A group of primary immunodeficiencies characterised by inability to class switch, so high IgM but low IgA and G, leading to susceptibility to infection but also autoimmune problems.

Misnomer because high IgM is a clue but not always found!

Various inheritance patterns but mostly X-linked so variable penetrance/severity. Most affect CD40 ligand production.

Usually presents in infancy – skin, lung, sinus, eye infections. Particularly prone to Pneumocystic pneumonia, histoplasmosis, cryptosporidium.

• Bronchiectasis seen
• Histoplasmosis leads to fever, cough, lymphadenopathy
• Chronic cryptosporidium diarrhoea, progressing to cholangitis and cirrhosis
• Failure to thrive
• Warty or chronic papular rash
• Osteomyelitis a particular problem for type 4 where there is less susceptibility to infection otherwise and presentation can be later in life.

Autoimmunity

• Neutropenia
• Thrombocytopenia
• Thyroid disease
• Kidney disease
• Inflammatory bowel disease

Malignancy

Increased rate of various malignancies seen.