Paediatrics: Immunodeficiency disorders

Immunodeficiency disorders

Immunodeficiency may be due to causes that are:

•   Primary: intrinsic abnormalities.

•   Secondary: cancer, immunosuppressive agents, HIV infection, splenectomy, nephrotic syndrome, SCD, etc.

Primary immunodeficiency

Caused by defects in the following.

B lymphocytes and antibody production

•   X-linked agammaglobulinaemia: presents in early childhood with severe bacterial infections

•   Hyper IgM syndrome: presents with bacterial infection and PCP

•   IgG subclass deficiency: minor immunodeficiency that may cause recurrent respiratory infection

Tests Immunoglobulin levels and functional vaccine responses as indicated by clinical presentation

T lymphocytes and cellular immunity

Severe combined immunodeficiency (SCID) Presents in first few months. Failure to thrive. Persistent infection due to viruses and fungi

Tests FBC, blood film, lymphocyte subsets and function 

Neutrophil defects

Leucocyte adhesion deficiency Presents in infancy with delayed healing of the umbilical cord, chronic skin ulcers, bacterial and fungal infection involving lymph nodes, liver, and lung

Tests Assessment of chemotaxis, neutrophil surface adhesion molecules, and killing (e.g. neutrophil oxidative burst test for chronic granuloma-tous disease)

Opsonization and other innate immunodeficiencies

Complement deficiency or mannose binding lectin deficiency Rare, but may present with severe meningococcal disease

Tests Complement levels, TOLL receptor pathway assays (second line tests directed by clinical presentation)

Multisystem syndromes

•   Ataxia telangiectasia: skin, neurological, and immune defects

•   Wiskott–Aldrich syndrome: eczema, thrombocytopenia, and immunodeficiency

•   DiGeorge syndrome: hypocalcaemia, branchial arch and heart defects, and immunodeficiency

•   Duncan syndrome: X-linked lymphoproliferative disease due to prior EBV infection

Tests Chromosomal fragility, genetic polymorphisms

The investigation for these conditions in children with a history of recur-rent or severe infection requires a broad screen of tests, which can be directed by the type of infection (e.g. viral, bacterial, fungal).

Treatment

A variety of therapies is required for children with primary immunode-ficiency and they should be cared for in designated centres. Therapy in-cludes:

• prophylactic antibiotics;

• supportive care and antibiotics for acute infections;

• replacement immunoglobulins and additional immunization;

• bone marrow transplantation;

• gene therapy (future).