X-linked agammaglobulinemia (XLA):Phenotype, diagnosis, and therapeutic challenges around the world

Zeinab A. El-Sayed, Irina Abramova, Juan Carlos Aldave, Waleed Al-Herz, Liliana Bezrodnik, Rachida Boukari, Ahmed Aziz Bousfiha, Caterina Cancrini, Antonio Condino-Neto, Ghassan Dbaibo, Beata Derfalvi, Figen Dogu, J. David M. Edgar, Brian Eley, Rasha Hasan El-Owaidy, Sara Elva Espinosa-Padilla, Nermeen Galal, Filomeen Haerynck, Rima Hanna-Wakim, Elham HossnyAydan Ikinciogullari, Ebtihal Kamal, Hirokazu Kanegane, Nadia Kechout, Yu Lung Lau, Tomohiro Morio, Viviana Moschese, Joao Farela Neves, Monia Ouederni, Roberto Paganelli, Kenneth Paris, Claudio Pignata, Alessandro Plebani, Farah Naz Qamar, Sonia Qureshi, Nita Radhakrishnan, Nima Rezaei, Nelson Rosario, John Routes, Berta Sanchez, Anna Sediva, Mikko RJ Seppanen, Edith Gonzalez Serrano, Anna Shcherbina, Surjit Singh, Sangeetha Siniah, Guiseppe Spadaro, Mimi Tang, Ana Maria Vinet, Alla Volokha, Kathleen E. Sullivan

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Abstract

Background: X-linked agammaglobulinemia is an inherited immunodeficiency recognized since 1952. In spite of seven decades of experience, there is still a limited understanding of regional differences in presentation and complications. This study was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to better understand regional needs, challenges and unique patient features. Methods: A survey instrument was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to collect both structured and semi-structured data on X-linked agammaglobulinemia. The survey was sent to 54 centers around the world chosen on the basis of World Allergy Organization participation and/or registration in the European Society for Immunodeficiencies. There were 40 centers that responded, comprising 32 countries. Results: This study reports on 783 patients from 40 centers around the world. Problems with diagnosis are highlighted by the reported delays in diagnosis>24 months in 34% of patients and the lack of genetic studies in 39% of centers Two infections exhibited regional variation. Vaccine-associated paralytic poliomyelitis was seen only in countries with live polio vaccination and two centers reported mycobacteria. High rates of morbidity were reported. Acute and chronic lung diseases accounted for 41% of the deaths. Unusual complications such as inflammatory bowel disease and large granular lymphocyte disease, among others were specifically enumerated, and while individually uncommon, they were collectively seen in 20.3% of patients. These data suggest that a broad range of both inflammatory, infectious, and autoimmune conditions can occur in patients. The breadth of complications and lack of data on management subsequently appeared as a significant challenge reported by centers. Survival above 20 years of age was lowest in Africa (22%) and reached above 70% in Australia, Europe and the Americas. Centers were asked to report their challenges and responses (n = 116) emphasized the difficulties in access to immunoglobulin products (16%) and reflected the ongoing need for education of both patients and referring physicians. Conclusions: This is the largest study of patients with X-linked agammaglobulinemia and emphasizes the continued morbidity and mortality of XLA despite progress in diagnosis and treatment. It presents a world view of the successes and challenges for patients and physicians alike. A pivotal finding is the need for education of physicians regarding typical symptoms suggesting a possible diagnosis of X-linked agammaglobulinemia and sharing of best practices for the less common complications.

Original languageEnglish
Article number100018
JournalWorld Allergy Organization Journal
Volume12
Issue number3
DOIs
Publication statusPublished - 2019

Keywords

  • Agammaglobulinemia
  • Autoimmunity
  • Immunoglobulin
  • Infection
  • Outcomes
  • Therapy
  • XLA

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    El-Sayed, Z. A., Abramova, I., Aldave, J. C., Al-Herz, W., Bezrodnik, L., Boukari, R., ... Sullivan, K. E. (2019). X-linked agammaglobulinemia (XLA):Phenotype, diagnosis, and therapeutic challenges around the world. World Allergy Organization Journal, 12(3), [100018]. https://doi.org/10.1016/j.waojou.2019.100018