16/10/2014 Classification and diagnosis of gastritis and gastropathy

http://www.uptodate.com/contents/classification-and-diagnosis-of-gastritis-and-gastropathy?topicKey=GAST%2F29&elapsedTimeMs=0&source=search 1/10

Official reprint from UpToDate www.uptodate.com 2014 UpToDate

AuthorsBeverly A Dickson, MDMark Feldman, MD, MACP, AGAF,FACG

Section EditorJ Thomas Lamont, MD

Deputy EditorShilpa Grover, MD, MPH

Classification and diagnosis of gastritis and gastropathy

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Sep 2014. | This topic last updated: Apr 23, 2014.

INTRODUCTION Gastritis is predominantly an inflammatory process, while gastropathy demonstratesminimal to no inflammation. The term gastritis is used to denote inflammation associated mucosal injury.However, epithelial cell injury and regeneration are not always accompanied by mucosal inflammation. Thisdistinction has caused considerable confusion since the term "gastritis" is often used to describe endoscopic orradiologic characteristics of the gastric mucosa rather than specific histologic findings. Epithelial cell damageand regeneration with minimal or no associated inflammation is properly referred to as "gastropathy."

The causes, natural history, and therapeutic implications of gastropathy differ from gastritis:

"Gastritis" is a term often used by endoscopists to describe the gastric mucosa rather than representing aparticular endoscopic entity. A gastric mucosal biopsy is necessary to establish a definitive diagnosis ofgastritis versus gastropathy.

This topic review will discuss the classification and diagnosis of gastritis and gastropathy. The causes of acuteand chronic gastritis are presented separately.

HISTORY The existence of gastric inflammation was debated during the 19 and early part of the 20century. It was recognized that postmortem digestion markedly altered the gastric mucosa; as a result thesignificance of gastric mucosal inflammation was uncertain. This was clarified by the histologic demonstrationof inflammation on gastric specimens prepared shortly after death [1] and by the use of gastroscopy beginningin the 1920s and gastric biopsy in the 1940s [2].

CLASSIFICATION OF GASTRITIS AND GASTROPATHY There is no universally accepted classificationof gastritis/gastropathy, although several classifications of gastritis and gastropathy (such as the Sydneysystem and the Operative Link for Gastritis Assessment [OLGA] staging system) have been proposed (table 1)[3-8]. The updated Sydney system is the most widely used classification; however, it does not yield actionableprognostic information concerning cancer risk in cases of chronic atrophic gastritis. The OLGA staging systemmay provide information about secondary gastric cancers in autoimmune gastritis [9,10]. The OLGA stagingsystem, which was proposed by an international group of pathologists for use in standardizing classification ofatrophic gastritis, incorporates histologic phenotypes with extent of disease to aid in prediction of cancer risks[11]. The high stage disease (OLGA III/IV) is associated with a high risk of gastric cancer. Operative Link onGastric Intestinal Metaplasia Assessment (OLGIM), another proposed system, shows less interobservervariability and is still prognostically useful [9,10,12]. Gastritis has been classified by histologic features, timecourse (acute versus chronic), etiology, and proposed pathophysiology. (See "Gastric intestinal metaplasia",section on 'Definitions'.)

However, classification remains controversial because of gaps in knowledge of etiology and pathogenesis,

Gastritis is commonly secondary to infectious or autoimmune etiologies, although it can also result fromdrugs or hypersensitivity reactions.

Gastropathy is commonly secondary to endogenous or exogenous irritants, such as bile reflux, alcohol, oraspirin and nonsteroidal antiinflammatory drugs. However, gastropathy can also be secondary toischemia, physical stress, or chronic congestion.

th th

16/10/2014 Classification and diagnosis of gastritis and gastropathy

http://www.uptodate.com/contents/classification-and-diagnosis-of-gastritis-and-gastropathy?topicKey=GAST%2F29&elapsedTimeMs=0&source=search 2/10

variation in nomenclature, and the coexistence of more than one type of gastritis or gastropathy in individualpatients. Furthermore, the entities overlap morphologically, and so some conditions are classified by etiologyand others by morphologic pattern. Thus, comparisons across studies using different nomenclature can bedifficult.

