AGA Clinical Practice Update on Esophageal Dysfunction Due to Disordered Immunity and Infection: Expert Review.

methodsThis expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Since systematic reviews were not performed, these BPA statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. DESCRIPTION: Infectious and immune-mediated esophageal disorders are poorly understood and often under-diagnosed conditions that lead to esophageal dysfunction and health care costs due to repeated procedures and a lack of understanding of their etiology and pathogenesis. Without a high index of suspicion, these disorders may be overlooked. Esophageal dysfunction may arise from active, localized infection and immune-mediated disease (ie, candida, etc.) or from an organ-specific manifestation of a more diffuse immune-mediated disease or infection (ie, systemic sclerosis, connective tissue disease, neurologic disease). These conditions can sometimes lead to neuromuscular dysfunction and subsequent esophageal dysmotility. Awareness of local and systemic processes that lead to esophageal dysfunction will improve patient outcomes by focusing therapeutics and limiting unnecessary procedures. Therefore, the purpose of this AGA Clinical Practice Update Expert Review is to provide BPA on diagnostic considerations of immune-mediated disorders that should be considered when encountering patients with dysphagia, heartburn, and odynophagia. Best Practice Advice Statements: BEST PRACTICE ADVICE 1: Gastroenterologists should be aware of the esophageal manifestations of systemic immunologic and infectious diseases to reduce diagnostic delay. Clinicians should identify if there are risks for inflammatory or infectious possibilities for a patient's esophageal symptoms and investigate for these disorders as a potential cause of esophageal dysfunction. BEST PRACTICE ADVICE 2: Once esophageal infection is identified, clinicians should identify whether accompanying signs/symptoms suggest immunocompromise leading to a more systemic infection. Consultation with an infectious disease expert will aid in guiding appropriate treatment. BEST PRACTICE ADVICE 3: If symptoms do not improve after therapy for infectious esophagitis, evaluation for refractory infection or additional underlying sources of esophageal and immunologic dysfunction should be performed. BEST PRACTICE ADVICE 4: In individuals with eosinophilic esophagitis (EoE) who continue to experience symptoms of esophageal dysfunction despite histologic and endoscopic disease remission, clinicians should be aware that some patients with EoE may develop motility disorders. Further evaluation of esophageal motility may be warranted. BEST PRACTICE ADVICE 5: In individuals with histologic and endoscopic features of lymphocytic esophagitis, clinicians should consider treatment of lymphocytic-related inflammation with proton-pump inhibitor therapy or swallowed topical corticosteroids and as needed esophageal dilation. BEST PRACTICE ADVICE 6: In patients who present with esophageal symptoms in the setting of hypereosinophilia (absolute eosinophil count [AEC] >1500 cells/uL), consider further work-up of non-EoE eosinophilic gastrointestinal (GI) disease, hypereosinophilic syndrome, and eosinophilic granulomatosis with polyangiitis (EGPA). Consultation with allergy/immunology may help guide further diagnostic work-up and treatment. BEST PRACTICE ADVICE 7: In individuals with rheumatologic diseases of systemic sclerosis (SSc), mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE), or Sjogren's disease, clinicians should be aware that esophageal symptoms can occur due to involvement of the esophageal muscle layer, resulting in dysmotility and/or incompetence of the lower esophageal sphincter. The degree of dysfunction is often especially significant in those with SSc or MCTD. BEST PRACTICE ADVICE 8: In individuals with Crohn's disease, clinicians should be aware that a minority of individuals can develop esophageal involvement from inflammatory, stricturing, or fistulizing changes with granulomas seen histologically. Esophageal manifestations of Crohn's disease tend to occur in individuals with active intestinal disease. BEST PRACTICE ADVICE 9: In individuals with dermatologic diseases of lichen planus or bullous disorders, clinicians should be aware that dysphagia can occur due to endoscopically visible esophageal mucosal involvement. Esophageal lichen planus, in particular, can occur without skin involvement and can be difficult to define on esophageal histopathology. BEST PRACTICE ADVICE 10: Clinicians should consider infectious and inflammatory causes of secondary achalasia during initial evaluation. One should query for any history of recent COVID infections, risks for Chagas disease, and symptoms or signs of eosinophilic disease.