Esophagitis


Article Author:
Catiele Antunes


Article Editor:
Ashish Sharma


Editors In Chief:
Jon Parham
Jon Sivoravong


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Kyle Blair
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
10/6/2019 2:23:29 PM

Introduction

Esophagitis refers to inflammation or injury to the esophageal mucosa. There are many causes of esophagitis and essentially the presentation is similar.[1][2]

Etiology

Professionals have identified several etiologies. Reflux or erosive esophagitis that occurs as a consequence of reflux of gastric contents into the stomach leading to mucosal injury is one of the most common causes of esophagitis. Radiation, infections, local injury caused by medications (pill esophagitis), and eosinophilic esophagitis (EoE) are also other possible etiologies.[3]

Epidemiology

Epidemiology varies depending on the subset to which one refers.[4][5][6]

  • Professionals estimate that 1% of the population suffers from erosive esophagitis.
  • Medication-induced esophagitis has an estimated incidence of 3.9 per 100,000 population per year with a mean age at diagnosis of 41.5 years.
  • Many studies have tried to identify the most accurate incidence and prevalence of eosinophilic esophagitis. The estimated incidence is 0.35 per 100,000 population with a prevalence of 55 per 100,000 population.
  • Radiation esophagitis is a relatively frequent complication of radiation therapy. Acute injury invariably occurs at doses of 6000 cGy given in fractions of 1000 cGy per week. Lower doses or longer schedules are associated with lower rates of radiation esophagitis.  
  • For infectious esophagitis, the numbers are not very easy to define. One thing that is certain is that is way more prevalent is patients who are immunocompromised such as HIV-infected patients and patients with hematological malignancies.

Pathophysiology

The pathophysiology also depends in large part on the subset of esophagitis to which one refers.[7][8][9]

  • Reflux esophagitis: This is the pathophysiology involved in reflux of gastric content into the esophagus leading to mucosal injury. Several mechanisms take place in the pathophysiology of reflux. See more information in the Gastroesophageal Reflux Disease (GERD) chapter. Briefly, the lower esophageal sphincter (LES) seems to have decreased tone and increased transient relaxations. These factors facilitate the anterograde flow of acid. Also, patients with large hiatal hernias seem to have a higher incidence of reflux for since they contribute to a decreased tone in the LES. In contrast, any conditions that decrease esophageal peristalsis or affects saliva content can affect the protective mechanisms in place to prevent esophageal injury, contributing to the development of reflux esophagitis.
  • Medication-induced esophagitis: The pathogenesis of medication-induced esophagitis involves a direct irritant effect and disruption of cytoprotective barriers. Researchers hypothesize that prolonged contact of irritants with the esophageal mucosa can lead to damage. Medications like doxycycline, tetracyclines, and ferrous sulfate can cause local caustic injury as they have a pH of less than three once dissolved in water or saliva. Other medications such as potassium chloride can cause tissue destruction and vascular injury due to its hyperosmolar nature.
  • Eosinophilic esophagitis: The pathogenesis of EoE is incompletely defined. Considerable evidence suggests that eosinophilic esophagitis is an allergic disorder induced by antigen sensitization either through foods and/or aeroallergens. Eotaxin, interleukin 5 (IL-5) and STAT6 may play important roles. Some patients have at least partially improved symptoms with acid suppression therapy suggesting that acid reflux may be a contributor.
  • Radiation esophagitis: The pathophysiology involves DNA damage and cell death from high-energy electrons leading to the formation of volatile oxygen free radicals. The radiation injury can be acute or chronic. In the acute phase, radiation destroys epithelial cells and interferes with proliferation. Small doses can lead to villous blunting and minor alterations in mucosal formation, but larger doses can denude extensive regions of the mucosa. The chronic injury seems to involve small vessel ischemic injury. Endothelial inflammation coupled with smooth muscle and fibroblast proliferation compromise blood flow into the small vessels. Excessive fibrosis and the presence of atypical fibroblasts characterizes the chronic radiation injury. Progressive injury can lead to stricturing, ulceration, fistulization and even perforation.
  • Infectious esophagitis: Candida albicans infection is the most common cause of infectious esophagitis. The first step in the pathophysiology involves colonization with mucosal adherence and proliferation. The second step involves impairing the host defense mechanisms. C. albicans is a normal component of oral flora, but it can become a problem if their number increases (e.g., with the use of antibiotics) or if the patient is immunosuppressed (e.g., by therapy with corticosteroids). Herpes simplex virus (HSV) is the most common cause of viral esophagitis. It infects the squamous epithelium leading to vesicles and then ulcerations. Cytomegalovirus (CMV), Epstein-Barr (EBV) and varicella-zoster (VZV) are other viral causes of viral esophagitis.

