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Esophagitis

Esophagitis is the inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation or irritation of the esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy. The major types of esophagitis are medication-induced, infectious, eosinophilic, corrosive, and acid reflux. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship typically present with odynophagia Odynophagia Epiglottitis, dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming "stuck." Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia, and retrosternal chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways. Diagnosis is by endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) and biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Laboratory tests and imaging are obtained, depending on the degree of damage and involvement of other organ systems. Treatment for esophagitis depends on the underlying etiology and includes dietary changes, avoidance of offending agents, antibiotic therapy, or proton pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols inhibitor use. In severe cases such as in corrosive injury, surgery may need to be performed. If left untreated, esophagitis can lead to complications such as strictures, metaplasia Metaplasia A condition in which there is a change of one adult cell type to another similar adult cell type. Cellular Adaptation of the esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy, and development of malignancy Malignancy Hemothorax.

Last updated: Jan 16, 2024

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

  • Esophagitis: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of or injury to the esophageal mucosa Esophageal Mucosa Circular innermost layer of the esophagus wall that mediates esophageal peristalsis which pushes ingested food bolus toward the stomach. Esophagus: Anatomy
  • Major etiologies:
    • Medication-induced/pill-induced esophagitis
    • Infectious esophagitis
    • Eosinophilic esophagitis
    • Corrosive esophagitis
    • Reflux esophagitis
  • Diagnosis is done by upper endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD); findings vary per etiology.

Mnemonic

To remember the common causes of esophagitis: “PIECE”

  • Pill-induced esophagitis
  • Infectious esophagitis
  • Eosinophilic esophagitis
  • Corrosive esophagitis
  • Etc. (reflux esophagitis)

Related videos

Medication-induced Esophagitis

Etiology

  • Antibiotics: tetracyclines Tetracyclines Tetracyclines are a class of broad-spectrum antibiotics indicated for a wide variety of bacterial infections. These medications bind the 30S ribosomal subunit to inhibit protein synthesis of bacteria. Tetracyclines cover gram-positive and gram-negative organisms, as well as atypical bacteria such as chlamydia, mycoplasma, spirochetes, and even protozoa. Tetracyclines, doxycycline, clindamycin Clindamycin An antibacterial agent that is a semisynthetic analog of lincomycin. Lincosamides
  • Anti-inflammatories: Nonsteroidal anti-inflammatory drugs ( NSAIDs NSAIDS Primary vs Secondary Headaches), aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs)
  • Bisphosphonates Bisphosphonates Bisphosphonates are pyrophosphate analogs most well-known for treating osteoporosis by preventing bone loss. Bisphosphonates end in the suffix “-dronate” or “-dronic acid” (e.g., alendronate, risedronate, pamidronate) and bind to hydroxyapatite crystals in bone, inhibiting osteoclast-induced bone resorption. Bisphosphonates: alendronate Alendronate A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis. Bisphosphonates, risedronate Risedronate Bisphosphonates
  • Others: potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes, quinidine Quinidine An optical isomer of quinine, extracted from the bark of the cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potentials, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission. Class 1 Antiarrhythmic Drugs (Sodium Channel Blockers), iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements supplements, ascorbic acid

Pathophysiology

  • Prolonged, direct contact between the medication(s) and the mucosa causes irritation, erosions Erosions Corneal Abrasions, Erosion, and Ulcers, and ulcerations
  • Frequently affects site(s) of anatomical narrowing (mid-esophagus, near level of the aortic arch Aortic arch Mediastinum and Great Vessels: Anatomy)
  • Mechanisms:
    • Disruption of the normal protective mucosal barrier: aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs), NSAIDs NSAIDS Primary vs Secondary Headaches
    • Local caustic damage (e.g., doxycycline is acidic once dissolved)
    • Hyperosmotic solutions contribute to tissue and vascular injury (e.g., potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes).

