Acute Gastritis

Acute gastritis is a term that encompasses a broad spectrum of entities that induce inflammatory changes in the gastric mucosa. Several different etiologies share the same general clinical presentation; however, they differ in their unique histologic characteristics. The inflammation may involve the entire stomach (eg, pangastritis) or a region of the stomach (eg, antral gastritis).

Acute gastritis can be divided into two categories: erosive (eg, superficial erosions, deep erosions, hemorrhagic erosions) and nonerosive (generally caused by Helicobacter pylori). See the images below.

Acute Gastritis. Acute gastritis with superficial erosions is observed.

Acute Gastritis. This image reveals mucosal erythema and edema consistent with acute gastritis.

No correlation exists between microscopic inflammation (histologic gastritis) and the presence of gastric symptoms (eg, abdominal pain, nausea, vomiting). In fact, most patients with histologic evidence of acute gastritis (inflammation) are asymptomatic. The diagnosis is usually obtained during endoscopy performed for other reasons. Acute gastritis may present with an array of symptoms, the most common being nondescript epigastric discomfort.

Other symptoms include nausea, vomiting, loss of appetite, belching, and bloating. Occasionally, acute abdominal pain can be a presenting symptom, as in cases of phlegmonous gastritis (gangrene of the stomach) in which severe abdominal pain accompanied by nausea and vomiting of potentially purulent gastric contents can be the presenting symptoms. Fever, chills, and hiccups also may be present.

The diagnosis of acute gastritis may be suspected from the patient's history and can be confirmed histologically by biopsy specimens taken at endoscopy.

See related CME at Evaluation of Acute Abdominal Pain Reviewed.

Acute gastritis has a number of causes, including certain drugs; alcohol; bile; ischemia; bacterial, viral, and fungal infections; acute stress (shock); radiation; allergy and food poisoning; and direct trauma. The common mechanism of injury is an imbalance between the aggressive and the defensive factors that maintain the integrity of the gastric lining (mucosa).

Acute erosive gastritis can result from exposure to a variety of agents or factors. This is referred to as reactive gastritis. These agents/factors include nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, cocaine, stress, radiation, bile reflux, and ischemia. The gastric mucosa exhibits hemorrhages, erosions, and ulcers. NSAIDs, such as aspirin, ibuprofen, and naproxen, are the most common agents associated with acute erosive gastritis. This results from both oral and systemic administration of these agents, either in therapeutic or supratherapeutic doses.

Because of gravity, the inciting agents lie on the greater curvature of the stomach. This partly explains the development of acute gastritis distally over or near the greater curvature of the stomach in the case of orally administered NSAIDs. However, the major mechanism of injury is the reduction in prostaglandin synthesis. Prostaglandins are chemicals responsible for maintaining the mechanisms that result in the protection of the mucosa from the injurious effects of gastric acid. Long-term effects of such ingestions can include fibrosis and stricture formation.

Bacterial infection is another cause of acute gastritis. The corkscrew-shaped bacterium H pylori is the most common cause of gastritis, and complications result from a chronic infection rather than from an acute infection. The prevalence of H pylori in otherwise healthy individuals varies depending on the patient's age, socioeconomic class, and country of origin. The infection is usually acquired in childhood. In the Western world, the number of people infected with H pylori increases with age.

Evidence of H pylori infection can be found in 20% of individuals younger than 40 years and in 50% of individuals older than 60 years. How the bacterium is transmitted is not entirely clear, but transmission is likely from person to person through the oral-fecal route or through the ingestion of contaminated water or food. This is why the prevalence is higher in those of lower socioeconomic classes and in developing countries. H pylori is associated with 60% of gastric ulcers and 80% of duodenal ulcers.

H pylori gastritis typically starts as an acute gastritis in the antrum, causing intense inflammation and, over time, it may extend to involve the entire gastric mucosa, resulting in chronic gastritis.

The acute gastritis encountered with H pylori is usually asymptomatic. The bacterium imbeds itself in the mucous layer, a protective layer that coats the gastric mucosa. H pylori protects itself from the acidity of the stomach through the production of large amounts of urease, an enzyme that catalyzes the breakdown of urea to the alkaline ammonia and carbon dioxide. The alkaline ammonia neutralizes the gastric acid in the immediate vicinity of the bacterium, thereby conferring protection.

H pylori also has flagella that enable it to move and help it to penetrate the mucous layer so that it comes into contact with the gastric epithelial cells. It also has several adhesion molecules that help it to adhere to these cells. H pylori produces inflammation by activating a number of toxins and enzymes that activate interleukin (IL)-8, which eventually attracts polymorphs and monocytes that cause acute gastritis.

