Background (NAMCS 2010, http://www.cdc.gov/nchs)

Abdominal pain is one of the top 20 reasons for ambulatory visits in US; complaint reflects wide array of potential etiologies & organ systems, varying in acuity & severity; careful hx & consideration of demographics key to guiding differential & identifying pts who merit emergent or specialty care

Evaluation (AFP 2008;77:971; Emerg Med Clin N Am 2011;29:159)

History: Pain hx: Acute vs. chronic, onset, location, radiation, severity, quality (colic → gallstone, nephrolithiasis, SBO); tempo/trajectory: worsening, stable, or improving?

Assoc sx: N/V, diarrhea, constipation, lack of flatus (SBO), fever, abd distention, edema (CHF, gut edema, cirrhosis), jaundice (hepatitis), rectal bleeding (IBD, infection), reflux (GERD), wt loss (↑ likelihood of organic disease/chronicity) Aggravating/alleviating factors: Eating, defecation (IBS), movement or lying still, pleuritic (thoracic), ↑ w/ tensing abd wall (hernia, myofascial abd wall pain) PMHx: Cancer hx (tumor, hypercalcemia), prior abd surgery, immunosuppression, CAD/PAD (mesenteric ischemia), endocrinopathy (thyroid, adrenal disease); in women, LMP, new sexual partners (see “Pelvic Pain”) Social hx: EtOH (pancreatitis, hepatitis), tobacco (AAA, vascular insufficiency), travel hx (infection) Medications: NSAIDs (PUD), abx (C. diff)

Physical exam: VS (fever, HoTN/HTN), general appearance, skin exam (zoster on abd wall, stigmata of liver disease, jaundice), LN exam (HIV, lymphoma), gyn exam in women w/ lower abd pain (see “Pelvic Pain”), rectal exam (stool impaction, stool color, rectal mass/lesion)

Abdominal exam: Distention, bowel sounds, bruits, palpation in each quadrant, assessing for tenderness, rebound, masses, organomegaly, percussion (organomegaly, gas, ascites, stool)

 

Carnett sign: ↑ or stable pain when abdominal muscles tensed (usually ask pt to lift head off pillow & repalpate; suggests abdominal wall > intra-abdominal process) Murphy sign: Inspiration interrupted w/RUQ pressure by examiner (acute cholecystitis) Psoas sign: Pain if supine pt lifts thigh against resistance (peritonitis, appendicitis [if pain on R])

Diagnostics: Guided by hx; may not be indicated in all pts (esp young, healthy pts w/o red flags & w/ nl-appearing exam)

Labs: Acute → hCG, CBC, BMP, LFTs, lactate, lipase, U/A; chronic

→ CBC, BMP (including Ca), LFTs, lipase, TSH, Fe studies, celiac testing Imaging: Radiograph (constipation, obstruction, perforated viscus); CT (↑ Se for structural abnormalities of alimentary tract, vascular disease, liver), U/S (biliary disease, organomegaly, hepatic thrombi) (Emerg Med Clin N Am 2011;29:175)

Endoscopy: Highest yield in the presence of alarm signs (unexplained weight loss, B-symptoms, new iron-deficiency anemia, change in stool caliber, etc.) or overt GIB; diagnostic colonoscopy may be useful in chronic abd pain if concern for inflammatory or neoplastic process

Acute Abdominal Pain

General approach: Organize differential by pain location (Fig. 5-1); Red flags → ED

Red flags: Fever (esp in immunosuppressed), protracted vomiting or intolerance to POs, HoTN or e/o hypovolemia, jaundice, severe pain; e/o peritonitis (rigid abdomen, pain w/ minimal movement, incl flex hips, cough)

Nongastrointestinal causes: Consider cardiac (MI, see “Chest Pain”), pulm (pleuritis), vascular (dissection), endocrine (DKA, ↑ Ca, adrenal insufficiency), GU (renal colic, pyelonephritis, cystitis)

Diffuse: Gastroenteritis (N/V/D, sick contacts, recent abx use → often supportive care, stool cx if ? bacterial, C. diff); peritonitis (peritoneal signs → ED ± CT); SBO (N/V, no BM/flatus, distention, ↑ bowel sounds, often hx CA or abd surgery → ED [KUB or CT])

Right upper quadrant: Acute cholecystitis (⊕ Murphy sign, fever) → ED; cholangitis (jaundice + fever + pain + low BP + AMS → Reynold pentad) → ED; sx cholelithiasis: recurrent, postprandial colicky RUQ pain, often nl bili & Aφ → RUQ U/S + surgical referral

 

Epigastric pain or dyspepsia: Gastritis (burning, can be assoc w/ reflux sx; see “GERD” & “Peptic Ulcer Disease”); pancreatitis (worse w/ fatty food, ⊕ N/V, radiates to back); ↑ lipase (& amylase), see “Pancreatitis”; mesenteric ischemia (pain out of proportion to exam, ± N/V, bloody diarrhea, ↑ lactate, often ↑ WBC → ED)

Right lower quadrant: Appendicitis (N/V, ± peritoneal signs, persistent pain) → ED

Left lower quadrant: Diverticulitis (fever, ↑ WBC, distention, ± BRBPR; see “Diverticular Disease”)

Pelvic pain: Ectopic pregnancy, ovarian cyst or torsion, PID (see “Pelvic Pain” & “PID”), testicular pain (see “Scrotal and Testicular Lesions”)

Left upper quadrant: Splenic infarct (embolic) or splenic rupture (trauma, EBV assoc), or colonic disease (mesenteric ischemia, colitis)

 

Figure 5-1. Differential of Acute Abdominal Pain by Location

 

 

 

Chronic Abdominal Pain

General approach: Red flags → urgent eval (imaging ± endoscopy); other than GERD/dyspepsia, may be helpful to organize differential by types of pathology

Red flags: Wt loss, hemoccult ⊕ stools or microcytic anemia, malnutrition, new pain in pt >50, new ascites, splenomegaly, hepatomegaly → urgent outpt w/u

Epigastric (Gastroenterology 2005;129:1756)

Dyspepsia: Epigastric pain, bloating, gas; EGD if alarm sx (see “Dyspepsia” subsection) GERD: Recurrent postprandial burning in epigastrium/chest ± sx of reflux (see “GERD”) PUD: Episodic burning epigastric pain 2-5h after meals or on empty stomach (see “PUD”)

Inflammatory (AFP 2011;84:1365; AFP 2007;76:1795; NEJM 1995;332:1482)

IBD: Diarrhea, hemoccult ⊕ or grossly bloody stools, anemia, ⊕ fever, ⊕ extraintestinal sx, increased urgency, wt loss → lower endoscopy w/ bx (see “IBD”) Celiac disease: Variable sx including diarrhea, fatigue, wt loss, abd distention; Fe deficiency, transaminitis (see “Celiac Disease”) Chronic pancreatitis: Recurrent episodes of upper abd pain, ± malabsorption, usually hx

↑ EtOH intake (see “Pancreatitis”)

Motility (Gastroenterology 2013;144:218; Gut 2010;59:1716)

Constipation: ↓ stool frequency, straining, hard stools, sense of incomplete evacuation; see “Constipation”

