Diagnosis and treatment of gastrointestinal disorders in patients with primary immunodeficiency

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.

Keywords: 6-MP; AZA; CGD; CVID; FOXP3; GI; GVHD; Hypogammaglobulinemia; IBD; IL; IPEX; Ig; Immune System; Inflammatory Intestinal Disease; NLH; SCID; STAT; TNF; WAS; WASp; Wiskott–Aldrich syndrome; Wiskott–Aldrich syndrome protein; X-linked agammaglobulinemia; XLA; azathioprine; chronic granulomatous disease; common variable immunodeficiency; forkhead box P3; gastrointestinal; graft-versus-host disease; immune dysfunction, polyendocrinopathy, enteropathy, X-linked; immunoglobulin; inflammatory bowel disese; interleukin; mercaptopurine; nodular lymphoid hyperplasia; severe combined immunodeficiency; signal transducer and activator of transcription; tumor necrosis factor.

Figure 1

H&E-stained duodenum from a patient with CVID showing mild to moderate villous flattening, active and chronic inflammation, and intraepithelial lymphocytosis with decreased numbers of plasma cells.

Figure 2

H&E (original magnification, ×40) from a patient with (A) CVID, (B) IBD, and (C) hypogammaglobulinemia. Patients with CVID lack plasma cells in the intestinal lamina propria in contrast to patients with classic IBD or hypogammaglobulinemia. Arrows represent plasma cells. Reprinted from Agarwal et al.