Diagnostic Odyssey of Patients With the Rare Immunodeficiency-Activated PI3 Kinase Delta Syndrome (APDS): Case Study With Expert Interviews and Patient Surveys
Author(s)
Fabio Candotti, MD1, Roman Spelsberg, MSc2, Hermann Maximilian Wolf, MD3, Georgios Sogkas, MD4, Hans-Holger Bless, MSc2, Kirsten Heike Herrmann, PhD5, Fabian Hauck, MD6.
1Divison of Immunology and Allergy, Laboratory of Inherited Immune Disorders, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland, 2Healthcare Research and Market Access, fbeta GmbH, Berlin, Germany, 3Faculty of Medicine, Sigmund Freud Private University Vienna (SFU), Vienna, Austria, 4Department of Rheumatology and Immunology, Hannover Medical School (MHH), Hannover, Germany, 5Pharming Group N.V., Ottobrunn, Germany, 6Ludwig-Maximilians-Universität München, Munich, Germany.
1Divison of Immunology and Allergy, Laboratory of Inherited Immune Disorders, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland, 2Healthcare Research and Market Access, fbeta GmbH, Berlin, Germany, 3Faculty of Medicine, Sigmund Freud Private University Vienna (SFU), Vienna, Austria, 4Department of Rheumatology and Immunology, Hannover Medical School (MHH), Hannover, Germany, 5Pharming Group N.V., Ottobrunn, Germany, 6Ludwig-Maximilians-Universität München, Munich, Germany.
OBJECTIVES: Activated phosphoinositide 3-kinase delta syndrome (APDS) is an ultra-rare inborn error of immunity (prevalence approx. 1-2:1.000.000) first described in 2013. We collected qualitative information on challenges in diagnosing and treating patients with APDS in Austria, Germany, and Switzerland.
METHODS: We conducted structured interviews with clinical immunologists familiar with the APDS patient pathway, as well as affected adult patients or legal guardians of children diagnosed with APDS.
RESULTS: A total of 4 physicians and 6 patients were included in this study. Prior to the diagnosis of APDS, various physicians were involved in treating APDS-related symptoms, depending on the affected organ systems. These included pediatricians, immunologists, rheumatologists, pulmonologists, and hematologist-oncologists. Diagnosis was often delayed for several years after the onset of the first symptoms, due to the rarity and lack of awareness of APDS, as well as its phenotypical heterogeneity. The interviewed experts estimated that 60-80% of patients with APDS were currently undiagnosed. Patients described the certainty of the diagnosis as a persistent psychological burden, but also highlight that it enabled targeted therapy and facilitated reintegration into the social community. Treatment was carried out by an interdisciplinary team led by immunologists. Both physicians and patients described APDS-specific therapy as a breakthrough innovation, which for the first time made it possible to stabilize the disease course with the potential to achieve symptom-free status.
CONCLUSIONS: These results highlight the need to further raise awareness of rare inborn errors of immunity such as APDS among healthcare professionals. Targeted education and training should focus on possible clinical patterns and appropriate indication for unbiased genetic testing. In clinical practice, early next-generation-sequencing genetics should be offered to patients with immunological symptoms. Developing an APDS-specific disease score that incorporates both clinician-reported findings and patient-reported outcomes could facilitate treatment decisions.
METHODS: We conducted structured interviews with clinical immunologists familiar with the APDS patient pathway, as well as affected adult patients or legal guardians of children diagnosed with APDS.
RESULTS: A total of 4 physicians and 6 patients were included in this study. Prior to the diagnosis of APDS, various physicians were involved in treating APDS-related symptoms, depending on the affected organ systems. These included pediatricians, immunologists, rheumatologists, pulmonologists, and hematologist-oncologists. Diagnosis was often delayed for several years after the onset of the first symptoms, due to the rarity and lack of awareness of APDS, as well as its phenotypical heterogeneity. The interviewed experts estimated that 60-80% of patients with APDS were currently undiagnosed. Patients described the certainty of the diagnosis as a persistent psychological burden, but also highlight that it enabled targeted therapy and facilitated reintegration into the social community. Treatment was carried out by an interdisciplinary team led by immunologists. Both physicians and patients described APDS-specific therapy as a breakthrough innovation, which for the first time made it possible to stabilize the disease course with the potential to achieve symptom-free status.
CONCLUSIONS: These results highlight the need to further raise awareness of rare inborn errors of immunity such as APDS among healthcare professionals. Targeted education and training should focus on possible clinical patterns and appropriate indication for unbiased genetic testing. In clinical practice, early next-generation-sequencing genetics should be offered to patients with immunological symptoms. Developing an APDS-specific disease score that incorporates both clinician-reported findings and patient-reported outcomes could facilitate treatment decisions.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
PCR65
Topic
Patient-Centered Research
Disease
Rare & Orphan Diseases, Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain)