Long term follow-up of 168 patients with X-linked agammaglobulinemia reveals increased morbidity and mortality

Background: X-linked agammaglobulinemia (XLA) is the prototype of primary humoral immunodeficiencies. Long-term follow-up studies regarding disease-related complications and outcome are scarse. Objective: To describe the natural history of X-linked agammaglobulinemia. Methods: A nationwide multicenter study based on the IPINet registry was established in 2000 in Italy. Affected patients were enrolled by documenting centers and patients' laboratory, clinical and imaging data were recorded on an annual base. Results: Patients' data (N=168) derived from a cumulative follow-up of 1370 patient years with a mean follow-up of 8.35 years per patient. Mean age at diagnosis decreased upon the establishment of the IPINet registry (84 months before versus 23 months after). Respiratory, skin and gastrointestinal manifestations were the most frequent clinical symptoms at diagnosis and during long-term follow-up. Regular immunoglobulin replacement treatment reduced the incidence of invasive infections. Affected patients developed chronic lung disease over time (47% after 40 years of follow-up) in the presence of chronic sinusitis (84%). Malignancies were documented in a minority of cases (3.7%). Overall survival for affected patients was significantly reduced when compared to the healthy male Italian population, and further deteriorated in the presence of chronic lung disease. Conclusions: This is the first detailed long-term follow-up study for XLA patients revealing that while immunoglobulin replacement treatment reduces the incidence of invasive infections, it does not appear to influence the development of chronic lung disease. Overall survival of affected patients is reduced. Further studies are warranted in order to improve patients' clinical management and increase awareness among physicians.