Bacille Calmette-Guérin (BCG) Immunotherapy-Induced Celiac Crisis: A First Manifestation of Silent Celiac Disease in an Elderly Patient

Abstract

Purpose: Introduction: Celiac disease (CD) is an immune-mediated glutensensitive enteropathy with various clinical presentations. BCG, in addition to its role as a vaccine against tuberculosis, has been used as an immunotherapeutic agent in patients with bladder cancer by intravesical instillation. We present an elderly patient with new onset of celiac disease after intravesical treatment with BCG, the first such report to our knowledge. Case Report: An 81-year-old woman with recently diagnosed superficial bladder cancer, treated with resection and intravesical BCG instillation, was seen because of multiple episodes of spurious non-bloody diarrhea for 3 days associated with colicky abdominal pain, nausea and non-bilious vomiting with no fever. On arrival, she was hypotensive requiring aggressive intravenous hydration. Physical examination was otherwise unremarkable. Similar episodes occurred twice 3 months ago, 2 weeks after her fourth BCG dose, requiring hospitalization and fluid resuscitation. At that time she was treated empirically for Clostridium difficile colitis and discharged without any definitive diagnosis. This admission, work up revealed normocytic anemia, +fecal WBC, and negative findings for C. difficile toxin and stool culture tests for cryptosporidia and ova and parasites. CT scan of the abdomen was unremarkable. Tissue transglutaminase antibody and gliadin IgG were mildly elevated. Endoscopy-guided small intestinal biopsy showed typical pathological characteristics of CD. The patient responded to a gluten-free diet with marked improvement in her symptoms. The diagnosis of latent CD was subsequently reconfirmed by genetic analysis. Discussion: The exact mechanism of BCG action is unknown, but intravesical instillation triggers a variety of local immune responses including stimulation of CD4 T cells, macrophages, cytokines and IFN-γ resulting in tumor destruction. The systemic response to intravesical BCG instillation has not been studied and has been thought to have only local effect. However, rare cases of BCG-induced HLA B27-positive arthritis have been reported. We propose that this new emergence of latent CD shortly after BCG therapy in our elderly patient is not just a coincidence. The impact of systemic immune response and possibly new onset of autoimmune disorders, such as CD, with intravesical BCG needs to be investigated. Clinicians should consider the diagnosis of activated CD (perhaps including other inflammatory bowel diseases) in patients with a new onset of unexplainable diarrhea after BCG therapy. More studies will need to be done to further validate this relationship, which suggests wider risks of activating remote immune reactions with BCG.