Varioliform Gastritis: Symptoms, Types, Causes and Treatment

Varioliform gastritis is a unique and often misunderstood form of gastritis characterized by distinctive lesions on the stomach lining. Although relatively rare, it can present with a range of symptoms and has several subtypes, each with its own clinical and histological features. Understanding the symptoms, types, causes, and treatment options is essential for both healthcare providers and patients. In this article, we delve into the latest research to provide a comprehensive, evidence-based overview of varioliform gastritis.

Symptoms of Varioliform Gastritis

Varioliform gastritis can be elusive, with symptoms that often mimic more common gastrointestinal conditions. Recognizing its presentation is the first step toward proper diagnosis and management.

Symptom	Description	Frequency/Severity	Source(s)
Upper GI pain	Epigastric discomfort, mimics ulcers	Common	1 2
Weight loss	Unintentional, sometimes significant	Variable	1 2 3
GI bleeding	Hematemesis, melena, or occult bleeding	Occasional, can be severe	2 3 13
Protein loss	Hypoproteinaemia, peripheral edema	Rare but notable	11 13
Dyspepsia	Indigestion, nausea	Common	2 4
Remitting bouts	Periods of symptom exacerbation/relief	Characteristic of disease	1 3

Table 1: Key Symptoms

Symptom Overview

The clinical presentation of varioliform gastritis is broad and often overlaps with other gastric pathologies. Patients can experience:

• Upper gastrointestinal pain: Most commonly, individuals report epigastric pain or discomfort similar to that seen in peptic ulcer disease. This can sometimes make diagnosis challenging, as the symptoms are non-specific 1 2.
• Weight loss: In cases where the disease process is more severe or chronic, unintentional weight loss can occur, raising concern for malignancy or other serious pathology 1 2 3.
• Gastrointestinal bleeding: Some patients present with signs of bleeding, ranging from iron deficiency anemia due to chronic occult loss, to severe, acute hematemesis requiring emergency intervention 2 3 13.
• Protein-losing gastroenteropathy: Rarely, varioliform gastritis is associated with significant protein loss into the gastrointestinal tract, leading to hypoproteinaemia and peripheral edema 11 13.
• Dyspepsia and non-specific symptoms: Nausea, bloating, and indigestion are also frequently reported, further complicating the clinical picture 2 4.
• Remitting and relapsing course: The disease often follows a subacute course, with periods of symptom exacerbation followed by remission, only to relapse again 1 3.

Symptom Patterns and Diagnostic Challenges

The overlapping nature of symptoms with peptic ulcers and even gastric cancer can lead to delayed or missed diagnoses. Not all patients will have dramatic presentations; some may only have mild, chronic discomfort. In rare instances, as seen in children, the disease may progress to life-threatening bleeding, necessitating surgical intervention 3. The presence of protein-losing gastroenteropathy, while uncommon, should prompt consideration of varioliform gastritis, especially when other causes are excluded 11 13.

Types of Varioliform Gastritis

Varioliform gastritis is not a single entity but encompasses several subtypes, distinguished by their endoscopic appearance, location, and histological features.

Type/Subtype	Main Features	Distinguishing Criteria	Source(s)
Diffuse	Widespread mucosal bulging, large folds	Involvement of fundus/body	1 3 6
Antral	Lesions limited to antrum	No distinct symptoms	1 5 8
Erosive/Chronic Erosive	Erosions with surrounding mucosal elevation	"Target" lesions endoscopically	2 7
Lymphocytic	Dense lymphocyte infiltration, "varioliform" endoscopic pattern	Confirmed by biopsy	4 5 8 11

Table 2: Types and Subtypes

Diffuse Varioliform Gastritis

• Distribution: Involves the fundus and body of the stomach, sometimes with extension to the antrum.
• Endoscopic features: Characterized by large, swollen gastric folds and multiple mucosal bulgings or erosions.
• Clinical significance: This form is less common but has a distinct clinical and histological profile, including a subacute, relapsing course 1 3 6.