Gastroparesis: Often assoc w/ autonomic neuropathy in DM or postinfectious, ♀ > ♂; c/o postmeal N/V, bloating, pain, early satiety → gastric emptying study

Vascular: Chronic mesenteric ischemia: PAD/CAD hx, postprandial pain & “food fear” with resultant wt loss → mesenteric Doppler U/S or angiography (JACC 2006;47:944)

Neoplastic:

CRC: Typically asymptomatic unless advanced or rectal disease; often p/w Fe-deficiency anemia → colonoscopy HCC:

 

LFT abnormalities, rarely s/sx of biliary obstruction or evidence of ESLD → triphasic CT, RUQ U/S, MRI (most Se) Gastric: Dyspepsia, early satiety, overt or occult UGI bleeding → CT or endoscopy Pancreatobiliary: S/sx of cholestasis (jaundice, ↑ Aφ, bili) → CT, RUQ U/S → MRCP/ERCP

Ovarian: Nonspecific bloating, fullness sensation, malignant ascites if late-stage → CT

Functional (NEJM 2008;358:1692)

Irritable bowel syndrome: Pain assoc w/ BM; pain onset assoc w/ change in stool freq/appearance; sx ↑ w/ stress; see “IBS”

Functional abd pain syndrome: After appropriate evaluation, sx not fully explained by another d/o AND all of the following: episodic or continuous abdominal pain that does not occur solely during physiologic events (e.g., eating, menses), occurs ≥4 times/mo for

≥2 mo, and insufficient criteria for IBS, functional dyspepsia, or cyclic vomiting syndrome/abd migraine Functional dyspepsia: By Rome IV criteria, defined as one or more of the following bothersome sx for ≥3 mo (with onset ≥6 mo to establish dx): postprandial fullness, early satiation, epigastric pain, or epigastric burning AND no evidence of structural disease (including via EGD) to explain sx Functional constipation: Presence of the following for

≥3 mo (onset ≥6 mo to dx): (1) ≥2 of the following for at least 25% of BMs: straining, lumpy or hard stools, sensation of incomplete evacuation, sensation of anorectal obstruction/blockage, manual maneuvers to facilitate, or fewer than 3 spontaneous BMs/wk (2) loose stools rarely present w/o laxatives

(3) does not meet criteria for IBS (see “Irritable Bowel Syndrome”)

Gynecology: See “Pelvic Pain”

DYSPEPSIA

 

Definition: Chronic or recurrent pain in upper abdomen, not assoc w/ bowel habits, & without e/o organic disease (Gastroenterology 2005;129:1756) Evaluation: EGD indicated for all pts >55 y w/ new-onset dyspepsia or alarm features

 

Dyspepsia Alarm Features
Age of sx onset >55 y	GI bleed/Fe-deficiency anemia
⊕ FHx upper GI cancer	Persistent vomiting
Unintended wt loss	Palpable mass/lymphadenopathy
Dysphagia/odynophagia	Jaundice

 

Figure 5-2. Dyspepsia evaluation

 

 

 

 

Background (NEJM 2008;359:16)

Definition: Reflux w/ troublesome sx or complications (Am J Gastroenterol 2006;101:1900); may have esophageal or extraesophageal sx (below) Complications: ♂ > ♀; esophageal: esophagitis, stricture, Barrett’s, adenoCA; extraesophageal: laryngitis, cough, asthma (& possibly sinusitis, pulm fibrosis, pharyngitis, recurrent otitis media), w/o heartburn sx, rarely due to GERD alone

Epidemiology: Affects 14–20% of US adults; most common GI-related

 

complaint

Risk factors: Central obesity, smoking, EtOH, hiatal hernia, ↓ LES pressure, delayed gastric emptying, loss of esophageal peristaltic function, gastric hypersecretion

Evaluation (Am J Gastroenterol 2013;108:308; Ann Intern Med 2008;149:ITC2-1)

General approach: Clinical dx; if CP, cardiac causes should be r/o (see “Chest Pain”)

 

Presentations of GERD
Typical	Heartburn: Retrosternal burning, often postprandial or at evening, worse w/ fatty meals, lying down, or after exertion (89% Sp) Regurgitation: Sensation of refluxed gastric contents → hypopharynx or pharynx, often assoc w/ sour taste (95% Sp) History of regurgitation and heartburn = 90% accurate for dx of GERD Assoc sx: Sleep disturbances, dyspepsia
Atypical	Exercise-induced heartburn (must be distinguished from angina), CP (GERD >> esophageal spasm), cough, wheezing/SOB, hoarseness; n.b. these sxs unlikely to be due to GERD w/o concurrent heartburn/regurgitation

History: Ask about RFs as above; PMHx, medications → esophagitis (NSAIDs, alendronate, tetracyclines); meds which can ↑ GERD sx (theophylline, anticholinergics, CCBs, α-antagonists, prostaglandins, nitrates, sedatives)

Features suggestive of alternative diagnosis/complications: Weight loss, dysphagia, early satiety, fevers, odynophagia, persistent vomiting

Exam: General, HEENT, cardiac, pulm, & abd exam

Differential diagnosis: CAD, PUD, esophageal dysmotility, biliary colic, esophagitis

Diagnostics: Not required for dx of uncomplicated GERD Empiric tx: 8–wk trial of omeprazole 20–40 mg QD with increase to

40 mg BID after 2 wk if no/partial effect; as sensitive as 24-h pH

monitoring in pts w/ erosive esophagitis Endoscopy: Up to 50% have nl EGD; indicated if hx/PE suggests complications or alternative dx, sx not responsive to tx, vomiting, concern for extraesophageal sx Other diagnostic techniques: pH test may be used if EGD unrevealing/sx refractory, but usually not

 

necessary H. pylori testing: Not routinely recommended for GERD sx (Am J Gastroenterol 2013;108:308)

Treatment (Gastroenterol 2008;135:1392; Am J Gastroenterol 2013;108:308)

General approach: May be treated empirically; if complications suspected (see above) → EGD referral; extraesophageal sx may benefit from tx as part of full eval

Nonpharmacologic treatment

Dietary: Avoiding foods that ↓ LES pressure or delay gastric emptying may help but not a long-term solution in chronic GERD (chocolate, peppermint, carbonated drinks, citrus/tomato, fatty foods, large meals) Behavioral: Weight loss, head of bed elevation if nocturnal sxs, avoid supine position 3 h after meals, avoid EtOH & tobacco

Pharmacotherapy (Ann Intern Med 2015;163:ITC1); Rx guided by sx frequency and severity; pt education on proper use of Rx key to effective tx (see table); consider “step-wise” tx

Occasional mild sx: PRN or standing H2-receptor antagonist (H2RA, 1st-line) or PRN antacid Moderate–severe sx: Standing PPI (1st- line) or H2RA

 

