Managing Dyspepsia for college health providers Cheryl Flynn

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Managing Dyspepsia for college health providers Cheryl Flynn, MD, MS, MA Syracuse University NYSCHA

Managing Dyspepsia for college health providers Cheryl Flynn, MD, MS, MA Syracuse University NYSCHA Oct 2010

Objectives Review differential diagnosis for patients with upper abdominal sx, including dyspepsia n Discuss

Objectives Review differential diagnosis for patients with upper abdominal sx, including dyspepsia n Discuss a cost-effective evaluation of a dyspeptic patient in college health setting n Review treatment strategies for the various etiologies of dyspepsia n

Consider a case… n 20 y/o college junior with burning pain in subxyphoid region

Consider a case… n 20 y/o college junior with burning pain in subxyphoid region off & on for a few months, particularly worse in last week or so with looming midterm exams.

Differential Dx: upper abd pain Peptic ulcer disease n Nonulcer dyspepsia, aka functional dyspepsia

Differential Dx: upper abd pain Peptic ulcer disease n Nonulcer dyspepsia, aka functional dyspepsia (60%) n GERD n n n n Biliary/hepatic Pancreatitis Gastroparesis GI malabsorptive d/o (lactose intol, celiac) Abd wall pain Meds, esp NSAIDs though many Ischemic, infiltrative, metabolic, malignancy…

Definition: Dyspepsia n Rome III criteria Post-prandial fullness &/or ä Early satiation &/or ä

Definition: Dyspepsia n Rome III criteria Post-prandial fullness &/or ä Early satiation &/or ä Epigastric pain or burning ä ä (Rome II included heartburn) n AGA Chronic or recurrent pain or discomfort centered in the upper abdomen ä Does not include reflux if heartburn is ONLY symptom ä Does not include acute abdomen ä

Dyspepsia definition for today n n Upper abdominal discomfort w/ or w/o reflux sx

Dyspepsia definition for today n n Upper abdominal discomfort w/ or w/o reflux sx Specifically will address evaluation of: GERD ä Undifferentiated dyspepsia ä n And management and treatment of: GERD ä PUD ä Functional dyspepsia ä

Epidemiology: Dyspepsia n Prevalence in US of ~25% (weekly sx) ä Rises to 40%

Epidemiology: Dyspepsia n Prevalence in US of ~25% (weekly sx) ä Rises to 40% if include heartburn ä Fewer than half seek medical care n Likely lower in college population ä US householder survey: prevalence of 13% – When IBS sx and GERD excluded, 3% ä Abdominal sx common in stress, eating d/o

Clinical approach: History n PQRST Provocation/Palliation ä Quality ä Region, Radiation ä Severity, associated

Clinical approach: History n PQRST Provocation/Palliation ä Quality ä Region, Radiation ä Severity, associated Sx ä Timing ä n Red Flag Sx Age >55 (some say 45) ä Unintended wt loss ä Persistent vomiting ä Dysphagia, odynophagia ä Sx of GI bleeding: hematemesis, melana, BRBPR ä

Clinical approach: PE n VS, including wt ä n Pertinent system ä n Orthostatics

Clinical approach: PE n VS, including wt ä n Pertinent system ä n Orthostatics only if ill Abdominal exam System above/system below Chest: heart/lungs ä Back: CVAs, M/S ä Consider u/a, esp female pt ä n Red Flag Signs GI bleed: heme+ stool or Fe Def anemia ä Orthostasis ä Peritoneal signs ä Abdominal mass ä Jaundice ä

Classic GERD Heartburn: substernal pain that may be associated with sense of acid regurgitation

Classic GERD Heartburn: substernal pain that may be associated with sense of acid regurgitation &/or sour taste n Epigastric pain radiating to chest n Sx worse w/ large meal, bending forward or lying down; sx better w/ antacids n n PE usually completely normal

Classic PUD/FD n Burning pain in epigastric region ä Possibly radiating to back n

Classic PUD/FD n Burning pain in epigastric region ä Possibly radiating to back n Better w/ eating, antacids; perhaps worsened by spicy/acidic foods n PE w/ mild subxyphoid or RUQ tenderness,

How helpful is H&P? Patients do not always present as text book cases… n

How helpful is H&P? Patients do not always present as text book cases… n Individual s/sx are not very helpful n ä Mostly b/c DDx so broad ä Symptoms so nonspecific