Most classification systems distinguish acute, short-term disease from chronic, long-term disease. The termsacute and chronic are also used to describe the type of inflammatory cell infiltrate. Acute inflammation isrepresented by neutrophilic infiltration, while chronic inflammation is characterized by a mixture of mononuclearcells, chiefly lymphocytes, plasma cells, and macrophages.

A clinicopathologic framework for the classification of gastritis and gastropathy based upon these factors hasbeen proposed (table 2) [13]. However, there are a number of cases with a diagnosis of chronic gastritis (oftenmild) for which a specific etiology cannot be determined by histopathologic examination [14].

DIAGNOSIS A mucosal biopsy is required to distinguish between acute, chronic active, or chronic gastritisfrom gastropathy, since the endoscopic and radiologic features may be similar and clinical features are ofteninaccurate for predicting histologic findings [15-22]. Histologic findings can vary over a wide spectrum rangingfrom epithelial hyperplasia to extensive epithelial cell damage with infiltration by inflammatory cells.

An illustrative study included 488 adults who were randomly selected from the general population and werescreened by gastroscopy and biopsy [21]. The authors determined the sensitivity and specificity ofmacroscopic features (including erythema, erosions, the absence or rugal folds and the presence of visiblevessels) compared to histologic findings. None of these findings had sensitivity greater than 57 percent fordetermining the presence of gastritis or H. pylori infection. Similar conclusions have been reached in otherreports [15,21]. Another problem with relying on endoscopy alone is the interobserver variability for somefeatures of gastritis such as erythema [20].

Laboratory evaluation Two types of laboratory tests have proven to be useful for predicting gastricmucosal findings: noninvasive testing for H. pylori infection and serologic biomarker measurements, bothbiochemical and immunologic.

Helicobacter pylori testing Noninvasive testing for Helicobacter pylori has high sensitivity andspecificity for gastritis. (See "Acute and chronic gastritis due to Helicobacter pylori" and "Indications anddiagnostic tests for Helicobacter pylori infection".)

Stomach-specific biochemical markers Pepsinogens are secreted by chief cells in the fundus andbody, and by mucous cells in the cardia, fundus, body, antrum, and pylorus. Pepsinogen I is mostly secretedby chief cells in the gastric fundus, whereas pepsinogen II is also secreted in the antrum. Thus, in conditionsassociated with gastritis of the fundus (as in pernicious anemia), serum pepsinogen (PG) I concentrations aredecreased relative to PG II.

Low serum PG I levels are strongly associated with extensive intestinal metaplasia [23]. Intestinal metaplasiawas found in 58 (88 percent) of 66 patients with a serum PG I value of less than 25 ng per milliliter [24]. Theratio of PG isozymes I and II in serum has good correlation with presence of metaplastic atrophic gastritis(principally autoimmune metaplastic atrophic gastritis and pernicious anemia) [25]. Measurement of amidatedgastrin-17 evaluated in tandem with PG I:II ratio has been advocated to reflect the degree of inflammation andgrade of atrophic gastritis [26]. The early diagnosis of atrophic gastritis is important as this condition is asignificant independent risk factor for the development of distal gastric tumors, both adenocarcinoma andcarcinoid [10,26]. (See "Metaplastic (chronic) atrophic gastritis", section on 'Hyperplastic and neoplasticlesions'.)

The ratio of serum PG I:II in the serum of people with normal gastric mucosa is approximately 6.2 [27]. In oneseries, the presence of fundic atrophic gastritis was accurately predicted by the concentration of pepsinogen Iand the ratio of pepsinogen isoenzymes in approximately 70 percent of patients [27]. The ratio may also beuseful for screening family members of patients with pernicious anemia and for identifying patients at high riskfor gastric cancer in endemic countries or other populations at increased risk for gastric atrophy [27-30]. On theother hand, measurement of serum PGs and their ratio do not accurately discriminate nonatrophic versusantrum-restricted/predominant atrophic gastritis in an asymptomatic population or first-degree relatives of

16/10/2014 Classification and diagnosis of gastritis and gastropathy

http://www.uptodate.com/contents/classification-and-diagnosis-of-gastritis-and-gastropathy?topicKey=GAST%2F29&elapsedTimeMs=0&source=search 3/10

patients with gastric cancer [31,32]. (See "Screening and prevention of gastric cancer".)