Antral Varioliform Gastritis

• Distribution: Restricted to the antrum.
• Symptoms: Tends not to have unique clinical symptoms, often detected during endoscopy for other reasons.
• Clinical individuality: Considered less clinically significant, but should be distinguished from diffuse forms 1 5 8.

Erosive/Chronic Erosive Varioliform Gastritis

• Appearance: Features erosions surrounded by elevated mucosa, giving a "target" appearance on imaging.
• Pathology: Includes acute and chronic inflammation, edema, fibrosis, and sometimes cellular atypia.
• Potential for misdiagnosis: Some cases may be mistaken for carcinoma histologically, highlighting the importance of comprehensive assessment 2 7.

Lymphocytic Gastritis

• Histological hallmark: Intense infiltration of the surface and foveolar epithelium by mature T lymphocytes.
• Endoscopic correlation: Presents with raised lesions and erosions, often indistinguishable from varioliform gastritis endoscopically.
• Overlap: The majority of varioliform gastritis cases (especially diffuse type) are now understood to represent lymphocytic gastritis upon histological examination 4 5 8 11.

Histological and Endoscopic Correlation

The relationship between endoscopic findings (varioliform appearance) and histological diagnosis (especially lymphocytic infiltration) is strong. Most cases with the classic endoscopic appearance of varioliform gastritis are confirmed as lymphocytic gastritis on biopsy, particularly when the lesions are diffuse and not limited to the antrum 5 8. However, exceptions exist, such as in Crohn’s disease or when the disease is focal 5.

Causes of Varioliform Gastritis

Understanding what leads to varioliform gastritis is complex, as it appears to involve a combination of immune, infectious, lifestyle, and possibly genetic factors.

Cause/Risk Factor	Mechanism/Association	Strength of Evidence	Source(s)
Immune response	Hypersensitivity, increased IgE cells	Strong	1 12
Lymphocytic infiltration	Abnormal T-cell response to local antigen	Strong	4 5 8
Helicobacter pylori	Infectious trigger, variable prevalence	Moderate	4 10 13
Allergic conditions	Association with allergic diseases	Strong	1 10 12
Lifestyle factors	Stress, irregular meals, spicy food	Moderate/Significant	10
Smoking	Increased risk in men	Moderate	10
Diet	Pickled food (risk), fresh fruit/vegetables (protective)	Significant	10
Protein loss	Consequence, not direct cause	Rare, but notable	11 13

Table 3: Causes and Risk Factors

Immune and Hypersensitivity Mechanisms

A leading hypothesis involves an abnormal immune response. Varioliform gastritis is marked by increased immunocyte infiltration in the gastric mucosa, particularly with a higher proportion of IgE cells, suggesting a role for type 1 hypersensitivity reactions 1 12. This is bolstered by the observation that medications stabilizing mast cells (such as sodium cromoglycate) are effective treatments.

Lymphocytic Infiltration and Local Antigens

The histological overlap with lymphocytic gastritis, a condition marked by dense T-cell infiltration, suggests that varioliform gastritis may represent an abnormal immune response to a local (possibly luminal) antigen 4 5 8. In some cases, this may be linked to celiac disease or other autoimmune processes, though not universally.

Infectious Triggers: Helicobacter pylori

The role of Helicobacter pylori infection remains unclear but is certainly implicated in a subset of cases. While not all patients with varioliform gastritis have H. pylori infection, its prevalence is still higher among affected individuals compared to the general population 4 10 13. Eradication may not always resolve the gastritis, indicating that other factors are at play.

Allergic and Environmental Factors

Notably, allergic respiratory diseases are strongly associated with the occurrence of gastric varioliform lesions, supporting the allergic/immune hypothesis 1 10 12.

Lifestyle and Dietary Factors

Several lifestyle factors have been linked to increased risk:

• Work-related stress and irregular meal patterns are associated with higher rates of gastric varioliform lesions 10.
• Dietary habits play a significant role; high intake of spicy or pickled foods increases risk, while consumption of fresh fruits and vegetables appears to be protective 10.
• Smoking is a risk factor, particularly in men 10.

