Lymphoplasmacytic Gastritis

Lymphoplasmacytic gastritis (LPG) is a chronic inflammatory condition of the gastric mucosa characterized by infiltration of lymphocytes and plasma cells. It is the most common form of chronic gastritis in dogs and cats, often associated with inflammatory bowel disease (IBD) when concurrent intestinal involvement exists. The disease can be classified based on the predominant cell type (lymphocytic, plasmacytic, or mixed), the distribution (antral, fundic, or diffuse), and the severity (mild, moderate, or severe). LPG is typically a sterile inflammation, but it can be secondary to chronic antigenic stimulation, food allergy, or bacterial overgrowth. It may progress to gastric atrophy, fibrosis, or, rarely, gastric neoplasia (e.g., lymphoma).

The exact etiology of lymphoplasmacytic gastritis is often idiopathic, but several factors are implicated. Chronic dietary antigens (e.g., beef, dairy, wheat, chicken) can trigger a type I hypersensitivity reaction in genetically predisposed animals. Bacterial infections, particularly Helicobacter spp. (e.g., H. pylori, H. felis, H. heilmannii), are known to cause lymphoplasmacytic infiltration in the gastric mucosa. Parasitic infections (e.g., Physaloptera spp., Ollulanus tricuspis) can also induce chronic inflammation. Adverse food reactions, including food allergy and food intolerance, are common triggers. Immune-mediated mechanisms, such as loss of oral tolerance and dysregulation of T-regulatory cells, play a central role. Genetic predisposition is suspected in certain breeds (e.g., Basenji, Soft-Coated Wheaten Terrier, Norwegian Lundehund). Chronic stress and environmental factors may exacerbate the condition. In some cases, no identifiable cause is found, and the disease is termed idiopathic.

Lymphoplasmacytic gastritis is diagnosed in both dogs and cats, with a higher prevalence in middle-aged to older animals (mean age 6-8 years). No strong sex predilection is reported. Certain breeds are overrepresented: in dogs, Basenjis, Soft-Coated Wheaten Terriers, Norwegian Lundehunds, and German Shepherds; in cats, Siamese and other purebred cats may be predisposed. The condition is more common in animals with concurrent inflammatory bowel disease (IBD) or food-responsive diarrhea. Geographic distribution is worldwide, with no clear seasonal pattern. The exact incidence is unknown, but it is considered the most common histologic diagnosis in gastric biopsies from dogs and cats with chronic vomiting.

The pathophysiology of lymphoplasmacytic gastritis involves a complex interplay of genetic susceptibility, mucosal barrier dysfunction, and aberrant immune responses. Chronic antigenic stimulation (dietary, bacterial, or parasitic) leads to activation of CD4+ T-helper cells, particularly Th1 and Th17 subsets, which secrete pro-inflammatory cytokines (e.g., IFN-γ, TNF-α, IL-17). These cytokines recruit lymphocytes and plasma cells into the lamina propria and submucosa. Plasma cells produce antibodies (IgG, IgA, IgE) against the inciting antigens, forming immune complexes that further amplify inflammation. The inflammatory infiltrate disrupts the gastric epithelial barrier, leading to increased permeability and exposure to luminal antigens. This triggers a vicious cycle of inflammation and tissue damage. Chronic inflammation can cause gastric gland atrophy, metaplasia, and fibrosis, impairing gastric acid secretion and motility. In severe cases, oxidative stress and DNA damage may predispose to gastric lymphoma or adenocarcinoma.

Predisposing factors include genetic susceptibility (breed-specific), dietary factors (highly processed diets, food additives, novel proteins), chronic Helicobacter infection, concurrent inflammatory bowel disease, chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) or corticosteroids, stress, and environmental factors (e.g., poor hygiene, overcrowding). Age is a risk factor, with older animals more commonly affected. Immunosuppression (e.g., due to FIV or FeLV in cats) may increase susceptibility. Additionally, animals with a history of adverse food reactions or antibiotic-responsive enteropathy are at higher risk.

Clinical signs are often chronic and intermittent. The most common sign is chronic vomiting, which may be bilious, foamy, or contain undigested food. Vomiting may occur hours after eating or in the morning on an empty stomach. Other signs include anorexia, weight loss, lethargy, and abdominal discomfort. In some cases, diarrhea may be present if concurrent intestinal involvement exists. Physical examination may reveal a thin body condition, mild dehydration, and pain on abdominal palpation. In severe cases, signs of gastric ulceration (e.g., hematemesis, melena) may occur. Cats may present with chronic vomiting and weight loss, sometimes with a history of hairballs. The severity of clinical signs often correlates with the degree of inflammation and the presence of complications.

