Gastrointestinal manifestations in children with primary immunodeficiency diseases

Introduction Primary immunodeficiency (PID) diseases are a heterogeneous group of rare genetic disorders that affect the development and function of immune cells. To date, more than 150 defects have been identified and the number is growing. These disorders are broadly classified into defects affecting the humoral (B cell) immunity, defects of the cellular (T cell) immunity or both T cell and B cell, neutrophil and macrophage defects, and defects in the innate immunity. The hallmark clinical feature is recurrent and/or severe infections. However, some type of immune defect may present with autoimmune manifestations, and increased risk of malignancy in association with their underlying immunodeficiency. In PID diseases, the gastrointestinal (GI) tract is the second target organ affected after the respiratory tract. In fact, the GI is largest lymphoid organ in the body with a unique function to handle the process of regulation and suppression of foreign antigens including viruses, bacteria, parasites, and food. Therefore, in PID the dysfunction of the regulatory mechanisms that maintain the balance between active immunity and tolerance in the gut may lead to mucosal damage and chronic GI diseases. The GI manifestations in PIDs can be categorized into five different forms: (1) Infection throughout the GI tract or hepatobiliary system such as giardiasis in humoral immunodeficiency; cytomegalovirus colitis and hepatitis in severe T cell dysfunction as well as hepatic abscess in phagocytic defect. (2) Autoimmune phenomena such as autoimmune hepatitis and enteropathy that are associated with some PIDs and may mimic classic forms of diseases such as celiac disease (CD), inflammatory bowel disease (IBD), and pernicious anemia, but differ in pathogenesis and are often unresponsive to conventional therapies. (3) Unregulated inflammatory conditions such as granulomatous colitis in common variable immunodeficiency (CVID) and chronic granulomatous disease (CGD). (4) Malignancies involving the GI tract and hepatobiliary system. (5) GI and hepatic complications secondary to therapeutic intervention such as liver or gut graftversus-host-disease and veno-occlusive disease post hematopoietic stem cell transplantation in certain PID diseases. This review focuses on the characteristic chronic GI manifestations that are commonly encountered in some PID diseases (Table 1).