eMedicine Specialties > Allergy and Immunology > Immunodeficiencies
Severe Combined Immunodeficiency: Treatment & Medication
Updated: May 5, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
- Severe combined immunodeficiency (SCID) is a pediatric emergency and must be worked up and treated promptly. Intravenous immunoglobulin (IVIG) should be administered promptly, and evaluation for bone marrow transplantation (BMT) should be started. Patients with SCID who are treated with BMT before the age of 3.5 months have markedly improved survival rates.
- Prophylaxis
- Because T cells are absent and/or dysfunctional, administer Pneumocystis jiroveci pneumonia prophylaxis to all patients until T-cell function is restored by a BMT or other therapy.
- Trimethoprim-sulfamethoxazole is the drug of choice and can be administered in a patient who is older than 2 months or in whom neonatal jaundice is no longer a concern.
- X-linked SCID and Janus-associated kinase 3 (JAK3) protein tyrosine kinase (PTK) deficiency
- A BMT is the primary treatment of choice for most types of SCID when an appropriate donor is found. Pretreatment with ablative chemotherapy is controversial.
- If B cells do not engraft, the patient may require monthly IVIG replacement therapy.
- Adenosine deaminase (ADA) deficiency
- The primary treatment is ongoing polyethylene glycol–conjugated ADA replacement (PEG-ADA) therapy.
- Gene therapy is in the experimental phase. Although some long-term benefits of gene therapy have been reported for ADA-deficient patients with SCID, serious complications have arisen in some cases of gene therapy in patients with common gamma chain deficiency.
- The development of leukemia is a complication of gene therapy and appears to be related to the site of insertion of the transgene. Some suggest that better outcomes may occur with different vectors or more specific insertion sites.20 Greater risk for cognitive abnormalities and emotional and behavioral problems has also been reported in ADA-deficient patients with SCID who received long-term enzyme replacement therapy.21
- Purinenucleotide phosphorylase (PNP) deficiency and bare lymphocyte syndrome: A BMT is the primary therapy when an appropriate donor is available.
- IL-2 production defects: Intravenous IL-2 replacement is the primary therapy, and a BMT is an alternative if an appropriate donor is available.
- Omenn syndrome: A BMT is the primary treatment; however, pretreatment ablative chemotherapy is necessary because of maternal cell engraftment.
Surgical Care
Surgical care is not part of the primary treatment.
Consultations
- Immunologist for diagnosis and treatment
- Hematology/immunology transplant team for an anticipated BMT
Diet
No diet limitations are necessary.
Activity
Only infections secondary to the immune deficiency limit activity. The disease itself does not require limitation of physical activity. Keep children with SCID in reverse isolation until BMT or other therapy is initiated.
Medication
Drug therapy is not a major part of therapy for the primary disease. Trimethoprim-sulfamethoxazole is prescribed routinely after the second month of life in children with severe combined immunodeficiency (SCID) until after bone marrow transplant (BMT) engraftment. This is Pneumocystis jiroveci prophylaxis. Intravenous immunoglobulin (IVIG) is used to prevent infection prior to BMT and, in selected patients, after BMT, if B-cell function remains poor.
Antibiotics
These agents are used as prophylaxis against Pneumocystis jiroveci pneumonia.
Trimethoprim-Sulfamethoxazole (Bactrim, Bactrim DS, Septra, Septra DS)
Used because of low levels of T cells or poor T-cell function in children with SCID.
Adult
1 DS tab PO bid
Pediatric
5-10 mg/kg PO divided bid 3 times per wk (Mon, Wed, Fri or Mon, Tue, Wed)
May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly; 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; G-6-PD deficiency, children <2 mo, porphyria
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
Can cause bone marrow suppression; hypersensitivity; hemolysis in patients with G-6-PD deficiency; use with caution in renal or hepatic failure
Immune globulins
IVIG is the usual choice. It is derived from human plasma and is composed of all 4 IgG subclasses. The antibody distribution of IVIG is approximately the same as human serum.
Intravenous immunoglobulins (Gammaimmune, Gammagard, Sandoglobulin)
Pooled human immunoglobulin provides IgG antibodies the patient cannot make.
Adult
400-500 mg/kg IV titrating trough IgG level to 900-1000 mg/dL. This is usually administered every 3-4 wk, but frequency of administration should also be titrated to keep desired level.
Pediatric
Not established; administer as in adults
Interferes with efficacy of MMR vaccine, but this should not be an issue in a child who does not make antibody since no vaccines are administered to these children; the IVIG replaces antibodies that vaccines would stimulate the production of in a healthy child; furthermore, live viral vaccines are contraindicated in these patients
Documented hypersensitivity; IgA deficiency; anti-IgE/IgG antibodies
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 before IVIG (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 (2-5 d postinfusion to 30 d)
Increases risk of renal tubular necrosis in elderly patients and in patients with diabetes, volume depletion, and preexisting kidney disease; lab result changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia
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
Fischer A. Severe combined immunodeficiencies. Immunodefic Rev. 1992;3(2):83-100. [Medline].
