https://orcid.org/0000-0002-4698-9948
CASE REPORT
We present a 32-year-old male sewer and water main laborer who reported a history of diarrhea since the age of 16. His past medical history was significant for recurrent sinus infections, community acquired pneumonia, and inguinal abscesses. Diarrhea worsened over years, leading to presentation with profound weight loss, anemia, and hypoalbuminemia. He had normal tissue transglutaminase levels, panhypogammaglobulinemia, and negative HLA-DQ2 and DQ8. Panendoscopy demonstrated flattened duodenal folds, and histology reported villous atrophy, intraepithelial lymphocytosis, plasma cell loss, and giardiasis. Abdomen CT scan showed panenteritis, incidental small bowel intussusception, and extensive mesenteric lymphadenopathy (Fig. 1), which were found to be reactive in nature on lymph node excision. Thorax CT scan showed features suggestive of bronchiectasis. Pneumococcal vaccination challenge to assess for a humoral response confirmed the diagnosis of common variable immunodeficiency (CVID).
Coronal CT image performed with IV and oral contrast shows 2 areas of enteroenteric intussusception (white arrows). Multiple prominent enlarged mesenteric lymph nodes are also present.
Initial treatment with corticosteroids led to marked improvement in diarrhea and weight gain, after which he was transitioned to mercaptopurine as a steroid-sparing agent. Diarrhea and weight loss returned after steroid taper, and thus vedolizumab was initiated off-label at standard dosing (300 mg IV at weeks 0, 2, and 6 for induction, then every 8 weeks in maintenance). Vedolizumab rapidly induced clinical improvement, with reduced diarrhea. Endoscopic and histological improvement was also observed on duodenal biopsies, but giardiasis recurred on vedolizumab, despite initial eradication and several subsequent courses of metronidazole.
DISCUSSION
Common variable immunodeficiency is the most common type of severe antibody deficiency with a prevalence of 1 in 50,000 to 200,000 individuals.1 It has many systemic manifestations, including recurrent respiratory and sinopulmonary infections. Gastrointestinal manifestations affect approximately 20%–50% of patients, most commonly presenting with chronic diarrhea, anemia, and villous atrophy.1,2 Diagnosing CVID can be difficult compared with more common conditions such as celiac disease, infections, and drug-related injury.
Many treatment modalities have been proposed for CVID-associated enteropathy including corticosteroids, antibiotics to treat concurrent bacterial overgrowth, and tumor necrosis factor antagonists.3 Here, we present a case of CVID-associated enteropathy successfully treated with an α4β7 integrin antagonist, vedolizumab. Vedolizumab inhibits intestinal T-cell translocation by blocking integrin interactions with mucosal vascular addressin cell adhesion molecule 1, reducing lymphocyte-mediated inflammation.4 Recently, Boland et al described in a case series that 2 out of 3 patients with CVID were able to achieve clinical and endoscopic remission with vedolizumab.5 Our case highlights that even deeper histological improvement can be achieved with vedolizumab for CVID-associated enteropathy, although the gut-targeted nature may paradoxically predispose to intestinal infection.
Conflicts of interest: VJ has received consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena pharmaceuticals, Genetech, Pendopharm, Sandoz, Merck, Takeda, Janssen, Robarts Clinical Trials, Topivert, Celltrion; speaker’s fees from Takeda, Janssen, Shire, Ferring, Abbvie, Pfizer. The remaining authors have no conflicts to declare.