Accuracy of individual sx to dx GERD

Accuracy of individual sx to dx GERD

…But overall gestalt not too bad

…But overall gestalt not too bad

Diagnostic tests n n n Esophageal manometry Bernstein test Ba swallow n n Endoscopy:

Diagnostic tests n n n Esophageal manometry Bernstein test Ba swallow n n Endoscopy: EGD p. H monitoring Upper GI Omeprazole challenge

Useful tests Dx GERD

Useful tests Dx GERD

Diagnosing GERD n Clinical gestalt usually suffices Omeprazaole test (~ treatment trial) wins gold

Diagnosing GERD n Clinical gestalt usually suffices Omeprazaole test (~ treatment trial) wins gold star! ä More cost effective than p. H or EGD ä n Consider additional testing if: Red flag symptoms present: EGD or Ba swallow/UGI ä Considering GERD as etiology of atypical sx presentation ä – chronic cough or laryngitis: p. H probe – chest pain: omeprazole challenge ä Lack of response to acid suppression therapy

Dx Tests: dyspepsia n Two categories of non. GERD dyspepsia ä Those w/ identifiable

Dx Tests: dyspepsia n Two categories of non. GERD dyspepsia ä Those w/ identifiable cause: ulcer, malignancy ä Those w/o identifiable cause: functional dyspepsia (FD) – aka nonulcer dyspepsia (NUD) or idiopathic dyspepsia n FD is dx of exclusion

Useful tests to dx PUD

Useful tests to dx PUD

Weighing pros & cons UGI less expensive EGD more accurate UGI EGD allows for

Weighing pros & cons UGI less expensive EGD more accurate UGI EGD allows for add’l testing UGI has fewer complications

The elephant in the room… H. Pylori NSAIDs

The elephant in the room… H. Pylori NSAIDs

Etiology of ulcers n Most PUD caused by H. pylori &/or NSAIDs ä Other

Etiology of ulcers n Most PUD caused by H. pylori &/or NSAIDs ä Other factors are synergistic: tobacco, ETOH, other meds ä 75% of pt w/ DU, GU have H. pylori ä Only 15% w/ H. pylori will develop ulcer n Eradicating H. pylori cures ulcer

Diagnosing H. Pylori Invasive tests (ie req’s GI involvement, EGD) n n n Biopsy

Diagnosing H. Pylori Invasive tests (ie req’s GI involvement, EGD) n n n Biopsy urease test Histology Bacterial culture Noninvasive tests n n n Urea breath test Serology Stool antigen

Urea breath test n n n Carbon labeled urea is hydrolyzed by H. Pylori

Urea breath test n n n Carbon labeled urea is hydrolyzed by H. Pylori CO 2 + NH 3 Sn~ 88 -95% ; Sp ~ 95 -100% False neg if on abx, acid suppression, bismuth Costs $50 -100 Check on local availability (ie not available at SU)

Serology n n n Detection of Ig. G antibodies Sn 90 -100%; Sp 76

Serology n n n Detection of Ig. G antibodies Sn 90 -100%; Sp 76 -96% Serology can remain + even after eradication 40% still + after 18 months ä Thus, not so useful for f/u testing ä Useful if low probability and never tested ä n Cost: ~$30

Stool antigen test n n Enzyme immunoassay of fecal sample Sn ~94%; Sp 86

Stool antigen test n n Enzyme immunoassay of fecal sample Sn ~94%; Sp 86 -92 Newer rapid stool Ag tests developed but lower sn Cost ~$80

Diagnosing H. Pylori? n Serology is appropriate 1 st line H. Pylori test in

Diagnosing H. Pylori? n Serology is appropriate 1 st line H. Pylori test in college pop Lower prevalence of H. Pylori in younger people ä Lower cost as first line test ä Likely better compliance vs stool Ag collection ä n Bottom line: if testing for HP, order serology unless known past + ä if testing for eradication (after treatment, or recurrent sx) then use stool Ag test, or breath test ä

Undifferentiated dyspepsia (ie no alarm s/sx & r/o GERD dominant clinically) Possible approaches: 1.

