What clinical features should prompt me to suspect a primary immunodeficiency in a child?

Primary immunodeficiency (PID) should be suspected in a child presenting with recurrent, severe, or unusual infections, particularly if these infections are persistent despite appropriate treatment or caused by opportunistic organisms.

Key clinical features include frequent ear infections, pneumonia, sinusitis, or skin abscesses that are unusually severe or recurrent.

Other important signs are failure to thrive, poor growth, and a family history of immunodeficiency or early childhood deaths from infections.

Additionally, unexplained lymphoproliferation, autoimmune manifestations, or persistent lymphadenopathy and hepatosplenomegaly may indicate an underlying PID.

Children with adverse reactions to live vaccines or persistent thrush and chronic diarrhoea should also raise suspicion.

Overall, the presence of multiple infections involving different sites, infections with unusual pathogens, or infections that do not respond to standard therapy should prompt consideration of PID and referral for immunological assessment.

This integrated approach aligns with UK clinical guidance emphasizing infection patterns and family history ¹, while recent literature highlights the importance of lymphoproliferative and autoimmune features as additional clues (Cant and Battersby, 2013; Peng and Kaviany, 2023; Costagliola et al., 2025).