GI Disorders in Patients With Primary Immunodeficiency
GI Disorders in Patients With Primary Immunodeficiency
Gastrointestinal disorders such as chronic or acute diarrhea, malabsorption, abdominal pain, and inflammatory bowel diseases can indicate immune deficiency. The gastrointestinal tract is the largest lymphoid organ in the body, so it is not surprising that intestinal diseases are common among immunodeficient patients. Gastroenterologists therefore must be able to diagnose and treat patients with primary immunodeficiency. Immune-related gastrointestinal diseases can be classified as those that develop primarily via autoimmunity, infection, an inflammatory response, or malignancy. Immunodeficient and immunocompetent patients with gastrointestinal diseases present with similar symptoms. However, intestinal biopsy specimens from immunodeficient patients often have distinct histologic features, and these patients often fail to respond to conventional therapies. Therefore, early recognition of symptoms and referral to an immunologist for a basic immune evaluation is required to select appropriate treatments. Therapies for primary immunodeficiency comprise immunoglobulin replacement, antibiotics, and, in severe cases, bone marrow transplantation. Treatment of immunodeficient patients with concomitant gastrointestinal disease can be challenging, and therapy with immunomodulators often is required for severe disease. This review aims to guide gastroenterologists in the diagnosis and treatment of patients with primary immunodeficiency.
Primary immunodeficiencies are a group of more than 150 disorders, often inherited, that are caused by intrinsic defects in the immune system. The immune defects can affect the humoral (B cell) immune system, such as in Bruton's agammaglobulinemia; the cellular (T cell) immune system, such as in DiGeorge syndrome; and both T- and B-cell immunity, such as in severe combined immunodeficiency (SCID) and in innate defects.
Gastrointestinal (GI) disorders present in 5% to 50% of patients with primary immunodeficiencies. This is in part because the gut is the largest lymphoid organ in the body, containing the majority of lymphocytes and producing large amounts of immunoglobulin (Ig). The mucosal immune system is uniquely regulated to manage its constant exposure to viruses, parasites, and bacterial antigens, all of which are in close proximity to a large reservoir of lymphocytes, macrophages, and dendritic cells. Its response is one of suppression or tolerance, unlike the systemic immune system. Dysfunction of the regulatory mechanisms maintaining this balance between active immunity and tolerance in the gut may lead to mucosal inflammation and damage and GI diseases. Therefore, it is not surprising that GI disorders are common manifestations, and often the initial presenting symptom, in patients with dysfunction in humoral immunity or cell-mediated immunity (Table 1).
GI manifestations can be broadly classified into 4 groups: infection, inflammation, malignancy, and autoimmune. The diversity of disorders involving the GI tract speaks to the differing forms of immune regulation along the length of the intestine, and the varying nature of the challenge (ie, food antigens in the small bowel and commensal flora in the colon). Many of these disorders mimic classic forms of disease (in the absence of immunodeficiency) such as celiac sprue, inflammatory bowel disease (IBD), and pernicious anemia but differ in pathogenesis and are often unresponsive to conventional therapies.
This review highlights the GI manifestations of the more common primary immunodeficiency disorders, focusing on the recognition of these diseases, appropriate diagnostic testing, and therapy.
Abstract and Introduction
Abstract
Gastrointestinal disorders such as chronic or acute diarrhea, malabsorption, abdominal pain, and inflammatory bowel diseases can indicate immune deficiency. The gastrointestinal tract is the largest lymphoid organ in the body, so it is not surprising that intestinal diseases are common among immunodeficient patients. Gastroenterologists therefore must be able to diagnose and treat patients with primary immunodeficiency. Immune-related gastrointestinal diseases can be classified as those that develop primarily via autoimmunity, infection, an inflammatory response, or malignancy. Immunodeficient and immunocompetent patients with gastrointestinal diseases present with similar symptoms. However, intestinal biopsy specimens from immunodeficient patients often have distinct histologic features, and these patients often fail to respond to conventional therapies. Therefore, early recognition of symptoms and referral to an immunologist for a basic immune evaluation is required to select appropriate treatments. Therapies for primary immunodeficiency comprise immunoglobulin replacement, antibiotics, and, in severe cases, bone marrow transplantation. Treatment of immunodeficient patients with concomitant gastrointestinal disease can be challenging, and therapy with immunomodulators often is required for severe disease. This review aims to guide gastroenterologists in the diagnosis and treatment of patients with primary immunodeficiency.
Introduction
Primary immunodeficiencies are a group of more than 150 disorders, often inherited, that are caused by intrinsic defects in the immune system. The immune defects can affect the humoral (B cell) immune system, such as in Bruton's agammaglobulinemia; the cellular (T cell) immune system, such as in DiGeorge syndrome; and both T- and B-cell immunity, such as in severe combined immunodeficiency (SCID) and in innate defects.
Gastrointestinal (GI) disorders present in 5% to 50% of patients with primary immunodeficiencies. This is in part because the gut is the largest lymphoid organ in the body, containing the majority of lymphocytes and producing large amounts of immunoglobulin (Ig). The mucosal immune system is uniquely regulated to manage its constant exposure to viruses, parasites, and bacterial antigens, all of which are in close proximity to a large reservoir of lymphocytes, macrophages, and dendritic cells. Its response is one of suppression or tolerance, unlike the systemic immune system. Dysfunction of the regulatory mechanisms maintaining this balance between active immunity and tolerance in the gut may lead to mucosal inflammation and damage and GI diseases. Therefore, it is not surprising that GI disorders are common manifestations, and often the initial presenting symptom, in patients with dysfunction in humoral immunity or cell-mediated immunity (Table 1).
GI manifestations can be broadly classified into 4 groups: infection, inflammation, malignancy, and autoimmune. The diversity of disorders involving the GI tract speaks to the differing forms of immune regulation along the length of the intestine, and the varying nature of the challenge (ie, food antigens in the small bowel and commensal flora in the colon). Many of these disorders mimic classic forms of disease (in the absence of immunodeficiency) such as celiac sprue, inflammatory bowel disease (IBD), and pernicious anemia but differ in pathogenesis and are often unresponsive to conventional therapies.
This review highlights the GI manifestations of the more common primary immunodeficiency disorders, focusing on the recognition of these diseases, appropriate diagnostic testing, and therapy.
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