Differential diagnoses include: (1) Helicobacter-associated gastritis – distinguished by identification of spiral bacteria on cytology or histopathology (Warthin-Starry stain) and response to antimicrobial therapy. (2) Eosinophilic gastritis – characterized by eosinophilic infiltration, often associated with parasites or food allergy. (3) Gastric lymphoma – especially in cats, can mimic LPG; requires cytology/histopathology with immunophenotyping (B-cell vs T-cell) and clonality testing (PCR for antigen receptor rearrangement). (4) Gastric adenocarcinoma – rare but can present with chronic vomiting and weight loss; diagnosed via biopsy. (5) Chronic renal disease – causes vomiting due to uremic gastritis; differentiated by blood work (elevated BUN, creatinine, SDMA). (6) Pancreatitis – causes vomiting and abdominal pain; diagnosed via serum lipase (cPLI/fPLI) and ultrasound. (7) Gastric foreign body – acute onset, imaging (radiography/ultrasound) reveals obstruction. (8) Inflammatory bowel disease (IBD) – often concurrent; requires intestinal biopsies. (9) Food allergy – may cause vomiting and diarrhea; diagnosed by dietary elimination trial. (10) Gastric ulceration – due to NSAIDs, stress, or mast cell tumor; diagnosed by endoscopy and histopathology.

The diagnostic algorithm begins with a thorough history and physical examination. Initial laboratory tests include complete blood count (CBC), serum biochemistry profile, urinalysis, and fecal examination (for parasites). If vomiting is chronic, abdominal imaging (radiography and ultrasonography) is recommended to rule out obstruction, masses, or other organ disease. Serum cobalamin and folate levels may be measured to assess intestinal involvement. If no obvious cause is found, gastroduodenoscopy is the next step. Endoscopic findings may include mucosal erythema, edema, erosions, or a cobblestone appearance. Multiple gastric biopsies (at least 6-8) should be obtained from the fundus, body, and antrum. Histopathology is the gold standard for diagnosis. Additional tests may include Helicobacter testing (rapid urease test, histopathology with special stains, PCR) and food elimination trials. In cases where lymphoma is suspected, immunophenotyping and clonality testing are recommended.

Hematology: Often unremarkable; may show mild anemia (chronic disease) or eosinophilia if concurrent parasitism. Serum biochemistry: May be normal; in severe cases, hypoproteinemia (due to protein-losing enteropathy) or elevated liver enzymes (if concurrent IBD). Electrolyte disturbances (hypokalemia, hypochloremia) may occur due to vomiting. Urinalysis: Usually normal; may show concentrated urine if dehydrated. Blood gas analysis: May reveal metabolic alkalosis due to vomiting. Specific biomarkers: Cobalamin (B12) and folate levels may be low if concurrent intestinal disease. Fecal alpha-1-proteinase inhibitor can be elevated in protein-losing enteropathy. Serology/PCR: For Helicobacter spp., FeLV/FIV in cats. Inflammatory markers (e.g., CRP) may be elevated but are nonspecific.

Radiography: Abdominal radiographs are often unremarkable; may show a gas-filled stomach or signs of gastric wall thickening (rare). Ultrasonography: May reveal thickening of the gastric wall, loss of normal layering, or enlarged gastric lymph nodes. Doppler ultrasound can assess blood flow. Computed Tomography (CT): Provides detailed assessment of gastric wall thickness and lymphadenopathy; useful for staging if neoplasia is suspected. Magnetic Resonance Imaging (MRI): Rarely used for gastric disease but can evaluate soft tissue detail. Endoscopy: The most valuable imaging modality; allows direct visualization of the gastric mucosa and biopsy collection. Fluoroscopy: May be used to assess gastric emptying. Echocardiography: Not directly relevant but may be performed to rule out cardiac causes of vomiting.

Cytology: Fine-needle aspiration of the gastric wall is rarely performed due to difficulty and low yield. Endoscopic brush cytology may reveal inflammatory cells but is not diagnostic. Histopathology: The hallmark is infiltration of the gastric mucosa by lymphocytes and plasma cells. The infiltrate may be diffuse or nodular, and may extend into the submucosa. In mild cases, the infiltrate is confined to the lamina propria. In severe cases, there may be glandular atrophy, fibrosis, and lymphoid follicle formation. Special stains (e.g., Warthin-Starry) can identify Helicobacter organisms. Immunohistochemistry (CD3 for T-cells, CD79a for B-cells) can differentiate LPG from lymphoma. In LPG, the infiltrate is mixed and polyclonal, whereas lymphoma is monoclonal and often composed of large atypical lymphocytes.

