Acute esophageal necrosis (black esophagus)

INTRODUCTION — Acute esophageal necrosis, also known as black esophagus and necrotizing esophagitis, is a rare syndrome characterized by a striking diffuse circumferential black appearance of the esophageal mucosa that almost universally affects the distal esophagus and stops at the gastroesophageal junction [1-5].

This topic will review the epidemiology, clinical manifestations, diagnosis, and management of acute esophageal necrosis. The clinical manifestations, diagnosis, and management of other causes of esophagitis are discussed in detail, separately. (See "Clinical manifestations and diagnosis of gastroesophageal reflux in adults" and "Medical management of gastroesophageal reflux disease in adults" and "Clinical manifestations and diagnosis of eosinophilic esophagitis (EoE)" and "Treatment of eosinophilic esophagitis (EoE)" and "Pill esophagitis".)

EPIDEMIOLOGY — Acute esophageal necrosis is rare with an estimated prevalence of up to 0.2 percent in autopsy series [6,7]. In endoscopy series, the prevalence of acute esophageal necrosis has ranged from 0.01 to 0.28 percent of cases [7-13]. The incidence of acute esophageal necrosis appears to be more than four times higher in men as compared with women, and patients have a mean age of 68 years at diagnosis [5,8,11]. Acute esophageal necrosis occurs in patients with poor nutritional status [14] and multiple comorbidities [15].

ETIOLOGY AND PATHOGENESIS — The etiology of acute esophageal necrosis is unclear, but ischemia and gastric outlet obstruction may be inciting events [16-18]. In case reports, acute esophageal necrosis has been associated with broad spectrum antibiotic use, infections (eg, Candida albicans, cytomegalovirus, herpes virus, and Klebsiella pneumoniae), gastric volvulus, a paraesophageal hernia, hyperglycemia, diabetic ketoacidosis, an underlying malignancy, Stevens-Johnson syndrome, prolonged vomiting following alcohol binging, cocaine use, alcoholic hepatitis, lactic acidosis, and aortic dissection [8,11,19-33].

According to the "two hit" hypothesis, there is an initial event (ie, low flow vascular state), which then predisposes the esophageal mucosa to a severe topical injury (ie, by reflux of acid and pepsin). Gastric outlet obstruction leads to an accumulation of fluid in the stomach, which can promote esophageal reflux resulting in direct injury with necrosis. In support of this hypothesis is the observation that temporary reduction of esophageal blood flow can result in extensive esophageal necrosis, which resolves rapidly when flow is restored [34]. Furthermore, acute esophageal necrosis tends to occur in the distal third of the esophagus, which is relatively hypovascular compared with other esophageal segments. Finally, the necrosis of the esophageal mucosa and submucosa, microscopic thrombosis, and rapid recovery are similar to the changes seen in ischemic colitis. (See "Colonic ischemia", section on 'Diagnosis'.)

CLINICAL MANIFESTATIONS

Clinical presentation — Approximately 70 percent of patients with acute esophageal necrosis present with upper gastrointestinal bleeding with hematemesis and melena. Symptoms can develop rapidly following an inciting event and have been reported to occur within 18 hours [8,11,14]. Other gastrointestinal symptoms include dysphagia, epigastric pain and chest pain. Patients may also have symptoms related to their underlying disorder and signs of sepsis, including tachycardia and hypotension. (See 'Etiology and pathogenesis' above.)

Laboratory findings — Laboratory findings are not specific to acute esophageal necrosis and are often due to the underlying disease. They include lactic acidosis, hypoalbuminemia, anemia, renal insufficiency, and hyperglycemia.

Prognostic factors — Advanced age, high pulse rate, low hemoglobin, and low albumin on presentation are associated with increased mortality during the initial hospital admission [35].

DIAGNOSIS — Acute esophageal necrosis is often diagnosed incidentally in patients undergoing upper endoscopy for evaluation of upper gastrointestinal bleeding. While the endoscopic appearance is suggestive, esophageal biopsies are needed to exclude other etiologies and establish the diagnosis of acute esophageal necrosis.

Endoscopy and biopsy — On upper endoscopy, acute esophageal necrosis is characterized by circumferential black discoloration with underlying friable hemorrhagic tissue and by a sharp transition to normal-appearing mucosa at the gastroesophageal junction (picture 1 and picture 2). It usually involves the distal third of the esophagus, although proximal involvement has been described [36,37]. As the disease progresses, the esophagus may become partially covered with thick, white exudates that can be dislodged easily to reveal pink granulation tissue. These exudates most likely represent sloughed mucosal cells [29].