Serologic immunologic markers Immunological markers of stomach health may be useful in clinicallyasymptomatic patients with early autoimmune gastritis (AIG) [33]. Testing for antibodies to intrinsic factor,parietal cells, and Helicobacter pylori in tandem with serum gastrin may provide noninvasive early evidence ofAIG and facilitate selection of patients for endoscopic examination [33].

Biopsy Accurate histologic assessment of gastritis and gastropathy depends upon optimizing the site andnumber of biopsy specimens. Magnification endoscopy may help in the identification of areas to biopsy. (See"Magnification endoscopy".)

Biopsy site preferences and number vary in clinical practice. However, there is general consensus amongexperts on the following biopsy approach [13]:

Biopsy of the incisura is also useful since it approximates the transition zone between the antrum and body,where intestinal metaplasia and atrophy are most frequently found in environmental metaplastic atrophicgastritis. However, biopsy of incisura only does not provide information on the extent of metaplastic atrophicgastritis, which is a major parameter in determination of cancer risk [10,12].

In first degree relatives of early onset gastric carcinoma patients, endoscopic evaluation with at least fourbiopsies in the gastric antrum and corpus are suggested. Multiple biopsies with adequate sampling arenecessary for scoring and staging of premalignant lesions in this subgroup of patients [10].

Biopsies of the duodenum may also be helpful for diagnosing some forms of chronic gastritis. As examples,duodenal biopsies may show evidence of Crohn disease in patients with granulomatous gastritis or of celiacdisease in patients with lymphocytic gastritis.

Communication with the pathologist Good communication between the endoscopist and pathologistcannot be overemphasized, and will optimize the interpretation of the biopsy specimens. This has becomegreatly facilitated by the availability of digital endoscopic pictures and readily available endoscopic proceduraldictation in the electronic medical record.

The pathologist should include a morphologic classification of the gastritis or gastropathy in the biopsy report(table 3) [34].

INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics"and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5 to 6grade reading level, and they answer the four or five key questions a patient might have about a givencondition. These articles are best for patients who want a general overview and who prefer short, easy-to-readmaterials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed.These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depthinformation and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail thesetopics to your patients. (You can also locate patient education articles on a variety of subjects by searching on"patient info" and the keyword(s) of interest.)

SUMMARY AND RECOMMENDATIONS

All gross abnormalities should be biopsied and submitted in separate containers.

Normal appearing mucosa adjacent to the lesional tissue should also be biopsied.

Multiple biopsies (two to five) of both the corpus and the antrum should be obtained when attempting toestablish the diagnosis of Helicobacter pylori or autoimmune gastritis.

th th

th th

Basics topics (see "Patient information: Gastritis (The Basics)" and "Patient information: Upperendoscopy (The Basics)")

Beyond the Basics topics (see "Patient information: Upper endoscopy (Beyond the Basics)")

Gastric inflammatory disease can be broadly categorized into gastritides and gastropathies. Gastritis is

16/10/2014 Classification and diagnosis of gastritis and gastropathy

http://www.uptodate.com/contents/classification-and-diagnosis-of-gastritis-and-gastropathy?topicKey=GAST%2F29&elapsedTimeMs=0&source=search 4/10

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

1. Faber K. Gastritis and its consequences, Oxford University Press, New York 1935.2. Wood IJ, Taft LI. Diffuse lesions of the stomach: An account with special reference to the value of

gastric biopsy, Edward Arnold, London 1958.3. Price AB. The Sydney System: histological division. J Gastroenterol Hepatol 1991; 6:209.4. Correa P. Chronic gastritis: a clinico-pathological classification. Am J Gastroenterol 1988; 83:504.5. Wyatt JI, Dixon MF. Chronic gastritis--a pathogenetic approach. J Pathol 1988; 154:113.6. Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney

System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol1996; 20:1161.

