and gastropathy: more than meets the eye This paper discusses the different types of gastritides and gastropathies, focusing on their wide range of aetiologies.

Willie Nel, MB ChB, M Med (Anat Path) Anatomical pathologist, Ampath Pathology Laboratories, Pretoria Willie Nel did his undergraduate training at the University of the Free State and postgraduate training at the University of Pretoria. He joined the private practice of doctors Du Buisson and partners (Ampath) after two years as a consultant at the Institute of Pathology in Pretoria. Amongst his special interests are motorcycling and cattle breeding.

Correspondence to: Willie Nel ([email protected])

Gastrointestinal symptoms such as chronic inflammatory changes which The different types of gastritides and dyspepsia, heartburn, epigastric pain, may eventually lead to mucosal atrophy gastropathies and their wide range of and vomiting are extremely and epithelial metaplasia. Gastritis is a aetiologies will now be discussed. common and have been experienced dynamic process, which can vary from by the majority of people at some stage acute to chronic (active or inactive), Acute gastritis in their lifetime. These complaints are present in different stages of recovery or Acute haemorrhagic gastritis often as a result of pathology in the upper atrophy and may lead to complications. Acute haemorrhagic gastritis is characterised . Correlation between The may be diffuse, or affect by the presence of hyperaemic, oedematous the clinical presentation (symptoms, signs predominantly the antrum or corpus. mucosa, erosions/ulcers and active bleeding, and endoscopic findings) and pathology, and is usually seen in stress situations (e.g. including the degree and precise localisation The mucosa of the is covered severe burns), patients in ICU and after of the disease process, is unfortunately by a thin surface mucus layer serving, ingestion of large doses of aspirin, and notoriously poor. This is mainly due to in conjunction with bicarbonate- other types of NSAID or large quantities of the absence of a somatic nerve supply to secreting surface epithelial cells and local alcohol. the gut wall. The stomach is a common prostaglandin production, as a protective site of pathology responsible for upper barrier against autodigestion and noxious Acute gastritis in gastrointestinal symptoms, which may have agents. The also has the infection an extremely wide range of causes. ability to proliferate and replace damaged The initial phase of Helicobacter infection epithelium very rapidly. causes an acute inflammatory reaction In pathological terms, and degenerative changes in the surface In 1990 the Sydney system was developed as epithelial cells of the gastric mucosa. gastritis is defined as a guideline for the classification and grading Symptoms may include epigastric pain, a inflammation of the of gastritis by a group of international bloated feeling and nausea; these most often experts in Sydney, Australia. This system resolve within a week. After approximately gastric mucosa. combines topographical, morphological two weeks the reaction evolves into an and aetiological information into a scheme active chronic gastritis. In pathological terms, gastritis is defined that helps generate a reproducible and as inflammation of the gastric mucosa. clinically useful diagnosis. Four years later Acute bacterial or phlegmonous It is, however, a term often used loosely this system was updated and subsequently gastritis for clinical conditions associated with modified to improve the criteria for This is exceedingly rare and in many any upper gastrointestinal symptoms evaluating atrophy. It recommends that at cases only identified at postmortem without clinical or radiological signs. least five biopsy specimens (two from the examination. Predisposing factors include Gastropathy, on the other hand, refers to greater and lesser curvatures of the corpus, immunosuppression, disability and a nonspecific microscopic injury pattern one from the incisura angularis and two chronic alcoholism. The most common of stomach mucosa, with minimal or from the larger and lesser curvatures of infective organism is Streptococcus, but no inflammatory cell infiltration. Both the antrum) with mucosa and muscularis Staphylococcus, Haemophilus influenzae, gastritis and gastropathy may be clinically mucosae represented in each biopsy be Escherichia coli and Proteus spp have also asymptomatic. evaluated. In practice, however, pathologists been implicated. These bacteria cause an are usually asked to make a diagnosis on one intense acute inflammatory response with Acute gastritis is an acute mucosal or two biopsy specimens as most types of ulceration and abscess formation involving inflammatory process, usually of transient gastritis can be diagnosed without extensive the full thickness of the gastric wall. nature, while chronic gastritis refers to tissue sampling. Patients present with nausea, vomiting,