Antigen-presenting cells (APCs) activate lymphocytes and other mononuclear cells that lead to chronic superficial gastritis. The infection is established within a few weeks after the primary exposure to H pylori. It produces inflammation via the production of a number of toxins and enzymes. The intense inflammation can result in the loss of gastric glands that are responsible for the production of acid. This is referred to as atrophic gastritis. Consequently, gastric acid production drops. The virulence genotype of the microbe is an important determinant for the severity of the gastritis and the formation of intestinal metaplasia, the transformation of gastric epithelium. This transformation can lead to gastric cancer.

Reactive gastropathy is the second most common diagnosis made on gastric biopsy specimens after H pylori gastritis. This entity is believed to be secondary to bile reflux and was originally reported after partial gastrectomy (Billroth I or II). It is now considered to represent a nonspecific response to a variety of other gastric irritants.

Helicobacter heilmannii is a gram-negative, tightly spiraled, helical-shaped organism with 5-7 turns. The prevalence of H heilmannii is extremely low (0.25-1.5%). The source of H heilmannii infection is unclear, but animal contact is thought to be the means of transmission.

Tuberculosis is a rare cause of gastritis, but an increasing number of cases have developed in patients who are immunocompromised. Gastritis caused by tuberculosis is generally associated with pulmonary or disseminated disease.

Secondary syphilis of the stomach is a rare cause of gastritis.

Phlegmonous gastritis is an uncommon form of gastritis caused by numerous bacterial agents, including streptococci, staphylococci, Proteus species, Clostridium species, and Escherichia coli. Phlegmonous gastritis usually occurs in individuals who are debilitated. It is associated with a recent large intake of alcohol, a concomitant upper respiratory tract infection, and acquired immunodeficiency syndrome (AIDS). Phlegmonous means a diffuse spreading inflammation of or within the connective tissue. In the stomach, it implies infection of the deeper layers of the stomach (submucosa and muscularis). As a result, purulent bacterial infection may lead to gangrene.

Phlegmonous gastritis is rare. The clinical diagnosis is usually established in the operating room, as these patients present with an acute abdominal emergency requiring immediate surgical exploration. Without appropriate therapy, phlegmonous gastritis can progress to peritonitis and death.

Acute necrotizing hemorrhagic gastritis (a rare variant of phlegmonous gastritis) is mostly related to bacterial infection, which could progress to gastric gangrene. More recently, it has also been associated with new chemotherapeutic drugs, such as multi-antityrosine kinase (midostaurin) which is used in acute myeloid leukemia. Necrotizing gastritis cases are severe and may mandate emergency gastrectomy.[1]

Cytomegalovirus (CMV) rarely causes gastritis; its prevalence among CMV patients is unknown.[2] CMV gastritis is usually, but not always, encountered in individuals who are immunocompromised, including those with cancer, on immunosuppression medications, after transplants, and AIDS. Yamamoto and Sakai described a case of gastritis due to concurrent infection with Epstein-Barr virus (EBV) and CMV in an immunocompetent adult.[3] Gastric involvement can be localized or diffuse. CMV gastritis is essentially diagnosed by gastroscopy and biopsy because viral load and immunoglobulin (Ig) M level could be misleading.[2]

Acute gastritis has been noted in patients receiving immune-checkpoint inhibitors for cancer immunotherapy, such as pembrolizumab. Histology shows lymphocytic infiltration, mostly of the CD8+ type along with CD3+. Treatment depends mainly on a short course of corticosteroids for lympholysis. Stopping immunotherapy is mandatory only when there is a risk of gastric perforation. The condition may be discovered accidentally during follow-up positron emission tomography (PET) computed tomography (CT) scanning, because patients could be asymptomatic despite having acute gastritis. Diagnosis occurs only after exclusion of other possible causes (eg, NSAID, CMV, etc).[4]

Fungal infections that cause gastritis include Candida albicans and histoplasmosis. Gastric phycomycosis is another rare lethal fungal infection. The common predisposing factor is immunosuppression. C albicans rarely involves the gastric mucosa. When isolated in the stomach, the most common locations tend to be within a gastric ulcer or an erosion bed; it is generally of little consequence. Disseminated histoplasmosis can involve the stomach; the usual presenting clinical feature is bleeding from gastric ulcers or erosions on giant gastric folds.