Biopsies of the esophageal mucosa serve to differentiate acute esophageal necrosis from other conditions in which the mucosa appears darkened and to rule out infectious causes of acute esophageal necrosis (eg, Candida albicans, cytomegalovirus, herpes simplex virus, and Klebsiella pneumoniae). On histology, there is severe necrosis of the esophageal mucosa and submucosa. Inflammation and partial destruction of adjacent muscle fibers may occasionally be seen and blood vessels are sometimes thrombosed or occluded. (See 'Differential diagnosis' below.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis includes other conditions in which the esophageal mucosa may also appear darkened. Acute esophageal necrosis can be differentiated from these conditions by history and by esophageal biopsy.

●Melanosis – Esophageal melanosis has been described in patients with underlying chronic esophagitis [38-40]. It is most commonly seen in the distal esophagus. In contrast to acute esophageal necrosis, the discoloration is often focal or scattered. Biopsies reveal melanocytes with pigment staining characteristics similar to melanin.

●Pseudomelanosis – Pseudomelanosis is due to tissue deposition of pseudomelanin, a "wear and tear" pigment derived from lysosomal degradation. On histology, a brown pigment composed of lipofuscin and melanin can be visualized within macrophages [41].

●Melanoma – Primary pigmented melanoma of the esophagus is rare. It usually originates in the mid and lower esophagus and has a polypoid appearance. The diagnosis is made by the presence of junctional melanocytic activity on histologic evaluation of the esophageal mucosa [42-44].

●Acanthosis nigricans – Acanthosis nigricans is characterized by velvety, verrucous, hyperpigmented skin and mucosal plaques. While it can be benign, it can also be a paraneoplastic phenomenon, commonly associated with intra-abdominal malignancies [45,46]. (See "Cutaneous manifestations of internal malignancy".)

●Coal dust – Coal dust or carbon is the most common exogenous pigment to deposit in human body tissues [47]. The mechanism by which coal dust is deposited in the esophagus is unclear.

●Caustic ingestion – Severe esophageal damage caused by ingestion of corrosive agents can cause sloughing of the mucosa and black discoloration of the esophageal wall. Such patients may be able to provide a history of caustic ingestion and may have associated oropharyngeal burns. (See "Caustic esophageal injury in adults".)

●Pseudomembranous esophagitis – Pseudomembranous esophagitis has generally been reported in association with serious systemic illness. A thin, yellow or black, concentric membrane coats the distal and, less commonly, the entire esophagus. It can be dislodged, revealing a friable underlying mucosa. On histology, the pseudomembrane has no basement membrane and is composed of fibrinous exudate and mixed inflammatory cells. The esophagitis involves the full thickness ulceration with acute or chronic inflammation [48]. Some cases of pseudomembranous esophagitis may represent a variant of acute esophageal necrosis.

The differential diagnosis of upper gastrointestinal bleeding is discussed in detail, separately. (See "Causes of upper gastrointestinal bleeding in adults".)

MANAGEMENT — There are limited data to guide the management of acute esophageal necrosis, and management is largely based upon clinical experience.

Initial management consists of volume expansion with intravenous fluids and treatment of the underlying illness. Gastric acid suppression with intravenous proton pump inhibitors should be used to reduce additional acid peptic injury to the esophagus. Oral intake should be avoided for at least 24 hours, after which sucralfate suspension should be considered because of its theoretical role in the prevention of further esophageal injury due to its cytoprotective effects and its ability to bind pepsin and stimulate mucus secretion [49]. The optimal timing for resuming oral intake is unclear. We initiate parenteral nutrition after 24 hours in patients with poor nutritional status.

Nasogastric tubes should be withheld unless used to decompress a gastric outlet obstruction or if persistent vomiting is present. A decision regarding antimicrobial and antifungal use should be made on an individual basis, especially in the setting of patients who are critically ill or appear to be septic. (See "Evaluation and management of suspected sepsis and septic shock in adults".)

Clinically significant bleeding can be treated with submucosal epinephrine injection [50]. If hemostasis is not achieved, endoscopic placement of a self-expandable metallic-covered stent has been successfully used [51]. Balloon tamponade should be avoided since it has been associated with esophageal perforation [52].

NATURAL HISTORY

Disease course — With supportive care, resolution of endoscopic findings occurs in most patients [11]. However, mortality rates in patients with acute esophageal necrosis range from 13 to 35 percent [8,9,11,53]. Mortality is largely due to the underlying disease with only 6 percent of deaths being directly attributable to complications of acute esophageal necrosis.

Complications

●Esophageal perforation – Esophageal perforation is an acute complication of esophageal necrosis that occurs in less than 7 percent of patients, but requires urgent surgical intervention given its high associated mortality [14]. The presence of persistent severe retrosternal or back pain may indicate the development of an esophageal perforation. Patients with an esophageal perforation may have crepitus on palpation of the chest wall due to subcutaneous emphysema. In patients with mediastinal emphysema, mediastinal crackling with each heartbeat may be heard on auscultation, especially if the patient is in the left lateral decubitus position (Hamman's sign). Within hours of the perforation, patients can develop odynophagia, dyspnea, and sepsis and have fever, tachypnea, tachycardia, cyanosis, and hypotension on physical examination. A pleural effusion may also be detected. The management of esophageal perforation is discussed in detail, separately (see "Surgical management of esophageal perforation"). Surgery is the most common treatment for esophageal perforations, however, placement of a fully covered self-expandable metallic stent [54] or the video-assisted thoracoscopic surgery to place an intrathoracic flushing-system-drain near the perforation [55] have also been used with success [56].  