GERD Pharmacotherapy
Class, Mechanism, & Sample Rx	Notes & Side Effects
H2-receptor antagonist Competitive inhibition of histamine receptors on parietal cells Ranitidine 75–150 mg BID	1st-line for mild or intermittent symptoms Kinetics: Onset in 1 h, lasts ∼9 h; S/e: P450 inhibitor (esp cimetidine) → ↑ levels of phenytoin, warfarin, other Rx; can build tolerance; ↓ B12, drowsiness, myelosuppression (rare)
Proton-pump inhibitor	1st-line for mod–severe disease, most effective tx (NNT 3–4), 80– 100% efficacy; no evidence for within class difference Kinetics: Cannot be taken PRN (ineffective; onset is up to 5 d) & may develop rebound acid hypersecretion with d/c (self-limited) S/e: Atrophic gastritis, ↓ Mg, ↓ B12, impaired Ca absorption (better with Ca citrate than Ca carbonate); growing body of literature/association studies ↑ SEs (see below); interaction with clopidogrel disproven (NEJM 2010;363:1909)
Irreversible deactivation of
parietal H+/K+ proton
pump
Omeprazole or
pantoprazole 20–40 mg
QD–BID, 30 min before
meals
Antacids (e.g.,	Used as PRN Kinetics: Shortest onset of action (30 m) S/e: Can affect absorption of other Rx; can → diarrhea or constipation (depends on compound)
CaCO4/Tums)
Neutralization of gastric
acid

 

CaCO4 1500–3000 mg   PRN sx (max 7.5 g q24h)

PPI Safety: Multiple associative/observational studies link PPI tx to risk of C. diff infection, hepatic encephalopathy in ESLD, osteoporosis, CKD, dementia, and ischemic stroke; further investigation needed but present consensus is that PPI tx results in only a modest increase in absolute risk of each of these complications and PPIs generally safe over short-term; for those with long-term need, downtitration to lowest effective dose, discussion of tx alternatives, and appropriate patient counseling is necessary; assess pts for taper if sx well controlled for several months

Combination tx: H2RA and PPI should not be taken together as ↓ PPI effectiveness; there may be benefit to adding QHS H2RA to PPI regimen (dosed several hours apart from PPI); CaCO₄ often used as adjunct for breakthrough symptoms

Other agents:

Sodium alginate 10–20 mL QID: Physical barrier between esophagus and acid; used as an adjunct to PPIs, availability varies SNRIs/TCAs: May modulate visceral hypertensitivity; used as adjunct in overlapping functional syndromes

Surgical therapy: May be considered in pts who have responded to medical tx but are concerned about consequences of long-term Rx; efficacious & may ↑ QoL, but medical tx likely safer/more cost-effective

(BMJ 2013;346:f1908)

Barrett esophagus: Distal esophageal metaplasia (squamous → columnar epithelium); premalignant lesion found in 10–15% of pts undergoing endoscopy; can occur in absence of sx of chronic reflux (Am J of Gastroenterol 2008;103:788; NEJM 2009;361:2548)

Screening: Incidence ↑ in obese/central adiposity, Caucasian, men, age >50 y, ⊕ reflux sx; decision to screen individualized but consider referral if ≥2 RFs Surveillance: If diagnosed, routine surveillance via EGD; no dysplasia → EGD q3–5 y; low-grade dysplasia → q6–12 mo; high-grade dysplasia → endoscopic mucosal resection > surveillance EGD (Gastroenterol 2011;140:1084; 2012;143:336)

 

When to Refer:

Gastroenterology: If failure to respond to PPI, suspect esophageal complications, or red flags (wt loss, dysphagia), for Barrett’s screening in ↑ risk pts on case-by-case basis ENT, allergy, pulmonary: As dictated by sx; for refractory extraesophageal sx attributed to GERD which do not respond to PPI

 

Background (Lancet 2002;360:933; J Clin Gastroenterol 1997;24:2)

Definition: PUD refers to focal mucosal damage in the stomach (gastric ulcer, GU) or proximal duodenum (duodenal ulcer, DU); can also occur in esophagus or more distal duodenum in pts w/ hypersecretory states; most frequent cause of UGIB

Epidemiology: Lifetime prevalence up to 10%; ♂ > ♀; most commonly affects 25–64 y/o; incidence is ↓ w/ widespread use of PPI & H. pylori eradication (J Glob Infect Dis 2011;3:366)

Risk factors: H. pylori infection (implicated in 48% of ulcers), NSAID/ASA use (24%); these 2 factors have synergistic effect; smoking (23%); some combination of the 3 accounts for 89–95% of all ulcers (J Clin Gastroenterol 1997;24:2); others: malignancy, hypersecretory states (Zollinger–Ellison syndrome), stress ulcers from serious illness ± corticosteroid use, postsurgical anastomotic ulcer

Evaluation (AFP 2007;76:1005)

General approach: Suspect ulcer disease in pts who present w/ epigastric pain or concern for UGIB; ask about risk factors (above) & red flags (below)

 

Classical Presentation of PUD
History	Episodic gnawing/burning epigastric pain; 2–5 h after meals or on empty stomach (classically GU has sx worst w/ food, DU sx worst after meal but not reliable); nocturnal pain which can → awakening Alleviating sx: Relieved by antacids or antisecretory agents Assoc sx: Bloating, fullness
Exam	Often exam findings relatively mild, may have epigastric TTP, ⊕ FOBT, melena

 

Red flags: Melena (see “GI Bleeding”), peritoneal signs, intractable vomiting → ED

Differential diagnosis: Dyspepsia, GERD, pancreatitis, biliary colic; see respective chapters

Diagnostics: EGD indicated if pt has occult bleeding or alarm sx (wt loss, melena or frank GI blood loss, early satiety, anemia, dysphagia),

1. pylori testing (see “H. pylori”)

Postulcer Care (Gastroenterology 2016;151:27; NEJM 2016;374:2367)

General approach: Once dx confirmed and complications (e.g., UGIB, see “GI Bleeding”) assessed/managed, reduce bleeding/recurrence risk using strategies below

Treat underlying cause(s): To promote healing & reduce risk of recurrence: smoking cessation, avoid EtOH, H. pylori: (see “H. pylori”), confirm eradication, avoid NSAIDs (see below) Medication management: For meds which may ↑ bleeding risk

NSAIDs: Permanently d/c NSAIDs if possible; if choose to restart, use selective COX-2 inhibitor (e.g., celecoxib) and concomitant PPI to ↓ rebleeding risk; risk of rebleeding 4–6% at 6 mo in pts restarted on either (1) standard NSAID + PPI or (2) COX-2 inhibitor alone Aspirin for ASCVD: Generally okay to continue (Ann Intern Med 2010;152:1) Primary prevention: In those w/ UGIB: consider risks/benefits

Secondary prevention: Restart w/in 7 d (mortality benefit and no ↑ rebleeding risk)

Gastric acid suppression: 8 wk for DU & 8–12 wk for GU; PPI > H2RA but both >90% resolution at f/u; consider long-term suppressive tx in pts on dual anti-PLT agents or otherwise at ↑ risk of recurrence (Dig Dis 2011;29:465)

Mucosal protectants: For gastroprotection, not as acute treatment: sucralfate (coats ulcer bed), misoprostol (stimulates mucus & bicarbonate secretion, can → diarrhea), antacids (neutralizes gastric acid)

Follow-up EGD: 6–12 wk after initial tx for gastric ulcer to r/o malignancy; indicated if ulcer large/complicated or symptoms (including bleeding) persist despite tx; repeat EGD not routinely needed for duodenal ulcers

