AKT · Haematology/Transfusion, spleen & immunitylow yield

Primary immunodeficiency

Inherited defects of immune components — antibody (B-cell), cellular (T-cell), combined, phagocyte, or complement

Overview

Inherited defects in components of the immune system, classified by the limb affected: antibody/B-cell (commonest — e.g. common variable immunodeficiency, selective IgA deficiency), T-cell/combined (e.g. DiGeorge, SCID), phagocyte (chronic granulomatous disease) and complement deficiencies. The pattern of infection points to the defect, and recurrent/severe/unusual/persistent infections (the 'SPUR' pattern) should prompt investigation rather than repeated courses of antibiotics.

Recognise

Recurrent, Severe, Persistent or Unusual infections ('SPUR'); failure to thrive in infants; family history
Pattern by defect: ANTIBODY (encapsulated bacteria — recurrent sinopulmonary infections, e.g. CVID/IgA deficiency); T-CELL/COMBINED (viral/fungal/opportunistic — SCID presents in infancy; DiGeorge — 22q11 deletion + hypocalcaemia + cardiac/facial); PHAGOCYTE (catalase-positive organisms, abscesses — chronic granulomatous disease); COMPLEMENT (recurrent Neisseria)
Selective IgA deficiency: often asymptomatic but risks anaphylaxis to blood products (give IgA-deficient/washed components)

Red flags

SCID (severe combined immunodeficiency) in infancy → paediatric emergency (avoid live vaccines; needs transplant)
Recurrent Neisseria infections → complement deficiency; IgA deficiency → anaphylaxis to blood products

Differentials & how to tell them apart

Secondary immunodeficiencyHIV, malignancy/chemo, immunosuppressants, splenectomy, malnutrition — far commoner; exclude first

Recurrent infection from a local/anatomical causee.g. bronchiectasis, structural problem — not a systemic immune defect

Atopy/allergyrecurrent symptoms without true immunodeficiency

Investigations

Immunoglobulin levels (IgG/A/M) + vaccine-response antibody titres; lymphocyte subsets (T/B/NK); complement (CH50/AH50); neutrophil function tests (chronic granulomatous disease); genetic testing; HIV test (exclude secondary immunodeficiency); the infection pattern guides which tests.

Management

Immunoglobulin replacement (antibody defects) + prophylaxis; transplant for SCID; specialist immunology

1Suspect primary immunodeficiency from recurrent/severe/persistent/unusual infections (SPUR) and the infection PATTERN (encapsulated → antibody; viral/fungal → T-cell; abscesses → phagocyte; Neisseria → complement). Exclude secondary causes (HIV) first, then test immunoglobulins/subsets/complement/neutrophil function.Gate: SCID in infancy is an emergency (no live vaccines, needs transplant); IgA deficiency risks anaphylaxis to blood products (use IgA-deficient/washed components).
2Antibody deficiencies → immunoglobulin replacement + prophylactic antibiotics; SCID/severe combined → stem-cell transplant; specialist immunology care and infection prevention.

Immunoglobulin replacement for antibody deficiencies — e.g. CVID — regular IVIG/SCIG; prevents infections

Prophylactic antibiotics + prompt treatment of infections — and aggressive treatment of breakthrough infections

Avoid LIVE vaccines in significant T-cell/combined defects — and use IgA-deficient/washed blood products in IgA deficiency (anaphylaxis risk)

Haematopoietic stem-cell transplant for SCID/severe defects — curative in SCID; specialist immunology care

Key points

Recurrent/Severe/Persistent/Unusual infections (SPUR) → think primary immunodeficiency (after excluding HIV/secondary causes). Pattern points to the defect: encapsulated bacteria → antibody (CVID); viral/fungal/opportunistic → T-cell/combined (SCID, DiGeorge 22q11 + hypocalcaemia); abscesses → phagocyte (CGD); recurrent Neisseria → complement. Antibody defects → immunoglobulin replacement; SCID → transplant. IgA deficiency → anaphylaxis to blood products.

Monitor & prognosis

Infection frequency, immunoglobulin levels/trough on replacement, organ damage (bronchiectasis).

Variable; antibody deficiencies manageable with immunoglobulin; SCID fatal without transplant.

Source: BSH/UK PIN; cross-ref child_health (DiGeorge/SCID), sexual_health (HIV)