Undifferentiated dyspepsia (ie no alarm s/sx & r/o GERD dominant clinically) Possible approaches: 1. 2. 3. 4. 5. Empirical acid suppression Noninvasive HP test, scope positives Noninvasive HP test, treat positives Empirical HP eradication w/o testing Endoscopy directly

And the cost effective winner is… 1. 2. 3. 4. 5. Empirical acid suppression

And the cost effective winner is… 1. 2. 3. 4. 5. Empirical acid suppression Noninvasive HP test, scope positives Noninvasive HP test, treat positives Empirical HP eradication w/o testing Endoscopy directly

Why? The thinking: n Prevalence of PUD (~15%) is much lower than FD (50

Why? The thinking: n Prevalence of PUD (~15%) is much lower than FD (50 -70%) in primary care pop ä n The evidence: n Multiple cost-effective analyses support n Few RCTs do Likely even lower in college pop Proven benefit of H Pylori eradication eliminating sx & curing ulcer (level 1 a) AND preventing relapse ä Metaanalysis of 5 trials shows equivalent cure, more cost n AGA guidelines concur n No studies specifically in college health If no funding for HP testing, empiric acid suppression not unreasonable n

Dyspepsia Work-up/Treat condition found Yes Suspect other causes (ie, biliary)? No NSAID/Cox-2 inhibitor use?

Dyspepsia Work-up/Treat condition found Yes Suspect other causes (ie, biliary)? No NSAID/Cox-2 inhibitor use? Yes No Stop/change med or add PPI unstable Red flag signs or symptoms age>45 (55) Send to ER immediately Yes stable Refer to GI for endoscopy No Clinicians gestalt supports GERD? Yes positive No Treat condition found H. pylori test GERD therapy negative positive Eradication therapy negative Empiric FD therapy

Pulling it all together… n Upper abdominal sx ä H&P n to direct what

Pulling it all together… n Upper abdominal sx ä H&P n to direct what is highest on DDx list If left w/ Dyspepsia ä On NSAIDs? If so, stop; if not… ä Red flag sx? If so, refer; if not… ä Does clinical gestalt suggest GERD? If so, tx GERD; if not, test for H. Pylori ä If pos for H. Pylori, eradicate; if negative, treat as functional dyspepsia

Treatment GERD n H. Pylori n Functional dyspepsia n n Discuss recurrent sx, lack

Treatment GERD n H. Pylori n Functional dyspepsia n n Discuss recurrent sx, lack of response

Treatment: GERD Goal: n symptom relief n healing of esophageal erosions n prevent complications

Treatment: GERD Goal: n symptom relief n healing of esophageal erosions n prevent complications

GERD: Nonpharm Tx n Lifestyle modification Elevated head of bed, esp if nocturnal sx*

GERD: Nonpharm Tx n Lifestyle modification Elevated head of bed, esp if nocturnal sx* ä Avoid tight fitting clothes ä Don’t eat before bed; remain elevated after eating ä Decrease/quit smoking ä Lose weight* ä n Dietary modification Limit ETOH ä Chew gum/use lozenges to promote salivation ä Avoid triggering foods ä – Some specific triggers: fatty foods, chocolate, peppermint, acid beverages (OJ, soda) Only * has evidence to demo benefit

Med Tx: GERD n Antacids (B) n Acid suppression medications (A) ä H 2

Med Tx: GERD n Antacids (B) n Acid suppression medications (A) ä H 2 Blockers are consistently effective ä All H 2 Bs are equivalent ä Proton pump inhibitors consistently better than H 2 Bs ä All PPIs are also equivalent

Med Tx: GERD n Acid suppression meds lower acidity ä Lessen sx; allow esophogeal

Med Tx: GERD n Acid suppression meds lower acidity ä Lessen sx; allow esophogeal healing ä Do NOT prevent actual refluxing n Pro-motility agents (C) ä ie bethanechol, metoclopramide ä No longer used/recommended b/c of significant adverse effects, drug interactions with very limited efficacy

Other considerations n n Step up vs step down approach as initial mng Managing

Other considerations n n Step up vs step down approach as initial mng Managing chronic sx Intermittent—sx resolved; resume last effective dose when sx recur ä Chronic—maintain on acid suppressive that manages sx if relapse within 3 months of stopping meds ä n When to refer Double to triple std dosing of PPI, and failure to respond ä Surgery for recalictrant, chronic, severe GERD (A) ä See GERD algorithm in handout

