Kenneth W. Simpson, BVM&S, PhD, MRCVS, DACVIM, DECVIM
Gastritis is a common finding in dogs, with 35% of dogs investigated for chronic vomiting and 26-48% of asymptomatic dogs affected. The prevalence in cats has not been determined. The diagnosis of chronic gastritis is based on the histological examination of gastric biopsies and it is usually sub-classified according to histopathological changes and aetiology.
Histopathological Features of Gastritis
Gastritis in dogs and cats is usually classified according to:
The predominant cellular infiltrate (eosinophilic, lymphocytic, plasmacytic, granulomatous, lymphoid follicular)
The presence of architectural abnormalities (atrophy, hypertrophy, fibrosis, edema, ulceration, metaplasia)
Its subjective severity (mild, moderate, severe)
A standardized visual grading scheme has been proposed by Happonen et al (1998) and has been adapted for pathologists (Wiinberg, 2005).
The most common form of gastritis in dogs and cats is mild to moderate superficial lymphoplasmacytic gastritis with concomitant lymphoid follicle hyperplasia.
Despite the high prevalence of gastritis an underlying cause is rarely identified and in the absence of systemic disease, ulcerogenic or irritant drugs, gastric foreign objects, parasites (Physaloptera, Ollulanus) or, in rare instances, fungal infections (Pythium insidiosum, Histoplasma), it is usually attributed to dietary allergy or intolerance, occult parasitism, or a reaction to bacterial antigens, or unknown pathogens. Treatment is often empirical but can serve to define the cause of gastritis e.g., diet-responsive, antibiotic-responsive, steroid-responsive or parasitic.
The major clinical sign of chronic gastritis is vomiting of food or bile. Decreased appetite, weight loss, melaena or haematemesis are variably encountered. The concurrent presence of dermatological and gastrointestinal signs raises the likelihood of dietary sensitivity. Access to toxins, medications, foreign bodies, and dietary practices should be thoroughly reviewed.
The patient details should not be overlooked as it may increase the probability that chronic gastritis is the cause of vomiting, e.g., Hypertrophy of the fundic mucosa is frequently associated with a severe enteropathy in Basenjis and stomatocytosis, haemolytic anaemia, icterus and polyneuropathy in Drentse Patrijshond. Hypertrophy of the pyloric mucosa is observed in small brachycephalic dogs such as Lhasa Apso and is associated with gastric outflow obstruction (see disorders of gastric emptying). Atrophy of the gastric mucosa that may progress to adenocarcinoma has been reported in Lundehunds with protein losing gastroenteropathy. Young, large breed, male dogs in the Gulf States of the USA may have granulomatous gastritis caused by Pythium spp. with infection more prevalent in autumn (fall), winter and spring.
Physical examination is often unremarkable in patients with chronic gastritis.
Abdominal distension may be related to delayed gastric emptying caused by obstruction or defective propulsion. Abdominal masses, lymphadenopathy or ocular changes may be encountered in dogs with gastric fungal infections.
Clinicopathological tests are often normal in patients with chronic gastritis.
A biochemical profile, complete blood count, urinalysis and T4 (cats) should be performed as a basic screen for metabolic, endocrine, infectious, and other non-GI causes of vomiting, as well as the acid base and electrolyte changes associated with vomiting, outflow obstruction or acid hypersecretion.
Eosinophilia may prompt the consideration of gastritis associated with dietary hypersensitivity, endoparasites, or mast cell tumours. Hyperglobulinaemia and hypoalbuminaemia may be present in Basenjis with gastropathy/enteropathy, or dogs with gastric pythiosis. Panhypoproteinaemia is a feature of gastroenteropathy in Lundehunds, moderate to severe generalized inflammatory bowel disease, GI lymphoma and GI histoplasmosis. More specific testing such as an ACTH stimulation test, or serology for Pythium insidiosum are performed on the basis of these initial test. Determination of food specific IgE has not been shown to be useful in the diagnosis of dietary sensitivity in dogs or cats. The utility of non-invasive tests, such as serum pepsinogen and gastric permeability to sucrose, used to diagnose gastritis in people has not been determined in dogs and cats.
Survey abdominal radiographs are frequently normal in dogs and cats with gastritis but may show gastric distention or delayed gastric emptying (food retained >12hrs after a meal).
Contrast radiography may reveal ulcers or thickening of the gastric rugae or wall but has largely been superceded by the combination of ultrasonography to detect mural abnormalities and endoscopy to observe and sample the gastric mucosa.
Endoscopic examination enables the visualization of foreign bodies, erosions, ulceration, haemorrhage, rugal thickening, lymphoid follicle hyperplasia (evident as mucosal pock marks), increased mucus or fluid (clear or bile stained) and increased or decreased mucosal friability.
