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Spanish Consensus on the Diagnosis and Management of Patients With Activated PI3K Delta Syndrome (APDS)

Neth O1, Alsina L2,3, Rivière JG4,5,6, López-Granados E7,8,9, Seoane-Reula ME10,11, González Granado LI12,13, Sánchez-Ramón S14, Rodríguez-Gallego C15,16,17,18, and the Spanish APDS Study Group

1Paediatric Infectious Diseases, Rheumatology and Immunology Unit, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, IBiS /Universidad de Sevilla/CSIC, Red de Investigación Translacional en Infectología Pediátrica (RITIP) Seville, Spain
2Clinical Immunology and Primary Immunodeficiencies Unit, Pediatric Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain
3Study Group for Immune Disfunction Diseases in Children, Institut de Recerca Sant Joan de Déu, Barcelona, Spain
4Infection and Immunity in Pediatric Patients Research Group, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain
5Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Infantil i de la Dona Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
6Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Spain
7Center for Biomedical Network Research on Rare Diseases (CIBERER U767), ISCIII, Madrid, Spain
8Lymphocyte Pathophysiology in Immunodeficiencies Group, La Paz Institute for Health Research (IdiPAZ), Madrid, Spain
9Clinical Immunology Department, La Paz University Hospital, Madrid, Spain
10Primary Immunodeficiencies Unit, Pediatric Allergy and Immunology Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
11Laboratory of Immune-Regulation, Gregorio Marañón Health Research Institute (IISGM), Madrid, Spain
12Primary Immunodeficiencies Unit, Pediatrics, Hospital 12 de Octubre, Research Institute Hospital 12 octubre (i+12), Madrid, Spain
13School of Medicine, Universidad Complutense de Madrid, Madrid, Spain 14Department of Immunology, IML and IdSSC, Hospital Clínico San Carlos, Madrid, Spain, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
15Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
16Department of Medical and Surgical Sciences, School of Medicine, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain
17Department of Clinical Sciences, University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain
18CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain

Spanish APDS Study Group 
Mejía MA 1, Belendez Bieler C1, Cardozo C2, Colino Gil E3, Del Rosal T4, Deyà Martinez A5, Diab L6, Domínguez-Pinilla N6, García-Soidán A7, Gimeno Díaz de Atauri A6, Martin Nalda A8, Montes-Ares O9, Moral Moral P10, Murciano Carrillo T11, Nuñez-Beltran M10, Ocejo-Vinyals G12, Olbrich P13, García AP5, Ramakers J14, Rodríguez Pena R4, Sabado C8, Solanich X15, Soler Palacín P8

1Hospital General Universitario Gregorio Marañón, Madrid, Spain
2Hospital Clinic, Barcelona
3Complejo Hospitalario Universitario Insular-Materno Infantil, Las Palmas, Spain
4Hospital la Paz, Madrid, Spain
5Hospital San Joan Déu, Barcelona, Spain
6Hospital Doce de Octubre, Madrid, Spain
7Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain
8Hospital Universitario Vall d’Hebron, Barcelona, Spain
9Hospital Universitario Virgen de la Arrixaca, Murcia, Spain
10Hospital Universitario y Politécnico La Fe, Valencia, Spain
11Pediatric Hematology and Oncology Department, Hospital Universitario Vall d’Hebron, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
12Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain
13Hospital Universitario Virgen del Rocío, Sevilla, Spain
14Department of Pediatrics, Hospital Universitari Son Espases. Multidisciplinary Group for Research in Pediatrics, Hospital Universitari Son Espases; Balearic Islands Health Research Institute (IdISBa), Palma, Spain
15Hospital Universitario Bellvitge, L’Hospitalet del Llobregat, Spain

J Investig Allergol Clin Immunol 2025; Vol. 35(2)
doi: 10.18176/jiaci.1059

Activated phosphoinositide 3-kinase (PI3K) delta syndrome (APDS) is an ultrarare genetic disorder characterized by overlapping immunodeficiency and immune dysregulation. Its diagnosis poses challenges owing to its clinical similarities with other inborn errors of immunity (IEIs), compounded by the absence of targeted treatments in today’s medical landscape. The standard approach involves symptom management, reducing infection through immunoglobulin replacement therapy and prophylactic antimicrobials, and treating immune dysregulation with immunomodulators. This approach considerably hampers effective management of APDS, as the diverse nature of the disease necessitates a personalized strategy, in which the advantages and risks of immunosuppression are weighed against the potential for recurrent infections and lymphoproliferative complications. To address these challenges, a group of Spanish experts in the management of IEIs, including APDS, collaborated to develop Delphi-based consensus recommendations. The primary goal of the initiative was to offer guidance on various aspects of this complex disease, marking a pioneering effort in Europe. The consensus aims to facilitate early diagnosis and provide clues for individual patient-based decisions that could favor balanced risk-benefit estimations for treatment.

Key words: APDS, Recommendations, IEI, Personalized medicine