INTRODUCTION

An accurate classification of chronic gastritis (CG) into different subgroups is desirable to understand its aetiopathogenesis, to compare data from different centers, to study the life-history, to suggest surveillance programme (if any), to plan treatment (in future), to prevent its progress or complications (gastric carcinoma, lymphoma), with a view to improve or cure this disease.1-3 Two major advances in our understanding of CG are (a) detection of immunological parameters-parietal cell antibody (PCA) (1962),4 intrinsic factor antibody (IFA) (1963)5 and (b) discovery of Helicobacter pylori (H. pylori) in endocsopic gastric mucosal biopsy (1983).6 The commonest cause of CG (more than 80%) is H. pylori infection; it affects about half the world population.3,7 Uncommon causes of CG - granulomatous, eosinophilic, lymphocytic, reflux (postoperative), corrosive, radiation-induced, CrohnÊs disease, sarcoidosis, tobacco-induced8 - are not discussed.

INVESTIGATIONS
Five investigations are required to accurately classify subgroups of patients with CG and the significance of each of them are shown in Table 1.

Gastric mucosal biopsy on upper gastrointestinal endoscopy is preferred and atleast five biopsies are obtained two each from antrum and body mucosa and one from incisura angularis. The diagnosis of CG is established as superficial gastritis, atrophic gastritis or gastric atrophy (pernicious anaemia : PA). The aetiology of H. pylori infection is indicated by presence of lymphoid follicles and/or polymorphonuclear leucocyte infiltration.9 H. pylori can be detected on rapid urease test (RUT) or identified near surface epithelium with routine haematoxylin-eosin stain and with greater ease on special stains (modified Giemsa, acridine orange, Warthin-Starry). To diagnose H. pylori infection in gastric mucosa, RUT, faecal antigen test (FAT),10 urea breath test (UBT)11 have a sensitivity of approximately 85%, 90%, 95% respectively.12 Culture of H. pylori in gastric mucosal biopsy or stool, helps to assess bacterial sensitivity to different antibiotics.

PCA detected on complement fixation test is present in serum or gastric juice.4 The antibody is formed against the antigen-alpha and beta subunits of proton pump.13 Its presence indicates CG even in healthy control subjects; its absence does not exclude CG (e.g. post-operative or corrosive).1 PCA in serum is present in 5 15% of control population, 20% with iron deficiency anaemia, 25% with diabetes mellitus, 30% with thyrotoxicosis, 35% with idiopathic AddisonÊs disease;14,15 the presence of PCA indicates the prevalence of CG in these diseases

IFA detected on radioimmunoassay is of 2 types.5 Type I : Blocking antibody blocks the union of IF to free vitamin B12, Type II : Binding antibody interferes with the binding of IF-vitamin B12 complex to ileal receptors. In serum, Type II IFA is found only in patients with Type I antibody and hence the latter is only looked for.16,17 In Western countries, the incidence of IFA in serum of patients with PA, thyrotoxicosis, diabetes mellitus, iron deficiency anaemia is 75%, 7%, 5%, 2% respectively.15,18 The rarity of IFA in Indian patients, including those with severe atrophic gastritis and histamine fast achlorhydria (HFA) with severe vitamin B12 malabsorption, was emphasized.19-22 Formation of IFA is independent of sex, age, duration of disease, degree of atrophic gastritis or the titre of PCA and is determined by hereditary factors.23,24 In relatives of patients with PA, the prevalence of IFA is higher than in control population.23,24 The diagnosis of PA should be restricted to only these patients with IFA in serum or gastric juice.21,25,26

Helicobacter pylori antibodies (HpA) (IgG) indicate past H. pylori infection. HpA crossreact with gastric autoantigens such as alpha and beta subunits of proton pump and determines the progress and localization (body or antrum) of gastric mucosal damage and explains the pathogenic link between H. pylori infection and CG.27 In patients with corporal atrophic gastritis, the incidence of positive serum HpA and negative tissue staining of H. pylori is present in more than 50% of patients, indicating H. pylori disappears as intestinal metaplasia develops in them.28,29

UBT can be performed with 14C or 13C urea meal test;11 14Co2 liberated by H. pylori is absorbed and exhaled in breath and is measured with liquid scintillation. The test should not be performed in pregnant women and children. 13Co2 is measured with mass spectrometry. UBT also provides some useful quantitative estimation of H. pylori infection in the whole stomach. One month after completion of H. pylori eradication treatment, the negative UBT confirms its eradication.