Coronavirus disease 2019 (COVID-19)

The angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane protease serine 2 (TMPRSS2) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter host cells. They are present in the gastrointestinal (GI) tract, acting as the point of viral entry and subsequent replication. Thus, GI manifestations are part of the COVID-19 disease presentation in the form of vomiting, nausea, and abdominal pain.[5] GI bleeding presentation is similar in COVID-19 patients to patients without the disease.[6]

In a cohort study of more than 11,000 patients, the rate of GI bleeding among hospitalized COVID-19 patients was 3%, with no identifiable cause, and proton-pump inhibitors (PPIs) were not protective against the GI bleeding.[7]  Moreover, anticoagulation given to COVID-19 patients to protect them from pulmonary thrombosis or hypercoagulable state did not increase the risk of GI bleeding. In a separate study of COVID-19 patients who underwent endoscopy for GI bleeding, only 16.6% were due to gastritis and 20.8% were due to duodenal ulcer.[8]  However, another multicenter study showed that GI bleeding caused by gastric and duodenal ulcers compose 80% of all upper GI bleeding etiologies.[6]

As noted earlier, the causes of acute gastritis include the following:

• Drugs: Nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, aspirin, ibuprofen, and naproxen); cocaine; iron; colchicine (when at toxic levels, as in patients with failing renal or hepatic function); kayexalate; chemotherapeutic agents (eg, mitomycin C, 5-fluoro-2-deoxyuridine, floxuridine, tyrosine kinase inhibitors such as midostaurin,[1] and cancer immunotherapeutic agents, such as pembrolizumab).[4]

• Drugs used in coronavirus disease 2019 (COVID-19) treatment: Interleukin-6 receptor antagonists (Tocilizumab and sarilumab are both associated with chronic gastritis,[9] whereas lopinavir-ritonavir is associated with acute gastritis.[10] )

• Potent alcoholic beverages, such as whisky, vodka, and gin

• Bacterial infections: H pylori (most frequent), H heilmannii (rare), streptococci (rare), staphylococci (rare), Proteus species (rare), Clostridium species (rare), E coli (rare), tuberculosis (rare), secondary syphilis (rare)

• Viral infections (eg, cytomegalovirus)

• Fungal infections: Candidiasis, histoplasmosis, phycomycosis

• Parasitic infection (eg, anisakidosis)

• Acute stress (shock)

• Radiation

• Allergy and food poisoning

• Bile: The reflux of bile (an alkaline medium is important for the activation of digestive enzymes in the small intestine) from the small intestine to the stomach can induce gastritis.

• Ischemia: This term is used to refer to damage induced by a decreased blood supply to the stomach. This rare etiology is due to the rich blood supply to the stomach.

• Direct trauma

Epidemiologic studies reflect the widespread incidence of gastritis. In the United States, it accounts for approximately 1.8-2.1 million visits to doctors' offices each year.

Data from a national administrative database (2009-2011) revealed standardized estimated prevalence rates of 6.3 per 100,000 population for eosinophilic gastritis and 3.3 per 100,000 population for eosinophilic colitis; women were affected more often.[11]

Gastritis affects all age groups; however, this condition is especially common in people older than 60 years. The incidence of H pylori infection increases with age.

Gastritis generally clears spontaneously. With treatment, the mortality rate of phlegmonous gastritis is 65%.

Morbidity/mortality

Morbidity/mortality is dependent on the etiology of the gastritis. Generally, most cases of gastritis are treatable once the etiology is determined. The exception to this is phlegmonous gastritis, which has a mortality of 65%, even with treatment.

Complications

Complications of acute gastritis include the following:

• Bleeding from an erosion or ulcer

• Gastric outlet obstruction due to edema limiting an adequate transfer of food from the stomach to the small intestine

• Dehydration from vomiting

• Renal insufficiency as a result of dehydration

Explain the disease to the patient.

Encourage cessation of smoking and alcohol consumption, and warn patients of the potential effects of noxious drugs and chemical agents.

For patient education resources, see Digestive Disorders Center, as well as Gastritis.

History

Patients with acute gastritis may experience gnawing or burning epigastric distress, occasionally accompanied by nausea and/or vomiting. The pain may improve or worsen with eating.

Obtain the following information, if available:

• Presence of a previous mucosal injury (eg, gastritis, peptic ulcer disease, endoscopic injury caused by polypectomy, injury caused by any surgery)

• History of eating raw fish

• Exposure to potentially noxious drugs or chemical agents. This includes corticosteroids or other prescription medications that can cause gastritis.

• Routine use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs), especially at high doses

Physical examination

The physical examination findings are often normal, with occasional mild epigastric tenderness. The examination tends to exhibit more abnormalities as the patient develops complications in relation to gastritis.

Laboratory tests ordered in cases of suspected gastritis including the following:

• Complete blood cell (CBC) count to assess for anemia, as acute gastritis can cause gastrointestinal bleeding[12]

• Liver and kidney function tests

• Gallbladder and pancreatic function tests

• Pregnancy test

• Stool for blood

Four radiologic signs of acute gastritis are fairly consistent regardless of the etiology: thick folds, inflammatory nodules, coarse area gastrica, and erosions.

Thick folds are defined by a size larger than 5 mm in caliber. These folds are measured on radiographs with the stomach moderately distended. If thick folds are found in a patient who is symptomatic, H pylori is generally involved.

