Esophagitis and its causes: Who is "guilty" when acid is found "not guilty"?

Esophagitis is mainly a consequence of gastroesophageal reflux disease, one of the most common diseases affecting the upper digestive tract. However the esophageal mucosa can also be targeted by some infectious, systemic or chemical conditions. Eosinophilic esophagitis (EoE) is an immune-mediated inflammatory disease, characterized by eosinophilic infiltration in the mucosa. Esophageal localization of Crohn's disease is not very common, but it should always be considered in patients with inflammatory bowel disease complaining of upper digestive tract symptoms. There are also forms of infectious esophagitis (e.g., Herpes simplex virus or Candida albicans) occurring in patients with a compromised immune system, either because of specific diseases or immunosuppressive therapies. Another kind of damage to esophageal mucosa is due to drug use (including oncologic chemotherapeutic regimens and radiotherapy) or caustic ingestion, usually of alkaline liquids, with colliquative necrosis and destruction of mucosa within a few seconds. Dysphagia is a predominant symptom in EoE, while infectious, drug-induced and caustic damages usually cause chest pain and odynophagia. Endoscopy can be useful for diagnosing esophagitis, although no specific pattern can be identified. In conclusion when a patient refers upper gastrointestinal tract symptoms and the diagnosis of gastro-esophageal reflux disease is not convincing we should always carefully investigate the patient's clinical history to consider possibilities other than the gastric refluxate.