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upper abdominal pain and tenderness, even atrophy, but there are no distinctive be performed 4 weeks after the end of usually associated with a neutrophilic endoscopic patterns of chronic HP gastritis. therapy, as the test may produce a false- leukocytosis. The condition has a high In the early phase an acute inflammatory negative result with persistent infection due mortality, but patients treated surgically response is elicited, which usually to temporary inactivation of the pathogen have a better chance of survival. progresses to an active chronic gastritis. shortly after treatment. HP serology is This may be antral-predominant, corpus- relatively sensitive and specific with no Chronic gastritis predominant or diffusely affect the stomach interference due to the intake of bismuth, Helicobacter pylori (HP) gastritis as a pangastritis (Fig. 1). After treatment, antibiotics and PPIs. There is no correlation These tiny spiral-shaped bacilli in the neutrophils disappear rapidly; their between the IgG antibody titres and the stomach were described for decades continued presence in biopsies is considered severity of the HP gastritis, however, and a by pathologists, but were dismissed as a valuable indicator of unsuccessful HP decrease in titres less than 6 months after irrelevant contaminants. In 1984 Warren eradication. After successful treatment therapy is of no diagnostic value in verifying and Marshall proposed their aetiological the intensity of the chronic inflammation successful eradication. role in chronic idiopathic gastritis due to declines, but patients may show persistence toxins released by the organisms directly of chronic inactive gastritis for several years. affecting the gastric epithelium and local Persistent infections may eventually lead to microcirculation. atrophic gastritis, which may be antrum- restricted or involve the stomach more Gastritis is a dynamic extensively. process, which can vary from acute to chronic (active or inactive), present in different Fig. 2. Curved Helicobacter pylori bacilli ad- jacent to the gastric epithelium on a methy- stages of recovery or lene blue stain. atrophy and may lead to complications. More than 50 species of Helicobacter have been described, but only a few have been Fig. 1. A biopsy demonstrating chronic shown to cause gastritis. In about 0.1 - HP gastritis has a high prevalence in active gastritis — a background of chronic 2.7% of cases H. heilmannii is identified. developing countries, but has been declining inflammation, with neutrophils present These organisms are twice as long as HP in areas due to improved sanitary conditions between the glandular epithelium. and usually cause a milder and patchier and the widespread use of antibiotics. gastritis. Treatment is similar to that for HP Natural acquisition of HP infection usually Diagnosis of HP infection can be rendered infections. occurs in childhood and may persist for life. using invasive and noninvasive tests. However, transient infections often occur. Invasive tests are based on endoscopy The initial phase of a Direct person-to-person spread is the most and histological examination of gastric likely mode of transmission, as no significant biopsies (Fig. 2). These have the advantage Helicobacter infection reservoir has been shown to exist outside of allowing direct evaluation the upper GI causes an acute the human stomach. Ingestion appears to tract for any superimposed complications. be the most common means of acquiring The number of organisms in biopsy material inflammatory reaction HP. Routes of transmission include gastric- may be markedly reduced (even absent) and degenerative oral (by refluxed gastric juice or vomitus), due to antibiotic treatment prior to biopsy, and the faecal-oral route (during episodes the use of proton pump inhibitors (PPIs) or changes in the surface of diarrhoea). Poor hygiene standards, in chronic atrophic gastritis. Noninvasive epithelial cells of the crowded households, deficient sanitation diagnostic tests include the C-urea breath gastric mucosa. and the absence of running water in the test (only performed in certain centres), home are associated with a high prevalence detection of serum IgG antibodies directed of HP infection. against HP and stool HP antigen tests, some Some patients with HP are asymptomatic of which can also be used for follow-up. and go undetected, but all patients in whom The endoscopist may find mucosal As a method to evaluate HP eradication, HP infection is identified should undergo hyperaemia, erosions, hypertrophy and the C-urea breath test should preferably treatment. If untreated, HP gastritis confers

