Dyspepsia Neil C. Jackson

General  Common symptom with extensive differential diagnosis and heterogenous pathophysiology.

Epidemiology  25% of general population/year  25% with evidence of organic cause  75% without

Symptoms  Chronic or recurrent pain or discomfort in the upper abdomen  Ulcer-like or acid dyspepsia  Burning pain, epigastric huger-like pain  Relief with food/antacids/antisecretory agents  Food-provoked dyspepsia or indigestion  Postprandial epigastric discomfort and fullness  Belching, early satiety, nausea, occasional vomiting  Reflux-like dyspepsia  Rome III Criteria  Postprandial fullness  Early satiation  Inability to finish a normal sized meal  Epigastric Pain or Burning

Organic dyspepsia  PUD  GERD  GE malignancy  Biliary  Meds (NSAIDs)  Other  Celiac / chronic pancreatitis  Infiltrative dz (Eosinophilic gastritis / crohn’s / sarcoid)  DM radiculopathy / hypercalcemia / heavy metal toxicity  Hepatoma / steatohepatitis / mesenteric ischemia

PUD  A spectrum from gastritis to ulceration complicated by bleeding, pain and perforation.  Poor correlation with reported symptoms and EGD findings  Includes Duodenal and gastric ulcers  Commonly due to H.Pylori and/or NSAID, tobacco, EtOH  Treatment = H.pylori eradication and removal of inciting agents

Duodenal vs. Gastric Ulcers  Gastric ulcer  Worse with meals  Poor response to antacids/otcs  Duodenal ulcer  Pain when acid is secreted in absence of a food buffer  Improves with meals, alkali, antisecretory agents  Worse 3-5 hours after a meal  Worse at night between 11pm – 2am  Maximal circadian stimulation of acid secretion

GERD  Some degree of reflux is physiologic  Montreal classification:  A condition that develops when reflux of stomach contents causes troublesome symptoms and/or complications  Prevalence= 10-20% in western world, <5% in Asia  Heartburn = retrosternal burning, most common  Regurgitation = gastric content into mouth/throat  Dysphagia = common in longstanding GERD due to  Reflux esophagitis  Stricture

More GERD  Globus sensation  Almost constant perception of a lump in the throat  Water brash (foaming at the mouth)  Rare hypersalivation caused by reflux  Chest pain  Mimics angina, typically squeezing/burning  Substernally with radiation to back/neck/jaw/arms  Lasts minutes to hours  Spontaneous resolution with antacids  Occurs after meals, awakens from sleep  Worse with emotional stress

GE Malignancy  Uncommon cause of chronic dyspepsia in Western Hemisphere  More common in Asian, Hispanic, Afro-Caribbean populations  Increases with age  Epigastric pain vague, mild in early disease – more severe and constant with progression  Weight loss from insufficient caloric intake  Dysphagia related to esophageal or proximal gastric malignancy

NSAIDs  Direct effect  Ionization upon absorption into gastric mucosa  Topical epithelial injury  Systemic effect  Inhibition of GI mucosal COX activity (COX1)  Decreased mucosal prostaglandin protection

History  Association of symptoms with meals  Heartburn / regurgitation / cough  NSAID use ??  Radiation to back, personal/fhx of pancreatitis  Significant weight loss / anorexia / vomiting / dysphagia / odynophagia / fhx of GI malignancy  Severe episodic epigastric / RUQ pain lasting more than one hour

Exam  Usually normal except for epigastric tenderness  Jaundice, pallor, ascites, muscle wasting  Palpable abdominal mass  Palpable lymphadenopathy  L supraclavicular = Virchow’s node  Periumbilical = Sister Mary Joseph’s node  Carnett sign  Double straight leg raise or head raise while supine  Finger presses point of tenderness  + test = Increased pain with muscle tensing

Labs  CBC  Electrolytes + Calcium  Hepatic Function Panel

Alarm Features  Age > 55 yrs with new-onset dyspepsia  FHx of upper GI malignancy  Unintended weight loss  GI bleeding  Progressive dysphagia  Odynophagia (painful swallowing)  Unexplained Iron deficiency  Persistent vomiting  Palpable mass or node  Jaundice

Diagnosis: Pt with alarm features  Upper endoscopy within two weeks  with stomach biopsy for H.pylori  Yield of EGD increases with age  Per meta-analysis of 9 studies, 5389 pts:  6% erosive esophagitis  8% PUD  If normal, most will have functional dyspepsia  Further evaluation warranted if alarm features  Age cutoff controversial  AGA suggests yrs  with Asian, Hispanic, Afro-Caribbean descent

Reflux Esophagitis

Barrett’s Esophagus

Gastric Ulcer

Esophageal Ulcer

Diagnosis: No alarm features  Test and treat for H.pylori  If local h.pylori prevalence >10 %  Empiric PPI / H2blocker  If local h.pylori presence <5%

Test and Treat for H.Pylori  Urea breath test or stool Ag  Serologic testing should not be used  NNT is 14

H. Pylori eradication  Quadruple Therapy  Triple therapy + bismuth 525mg 4xdaily for days  With clarithromycin/metronidazole resistance > 15%  With recent/repeated exposure to clarithro/flagyl  Triple Therapy  PPI (multiple options)  Omeprazole 20mg bid  Pantoprazole 40mg bid  Amoxicillin: 1g BID 7-14 days  Clarithromycin: 500mg BID 7-14 days  Alternative antibiotics  Doxycycline 100mg bid / Flagyl 250mg 4xdaily

Anti-Secretory Therapy  PPIs > H2 blockers  PPI (Omeprazole / pantoprazole / lansoprazole )  Irreversibly binds/inhibits H/K atp pump on parietal cells  Only effective in active parietal cells  Must be taken minutes before meals  Twice daily dosing if :  Failed standard therapy  Large gastric ulcer  H2 blockers (Ranitidine / cimetidine / famotidine)  Inhibit Histamine H2 receptors on parietal cells

Functional Dyspepsia  Presence of one or more:  Postprandial fullness  Early satiation  Epigastric pain/burning  Negative diagnostic evaluation for organic disease  Symptoms for last three months  Onset more than 6 months previously

Pathophysiology  Gastric motility / compliance  Delayed gastric emptying (30%)  rapid gastric emptying (10%)  Visceral hypersensitivity  Increased pain with normal gastric stretching/compliance  Independent of delayed gastric emptying  H.pylori infection  Unclear mechanism, ?smooth muscle dysfunction 2/2 inflammatory modulation of enteric nervous system  Altered gut microbiome  Symptoms more likely after episode of AGE  Psychosocial dysfunction  Association with GAD, somatization, Major Depression  Higher prevalence in pts with self-reported hx of child abuse

Treatment  H.Pylori test and treat  Tricyclic anti-depressants  If persistent symptoms despite PPI x8wks  PPI / H2 blockers  Metoclopramide (Prokinetic)  If failed above therapy  5-10 mg TID half hour before meals and at night x4wks

References  Uptodate  Approach to the Adult with Dyspepsia  Functional dyspepsia in adults  Clinical manifestations of peptic ulcer disease  Clinical manifestations and diagnosis of GERD in adults  Clinical features,diagnosis,staging of gastric cancer  Epidemiology, pathobiology and clinical manifestations of esophageal cancer  Differential diagnosis of abdominal pain in adults  AGA  AGA medical position statement: evaluation of dyspepsia – Gastroenterology, 2005  AFP  Evaluation and management of non-ulcer dyspepsia  H.Pylori Infection