Nodularity of the gastric mucosa (bumpy appearance) is a second sign of acute or subacute gastritis. Its origin is uncertain. Nodules may represent erosions that have epithelialized (healed) but still have the associated edema. Compared with benign neoplastic polyps, gastritis-related nodules are smaller, and their edges are less well defined. They taper onto the adjacent mucosa, and they are seen most often in the distal stomach. Nodules due to gastritis are referred to as inflammatory. They generally line up on the folds of the gastric antrum and are a characteristic appearance of gastritis.

Enlarged area gastrica are a sign of gastritis that is not strongly associated with a specific cause. Area gastrica are small polygonal areas, 1-3 mm in diameter, separated by linear depressions on the surface of the mucous membrane of the stomach; they contain the gastric pits. Enlargement of these areas may reflect inflammatory swelling, and it is often associated with gastritis. Because of the loss of the mucosal layer, the barium suspension can more completely fill the intervening grooves.

Gastric erosions are noted to be one of the most specific signs of gastritis. Erosions may be linear or serpiginous. They may be accompanied by edema and may be seen on or near the greater curvature of the stomach. A double-contrast examination is usually required to best reveal gastric erosions.

Tomography scans and plain films of the abdomen can demonstrate thickening of the gastric wall in the case of phlegmonous gastritis.

Double-contrast barium radiography can demonstrate the nematodes that cause anisakidosis.

A number of H pylori tests are available. These tests are classified as either nonendoscopy or endoscopy based.

Nonendoscopy-based H pylori tests

H pylori stool antigen test (HpSA)

This test is based on the detection of the H pylori antigen in the stool. It has sensitivity and specificity above 90%. The HpSA can be used both for the diagnosis of H pylori and the confirmation of eradication after therapy.

Urea breath test

This study uses 13C- or 14C-labeled urea taken orally. H pylori metabolizes the urea and liberates the labeled carbon dioxide that is exhaled. This, in turn, can be quantified in breath samples. The sensitivity and specificity of the urea breath test is greater than 90%. This test is considered the noninvasive diagnostic method of choice in situations where endoscopy is not indicated. It can also be used to confirm eradication after therapy.

Serum antibodies test

The third nonendoscopy H pylori test depends on the presence of antibodies to H pylori in the serum. The major drawback to this test is that serologic assays may remain positive for as long as 3 years after eradication of the bacteria. Therefore, serologic assays are often unreliable to document eradication of H pylori. This test can be used for the diagnosis of H pylori, provided that the patient has not received any prior therapy for it.

Endoscopy-based H pylori tests

Rapid urease test (RUT)

The RUT is performed by placing a gastric biopsy specimen, obtained at endoscopy, onto a gel- or membrane-containing urea and a pH-sensitive indicator. If H pylori is present, the bacterial urease hydrolyzes urea and changes the color of the media. The sensitivity and specificity of this test is greater than 90%.

Bacterial culture

Bacterial culture of H pylori is highly specific but not widely used because of the degree of expertise required. It is used when antibiotic susceptibilities are necessary.

Histology

Histologic detection of H pylori in the biopsy specimen is another endoscopy-based test. Appropriate staining is achieved using such stains as hematoxylin and eosin, Warthin-Starry, Giemsa, or Genta.

Other considerations

American Society for Gastrointestinal Endoscopy (ASGE) guidelines suggest endoscopic evaluation for patients older than 45 years who have alarm features such as weight loss and anemia.[13] For patients younger than 40 years with no alarm features who are H pylori negative, endoscopic evaluation may be considered.

Mycobacterium tuberculosis may be diagnosed when acid-fast stain detects the bacilli in a biopsy specimen.

Syphilis may be diagnosed when the organism is found in the gastric mucosa. Endoscopic biopsy, silver impregnation, and fluorescent antibody techniques can also be used.

Endoscopy in a patient with acute gastritis may reveal a thickened, edematous, nonpliable gastric wall with erosions and reddened gastric folds. The edema can be severe, resulting in gastric outlet obstruction. Ulcers and frank bleeding may be present.

The nematodes that cause anisakidosis can be seen on endoscopy.

Endoscopy can also be used to help diagnose gastric syphilis and tuberculosis.

A meta-analysis has shown that for individuals who undergo endoscopy for dyspepsia, the most common finding is erosive esophagitis (although the prevalence was lower when the Rome criteria were used to define dyspepsia), followed by peptic ulcers.[14]

Histologic examination of a biopsy specimen can help in establishing the etiologic agent of gastritis.

The diagnosis of H heilmannii is improved by using smears with Giemsa or Warthin-Starry silver stains than by gastric biopsy specimens via observation of a distinct morphology. A culture of H heilmannii has not yet been established; thus, the diagnosis of this bacterial infection is based on morphological identification by histologic examination and tissue smear cytology.

