Atrophic gastritis is a chronic inflammatory condition characterized by destruction of gastric cells and replacement with fibrous and intestinal-type tissues.
The disease is related to the following processes: degenerative and has an incidence of about 137 / 100.000.
Atrophic gastritis is a chronic inflammatory condition of the gastric mucosa with progressive destruction and loss of the glandular structures of the stomach and replacement of these cells by fibrous tissue and intestinal-type tissues.
There are two types of atrophic gastritis based on etiological and pathological characteristics. These include type A and type B. Type A atrophic gastritis is also referred to as autoimmune gastritis and type B mostly results from Helicobacter pylori (H. pylori) infection.
Approximately half of the world's population is infected with H. pylori which are most common in developing countries. Gastritis occurring due to autoimmune causes is relatively rare, and most commonly affects the Northern European and African American population. Generally, atrophic gastritis shows no sex predilections, however, autoimmune gastritis is common among women.
Both forms of atrophic gastritis have a high risk of malignant transformation. This risk of gastric cancer in H. pylori-associated atrophic gastritis reduces with H. pylori eradication . In addition to the risk of gastric carcinoma, chronic atrophic gastritis is also strongly associated with the development of enterochromaffin-like (ECL) cell hyperplasia and carcinoid tumors .
Endoscopy and biopsy are the definitive tests for confirming a diagnosis of atrophic gastritis. There are several other investigations specific for each type of atrophic gastritis including culture and rapid urease test of gastric biopsy samples for making a diagnosis of H. pylori-associated gastritis and serology for autoimmune gastritis.
Atrophic gastritis, as stated earlier, can be caused by autoimmune causes or H. pylori infection. Both forms of gastritis have unique and different histopathological features as also observed by Yagi et al from results of gastric analysis using magnifying endoscopy .
Autoimmune atrophic gastritis, the sequel to anti-gastric parietal cell antibodies (APCA), causes marked diffuse destruction and atrophy of parietal cells. The presence of serum anti-intrinsic factor antibodies leads to pernicious anemia from lack of transport/absorption of vitamin B12. Autoimmune atrophic gastritis also has a genetic predisposition with an autosomal dominant mode of inheritance. Research has found that the severity of autoimmune atrophic gastritis is directly proportional to the titers of APCA.
Approximately half of the world's population is infected with H. pylori and the infection is most commonly found in developing countries and in Asia. In the United states, H. pylori affect about 20% of individuals under 40 years and more than half of all persons above 60 years.
Autoimmune gastritis is relatively rare and it commonly affects Northern Europeans and African Americans. An estimated 127 cases per 100,000 individuals in Sweden, Denmark, and the United kingdom are said to have pernicious anemia/autoimmune gastritis. Concomitant immunological diseases, including Graves disease, Addison's disease, myxedema, and diabetes mellitus raise the risk of autoimmune gastritis.
Regardless of the cause, atrophic gastritis increases the risk of developing gastric carcinoma and carcinoid tumors. There is a further risk of developing esophageal squamous carcinoma in autoimmune gastritis and pernicious anemia. Autoimmune gastritis also increases the risk of iron deficiency anemia. All these complications of atrophic gastritis greatly increase the morbidity and mortality from the disease.
Atrophic gastritis, being chronic condition presents late in life. H. pylori-associated atrophic gastritis is detected in individuals above 50 years while pernicious anemia secondary to autoimmune atrophic gastritis can be detected from the sixth decade of life.
H. pylori-associated atrophic gastritis
H. pylorus is a gram-negative bacterium that infects and inhabits the stomach. The bacterium resides within the gastric mucosa. An individual is often infected with H. pylori during childhood and the bacteria remain in the stomach throughout life, if untreated.
The presence of H. pylori triggers a host response mainly comprising T and B lymphocytes. Subsequently, there is infiltration of the gastric mucosa and lamina propria by polymorphonuclear leukocytes (PMNs) which remove the bacteria by phagocytosis. The release of toxic products which characterize such inflammatory process damages the gastric mucosa, eventually leading to atrophic gastritis. According to a study published by Weck, the association between H. pylori and atrophic gastritis is stronger than that estimated by epidemiological findings because the infection usually clears off in late stages of atrophic gastritis . As reported by another study, the presence of mannan-binding lectin allele (MBL2 codon 54 B) corresponds to a more severe form of atrophic gastritis in Japanese patients infected with H. pylori .
The process of gastric atrophy results in erosion of the glandular structures and replacement with fibrous tissue and intestinal-type tissues expanding the lamina propria . This, consequently, results in parietal cell loss and a reduced gastric acid secretion. Alcohol has been shown to have potentiating effects in the development of H. pylori-associated atrophic gastritis .