Molecular and Genetic Aspects

Recent proteomic studies have shown distinct changes in protein expression in varioliform gastritis, such as upregulation of TXNDC5 and downregulation of PEBP1, indicating alterations in cellular stress responses, apoptosis, and metabolism 9. While the clinical significance of these changes is still being elucidated, they may point to novel disease mechanisms.

Treatment of Varioliform Gastritis

Managing varioliform gastritis requires a targeted approach, considering its underlying immune, infectious, and environmental factors.

Treatment	Mechanism/Use	Efficacy	Source(s)
Sodium cromoglycate	Stabilizes mast cells, blocks hypersensitivity	Effective in most cases	1 6 12
Histamine antagonists (H2 blockers)	Reduces gastric acid, symptom control	Moderately effective	1 2 12
Proton pump inhibitors (PPIs)	Reduces acid, heals mucosa, controls protein loss	Effective, especially with protein leakage	13
Antacids	Symptomatic relief	Supportive	2
H. pylori eradication	Antibiotics for positive cases	Mixed results	4 13
Dietary/lifestyle modification	Reduce risk factors (e.g., spicy food, smoking)	Supportive	10

Table 4: Treatment Approaches

Pharmacological Therapy

• Sodium cromoglycate: This mast cell stabilizer is the mainstay of treatment for diffuse varioliform gastritis with an immune-mediated mechanism. It has shown superior efficacy compared to H2 blockers and placebo, leading to both symptomatic and histological improvement 1 6 12.
• Histamine antagonists (H2 blockers): Drugs like cimetidine offer moderate relief by reducing gastric acidity and inflammation, though they are less effective than cromoglycate in this specific condition 1 2 12.
• Proton pump inhibitors (PPIs): Omeprazole and similar agents are highly effective, especially in cases presenting with protein-losing gastroenteropathy or significant mucosal damage. PPIs reduce acid secretion, promote mucosal healing, and can reverse protein loss 13.
• Antacids: Provide symptomatic relief and may help in acute settings or in combination with other therapies 2.

Eradication of H. pylori

In patients with confirmed H. pylori infection, eradication therapy may be warranted. However, the relationship between H. pylori and varioliform gastritis is not straightforward, and not all patients respond fully to eradication 4 13.

Dietary and Lifestyle Modification

Since dietary habits and lifestyle factors contribute to disease risk, interventions such as reducing spicy and pickled food intake, increasing fresh fruits and vegetables, quitting smoking, and managing stress are recommended as adjunctive measures 10.

Management of Complications

• Protein-losing gastroenteropathy: Requires aggressive acid suppression and nutritional support. PPI therapy has been shown to successfully reverse protein loss in affected patients 11 13.
• Severe bleeding: Rare but may necessitate surgical intervention if not controllable by medical means 3.

Monitoring and Prognosis

Repeat endoscopy is often used to monitor mucosal healing. Most patients respond well to therapy, with resolution of symptoms and endoscopic lesions 2 6 13. However, since varioliform gastritis is associated with premalignant changes such as glandular atrophy and intestinal metaplasia, long-term follow-up may be necessary to monitor for progression or malignant transformation 10.

Conclusion

Varioliform gastritis is a rare, multifaceted form of gastritis with distinctive clinical and pathological features. Here is a summary of the main points:

• Symptoms: Often mimic peptic ulcers or gastric cancer; include upper GI pain, weight loss, bleeding, and occasionally protein loss.
• Types: Includes diffuse, antral, erosive/chronic erosive, and lymphocytic subtypes, with significant overlap.
• Causes: Involve immune-mediated mechanisms, lymphocytic infiltration, H. pylori infection, allergic and lifestyle factors, and possibly genetic predisposition.
• Treatment: Centers around mast cell stabilizers (sodium cromoglycate), acid suppression (H2 blockers, PPIs), dietary/lifestyle modification, and management of complications.

Key takeaways:

• Early recognition and accurate differentiation from other gastric diseases are essential.
• Treatment tailored to the underlying cause and severity leads to favorable outcomes.
• Long-term monitoring is advised due to premalignant potential in some cases.

By understanding the unique characteristics of varioliform gastritis, patients and clinicians can work together to achieve optimal management and improved quality of life.