NONULCER DYSPEPSIA

I. Definition: Dyspepsia (epigastric discomfort, in some cases related to meals and/or ass'd with nausea, vomiting, early satiety, belching, or bloating; sometimes also reflux sx) without ulcer

II. Etiology

  1. No clear association with H. pylori Infection in the absence of ulcer
  2. Differential diagnosis of Dyspepsia:
  1. Peptic Ulcer Disease (about 20% of pts w/o identifiable systemic or medication-related cause)
  2. GERD (about 25% of ditto)
  3. Gastritis (about 21% of ditto)
  4. Irritable bowel syndrome
  5. Cholelithiasis (n.b. may have asymptomatic gallstones as a red herring; don't take out gallbladder if all pt has is dyspepsia!)
  6. Chronic pancreatitis
  7. Gastroparesis, e.g. Diabetic Gastroparesis
  8. Malabsorption syndromes
  9. Mesenteric Ischemia
  10. Alcohol use
  11. Intestinal parasitosis (e.g. Giardiasis, Strongyloides)
  12. Intra-abdominal neoplasm, particularly Gastric Cancer (almost always in pts > 45yo) and Pancreatic Cancer
  13. Non-gastroenterological causes
    1. Medications (especially Theophylline, Digitalis, NSAIDs, Iron, Potassium, Serotonin Reuptake Inhibitors, Bisphosphonates)
    2. Myocardial Ischemia
    3. Hyperparathyroidism
    4. Thyroid Disorders (both hypo- and hyperthyroidism)
    5. Pregnancy
    6. Collagen-vascular diseases
  1. Commonly cited "alarm" signs for pts with dyspepsia, suggesting possibility of serious etiologies:
    1. Vomiting
    2. Odynophagia
    3. Dysphagia
    4. Jaundice
    5. Hematemesis
    6. Hematochezia
    7. Melena
    8. Anemia
    9. Anorexia
    10. Palpable abdominal mass
    11. Unintended weight loss
    12. Lack of response to therapy
    13. Chronic NSAID use
    14. Alcohol overuse

III. Evaluation of a patient with Dyspepsia

  1. In a prospective study in 2,741 pts with dyspepsia (by "Rome II" criteria) without "alarm symptoms" and without current NSAID use > 2d/wk, recent H. pylori tx, or sx of GERD all of whom underwent upper endoscopy, prevalence of cancer identified on endoscopy was 0.2% (only one in pts < 50yo) (Clin. Gastroent. Hepatol. 7:756, 2009-JW)
  2. The sx pattern & the presence/absence of epigastric tenderness do not reliably distinguish among the underlying causes of Dyspepsia (Scan J Gastroenterol 1997;32:118-25; Gastroenterology 1982;82:16-9. --Ref'd in UW Guidelines)
  3. Workup with esophagogastroduodenoscopy (EGD):
    1. Consider EGD for all who have no alterable systemic or medication-related cause, b/c of sig. incidence of ulcer
    2. Consider earlier EGD if older (60% of pts > 60yo w/dyspepsia will have PUD; Ann. Int. Med. 108:865, 1988; acommonly used cutoff is onset > 45yo)
    3. Consider EGD if any of the above "alarm" signs are present
    4. For pts at low risk of PUD (e.g. young, nonsmokers, no NSAID use) and malignancy can consider empiric tx, e.g. promotility agents (see below) before EGD
  4. H. pylori serology may be a useful "triage" tool in that pts < 45yo with dyspepsia but negative H. pylori serology, no NSAID use, and no "alarm" sx (persistent vomiting, dysphagia, odynophagia, evidence of GI bleed, unintentional weight loss, etc.) suggests a VERY low likelihood of ulcer (UW Guidelines)
  5. Labs--Consider:
    1. CBC (rule out anemia from slow GIB)
    2. Serum Calcium (rule out hyperparathyroidism)
    3. LFT's (look for hepatobiliary etiologies)
    4. Thyroid function tests
    5. Amylase (rule out chronic pancreatitis)
    6. H. pylori serology, for low-risk pts (to r/o need for EGD; see "C" above)

IV. Treatment of Dyspepsia

  1. Promotility agents (e.g. metoclopramide 10mg TID-QID, domperidone) shown to be effective in sx control in randomized trials (Treatment of Functional Dyspepsia. Scand J Gastroenterol 1991;26:47-60--Ref'd in UW Guidelines)
  2. H2 Blockers & Proton-Pump Inhibitors
    1. Only a modest symptomatic benefit c/w placebo (meta-analysis done in J Clin Gastroenterol 1989;11:69-77--Ref'd in UW Guidelines)
    2. In a study in 224 primary care patients with "functional dyspepsia" (> 12wks in the last 12mos of upper abd pain/discomfort, no evidence of organic disease, and sx not releaved by defecation; no change in stool frequency or form) and normal EGD randomized to esomeprazole 40mg/d vs. placebo; at 4wks, active-tx pts had sig. greater incidence of sx relief (51% vs. 32%) but no sig. diff. at 8wks (Am. J. Gastroent. 101:2096, 2006--JW) 
  3. Tx of H. pylori infection in pts with dyspepsia who have not yet undergone EGD--Controversial, may not offer any cost benefit over proceeding straight to EGD
  4. Tx of H. pylori infection in pts with non-ulcer dyspepsia and H. pylori infection--Benefit is quite small