Helicobacter pylori

**ONE** · 31-07-08 09:26 AM

Background
Helicobacter pylori (Hp) is a gram-negative bacillus responsible for one of the most common infections found in humans worldwide.1 Warren and Marshall first cultured and identified the organism as Campylobacter pylori in 1982. By 1989, it was renamed and recognized to be associated closely with antral gastritis (gastric and duodenal ulcers in adults and children). By the early-to-mid 1990s, further evidence supported a link between chronic gastritis of H pylori infection in adults and malignancy, specifically gastric lymphoma and adenocarcinoma.
Objectives of current and future research on H pylori include improving the understanding of the immunopathogenesis of gastric disease associated with H pylori infection, elucidating the modes of transmission, and improving the safety and efficacy of vaccines to prevent H pylori infection.

Pathophysiology
H pylori organisms are spiral-shaped gram-negative bacteria that are highly motile because of multiple unipolar flagella. They are microaerophilic and potent producers of the enzyme urease. H pylori inhabits the mucus adjacent to the gastric mucosa.
Important adaptive features that enhance survival of the organism in an acidic environment include its shape and motility, its reduced oxygen requirement, its adhesion molecules that are trophic to certain gastric cells, and its urease production. Bacterial urease converts urea to ammonium and bicarbonate, neutralizing gastric acid and providing protection in the hostile, highly acidic gastric environment.
H pylori produces suspected disease-inducing factors, including urease, vacuolating cytotoxin, catalase, and lipopolysaccharide (LPS). Urease, a potent antigen, induces increased immunoglobulin G and immunoglobulin A production. Expression of vacuolating cytotoxin, which induces inflammatory cytokines, may be associated with more pronounced inflammation and increased propensity to cause disease. Catalase helps H pylori survive in the host by preventing the formation of reactive oxygen metabolites from hydrogen peroxide. The LPS outer membrane of H pylori is a less potent inducer of the host complement cascade and enhances the ability of H pylori to colonize the stomach.

H pylori colonizes the stomach, induces inflammatory cytokines, and causes gastric inflammation. Individuals with H pylori–associated antral-predominant gastritis with increased gastric acid production are prone to peptic ulcer disease (PUD).2 In contrast, H pylori pan-predominant gastritis or corpus-predominant gastritis with decreased gastric acid production are more prone to developing gastric atrophy (intestinal metaplasia and gastric adenocarcinoma).

H pylori has recently been associated with iron-deficiency anemia. The 2 main hypotheses that potentially explain this relation are (1) sequestration of iron due to antral H pylori infection and (2) decreased non-heme iron absorption caused by hypochlorhydria.

H pylori infection and its association with gastric malignancy have been well described in several epidemiologic studies.3 However, the course of progression from inflammation to cancer remains unclear. One model describes the stepwise progression of H pylori infection to hypochlorhydria, chronic gastritis, atrophic gastritis, intestinal metaplasia, and gastric cancer. Increased production of the cytokine interleukin 1β has been linked to an increased risk of hypochlorhydria and gastric cancer in infected subjects.
Frequency
United States
Overall, approximately one-third of the population is infected with H pylori, increasing with age. See Age.
International
In general, the prevalence is high in developing countries and the infection is acquired at a young age. The prevalence of H pylori infection is not only lower in industrialized countries than in developing countries, but the incidence of H pylori infection, gastric cancer, and ulcer disease are also declining. Worldwide, more than 1 billion people are estimated to be infected with H pylori. See Age.
Mortality/Morbidity
• Most children infected with H pylori are asymptomatic.
• Antral gastritis is the most common manifestation in children. Duodenal and gastric ulcers may be associated with H pylori gastritis in adults but is uncommon in children. The risk of gastric cancers, including non-Hodgkin lymphoma (eg, mucosa-associated lymphoid tissue [MALT]) and adenocarcinoma, is increased in adults.
• The relationship between H pylori gastritis and recurrent abdominal pain (RAP) is controversial. The incidence of H pylori gastritis in patients with RAP is not significantly higher than the incidence of H pylori infection in the general population. Although some studies demonstrate an improvement in symptoms in children with RAP and H pylori gastritis after eradication therapy for H pylori, data from a recent double-blind controlled trial did not confirm that finding.4
Race
The prevalence is increased in African American, Hispanic, Asian, and Native American populations.
Sex
Infection rates are similar in males and females.
Age
Infection in young children is rare.
• In developed countries, less than 10% of children younger than 12 years are infected; however, seropositivity increases with age at a rate of 0.3-1% per year. Studies of seropositivity in adults in developed countries revealed prevalences of 30-50%.
• In the United States, the estimated prevalence is 20% for people younger than 30 years and 50% for those older than 60 years.
• See Mortality/Morbidity.