History and Physical

The most common symptoms are chest pain, odynophagia, and dysphagia. Patients with EoE can present with food impaction. If the esophagitis is severe and leads to strictures, fistulization, and perforation, patients can present with symptoms related to those.

Evaluation

Diagnosis is usually achieved with endoscopy and biopsies. If the history is very suggestive of medication-induced (pill) esophagitis, endoscopy may not be initially required. Patients with eosinophilic esophagitis will have a characteristic eosinophilic infiltration (> 15 eosinophils per high-power field). Histology can also be helpful in diagnosis infectious etiologies. Multinucleated giant cells with ballooning and degeneration of squamous cells are diagnostic of HSV esophagitis with Cowdry type A inclusions being pathognomonic. Large cells with both intracytoplasmatic inclusions and amphophilic intranuclear inclusions are suggestive of CMV esophagitis.[10][4]

Patients with eosinophilic esophagitis will have a characteristic eosinophilic infiltration (> 15 eosinophils per high-power field). Histology can also be helpful in diagnosis infectious etiologies. Multinucleated giant cells with ballooning and degeneration of squamous cells are diagnostic of HSV esophagitis with Cowdry type A inclusions being pathognomonic. Large cells with both intracytoplasmatic inclusions and amphophilic intranuclear inclusions are suggestive of CMV esophagitis.

Furthermore, the appearance of the mucosal lesions on endoscopy can help with diagnosis. In patients with suspected eosinophilic esophagitis, endoscopy may reveal white exudates or papules, red furrows, corrugated concentric rings, and strictures; but endoscopy may be normal in up to 10% of patients. Endoscopic signs of candidiasis are diffuse, linear, yellow-white plaques adherent to the mucosa. CMV esophagitis is characterized by several large, shallow, superficial ulcerations. HSV esophagitis results in multiple small, deep ulcerations.

Treatment / Management

Treatment depends on the etiology. If the etiology is acid reflux, use of H2 blockers or proton-pump inhibitors is indicated, along with lifestyle modifications. If the etiology is medication-induced esophagitis, the medication should be stopped if possible or otherwise; the patient should be instructed to take pills with 4 oz of water and remain upright for 30 min after taking the pills. If EoE is the etiology, the treatment will include acid suppression, topical or systemic steroids, dietary modification and endoscopic therapies such as dilations is strictures are present. If etiology is infectious, target therapy is indicated. For C.  albicans, esophagitis treatment is with Nystatin or Fluconazole. For HSV esophagitis, treatment is oral or intravenous acyclovir and Foscarnet for those who are non-responders. For CMV esophagitis, treatment is with Gancyclovir intravenously.[11][12][13]

Surgical Oncology

  • Pericarditis
  • Esophageal stricture
  • Coronary artery disease
  • Pneumonia
  • Peptic ulcer disease
  • Pulmonary embolism

Complications

  • Bleeding
  • Stricture
  • Barrett esophagus
  • Perforation
  • Laryngitis
  • Aspiration pneumonitis

Enhancing Healthcare Team Outcomes

There are many causes of esophagitis and healthcare workers in many disciplines will encounter these patients. To avoid delay in diagnosis, a multidisciplinary approach is necessary. The prognosis for most patients is good with prompt treatment, but ultimately the outcomes depend on the underlying cause. When esophagitis is recurrent, it can lead to anxiety and absenteeism from work because of the need to rule out other more serious causes of chest pain. Untreated esophagitis can lead to stricture formation and malnutrition. Both bleeding and perforation are also relatively common complications. Some patients may aspirate and develop pneumonitis or worsening of asthma. In most patients who do not change their lifestyle, recurrences are common, and thus life long therapy is required. In immunocompromised patients, both candida and herpes can lead to severe pain, dysphagia, and weight loss. Patient education is key when a diagnosis of esophagitis is made. The patient should be told to sleep with the head of bed elevated, avoid lying supine after a meal and lose weight. The patient should also avoid caffeinated beverages, alcohol and discontinue smoking. Finally, the patient should be told to avoid NSAIDS.[14][15]


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Esophagitis - Questions

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Which of the following infections can cause esophagitis?



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Which statement about esophagitis is false?



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A 60-year-old obese, White male is diagnosed with esophagitis during an endoscopy performed for epigastric pain. He asks you about the therapeutic options. Which statement about the treatment of esophagitis is false?



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Which of the following organisms does not cause viral esophagitis?



