Gastrointestinal disorders common in primary immunodeficiency

About one-third of persons with primary immunodeficiency (PI) experience gastrointestinal (GI) health problems, and it’s essential to seek a diagnosis that addresses how the PI is causing the symptoms. To provide the PI community with guidance, Dr. Sarah Glover, a mucosal immunologist and professor at the University of Mississippi Medical Center, presented an IDF forum, “Managing GI Issues and Primary Immunodeficiency.”

GI disorder symptoms and complications are often the initial signs of PI. Symptoms may include infectious diarrhea, IBD, cancer-related diseases, and difficulty with the digestion or absorption of nutrients from food. If a patient comes into Glover’s office having suffered inflammatory bowel disease (IBD) since childhood, she tests for PI. 

A primary reason why a person with PI develops GI issues is that they don’t have the immune system cells required to maintain the GI tract. The GI tract is a barrier tissue that helps a person digest their food and absorb nutrients while also providing protection against harmful bacteria and toxins. The GI tract has many immune system cells, including T cells, natural killer cells, macrophages, dendritic cells, innate lymphoid cells, and neutrophils, that aid in preventing infection should a bacteria or toxin enter the gut.

Infectious diarrhea is one GI problem that occurs due to a compromised immune system. Bacteria, fungi, and viruses all play a role in causing infection for those with PI, particularly in common variable immunodeficiency (CVID), selective IgA deficiency, X-linked agammaglobulinemia (XLA), and chronic granulomatous disease (CGD). 

PI disorders are also associated with microbiome dysbiosis (an imbalance in the microbes that live in the gut) and systemic inflammation, particularly in the presence of immune dysregulation conditions. One example of immune dysregulation is autoimmunity, a condition in which the body attacks itself, including organs like the intestines.

A person with immune dysregulation may experience uncontrolled inflammation in the gut, Celiac disease, IBD, and pernicious anemia (anemia caused by a weakened stomach lining due to autoimmunity).

Celiac disease is an autoimmune disease triggered by gluten that may result in malabsorption, weight loss, diarrhea, anemia, bloating, and abdominal pain. It is more common in persons with CVID and selective IgA deficiency.

IBDs include Crohn’s disease and ulcerative colitis, both of which are characterized by diarrhea, abdominal pain, bloody stools, vomiting, and weight loss. Those with CGD and antibody deficiencies like XLA are at greater risk for IBD.

Because some PIs can lead to cancer in the stomach, pancreas, and liver, Glover recommends regular colon screenings beginning at age 45. If there is a history of cancer, screenings should be performed more frequently than every 10 years.

To find a gastroenterologist specializing in PI, look for major academic centers in your area that either have providers on staff or can recommend providers. Ensure providers understand the symptoms and read the latest literature about PI and GI issues.