Risk factors

  • Occurs more often in elderly patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Position of patient (supine > upright)
  • Size of medication (delayed transit with large tablets)
  • Amount of fluid ingested with medication (intake of at least > 100 mL advised)

Clinical presentation

  • Heartburn Heartburn Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. Gastroesophageal Reflux Disease (GERD)
  • Retrosternal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Odynophagia Odynophagia Epiglottitis, dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia

Diagnosis

  • Clinical diagnosis based on history
  • Upper endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD):
    • Perform if with severe or persistent symptoms (despite discontinuation of the offending medication) 
    • Findings: discrete ulcer, with normal bordering mucosa
Cloxacillin-induced esophagitis

Stellate erosions in the midesophagus (white arrows) in a patient with cloxacillin-induced esophagitis

Image: “Cloxacillin: A New Cause of Pill-Induced Esophagitis” by Zezos P, Harel Z, Saibil F. License: CC BY 4.0

Prevention and management

  • Avoid the medication. 
  • Resolution expected in < 2 weeks after discontinuation.
  • If medication is necessary, take the medication with enough water and maintain an upright position for at least 30 minutes. 

Infectious Esophagitis: Cytomegalovirus (CMV)

Etiology

  • Past CMV infection + CD4 cell count < 50 cells/microL → ↑ risk of reactivation Reactivation Herpes Simplex Virus 1 and 2 → infection of organs such as the esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy
  • Gastrointestinal (GI) disease from CMV is not frequent but is a serious complication of AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS (acquired immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome syndrome).

Risk factors

  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS (occurrence decreased since availability of antiretroviral therapy Antiretroviral therapy Antiretroviral therapy (ART) targets the replication cycle of the human immunodeficiency virus (HIV) and is classified based on the viral enzyme or mechanism that is inhibited. The goal of therapy is to suppress viral replication to reach the outcome of undetected viral load. Anti-HIV Drugs)
  • Solid-organ and bone marrow transplant Bone marrow transplant Transfer of hematopoietic stem cells from bone marrow or blood between individuals within the same species (homologous transplantation) or transfer within the same individual (autologous transplantation). Hematopoietic stem cell transplantation has been used as an alternative to bone marrow transplantation in the treatment of a variety of neoplasms. Organ Transplantation recipients
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship receiving immunosuppressive therapy and chemotherapy Chemotherapy Osteosarcoma

Clinical presentation

  • Odynophagia Odynophagia Epiglottitis with dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, substernal burning pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Can have concurrent infection in retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy, lung, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy

Diagnosis

Diagnosis is done by upper endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD).

Cytomegalovirus esophagitis

Upper gastrointestinal endoscopic findings in a patient with cytomegalovirus esophagitis. An ulcer with a white base is seen in the esophagus.

Image: “Cytomegalovirus esophagitis developing during chemoradiotherapy for esophageal cancer” by Journal of Medical Case Reports. License: CC BY 4.0

Management

  • Ganciclovir Ganciclovir An acyclovir analog that is a potent inhibitor of the herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from aids-associated cytomegalovirus infections. Antivirals for Herpes Virus or foscarnet Foscarnet An antiviral agent used in the treatment of cytomegalovirus retinitis. Foscarnet also shows activity against human herpesviruses and HIV. Antivirals for Herpes Virus
  • With AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS: antiretroviral therapy Antiretroviral therapy Antiretroviral therapy (ART) targets the replication cycle of the human immunodeficiency virus (HIV) and is classified based on the viral enzyme or mechanism that is inhibited. The goal of therapy is to suppress viral replication to reach the outcome of undetected viral load. Anti-HIV Drugs

Infectious Esophagitis: Herpes Simplex Virus (HSV)

Etiology

Risk factors

  • AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS
  • Organ or bone marrow transplant Bone marrow transplant Transfer of hematopoietic stem cells from bone marrow or blood between individuals within the same species (homologous transplantation) or transfer within the same individual (autologous transplantation). Hematopoietic stem cell transplantation has been used as an alternative to bone marrow transplantation in the treatment of a variety of neoplasms. Organ Transplantation recipients
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship on immunosuppressive therapy

Clinical presentation

  • Odynophagia Odynophagia Epiglottitis with dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia
  • Retrosternal chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, +/- fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, concurrent oropharyngeal ulcers

Diagnosis

Diagnosis is done by upper endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD).