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a 15 - 20% lifetime risk of developing Endoscopically, the mucosa of the corpus is or NSAID use, or in association with (Fig. 3). Eradication thinner than normal. Often a reduction or lymphocytic/collagenous . Treatment of HP facilitates healing of these ulcers absence of rugal folds and small mucosal is steroids and management of any and prevents their recurrence. More than elevations due to the presence of islands of underlying cause. 90% of primary gastric mucosa-associated intestinal metaplasia are seen. In the florid lymphoid tissue (MALT) lymphomas are phase microscopy reveals a dense infiltrate Collagenous gastritis seen in patients with HP gastritis, and of lymphocytes and plasma cells involving This is a rare entity characterised by a more than 75% will regress for extended the entire thickness of the corpus mucosa thickened subepithelial band of collagen periods upon successful eradication of with destruction of the oxyntic glands. and chronic inflammatory infiltrate in the infection. Atrophic gastritis is also a As atrophy sets in, the mucosa shows a the gastric mucosa, similar to that seen risk factor for dysplasia and intestinal type marked reduction of these glands, reduced in . The disease may adenocarcinoma. inflammation and increasing degrees of be limited to the stomach, then usually intestinal and pyloric metaplasia. Metaplasia in children and young adults presenting refers to replacement of normal gastric with anaemia due to gastric bleeding, and epithelium by modified cells of intestinal demonstrate focal nodularity of the gastric or pyloric variety. The hypo-/ mucosa on endoscopy. It may also be found cause physiological hypergastrinaemia, in adults with collagenous colitis and present which in turn stimulates proliferation with a chronic watery diarrhoea. of neuroendocrine cells and can lead to development of neuroendocrine tumours Eosinophilic gastritis (‘’). These tumours are relatively Eosinophilic gastritis and may innocuous, in contrast to the less common affect all age groups and present with failure solitary, sporadic type which is more to thrive (in children), abdominal pain, Fig. 3. Macroscopic appearance of a gastric aggressive. irritability, gastric dysmotility, vomiting, chronic peptic ulcer (courtesy of Dr M Louw, diarrhoea, dysphagia and (in severe cases) Department of Anatomical Pathology, Uni- Lymphocytic gastritis protein-losing . Many patients versity of Pretoria). A diagnosis of lymphocytic gastritis can are atopic and have increased serum total only be made on histology, but many IgE and food-specific IgE, as well as blood Triple therapy with either amoxicillin patients have the endoscopic features of eosinophilia. This entity is characterised or metronidazole, clarithromycin and varioliform gastritis with mucosal nodules, by eosinophil-rich inflammation of all or a PPI given twice daily for 7 - 14 days chronic persistent erosions and thickened is recommended as first-line therapy. mucosal folds. The disease is characterised As second line therapy levofloxacin, by an infiltrate of lymphocytes in the lamina amoxicillin and PPI for 10 -14 days or propria with large numbers of lymphocytes bismuth-based quadruple therapy are among the epithelial cells lining the surface recommended. Increasing HP resistance to and foveolae. various antibiotics is a significant concern, however. More than 50 species of Autoimmune gastritis Helicobacter have been This corpus-restricted gastritis is associated described, but only a with circulating autoantibodies against the microsomes of parietal cells as well as few have been shown to . Intrinsic factor plays a key cause gastritis. role in the absorption of , and gastric acid is important for absorption of The aetiology remains uncertain, although iron. Destruction of the cells producing an allergic or autoimmune pathogenesis and intrinsic factor, is proposed. Lymphocytic gastritis may be respectively, results in hypochlorhydria found in association with and a reduction in activity within (gluten-sensitive enteropathy), Menetrier’s gastric juices and may lead to pernicious disease (hypertrophic gastropathy or iron deficiency anemia. The finding of characterised by a hypertrophic gastric a low pepsinogen I level in the serum is a mucosa with convoluted, thickened mucosal sensitive and specific indicator of gastric folds and protein-losing enteropathy), as atrophy. an abnormal response to HP infection