There are two main histopathologic forms of H. pylori-associated atrophic gastritis; antral predominant form and the multifocal form. The antral predominant form is limited to the gastric antrum and is most often seen in western countries. It is the form of gastritis mostly associated with peptic ulcers. The multifocal form involves the atrium, fundus, and corpus of the stomach. This form is frequently observed in developing countries and is the form of atrophic gastritis mostly associated with gastric carcinoma.
Autoimmune atrophic gastritis
Autoimmune atrophic gastritis is limited to the gastric fundus and corpus and is characterized by diffuse parietal cell loss. Autoimmune gastritis is caused by the effects of serum anti-intrinsic factor and anti-parietal antibodies. As reported by Palladino et al., methylenetetrahydrofolate reductase (MTHFR) polymorphisms may also be associated with autoimmune atrophic gastritis . Generally in autoimmune gastritis, the autoantibodies target at least 3 antigens, including intrinsic factor (IF), cytoplasmic and plasma membrane antigens. There are two types of IF antibodies; types I and II. Type I IF antibodies block the IF-vitamin B12 binding site, preventing the uptake and therefore, transport of vitamin B12.
Cell-mediated immunity also plays a role in the development of the disease . T lymphocytes infiltrate the gastric mucosa and contribute to the epithelial cell destruction and consequent atrophy. Stummvoll showed that Th17 cells caused the most gastric damage with cellular infiltrates mainly made up of eosinophils associated with high serum IgE levels . Regulatory T cells (Treg) have been noted to inhibit the expansion of the effector T cells. However, effector cells isolated from protected animals were found to proliferate and produce effector cytokines ex vivo . This inhibitory capacity of polyclonal Treg on the proliferation of some effector cells describes its clinical use in the treatment of autoimmune disease. These findings stimulated a study by Huter et al, which showed that antigen-specific-induced Treg suppresses autoimmune gastritis induced by fully differentiated Th17 and Th1 effector cells .
H pylori-associated atrophic gastritis is often clinically asymptomatic. Symptomatic cases present with epigastric pain, malaise, nausea, vomiting, flatulence, and, occasionally, fever. The symptoms usually disappear, spontaneously, but a persistence of the infection leads to atrophic gastritis which presents just as above and also with considerable weight loss.
In autoimmune gastritis, consequent to IF deficiency and destruction, vitamin B12 is inadequately transported and absorbed. This results in a number of complications including megaloblastic anemia and certain neurological impairments.
Neurologic sequelae of vitamin B12 deficiency occur consequent to neuronal death and axonal degeneration primarily affecting the anterior and posterior spinal cord columns, the cerebrum and peripheral nerves. This, typically, manifests as paresthesias, weakness, and numbness of the limbs, ataxia and loss of sphincteric control. Cognitive impairments could occur, ranging from mild disturbances to psychosis.
There is a considerable increase in the risks of gastric polyps and carcinoma in patients with pernicious anemia. Iron deficiency anemia which is unresponsive to iron therapy is also a complication of autoimmune gastritis. Patients with pernicious anemia have an increased frequency of gastric polyps and carcinoma in patients with autoimmune gastritis.
Physical examination is not critical in the diagnosis of atrophic gastritis. General signs include epigastric tenderness, signs of anemia including pallor, palpitations and in severe cases, signs of congestive cardiac failure. In autoimmune gastritis, neurologic complications of vitamin B12 deficiency such as ataxia may also be elicited.
Upper GI endoscopy and biopsy of the gastric samples is the definitive test to confirm atrophic gastritis. One requires at least two samples taken from the antrum, two samples from the corpus and one from the incisure and submit separately for histopathologic evaluation.
Determination of serum pepsinogen levels with the ratio of serum pepsinogen I to pepsinogen II have high specificity and sensitivity in diagnosing gastric atrophy.
Although, there are a number of laboratory investigations to further confirm the type of atrophic gastritis, biopsy remains the gold standard. However, because in late stages of H. pylori-associated atrophic gastritis, the concentration of the organism is markedly reduced because of the unfavorable environment created by the malignant change , other investigations to detect H. pylori like urea breath test should be employed. Culture and rapid urease test of gastric biopsy samples, and serology for anti-H. pylori antibodies are alternative investigations in confirming H. pylori-associated atrophic gastritis.
Histologic findings in H. pylori-associated atrophic gastritis includes the presence of the bacteria within the gastric mucosa, usually more numerous in the antral region in early stages of the disease. PMNs are found in the lamina propria and the glands while lymphoid follicles can be observed within the lamina propria causing its expansion. Significant glandular atrophy is observed with disease progression. In advanced stages of the disease also, there is the extensive replacement of gastric architecture with intestinal metaplasia.
