Severe combined immunodeficiency

Severe combined immunodeficiency (SCID) is a group of inherited genetic disorders characterised by a profound deficiency in cellular and humoral immunity, due to a markedly decreased number of lymphocytes.

Infants with SCID usually appear healthy at birth. Over time, they may develop: recurrent or unusually severe infections; increased susceptibility to opportunistic infections; failure to thrive; and/or chronic diarrhoea.

Early diagnosis is imperative as, without curative treatment (e.g., haematopoietic stem cell transplantation, gene therapy, enzyme replacement therapy), the condition can be fatal in the first year of life.

Key findings on examination include the absence of lymphoid tissue, poor weight gain, or diffuse erythematous rash. Other factors alerting for SCID include absolute lymphopenia and absent thymus.

Newborn screening for T-cell deficiency can alert for SCID before infections and other signs of SCID develop.

Antibacterial, antifungal, and antiviral prophylaxis should be considered for patients with suspected or confirmed SCID.

Live vaccines (e.g., BCG, rotavirus, and oral polio) should not be given to infants with suspected SCID. Cytomegalovirus (CMV) infection by breastfeeding should be prevented if possible.

Blood or blood products should be irradiated, leukocyte depleted, and negative for CMV before being administered to patients with confirmed or suspected SCID.

Severe combined immunodeficiency (SCID) is a group of inherited genetic disorders characterised by a profound deficiency in cellular and humoral immunity, due to a markedly decreased number of lymphocytes.[1]Rivers L, Gaspar HB. Severe combined immunodeficiency: recent developments and guidance on clinical management. Arch Dis Child. 2015 Jul;100(7):667-72. http://www.ncbi.nlm.nih.gov/pubmed/25564533?tool=bestpractice.com

T cells are absent in most forms of SCID; however, the absence and presence of B cells and natural killer cells varies depending on the type of SCID.[2]Bousfiha A, Jeddane L, Picard C, et al. The 2017 IUIS phenotypic classification for primary immunodeficiencies. J Clin Immunol. 2018 Jan;38(1):129-43. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742599 http://www.ncbi.nlm.nih.gov/pubmed/29226301?tool=bestpractice.com [3]Picard C, Bobby Gaspar H, Al-Herz W, et al. International Union of Immunological Societies: 2017 Primary immunodeficiency diseases committee report on inborn errors of immunity. J Clin Immunol. 2018 Jan;38(1):96-128. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742601 http://www.ncbi.nlm.nih.gov/pubmed/29226302?tool=bestpractice.com

Clinical manifestations begin early in life and include: severe and recurrent infections; increased susceptibility to opportunistic infections; failure to thrive; and/or chronic diarrhoea.[4]Bonilla FA, Khan DA, Ballas ZK, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015 Nov;136(5):1186-205.e1-78. http://www.jacionline.org/article/S0091-6749(15)00883-0/fulltext http://www.ncbi.nlm.nih.gov/pubmed/26371839?tool=bestpractice.com [5]Routes J, Abinun M, Al-Herz W, et al. ICON: The early diagnosis of congenital immunodeficiencies. J Clin Immunol. 2014 May;34(4):398-424. http://www.ncbi.nlm.nih.gov/pubmed/24619621?tool=bestpractice.com