As mentioned earlier, H pylori can be found by histologic staining of a gastric mucosal biopsy specimen. It has a sensitivity and specificity of greater than 90%.

The main histologic feature of cytomegalovirus (CMV) infection is cytomegalic cells with intranuclear inclusions. Viral cultures, immunocytochemistry, and in situ hybridization can further aid in establishing the diagnosis.

The main histologic feature of C albicans infection is yeast forms in a biopsy specimen.

The main histologic feature of tuberculosis is necrotizing granulomas.

The main histologic feature of histoplasmosis is the presence of nonnecrotizing granulomas containing the organisms. The diagnosis of histoplasmosis requires a positive culture result from the gastric mucosal biopsy specimen.

In ulcero-hemorrhagic gastritis, the epithelium appears eroded with edema and hemorrhage but typically little inflammation. In severe cases, the lumen of the stomach may be coated with fibropurulent exudates, and the lamina propria may be replaced by eosinophilic hyaline material.

In iron-induced gastritis, erosions, foveolar hyperplasia, or even hyperplastic-type polyps can be detected. Iron has been associated with infarctlike necrosis, given its corrosive properties. Iron stains can highlight the golden brown pigment in tissue samples, but these are often easily visible. Of note, such findings should be differentiated from the glandular siderosis seen in systemic iron overload or hemochromatosis.

Histologic features of chemotherapy-induced gastritis may include atypical epithelial cells with bizarre features at the base of the glands, limited mitoses, and pleomorphic nuclei. These characteristics may make it difficult to differentiate from an adenocarcinoma.

The findings at histology of radiation-induced gastritis include nuclear karyorrhexis (destructive fragmentation of the nucleus of a dying cell) and cytoplasmic eosinophilia of the gastric pit epithelium during the first 10 days following treatment, followed by mucosal edema, congestion, submucosal collagen bundle swelling, fibrin deposition, and telangiectasia. If extensive, hemorrhage and ulceration may be evident.

In eosinophilic gastritis, a prominent eosinophilic infiltrate is present in the gastric wall or epithelium. Distribution can be patchy, so multiple biopsy specimens should be obtained during endoscopy.

Surgical intervention is not necessary for gastritis, except in the case of phlegmonous gastritis or acute necrotizing gastritis. With the latter entity, surgical intervention with resection of the affected area may be the most effective form of treatment.

Consult a gastroenterologist in complicated cases.

In cases of suspected upper gastrointestinal (GI) bleeding (decreased hemoglobin, melena, hematemesis), diagnostic endoscopy is mandatory to exclude bleeding ulcers, angiomatous malformations, erosions and malignant transformation. Severe cases with upper GI bleeding can be treated by cautery, hemoclips, local epinephrine injection, or hemostatic spraying of the bleeding area[15] along with an intravenous (IV) proton-pump inhibitor (PPI) bolus, then continuous infusion for 72 hours to stabilize the bleeding.[16]

Over-the-counter (OTC) drugs such as mucosal coating (sucralfate, antacids) agents or short-term histamine-2 antagonists can stabilize mild to moderate cases in the short term.[17] In the long term, treatment of the underlying cause (ie, avoid nonsteroidal anti-inflammatory drugs, caffeine, smoking; H Pylori eradication; etc.) is the most satisfactory course of action.

Proton-pump inhibitor (PPI) treatment and coronavirus disease 2019 (COVID-19) infection

There is an association between the use of PPIs and the severity of COVID-19 infection. This is explained by the increased viral infection after swallowing the viral particles in patients who have low gastric acidity, most commonly due to PPI ingestion. Viral inactivation takes place in a low acidic medium, protecting the patient from viral entry through the gastrointestinal tract. However, using PPIs does not increase the risk of acquiring infection.[18, 19, 20, 21]

Lee et al also found that increasing the dose of PPIs is associated with increased severity of COVID-19 infection.[20]  Furthermore, there is a debate over whether antihistamines such as famotidine could be more protective of severe infection. It is postulated that famotidine can inhibit the replication of human immunodeficiency virus (HIV); further computational methods showed that this agent could be effective in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well. A retrospective cohort proved this preliminary hypothesis: Hospitalized patients who received famotidine showed a lower risk of intubation or mortality than those who didn’t receive the drug. Moreover, famotidine was associated with mildly lowering ferritin levels (used as a surrogate marker for the cytokine storm). Unfortunately, when the authors repeated the study on another set of patients, the results were not replicable (ie, no protective effect of famotidine).[21, 22]

Administer medical therapy for patients with acute gastritis as needed, depending on the underlying cause and the pathological findings.

