Peptic Ulcer Disease

Peptic Ulcer Disease (PUD) / H Pylori

Definitions:

Peptic Ulcer: Deep mucosal lesions that disrupt the muscularis mucosa of the gastric or duodenal wall (4)
Parietal Cells secrete acid following acetylcholine (Vagal), histamine, and gastrin stimulation
Helicobacter Pylori (H pylori) - gram neg spiral rod. Potentially damages mucosa by urease secretion. Urease hydrolyzes urea to ammonia and bicarb
Classification

Primary Ulcer = chronic, more often duodenal

Secondary Ulcer = acute in onset, more often gastric

Physiology review

Acid secretion approximates adult levels around 3-4yo
Excessive Acid secretion:

large parietal cell mass
increased vagal tone increases acetylcholine
increased histamine secreted by enterochromaffin cells
increased gastrin secreted by G cells of the antrum

Mucosal Defense

Mucous production stimulated by Prostaglandin E2
secretion of bicarb into the mucous coat is also regulated by prostaglandins
Mucosal injury triggers epithelial growth factor, transforming growth factor alpha, insulin like growth factor, gastrin, bombesin which all trigger active proliferation and migration of mucosal cells to cover the area of damage

Epidemiology

H Pylori infection = 50% worldwide, higher rates with lower SES but only 10-15% develop PUD
Often Family history of PUD
Hypersecretory state (Zollinger-Ellison)

autonomous secretion of gastrin by neuroendocrine tumor (gastrinoma)
look for recurrent, multiple or atypically located ulcers
Common in patients with MEN1
Clinical presentation is same as PUD but with Diarrhea

Inpatient Setting:

Stress (Critical Illness)

up to 25% of patients in PICU have macroscopic evidence of gastric bleed

typically occurs within 24hrs from onset of physiologic stress of critical illness

Increased ICP (Cushing Ulcer)
Burn (Curling Ulcer)

NSAIDs or other medications

inhibit cyclooxygenase and prostaglandin synthesis
location of ulcers - stomach (antrum) is more common than duodenum

Tumors (Cancer, Lymphoma)
IBD
Viral Infections (CMV, HSV - usually in immunocompromised host)
Hiatal Hernia passes through diaphragmatic hiatus and causes an ulcer (Cameron Ulcer)
Short Bowel
Systemic mastocytosis
True Idiopathic

Clinical Manifestations

Older children: Recurrent epigastric pain - poorly localized, periumbilical

postprandial
nocturnal;
w or w/o N/V or food regurgitation
classic symptom of improvement in pain with food ingestion is actually rare in children

Younger children: FTT

feeding difficulty, vomiting, crying episodes
in neonates, gastric perforation can be the initial presentation

UGI Bleed

hematemesis or melana is reported in up to 50% of patients with PUD

Chronic Anemia

In a patient with normal diet for age, Fe deficiency anemia may suggest peptic ulceration

Labs:

CBC w/ diff - look for anemia
ESR - look for IBD
LFTs
electrolytes - if recurrent vomiting
stool eval for O&P - if exposure or diarrhea present
H pylori IgG - can't distinguish between current and prior infection

Sensitivity = 54-95%, Specificity 59-97%
not sens or spec in children due to lower titer cutoffs and shorter duration of infection

Stool Antigen testing for H pylori (where available)

98% sensitive / 99% specific
monoclonal antibody based test 95% / 97%
polyclonal based test 94% / 86%
reports of association between gastritis severity and stool test positivity
False negative with PPI

Urea Breath Test

patient ingests urea labeled with C13 isotope
within minutes CO2 labeled with C13 appears in the breath
Sens 88-95%/ Spec 95-100%
False negative is possible with antisecretory therapy (acid suppression) or antibiotics

stop PPI 2 wks prior to test

False positive can be seen in children <3yo due to discoordinated swallow (oral bacteria)

Serology: (latest consensus report recommends against using antibody-based tests)

IgM (Early Specific), IgA and IgG (Later, persistent, specific)

immunoglobulins not sensitive or specific enough to use as sole diagnostic marker
Specific IgG have better sensitivity than IgA but cannot differentiate between current and past infection

Gold Standard:

Upper GI endoscopy with Bx

Most reliable, Multiple Bx increase yield

Antral mucosa appears normal in a number of affected patients, therefore; Bx should be taken from the body and antrum regardless of endoscopic appearance

