Diagnostic associations of hypergammaglobulinaemia in a paediatric hospital: a retrospective study

The aetiology of polyclonal hypergammaglobulinaemia affecting one or more immunoglobulin (Ig) classes has not been well defined in paediatrics, with previous studies focusing on adults or single Ig classes. We retrospectively analysed the clinical diagnoses in 2,251 patients from paediatric in-patients with significantly elevated (>2 standard deviations above age mean) IgG, IgA and/or IgM levels. Non-iatrogenic elevated Ig was found in 121 (5.4%) patients. Isolated high IgG, IgA and IgM occurred in 37%, 32% and 11% of cases, respectively, with multiple class elevation in 20%. Infection was the predominant diagnosis in 49%, especially bacterial streptococcal infections, followed by autoimmune diseases and malignancies. IgG levels were significantly higher in autoimmune patients, whereas isolated elevated IgM was associated with infection and malignancy but absent in autoimmune patients. These findings highlight that hypergammaglobulinaemia in children often signals serious underlying conditions, warranting prompt and thorough clinical evaluation to guide diagnosis and management.