The US Food and Drug Administration announced voluntary recalls of ranitidine from the market between December 2019 and February 2020[3] after raising major concerns in September 2019 about drug contamination with the impurities of the carcinogenic molecule N-nitrosodimethylamine (NDMA).[23] A total withdrawal of all ranitidine products was requested in April 2020.[24]

No specific therapy exists for acute gastritis, except for cases caused by H pylori. The American College of Gastroenterology (ACG) guidelines suggest that the current evidence does not support the notion that treating H pylori worsens gastroesophageal reflux disease (GERD).[25] For patients who need eradication of H pylori, this should not be a concern.

First-line H pylori eradication therapy

First-line therapy for H pylori eradication consists of bismuth quadruple therapy with a proton-pump inhibitor (PPI), a nitroimidazole, and tetracycline for 10-14 days or clarithromycin-based triple therapy with amoxicillin or amitronidazole and a PPI for 14 days (both strong recommendations).[25] Other first-line options are concomitant (14 days of clarithromycin, amoxicillin, and a nitroimidazole) or sequential (first week with amoxicillin and second week with clarithromycin and a nitroimidazole) or hybrid therapy (amoxicillin for 14 days, then adding clarithromycin and a nitroimidazole on the second week only).[25]

Note that the guidelines mention a nitroimidazole molecule in general (metronidazole or tinidazole), as they have similar efficacy, although tinidazole is not recommended as first-line therapy to avoid drug resistance.[25] As for levofloxacin-containing regimens, the quality of evidence is very low; these regimens could be used for 10-14 days, on a triple regimen of levofloxacin, amoxicillin, and a PPI. Another first-line therapy regimen is a fluoroquinolone sequential therapy with amoxicillin in the first week, followed by a PPI, fluoroquinolone with nitroimidazole in the second week.

Second-line or salvage therapy

Second-line therapy or salvage therapy depends on the antibiotics used in the first course of treatment and the culture results in cases of resistant strains. Levofloxacin- and rifabutin-based salvage regimens have a better degree of evidence than bismuth- or clarithromycin-based regimens.[25, 26] See the table below.

Acute Gastritis. Acute gastritis treatment options according to latest American College of Gastroenterology (ACG) guidelines are shown.

In a 2020 systematic review, investigators found nitazoxanide was effective in treatment-naïve patients as well as for salvage therapy.[27] This anti-protozoal drug increases the efficacy of multidrug regimens and could provide a good alternative in regions where multidrug resistance is endemic. Nitazoxanide is generally well tolerated and could also be of benefit in children.[27]

Other management

Administer fluids and electrolytes as required, particularly if the patient is vomiting.

Discontinue the use of drugs known to cause gastritis (eg, nonsteroidal anti-inflammatory drugs [NSAIDs], alcohol). A long-term prospective study found that patients with arthritis who were older than 65 years and regularly took low-dose aspirin were at an increased risk for dyspepsia severe enough to necessitate the discontinuation of NSAIDs.[28] This suggests that better management of NSAID use should be discussed with older patients to reduce NSAID-associated upper gastrointestinal events.

There has been a growing concern in recent years regarding the interaction between PPIs and clopidogrel. A decrease in the antiplatelet activity of clopidogrel with a possible increase in adverse cardiac events is postulated. Pharmacokinetically, it has been shown that omeprazole and lansoprazole interact significantly with clopidogrel, and that omeprazole, rabeprazole, and esomeprazole interact with prasugrel. Pantoprazole has been shown to have the least interaction and, thus, pantoprazole has low CYP2C19-inhibiting properties.[29, 30]

PPIs when used with clopidogrel will increase the risk of myocardial infarction and stent thrombosis, but this combination will not increase the risk of death or bleeding after percutaneous coronary intervention according to a 2019 meta-analysis.[31] Pantoprazole and lansoprazole have shown the least interaction with clopidogrel and appear to be safer than esomeprazole and omeprazole according to the latest FDA recommendations.[31]

Rebamipide is a drug that provides mucosal protection through activation of prostaglandins and inhibition of neutrophil response in the stomach lining, thus increasing the mucosal healing in NSAID-induced gastritis and H pylori infection. In separate 2018 and 2019 meta-analyses, rebamipide was effective when combined with H pylori eradication dual-therapy regimens, although its effect could be limited by ethnicity (ie, effective in Asian but not Caucasoid populations). This drug is not approved by the FDA, but it is used extensively in Korea, Japan, and Russia.[32, 33]

In 2015, a relatively new group of reversible PPIs known as potassium-competitive acid blockers (PCAB) was first approved in Japan. Vonoprazan causes 350 times more inhibition of acid secretion than lansoprazole does.[34]  In May 2022, the FDA approved vonoprazan (the first in the PCAB class) for the treatment of H pylori as a part of triple therapy. Two combination packs are available: vonaprazon + amoxicillin and vonoprazan + amoxicillin + clarithromycin.

