Symptoms of APDS can vary, even among family members carrying the same genetic condition.¹
While some APDS patients are asymptomatic, others present with severe, recurrent sinopulmonary infections; persistent, severe, or recurrent herpesvirus infections, particularly Epstein-Barr Virus (EBV) and cytomegalovirus (CMV); lymphadenopathy, hepatomegaly, splenomegaly, and/or nodular lymphoid hyperplasia; autoimmune cytopenias and autoinflammatory diseases; enteropathy; or lymphoma.2
APDS is a progressive disease that can lead to end-organ damage and early mortality.2 Most commonly, manifestations begin in infancy with severe, recurrent sinopulmonary infections, while the lympholiferative and autoimmune disorders mentioned above often occur later in childhood.3
“Typically, a person with APDS will present to a hospital within the first 5 years of life with a predominant and recurring respiratory tract infection. They can also present with swollen lymph nodes. Unfortunately these general patient symptoms often result in medical professionals pre-diagnosing a range of autoimmune disorders before a primary immunodeficiency (PI) diagnosis is considered.
Even if a PI classification is given, a patient can be misdiagnosed with Common Variable Immune Deficiency (CVID) or Hyper IgM. This leads to APDS patients being cared for by a variety of physicians, and symptoms being managed without recognizing the underlying genetic defect.”
Nicholas Hartog, MD, is a board-certified pediatric and adult allergy and immunology physician.
In addition to the physical impacts of disease, hospitalizations and surgical interventions are common. Polypharmacy is often necessary to manage symptoms, and patients see multiple doctors throughout both the diagnosis and management stages.2 These factors can cause patients to miss school, work, or social activities, and cause anxiety, depression and stress.9-11
Fatigue is also common among patients with primary immunodeficiencies such as APDS and can negatively impact quality of life.9-12
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PI is also referred to as an Inborn Error of Immunity (IEI).
1. Lucas CL, Kuehn HS, Zhao F, et al. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110δ result in T cell senescence and human immunodeficiency. Nat Immunol. 2014;15(1):88-97. doi:10.1038/ni.2771 2. Maccari ME, Abolhassani H, Aghamohammadi A, et al. Disease Evolution and Response to Rapamycin in Activated Phosphoinositide 3-Kinase δ Syndrome: The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome Registry. Front Immunol. 2018;9:543. Published 2018 Mar 16. doi:10.3389/fimmu.2018.00543 3. Jamee M, Moniri S, Zaki-Dizaji M, et al. Clinical, Immunological, and Genetic Features in Patients with Activated PI3Kδ Syndrome (APDS): a Systematic Review. Clin Rev Allergy Immunol. 2020;59(3):323-333. doi:10.1007/s12016-019-08738-9 4. Coulter TI, Chandra A, Bacon CM, et al. Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study. J Allergy Clin Immunol. 2017;139(2):597-606.e4. doi:10.1016/j.jaci.2016.06.021 5. Elkaim E, Neven B, Bruneau J, et al. Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase δ syndrome 2: A cohort study. J Allergy Clin Immunol. 2016;138(1):210-218.e9. doi:10.1016/j.jaci.2016.03.022 6. Condliffe AM, Chandra A. Respiratory Manifestations of the Activated Phosphoinositide 3-Kinase Delta Syndrome. Front Immunol. 2018;9:338. Published 2018 Mar 5. doi:10.3389/fimmu.2018.00338 7. Carpier JM, Lucas CL. Epstein-Barr Virus Susceptibility in Activated PI3Kδ Syndrome (APDS) Immunodeficiency. Front Immunol. 2018;8:2005. Published 2018 Jan 16. doi:10.3389/fimmu.2017.02005 8. Wang Y, Wang W, Liu L, et al. Report of a Chinese Cohort with Activated Phosphoinositide 3-Kinase δ Syndrome. J Clin Immunol. 2018;38(8):854-863. 9. Rider NL, Kutac C, Hajjar J, et al. Health-Related Quality of Life in Adult Patients with Common Variable Immunodeficiency Disorders and Impact of Treatment. J Clin Immunol. 2017;37(5):461-475. 10. Jiang F, Torgerson TR, Ayars AG. Health-related quality of life in patients with primary immunodeficiency disease. Allergy Asthma Clin Immunol. 2015;11:27.11. Kuburovic NB, Pasic S, Susic G, et al. Health-related quality of life, anxiety, and depressive symptoms in children with primary immunodeficiencies. Patient PreferAdherence. 2014;8:323-330. 11. Hajjar J, Guffey D, Minard CG, Orange JS. Increased Incidence of Fatigue in Patients with Primary Immunodeficiency Disorders: Prevalence and Associations Within the US Immunodeficiency Network Registry. J Clin Immunol. 2017;37(2):153-165. 12. Seeborg FO, Seay R, Boyle M, Boyle J, Scalchunes C, Orange JS. Perceived Health in Patients with Primary Immune Deficiency. J Clin Immunol. 2015;35(7):638-650. 13. Tabolli S, Giannantoni P, Pulvirenti F, et al. Longitudinal study on health-related quality of life in a cohort of 96 patients with common variable immune deficiencies. Front Immunol. 2014;5:605.