Herpetic esophagitis

Upper digestive endoscopy of a patient showing numerous injuries on the esophageal surface that are yellow-whitish in color, pleomorphic, and isolated small circular plaques with central erosions.

Image: “Herpetic esophagitis in immunocompetent medical student” by Marinho AV, Bonfim VM, de Alencar LR, Pinto SA, de Araújo Filho JA. License: CC BY 3.0

Management

  • Acyclovir Acyclovir A guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. Herpes Zoster (Shingles)
  • With HIV HIV Anti-HIV Drugs/ AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS: antiretroviral therapy Antiretroviral therapy Antiretroviral therapy (ART) targets the replication cycle of the human immunodeficiency virus (HIV) and is classified based on the viral enzyme or mechanism that is inhibited. The goal of therapy is to suppress viral replication to reach the outcome of undetected viral load. Anti-HIV Drugs

Infectious Esophagitis: Candidiasis

Etiology

  • Candida albicans Candida albicans A unicellular budding fungus which is the principal pathogenic species causing candidiasis (moniliasis). Candida/Candidiasis: most frequently occurring
  • Candida Candida Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis glabrata, Candida Candida Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis krusei: less common

Risk factors

Clinical presentation

  • Odynophagia Odynophagia Epiglottitis with dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia
  • May or may not have oral thrush

Diagnosis

Diagnosis is done by upper endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD).

  • White pseudomembrane Pseudomembrane Candida/Candidiasis or plaque Plaque Primary Skin Lesions lesions
  • Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma: yeasts and hyphae Hyphae Microscopic threadlike filaments in fungi that are filled with a layer of protoplasm. Collectively, the hyphae make up the mycelium. Mycology in mucosal cells
  • Culture shows Candida Candida Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis
Epigastric distress caused by esophageal candidiasis

Esophagogastroduodenoscopy illustrates diffuse white lesions in the esophagus characteristic of Candida esophagitis.

Image: “Epigastric Distress Caused by Esophageal Candidiasis” by Chen KH, Weng MT, Chou YH, Lu YF, Hsieh CH. License: CC BY 4.0

Management

  • Candida Candida Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis: oral fluconazole Fluconazole Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in aids. Azoles ( nystatin Nystatin Macrolide antifungal antibiotic complex produced by streptomyces noursei, s. Aureus, and other streptomyces species. The biologically active components of the complex are nystatin a1, a2, and a3. Polyenes for concurrent oral thrush)
  • With HIV HIV Anti-HIV Drugs/ AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS: antiretroviral therapy Antiretroviral therapy Antiretroviral therapy (ART) targets the replication cycle of the human immunodeficiency virus (HIV) and is classified based on the viral enzyme or mechanism that is inhibited. The goal of therapy is to suppress viral replication to reach the outcome of undetected viral load. Anti-HIV Drugs

Eosinophilic Esophagitis

Etiology

  • Allergic disorder associated with:
  • Note: Eosinophils Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Innate Immunity: Phagocytes and Antigen Presentation are not normally found in the esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy.

Risk factors

  • Asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma
  • Atopy Atopy Atopic Dermatitis (Eczema)
  • Allergies Allergies A medical specialty concerned with the hypersensitivity of the individual to foreign substances and protection from the resultant infection or disorder. Selective IgA Deficiency

Epidemiology

  • Men > women
  • Common age of presentation: 20–30 years
  • Caucasians are more affected.

Pathophysiology

  • Eosinophils Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Innate Immunity: Phagocytes and Antigen Presentation are recruited on exposure to inhaled or congested allergens.
  • Eosinophilic infiltration occurs → eosinophils Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Innate Immunity: Phagocytes and Antigen Presentation release interleukins Interleukins Interleukins are a type of cytokines (signaling proteins) that communicate messages between different parts of the immune system. The majority of interleukins are synthesized by helper CD4 T lymphocytes along with other cells such as monocytes, macrophages, and endothelial cells. Interleukins → inflammatory response

Clinical presentation

  • Dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia (to solid foods)
  • Food impaction
  • Odynophagia Odynophagia Epiglottitis

Diagnosis

Diagnosis is done by upper endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD).

