Inflammatory bowel disease–like conditions: immune deficiencies

Abbreviations

Introduction

Primary or secondary immune defects can occur in both children and adults. Primary immune defects are mainly seen in pediatric patients. In contrast, immune defects in adults often result from secondary causes. Secondary immune disorders can be caused by various medical conditions or treatments for these conditions, such as diabetes mellitus, cirrhosis, hemoglobinopathy, malnutrition, nephrotic syndrome, protein-losing states (such as enteropathies, severe exudative skin disease, and peritoneal dialysis), splenectomy, malignancy, and radiation therapy. One of the common etiologies of secondary immune deficiency is the use of immunosuppressive therapy, including cytotoxic chemotherapy for malignancy, immunomodulator therapy for autoimmune diseases, antirejection therapy for solid organ or bone marrow transplantation, bone marrow ablation before transplantation, and management of graft-versus-host disease. Corticosteroids, immunomodulators, and immunosuppressive biological therapy are widely used in the management of Crohn's disease (CD) and ulcerative colitis (UC). Patients with inflammatory bowel disease (IBD) may develop primary or secondary treatment failure to these agents.

Components of immune deficiency include defects in immunoglobulins (Ig), complements, granulocytes, and cell-mediated immunity. There is reciprocal relationship between immune deficiency and infection. While viral, bacterial, and fungal infections, such as human immunodeficiency virus (HIV) can result in immune defects, secondary immune deficiency may cause infections from these pathogens. The predominant presentations of immunodeficiency are stereotypic patterns of recurrent infections. The pattern of recurrent infections may suggest the deficient component of immune system is involved. Gastrointestinal (GI) tract infections from viral, bacterial, fungal, and parasitic agents are common presentations in patients with primary or secondary immune deficiency. In addition, immune deficiency may present with acute and chronic inflammation in the GI tract with or without identifiable pathogens.

Evaluation of immune deficiency

A detailed evaluation of family history is important for the detection of primary immunodeficiencies. Testing for HIV is a necessary next step. Selective primary immunodeficiencies, including mutations in IL10/IL10 receptor, IL-21, NADPH oxidase complex, XIAP, LRBA, and CTLA-4, are found to be associated with early-onset or pediatric IBD . Primary immune deficiency disorders as a cause for IBD or IBD-like conditions appears to be restricted to those with pediatric-onset and severe disease . Monogenetic, early-onset IBD conditions are discussed in Chapter 31 , Inflammatory bowel disease–like conditions: monogenic gastrointestinal (GI) disorders.

Granulocytes and lymphocytes can be measured by complete blood counts with white blood cell counts. Chronic granulomatous disease can be assessed flow cytometric testing of dihydrorhodamine. Screening complement testing with C3, C4, C5 through C9, and CH50 may be performed.

The evaluation of humoral immunity consists of serum levels of IgG, IgA, IgM, and IgE as screening tests for antibody defects. Flow cytometry is used to quantify T- and B-cell subsets. NK-cell functional assessment can also be performed.

A GI evaluation may be of diagnostic for some immune deficient disorders, such as duodenal biopsy for the diagnosis of common variable immune deficiency (CVID).

Gastrointestinal infections

Patients with primary or secondary humoral or cellular immune deficiencies or deficiencies in the innate immunity are prone to the development of various forms of GI infections. IBD-like GI infections are discussed in Chapter 23 , Superimposed infections in inflammatory bowel diseases, and Chapter 25 , Inflammatory bowel disease–like conditions: infectious.