Severe Combined Immunodeficiency (SCID) Diseases

Key Features

Essentials of Diagnosis

• Onset in first year of life

• Recurrent infections caused by bacteria, viruses, fungi, and opportunistic pathogens

• Chronic diarrhea and failure to thrive

• Absent lymphoid tissue

General Considerations

• Defining characteristic is severe deficiency of T-cell function and number

• Due to the centrality of T cells in the immune system, the severity of T-cell deficit results in widespread immunologic dysfunction and broad susceptibility to infection

• Suspected SCID is a medical emergency; confirming diagnosis and initiating treatment must be done rapidly

Clinical Findings

• Frequently presents with opportunistic, unusual, and persistent infection

• Common organisms include but are not limited to Pneumocystis jirovecii, candida, and cytomegalovirus

• In the absence of an identified microorganism, SCID may present with any combination of the following: failure to thrive, chronic diarrhea, or unexplained chronic respiratory illness

• Physical examination is notable for a lack of lymphoid tissue, including tonsils and lymph nodes

Diagnosis

Laboratory Findings

• Characteristic feature is the deficiency in production of T cells

• Associated laboratory findings can include decreases in numbers of NK cells and B cells, poor lymphocyte proliferative response to mitogens, and low immunoglobulin levels

Imaging

• Chest radiograph usually demonstrates an absent thymic shadow

Diagnostic Procedures

• Genetic testing should be pursued to confirm the diagnosis; treatment should not be delayed while awaiting results

Treatment

• A variety of therapies are used, including

  • Hematopoietic stem cell transplantation (HSCT)

  • Gene therapy

  • Thymus transplant

  • Enzyme replacement

• Choice of therapy depends on the specific genetic defect, age at diagnosis, access to a suitable HSCT donor, and comorbidities

• Replacement Ig therapy should be initiated

• Patients in whom SCID is suspected should not receive any live vaccines

• If transfusion is needed, patients should only receive CMV-negative, irradiated blood products

• If the patient has received BCG vaccination, specific therapy should be considered

Outcome

Prevention

• Antimicrobial prophylaxis should be initiated with the aim of preventing pulmonary infection with Pneumocystis as well as other fungal pathogens

• Antiviral prophylaxis can be considered as well

Prognosis

• Left untreated, SCID uniformly results in death before the first year of life

• Transplant outcomes are favorable if performed within the first 3 months of life, or if performed prior to the onset of SCID-associated chronic infections

References