Eosinophilic esophagitis

Images of eosinophilic esophagitis:
A. Esophagram in a patient with history of recurrent food impactions and dysphagia shows multiple esophageal rings (white arrow), giving the appearance of a corrugated or ringed esophagus, and mucosal irregularity (black arrow).
B. Endoscopy shows multiple transverse rings (arrows) and mucosal furrowing (arrowhead).

Image: “Eosinophilic esophagitis” by Al-Hussaini A, AboZeid A, Hai A. License: CC BY 4.0

Management

  • Referral to an allergist for guidance (dietary therapy)
  • Avoid known food allergens (e.g., cow’s milk).
  • Medication therapy:
    • Topical glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids (e.g., swallowed fluticasone Fluticasone A steroid with glucocorticoid receptor activity that is used to manage the symptoms of asthma; allergic rhinitis, and atopic dermatitis. Glucocorticoids)
    • Systemic glucocorticoids Systemic Glucocorticoids Glucocorticoids if with significant dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia, weight loss Weight loss Decrease in existing body weight. Bariatric Surgery, dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration
    • PPI for reflux symptoms
    • IL-4 receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors antagonists (e.g., dupilumab Dupilumab Asthma Drugs) may be considered for refractory disease.

Corrosive Esophagitis

Etiology

  • Alkali:
    • Drain cleaners, household cleaning products, batteries, bleaches
    • Viscous, tasteless, colorless
  • Acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance:
    • Battery fluid, toilet bowl cleaners, metal-cleaning liquids, anti-rust solutions
    • Unpleasant taste, malodorous

Risk factors

  • Intentional (suicidality, underlying psychiatric illness)
  • Accidental (usually in children)

Pathophysiology

  • Alkali-induced injury:
    • Rapid damage, affecting esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy more than the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy
    • Large amounts, however, result in gastric injury.
    • Process: liquefactive necrosis Liquefactive Necrosis Cell Injury and Death in the esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy
  • Acid-induced injury:
    • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways on contact with the oropharynx Oropharynx The middle portion of the pharynx that lies posterior to the mouth, inferior to the soft palate, and superior to the base of the tongue and epiglottis. It has a digestive function as food passes from the mouth into the oropharynx before entering esophagus. Pharynx: Anatomy limits the amount ingested.
    • More oropharyngeal and airway Airway ABCDE Assessment damage than with alkali solutions
    • Acid passes down faster, causing more stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy damage.
    • Process: superficial coagulation necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage in the esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy

Complications of severe damage

  • Perforation
  • Bleeding
  • Mediastinitis Mediastinitis Mediastinitis refers to an infection or inflammation involving the mediastinum (a region in the thoracic cavity containing the heart, thymus gland, portions of the esophagus, and trachea). Acute mediastinitis can be caused by bacterial infection due to direct contamination, hematogenous or lymphatic spread, or extension of infection from nearby structures. Mediastinitis
  • Obstruction
  • Strictures
  • Fistulas
  • Laryngeal and tracheobronchial damage from aspiration
  • Increased risk for squamous cell cancer (SCC) of the esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy

Clinical presentation

  • Oropharyngeal, retrosternal, or epigastric pain Epigastric pain Mallory-Weiss Syndrome (Mallory-Weiss Tear)
  • Odynophagia Odynophagia Epiglottitis and/or dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia
  • Hypersalivation
  • Stridor Stridor Laryngomalacia and Tracheomalacia or wheezing Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. Wheezing from burning of the larynx Larynx The larynx, also commonly called the voice box, is a cylindrical space located in the neck at the level of the C3-C6 vertebrae. The major structures forming the framework of the larynx are the thyroid cartilage, cricoid cartilage, and epiglottis. The larynx serves to produce sound (phonation), conducts air to the trachea, and prevents large molecules from reaching the lungs. Larynx: Anatomy
  • Dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics/ vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Severe retrosternal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways (perforation and mediastinitis Mediastinitis Mediastinitis refers to an infection or inflammation involving the mediastinum (a region in the thoracic cavity containing the heart, thymus gland, portions of the esophagus, and trachea). Acute mediastinitis can be caused by bacterial infection due to direct contamination, hematogenous or lymphatic spread, or extension of infection from nearby structures. Mediastinitis)
  • Abdominal tenderness and rigidity Rigidity Continuous involuntary sustained muscle contraction which is often a manifestation of basal ganglia diseases. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity. Megacolon (perforation and peritonitis Peritonitis Inflammation of the peritoneum lining the abdominal cavity as the result of infectious, autoimmune, or chemical processes. Primary peritonitis is due to infection of the peritoneal cavity via hematogenous or lymphatic spread and without intra-abdominal source. Secondary peritonitis arises from the abdominal cavity itself through rupture or abscess of intra-abdominal organs. Penetrating Abdominal Injury)