Costs of Acid Suppression Meds H 2 -receptor blockers n Ranitidine 150 mg bid

Costs of Acid Suppression Meds H 2 -receptor blockers n Ranitidine 150 mg bid ($12/ month) n Famotidine 20 mg QD ($20) n Cimetidine 800 mg bid ($36) Proton Pump Inhibitors n Omeprazole 20 mg QD ($13 generic; >$200 if brand) n Lansoprazole 30 mg QD ($15 generic; $80+ if brand) n Pantoprazole 40 mg QD (~$100 not generic yet)

Treatment: PUD n Goal of treatment Sx relief ä Eradication of H. Pylori infection

Treatment: PUD n Goal of treatment Sx relief ä Eradication of H. Pylori infection to heal ulcer, prevent relapse ä Manage sx following HP cure (equiv to functional dyspepsia tx) ä

Treatment: HP+ dyspepsia n H pylori eradication requires abx + acid suppression 10 -14

Treatment: HP+ dyspepsia n H pylori eradication requires abx + acid suppression 10 -14 day better efficacy vs 7 d or shorter ä Complicated strategies, numerous RCTs, drug resistance ä Changes frequently, so worthwhile to update at least annually: AGA or Sanford guide ä n Specific factors affecting choice: Efficacy of eradication ä Cost ä Compliance: ease of regimen and side effects ä

Categories of HP eradication Tx n Dual therapy = PPI + one abx ä

Categories of HP eradication Tx n Dual therapy = PPI + one abx ä n *Triple therapy = PPI + 2 abx ä n n Not recommended now b/c of low efficacy rates Usually preferred for efficacy + compliance Quadruple therapy = PPI + 2 abx + bismuth **Sequential therapy = PPI + 1 abx x 5 days followed by PPI + 2 new abx for next 5 days ä Newer, proven effective; newly used to address resistance *AGA rec’d 1 st line; **Sanford rec’d 1 st line

1 st line in HP eradication Triple therapy x 10 -14 d 1. PPI

1 st line in HP eradication Triple therapy x 10 -14 d 1. PPI (doesn’t matter which one, just std dosing bid) ä Omeprazole 20 mg bid or ($26 generic) + If allergic to PCN or 2. Amoxicillin 1 g bid ($15) macrolide, substitute + metronidazole 500 mg 3. Clarithromycin 500 mg bid ($100) bid Note: prevpac = prevacid + amox + clarithro; convenient ordering but cost is $360

Sequential therapy option n PPI std dose bid x 10 days n n Amoxicillin

Sequential therapy option n PPI std dose bid x 10 days n n Amoxicillin 1 g bid x 5 days (day 1 -5) followed by Clarithromycin 500 mg bid + tinidizole 500 mg bid x 5 days (day 6 -10) Rec’d by Sanford due to higher rates of cure Not 1 st line rec’d in US; used for failed eradication

Test of cure? n Upwards of 20% HP not successfully eradicated ä Drug n

Test of cure? n Upwards of 20% HP not successfully eradicated ä Drug n resistance, noncompliance Insufficient evidence to warrant routine test of cure ä Cost effective analyses suggesting not valuable

When/how should I retest for HP? n Treat w/ full course of eradication tx

When/how should I retest for HP? n Treat w/ full course of eradication tx and sx have not responded ä Question compliance w/ regimen ä Check stool antigen to ensure HP infx resolved n Known h/o +HP, responded to treatment with sx resolution &/or healing via EGD ä If sx recur, check stool antigen for re-infection.

If HP+, treat again, perhaps w/ sequential or quadruple tx If HP-, treat with

If HP+, treat again, perhaps w/ sequential or quadruple tx If HP-, treat with PPIs x 4 wk more If no response, refer to GI for EGD Refer to algorithms in handout for dyspepsia

Treatment: Functional Dyspepsia Goal: n Decrease sx Delayed goal… n Accept/cope with sx if

Treatment: Functional Dyspepsia Goal: n Decrease sx Delayed goal… n Accept/cope with sx if not resolving and become more chronic

FD: pharm approach n Following the original algorithm… ä Actually 1 st stage: treating