 

When to refer: Indications for EGD, above; GI referral for persistent/severe sx

 

Background (Lancet 2009;374:1449; AFP 2007;75:351; Epidemiol Rev 2000;22:283)

Helicobacter pylori is a gram ⊖ microaerophilic bacterium found in the stomach & proximal duodenum; thought to be oral–oral, fecal–oral, & contaminated water transmission

Epidemiology: Estimated >30% of US adults infected w/ H. pylori; ↑ w/ age, immigrants from developing countries, African–American, & Hispanic populations; ⊕ FHx

1. pylori infection is asx in majority of those infected & reflects

colonization but accounts for majority (>80%) of PUD & implicated in dyspepsia; infection also assoc w/ ↑ risk of gastric CA (although eradication not assoc w/ ↓ risk, so tx not indicated for that purpose)

Evaluation (World J Gastro 2011;17:3971; Am J Gastroenterol 2007;102:1808)

Indications for H. pylori testing: PUD (current or prior hx), gastric MALT lymphoma, or functional dyspepsia (not a substitute for complete eval in pts w/ alarm features; see “Dyspepsia”); may consider if long- term NSAID use or other ↑ risk of developing ulcer

Testing while on PPI: PPI use ↓ Se of all tests except serology (which

→ more false [-]); hold PPI 1 wk prior to nonserologic testing if possible

 

H. pylori Testing Options
Serology	Indicates current or past infection; not appropriate for pts previously treated, as remains ⊕ for years; Se/Sp 85/79% (Am J Gastroenterol 1996;91:1138) Best test if ↑ pretest probability (PPV heavily influenced by local prevalence); Only test unaffected by concurrent PPI tx
Stool Antigen	⊕ only in current infection; used to confirm eradication; RNA testing; Se/Sp >90/90%; ↓ Sp w/ GIB Better than serology if ↓ pretest probability
Urea Breath Test	Can be used for initial dx or to confirm eradication; Se/Sp 95/95% (Gastroenterol Clin N Am 2000;29:895) Radiolabeled urea ingested by pts; exhaled breath measured for labeled CO2 generated by bacterial urease; expensive, variable reimbursement

 

 

Endoscopic Tests

Biopsy-based: tissue culture, histology, or rapid urease test (aka “CLO test”): performed on tissue bx to detect for urease-splitting organism

Treatment (Gastroenterology 2016;151:51)

Choice of regimen: Given ↑ antibiotic resistance, 4-drug regimen “quadruple therapy” now 1st-line; triple therapy reserved for local areas with known (1) clarithromycin resistance <15% and (2) triple- therapy success >85%; recall that more complex regimens generally →

↓ adherence

PCN allergy: PBMT first-line

Duration: Should be 14-d course for all patients

 

First-Line Treatment of H. pylori
Regimen (% eradication)	Medications (example Rx)
PAMC (88%)	PPI (omeprazole 20 mg BID) Amoxicillin 1 g BID Metronidazole 500 mg BID Clarithromycin 500 mg BID
PBMT (77–80%)	PPI (omeprazole 20 mg BID) Bismuth subsalicylate (262 mg) 2 tabs QID Metronidazole 500 mg TID Tetracycline 500 mg QID
Regimen Notes	PPI: All dosing BID; higher doses okay; may also use, e.g., pantoprazole 40 mg BID Metronidazole: For PBMT, QID dosing may be simpler than TID Bismuth: Doubling standard dose BID may also be effective; multiple alternative formulations available: (1) Colloidal bismuth subcitrate (120 mg): 2 tabs BID or 1 tab QID (2)  Bismuth biskalcitrate (140 mg): 3 tabs QID (3)  Bismuth subcitrate potassium (140 mg): 3 tabs QID
Triple-Therapy Regimens (see indications, above)
PAC (68.9%)	PPI (omeprazole 20 mg BID) Amoxicillin 1 g BID Clarithromycin 500 mg BID
PMC	PPI (omeprazole 20 mg BID) Metronidazole 500 mg BID Clarithromycin 500 mg BID
PAM	PPI (omeprazole 20 mg BID) Amoxicillin 1 g BID Metronidazole 500 mg BID

 

Rescue Regimens (for treatment failure)
PAL (77–79%)a	PPI (omeprazole 20 mg BID) Amoxicillin 1 g BID Levofloxacin 500 mg QD Some evidence that adding bismuth may improve outcomes
PBMT (67–69%)a	If not used as initial regimen; see regimen details above

aNo statistical significance between the 2 regimens in comparative studies

Follow-up: If assoc w/ PUD or persistent dyspepsia after tx, eradication should be confirmed with stool testing 4 wk after tx completed (with pt off PPI × 1 wk before testing if possible); should also be confirmed in pts w/ gastric MALT lymphoma or early gastric CA When to Refer: >1 treatment failure → infectious disease and/or gastroenterology

 

Background (AFP 2000;61:3639; BMJ 2003;326:433)

Definition: Difficulty passing solids, liquids, or both from oropharynx to stomach

Classification: Oropharyngeal: Difficulty transferring food from OP to esophagus

Esophageal: Difficulty passing food from esophagus to stomach Dysphagia can be due to wide variety of disorders, can result in significant morbidity or mortality, and is an alarm symptom that always

merits further investigation

Epidemiology: Prevalence ↑ w/ age; affects 7–10% of pts >50 y; cancer more likely when pts ♂, >40 y, & present w/ wt loss; in otherwise healthy young men w/ or w/o history of atopy, esophageal dysphagia should warrant GI referral given increased prevalence of eosinophilic esophagitis (Gastrointest Endosc 2005;61:80)

Evaluation (Gastroenterology 1999;116:455; 1999;117:233)

General approach: First, determine likely location of dysfunction based on predominant symptom (may be multifactorial), then further

 

narrow Ddx based on additional hx

 

Presentation of Dysphagia Disorders
Oropharyngeal	Difficulty initiating swallow; coughing, choking/aspiration Structural (abscess, Zenker diverticulum, tumor, post-XRT) Neuromuscular (dementia, MG, Parkinson, stroke)
Esophageal	Sensation of food ± liquids being “stuck” Mechanical: Solid > liquid; external or intrinsic compression (stricture, tumor, web, Schatzki ring, web, mediastinal mass) Motility: Solid & liquids affected equally (achalasia, scleroderma)

History: Gradual or sudden onset, intermittent (Schatzki ring) vs. progressive (stricture, neoplasm); perceived location of food becoming “stuck” unreliable

Assoc sx: Heartburn, pulm infections, fever, odynophagia (esophagitis), weight loss, CP, xerostomia, regurgitation (achalasia), drooling, dysarthria, “nasal” change in speech caliber; hoarseness, tremor, ataxia, diplopia PMHx: GERD, COPD, head/neck malignancy, surgery, or XRT; stroke, autoimmune disease, celiac disease, allergy/asthma (eosinophilic esophagitis), Raynaud’s Meds/toxins: Smoking, EtOH, NSAIDs, alendronate, doxycycline, potassium (pill esophagitis)