Autoimmune atrophic gastritis can be confirmed via the following laboratory investigations; serologic detection of serum anti-IF and anti-parietal cell antibodies, serum cobalamin levels , serum gastrin levels and schilling test. Serum gastrin levels are usually high and cobalamin levels are low in autoimmune gastritis. Achlorhydria, either basal or stimulated, also suggests autoimmune atrophic gastritis.
The histologic findings in autoimmune atrophic gastritis vary with the phase of the disease. During the early phase, there is diffuse distortion in the architecture of gastric structures due to infiltration of the lamina propria by eosinophils and mononuclear cells and of the oxyntic glands by T-lymphocytes. Hypertrophy of parietal cells is also found. Over time, there is increased lymphocytic inflammatory changes with atrophy of the oxyntic glands, and intestinal metaplasia. Intestinal metaplasia with widespread involvement of the fundus and corpus marks the end stage of the disease. The antrum is usually spared in autoimmune gastritis. Autoimmune gastritis may also present with gastric polyps which are non-neoplastic hyperplasia of spared oxyntic glands.
If H. pylori are detected as the underlying cause of gastritis, its eradication is initiated. Current therapies for H. pylori infection offer 80-95% cure rates. Currently, the most common and effective therapies to eradicate H. pylori are triple therapies, which are considered as first-line treatments and quadruple therapies. Quadruple therapies are recommended as second-line treatments to be used when the first line treatment fails. In both treatment protocols, treatment duration of 10-14 days is associated with best outcomes, although some studies suggest a duration of treatment of 7 days. H. pylori infection is considered cured and the bacteria considered eradicated if there is no trace of the bacterium after at least 4 weeks of treatment.
Triple therapy consists of two antibiotics and one proton pump inhibitor or bismuth salicylate and includes the following:
Another protocol for triple-therapy includes bismuth subsalicylate 525 mg (two 262.4-mg chewable tabs) qid along with metronidazole 250 mg PO qid and tetracycline HCL 500 mg qid.
Quadruple therapy consists of one PPI, two antibiotics plus bismuth salicylate. This therapy includes PPI bid, including lansoprazole 30 mg PO bid or omeprazole 20 mg PO bid plus tetracycline HCl 500 mg PO qid, bismuth subsalicylate 120 mg PO qid, and metronidazole 500 mg PO three times per day.
Autoimmune gastritis cannot be prevented mainly because of its strong genetic and immunological predispositions. H. pylori infection, however, can be prevented. This can be achieved by healthy hygiene practices including proper handwashing before and after eating and after using the bathroom. Caregivers should also maintain proper handwashing after handling soiled baby clothing.
What is atrophic gastritis?
Atrophic gastritis is a condition characterized by prolonged inflammation of the stomach's lining. This condition could be caused by a bacterium called Helicobacter pylori, or by the body's antibodies attacking the stomach lining (autoimmunity).
H. pylori infect and lodges in the stomach in the early years of life and results in inflammatory changes by destroying the stomach's protection against its acid contents. H. pylori can be transmitted through contact with feces or saliva of an infected person. It could also be contracted through contaminated food and water. Autoimmune atrophic gastritis usually results in damage to the cells which produce vitamin B12, resulting in anemia.
H.pylori infection is the commonest risk factor for developing atrophic gastritis. This infection is commonly found among persons with low socioeconomic status and those who live in overcrowded areas.
The risk of autoimmune atrophic gastritis is increased in people who have other immune conditions and in African Americans and Northern Europeans.
The problem with atrophic gastritis is the development of stomach cancer.
Atrophic gastritis often presents with no symptoms at all. However, H. pylori-associated atrophic gastritis presents with abdominal pain, loss of appetite, vomiting, and weight loss. Autoimmune atrophic gastritis causes anemia which presents with dizziness, lightheadedness, and palpitations. Vitamin B12 deficiency, also a sequel of autoimmune atrophic gastritis presents with numbness and pain in the arms and feet.
Diagnosis and workup
A diagnosis of atrophic gastritis can be made by clinical examination and blood tests. The doctor would examine for features of atrophic gastritis including upper abdominal pain, and signs of complications of autoimmune gastritis including anemia ( pallor, palpitations) and vitamin B12 deficiency.
Blood tests for pepsinogen (produced by the stomach cells) and gastrin, a substance that stimulates acid production in the stomach, vitamin B12, and antibodies against stomach cells would be necessary.
Biopsy of the stomach carried out by using a long tube (endoscope) inserted through the mouth into the stomach may also be needed to confirm autoimmune gastritis.
Treatment of H. pylori-associated gastritis is with antibiotics. Autoimmune gastritis is treated with steroids and vitamin B12. Drugs which lower production or neutralize stomach acid are also prescribed.