Severe Combined Immunodeficiency (SCID)
SCID is a group of rare, inherited disorders characterised by a profound defect in both T-cell and B-cell immunity. Without treatment, affected infants are highly susceptible to severe, opportunistic infections and usually do not survive beyond their first year. The diagnosis is often based on the absence of T cells (T-cell lymphopenia), which can be identified through newborn screening.
Key clinical features to be aware of in an infant presenting with an atypical or severe infection include:
Recurrent or persistent infections with common pathogens, and/or severe infections with opportunistic organisms like Pneumocystis jirovecii.
Failure to thrive and chronic diarrhoea.
Persistent oral or dermal candidiasis.
A family history of infant deaths or immunodeficiency.
Diagnosis & Management
1. Newborn Screening (NBS) and Diagnosis
In the UK, newborn screening for SCID is not a universally adopted national programme but has been subject to a large-scale in-service evaluation (ISE). This has been a significant recent development. The evaluation, which uses a TREC (T-cell receptor excision circles) assay on the standard heel-prick test, aims to assess the effectiveness and cost-effectiveness of a full roll-out. Findings from the ISE have shown that screening can detect SCID early, leading to improved outcomes.
Clinical suspicion remains paramount. If a neonate or infant presents with suggestive symptoms, an urgent referral to a regional immunology centre is essential. Do not wait for a screening result or presume a “normal” result rules out the condition if there is a strong clinical picture.
2. Immediate Management and Prophylaxis
Once SCID is suspected, the immediate priorities are to:
Place the infant in reverse isolation to protect against environmental pathogens.
Avoid all live vaccines (e.g., BCG, MMR, oral polio, rotavirus) in the infant and close family contacts. Ensure this is noted on the baby’s Red Book.
Commence prophylactic antibiotics (e.g., co-trimoxazole to prevent P. jirovecii pneumonia), antifungal, and antiviral medications as per local and national protocols.
Administer intravenous immunoglobulin (IVIG) to provide passive immunity while awaiting definitive treatment.
Any blood products required (e.g., transfusions) must be irradiated to prevent graft-versus-host disease (GvHD) from donor T-cells. They must also be CMV-negative if the mother is seronegative.
Recent Developments in Treatment
The definitive treatment for SCID is early immune reconstitution. Recent advancements have significantly improved survival rates.
Haematopoietic Stem Cell Transplantation (HSCT): This remains the primary curative therapy. Recent literature highlights improved survival and long-term immune reconstitution, especially with early transplantation (within the first 3.5 months of life), regardless of donor type. Outcomes with haploidentical (parental) and matched unrelated donors are now approaching those of matched sibling donors.
Gene Therapy: This is a rapidly advancing field, now a viable and in some cases preferred treatment option for specific subtypes of SCID, particularly Adenosine Deaminase (ADA) deficiency and X-linked SCID. The process involves harvesting the patient’s own stem cells, correcting the genetic defect ex vivo, and re-infusing them. This avoids the risks associated with GvHD and finding a donor.
Enzyme Replacement Therapy: For ADA-SCID, an enzyme replacement therapy (PEG-ADA) can be used as a bridge to definitive treatment.
Early diagnosis and rapid commencement of supportive care and definitive treatment are the cornerstones of modern SCID management, offering previously unimaginable survival rates and quality of life for these patients.