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a portion of the GI tract wall. Gastroscopy such as cytomegalovirus and herpes are better tolerated by the gastric may reveal antral mucosal swelling and simplex virus more commonly affect the mucosa. Endoscopically, long-term redness with narrowing of the and oesophagus, but may also demonstrate users of NSAIDs may show mucosal diminished peristalsis. gastric involvement with ulceration. erythema, congestion, erosions and Toxoplasmosis and cryptosporidiosis (Fig. ulcers. Histologically the mucosa reveals Chemical gastropathy 4) are protozoal infections which may affect oedema, foveolar hyperplasia, smooth- the stomach. muscle proliferation, regeneration and, refers to endoscopic and on occasion, erosion with a relatively histological changes mild inflammatory cell response. • Duodenopancreatic (bile) reflux is seen caused by chemical particularly in patients with a Billroth II injury to the gastric partial gastrectomy. A chronic gastritis with marked foveolar hyperplasia, which mucosa. may be cystic or polypoid, develops proximal to the stoma. Improvement after elimination of certain • Acids, alkalis and large quantities of foods from the diet supports an allergic alcohol. Most of these cause extensive aetiology. Parasites and drug reactions are a severe, necrotising lesions. much less common cause. Fig. 4. Gastric biopsy showing Cryptospo- ridium spp. infection, with large numbers of Vascular gastropathy Granulomatous gastritis small spherical parasitic organisms adjacent Vascular gastropathy refers to a group This group of conditions is characterised to the epithelium. of disorders characterised by distinct by multiple granulomas in the gastric alterations in the gastric mucosal blood mucosa and has a long list of possible Gastropathy vessels and a paucity or absence of causes. This includes infections such Chemical (reactive) gastropathy inflammation. as tuberculosis and histoplasmosis, Chemical gastropathy was recommended • Gastric antral vascular ectasia (GAVE or foreign body reaction directed against as the preferred term to synonyms such ‘watermelon stomach’) is a rare condition postoperative sutures or food trapped in as chemical gastritis, type C gastritis ulcers, tumours such as mucus-producing and , and refers to Table I. Aetiology of gastritis and adenocarcinomas and lymphomas, as well endoscopic and histological changes caused gastropathy as systemic granulomatous diseases such as by chemical injury to the gastric mucosa. sarcoidosis, Crohn’s disease and Wegener’s Gastritis granulomatosis. • Acute Immunocompromised Stress Opportunistic infections of the patients are at risk NSAIDs stomach Alcohol for opportunistic Helicobacter (early phase) Immunocompromised patients are at Bacteria (phlegmonous) risk for opportunistic GI infections, with gastrointestinal the stomach relatively rarely affected in • Chronic infections, with the Helicobacter comparison to the rest of the gut. stomach relatively rarely Autoimmune Allergy Fungal infections include gastric affected in comparison Tuberculosis candidiasis, which may appear as a white to the rest of the gut. Opportunistic infections plaque which can be removed to reveal Idiopathic a reddened underlying mucosa, or as Gastropathy a saprophyte colonising the necrotic Chemical agents commonly associated • Chemical debris in an ulcer base, aggravating the with mucosal damage include: Medications disease. GI phycomycosis (zygomycosis, • Medications, particularly NSAIDs, but Bile reflux mucormycosis) is rare, may be associated also drugs such as PPIs, iron, kayexalate, Acids, alkalis, alcohol with diabetes mellitus and results in colchicine, antineoplastics and ulceration and invasion of blood vessels by corticosteroids. NSAIDs cause mucosal • Vascular the fungus. Cryptococcus and Histoplasma damage by reducing prostaglandin Vascular ectasia (idiopathic) gastric infections are seen in conjunction synthesis. Second-generation and with disseminated disease. Viral infections selective NSAIDs and COX-2 inhibitors

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of unknown aetiology. Endoscopy shows most prominent in the proximal stomach. range of causes. H. pylori infection is longitudinal mucosal folds with ectatic The endoscopic appearance may resemble common worldwide and, if left untreated, vessels converging from the proximal snake skin, cherry red spots or have a is associated with complications including antrum into the pylorus. Histology reveals mosaic pattern. Decompression of the peptic ulcer disease, atrophic gastritis and marked dilated mucosal capillaries, some portal hypertension by means of bypass gastric neoplasms. Chemical injury to the of which may be thrombosed, and features surgery reduces the risk of haemorrhage. gastric mucosa due to medications such as of reactive gastropathy. Patients may NSAIDs, bile reflux and the intake of large present with occult bleeding, melaena, The varied aetiologies of gastritis and quantities of alcohol is well known, as are haematemesis and anaemia. gastropathy are summarised in Table I. autoimmune reactions causing atrophic • Portal hypertensive gastropathy is seen gastritis and allergies to food which may in patients with portal hypertension who Conclusion result in an eosinophilic gastritis. may present with gastric haemorrhage Gastritis and gastropathy may be clinically due to dilatation, congestion and silent or present with central upper proliferation of mucosal blood vessels, abdominal symptoms, and have a wide Further reading available at www.cmej.org.za

IN A NUTSHELL • Gastritis and gastropathy are common causes of upper gastrointestinal symptoms. • Correlation between clinical presentation, endoscopic features and biopsy findings is poor. • Gastritis refers to inflammation of the gastric mucosa, whereas gastropathy is a nonspecific microscopic injury pattern with little or no inflam- matory cell infiltration. • Gastritis and gastropathy are associated with a wide range of aetiologies (causes). • Gastritis is divided into acute and chronic forms. • The commonest form of acute gastritis is acute haemorrhagic gastritis. • Helicobacter-associated and autoimmune gastritis are the commonest types of chronic gastritis. • Less common and more unusual forms of gastritis include eosinophilic, lymphocytic, collagenous and granulomatous gastritis. • Opportunistic gastric infections may be caused by numerous fungi, parasites and viruses. • Gastropathy is most often due to chemical irritation of the gastric mucosa.

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