History
When obtaining the history, one should pay particular attention to anorexia and weight loss, pallor or laboratory findings of anemia, vomiting, abdominal pain associated with meals or nighttime, and any description of GI bleeding. A history of such findings raises the concern of PUD.
In the child in whom H pylori infection is suspected, the history should include the following:
• Character, location, frequency, duration, severity, and exacerbating and alleviating factors of abdominal pain
• Bowel habits and description of stool
• Appetite, diet, and weight changes
• Halitosis, vomiting, and description of gastric material
• Family history of ulcer disease or GI conditions (eg, Crohn disease)
• Medications (prescribed and over the counter)
• Previous diagnostic testing and specific therapy in the GI tract
• Family and social stressors
• Alcohol ingestion and smoking habits

Physical
Physical examination of an asymptomatic child with H pylori infection usually yields unremarkable findings. In the child with chronic gastritis, duodenitis, and PUD, important examination findings include epigastric tenderness or findings consistent with GI bleeding (eg, guaiac-positive stools, tachycardia, pallor).
Children with PUD leading to complications (eg, severe blood loss in the GI tract, perforation, obstruction) can appear ill and have evidence of hemodynamic instability or signs of an acute abdomen. Children with long-standing PUD from H pylori may become profoundly anemic from undetected chronic bleeding and have no complaints.
• Assess the general appearance of the child.
• Assess vital signs.
• Assess perfusion, with attention to mental status, heart rate, pulses, and capillary refill.
• Assess hydration status, with attention to the presence of moisture in the mucous membranes and skin turgor.
• Assess the skin and conjunctivae for pallor.
• Perform a thorough heart and lung examination.
• Inspect, auscultate, and palpate the abdomen.
• Perform rectal examination and a stool guaiac test.
• Perform pelvic examination in the sexually active female patient with pain.

Causes
Epidemiologic studies have addressed various factors, such as bacterial, host, genetic, and environmental factors, to determine the causative links to H pylori infection. Data support person-to-person spread of infection, possibly related to dental plaque, but knowledge of reservoirs and transmission modes is incomplete.
Causes of H pylori infection include the following:
• Person-to-person transmission of H pylori infection is noted.
•
o Infection clusters are noted, particularly in families with infected children. Mother-to-child transmission was strongly suggested in a study of DNA analysis of the H pylori strains.5 The data showed identical H pylori strains between mothers and their toddler-aged children.
o Crowding and poor personal hygiene may also play a role.
o An increased prevalence of H pylori infection is noted in developing countries. This may reflect the combined effects of poor living conditions, poor hygiene, and crowding.
o In the United States, socioeconomic level is strongly and inversely related to the prevalence of H pylori infection, a finding that may also reflect the same factors as those noted in developing countries.
• Bacterial factors may play a role in the clinical manifestations of H pylori infection.
•
o Patients with H pylori infection have 2 basic phenotypes based on the presence or absence of a vacuolating cytotoxin.
o People with cytotoxin-positive infection have endoscopically proven inflammation that is more pronounced than those of patients with cytotoxin-negative H pylori infection.
• Host factors may play a role in the acquisition of H pylori infection.
•
o Children may be better able to clear acute infection than adults (2% per year).
o Hypochlorhydria may be necessary to allow H pylori to colonize in the stomach.
o Normal gastric epithelial cells that line the stomach are necessary for H pylori persistence. H pylori is not found in atrophied metaplastic epithelium.
• Genetic factors may play a role in H pylori infection.
•
o The incidence of H pylori infection is increased in first-degree relatives of children with PUD.
o Concordance for PUD is higher in monozygotic than in dizygotic twins.
• Data from only one study links an increased prevalence of H pylori infection with a community's water supply.6
• H pylori isolates are found more often in personnel who work in the endoscopy suite than in the general population.

