Evolution and Associations of Helicobacter pylori Gastritis

H.pylori gastritis is a life-long infection that can be viewed as a spectral disease. At the one end of the spectrum, inflammation remains mostly confined to the antrum and the cardia, the oxyntic mucosa is mildly affected, and atrophy is absent or minimal. At the other end, severe inflammatory changes involve the entire gastric mucosa and inflict progressive damage that results in loss of the normal gastric glands and their replacement by fibrous tissue and metaplastic epithelia. Although these are aspects of the same disease that can be placed on a continuous scale, the epidemiologic distribution and the associations of the two extremes are profoundly different. Gastritis confined to the antrum and without significant atrophy does not impair acid secretion, is commonly present in patients with duodenal ulcer, and has not been linked to increased cancer risk. Conversely, generalized gastritis with atrophy reduces acid secretion and is strongly associated with gastric adenocarcinoma. Thus, for the practical purposes of classification and prognostic evaluation, it has been expedient to divide gastritis into two phenotypes: nonatrophicantrum-predominant gastritis and multifocal atrophic gastritis.

Antrum-Predominant Gastritis This is the most common form of gastritis in the Western world. Its characteristics are as follows: a moderately to severely inflamed antrum; a mildly inflamed or normal corpus; minimal or absent atrophy or intestinal metaplasia, limited to the antrum; and normal or increased acid secretion. Most patients with this type of gastritis have neither symptoms nor complications. However, they have a risk of duodenal ulcer, estimated at 20% over their lifetime.

Atrophic Gastritis Also called multifocal atrophic gastritis, metaplastic atrophic gastritis, and atrophic pangastritis, this disorder is characterized by marked diffuse mucosal inflammation, often more severe in the oxyntic mucosa, by patches of atrophy and intestinal metaplasia in both antrum and corpus, and by variously reduced acid secretion. Atrophic gastritis is most prevalent in populations that are—or were, until a few decades ago—living in suboptimal sanitary conditions, including much of South and East Asia, Latin America, and parts of Central, Eastern, and Southern Europe. Socioeconomic factors may be a surrogate for other unknown agents that modulate the evolution of gastritis, because there are notable epidemiologic exceptions to this association. Japan, a country with high levels of sanitation and personal hygiene, has one of the world’s highest prevalences of atrophic gastritis and a high incidence of gastric adenocarcinoma. In contrast, Equatorial Africa, in spite of its precarious socioeconomic texture, inadequate sanitary standards, and a prevalence of H.pylori close to 90%, appears to have a low prevalence of atrophic gastritis and a low incidence of gastric adenocarcinoma. Several explanations have been proposed for this ‘African enigma,” ranging from diet, human and bacterial genetics, to unreliable statistics. Atrophic gastritis is a risk factor for gastric epithelial dysplasia, a precursor of the intestinal-type adenocarcinoma of the stomach. It also predisposes patients to gastric ulcer.

Peptic Ulcers, Carcinoma, and Lymphoma In addition to peptic ulcer disease and gastric carcinoma, H.pylori infection is also epidemiologically related to primary gastric MALT-lymphomas.

Extragastrointestinal Manifestations of Helicobacter pylori infection H.pylori infection has been proposed to be associated with an ever-growing number of extragastric manifestations of H.pylori infection, even if their causal relationship with H.pylori is far from conclusively demonstrated. Most of these associations are founded on epidemiologic data; however, both H.pylori infection and of some of the conditions allegedly associated with it (e.g., atherosclerosis) have a very high prevalence in many populations. Thus, biologic rather than epidemiologic data will be needed to prove causation. For one of these conditions, rosacea, there are several randomized trials that essentially disprove the association with H.pylori. Conversely, several clinical studies based on treatment results lend some support to the possibility of a pathogenetic involvement of H.pylori in iron deficiency anemia and autoimmune thrombocytopenic purpura. For most other conditions, data are insufficient to reach informed conclusions; however, the biologic plausibility in some of the proposed associations (e.g., with migraine) is so low that one must wonder whether attempts to prove causality are worth the effort.

INFECTIOUS GASTRITIS (EXCLUDING HELICOBACTER)

Because of the high acid content of the normal stomach, the gastric environment is inhospitable to most infectious agents. However, in patients with atrophic gastritis and decreased acid secretion, in patients with impaired immune responses, or as part of systemic infections, numerous viruses, bacteria, and parasites can infect the stomach. Although rare, some of these infectious gastritides have characteristic clinical and pathological features.

