Clinical, Endoscopic and Histologic Features of Common Variable Immunodeficiency

Introduction: Common variable immunodeficiency (CVID) is a rare illness with estimated prevalence of 1/25,000 individuals. Studies describing endoscopic (endo) and histopathological (histo) findings, and therapeutic options are lacking. Our goal was to describe gastrointestinal (GI) symptoms, endo and histo findings, as well as real-world experience with treatment of patients with CVID and GI involvement. Methods: This was a retrospective review of patients ≥16 years of age diagnosed with CVID who underwent endo evaluation for GI symptoms at a major three site academic medical center. Patients with secondary CVID were excluded. Patients were identified by searching our institution’s database using CVID, upper endoscopy and/or colonoscopy as key words. Demographics, GI symptoms, endo and histo findings, and treatments were abstracted. Descriptive statistics were used to analyze the results. Results: A total of 57 patients were included; 53% female, median age at CVID diagnosis was 32 years (range 4-66). A total of 147 procedures were included (Table 1). The most common GI symptoms leading to endo evaluation were diarrhea (50%) and abdominal pain (29%); other indication included nausea (23%), weight loss (17%), vomiting (14%), and rarely (<10%): hematochezia/rectal bleeding, bloating, anorexia/early satiety, heartburn, dysphagia, iron and vitamin B12 deficiency. Endo and histo findings are described in Table 1. Only 45% of the procedures with normal endoscopic appearance had normal histology. Patients were diagnosed with CVID enteropathy (CVIDe) (12), microscopic colitis (8), autoimmune enteropathy (1), Crohn’s disease (1). Patients diagnosed with CVIDe were treated with budesonide (9), prednisone (1), mesalamine (1), vedolizumab (2), infliximab (2), ustekinumab (1), sirolimus (1), abatacept (1), cholestyramine (1) in addition to intravenous or subcutaneous immunoglobulin. One patient underwent bone marrow transplant for medically refractory disease. Conclusion: GI symptoms are frequent in patients with CVID. While endo and histo findings may be normal, decreased plasma cells and apoptosis are characteristic of CVIDe. In our series, 21% of the patients were diagnosed with CVIDe, similar to 15-20% as described by the literature. Most patients were treated with budesonide and 25% of patients eventually required biologics. Despite the lack of randomized controlled trials, patients with CVIDe may benefit from treatment with immunomodulators/biologics to reduce morbidity and mortality. Table 1. - Endoscopic and Histopathological Findings Number of Procedures n = 147 (%) Type of procedure EGD Upper DBE Colonoscopy Flexible sigmoidoscopy Lower DBE 73 (50)1 (1)63 (43)9 (6)1 (1) EGD/Upper DBE endoscopic findings (n=74) Normal Esophagitis Gastric erythema and/or erosions/ulcer Gastric atrophy Gastric polyp Duodenal erythema Scalloping duodenum/Villous blunting Nodular mucosa duodenum Ulcers duodenum/jejunum 30 (41)5 (7)23 (31)4 (5)4 (5)2 (3)16 (22)4 (5)1 (1) Colonoscopy/Flexible sigmoidoscopy/Lower DBE endoscopic findings (n=73) Normal Nodular mucosa terminal ileum Atrophic mucosa terminal ileum Aphtha/erosion/ulcer terminal ileum Granularity terminal ileum Inflammatory changes in 1 or more colonic segments Inflammatory changes ileocolonic anastomosis Pseudopolyps Other polyps/polypoid lesions 41 (56)2 (3)1 (1)3 (4)1 (1)11 (15)1 (1)2 (3)17 (23) EGD/Upper DBE histopathology findings (n=74) Normal Apoptosis Decreased/absent plasma cells Decreased goblet and Paneth cells Villous blunting Crypt distortion Brunner gland hyperplasia Lymphoid aggregates Prominent lymphoid follicle/lymphoid hyperplasia Increased intraepithelial lymphocytes (duodenum) Active duodenal inflammation Chronic duodenal inflammation (peptic and non-peptic) Increased eosinophils Reactive gastropathy Active chronic gastritis Chronic gastritis Lymphocytic gastritis Autoimmune gastritis/atrophic gastritis Gastric mucin cell or foveolar metaplasia Multinucleated giant cells Increased epithelial lymphocytes (esophagus) Active inflammation esophagus Active chronic inflammation esophagus Giardia in the duodenum Positive Helicobacter pylori No biopsies 16 (22)2 (3)21 (28)1 (1)19 (26)7 (9)1 (1)2 (3)4 (5)14 (19)3 (4)8 (11)1 (1)14 (19)2 (3)13 (18)3 (4)6 (8)6 (8)1 (1)4 (5)2 (3)1 (1)3 (4)1 (1)2 (3) Colonoscopy/Flexible sigmoidoscopy/Lower DBE histopathological findings (n=73) Normal Apoptosis Decreased/absent plasma cells Villous blunting terminal ileum Lymphoid aggregates Prominent lymphoid follicle/lymphoid hyperplasia Active ileitis Active chronic ileitis Active colitis Active on chronic colitis Chronic colitis/crypt distortion Increased subepithelial collagenous band Increased intraepithelial lymphocytosis Decreased goblet cells Pseudopolyp CMV Other polyps: TA, serrated, hyperplastic 21 (29)7 (10)13 (18)2 (3)7 (10)3 (4)6 (8)1 (1)13 (18)2 (3)5 (7)4 (5)14 (19)1 (1)1 (1)2 (3)11 (15) EGD = upper endoscopy, DBE = double balloon enteroscopy, CMV = Cytomegalovirus, TA = tubular adenoma.EGD = upper endoscopy, DBE = double balloon enteroscopy, CMV = Cytomegalovirus, TA = tubular adenoma.