Recommendations for using vonoprazan in erosive esophagitis in induction and maintenance therapy were presented in the 2022 AGA and Chinese guidelines.[35] The FDA had been expected to make a decision in January 2023 for the use of vonoprazan for erosive esophagitis; it is now requiring the manufacturer to provide additional stability data that demonstrates levels of a nitrosamine impurity (N-nitroso-vonoprazan [NVP]), which had been detected in trace amounts in commercial batches, remain below acceptable daily intake limits (96 ng/day) throughout the product's proposed shelf life.[36]

In a meta-analysis that examined the efficacy and safety of vonoprazan in the eradication of H pylori as compared to that of PPI-based triple-therapy, vonoprazan was associated with greater eradication (91.4% vs 74.8%) and fewer adverse events (32.7% vs 40.5%) in treatment-naïve patients.[37]

In H pylori eradication, vonoprazon action is not affected by changes in pH, thereby increasing its potency up to twice that of PPIs along with good cost-effectiveness.[38]  In addition, 1-week of vonoprazan-based triple therapy had similar efficacy (87.4%) as 2-weeks of PPI-based triple therapy (88%), without an increase in the adverse events.[39]

However, Japanese investigators have noted the prevalence of gastric mucosal redness, as detected by upper gastrointestinal endoscopy, was highest in patients who received vonoprazan (8.7%), as compared to those taking PPIs (6.2%) or antihistamines (1.5%), and relative to a control group (1.9%).[40]

Moreover, a 2022 postmarketing report raised a safety concern for vonoprazan-related nephrotoxicity. Time-to-onset (TTO) analysis until the occurrence of interstitial nephritis revealed a shorter TTO in those taking vonoprazan (average: 25 days) than those receiving PPIs (average: 41 days), whereas the TTO for acute kidney injury was similar for vonoprazon (average: 10.5 days) and PPIs (average: 11 days). These results have yet to be validated, and the impact of concomitant medications such as NSAIDs or chemotherapy remains unknown. Potential causes of such nephrotoxicity may be related to the mechanism of action of the drug, in which vonoprazon competes reversibly with the K+ ion on the H+–K+ pump.[34] Also, vonoprazon may induce the immune system through antigen mimicry, new antigen formation, or haptenization.[34]

In patients with gastritis, it is recommended to eradicate H pylori infection before starting nonsteroidal anti-inflammatory drug (NSAIDs)/aspirin treatment for the first time, as this will decrease the possibility of inducing gastroduodenal ulceration. Unfortunately, this therapy's effectiveness decreases with chronic use. However, chronic NSAIDs/aspirin users with known history of peptic ulcer or gastrointestinal bleeding could benefit from H pylori eradication by reducing the rebleeding risk.[41]

H pylori eradication testing can be performed 4 weeks after completing therapy for gastritis. It is carried out using either rapid urease breath testing or stool antigen testing. However, this is not cost effective and is not always done.

The current recommendation is that patients with ulcers from H pylori, mucosa-associated lymphoid tissue (MALT) lymphoma, a history of gastric cancer, and those with no improvement of symptoms despite treatment must be checked for resolution of H pylori infection.[25]

Specific treatment of gastritis is dependent on the underlying etiology.

According to the Centers for Disease Control and Prevention (CDC), the treatment of tuberculosis consists of a 2-month course of daily isoniazid, rifampin, and pyrazinamide, followed by 4-7 months of daily isoniazid along with rifampin.[42] See Tuberculosis.

Medical management (antibiotics, supportive care) is generally ineffective in treating phlegmonous gastritis; surgical intervention is typically required.

Several drugs are available for the treatment of cytomegalovirus (CMV) infection. These include ganciclovir, valganciclovir, foscarnet, and cidofovir. It should be noted that the majority of immunocompetent individuals recover from CMV infection without any therapeutic intervention. See Cytomegalovirus.

The treatment of C albicans includes a variety of agents, including nystatin, oral clotrimazole, itraconazole, fluconazole, amphotericin B, and ketoconazole. See Candidiasis.

The treatment of disseminated histoplasmosis includes several effective agents, including amphotericin B, itraconazole, and fluconazole. See Histoplasmosis.

No drugs are available to treat anisakidosis. Endoscopic removal may be necessary.

Class Summary

Used for general prophylaxis. Antacids containing aluminum and magnesium can help relieve symptoms of gastritis by neutralizing gastric acids. These agents are inexpensive and safe.

Aluminum and magnesium hydroxide, magnesia and alumina oral suspension (Rulox)

Drug combination that neutralizes gastric acidity and increases pH of the stomach and duodenal bulb. Aluminum ions inhibit smooth-muscle contraction and inhibit gastric emptying. Magnesium/aluminum antacid mixtures are used to avoid bowel function changes.

