Objective: In Japan, few comprehensive reports on the clinical features of X-linked agammaglobulinemia (XLA) have been available since 2001. We retrospectively investigated the clinical characteristics, diagnosis, and treatment of XLA patients at our hospital.
　Methods: This study retrospectively focused on 10 XLA patients treated at our hospital between April 2023 and March 2024. We collected data on age at diagnosis, family history, initiation and status of Ig replacement therapy, and incidence of infections.
　Results: The median age at diagnosis for the 10 patients was 2.80 years. Five patients had a family history of XLA. The median age at initiation of Ig replacement therapy was 2.85 years, with 60% of the patients receiving subcutaneous immunoglobulin (SCIg) therapy. Patients with a family history received an earlier diagnosis and started Ig replacement therapy sooner than those without a family history (p=0.047). The incidence of otitis media and pneumonia decreased after the initiation of Ig replacement therapy, while sinusitis, conjunctivitis, and skin infections recurred. The IVIg group outperformed the SCIg group in terms of IgG levels.
　Discussion: In this study, XLA patients were diagnosed at a younger age. Patients without a family history experienced delays in diagnosis and treatment. In some of these cases, bronchiectasis developed as a complication. SCIg therapy may achieve higher IgG levels with smaller doses and potentially improve patients’ quality of life. The TREC and KREC based newborn screening offers potential to early diagnosis of asymptomatic cases without a family history. Further large-scale studies for a detailed examination needs to be conducted.

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　Schnitzler syndrome (SchS) is a rare acquired autoinflammatory disease characterized by urticarial-like rash and monoclonal IgM (rarely IgG) gammopathy. A placebo-controlled double-blind trial conducted in Germany demonstrated the efficacy of canakinumab in treating SchS. Based on these findings, we conducted a Phase II trial (SCan trial) targeting Japanese patients with SchS and reported the clinical utility of canakinumab in Japanese SchS patients using data from the first 24 weeks (Period I) after an initial dose of 150 mg. However, due to the limited number of cases in Japan, the SCan trial was conducted as a single-arm, open-label study. Therefore, it was necessary to demonstrate that the sustained stabilization of clinical symptoms and laboratory findings observed in this trial was not present before canakinumab administration and that inflammation frequently relapsed under conventional treatments. To clarify this, we examined the pre-treatment clinical course of the five patients enrolled in the SCan trial. Our analysis revealed that none of the patients achieved sustained remission under either no treatment or conventional therapy, and all experienced repeated symptom relapses. These results strongly support that the clinical benefits of canakinumab were not coincidental but rather demonstrate its efficacy in SchS treatment.

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