Patients with combined immunodeficiency disorder (T and B lymphocyte deficiency) present with recurrent infections usually early in life. These patients are susceptible to infection by many organisms. Immunotherapy sometimes is not available to treat these recurrent infections. Severe combined immunodeficiency disease (SCID) is the most severe expression among the combined immunodeficiency disorders. The onset of the clinical manifestations occurs by 6 months of age or before, with bacterial, viral, fungal and protozoal infections. Also, these infections may lead to early death in severe combined immunodeficiency disease, differentiating this condition from other forms or combined immunodeficiency.
Both T and B cell functions are disturbed or absent entirely in severe combined immunodeficiency disease. Autosomal, sporadic, or the X-linked form may affect the neonate, and without treatment, patients rarely survive beyond one year of age before succumbing to opportunistic infections.
The Jeffrey Modell Foundation implemented public awareness and physician education about primary immunodeficiencies, including severe combined immunodeficiency disease beginning in 2003. The network has implemented population-based newborn screening for SCID and T cell lymphopenia, covering 96% of the total newborns in the US.
The majority of the patients (89%) presented with the first symptoms within six months of age. The clinical manifestations observed were recurrent pneumonia (66%), followed by failure to thrive (60%) and chronic diarrhea (35%).
Genetic mutation is the root cause of SCID. Specifically, the genes which are responsible for the function of T and B cells are affected in SCID. Profound T-cell abnormalities can prevent B cells from functioning normally because the B cells require signals from T cells to produce appropriate antibodies. Therefore, in some instances, SCID may be present with only T cell dysfunction. Natural killer (NK) cells develop separately from T and B cells and can provide a degree of protection in individuals with T and B cell dysfunction. Assessing for the presence of NK cells helps determine the severity and prognosis of the SCID.
In SCID, microscopic examination of the thymic stroma reveals an absence of lymphoid cells, as well as the absence of Hassall's corpuscles. In essence, the thymus gland has a fetal appearance.
Additionally, numerable Giardia lamblia can present in the gastrointestinal tract, specifically over the mucosa of the jejunum. The lack of protective immunity results in an inability to fight against these intestinal parasites.
Biopsy of lymph nodes (if detectable) shows severe depletion, without cortico-medullary differentiation or follicle formation. Biopsy of the intestinal tract may demonstrate a complete absence of plasma cells.
Major immunological features of severe combined immune deficiency include the following:
The immunological investigation of a patient with SCID includes the assessment of immunoglobulins, including isohemagglutinins and antibody activity, B and T-lymphocyte counts, lymphocyte stimulation assays, NK cell function, quantification of components of the complement system and phagocytic activity.
Blood lymphocyte subpopulations
Lymphocyte stimulation assays
Quantitative Serum Immunoglobulins
IgG antibodies (post-immunization)
IgG antibodies (post-exposure)
Detection of isohemagglutinins (IgM)
Nitroblue tetrazolium (NBT) test (before and after stimulation with endotoxin)
Complement System Evaluation
Measurement of individuals components by immunoprecipitation tests, ELISA, or Western blotting
Other investigations of immunodeficiency disorders
A bone marrow transplant may be beneficial in the following sub-groups:
Use of gammaglobulin may show benefit in the following sub-groups:
Other treatment options include the following:
At the top of the differential for SCID are other forms of combined immunodeficiency. These patients have several characteristics that overlap in their clinical presentation. Patients with agenesis of the thymus or T cell deficiency (such as in DiGeorge syndrome or CHARGE syndrome) may present with opportunistic infections similar to SCID.
Additional immunodeficiencies that merit consideration in the differential include the following:
Malabsorption syndromes that cause extreme malnutrition may also have similar presentations to SCID.
SCID has the poorest prognosis among combined immunodeficiencies unless bone marrow transplantation or gene therapy (experimental) is successfully performed. In general, for improving the quality of life of patients with primary immunodeficiencies, long-term management with antimicrobials is needed. Most primary immunodeficiencies require personalized management, e.g., genetic testing for various enzyme impairments.
SCID should be managed by an interprofessional team that likely includes a pediatrician, geneticist, clinical immunologist, pediatrician, nurse practitioner, and an infectious disease specialist. The treatment team may also provide counseling to the parents, given the poor prognosis associated with the disease. Because of the high morbidity of the disorder, a palliative team consisting of a nurse, a social worker, and a pain specialist should also have involvement in the care. Pediatric hematology nurses assist in the care of these patients and report changes to the team. Pharmacists review medications, check for interactions and educate patient's families about side effects and compliance. [Level 5]
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