Nodularity in stomach more common in children

cobblestone appearance 1-4mm in diameter uniform color and smooth, most often seen in antrum

Histology

superficial infiltrate of plasma cells and lymphocytes
lymphoid follicles with germinal centers (very suggestive of infxn)
Atrophy

rarely seen in western medicine
loss of granular tissue

Specific stains to identify H Pylori in children

Silver: Warthin-Starry, Dieterle, Steiner, Genta
Modified Romanovsky
Sayeed Stains

Site of Bx

Mid Antrum is best for children (in adults, cardia is also a good site)
Long term PPI use may shift antrum predominant disease to Corup-Dominant disease

Culture: requires microaerophilic environment and complex media

allows for antibiotic sensitivity testing

Radiographic UGI studies are less sensitive

Treatment:

Treatment is for eradication of infection. Must test for successful eradication 4-6wks after completion of antibiotics (2wks off PPI)

Test for eradication with Breath test or stool antigen

Regimens:

Antisecretory agent + 2 or 3 antimicrobial agents for 10-14 days

PPI (1-2mg/kg/d) + Clarithromycin (15mg/kg/d) + Metronidazole (20mg/kg/d)

PPI increases eradication potentially due to inhibition of acid allowing acid sensitive antibiotics to be more effective (e.g. clarithromycin)
Other Antibiotics often prescribed: amoxicilin (50mg/kg/d), metronidazole, clarithromycin, tetracycline (not recommended in children < 12yo)

70% cure rate at 7 days of therapy --> recommendation to treat for 14 days
Bismuth contraindicated due to assoc w/ encephalopathy and acute renal failure

Sequential regimen:

PPI + amox x 5 days, then 5 days of triple therapy (see above)

amox can lower bacterial load and prevent clarithromycin resistence

Tx Failure:

Patient noncompliance
Antibiotic resistance

rates increasing
high resistance to metronidazole and clarithromycin reported

if clarithromycin resistance >15% in community, use alternative

Inadequate drug delivery

Probiotics

questionable role and effectiveness in improving eradication

For idiopathic ulcers only - PPI alone is the preferred treatment with close and recurrent follow up
Vaccine

under development? trials?

Treatment for Erosion or Ulceration with GI Bleed

Acute Hemorrhage

serial monitoring:

HR/BP/Hct/Lytes
Volume resuscitation with NS - follow with pRBCs for Sx/Anemia

Type/Crossmatch
NG Tube to assess for resolution of gastric bleed

Most acute peptic ulcer bleeding stops spontaneously
High dose IV PPI to reduce risk of rebleed

some centers use octreotide (lowers splanchnic blood flow and gastric acid production) or prokinetic agents

Once hemodynamically stable, Endoscopy should be performed within 24hrs to assess and potentially treat source of bleeding

clipping
Thermal source - cautery
injection -diluted epinephrine

Complications

Atrophic gastritis +/- metaplasia (high risk if PPI use without eradication)
Gastric Cancer (WHO classified H Pylori as a group I carcinogen)

seen in 1% of infected

Gastric mucosa associated lymphoid tissue lymphoma (MALT) 0.1%
Rarely associated with Chronic Autoimmune Thrombocytopenia

References:

Kliegman, Robert. Nelson Textbook of Pediatrics. Edition 21. Philadelphia, PA: Elsevier, 2020.
Tortora, Gerard J. Principles of Anatomy and Physiology. 15th ed. Hoboken, NJ: J. Wiley, 2009. Print.
Moore, Keith L.,, Arthur F. Dalley, II, and Keith L Moore. Clinically Oriented Anatomy. Fifth edition. Baltimore: Wolters Kluwer Health, 2009. Print.
Kleinman RE, Goulet O, Mieli-Vergani G, et al, eds. Walker's Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis, and Management. 5th ed. Hamilton, Ontario: BC Decker; 2008.
The NASPGHAN fellows concise review of pediatric gastroenterology, hepatology, and nutrition. 1st edition (2011)
Wyllie, Robert & Hyams, J.S.. (2011). Pediatric Gastrointestinal and Liver Disease. 10.1016/C2009-0-53242-4. (Accessed online Feb 2020)
Coran, Arnold G, and N S. Adzick. Pediatric Surgery. Philadelphia, PA: Elsevier Mosby, 2012. Internet resource.
Pocket Pediatrics : Prasad 2010 (7-1,7-2)