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X-Linked Agammaglobulinemia (Xla):Phenotype, Diagnosis, and Therapeutic Challenges Around the World Publisher



Elsayed ZA1 ; Abramova I2 ; Aldave JC3 ; Alherz W4 ; Bezrodnik L5 ; Boukari R6 ; Bousfiha AA7 ; Cancrini C8 ; Condinoneto A9 ; Dbaibo G10 ; Derfalvi B11 ; Dogu F12 ; Edgar JDM13 ; Eley B14 Show All Authors
Authors
  1. Elsayed ZA1
  2. Abramova I2
  3. Aldave JC3
  4. Alherz W4
  5. Bezrodnik L5
  6. Boukari R6
  7. Bousfiha AA7
  8. Cancrini C8
  9. Condinoneto A9
  10. Dbaibo G10
  11. Derfalvi B11
  12. Dogu F12
  13. Edgar JDM13
  14. Eley B14
  15. Elowaidy RH1
  16. Espinosapadilla SE15
  17. Galal N16
  18. Haerynck F17, 18
  19. Hannawakim R10
  20. Hossny E1
  21. Ikinciogullari A12
  22. Kamal E19
  23. Kanegane H20
  24. Kechout N6
  25. Lau YL20
  26. Morio T21
  27. Moschese V22
  28. Neves JF23
  29. Ouederni M24
  30. Paganelli R25
  31. Paris K26
  32. Pignata C27
  33. Plebani A28
  34. Qamar FN29
  35. Qureshi S29
  36. Radhakrishnan N30
  37. Rezaei N31
  38. Rosario N32
  39. Routes J33
  40. Sanchez B34
  41. Sediva A35
  42. Seppanen MR36
  43. Serrano EG15
  44. Shcherbina A2
  45. Singh S37
  46. Siniah S38, 39, 40
  47. Spadaro G26
  48. Tang M41
  49. Vinet AM42
  50. Volokha A43
  51. Sullivan KE44
Show Affiliations
Authors Affiliations
  1. 1. Pediatric Allergy and Immunology Unit, Children's Hospital, Ain Shams University, Cairo, Egypt
  2. 2. Department of Immunology, National Medical and Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
  3. 3. Primary Immunodeficiency Unit, Allergy and Immunology Division, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru
  4. 4. Department of Pediatrics, Faculty of Medicine, Kuwait University, Allergy and Clinical Immunology Unit, Al-Sabah Hospital, Kuwait City, Kuwait
  5. 5. Immunology Unit Hospital de Ninos Ricardo Gutierrez and CIC (Clinical Immunology Center), CABA, Buenos Aires, Argentina
  6. 6. Department of Immunology, Institut Pasteur d'Algerie, Faculty of Medicine, Algiers, Algeria
  7. 7. Clinical Immunology Unit, P1, Ibn Rushd Hospital, Laboratoire d'Immunologie Clinique, Inflammation et Allergie LICIA and Medicine and Pharmacy Faculty of Hassan II University, Casablanca, Morocco
  8. 8. University Department of Pediatrics, Unit of Immune and Infectious Diseases, Childrens' Hospital Bambino Gesu, “University of Rome Tor Vergata�, Rome, Italy
  9. 9. Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo – Sp, Brazil
  10. 10. Division of Pediatric Infectious Diseases and Center for Infectious Diseases Research, Department of Pediatrics and Adolescent Medicine, American University of Beirut, Beirut, Lebanon
  11. 11. Dalhousie University, IWK Health Centre, Halifax, Nova Scotia, Canada
  12. 12. Ankara University School of Medicine, Department of Pediatric Immunology and Allergy, Ankara, Turkey
  13. 13. The Royal Hospitals & Queen's University Belfast, United Kingdom
  14. 14. Paediatric Infectious Diseases Unit, Red Cross War Memorial Children's Hospital and the Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa
  15. 15. The Immunodeficiencies Research Unit, National Institute of Pediatrics, Mexico City, Mexico
  16. 16. Department of Pediatrics, Faculty of Medicine, Cairo University, Egypt
  17. 17. Primary Immunodeficiency Research Lab, Ghent University, Belgium
  18. 18. Centre for Primary Immunodeficiency, Department of Pediatric Pulmonology and Immunology, Ghent University Hospital, Belgium
  19. 19. Department of Microbiology, Parasitology and Immunology, Faculty of Medicine, University of Khartoum, Sudan
  20. 20. Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
  21. 21. Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong
  22. 22. Pediatric Immunopathology and Allergology Unit, Tor Vergata University Hospital, University of Rome Tor Vergata, Rome, Italy
  23. 23. Primary Immunodeficiencies Unit, Hospital Dona Estefania, Centro Hospitalar de Lisboa Central and CEDOC Nova Medical School, Lisboa, Portugal
  24. 24. Pediatric Immuno-hematology Unit, Bone Marrow Transplantation Center, University Tunis El Manar, Faculty of Medicine, Tunis, Tunisia
  25. 25. Department of Medicine and Sciences of Aging, University “G. d'Annunzio� of Chieti-Pescara, Italy
  26. 26. LSU Health Sciences Center, New Orleans, LA, United States
  27. 27. Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy
  28. 28. Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST-Spedali Civili of Brescia, Brescia, Italy
  29. 29. Department of Pediatric and Child Health, Aga Khan University Hospital, Karachi, Pakistan
  30. 30. Department of Pediatric Hematology Oncology, Super Speciality Pediatric Hospital and PG Teaching Institute, Noida, India
  31. 31. Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, and Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
  32. 32. Federal University of Parana, Curitiba, Brazil
  33. 33. Division of Allergy and Clinical Immunology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States
  34. 34. Servicio de Inmunologia, Hospital Universitario Virgen del Rocio, Seville, Spain
  35. 35. Department of Immunology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
  36. 36. Rare Diseases Center, Children's Hospital and Adult Immunodeficiency Unit, Infectious Diseases, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
  37. 37. Department of Pediatrics and Chief, Allergy Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
  38. 38. Paediatric Institute Kuala Lumpur General Hospital, Kuala Lumpur, Malaysia
  39. 39. Department of Allergy and Immunology, The Royal Children's Hospital Melbourne, Australia
  40. 40. Murdoch Children's Research Institute, Melbourne, Australia
  41. 41. The University of Melbourne, Australia
  42. 42. Hospital HHA, Universidad de la Frontera, Temuco, Chile
  43. 43. Department of Pediatric Infectious Diseases and Immunology, Shupyk National Medical Academy of Postgraduate Education and Center for Clinical Immunology, City Children's Hospital N1, Kiev, Ukraine
  44. 44. Division of Allergy Immunology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, United States

Source: World Allergy Organization Journal Published:2019


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. © 2019 The Authors
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