Exam: Neuro exam w/ careful CN eval; oral cavity: xerostomia, thrush; neck exam: thyromegaly, LAD; abd exam

Diagnostics: Varies by location of dysfunction

 

Dysphagia Testing
Oropharyngeal	Modified Barium Swallow (MBS): Pt consumes foods of varying volume/consistency coated w/ barium under fluoroscopy; images then analyzed for presence/mechanism of swallowing dysfunction If this is nl or concern for structural cause, consider ENT eval; EGD indicated unless clear contraindications
Esophageal	EGD: Most common findings stricture > nl ≥ esophagitis/ulcer > tumor (Dysphagia 2012;27:101) If nl, consider MBS → if nl or concern for motility d/o, consider esophageal manometry

Referral: Oropharyngeal → SLP eval & tx, ± neurology (e.g., ALS, MG) or ENT (structural); all patients: unless clearly OP dysphagia, refer to GI for consideration of endoscopy

 

 

Background (NEJM 2003;349:1360; Gastroenterology 2013;144:211)

Definition: Constipation characterized by a history of straining, lumpy/hard stools, sense of incomplete evacuation, anorectal obstruction/blockade, <3 defecations/wk

Epidemiology: Chronic constipation affects ∼16% of adults; 33% of

pts >60 y; risk ↑ in women, non-Caucasian ethnicity, lower SES, depression, ↓ physical activity

Etiology/classification: Majority of cases are functional (2/2 colonic and/or pelvic floor/anorectal dysfunction); however, can also be due to structural disease (stricture, CA, fissure, proctitis), systemic disease (hypothyroid, DM, ↑ Ca, neuro disease such as Parkinson disease, spinal cord injury), or medication-induced

Evaluation (AFP 2011;84:299)

General approach: Consideration of dangerous or correctable causes w/ appropriate eval, & then emphasis on treating sx

History: Onset, diet, fiber/fluid intake, bowel habits, rectal bleeding, alternation w/ diarrhea, abd pain; current & past treatment, including medications

PMHx: Thyroid, depression, DM, IBS, anorectal disease (fissures), neuro (Parkinson, MS, stroke, spinal cord injury), electrolyte abnormalities, history of vaginal deliveries Meds: Many can → constipation, including antacids, iron, opioids, CCBs, TCAs, antihistamines, anticholinergics, antiparkinsonian, Ca supplements, antipsychotics

Exam: General appearance, BMI; abdominal exam (masses, tenderness)

Perineal/rectal exam: Often most revealing part of evaluation

Inspection: Look for hemorrhoids, scars, fissures; nl perineum should descend 1–3.5 cm w/ pt bearing down (abnl descent may be either reduced or excessive) Digital exam: R/o impaction, anal stenosis, rectal CA; tight sphincter suggests anismus, pain may indicate fissure; patulous anal sphincter may suggest trauma or neuro d/o

 

Diagnostics: FOBT, CBC; consider glucose, Ca, TSH as guided by hx Red flags: Hematochezia, unintended wt loss, ⊕ FHx colon cancer, anemia, ⊕ FOBT, acute-onset constipation in older pt, or no previous colonoscopy in pt >50 y/o → colonoscopy (may consider flex sig, CT colonography, barium enema as alternative depending on circumstances, see “Disease Screening”)

Assess type of 1° constipation (recognizing that pt may have >1 process)

 

Types of Primary Constipation (NEJM 2003;349:1360)
Type	Presenting Features
Normal Transit Constipation (NTC)	Most common, nl BM frequency but subjective sensation of constipation → sensory dysfunction (IBS-C)
Slow Transit Constipation (STC)	Often in young women, onset at puberty, infrequent urge to defecate, BMs 1×/wk or less
Defecatory disorder	Hx of need for manual disimpaction, abnl perineal descent or anismus (↑ anal resting pressure) on exam

Treatment (NEJM 2003;349:1360; Gastroenterology 2013;144:218)

Tx approach varies by subtype:

Defecatory disorder: Sx (e.g., straining, incomplete evacuation) do not always correlate with level of dysfunction; often requires biofeedback-aided pelvic floor retraining (efficacy well documented in RCTs: >60% respond w/ 5–6 sessions, 30–60 min each) (Gastroenterology 2005;129:86) Slow or normal transit: Managed as below; STC may be ↓ responsive to osmotics, ↑ responsive to stimulants; emphasis of NTC treatment should be on alleviating subjective symptoms of constipation given normal function

Initial treatment: Should be initiated as maintenance tx

Lifestyle: ↑ Physical activity may correlate w/ ↓ constipation; ↑ fluid intake does not improve chronic constipation unless pt also dehydrated; d/c offending meds as feasible Fiber: 1st-line treatment, particularly for NTC: Data limited but safe, inexpensive, & may have other health benefits; can take weeks for desired effect; soluble fibers generally superior to insoluble fibers Mechanism: ↑ Stool bulk, ↓ colonic transit time → ↑ GI motility

Administration: 2 doses w/ fluids and/or meals; may ↑ dose after 1-

 

wk period, up to 20 g/d S/e: Bloating, gas/flatulence, ↓ after a few d of tx; may be milder w/ synthetic/semisynthetic fibers (e.g., methylcellulose) than natural fibers (psyllium, bran) which undergo bacterial digestion

Additional therapy: If sx persistent, osmotic laxative next choice; well- tolerated, effective (NNT = 3), but may take a few days to take effect; stimulants typically used as “rescue” medication

 

Selected Pharmacotherapy in Constipation
Class	Medication	Notes
Osmotic	Polyethylene glycol 17 g QD–BID Mg hydroxide, Mg citrate lactulose	PEG preferred due to ↑ efficacy & ↓ bloating vs. lactulose (Cochrane Data Syst Rev 2010;7:CD007570) S/e: Gas, bloating; caution w/ Mg-containing compounds in CKD (can ↑ serum Mg)
Stimulant	Senna (8.6-mg tabs) 2 tabs QD–4 tabs BID Bisacodyl 10 mg PR or 5–10 mg PO up to TIW	Preferred as PRN, effects of long- term use unknown S/e: Malabsorption, abd cramps, senna can → reversible staining of colonic wall “melanosis coli”
Secretory	Lubiprostone (typically Rx’d by GI)	Chloride channel activator S/e: N/V, teratogen
	Linaclotide (typically Rx’d by GI)	Well tolerated; activates CFTR to stimulate intestinal chloride & fluid secretion (NEJM 2011;365:527)
Other	Enemas (tap water, mineral oil, soap suds)	May be stool softener (mineral oil), mechanical lavage (tap water, soap suds), avoid phosphate enema in CKD S/e: Mechanical trauma
	Mineral oil (PO or enema)	Lubricant; s/e: incontinence, can → malabsorption over time
	Stool softener (Colace)	Well tolerated, limited data re: efficacy

When to refer: If severe/refractory disease, suspected neurologic or structural component → referral to GI for additional testing; may include anorectal manometry, defecography, & colonic transit testing (sitz marker study); surgery may be considered for pts w/ STC or defecatory

 

d/o only in severe disease refractory to medical management

 

Background (NEJM 2009;361:1560)

Definition: Increase in stool frequency, volume (>200 g/d), urgency, and decrease in stool consistency; acute: occurring for <4 wk; chronic: occurring for >4 wk