Uribe L, Weinberg KI. X-linked SCID and other defects of cytokine pathways. Semin Hematol. Oct 1998;35(4):299-309. [Medline].
Hong R. Disorders of the T cell system. In: Stiehm ER, ed. Immunologic Disorders in Infants and Children. 4th ed. Philadelphia, Pa: WB Saunders; 1996:339-408.
Macchi P, Villa A, Giliani S, et al. Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). Nature. Sep 7 1995;377(6544):65-8. [Medline].
Candotti F, O'Shea JJ, Villa A. Severe combined immune deficiencies due to defects of the common gamma chain-JAK3 signaling pathway. Springer Semin Immunopathol. 1998;19(4):401-15. [Medline].
Hirschhorn R, Vawter GF, Kirkpatrick JA Jr, Rosen FS. Adenosine deaminase deficiency: frequency and comparative pathology in autosomally recessive severe combined immunodeficiency. Clin Immunol Immunopathol. Sep 1979;14(1):107-20. [Medline].
Reith W, Mach B. The bare lymphocyte syndrome and the regulation of MHC expression. Annu Rev Immunol. 2001;19:331-73. [Medline].
DeSandro A, Nagarajan UM, Boss JM. The bare lymphocyte syndrome: molecular clues to the transcriptional regulation of major histocompatibility complex class II genes. Am J Hum Genet. Aug 1999;65(2):279-86. [Medline].
Mach B, Steimle V, Reith W. MHC class II-deficient combined immunodeficiency: a disease of gene regulation. Immunol Rev. Apr 1994;138:207-21. [Medline].
Elder ME, Lin D, Clever J, et al. Human severe combined immunodeficiency due to a defect in ZAP-70, a T cell tyrosine kinase. Science. Jun 10 1994;264(5165):1596-9. [Medline].
Villa A, Santagata S, Bozzi F, Imberti L, Notarangelo LD. Omenn syndrome: a disorder of Rag1 and Rag2 genes. J Clin Immunol. Mar 1999;19(2):87-97. [Medline].
O'Driscoll M, Cerosaletti KM, Girard PM, et al. DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. Mol Cell. Dec 2001;8(6):1175-85. [Medline].
Kung C, Pingel JT, Heikinheimo M, et al. Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease. Nat Med. Mar 2000;6(3):343-5. [Medline].
Rieux-Laucat F, Hivroz C, Lim A, et al. Inherited and somatic CD3zeta mutations in a patient with T-cell deficiency. N Engl J Med. May 4 2006;354(18):1913-21. [Medline].
Dadi HK, Simon AJ, Roifman CM. Effect of CD3delta deficiency on maturation of alpha/beta and gamma/delta T-cell lineages in severe combined immunodeficiency. N Engl J Med. Nov 6 2003;349(19):1821-8. [Medline].
Ege M, Ma Y, Manfras B, Kalwak K, Lu H, Lieber MR. Omenn syndrome due to ARTEMIS mutations. Blood. Jun 1 2005;105(11):4179-86. [Medline].
Hitzig WH, Landolt R, Müller G, Bodmer P. Heterogeneity of phenotypic expression in a family with Swiss-type agammaglobulinemia: observations on the acquisition of agammaglobulinemia. J Pediatr. Jun 1971;78(6):968-80. [Medline].
Chan K, Puck JM. Development of population-based newborn screening for severe combined immunodeficiency. J Allergy Clin Immunol. Feb 2005;115(2):391-8. [Medline].
Lebet T, Chiles R, Hsu AP, Mansfield ES, Warrington JA, Puck JM. Mutations causing severe combined immunodeficiency: detection with a custom resequencing microarray. Genet Med. Aug 2008;10(8):575-85. [Medline].
Aiuti A, Cattaneo F, Galimberti S, et al. Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N Engl J Med. Jan 29 2009;360(5):447-58. [Medline].
Booth C, Hershfield M, Notarangelo L, et al. Management options for adenosine deaminase deficiency; proceedings of the EBMT satellite workshop (Hamburg, March 2006). Clin Immunol. May 2007;123(2):139-47. [Medline].
Further Reading
Keywords
SCID, severe combined immunodeficiency, T-cell dysfunction, T cell dysfunction, B-cell dysfunction, B cell dysfunction, graft versus host disease, GVHD, graft-versus-host disease, graft-vs-host disease, severe infection, Swiss-type agammaglobulinemia, Janus-associated kinase 3 deficiency, JAK3 deficiency, adenosine deaminase deficiency, ADA deficiency, purine nucleoside phosphorylase deficiency, PNP deficiency, bare lymphocyte syndrome, interleukin-2 deficiency, IL-2 deficiency, ZAP-70 protein tyrosine kinase deficiency, PTK deficiency, reticular dysgenesis, Omenn syndrome, Pneumocystis carinii/jiroveci pneumonia, PCP, systemic candidiasis, generalized herpetic infections, ARTEMIS, Artemis, RAG1 deficiency, RAG2 deficiency