Diagnosis

  • History: Note type and amount of ingested agent.
  • X-rays X-rays X-rays are high-energy particles of electromagnetic radiation used in the medical field for the generation of anatomical images. X-rays are projected through the body of a patient and onto a film, and this technique is called conventional or projectional radiography. X-rays:
  • Computed tomography (CT) scan: checks depth of necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage and helps assess need for emergency surgery
  • Upper endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD):
    • Within 24 hours if without contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation 
    • Contraindicated in hemodynamic instability, gastrointestinal perforation
Pyloric stenosis esophagitis

Upper endoscopy finding in a child with alkali ingestion: Pyloric stenosis developed 2 months after injury.

Image: “Pyloric stenosis after 2 months” by Dehghani SM, Aldaghi M, Javaherizadeh H. License: CC BY 3.0

Classification of injury

  • 1st-degree injury: superficial mucosa affected; erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion, edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema, hemorrhage, with healing expected
  • 2nd-degree injury: ulcers, exudates affect up to submucosal layer; scarring Scarring Inflammation and strictures possible
  • 3rd-degree injury: transmural in-depth, with deep ulcers and perforation of the wall

Management

Reflux Esophagitis

Reflux esophagitis is also known as gastroesophageal reflux disease Gastroesophageal Reflux Disease Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD) ( GERD GERD Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD)).

Etiology and pathophysiology

  • Retrograde flow Retrograde flow Veins: Histology of stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy acid into the esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy due to transient relaxation of the lower esophageal sphincter Lower Esophageal Sphincter Esophagus: Anatomy (LES) 
  • Most episodes of relaxation are triggered by gastric distention.
  • Some have incompetent LES.
  • Toxic substances ( gastric acid Gastric acid Hydrochloric acid present in gastric juice. Gastroesophageal Reflux Disease (GERD), pepsin Pepsin Pepsin breaks down proteins into proteoses, peptones, and large polypeptides. Proteins and Peptides, bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy salts) cause damage to the distal esophageal mucosa Esophageal Mucosa Circular innermost layer of the esophagus wall that mediates esophageal peristalsis which pushes ingested food bolus toward the stomach. Esophagus: Anatomy.

Risk factors

  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
  • Alcohol consumption
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
  • Hiatal hernia Hiatal hernia Stomach herniation located at or near the diaphragmatic opening for the esophagus, the esophageal hiatus. Congenital Diaphragmatic Hernias
  • Stress
  • Scleroderma Scleroderma Scleroderma (systemic sclerosis) is an autoimmune condition characterized by diffuse collagen deposition and fibrosis. The clinical presentation varies from limited skin involvement to diffuse involvement of internal organs. Scleroderma
  • Zollinger-Ellison syndrome causing increased acid secretion Secretion Coagulation Studies

Clinical presentation

Complications

  • Erosive esophagitis
  • Barrett’s esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy (at risk for adenocarcinoma)
  • Esophageal stricture Stricture Primary Sclerosing Cholangitis