DIFFERENTIALS

Cholecystitis
Cholelithiasis
Crohn Disease
Esophagitis
Gastroesophageal Reflux
Pancreatitis and Pancreatic Pseudocyst
Peptic Ulcer Disease
Ureteropelvic Junction Obstruction
Zollinger-Ellison Syndrome
Other Problems to be Considered
Eosinophilic esophagitis
Eosinophilic gastroenteritis
Gastritis, induced by nonsteroidal anti-inflammatory drugs (NSAIDs)
Gastritis, stress induced
Functional abdominal pain
Functional dyspepsia
Celiac disease

WORKUP

Lab Studies
• Serologic assay of H pylori immunoglobulin G
•
o This test has good specificity, but its sensitivity is rather poor, with better correlation with active disease in adults than in children.
o In the pediatric population, serology has a sensitivity of 69%, a specificity of 78%, but a positive predictive value of only 31%.
o The test is most useful when the result is negative and excludes H pylori.
o Antibody levels are persistently high long (6-12 mo) after treatment.
• Fecal H pylori-antigen test: A test to detect H pylori antigen in feces is available as both a pretreatment tool and, especially, as a posttreatment diagnostic tool.
• Antibody testing of urine and H pylori DNA polymerase chain reaction (PCR) in saliva7
•
o The sensitivity is lower than that of serology.8
o A PCR assay in which primers are used against part of the H pylori urease gene (urea) has been developed and reportedly has a sensitivity and a specificity similar to that of histologic examination.
Imaging Studies
• Upper-GI series findings help in detecting PUD in approximately 70% of children with the disease. A double-contrast study has a detection rate higher than that of a single-contrast study, but the child must be older and cooperative, and the test increases the radiation exposure.
• No radiologic test is equal to esophagogastroduodenoscopy (EGD) in assessing PUD (see Procedures).
• Radiologic findings of duodenal ulcers include filling defects or deformities of the duodenal bulb.
• A fibrinous clot in the ulcer may lead to a false-normal radiologic appearance. False-positive findings with barium studies have been noted to be especially high in pediatric patients.
• Findings on an upper-GI series can depict gastric-outlet obstruction, the result of pyloric lesions.
Other Tests
• Urea breath test: The patient ingests a test meal that contains urea labeled with carbon-13 (13C), which is a nonradioactive isotope. H pylori urease activity produces labeled 13C dioxide that can be detected in exhaled air. A positive result confirms urease activity and H pylori infection. This test is very specific and sensitive. Its most useful application is to verify H pylori eradication after treatment.
Procedures
• Upper endoscopy (EGD) is the procedure of choice for detecting gastritis, duodenitis, and PUD in the pediatric population.
•
o EGD allows for direct visualization of the mucosa; for localization of the source of bleeding; for the detection of H pylori by means of biopsy, culture, and cytology analysis; and for DNA testing by using PCR.
o In addition, a quick test based on detection of urease activity (a highly specific marker of H pylori) can be performed. The test, termed the Campylobacter-like organism (CLO) test allows for a diagnosis of H pylori infection within 24 hours.
o Two modified, rapid urease test kits are now commercially available and are reported to have better accuracy, a shorter reaction time, and better cost-effectiveness than those of the CLO test.
o In children, endoscopy may reveal a nodular appearance in the gastric antrum resulting from lymphoid hyperplasia.9 However, only approximately 50% of affected children have endoscopic evidence of changes of H pylori gastritis.
o The gross appearance of an active ulcer is a round or oval, punched-out lesion with a smooth, white base and with surrounding mucosa that is red and edematous. In H pylori infection, the most common location for ulceration is the duodenal bulb.
o Therapeutic endoscopy for acute bleeding (ie, the injection of sclerosing or vasoconstricting agents) is only rarely necessary for patients with H pylori but is another important indication for EGD.
• Endoscopic biopsy is indicated for the following reasons:
•
o Histologic examination of gastric tissue
o Rapid urease testing (eg, CLO test)
o Culture of organisms
o PCR testing to identify H pylori DNA
Histologic Findings
Histologic findings include a superficial infiltrate with substantial numbers of plasma cells and lymphocytes within the gastric mucosa and organisms visible on Giemsa, Diff-Quick, or hematoxylin and eosin staining. Sensitive staining for small numbers of bacteria is possible using silver stains such as Genta or Warthin-Starry.

treatment