7. Carpenter HA, Talley NJ. Gastroscopy is incomplete without biopsy: clinical relevance of distinguishinggastropathy from gastritis. Gastroenterology 1995; 108:917.

8. Rugge M, Meggio A, Pennelli G, et al. Gastritis staging in clinical practice: the OLGA staging system.Gut 2007; 56:631.

9. Rugge M, Fassan M, Pizzi M, et al. Autoimmune gastritis: histology phenotype and OLGA staging.Aliment Pharmacol Ther 2012; 35:1460.

10. Marcos-Pinto R, Carneiro F, Dinis-Ribeiro M, et al. First-degree relatives of patients with early-onsetgastric carcinoma show even at young ages a high prevalence of advanced OLGA/OLGIM stages anddysplasia. Aliment Pharmacol Ther 2012; 35:1451.

11. Rugge M, Correa P, Di Mario F, et al. OLGA staging for gastritis: a tutorial. Dig Liver Dis 2008; 40:650.12. Park JY, Lam-Himlin D, Vemulapalli R. Review of autoimmune metaplastic atrophic gastritis.

Gastrointest Endosc 2013; 77:284.13. Dixon MF, Genta RM, Yardley JH, Correa P. Histological classification of gastritis and Helicobacter

pylori infection: an agreement at last? The International Workshop on the Histopathology of Gastritis.Helicobacter 1997; 2 Suppl 1:S17.

14. Sepulveda AR, Patil M. Practical approach to the pathologic diagnosis of gastritis. Arch Pathol Lab Med2008; 132:1586.

15. Khakoo SI, Lobo AJ, Shepherd NA, Wilkinson SP. Histological assessment of the Sydney classificationof endoscopic gastritis. Gut 1994; 35:1172.

16. Cronstedt JL, Simson IW. Correlation between gastroscopic and direct vision biopsy findings.Gastrointest Endosc 1973; 19:174.

17. Elta GH, Appelman HD, Behler EM, et al. A study of the correlation between endoscopic and histologicaldiagnoses in gastroduodenitis. Am J Gastroenterol 1987; 82:749.

18. Jnsson KA, Gotthard R, Bodemar G, Brodin U. The clinical relevance of endoscopic and histologicinflammation of gastroduodenal mucosa in dyspepsia of unknown origin. Scand J Gastroenterol 1989;24:385.

19. Tytgat GN. The Sydney System: endoscopic division. Endoscopic appearances in gastritis/duodenitis. J

predominantly an inflammatory process while gastropathy demonstrates minimal to no inflammation. (See'Introduction' above.)

There is no universally accepted classification of gastritis/gastropathy, although several classifications ofgastritis and gastropathy (such as the Sydney system) have been proposed. (See 'Classification ofgastritis and gastropathy' above.)

A mucosal biopsy is required to distinguish between acute, chronic active, and chronic gastritis andgastropathy. (See 'Diagnosis' above.)

There is general consensus among experts on a biopsy approach. (See 'Biopsy' above.)

Good communication between the endoscopist and pathologist cannot be overemphasized, and willoptimize the interpretation of the biopsy specimens. (See 'Communication with the pathologist' above.)

16/10/2014 Classification and diagnosis of gastritis and gastropathy

http://www.uptodate.com/contents/classification-and-diagnosis-of-gastritis-and-gastropathy?topicKey=GAST%2F29&elapsedTimeMs=0&source=search 5/10

Gastroenterol Hepatol 1991; 6:223.20. Laine L, Cohen H, Sloane R, et al. Interobserver agreement and predictive value of endoscopic findings

for H. pylori and gastritis in normal volunteers. Gastrointest Endosc 1995; 42:420.21. Reden S, Petersson F, Jnsson KA, Borch K. Relationship of gastroscopic features to histological

findings in gastritis and Helicobacter pylori infection in a general population sample. Endoscopy 2003;35:946.