Diagnosis

  • Clinical (classic signs of heartburn Heartburn Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. Gastroesophageal Reflux Disease (GERD) and regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD))
  • Confirmed with esophageal pH monitoring Esophageal ph monitoring Analysis of the hydrogen ion concentration in the lumen of the esophagus. It is used to record the pattern, frequency, and duration of gastroesophageal reflux. Dysphagia if:
    • With unsatisfactory treatment
    • With atypical symptoms
    • Antireflux surgery being considered
  • Upper endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) is performed if with:
    • Dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia
    • Unexplained weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
    • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types or evidence of gastrointestinal bleeding Gastrointestinal bleeding Gastrointestinal bleeding (GIB) is a symptom of multiple diseases within the gastrointestinal (GI) tract. Gastrointestinal bleeding is designated as upper or lower based on the etiology’s location to the ligament of Treitz. Depending on the location of the bleeding, the patient may present with hematemesis (vomiting blood), melena (black, tarry stool), or hematochezia (fresh blood in stools). Gastrointestinal Bleeding
    • Refractory symptoms
    • New-onset GERD GERD Gastroesophageal reflux disease (GERD) occurs when the stomach acid frequently flows back into the esophagus. This backwash (acid reflux) can irritate the lining of the esophagus, causing symptoms such as retrosternal burning pain (heartburn). Gastroesophageal Reflux Disease (GERD) > 60 years
    • Odynophagia Odynophagia Epiglottitis
    • High risk for Barrett’s esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy
    • 1st-degree relative with gastrointestinal cancer
Reflux esophagitis

Reflux esophagitis in upper endoscopy:
A: high-definition image of esophageal changes in GERD
B: tone-enhancement image of GERD

Image: “Reflux esophagitis” by Netinatsunton N, Sottisuporn J, Attasaranya S, Witeerungrot T, Chamroonkul N, Jongboonyanuparp T, Geater A, Ovartlarnporn B. License: CC BY 4.0

Management

  • Lifestyle modification:
    • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery 
    • Elevation of the head of the bed
    • Elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy of dietary triggers
    • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases/alcohol cessation
  • Medication therapy: PPIs
  • Surgical options include fundoplication, which is indicated for refractory symptoms.

References

  1. Azer, S., Reddivari, A. (2020). Reflux esophagitis. Retrieved Nov 9, 2020, from https://www.ncbi.nlm.nih.gov/books/NBK554462
  2. Bonnis, P., Kotton, C., Hirsch, M., Mitty, J. (2020). Herpes simplex virus infection of the esophagus. UpToDate. Retrieved Nov 8, 2020, from https://www.uptodate.com/contents/herpes-simplex-virus-infection-of-the-esophagus
  3. Castell, D., Lamont, J., Grover, S. (2020). Medication-induced esophagitis. UpToDate. Retrieved 8 Nov 2020, from https://www.uptodate.com/contents/medication-induced-esophagitis
  4. De Lusong, M., Timbol, A., Tuazon, D. (2017). Management of esophageal caustic injury. World Journal of Gastrointestinal Pharmacology and Therapeutics 6; 8(2): 90–98.
  5. Greenberger, N.J. (2016). Eosinophilic esophagitis. Greenberger N.J., Blumberg R.S., Burakoff, R. (Eds.) Current Diagnosis & Treatment: Gastroenterology, Hepatology, & Endoscopy, 3rd ed. McGraw-Hill.
  6. Jacobson, M., Bartlett, J., Mitty, J. (2019). AIDS-related cytomegalovirus gastrointestinal disease. UpToDate. Retrieved Nov 8, 2020 from https://www.uptodate.com/contents/aids-related-cytomegalovirus-gastrointestinal-disease
  7. Kardon, E., Vearrier, D. (2018). Caustic ingestions. Medscape. Retrieved 8 Nov 2020, from https://emedicine.medscape.com/article/813772-overview
  8. McQuaid K.R. (2021). Caustic esophageal injury. Papadakis M.A., McPhee S.J., Rabow M.W. (Eds.) Current Medical Diagnosis & Treatment 2021. McGraw-Hill.
  9. McQuaid K.R. (2021). Gastroesophageal reflux disease. Papadakis, M.A., McPhee S.J., Rabow M.W. (Eds.) Current Medical Diagnosis & Treatment 2021. McGraw-Hill.
  10. Triadafilopoulos, G., Saltzman, J., Grover, S., Chen, W. (2019). Caustic esophageal injury in adults. UpToDate. Retrieved Nov 8, 2020 from https://www.uptodate.com/contents/caustic-esophageal-injury-in-adults

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