An Unusual Cause of Esophagitis

Question: A 45-year-old man who had unremarkable past digestive disease history was admitted with a 1-day history of chest discomfort. He developed chest tightness, chest pain, nausea, and swallowing obstruction in a few minutes after chewing an areca nut. His physical and electrocardiogram examinations were unremarkable for abnormalities. The pertinent laboratory testing revealed white blood cell count of 14.28 ⅹ 109/L, neutrophils of 11.89 ⅹ 109/L, total bilirubin of 46.3 μmol/L, and γ-glutamyl transferase of 96 U/L. A computed tomography scan found a soft tissue mass in the middle and lower esophagus, and the esophageal wall was swollen. The esophagogastroduodenoscopy showed a space-occupying lesion with ulceration and bleeding on the surface, which was located 25 cm from the incisors down to the gastric cardia, blocking the lumen (Figures A and B, the 3rd day after onset). The patient was given acid suppression, antibacterial, and nutritional replacement therapies in a community hospital. The symptoms of chest discomfort and nausea were relieved; however, the swallowing obstruction was not alleviated. On the 7th day after onset, the results of routine laboratory testing were within normal limits other than total bilirubin (27.5 μmol/L). Enhanced computed tomography showed eccentric stenosis of the lower esophageal lumen, considering an esophageal space-occupying lesion, which was likely to be malignant (Figures C and D). The double-contrast esophagogram showed that in the lower esophagus, about 5 cm away from the cardia, the esophageal wall was stiff, and the mucosa was discontinuous (Figures E and F). The second esophagogastroduodenoscopy showed a longitudinal ulcer covered with white fur, and the surrounding mucosa was elevated (Figures G and H, the 12th day after onset). Esophageal biopsy specimens showed areas of chronic inflammation, with no tumor cells being found (Figure I, hematoxylin and eosin stain, original magnification ⅹ40). The third esophagogastroduodenoscopy showed a longitudinal ulcer in the healing period, with white fur in the center and a slightly raised edge of the ulcer (Figures J and K, the 21st day after onset). Esophageal biopsy specimens showed areas of chronic inflammation (Figure L, hematoxylin and eosin stain, original magnification ⅹ40). What is the most likely diagnosis? See the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. The areca nut is the ripe seed of the palm tree that is widely cultivated in many Southeast Asian and tropical areas. Areca nut chewing is common in many areas, especially in the Asia-Pacific area. Both betel quid and areca nut have been classified as carcinogenic to human beings (Group 1) by the International Agency for Cancer Research,1Mehrtash H. Duncan K. Parascandola M. et al.Defining a global research and policy agenda for betel quid and areca nut.Lancet Oncol. 2017; 18: e767-e775Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar and they are significantly associated with oral and esophageal cancers. The predominant psychoactive agent in areca nut is arecoline, an alkaloid that operates as an agonist at muscarinic receptors.1Mehrtash H. Duncan K. Parascandola M. et al.Defining a global research and policy agenda for betel quid and areca nut.Lancet Oncol. 2017; 18: e767-e775Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar In addition, research also suggests that arecoline has weak nicotine agonism.2Papke R.L. Horenstein N.A. Stokes C. Nicotinic activity of arecoline, the psychoactive element of "betel nuts", suggests a basis for habitual use and anti-inflammatory activity.PLoS One. 2015; 10e0140907Crossref Scopus (75) Google Scholar Areca nut can produce various autonomic and psychoneurologic effects, including palpitations, increased blood pressure, a warm sensation, euphoria, and alertness. Previous studies have reported acute toxicity events caused by chewing of areca nuts, such as nausea, vomiting, dizziness, and even myocardial infarction, asthma, and tachypnea/dyspnea.3Li D.F. Xu Z.L. Yao J. A rare cause of esophageal mucosal and submucosal lesions.Rev Esp Enferm Dig. 2020; 112: 158Crossref PubMed Google Scholar However, acute areca nut poisoning with esophageal lesions as the primary manifestation is rarely reported. Regarding the currently reported cases, it mainly occurred in men aged 45–60 years who have the habit of chewing areca nut. The incidence of this disease is not yet available. The pathogenesis may be related to the cholinergic effect of arecoline and the direct stimulation of esophageal mucosa by arecoline. In addition, slaked lime is usually added to neutralize the weak acidity of areca nut during the processing of betel quid. Slaked lime can also stimulate the mucous of the digestive tract, causing corrosive esophagitis similar to the oral administration of strong alkali. Symptoms occurred within minutes of areca nut ingestion, such as chest tightness, chest pain, palpitations, dyspnea, nausea, and swallowing obstruction. Subxiphoid tenderness may be present on physical examination.3Li D.F. Xu Z.L. Yao J. A rare cause of esophageal mucosal and submucosal lesions.Rev Esp Enferm Dig. 2020; 112: 158Crossref PubMed Google Scholar Endoscopic findings are not specific, including mucosal congestion, edema, longitudinal erosions, and ulcers.3Li D.F. Xu Z.L. Yao J. A rare cause of esophageal mucosal and submucosal lesions.Rev Esp Enferm Dig. 2020; 112: 158Crossref PubMed Google Scholar,4Chen F. Zheng K. Liu W. Arecagenic oesophagitis: case report with imaging findings.Chin Med J (Engl). 2000; 113: 1054-1056PubMed Google Scholar In our case, the patient’s endoscopic findings were special. In the early stage of the disease, a space-occupying lesion can be seen in the lumen of the esophagus, with congestion, edema, and erosion on the surface blocking the lumen, similar to esophageal cancer. In the late stage of the disease, the esophageal mucosa developed longitudinal ulcers, which evolved into healing ulcers. At the same time, the patient’s symptoms of swallowing obstruction alleviated and then disappeared. Enhanced computed tomography and double-contrast esophagogram findings were similar to esophageal cancer. Nevertheless, biopsy specimens only showed chronic inflammation. The course of arecoline-related esophagitis is about 10–20 days,3Li D.F. Xu Z.L. Yao J. A rare cause of esophageal mucosal and submucosal lesions.Rev Esp Enferm Dig. 2020; 112: 158Crossref PubMed Google Scholar,4Chen F. Zheng K. Liu W. Arecagenic oesophagitis: case report with imaging findings.Chin Med J (Engl). 2000; 113: 1054-1056PubMed Google Scholar and the prognosis is good. The therapy focuses on a bland diet, acid suppression, mucosal protection, mucosal repair promotion, and supportive treatment. Our case ultimately showed the evolution of arecoline-related esophagitis. At the onset, endoscopic and radiological presentations were similar to those of esophageal cancer. When the patient has a history of chewing areca nut and experiences retrosternal discomfort or swallowing obstruction, physicians should consider the possibility of arecoline-related esophagitis. Endoscopy and biopsy are helpful for diagnosis. In addition, this disease may be misdiagnosed as acute myocardial infarction or aortic dissection. The patient’s symptoms gradually alleviated through acid suppression, protection of esophageal mucosa, and symptomatic supportive treatment and the esophageal mass disappeared in a short time. At present, the specific mechanism of arecoline-induced acute esophageal mucosal injury remains unclear; however, the mucosal injury gradually healed after stopping areca nut chewing and applying acid-suppressing and gastric mucosal protective drugs. Physicians should enhance their understanding of arecoline-related esophagitis and improve their ability to identify the cause of chest pain. If necessary, gastroscopy can be performed to clarify the cause. Avoid serious complications such as hematemesis and esophageal perforation caused by esophageal ulcers.