Dec. 15, 2022
Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by decreased levels of serum immunoglobulin (Ig), with an estimated prevalence of 1 in 25,000 individuals. Patients with CVID are at increased risk of impaired antibody responses, as well as noninfectious, inflammatory manifestations.
Antibody deficiencies associated with CVID can lead to recurrent infections of the upper respiratory and gastrointestinal (GI) tracts. Noninfectious complications affect at least 50% of individuals with CVID and can include autoimmune disorders, lung diseases, gastrointestinal and hepatic disorders, granulomatous diseases, lymphoproliferative disorders, and malignancy.
Mayo Clinic gastroenterologists Jana G. Al Hashash, M.D., M.S., and Francis (Frank) A. Farraye, M.D., M.S., discuss the clinical presentations, diagnostic considerations and therapeutic options for the GI manifestations of CVID. Drs. Al Hashash and Farraye are gastroenterologists at Mayo Clinic's campus in Jacksonville, Florida. Together, with co-author Jacqueline D. Squire, M.D., they published a review article on this topic in The American Journal of Gastroenterology in 2022. Dr. Squire is a specialist in allergy and immunology at Mayo Clinic in Florida.
Who does CVID most often affect and at what age do symptoms typically appear?
Several studies have demonstrated that CVID is more common in males during childhood and in females during adulthood. Although patients can be diagnosed with CVID anytime during their lives, studies have demonstrated bimodal peaks for diagnosis occurring in the first and third decades of life, with a mean age of 35.3 years. Most patients experience symptoms for 5 to 9 years before the diagnosis.
What can you tell us about the clinical presentation of CVID involving the GI tract?
Between 9% and 34% of patients diagnosed with CVID have immune dysregulation causing symptomatic GI inflammation. Infectious and noninfectious complications associated with CVID involving the GI tract can mimic celiac disease, inflammatory bowel disease, pernicious anemia and other disorders. Infectious complications associated with CVID include protozoal infections — primarily Giardia lamblia — as well as chronic viral infections with norovirus. Additional GI infections to consider and evaluate for include Campylobacter jejuni, Salmonella spp and cytomegalovirus.
How is CVID diagnosed?
Early identification and treatment are critical to improve outcomes of these patients. Diagnosis typically begins with a detailed history focusing on both the infectious and noninfectious manifestations of the disease. Our review article provides a list of the most encountered warning signs, which include recurrent sinus infections or pneumonias.
If CVID is suspected, the initial work-up should include checking levels of immunoglobulins (including IgG, IgA and IgM). In general, a diagnosis of CVID is made in patients who have low IgG levels (defined by age-adjusted reference ranges) on at least two measurements taken more than three weeks apart, along with either a low IgA or IgM level, and evidence of impaired vaccine response.
Before diagnosing CVID, it is necessary to rule out the presence of other factors associated with hypogammaglobulinemia. These factors include oncologic disorders such as monoclonal gammopathies, chronic lymphocytic leukemia and non-Hodgkin lymphoma, and certain medications. The list of medications associated with hypogammaglobulinemia includes chronic glucocorticosteroids and sulfasalazine, anti-CD20 monoclonal antibodies (rituximab) as well as anti-epileptic and antimalarial agents. Nephrotic syndrome, severe burns, lymphangiectasia and protein-losing enteropathy also can lead to excessive loss of immunoglobulins.
What treatments are available for GI manifestations of CVID?
As there are no consensus guidelines for the treatment of noninfectious gastrointestinal complications of CVID, treatment plans should be individualized and based on symptoms, histologic findings and patient preferences. Immunoglobulin replacement therapy has been shown to have a positive impact on the manifestations related to antibody deficiency and infectious complications. This treatment is generally initiated and continued in patients with CVID.
To address noninfectious complications related to immune dysregulation involving B cells and T cells, most patients will require other therapies in conjunction with Ig replacement. Many patients with noninfectious complications require treatment with immunosuppressive therapies. Management of CVID-related symptoms that mimic inflammatory bowel disease, for example, typically involves steroids, 5-aminosalicylates, thiopurines or biologics. Our review article contains a proposed treatment algorithm for patients with CVID describing additional details. Good communication among all members of a multidisciplinary team involving immunologists, gastroenterologists and nutritionists is essential for the successful management of these patients.
For more information
Hashash JG, et al. An expert opinion/approach: Clinical presentations, diagnostic considerations, and therapeutic options for gastrointestinal manifestations of common variable immune deficiency. The American Journal of Gastroenterology. 2022;117:1743.
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