22. Kaur G, Raj S. A study of the concordance between endoscopic gastritis and histological gastritis in anarea with a low background prevalence of Helicobacter pylori infection. Singapore Med J 2002; 43:90.

23. Miki K, Urita Y. Using serum pepsinogens wisely in a clinical practice. J Dig Dis 2007; 8:8.24. Urita Y, Hike K, Torii N, et al. Serum pepsinogens as a predicator of the topography of intestinal

metaplasia in patients with atrophic gastritis. Dig Dis Sci 2004; 49:795.25. Samloff IM. Peptic ulcer: the many proteinases of aggression. Gastroenterology 1989; 96:586.26. Agrus L, Kuipers EJ, Kupcinskas L, et al. Rationale in diagnosis and screening of atrophic gastritis with

stomach-specific plasma biomarkers. Scand J Gastroenterol 2012; 47:136.27. Samloff IM, Varis K, Ihamaki T, et al. Relationships among serum pepsinogen I, serum pepsinogen II,

and gastric mucosal histology. A study in relatives of patients with pernicious anemia. Gastroenterology1982; 83:204.

28. Yoshihara M, Sumii K, Haruma K, et al. Correlation of ratio of serum pepsinogen I and II with prevalenceof gastric cancer and adenoma in Japanese subjects. Am J Gastroenterol 1998; 93:1090.

29. Graham DY, Nurgalieva ZZ, El-Zimaity HM, et al. Noninvasive versus histologic detection of gastricatrophy in a Hispanic population in North America. Clin Gastroenterol Hepatol 2006; 4:306.

30. Oishi Y, Kiyohara Y, Kubo M, et al. The serum pepsinogen test as a predictor of gastric cancer: theHisayama study. Am J Epidemiol 2006; 163:629.

31. Ricci C, Vakil N, Rugge M, et al. Serological markers for gastric atrophy in asymptomatic patientsinfected with Helicobacter pylori. Am J Gastroenterol 2004; 99:1910.

32. Haj-Sheykholeslami A, Rakhshani N, Amirzargar A, et al. Serum pepsinogen I, pepsinogen II, andgastrin 17 in relatives of gastric cancer patients: comparative study with type and severity of gastritis.Clin Gastroenterol Hepatol 2008; 6:174.

33. Antico A, Tampoia M, Villalta D, et al. Clinical usefulness of the serological gastric biopsy for thediagnosis of chronic autoimmune gastritis. Clin Dev Immunol 2012; 2012:520970.

34. Owen DA. Gastritis and carditis. Mod Pathol 2003; 16:325.

Topic 29 Version 8.0

16/10/2014 Classification and diagnosis of gastritis and gastropathy

http://www.uptodate.com/contents/classification-and-diagnosis-of-gastritis-and-gastropathy?topicKey=GAST%2F29&elapsedTimeMs=0&source=search 6/10

GRAPHICS

Updated Sydney system for the classification and grading ofgastritis

Type of gastritis Etiologic factors Gastritissynonyms

Nonatrophic Helicobacter pylori

? Other factors

Superficial

Diffuse antral gastritis(DAG)

Chronic antral gastritis(CAG)

Interstitial - follicular

Hypersecretory

Type B*

Atrophic

Autoimmune Autoimmunity Type A*

Diffuse corporal

Pernicious anemia-associated

Multifocal atrophic Helicobacter pylori Type B*, type AB*

Dietary Environmental

? Environmental factors Metaplastic

Special forms

Chemical Chemical irritation Reactive

Bile Reflux

NSAIDs NSAID

? Other agents Type C*

Radiation Radiation injury

Lymphocytic Idiopathic? Immune mechanisms Varioliform(endoscopic)

Gluten Celiac disease-associated

Drug (ticlopidine)