Discreet focal or multifocal mucosal nodules may be observed with Ollulanus infection. Parasites such as Physaloptera may be observed as 1-4cm worms.
Gastric phycomycosis can be associated with irregular masses in the pyloric outflow tract and may prompt serological testing by ELISA, Western blotting, and culture of fresh gastric biopsies.
Large amounts of bile stained fluid is suggestive of duodenogastric reflux associated gastritis, whereas lots of clear fluid may indicate hypersecretion of gastric acid.
Gastric fluid can be aspirated for cytology (Helicobacter, parasite ova or larvae) and pH measurement. Impression smears of gastric biopsies are an effective way of looking for Helicobacter spp. (5-12 µm spirals) and are more sensitive than the biopsy urease test (Helicobacter spp. produce urease).
Serum gastrin should be measured in the face of unexplained gastric erosions, ulcers, fluid accumulation or mucosal hypertrophy.
Gastroscopic food sensitivity testing (GFST), the endoscopic procedure of dribbling dietary antigens onto the gastric mucosa to ascertain the presence of food allergy has not been useful in dogs or cats. GFST is highly subjective, detects only immediate hypersensitivity, and does not correlate with the results of dietary elimination trials.
The stomach should be biopsied even when it looks grossly normal (usually 3 biopsies from each region--pylorus, fundus and cardia).
Thickened rugae may require multiple biopsies, and a full thickness biopsy is often required to differentiate gastritis from neoplasia or fungal infection, and to diagnose submucosal or muscular hypertrophy.
Examination of Gastric Biopsies
The interpretation of gastric biopsies has important implications for patient care as biopsy findings are often used to guide treatment, e.g., moderate lymphoplasmacytic gastritis without Helicobacter is often treated with corticosteroids, whereas mild lymphoplasmacytic gastritis may be treated with a change in diet. As the histopathological evaluation of gastric biopsies has not been standardized the prudent clinician should carefully review histological sections to get a feel for their pathologist's interpretation. Even with optimum evaluation similar histological changes can be observed in patients with different underlying aetiologies so well structured treatment trials often form the basis of an aetiological diagnosis.
Gastric sections should be stained with H&E for evaluation of cellularity and architecture, and modified Steiner stain for gastric spiral Further special stains, e.g., Gomori's methenamine silver are indicated to detect fungi if pyogranulomatous inflammation is present.
Treatment of chronic gastritis initially centers on the detection and treatment of underlying metabolic disorders and the removal of drugs, toxins, foreign bodies, parasites and fungal infections.
Ollulanus tricuspis is a microscopic worm (0.7-1mm long, 0.04mm wide) infecting the feline stomach. Mucosal abnormalities range from none, to rugal hyperplasia, and nodular (2-3mm) gastritis. Histological findings include lymphoplasmacytic infiltrates, lymphoid follicular hyperplasia, fibrosis and up to 100/hpf globular leukocytes. Ollulanus is not detected by faecal examination, and requires evaluation of gastric juice, vomitus or histological sections for larvae or worms. Gastric lavage and xylazine induced emesis have been described to aid diagnosis. Treatment with fenbendazole 10mg/kg PO SID for 2d may be effective.
Physaloptera species are 2 to 6 cm long worms that are sporadically detected in the stomachs of dogs and cats. Diagnosis is difficult as worm burden is often low and the eggs are transparent and difficult to see in sugar floatation. Treatment with pyrantel pamoate (5mg/kg PO: dogs single dose; cats two doses 14d apart) may be effective.
Control of infection may be difficult due to the ingestion of intermediate hosts such as cockroaches and beetles and paratenic hosts such as lizards and hedgehogs.
Given the difficulty of diagnosing Ollulanus and Physaloptera empirical therapy with an anthelminthic such as fenbendazole may be warranted in dogs and cats with unexplained gastritis.
The presence of transmural thickening of the gastric outflow tract and histology indicating pyogranulomatous inflammation raise the possibility of infection with fungi such as Pythium insidiosum. Special staining (Gomori's methenamine silver), culture, serology and PCR of infected tissues can be used to help confirm the diagnosis. Treatment consists of aggressive surgical resection combined with itraconazole (10mg/kg PO SID) and terbinafine (5-10mg/kg PO SID) for 2-3 months post-surgery. ELISA titres of pre- and post-treatment samples may show a marked drop during successful treatment and drugs can be stopped. Medical therapy is continued for another 2-3 months if titres remain elevated. The prognosis is poor and only <25% are cured with medical therapy alone.
