Esophagitis: Types and Causes

• Upper Gastrointestinal Tract Pathology involves the esophagus, stomach, and duodenum
• The role of Helicobacter pylori in the development of peptic ulcer disease should be discussed

Esophagitis

• Esophagitis is the inflammation of the esophagus
• Esophagitis occurs when the squamous epithelial lining is damaged by irritants, infections, or other factors
• Types/Causes of Esophagitis include:
• Reflux
• Eosinophilic
• Infectious
• Caustic/chemical
• Iatrogenic (e.g., cytotoxic chemotherapy, radiation therapy, graft-versus-host disease)
• Systemic skin diseases (e.g., Bullous pemphigoid, epidermolysis bullosa)
• Crohn disease

Reflux Esophagitis

• Most frequent cause of esophagitis
• Common outpatient GI diagnosis, also known as gastroesophageal reflux disease (GERD)
• Pathogenesis is the transient lower esophageal sphincter relaxation and gastric distention/pressure
• Associated conditions include alcohol use, nicotine use, obesity, central nervous system depressants, pregnancy, hiatal hernia, delayed gastric emptying and increased gastric volume
• Symptoms include heartburn. dysphagia, regurgitation of gastric contents and chest pain
• Endoscopic findings include simple hyperemia and erosions/ulcerations
• Under microscopic morphology, basal zone hyperplasia, elongation of lamina propria papillae, intraepithelial lymphocytes within squamous mucosa ("squiggle cells"), and intraepithelial eosinophils are observed and neutrophils are not common
• Complications include ulceration, strictures, Barrett's esophagus (BE), dysplasia and adenocarcinoma (2º BE)

Eosinophilic Esophagitis

• Atopic disease associated with atopic dermatitis, allergic rhinitis, asthma, or modest peripheral eosinophilia
• Symptoms include food impaction, dysphasia, and vomiting
• The pathogenesis is increased eosinophils and +/- mast cells
• Endoscopic findings include stacked circular rings, strictures and linear furrows
• Microscopic findings show ++++ eosinophils with intraepithelial eosinophils (superficially concentrated), eosinophil aggregates/microabscesses, and eosinophilic degranulation
• Complications include strictures
• Eosinophilic Esophagitis is NOT associated with BE

Infectious Esophagitis

• Causes include:
• Herpes Simplex virus (HSV)
• Cytomegalovirus (CMV)
• Fungal organisms, such as Candidiasis (most common, candida), Mucormycosis (genera Rhizopus and Mucor) and Aspergillosis (Aspergillus)

Herpes Simplex Virus Esophagitis

• Endoscopic appearance includes punched out ulcers, overlapping ulcers and vesicles
• Microscopic morphology shows "3 M's:" margination of chromatin, multinucleation, and molding of nuclei and viral nuclear inclusions

Cytomegalovirus

• Generally seen in immunocompromised individuals
• Difficult to differentiate from HSV
• Consists of punched out ulcers with larger areas of irregular ulceration and hemorrhage
• Microscopic findings show nuclear and cytoplasmic inclusions ("owl eye" appearance), active inflammation and viral changes seen mainly in stromal cells or endothelial cells

Candida

• Endoscopic findings include grey-white pseudo-membranes
• White plaque and erythema
• Microscopic Findings show pseudo-hyphae and budding spores, inflammatory exudate and fibrin, active inflammation (with neutrophils) and necrotic debris

Acute Gastritis

• Acute Gastritis is the inflammation of the stomach
• Acute Gastritis requires neutrophils
• Symptoms include epigastric pain, nausea, vomiting and can be asymptomatic
• Causes: Helicobacter pylori infection, alcohol, infections, bile injury, NSAIDs, radiation, and chemotherapy
• Disruptions of protective mechanisms include:
• Inhibition of cyclooxygenase: NSAIDs inhibit COX-dependent synthesis of prostaglandins E2 and 12
• Inhibition of gastric bicarbonate transporters: in uremic patients and infection of urease-secreting H. Pylori
• Reduced mucin and bicarbonate secretion in older adults
• Decreased oxygen delivery due to high acute gastritis at high altitudes, low oxygen states
• Direct cellular injury from caustic injury, alcohol, radiation therapy and chemotherapy
• Endoscopic findings may appear normal but can be erythematous, with erosions/ulcerations and hemorrhage
• Microscopic appearance shows NEUTROPHILS in epithelial cells or lamina propria (Neutrophils are abnormal in all parts of the Gl tract), cryptitis or crypt abscesses, erosions and fibrin-containing exudate

Peptic Ulcer Disease

• An imbalance of defensive and damaging factors
• Usually occurs with background chronic gastritis
• Most commonly due to H. pylori
• Causes: H. pylori infection, NSAIDs, cigarette smoking, Ectopic gastric mucosa (esophagus or duodenum), Ileal Meckel diverticulum
• Solitary in >80% patients
• Sharply punched-out defect
• Perforation into peritoneal cavity may occur
• Risk factors include: Helicobacter pylori infection, Cigarette use, Chronic obstructive pulmonary disease, Illicit drugs (cocaine), NSAIDs, Alcoholic cirrhosis, Psychological stress, Endocrine cell hyperplasia, Zollinger-Ellison syndrome and Viral infection.
• Microscopic Features include fibrinoid debris, neutrophils, granulation tissue with/ immature vessels, leukocytes, collagenous scar formation, and larger vessels within scar

Helicobacter Gastritis

• Historically thought Peptic Ulcer Disease (PUD) caused by stress, spicy foods, and increased acid
• Isolated by Drs. Barry Marshall and Robin Warren in 1982
• Hypothesis was bacteria is the cause of peptic ulcer and gastric cancer
• 1984: Marshall has baseline endoscopy completed and drank H. pylori culture, developed nausea, halitosis
• Day 8 endoscopy showed massive inflammation
• Helicobacter pylori are spiral shaped or curved bacilli with symptoms of chronic infection over acute
• It is associated with poverty, household crowding, rural areas, and age > 60 with environment during childhood a critical risk factor for colonization
• Pathogenesis:
• Increased gastric acid production, decreased duodenal bicarbonate production and virulence factors
• Flagella helps to be mobile in viscous mucus
• Urease generates ammonia & elevates gastric pH in the bacteria’s surrounding environment
• Adhesions enhances bacterial adherence to surface foveolar cells
• Toxins: cytotoxin-associated gene A (CagA)
• Microscopic Findings
• Acute (active gastritis) -Chronic gastritis
• Increased plasma cells
• Increased lymphocytes, macrophages, neutrophils
• Atrophic gastritis
• Loss of parietal cells -Intestinal metaplasia -Prominent lymphoid follicles
• Complications of H. pylori infection include: complications of acute gastritis, peptic ulcer disease, intestinal metaplasia, gastric polyps, dysplasia, adenocarcinoma, marginal zone B-cell lymphoma and Diffuse large B-cell lymphoma