Treatment is multimodal and aimed at reducing inflammation, managing clinical signs, and addressing underlying causes. Dietary management is crucial: a highly digestible, novel protein or hydrolyzed protein diet is recommended. In food-responsive cases, a dietary elimination trial may be diagnostic and therapeutic. Antimicrobial therapy is indicated if Helicobacter infection is confirmed; a combination of amoxicillin (20 mg/kg PO q12h), clarithromycin (7.5 mg/kg PO q12h), and a proton pump inhibitor (e.g., omeprazole 1 mg/kg PO q12h) for 14 days is commonly used. Anti-inflammatory/immunosuppressive therapy: Prednisolone (dogs: 1-2 mg/kg PO q24h; cats: 2-4 mg/kg PO q24h) is the mainstay, tapered over weeks to months. In refractory cases, additional immunosuppressants such as chlorambucil (cats: 2-6 mg/m² PO q48h) or cyclosporine (5 mg/kg PO q24h) may be added. Antiemetics: Maropitant (1 mg/kg SC q24h or 2 mg/kg PO q24h) or metoclopramide (0.2-0.5 mg/kg PO q8h) can control vomiting. Gastroprotectants: Sucralfate (0.5-1 g PO q8h) or omeprazole may be used if ulceration is present. Probiotics and prebiotics may support gut health. In severe cases, hospitalization with fluid therapy and nutritional support (e.g., feeding tube) may be necessary.

The prognosis for lymphoplasmacytic gastritis is generally good to fair with appropriate treatment. Many animals respond to dietary modification and immunosuppressive therapy, with improvement in clinical signs within 1-2 weeks. However, the disease is often chronic and may require long-term management. Relapses are common if treatment is discontinued prematurely. The prognosis is worse in cases with severe fibrosis, atrophy, or concurrent neoplasia. In cats, the risk of progression to lymphoma is a concern, especially if the inflammation is severe and unresponsive to therapy. Overall, the median survival time in dogs with IBD (including gastritis) is several years, but varies widely.

Follow-up is essential to monitor response to therapy and adjust medications. Recheck examinations should be performed every 2-4 weeks initially, then every 1-3 months. Serial blood work (CBC, biochemistry) is recommended to monitor for drug side effects (e.g., steroid-induced changes). Repeat endoscopy and biopsy may be indicated if clinical signs do not improve or if there is suspicion of neoplasia. Dietary compliance should be reinforced. Tapering of immunosuppressive drugs should be gradual, over weeks to months, to avoid relapse. Long-term monitoring for signs of lymphoma (e.g., weight loss, persistent vomiting) is important, especially in cats.

Pearls: (1) Always obtain multiple gastric biopsies during endoscopy, as lesions can be patchy. (2) Consider food-responsive disease before starting immunosuppressants; a dietary trial may be diagnostic. (3) In cats, always rule out lymphoma with immunophenotyping and clonality testing. (4) Helicobacter infection is common but not always pathogenic; treat only if clinical signs correlate. (5) Use a stepwise approach: diet, then antibiotics, then immunosuppressants. Pitfalls: (1) Failing to biopsy the stomach during endoscopy for chronic vomiting. (2) Misinterpreting lymphocytic infiltration as lymphoma without immunophenotyping. (3) Using corticosteroids without addressing dietary triggers. (4) Overlooking concurrent diseases (e.g., pancreatitis, renal disease). (5) Tapering steroids too quickly, leading to relapse.

Based on Plumb's Veterinary Drug Handbook, the following protocols are recommended: (1) Prednisolone: Dogs – 1-2 mg/kg PO q24h, then taper by 25% every 2-4 weeks; Cats – 2-4 mg/kg PO q24h, taper similarly. (2) Chlorambucil: Cats – 2-6 mg/m² PO q48h, adjust based on response and CBC. (3) Cyclosporine: Dogs – 5 mg/kg PO q24h, monitor trough levels (target 400-600 ng/mL). (4) Metronidazole: 10-15 mg/kg PO q12h (may be used for its immunomodulatory effects). (5) Amoxicillin: 20 mg/kg PO q12h for 14 days (for Helicobacter). (6) Clarithromycin: 7.5 mg/kg PO q12h for 14 days. (7) Omeprazole: 1 mg/kg PO q12h (for Helicobacter or ulceration). (8) Maropitant: 1 mg/kg SC q24h or 2 mg/kg PO q24h for vomiting. (9) Sucralfate: 0.5-1 g PO q8h for gastric protection. (10) Metoclopramide: 0.2-0.5 mg/kg PO q8h for prokinetic effect. Adjust dosages for renal or hepatic impairment; monitor for drug interactions (e.g., cyclosporine with ketoconazole).

Evidence-based literature supports the use of dietary modification and immunosuppressive therapy in lymphoplasmacytic gastritis. A landmark study by Jergens et al. (1992) demonstrated that a combination of dietary therapy and prednisolone improved clinical signs in dogs with IBD. More recent studies (e.g., Allenspach et al., 2007) have shown that food-responsive disease is common and should be addressed first. ACVIM consensus guidelines (2010) recommend a stepwise approach to IBD, including gastritis. Studies on Helicobacter therapy (e.g., Leib et al., 2007) show that triple therapy with amoxicillin, clarithromycin, and omeprazole is effective in eliminating infection, but clinical response is variable. In cats, a study by Kiselow et al. (2008) found that chlorambucil and prednisolone are effective in treating IBD, including gastritis. The use of cyclosporine has been evaluated in dogs with refractory IBD (e.g., Allenspach et al., 2006) with promising results. Overall, the evidence supports a multimodal approach, but large randomized controlled trials are lacking.