●Esophageal stricture – Esophageal strictures are long-term complications of acute esophageal necrosis and occur in 25 to 40 percent of patients [5]. Patients with esophageal strictures usually present with gradually progressive dysphagia and require endoscopic dilation (see "Endoscopic interventions for nonmalignant esophageal strictures in adults"). Placement of a fully covered self-expandable metallic stent has been successfully used to treat long esophageal strictures [57]. Surgery is reserved for patients with strictures that are refractory to endoscopic management [26,58].

●Bleeding – Approximately 70 percent of patients with acute esophageal necrosis present with upper gastrointestinal bleeding. Most patients respond to conservative treatment and proton pump inhibitors. Placement of a fully covered self-expandable metallic stent has been successfully used to control bleeding in a patient requiring anticoagulation on presentation [59].

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Acute esophageal necrosis is a rare syndrome characterized by a striking diffuse circumferential black appearance of the esophageal mucosa that almost universally affects the distal esophagus and stops at the gastroesophageal junction. The incidence of acute esophageal necrosis appears to be more than four times higher in men as compared with women, and patients have a mean age of 68 years at diagnosis. (See 'Epidemiology' above.)

●Etiology – The etiology of acute esophageal necrosis is unclear, but ischemia and gastric outlet obstruction with gastroesophageal reflux may be inciting events. Acute esophageal necrosis has been associated with broad spectrum antibiotic use, infections (eg, Candida albicans, cytomegalovirus, herpes simplex virus, and Klebsiella pneumoniae), gastric volvulus, a paraesophageal hernia, hyperglycemia, diabetic ketoacidosis, an underlying malignancy, Stevens-Johnson syndrome, prolonged vomiting following alcohol binging, alcoholic hepatitis and lactic acidosis, and aortic dissection. (See 'Etiology and pathogenesis' above.)

●Clinical manifestations – Approximately 70 percent of patients with acute esophageal necrosis present with upper gastrointestinal bleeding with hematemesis and melena. Other gastrointestinal symptoms include dysphagia and epigastric or retrosternal chest pain. Patients may also have symptoms related to their underlying disorder and signs of sepsis, including tachycardia and hypotension. (See 'Clinical manifestations' above.)

●Diagnosis

•Endoscopic appearance – Acute esophageal necrosis is often diagnosed incidentally in patients undergoing upper endoscopy for evaluation of upper gastrointestinal bleeding. On upper endoscopy, acute esophageal necrosis is characterized by circumferential black discoloration with underlying friable hemorrhagic tissue and by a sharp transition to normal-appearing mucosa at the gastroesophageal junction (picture 1 and picture 2). It usually involves the distal third of the esophagus. As the disease progresses, the esophagus may become partially covered with thick, white exudates that can be dislodged easily to reveal pink granulation tissue. (See 'Endoscopy and biopsy' above.)

•Histology – While the endoscopic appearance is suggestive, esophageal biopsies are needed to exclude other etiologies and establish the diagnosis of acute esophageal necrosis. The differential diagnosis includes melanosis, pseudomelanosis, acanthosis nigricans, malignant melanoma, and charcoal/dust adsorption. (See 'Diagnosis' above and 'Differential diagnosis' above.)

●Management – Initial management consists of volume expansion with intravenous fluids and treatment of the underlying illness. Patients should be treated with an intravenous proton pump inhibitor and be kept nil per os (NPO) for at least 24 hours. A nasogastric tube should be avoided unless patients are vomiting or have gastric outlet obstruction. Antibiotics should be considered on an individual patient basis, usually depending on the severity and cause of the underlying illness. (See 'Management' above.)

●Disease course and complications – Esophageal perforation is an acute complication of esophageal necrosis that occurs in less than 7 percent of patients. It should be suspected in patients with persistent severe retrosternal or back pain and requires prompt surgical intervention. Mortality rates in patients with acute esophageal necrosis range from 13 to 35 percent. Mortality is largely due to the underlying disease with only 6 percent of deaths being directly attributable to complications of acute esophageal necrosis. With supportive care, resolution of endoscopic findings occurs in most patients. The most common long-term complication is esophageal stricture formation, which often requires esophageal dilation. (See 'Natural history' above and "Overview of esophageal injury due to blunt or penetrating trauma in adults" and "Endoscopic interventions for nonmalignant esophageal strictures in adults".)