BACKGROUND: Allergies have long been observed in Inborn Errors of Immunity (IEI) and might even be the first presentation resulting in delayed diagnosis or misdiagnosis in some cases. However, data on the prevalence of allergic diseases among IEI patients are limited and contradictory. OBJECTIVE: To provide a worldwide view of allergic diseases, across a broad spectrum of IEI, and their impact on the timely diagnosis of IEI. METHODS: This is a worldwide study, conceived by the World Allergy Organization (WAO) Inborn Errors of Immunity Committee. A questionnaire was developed and pilot-tested and was sent via email to collect data from 61 immunology centers known to treat pediatric and/or adult IEI patients in 41 countries. In addition, a query was submitted to The United States Immunodeficiency Network (USIDNET) at its website. RESULTS: Thirty centers in 23 countries caring for a total 8450 IEI patients responded. The USIDNET dataset included 2332 patients. Data from responders showed that a median (IQR) of 16.3% (10-28.8%) of patients experienced allergic diseases during the course of their IEI as follows: 3.6% (1.3-11.3%) had bronchial asthma, 3.6% (1.9-9.1%) atopic dermatitis, 3.0% (1.0-7.8%) allergic rhinitis, and 1.3% (0.5-3.3%) food allergy. As per the USIDNET data, the frequency of allergy among IEI patients was 68.8% (bronchial asthma in 46.9%). The percentage of IEI patients who presented initially with allergic disorders was 8% (5-25%) and diagnosis delay was reported in 7.5% (0.9-20.6%). Predominantly antibody deficiencies had the highest frequency of allergic disease followed by combined immunodeficiency with a frequency of 40.3% (19.2-62.5%) and 20.0% (10-32%) respectively. As per the data of centers, anaphylaxis occurred in 25/8450 patients (0.3%) whereas per USIDNET dataset, it occurred in 249/2332 (10.6%); drugs and food allergy were the main causes in both datasets. CONCLUSIONS: This multinational study brings to focus the relation between allergic diseases and IEI. Major allergies do occur in IEI patients but were less frequent than the general population. Initial presentation with allergy could adversely affect the timely diagnosis of IEI. There is a need for policies to raise awareness and educate primary care and other referring specialties on the association of allergic diseases with IEI. This study provides a network among centers for future prospective studies in the field.

Allergy and Clinical Immunology Hospital Nacional Edgardo Rebagliati Martins Peru

Allergy and Clinical Immunology Unit Pediatric Department AlSabah Hospital Faculty of Medicine Kuwait University Kuwait

Allergy and Immunology Unit Soba University Hospital and Faculty of Medicine University of Khartoum Sudan

Clínica de Alergia Pediátrica Mexico

Department of Allergy and Clinical Immunology Children's Hospital of Wisconsin Medical College of Wisconsin USA

Department of Allergy and Immunology Royal Children's Hospital Australia

Department of Immunology Institute of Biomedical Sciences University of Sao Paulo Sao Paulo Brazil

Department of Immunology Pasteur Institute of Algeria Algeria

Department of Immunology University Hospital Motol and the 2nd Faculty of Medicine Charles University Czech Republic

Department of Internal Medicine and Clinical Immunology Hotel Dieu de France Hospital Beirut Lebanon

Department of Medicine and Sciences of Aging University G D'Annunzio Chieti Pescara and YDA Institute of Clinical Immunotherapy and Advanced Biological Treatments Pescara Italy

Department of Molecular Medicine PID Reference Centre Sapienza University of Rome Italy

Department of Pediatric Hematology Oncology Super Specialty Pediatric Hospital and Post Graduate Teaching Institute Noida Delhi NCR 201303 India

Department of Pediatric Infectious Diseases and Immunology Shupyk National Medical Academy of Postgraduate Education Ukraine

Department of Pediatrics and Chief Allergy Immunology Unit Advanced Pediatrics Centre Post Graduate Institute of Medical Education and Research Chandigarh India

Department of Pediatrics and Child Health Aga Khan University Hospital Karachi Pakistan

Department of Pediatrics Children's Hospital of Philadelphia USA

Department of Pediatrics Division of Immunology Cairo University Egypt

Department of Pediatrics Federal University of Parana Brazil

Department of Pediatrics Immuno hematology and Stem Cell Transplantation Bone Marrow Transplantation Center Tunisia

Department of Pediatrics Pulmonary Division Allergy and Immunology Section Qatar

Department of Pediatrics Tokyo Medical and Dental University Japan

Department of Pulmonology Division of Allergy University Hospital of Montpellier Montpellier France

Desbrest Institute of Epidemiology and Public Health UMR UA11 INSERM University of Montpellier Montpellier France

Division of Pediatric Allergy University of Cape Town South Africa

Gaafer Ibn Ouf Specialist Paediatric Hospital Sudan

Hospital Tunku Azizah Women and Children Hospital Kuala Lumpur Malaysia

Immunoallergy Department Coimbra Hospital and University Centre Portugal

Instituto Nacional de Pediatría Immunodeficiencies Laboratory Mexico

National Human Genome Research Institute National Institute of Health USA

Network of Immunity in Infection Malignancy and Autoimmunity Tehran Iran

Paediatric Infectious Diseases Unit Red Cross War Memorial Children's Hospital and the Department of Paediatrics and Child Health University of Cape Town South Africa

Pediatric Allergy Immunology and Rheumatology Columbia University Medical Center New York USA

Pediatric Allergy Immunology and Rheumatology Unit Children's Hospital Ain Shams University Cairo Egypt

Research Center for Immunodeficiencies Children's Medical Center Tehran University of Medical Sciences Tehran Iran

Translational Medical Sciences Pediatric Immunology Italy

WHO Collaborating Centre on Classification Scientific Support Montpellier France

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