Class Summary

This class includes drugs whose mechanism of action is competitive inhibition of histamine at the histamine 2 (H2) receptor. Histamine plays an important role in gastric acid secretion, thereby making H2 blockers effective suppressors of basal gastric acid output and acid output stimulated by food and the neurological system. There are different drugs with different potencies and half-lives (eg, cimetidine, ranitidine, famotidine, nizatidine). Cimetidine will be discussed below as a representative of this class of drugs.

Cimetidine (Tagamet)

Inhibits histamine at H2 receptors of gastric parietal cells, which results in reduced gastric acid secretion, gastric volume, and hydrogen concentration.

Class Summary

Proton pump inhibitors are potent inhibitors of the proton (acid) pump (ie, the enzyme H+,K+-ATPase), located in the apical secretory membrane of the gastric acid secretory cells (parietal cell). Proton pump inhibitors can completely inhibit acid secretion and have a long duration of action. They are the most effective gastric acid blockers. Omeprazole will be discussed as a representative of this class of drugs.

Omeprazole (Prilosec)

Decreases gastric acid secretion by inhibiting the parietal cell H+/K+-ATPase pump.

Class Summary

Bacterial infections also can cause gastritis. The most common causative organism is H pylori. A number of therapeutic regimens are effective against H pylori. Single antimicrobial agents generally are not recommended because of the potential development of resistance.

Dual therapy includes a proton pump inhibitor plus amoxicillin (no longer recommended because eradication rates are only 30-80%) or a proton pump inhibitor plus clarithromycin (eradication rate of roughly 71%). Adding a second antimicrobial agent is recommended for successful eradication.

Triple regimens are preferred in clinical practice. One drug is a proton pump inhibitor or a bismuth-based drug, the second drug is clarithromycin, and the third drug is amoxicillin or metronidazole. Quadruple therapy regimens (ie, 2 antibiotics, bismuth, antisecretory agent) generally are effective; however, because more drugs are prescribed and taken, increased adverse effects and decreased patient compliance can occur. This regimen is used in the event that triple therapy fails.

The decision as to which medications to use is based on the following 4 criteria: (1) the different toxicities of the various medications, (2) the relative costs of each medication and regimen, (3) the emergence of antimicrobial-resistant bacteria, and (4) the level of patient compliance.

Amoxicillin (Amoxil, Trimox)

Interferes with the synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.

Tetracycline (Sumycin)

Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunit(s).

Metronidazole (Flagyl)

Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa.

Clarithromycin (Biaxin)

Inhibits bacterial growth, possibly by blocking the dissociation of peptidyl t-RNA from ribosomes and causing arrest of RNA-dependent protein synthesis.

Rifabutin (Mycobutin)

Mycobutin is a drug that is used off label to treat tuberculosis. It inhibits DNA-dependent RNA polymerase and is metabolized by hepatic CYP3A4 to active and inactive metabolites.

Class Summary

Used in combination with antibiotics and proton pump inhibitors/H2 receptor antagonists to eradicate H pylori.

Bismuth subsalicylate (Bismatrol, Pepto-Bismol)

Drug combination that treats active duodenal ulcer associated with H pylori.

Nitazoxanide (Alinia)

Nitazoxanide is an antiparasitic agent. It inhibits the growth of sporozoites and oocysts of Cryptosporidium and trophozoites of Giardia, as well as interferes with pyruvate:ferredoxin oxidoreductase (PFOR), essential to anaerobic energy metabolism.

It is metabolized by hydrolysis and glucuronidation, and excreted in the urine, bile, and feces.

Tinidazole (Tindamax)

Tinidazole is an antiprotozoal; it may cause cytotoxicity by damaging DNA and preventing further DNA synthesis.

This drug undergoes oxidation, hydroxylation, and conjugation, and is excreted mainly in the urine and feces.

Bismuth subsalicylate (Kaopectate, Kaopectate Extra Strength, Maalox Total Relief)

This agent has antimicrobial anti-inflammatory action (bismuth) and an antisecretory effect (salicylate).

Bismuth subsalicylate is hydrolyzed in stomach to form slightly soluble bismuth oxychloride (BiOCl) and salicylic acid. Bismuth is excreted through the feces, and salicylate is excreted through the urine.

Vonoprazan

A relatively new group of reversible proton-pump inhibitors known as potassium-competitive acid blockers (PCAB) was first approved in Japan in 2015. In May 2022, the FDA approved vonoprazan (the first in the PCAB class) for the treatment of H pylori as a part of triple therapy. There are two combination packs available: vonaprazon + amoxicillin) and vonoprazan + amoxicillin + clarithromycin.