? H. pylori

Noninfectiousgranulomatous

Crohn's disease

Sarcoidosis

Granulomatosis with polyangiitis and othervasculitides

Foreign substances

Idiopathic Isolatedgranulomatous

16/10/2014 Classification and diagnosis of gastritis and gastropathy

http://www.uptodate.com/contents/classification-and-diagnosis-of-gastritis-and-gastropathy?topicKey=GAST%2F29&elapsedTimeMs=0&source=search 7/10

Eosinophilic Food sensitivity Allergic

? Other allergies

Other infectiousgastritides

Bacteria (other than H. pylori) Phlegmonous

Viruses

Fungi

Parasites

NSAIDs: nonsteroidal antiinflammatory drugs.* Alphabetic designations of gastritis were abandoned in the original presentation of the SydneySystem. That approach is also recommended here. Use of "Type B" to denote either atrophic or non-atrophic gastritis is considered to be especially misleading. Many participants favor substitution of gastropathy for gastritis to describe conditions that resultfrom chemical injury.

Reproduced with permission from: Dixon M, Genta R, Yardley J, Correa P; the Participants in theInternational Workshop on the Histopathology of Gastritis, Houston. Classification and grading ofgastritis: The updated Sydney system. Am J Surg Pathol 1996; 20:1161. Copyright 1996Lippincott Williams & Wilkins.

Graphic 58995 Version 11.0

16/10/2014 Classification and diagnosis of gastritis and gastropathy

http://www.uptodate.com/contents/classification-and-diagnosis-of-gastritis-and-gastropathy?topicKey=GAST%2F29&elapsedTimeMs=0&source=search 8/10

Classification of gastritides and gastropathies

Acute formsAcute hemorrhagic and erosivegastropathy

Acute Helicobacter pylori gastritis

Uncommon acute infectious gastritides

Common formsHelicobacter pylori gastritis

Chemical gastropathy

Aspirin and other nonsteroidalantiinflammatory drugs

Bile reflux

Alcohol

Others (?)

Metaplastic atrophic gastritis

Autoimmune

Environmental

Chronic gastritis/gastropathy ofindeterminate type

Uncommon formsPostantrectomy atrophic gastritis

Eosinophilic gastritis

Infectious gastritis

Bacterial, other than Helicobacter pylori

Helicobacter heilmannii

Phlegmonous

Mycobacterial

Syphilitic

Viral

Parasitic

Fungal

Crohn disease

Sarcoidosis

Isolated granulomatous gastritis

Lymphocytic gastritis

Mntrier's disease

Focally-enhanced gastritis

Graphic 73286 Version 6.0

16/10/2014 Classification and diagnosis of gastritis and gastropathy

http://www.uptodate.com/contents/classification-and-diagnosis-of-gastritis-and-gastropathy?topicKey=GAST%2F29&elapsedTimeMs=0&source=search 9/10

Morphologic classification of gastritis or gastropathy

Location of process: Antral predominant, corpus predominant, or pangastritis

Type of inflammation: Acute, chronic, mixed, eosinophilic, or granulomatous

Topography of inflammation: Diffuse or focal

Gastric site

Atrophy: Present or absent, graded*

Intestinal metaplasia: Present or absent, graded*

Infectious agent: Helicobacter pylori, Helicobacter heilmannii, virus, other

* Mild, moderate, or marked.

Graphic 80329 Version 1.0

16/10/2014 Classification and diagnosis of gastritis and gastropathy

http://www.uptodate.com/contents/classification-and-diagnosis-of-gastritis-and-gastropathy?topicKey=GAST%2F29&elapsedTimeMs=0&source=searc 10/10

Disclosures: Beverly A Dickson, MD Nothing to disclose. Mark Feldman, MD, MACP, AGAF, FACG Nothing to disclose. JThomas Lamont, MD Nothing to disclose. Shilpa Grover, MD, MPH Employee of UpToDate, Inc.Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vettingthrough a multi-level review process, and through requirements for references to be provided to support the content. Appropriatelyreferenced content is required of all authors and must conform to UpToDate standards of evidence.Conflict of interest policy

Disclosures