An uncontrolled treatment trial of dogs and cats with gastritis and Helicobacter infection showed that clinical signs in 90% of 63 dogs and cats responded to treatment with a combination of metronidazole, amoxicillin and famotidine, and that 14 of the 19 animals re-endoscoped had resolution of gastritis and no evidence of Helicobacter in gastric biopsies.
Controlled clinical trials have been hampered by a much higher apparent recrudescence or re-infection rate than the 1-2%/yr observed after treatment of H. pylori infected people.
Only symptomatic patients with biopsy confirmed Helicobacter infection and gastritis should be treated.
The combination of amoxicillin (20mg/kg PO BID), clarithromycin (7.5mg/kg PO BID) and metronidazole (10mg/kg PO BID) for 14days may be effective.
Ideally eradication should be confirmed by the evaluation of gastric juice or biopsies 1 month after stopping treatment, and non-responsive patients should be evaluated for resistant infections.
Chronic Gastritis of Unknown Cause
Lymphocytic plasmacytic gastritis of unknown cause is common in dogs and cats. It may be associated with similar infiltrates in the intestines, particularly in cats (who should also be evaluated for the presence of pancreatic and biliary disease). The cellular infiltrate varies widely in severity and it may be accompanied by mucosal atrophy or fibrosis, and less commonly hyperplasia.
Mild lymphoplasmacytic gastritis is initially treated with diet.
The diet is usually restricted in antigens to which the patient has been previously exposed, e.g., a lamb based diet if the patient has previously been fed chicken and beef, or contains hydrolyzed proteins (usually chicken or soy) that may be less allergenic than intact proteins. The test diet is fed exclusively for a period of about 1-2 weeks while vomiting episodes are recorded. If vomiting is improved a challenge with the original diet is required to confirm a diagnosis of dietary sensitivity. The introduction of a specific dietary component to the test diet, e.g., beef, is required to confirm dietary sensitivity. If vomiting is unresponsive the patient may be placed on a different diet for another 1-2 weeks, usually the limit of client tolerance, or started on prednisolone (1-2mg/kg/day PO, tapered to every other day at the lowest dose that maintains remission over 8-12 weeks).
Moderate to severe lymphoplasmacytic gastritis is usually treated with a combination of a test diet and prednisolone. If the patient goes into remission they are maintained on the test diet while prednisolone is tapered, and potentially discontinued.
Antacids and mucosal protectants are added to the therapeutic regimen if ulcers or erosions are detected at endoscopy or if haematemesis or melaena are noted. If gastritis is unresponsive to diet, prednisolone, and antacids, the diagnosis should be re-evaluated prior to aggressive immunosuppression. In dogs immunosuppression is usually increased with azathioprine (PO 2mg/kg SID for 5d then EOD, on alternating days with prednisolone). Chlorambucil may be a safer alternative to azathioprine in cats (PO) and has been successfully employed in the management of inflammatory bowel disease and small cell lymphoma. Prokinetic agents e.g., metoclopramide, cisapride, erythromycin can be used as an adjunct where delayed gastric emptying is present and are discussed below.
Diffuse eosinophilic gastritis of undefined aetiology is usually approached in a similar fashion to lymphoplasmacytic gastritis.
Atrophic gastritis has been infrequently described in dogs and cats but is often associated with a marked cellular infiltrate. Atrophy has also been associated with gastric adenocarcinoma in Lundehunds and in dogs with lymphoplasmacytic gastritis of undetermined cause atrophy correlates with the expression of mRNA for IL-1b and IL-10 and the presence of neutrophils. There is no clear evidence that lymphoplasmacytic gastritis progresses to atrophy and gastric cancer in dogs or cats, and the role of Helicobacter or antigastric antibodies in the development of atrophy in dogs and cats remains to be determined. Dogs and cats with atrophic gastritis have not been reported to develop cobalamin deficiency, unlike in man. This is probably because the pancreas, rather than the stomach, is the main source of intrinsic factor in these species. Achlorhydria has been described in dogs, and may enable the proliferation of bacteria in the stomach and upper small intestine, though this has not been proven. The treatment of atrophic gastritis has received limited attention, but Helicobacter eradication and immunosuppression have been effective in people.
Hypertrophy of the fundic mucosa is uncommon and is often part of the breed specific gastropathies or gastroenteropathies mentioned above.
Concurrent hypergastrinaemia should prompt consideration of underlying hepatic or renal disease, achlorhydria, or gastrin producing tumors, which should be pursued appropriately. Basenji gastroenteropathy is variably associated with fasting hypergastrinaemia and exaggerated secretin stimulated gastrin, and anecdotal reports suggest that affected Basenjis may respond to antimicrobial therapy. Antral hypertrophy of brachycephalic dogs causes outflow obstruction and is treated with surgery.