dose 10 U/kg IM; second dose 15 U/kg IM; third dose 20 U/kg IM; give a dose q7d
Maintenance dose: 20 U/kg/wk IM; if necessary, increase weekly dose by 5 U/kg; not to exceed a single dose of 30 U/kg
Pediatric
Administer as in adults
Decreases effect of vidarabine
Documented hypersensitivity; IV use
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 patients with thrombocytopenia; pain may occur at injection site
More on Severe Combined Immunodeficiency |
| Overview: Severe Combined Immunodeficiency |
| Differential Diagnoses & Workup: Severe Combined Immunodeficiency |
 Treatment & Medication: Severe Combined Immunodeficiency |
| Follow-up: Severe Combined Immunodeficiency |
| References |
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References
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Further Reading
Keywords
combined immunodeficiency, SCID, primary immunodeficiency, SCID with B cells, SCID without B cells
