Characterization and Health Related Quality of Life Among Children With Inborn Error of Immunity

Inborn Errors of Immunity (IEI) are a group of approximately 430 heterogeneous immunity disorders that are characterized by decreased immunity at the innate level involving disorders of phagocytosis and the complement system or at the adaptive level including B-cell, T-cell, or combined immunodeficiencies [1]. Another updated phenotypic classification of IEI suggested by the International Union of Immunological Societies (IUIS) in 2021, identifies 10 categories that include immunodeficiencies affecting cellular and humoral immunity (severe combined immunodeficiency: SCID or combined immunodeficiency), combined immunodeficiencies with associated or syndromic features (such as congenital thrombocytopenia, DNA repair defects, etc.), predominantly antibody deficiencies with recurrent bacterial infections (IgG, IgA, IgM deficiencies), diseases of immune dysregulation and autoinflammatory disorders [2]. The most common of these are the primary antibody deficiencies [3] which include common variable immunodeficiency, IgA, or IgG deficiency, X-linked agammaglobulinemia and other specific antibody deficiencies [1].

Severity of IEI also vary between asymptomatic as in the case of IgA deficiencies to life-threatening forms such as SCID (sever combined immunodeficiencies) [4]. Diagnosed IEI patients are more susceptible to acquiring infections, malignancies, autoimmunity, and lympho-proliferative disorders [5]. Most IEI are diagnosed at an early age but can present later in adulthood. Early detection and management are associated with better outcomes. Hence, screening [6-8] and employing a high level of suspicion is a key factor in improving detection rates of IEI [9]. Newborn screening for treatable and severe forms of IEI is now a common practice in many countries. As for management, the mainstay of treatment for most antibody deficiency is regular intravenous or subcutaneous immunoglobulin therapy [10-11] and bone marrow transplantation for combined immunodeficiencies; these therapies are associated with an improved quality of life (QOL) [12-13].

The burden imposed by IEI on patients is huge and encompasses both physical and emotional consequences especially due to the severity and chronicity of the disorder. Children with IEI have lower health related quality of life (HRQOL) scores [14], and more limitations in physical and social functioning [15-18]. The literature also shows a high disease burden for IEI which includes a higher number of hospitalizations per year, emergency room visits, monthly visits to clinics as well as family monthly expenses related to the disease and absenteeism from school or work [19]. The most widely used tool for assessing HRQOL in pediatric IEI patients is the Pediatric Quality of Life Inventory (PedsQL) which measures 4 domains, which are physical, emotional, social, and school functioning as reported by either parent or child [20]. Several studies assess the QOL of pediatric IEI patients and reveal a poor quality of life that is associated with delayed diagnosis and type of disease. There is a paucity of literature on the QOL of pediatric IEI patients, even though it is more common in upper Egypt where consanguinity is a prevalent occurrence. Therefore, this study is the first to assess the QOL of pediatric IEI patients using the PedsQL questionnaire.