eMedicine Specialties > Pediatrics: General Medicine > Allergy & Immunology
Severe Combined Immunodeficiency: Follow-up
Updated: Aug 18, 2009
Follow-up
Further Inpatient Care
- Coordinating medical management of severe combined immunodeficiency (SCID), including immunology, infectious disease, pulmonary, and gastroenterology specialists, can be challenging.
- The need for excellent laboratory and radiology support mandates hospitalization in tertiary pediatric medical centers.
- Bone marrow transplantation (BMT) should be coordinated between immunology and the BMT team.
Further Outpatient Care
- Isolation to avoid transmission of infection is required. Usually, contacts are restricted to immediate family members and friends whose risks for infection can be monitored. Visits to doctors' offices and hospitals must be orchestrated carefully to avoid exposure to infection.
- Although allogeneic hematopoietic stem cell transplantation (HCST) is curative for severe combined immunodeficiency, the long-term outcome in a 90-patient cohort followed for 2-34 years showed almost half experienced one or more significant clinical events, including persistent chronic graft versus host disease (GVHD), autoimmune and inflammatory manifestations, opportunistic and nonopportunistic infections, and a requirement for nutritional support.9 These late-onset complications suggest the need for prevention and careful follow-up.
Inpatient & Outpatient Medications
- See Medical Care.
Transfer
- As with any primary immunodeficiency disease, subtle signs of infection, morbidity/mortality from common infections, and the need to offer stem cell transplantation reinforces the importance of frequent monitoring and management by a clinical immunologist.
Deterrence/Prevention
- Prenatal diagnosis is possible by chorionic villus sampling at 10 weeks' gestation (or later) by amniocentesis, using DNA methodology in families for whom the exact mutations have been established. Molecular techniques include single-strand conformation polymorphism (SSCP) and dideoxy fingerprinting (ddF); actual sequencing of DNA to detect the mutation may be required in some situations. Linkage analysis and restriction fragment length polymorphism (RFLP) are other options that are needed less frequently with the advent of specific mutation analysis. Fetal blood sampling for fluorocytometric testing, mitogen responses, and enzyme levels can establish the diagnosis when DNA analysis is not available.
- After exposure to varicella-zoster virus (VZV), prophylaxis with VZIG should be administered within 48 hours, if possible; VZIG may be efficacious up to 96 hours postexposure. Beyond that interval, acyclovir has been administered and may prevent or modify the severity of VZV.
Complications
- Opportunistic infections usually follow more common infections. P jiroveci and fungal pneumonias cause death in classic cases. Cytomegalovirus (CMV), VZV, and herpes simplex virus are viral infections that typically occur in the infant who already has had treatable infections. Poliomyelitis from the attenuated oral vaccine is well recognized. Neurologic compromise from polio and other enteroviruses precludes stem cell reconstitution.
- Graft failure with BMT and posttransplant GVHD are well recognized, although both have decreased with improved BMT preparatory techniques.
- Cancer, usually non-Hodgkin lymphoma, is seen in patients with cartilage-hair hypoplasia who survive beyond early childhood.
Prognosis
- With bone marrow and other stem cell reconstitution techniques, many patients with severe combined immunodeficiency are fully reconstituted without complications. The risk for GVHD or graft failure has declined significantly with newer techniques that include T-cell depletion using monoclonal antibodies and, possibly, the use of cord blood CD34+ stem cells. In selected patients with severe combined immunodeficiency, pretransplantation immunosuppression is not necessary (see Medical Care).
- Patients who are well-nourished, uninfected, and younger than 6 months before transplantation have the best outcomes.
- Patients with common g chain (XL severe combined immunodeficiency) or JAK3 mutations have an increased risk of hypogammaglobulinemia posttransplantation, based on retention of recipient B cells that do not respond adequately to donor T-cell communication.
- Without stem cell reconstitution, a patient with severe combined immunodeficiency rarely survives. However, gene therapy for XL severe combined immunodeficiency and adenosine deaminase (ADA) deficiency may be viable alternatives for patients unable to find donors if the complication of acute lymphoblastic leukemia is effectively prevented.
- Patients with less severe mutations in ADA have survived into adulthood; optional treatment for ADA deficiency is polyethylene glycol–treated (PEG)-ADA replacement, although this does not return immune function to normal.
