Gastrointestinal tract pathology in patients with common variable immunodeficiency (CVID): A clinicopathologic study and review

BACKGROUND: Common variable immunodeficiency (CVID) is characterized by a host of gastrointestinal (GI) lesions that can mimic other conditions. METHODS: We reviewed clinical documentation and samples from 132 separate GI biopsy or resection sites on 20 CVID patients obtained over a 26-year period, including biopsies from the colon (34), esophagus (19), small intestine (38), and stomach (35), a partial gastrectomy, small bowel resection, colectomy, 2 cholecystectomies, and 1 appendectomy. RESULTS: There were 13 males and 7 females. Nine patients were children (10 y and younger) and 11 were adults. Age at diagnosis ranged from 6 months to 62 years (median, 35.5 y), and age at biopsy ranged from 10 months to 67 years (median, 38 y). Esophageal samples often showed intraepithelial neutrophils, accompanied by candida. Half of patients' esophageal biopsies had prominent intraepithelial lymphocytosis, one of which also had prominent apoptosis. The stomachs of 67% of patients lacked plasma cells. Most showed lymphoid aggregates. An increase in apoptosis was detected in biopsies from a third. About 20% had a lymphocytic gastritis pattern. Intraepithelial neutrophils were found in a subset, accompanied by various infections [cytomegalovirus (CMV), Helicobacter pylori, and Cryptosporidium]. Granulomas were found in 1 patient. Gastric adenocarcinoma was identified in one patient. There was a paucity of small bowel plasma cells in the majority of patients (68%). The small bowel showed prominent lymphoid aggregates in about half (47%). An increase in apoptosis was detected in specimens from about 20%. Increased intraepithelial lymphocytes (IELs) were found in samples from over half of patients (63%), most of whom (83%) also had villous blunting, mimicking celiac disease. Intraepithelial neutrophils were found in a subset (32%) and correlated with CMV and Cryptosporidium infections. Granulomas were seen in biopsies from 2 patients (11%). One patient had a collagenous enteritis pattern (accompanied by a collagenous colitis pattern). One patient had autoimmune enteritis; biopsies from this patient were initially relatively normal but later displayed prominent crypt apoptosis and loss of goblet cells. In colon samples, a paucity of plasma cells was seen in 10 patients (63%). The colon showed lymphoid aggregates in most patients (81%). Apoptosis was prominent in samples from half of the patients (50%). Biopsies from 6 patients had a lymphocytic colitis pattern (38%) and 2 patients had a collagenous colitis pattern. Intraepithelial neutrophils were found in samples from most patients (88%). Crypt distortion was seen in 6 of these patients (43%), thereby mimicking ulcerative or Crohn colitis. Granulomas were found in 3 patients (19%). CMV was detected in 1 patient. The appendix from 1 patient showed Cryptosporidium and acute serositis with a paucity of plasma cells and an increase in apoptosis. The gallbladder from 1 patient showed acute cholecystitis, and another patient's gallbladder lacked plasma cells. CONCLUSIONS: GI tract CVID displays a wide spectrum of histologic patterns. Its features can mimic lymphocytic colitis, collagenous enterocolitis, celiac disease, lymphocytic gastritis, granulomatous disease, acute graft-versus-host disease, and inflammatory bowel disease. In fact, in our series, we found patients with a prior diagnosis of celiac disease (25%) and inflammatory bowel disease (35%), including Crohn disease (15%). The diagnosis of CVID may be suspected on the basis of the lack of plasma cells in a GI biopsy, but because this feature is only present in about two-thirds of patients, the diagnosis cannot always be suggested in isolation of other clinical and laboratory findings.