FAT for H. pylori is another alternative method to confirm the absence or presence of H. pylori in the gastric mucosa;10 in children, this test is preferred. To confirm eradication of H. pylori in patients of duodenal ulcer (associated with antral gastritis) or gastric ulcer (associated with corpus gastritis), UBT or FAT is absolutely necessary, as sensitivity of histology or RUT on gastric mucosal biopsy is poor, when few organisms are present in the gastric mucosa.

To conclude, the result of these five tests (Table 1) will indicate present or past H. pylori infection, the contribution of hereditary factors (IFA present or absent), and the success or failure of H. pylori eradication treatment. These investigations should be available in institutions desiring to diagnose and classify patients of CG accurately. Future progress of CG depends on the availability of such information from various countries.

DISCUSSION

The most popular Sydney classification30,31 of CG has serious limitations : (i) the immunological parameters which determine the progress and localization (antrum or body mucosa) of diseases are not mentioned, and (ii) the endoscopic findings which has a poor correlation with histology are given too much importance.

Any classification of CG should be based on immunological parameters and detection of present or past H pylori infection. Amongst ten classifications of CG,25,26,30,32-38 only four classifications of CG (all prior to H pylori detection) include immunological data.25,26,33,34 The earliest immunological classification of CG was reported from Mumbai (India).26 Desai and Antia (March 1973)26 classified CG into 3 types: Type I : absence of both PCA and IFA (simple gastritis); Type II : presence of PCA and absence of IFA (superficial or atrophic gastritis), Type III : presence of both PCA and IFA (PA). The separation of CG should be as environmental (Type II : H. pylori infection-present or past) and hereditary (Type III: IFA present)21,25,26

Desai and Antia26 separated CG on the basis of absence or presence of PCA. CG patients with PCA have a normal antrum, G cell hyperplasia and basal hypergastrinaemia while those negative for PCA have a damaged antral mucosa, decreased ÂGÊ cell mass and normal basal serum gastrin level.39-41 They indicated patients with severe atrophic gastritis with HFA and poor vitamin B12 excretion (<5% on Schilling test) were wrongly grouped with PA on the basis of vitamin B12 excretion test; the two conditions should be separated on the basis of absence or presence of IFA.

Strickland and Mackay (May 1973)33 classified CG into 2 Types : Type A (Autoimmune) showing PCA in 95% and IFA in 75% of patients; Type B (Environmental) was inaccurately reported as showing absence of PCA; both Type A and Type B CG shows PCA and hence does not help to differentiate these 2 types.42,43 Glass and Pitchumoni (1975)34 modified this classification by including Type AB PCA positive and Type AB PCA negative CG, in which both the antrum and body mucosa of stomach are involved.

The accurate immunological classification of diseases such as hepatitis, thyroiditis, arthritis and glomerulonephritis has significantly improved our understanding of these diseases. To achieve such significant advances in our knowledge of CG, the importance of immunological classification (PCA, IFA) and the role of hereditary factor in formation of IFA, needs to be widely appreciated (Fig. 1).

CONCLUSIONS

Prior to the availability of fiberoptic endoscope and immunological parameters, the patients of CG were investigated with gastric mucosal biopsy (blindly with Crosby- Kugler capsule), augmented histamine test to detect hypochlorhydria or HFA, 58Co vitamin B12 excretion (Schilling test) to detect mild (> 5% excretion) or severe (< 5% excretion) vitamin B12 malabsorption, to separate patients of atrophic gastritis from those with PA respectively (Fig. 1). At present, patients of CG should be investigated with endoscopic gastric mucosal biopsy (histology + RUT) and immunological parameters (PCA, IFA, HpA) (Table 1).

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