- Cartilage-hair hypoplasia, particularly in the Finnish population, may be less severe.
Patient Education
- Families must be informed about the risks of infection so that appropriate steps to avoid exposure to infection are instituted. They should be aware that live viral vaccines are contraindicated.
- Genetic counseling is an essential part of medical care for the family. Parents must be informed of the risk of severe combined immunodeficiency in subsequent children depending on the X-linked or autosomal etiology. The risk for daughters to be carriers for X-linked immunodeficiencies also must be clarified.
- Communicate the high risk for life-threatening infection during the preparative immunosuppressive regimen (when indicated), in addition to the risk for failure to engraft and GVHD. Adequate informed consent for stem cell reconstitution must review these points. Although successful complete immune reconstitution from BMT is reported using fully matched related and unrelated donors or haploidentical parents, patients with severe combined immunodeficiency may fail to engraft or develop GVHD posttransplant. Other forms of stem cell reconstitution that can be offered include cord cell transplantation. Gene therapy is an option for XL severe combined immunodeficiency and ADA severe combined immunodeficiency.
- The Immune Deficiency Foundation is an important resource for education and support for patients and families with any primary immunodeficiency disease. The current address is 25 West Chesapeake Avenue, Suite 206, Towson, MD 21204. Some US states have local chapters. For consultation, contact 1-877-666-0866 or www.primaryimmune.org. The Jeffrey Modell Foundation, located at 747 3rd Avenue, New York, NY 10017, also provides educational support for families and patients (1-800-JEFF-844).
Miscellaneous
Medicolegal Pitfalls
- Mutational analysis must be offered, and the opportunity for prenatal diagnosis must be discussed with the family. The risk for occurrence of X-linked (XL) severe combined immunodeficiency (SCID) in another child is 50% for male infants; female infants are not affected, but they have a 50% risk for being carriers. Any autosomal recessive mutation causing severe combined immunodeficiency places siblings at a 1 in 4 risk for severe combined immunodeficiency.
- Misdiagnosing severe combined immunodeficiency as hypogammaglobulinemia is a common error.
- Administration of nonirradiated blood products or live-virus vaccines to a patient suspected of having severe combined immunodeficiency or undergoing a workup for severe combined immunodeficiency is another potentially fatal error if that patient turns out to have severe combined immunodeficiency.
- Dismissing an infant's death caused by an overwhelming common bacterial or viral infection without further investigation is another mistake. Any infant with the history of an unusual frequency and severity of common infections prior to death from infection should have an autopsy performed to assess lymphoid and thymic tissue. Peripheral blood lymphocytes can survive for several days; thus, blood should be saved for the assessment of T-cell and B-cell markers by flow cytometry and for responses to mitogens.
- Stem cell reconstitution must be discussed carefully with the family for informed consent, particularly since the donor may be a sibling too young to understand the risks and benefits of the procedure. Under these circumstances, a guardian outside the family may most effectively guide this decision. Furthermore, in weighing the likelihood of death unless stem cell reconstitution is attempted, it is equally essential that families are made aware of the high risk for fatal infection or graft versus host disease (GVHD) in the recipient after transplantation.
The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Ann O'Neill Shigeoka, MD, to the development and writing of this article.
More on Severe Combined Immunodeficiency |
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| Differential Diagnoses & Workup: Severe Combined Immunodeficiency |
| Treatment & Medication: Severe Combined Immunodeficiency |
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| Multimedia: Severe Combined Immunodeficiency |
| References |
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Further Reading
Keywords
severe combined immunodeficiency, SCID, X-linked SCID, XL-SCID, MHC class II deficiency, bare lymphocyte syndrome, adenosine deaminase–deficient SCID, ADA-deficient SCID, recurrent infections, failure to thrive, dermatitis, bone marrow transplantation, DiGeorge syndrome, CHARGE syndrome, hematopoietic stem cell transplantation, HSCT, otitis media, cytomegalovirus infection, CMV, varicella, respiratory syncytial virus, RSV, rotavirus, parainfluenza virus, Epstein-Barr virus, EBV, enterovirus, adenovirus, non-Hodgkin lymphoma, herpes simplex virus, cryptosporidiosis, Crohn disease, HIV infection, graft versus host disease, GVHD, Omenn syndrome, treatment, diagnosis