Viruses

Enteric rotaviruses and caliciviruses probably infect the stomach during the course of gastroenteritis, but no pathological changes in the gastric mucosa have been documented in volunteer studies with these agents. Only cytomegalovirus (CMV) infection is known to have a distinct pathological appearance in the stomach. CMV gastritis is seen almost exclusively in young children and immunocompromised patients, and it is usually associated with concurrent CMV infection of other sites of the digestive tract. Endoscopically, the gastric mucosa may appear completely normal or may show erosions, shallow ulcers, or hemorrhagic gastritis. Rarely, the condition may present as grossly nodular mucosa that has been referred to as a pseudotumor. CMV inclusions may be abundant and thus easily detected using the routine hematoxylin and eosin stain, or they may be rare and impossible to demonstrate without using immunohistochemi­stry or in situ hybridization techniques. A characteristic manifestation of CMV infection in the stomach of young children is massive foveolar hyperplasia accompanied by edema and mild inflammation of the lamina propria. The resulting endoscopic appearance is that of a giant-fold hypertrophic gastropathy indistinguishable from Ménétrier disease.

The diagnosis of gastric CMV infection is made by demonstrating the characteristic nuclear or cytoplasmic viral inclusions. The only effective therapeutic agent is ganciclovir, a guanosine derivative that selectively inhibits CMV DNA polymerase. In patients with acquired immunodeficiency syndrome (AIDS) and CMV colitis, ganciclovir has a response rate of 70% to 90%.

Bacteria

Bacterial overgrowth may occur in stomachs that have become achlorhydric as a result of atrophy, complete antrectomy, or vagotomy or as a result of long-term use of histamine H 2-receptor antagonists or proton pump inhibitors. Patients with scleroderma and other severe motility impairments are also prone to bacterial overgrowth. In contrast to H.pylori, however, these bacteria colonize rather than infect the gastric mucosa, and they neither elicit inflammatory responses nor cause symptoms.

An extremely rare condition is acute suppurative gastritis, also known as phlegmonous gastritis. This life-threatening condition is caused by pyogenic bacteria (streptococci, staphylococci, Escherichia coli, Proteus, and Haemophilus spp.) and is characterized by large areas of purulent necrosis involving the full thickness of the gastric wall. When it is caused by gas-forming organisms, the term emphysematous gastritis has been used. Few cases have been reported, mostly in very young children, elderly persons, patients with alcoholism, and immunocompromised patients. Potential iatrogenic causes include polypectomy and mucosal injection with India ink. The diagnosis is made endoscopically or at surgery. Antibiotic treatment may have to be accompanied by surgical intervention.

Primary gastric tuberculosis is rare, particularly in industrialized countries. However, in patients with disseminated tuberculosis, necrotizing granulomata may be found in the gastric mucosa. Another Mycobacterium that has gained prominence with the spread of AIDS is Mycobacterium avium-intracellulare complex, but the stomach is rarely involved; when it is, typical lesions consist of accumulations of foamy histiocytes in the lamina propria, sometimes with formation of ill-defined granulomata without necrosis.

In the 1980s and early 1990s, increasing numbers of cases of gastric syphilis were reported in patients infected with human immunodeficiency virus. When associated with secondary syphilis, syphilitic gastritis is characterized by a prominent mixed inflammatory infiltrate consisting predominantly of plasma cells and with mucosal ulcerations. The infiltrate may be dense enough to cause the swelling of gastric folds, which may also undergo erosion and ulceration, sometimes mimicking the endoscopic appearance of lymphoma or infiltrating carcinoma. Symptoms include severe dyspepsia, nausea, vomiting, and anorexia, with rapid weight loss. The diagnosis is often delayed by a low index of suspicion. Although spirochetes may be seen in sections stained with appropriate silver stains (Dieterle, Steiner, or Warthin-Starry), the search may be painstaking and is usually beyond the reach of the nonspecialist pathologist. Standard treatment for secondary syphilis is rapidly effective.

Fungi

Candida species, Histoplasmacapsulatum, and Mucoraceae have been found in the stomach of immunocompromised patients, particularly those with AIDS, with disseminated infections, but none of these fungi have been reported as a primary cause of gastritis.

Parasites

The stomach is not a preferred site for human parasitic infections, but Cryptosporidium spp. and Giardia intestinalis have been identified in the gastric mucosa. Strongyloidesstercoralis has been found in the stomach of a few patients with widespread infections.

The only nematodes that invade the human gastric wall are those of the family collectively known as Anisakidae, or “sushi worms.” Anisakiasis is an important cause of morbidity in countries such as Japan, where large quantities of raw fish are consumed. The muscle of many species of edible fishes contain larvae of Anisakidae. In a small proportion of persons who eat infected fish, larvae penetrate the gastric wall and cause a sudden onset of epigastric pain. Because the worms can be easily removed endoscopically by an experienced operator and the disease is self-limited in any case, patients presenting with epigastric pain in high-prevalence countries should be asked routinely about ingestion of raw or undercooked fish within 12 hours before the onset of symptoms. This practice would help to avoid unnecessary surgery.

Дата добавления: 2015-11-14