Pathophysiology: Mechanisms of diarrhea include ↑ mucosal secretion, ↓ epithelial absorption, altered motility, and/or ↑ in intraluminal osmolarity

Epidemiology: 2.4–5.9% of adults experienced an episode of acute diarrhea in the past month (avg ∼0.6 episodes/y); chronic diarrhea affects 3–5% of US adults (Epidemiol Infect 2007;135:293; Gastroenterology

1999;116:1464)

Distinct evaluation, differential, & management for acute vs. chronic diarrhea

ACUTE DIARRHEA

 

Evaluation (Clin Infect Dis 2001;32:331; Am J Gastroenterol 1997;92:1962)

General approach: Assess for inflammatory features (below), hypovolemia, or historical features (immunosuppression, travel) which may alter Ddx & mgmt

Differential diagnosis: Infectious (viral, bacterial, parasitic), medications, IBD, ischemia

History: Onset, stool features (watery, presence of blood, pus, mucus), freq/volume of BMs, ability to maintain PO intake, sick contacts, daycare or SNF exposure

Assoc sx: Inflammatory sx (fever, N/V, abd pain, tenesmus, blood, pus in stool) hypovolemia (thirst, ↓ UOP, orthostasis), myalgias Exposures: Recent hospitalization, travel (see “Travel Medicine”), camping, anal receptive intercourse (infection including STIs), exposure to infants in daycare PMHx: Immunosuppression, meds,

 

recent abx (antibiotic-assoc diarrhea, C. diff)

Physical exam: VS: fever, HoTN, tachycardia, general appearance; HEENT: mucous membranes, JVP; GI: severe pain (mesenteric ischemia), distention; derm: jaundice, rash, skin turgor

Labs: Dictated by hx/PE; noninflammatory generally self-limited & does not require additional testing unless persistent (>10–14 d)

 

Acute Diarrheal Laboratory Testing
Test	Indications
C. diff	Recent abx, hospitalization, immunosuppression, chemotherapy
Fecal WBC	Mod–severe diarrhea, inflammatory sx (low Se)
FOBT	Mod–severe diarrhea, inflammatory sx
Stool Culture	Should not be ordered routinely, dictated by history (<2% of tests yield ⊕ result); definite fever, fecal WBC/FOBT ⊕, persistent diarrhea not already tx w/ abx
Stool Ova + Parasites	Should not be ordered routinely; MSM, HIV ⊕, sx for >14 d, bloody diarrhea but fecal WBC ⊖, travel to developing world, infant daycare exposure
Specific Organisms	Enterohemorrhagic E. coli (EHEC, O157:H7): Foodborne dysentery Vibrio if exposure to raw or undercooked seafood Consider microsporidia, isospora, MAC if >7 d & HIV ⊕
Other	CBC, BMP, U/A, blood Cx: May be indicated by hx/PE or ↑ severity

Imaging: Generally not indicated; consider CT/KUB if concern for toxic megacolon or severe abdominal pain (see “Abdominal Pain”)

Treatment (Clin Infect Dis 2001;32:331; Am J Gastroenterol 2016;111:602)

Noninflammatory: Often self-limited; supportive tx (oral rehydration, loperamide, bismuth subsalicylate; probiotics can ↓ stool freq & duration of sx × 24 h and assist with the gut dysbiosis that can result from antibiotic-associated diarrhea (Cochrane Database 2010;11:CD003048) Traveler’s diarrhea (see “Travel Medicine”)

Inflammatory: Supportive Rx as above

Empiric abx: (E.g., ciprofloxacin 500 mg BID × 3–5 d) if: >50 y or immunocompromised, fever >102°F, severe dysentery, sx >1 wk, severe dehydration; typically discouraged as most community-

 

acquired diarrhea is viral, not shortened by antibiotics Selective abx: Shigella (TMP–SMX), Campylobacter (erythromycin), Giardia (MNZ); Salmonella (TMP-SMX, tx if disease severe, pt >50 y or CAD (aortitis risk) C. diff (see “C. difficile”): D/c other abx if possible, MNZ for 10–14 d (or through 14 d past last dose of other abx); if appears ill (↑ WBC, abnl VS, severe abd pain) → ED

EHEC: Suspect if bloody diarrhea, no fever, WBC >10 K, abd tenderness; avoid abx due to ↑ risk HUS & unclear benefit (Ann Int Med 1997;126:505)

When to Refer: If concerned for mod–severe C. diff, elderly, immunocompromised, chronically ill, & severe dehydration or unable to maintain PO intake → ED/inpatient

CHRONIC DIARRHEA

 

Evaluation (Gastroenterology 1999;116:731; 2004;127:287; NEJM 1995;332:725)

General approach: May be due to a variety of causes, attempt to narrow Ddx by determining if sx are predominantly watery (secretory, motility, or osmotic), fatty (malabsorptive), or inflammatory

History: Onset (postinfectious), stool characteristics, frequency, exacerbating factors (e.g., fatty meals), intermittent constipation (“pseudodiarrhea” 2/2 fecal impaction, IBS)

Effect of fasting: Osmotic, malabsorptive sx improve; inflammatory, secretory do not PMHx: Prior XRT, surgery (CCY, bowel resection), pancreatitis, thyroid disease Meds/toxins: Metformin, colchicine, motility agents/laxatives, digoxin, PPI, Mg-containing antacids, abx, acarbose, orlistat Assoc sx: Abd pain, wt loss, incontinence (sometimes reported as “diarrhea”), hyperthyroid sx (see “Thyroid Disease”) Exposures: Travel, hospitalization, abx use

Physical exam: BMI, volume status, lymph nodes, abd exam (distention, hyperactive bowel sounds, masses), rectal exam (anal fistula, ↓ sphincter tone, impacted stool)

Initial diagnostics:

Labs: CBC, BMP, albumin, anti-TTG/total IgA (see “Celiac”), ESR,

 

LFTs, TSH

Stool studies: FOBT, fecal calprotectin (⊕ suggests infectious/inflammatory), fecal pH (<5.3 suggests CHO malabsorption such as lactose intolerance)

Red flags: Sx <3 mo duration, >5-kg wt loss, nocturnal predominance, continual (rather than intermittent) sx, ↑ ESR, anemia, ↓ albumin all suggest organic, not functional etiology

If above tests all nl & no red flags, consider IBS (see “IBS”) or functional diarrhea

Further diagnostics: As dictated by phenotype

 

Additional Diagnostics in Chronic Diarrhea
Phenotype	Further Testing
Watery	Stool osmolar gap: Osmolar gap = 290 – 2(Nastool + Kstool) Best to calculate rather than measure directly as measured may be artificially ↑ w/ delayed sample processing Gap >125 (osmotic): Osmotically active substance drawing water into intestinal lumen → consider lactose intolerance, ↑ sorbitol ingestion (in “sugar-free” items), laxative usage Gap 50–125 (nl/mixed): Consider IBS, celiac Gap <50 (secretory): Infection (Aeromonas, Giardia), anatomic abnl, endocrinopathy (hyperthyroid, Cushing), malignancy (pheo, VIPoma, carcinoid); bile acid malabsorption s/p ileal resection or CCY
Inflammatory	Fecal calprotectin, colonoscopy, stool culture, Giardia Ag testing
Malabsorptive	Fecal fat, stool O+P, consider stool chymotrypsin or stool elastase testing for pancreatic insufficiency, stool alpha-1-antitrypsin if concern for protein- losing enteropathy, colonoscopy with random bx if RFs for microscopic colitis (>age 60, compatible medication usage, etc)