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Which condition is most likely to cause non-radiating pain that is midepigastric?



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Regarding acute esophagitis, which statement is false about the mnemonic "CRIER" when recalling etiologies?



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A 37-year-old female with chronic renal failure is admitted with hematemesis and odynophagia. An HIV test is negative, and vital signs are stable. Esophagogastroduodenoscopy (EGD) reveals pan-erosive esophagitis that is treated with intravenous pantoprazole and fluconazole without improvement. What is the next step in management?



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Which of the following organisms does not cause esophagitis?



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Esophagitis - References

References

Habbal M,Scaffidi MA,Rumman A,Khan R,Ramaj M,Al-Mazroui A,Abunassar MJ,Jeyalingam T,Shetty A,Kandel GP,Streutker CJ,Grover SC, Clinical, endoscopic, and histologic characteristics of lymphocytic esophagitis: a systematic review. Esophagus : official journal of the Japan Esophageal Society. 2018 Oct 29     [PubMed]
Gomez Torrijos E,Gonzalez-Mendiola R,Alvarado M,Avila R,Prieto-Garcia A,Valbuena T,Borja J,Infante S,Lopez MP,Marchan E,Prieto P,Moro M,Rosado A,Saiz V,Somoza ML,Uriel O,Vazquez A,Mur P,Poza-Guedes P,Bartra J, Eosinophilic Esophagitis: Review and Update. Frontiers in medicine. 2018     [PubMed]
Hoversten P,Kamboj AK,Katzka DA, Infections of the esophagus: an update on risk factors, diagnosis, and management. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus. 2018 Oct 8     [PubMed]
Kim HP,Dellon ES, An Evolving Approach to the Diagnosis of Eosinophilic Esophagitis. Gastroenterology     [PubMed]
Wang F,Li G,Ning J,Chen L,Xu H,Kong X,Bu J,Zhao W,Li Z,Wang X,Li X,Ma J, Alcohol accumulation promotes esophagitis via pyroptosis activation. International journal of biological sciences. 2018     [PubMed]
Ansari SA,Iqbal MUN,Khan TA,Kazmi SU, Association of oral Helicobacter pylori with gastric complications. Life sciences. 2018 Jul 15     [PubMed]
Nejat Pish-Kenari F,Qujeq D,Maghsoudi H, Some of the effective factors in the pathogenesis of gastro-oesophageal reflux disease. Journal of cellular and molecular medicine. 2018 Oct 15     [PubMed]
Goyal A, Eosinophilic esophagitis: short and long-term considerations. Current opinion in pediatrics. 2018 Oct     [PubMed]
Davis BP, Pathophysiology of Eosinophilic Esophagitis. Clinical reviews in allergy     [PubMed]
DeBoer EM,Kinder S,Duggar A,Prager JD,Soden J,Deterding RR,Ruiz AG,Jensen EL,Weinman J,Wine T,Fortunato JE,Friedlander JA, Evaluating the yield of gastrointestinal testing in pediatric patients in aerodigestive clinic. Pediatric pulmonology. 2018 Nov     [PubMed]
Ishimura N,Sumi S,Okada M,Mikami H,Okimoto E,Nagano N,Araki A,Tamagawa Y,Mishiro T,Oshima N,Ishihara S,Maruyama R,Kinoshita Y, Is Asymptomatic Esophageal Eosinophilia the Same Disease Entity as Eosinophilic Esophagitis? Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2018 Aug 23     [PubMed]
Huang KZ,Jensen ET,Chen HX,Landes LE,McConnell KA,Almond MA,Johnston DT,Durban R,Jobe L,Frost C,Donnelly S,Antonio B,Safta AM,Quiros JA,Markowitz JE,Dellon ES, Practice Pattern Variation in Pediatric Eosinophilic Esophagitis in the Carolinas EoE Collaborative: A Research Model in Community and Academic Practices. Southern medical journal. 2018 Jun     [PubMed]
James C,Assa'ad A, The Global Face of Eosinophilic Esophagitis: Advocacy and Research Groups. Clinical reviews in allergy     [PubMed]
Jensen ET,Gupta SK, Early Life Factors and Eosinophilic Esophagitis: Building the Evidence. Journal of pediatric gastroenterology and nutrition. 2018 Nov     [PubMed]
Pan J,Cen L,Chen W,Yu C,Li Y,Shen Z, Alcohol Consumption and the Risk of Gastroesophageal Reflux Disease: A Systematic Review and Meta-analysis. Alcohol and alcoholism (Oxford, Oxfordshire). 2018 Sep 4     [PubMed]

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