FD: pharm approach n Following the original algorithm… ä Actually 1 st stage: treating H. Pylori negative dyspepsia ä FD is a dx of exclusion and we have not yet fully excluded other causes. n 1 st line HP negative dyspepsia: 4 wk trial of PPIs

If no response… n Reassess diagnosis Are there new sx to suggest different dx

If no response… n Reassess diagnosis Are there new sx to suggest different dx or raise concern? ä Address stress/functioning issues ä n Consider trial of higher dosing PPI Not proven to aid, but at this point, EGD still most likely neg ä Double dose (ie 20 bid omeprazole) ä n If sx particularly troubling, refer to GI for scope to r/o other etiology Refer to algorithms in handout for dyspepsia

Options to manage documented FD 1. 2. 3. Cont’n GI treatments Cont’n exploring other

Options to manage documented FD 1. 2. 3. Cont’n GI treatments Cont’n exploring other dx other “non. GI” treatments

1. GI treatments n Mild benefit noted in RCTs of FD for: H 2

1. GI treatments n Mild benefit noted in RCTs of FD for: H 2 Bs (B) ä PPIs (A-) ä Prokinetic agents (C) ä Antispasmodics (B) ä n n Most short term studies, heterogeneous population Benefit found relative small; more apt to reduce, not resolve sx

2. Other dx options? n Always re-evaluate ä Delayed gastric emptying? IBS? Celiac? ä

2. Other dx options? n Always re-evaluate ä Delayed gastric emptying? IBS? Celiac? ä Panic/anxiety/other psychological issues n May be more helpful to introduce this concept before referral to GI for scope ä Introduce mind-body connection ä Sx diary to help id personal triggers

3. Other “non-GI” options n Lifestyle modification ä Dietary changes to limit triggers ä

3. Other “non-GI” options n Lifestyle modification ä Dietary changes to limit triggers ä Nutrition consult n Psychotherapy ä Important to not convey message “this is in pt’s head” ä Useful to id/manage triggers, aid in coping with chronic physical sx

3. “non-GI” options cont’n n Antidepressants ä Limited RCT data, some negative ä May

3. “non-GI” options cont’n n Antidepressants ä Limited RCT data, some negative ä May help if associated sx such as insomnia ä Taking approach of “chronic pain management” ä Low dose tricyclics (10 mg amitriptyline QHS), or trazadone (25 mg QHS)

Summary: key points H&P to sort dyspepsia from other etiologies n Follow algorithm n

Summary: key points H&P to sort dyspepsia from other etiologies n Follow algorithm n ä Clinical dx of GERD dominant ä If not GERD, test/treat HPylori ä Refer to GI if significant alarm s/sx or failure to respond n Most dyspepsia in college students will not require GI involvement/referral

Case discussions

Case discussions

Case 1 20 y/o college junior with burning pain in subxyphoid region off &

Case 1 20 y/o college junior with burning pain in subxyphoid region off & on for a few months, particularly worse in last week or so with looming midterm exams. Eats lots of junk food; binge ETOH on weekends n PMHx: no GI problems; recurrent knee injury uses rx naprosyn prn n Exam basically negative n

Case 2 26 yo female grad student w/ mid upper abd pain, radiates upwards;

Case 2 26 yo female grad student w/ mid upper abd pain, radiates upwards; occ wakes her from sleep. nausea, no vomiting; no alarm sx n PMHx: neg n SHx: no tob, ETOH social, max of 3 drinks; is sexually active w/ same partner of 2 years n Exam benign n

Case 3 n n n 20 y/o pledging a sorority notes worsening upper abdominal

Case 3 n n n 20 y/o pledging a sorority notes worsening upper abdominal pain, nausea but no vomiting. Worse when eats so has decreased intake; tolerates low fat food better. Lost ~5# in last month but is happy w/ that PMHx: past abd sx but never evaluated Exam: pt thin, mild epigastric tenderness, no mass; noted to have Fe Def anemia

Case 4 47 y/o veteran returning to grad work noting new onset RUQ pain,

Case 4 47 y/o veteran returning to grad work noting new onset RUQ pain, occ feeling like food sticks with swallowing. OK w/ liquids. No bleeding, no change in weight. n PMHx: mild HTN controlled behaviorally n SHx: former smoker; ETOH usually beers w/ dinner n Exam negative n