Imaging: May be indicated in secretory or inflammatory d/o as guided by hx

Colonoscopy: Frequently indicated in setting of abnl studies or clinical features & ongoing diarrhea of unclear etiology; random bx useful if concern for microscopic colitis as above

Management (AFP 2011;84:1119)

 

Selected Causes of Chronic Diarrhea
Phenotype	Differential Diagnosis
Watery	IBS: Alternating constipation & diarrhea, ♀ > ♂; see “IBS” Lactose intolerance: Can be postinfectious or occur with aging,

 

	can be implicated on basis of timing symptoms to intake, improves w/ lactose-free diet and worsens with rechallenge Other: Medication-or diet-induced: Mg ingestion, endocrinopathy, CA, bile acid malabsorption (may trial empiric cholestyramine)
Inflammatory	CD: Recurrent abd pain, fever, ± perianal fistulae, ⊕ FOBT UC: Recurrent abd pain, fever, tenesmus, rectal bleeding, or ⊕ FOBT; see “IBD” Microscopic colitis: Elderly, ♀ nocturnal diarrhea, ?NSAID assoc C. diff: Subacute, recent abx use or hospitalization, fever Other infections: Aeromonas, Cryptosporidium, Cyclospora, Entamoeba, Giardia, microsporidia, Strongyloides
Malabsorptive	Celiac disease: Fatigue, bloating, anemia; see “Celiac Disease” Giardia: Gas, “frothy” stool, foul odor, camping/daycare/travel hx Pancreatic insufficiency: hx pancreatitis, CF, steatorrhea, wt loss

(Gastroenterology 1999;116:731; AFP 2011;84:1119)

Tx of underlying cause as appropriate/feasible; indications for empiric tx: (1) sx mgmt during eval, (2) idiopathic diarrhea, or (3) tx of underlying cause not feasible or can be used as temporizing measure; consider trial of abx for infectious causes, bile acid sequestrants, or pancreatic enzyme as dictated by history; tx as per “Acute Diarrhea,” above

When to refer: Suspected inflammatory disease, dx unclear despite lab abnormalities, endoscopy indicated, or persistent/severe sx

 

Background (JAMA 2015;313:949; Gastroenterology 2016;150:1262)

Definition: 2016 Rome diagnostic criteria: recurrent abd pain or discomfort occurring, on average, ≥1 d/wk in the last 3 mo, assoc w/ ≥ 2 of the following:

1. Related to defecation
2. Onset assoc w/ change in stool frequency
3. Onset assoc w/ change in stool form or appearance Classification: Subtype based on bowel habits but IBS now considered a spectrum of disease; IBS-C (constipation) hard stools

≥25%; IBS-D (diarrhea) loose stools ≥25%; IBS-M (mixed) hard stools

 

≥25% & loose stools ≥25%, sometimes called “alternators”;

Unsubtyped: Does not fit subtype criteria

Pathophysiology: Thought to be multifactorial; genetic predisposition, mucosal barrier disruption & increased permeability, stress response & gut mucosal immune activation, altered gut microbiota → dysfunction of neurohormonal CNS–GI system & altered neurotransmitter release/visceral hypersensitivity

Epidemiology: Affects ∼12% of US adults, ♀ > ♂ 2:1, onset typically prior to age 50; over half of pts have comorbid Ψ d/o (mood, anxiety) IBS pts have ↓ QoL & often receive ↑ meds, ↑ tests, & more provider visits than other pts w/o IBS; however, many also do not seek medical attention

Evaluation (Nat Rev Gastroenterol Hepatol 2010;7:565)

General approach: Clinical dx based on classic hx & benign PE; features suggestive of alt dx should prompt further eval; as sx frequently chronic, attempt to determine what prompted pt to seek care now (↑ in sx, ↑ stress) & what they attribute sx to (e.g., fear of malignancy), as this will be important in guiding tx

History: Hallmark sx are abd pain/bloating (96%); bowel habits, hard/loose stools, frequency, urgency, straining, sense of incomplete evacuation, mucous in stool; aggravating/alleviating factors (defecation, stress, diet)

PMHx: Depression, anxiety, thyroid or autoimmune d/o, immunosuppression, travel hx Meds: Substances which can alter bowel habits (see “Constipation” and “Diarrhea”) FHx: Autoimmune, GI malignancy, celiac, IBS, IBD

Social hx: Exercise, current stressors, hx abuse/IPV (see “Intimate Partner Violence”)

Exam: Complete exam at time of initial dx, including exam of thyroid, skin, oropharynx, abd & rectal exam w/ FOBT; this reassures pt & provider that alternative dx is not missed

Features suggestive of alternative diagnosis (“alarm” symptoms): New sx at ≥50 y, progressive sx, unintentional wt loss, nocturnal diarrhea, anemia, bloody stools, ⊕ FHx of colorectal CA, celiac disease, IBD

Differential diagnosis: Thyroid disease, celiac, IBD, infection,

 

malignancy, diverticular disease, microscopic colitis, medication effect, lactose intolerance, chronic mesenteric ischemia, bile acid maldigestion Diagnostics (Am J Gastroenterol 2009;104:S1): Not recommended if pt meets IBS criteria w/o alarm signs; may consider celiac serology (below)

 

Diagnostic Screening in IBS (Nat Rev Gastroenterol Hepatol 2010;7:565)
Celiac disease serology	Recommended in IBS-D & IBS-M
Colonoscopy	Indications: Alarm sx present or for age-appropriate (>50 y) routine screening If IBS-D or IBS-M pt referred for screening colonoscopy, request random bx for ? of microscopic colitis
BMP, CBC, TSH, stool tests, abd imaging	Low yield; should only be performed if alarm sx or features suggestive of alternative dx

Management (Gastroenterology 2006;130:1377; AFP 2012;86:419)

Counseling: Effective mgmt of IBS requires effective pt–provider relationship

Support: Express belief that sx are result of real d/o

Education: Explain current understanding of disease; intestine under complex neuroregulation & overly responsive to stimuli (food, hormones, medication, stress) → spasm or stretching → pain & changes in GI function Reassurance: Explain eval & assessment that this does not reflect dangerous d/o

Complementary/alternative therapies: Acupuncture no more effective than sham acupuncture in meta-analysis; however both more effective than no intervention (Am J Gastroenterol 2012;107:835)

Diet: Evolving role for dietary modification for IBS sx; small trials reveal significant benefit from gluten-free trial (Am J Gastroenterol 2011;106:508; Gastroenterology 2013;144:903); FODMAPs may be a trigger of meal-related symptoms in IBS patients, thought 2/2 underlying abnormalities in gut physiology and visceral sensation (Am J Gastroenterol 2013;108:707)

Fiber: Soluble fiber supplements (i.e., psyllium, methylcellulose, wheat dextrin, calcium polycarbophil) shown to be effective in ↓ overall IBS sx (Am J Gastroenterol 2014;109:1367) Allergies/Intolerance: Pts w/ IBS have a ↑ prevalence of lactose intolerance than healthy controls; pts should keep a food diary to see if their sxs are related to dairy intake; fructose intolerance also increasingly recognized in IBS; true food allergies usually coexist w/ IBS rather than reflect

 

the 1° cause of sx

Exercise: Evidence that physical activity can ↓ IBS sx (Am J Gastroenterol

2011;106:915)

Psychotherapy: CBT, psychotherapy, hypnotherapy, & stress mgmt all

↓ sx of IBS; most benefit in pts willing to accept psych component of sx or those who prefer talking Rx over medications (Nat Rev Gastroenterol Hepatol 2010;7:565)

Probiotics: Vary in species, strains, preps, & doses, with poor-quality evidence overall but best evidence for improvement in IBS sxs w/ Bifidobacterium infantis; some evidence for Bifidobacterium lactis in treating abdominal distention (J Clin Gastroenterol 2015;49:S60) Pharmacotherapy: Tailored to pt’s symptoms & their severity

 

Pharmacotherapy in IBS (Nat Rev Gastroenterol Hepatol 2010;7:565)
Symptoms	Drugs	Comments
Pain/bloating	TCAs	Likely impact on central/visceral pain sensation NNT is 3.2 to benefit 1 pt (NEJM 2003;349:2136) Caution in IBS-C given potential constipation
	SSRIs	Less e/o efficacy in IBS, may offer ↑ benefit to pts w/ comorbid mood/anxiety d/o
	Antispasmodics (e.g., hyoscyamine, dicyclomine)	Effective for short-term relief (Cochrane Database Syst Rev 2011:CD003460); ↓ postprandial sxs if given 30 min before meals S/e: dry mouth, dizziness, blurred vision Long-term effects unknown
	Peppermint oil	Safe and well-tolerated, felt to provide selective inhibition of GI smooth muscle to reduce colonic motor activity in patients with postprandial pain, gas, bloating, and urgency
Diarrhea	Antidiarrheals	Helpful for sx control, no improvement in global sx
	Eluxadoline	New oral agent with mixed opioid effects, reduced symptoms of IBS-D, can result in constipation, nausea, pancreatitis (NEJM 2016;374:242)

 

 

	Rifaximin (2-wk course)	Global ↓ in sxs/↓ bloating in IBS-D, recently FDA approved for this indication (NEJM 2011;364:22)
Constipation	Bulking agents	↓ Straining/hard stools primarily seen w/ psyllium, but caution given potential bloating
	Laxatives	IBS efficacy not well established, polyethylene glycol best-studied (see “Constipation”)
	Other (usually Rx’d by GI)	Lubiprostone: Cl− channel activator for IBS-C Linaclotide: cGMP activator, used for IBS- C

When to refer: Severe/refractory sx, dx uncertain, or presence of alarm sx → GI

 

Background (Gastroenterology 2006;131:1977)

Definition: Celiac disease (“celiac sprue”) is a systemic immune- mediated disorder, precipitated by exposure to dietary gluten (protein found in wheat, rye, & barley) in genetically predisposed individuals, characterized by malabsorptive enteropathy (NEJM 2012;367:2419; Gut 2013;62:43)

Epidemiology: Frequently undiagnosed; US prevalence ∼0.7% (Am J Gastroenterol 2012;107:1538); incidence ↑ in women (♀ : ♂ ∼1.5:1); occurs in people of all races/ethnicities but less common in pts of Asian, sub- Saharan African, Inuit descent (JAMA 2011;306:1582)

Risk factors: ⊕ FHx (10–15% if 1st-degree relative), DM1 (2–16%), Hashimoto thyroiditis (5%), other autoimmune disease, Down syndrome (5%), Turner syndrome (3%), IgA deficiency (9%) Pathophysiology: Gluten exposure, change in intestinal permeability

→ transglutaminase-modified gluten → HLA recognition → Ab against transglutaminase/gluten complex → celiac enteropathy (Gastroenterology

2009;137:1912)

Evaluation (NEJM 2012;367:2419)

 

General approach: Celiac disease should be considered in pts w/ diarrhea from malabsorption or pancreatic insufficiency, chronic abd pain, or unexplained nutritional deficiencies including iron and fat- soluble vitamins; testing for celiac is part of complete eval for these sx, & celiac dx often delayed due to nonspecific presentation Presentation: Typical: Diarrhea, steatorrhea, wt loss, abd pain/bloating, poor appetite; common: recurrent abd pain, aphthous ulcers, fatigue, Fe deficiency (± anemia), ↓ BMD ↑ ALT/AST; rare: dermatitis herpetiformis (vesicular rash on extensor surfaces)

 

Whom to Test for Celiac Disease
Pretest Probability	Presenting Features
High (>10%): Test; consider bx even if serology ⊖	Autoimmune disease, IgA deficiency, or ⊕ FHx celiac and ≥1 of the following: Abd pain/bloating, chronic diarrhea; dermatitis herpetiformis, Fe- deficiency anemia unresponsive to PO supplementation
Mod (4–10%) Test; ⊖ serology adequate to r/o disease	IBS, ↑ LFTs, Fe-deficiency anemia (if unclear etiology), chronic GI sx, fatigue/lethargy, chronic abd pain/bloating, peripheral neuropathy, recurrent aphthous ulcers, microscopic colitis, infertility/recurrent miscarriage, Down syndrome, Turner syndrome, IgA deficiency
Low (<4%) Consider testing only if more likely causes excluded	↓ BMD, fibromyalgia, chronic fatigue, GERD, chronic or recurrent pancreatitis, alopecia, myalgias/arthralgias, autoimmune liver disease, personal hx, other skin rashes, HA, mood d/o, ADHD, dementia, epilepsy, RLS

Complications: Osteoporosis, ↓ splenic function, neuropathy, ataxia (rare), infertility/ recurrent miscarriage, ulcerative jejunoileitis, & small bowel lymphoma (rare, complication of long-standing, untreated celiac disease)

Diagnosis: Generally made by serologic screening, followed by confirmatory bx; avoid starting gluten-free diet prior to testing and consider rechallenge if already on GF-diet (↓ Se of both serology and bx off gluten resulting in FN); additionally, trial of gluten-free diet not Se/Sp or specific as test for celiac disease, so should be avoided (JAMA

2011;306:1582)

Gluten disease Ddx: Gluten allergy (IgE-mediated food, contact, or asthmatic reactions) & gluten (wheat) sensitivity (nonimmune, idiopathic response to gluten, improves on GFD)

 

Serology: Celiac antibodies include anti-tissue transglutaminase (anti- TTG), anti-endomysial antibody (EMA), and anti-deamidated gliadin peptide (DGP)

 

Celiac Disease Diagnosis
Standard	✓ Anti-TTG IgA (Se/Sp 95/95%) ± total IgA; pts w/ IgA deficiency are at risk of false ⊖ & should have IgG-based DGP or TTG testing; false ⊕ can occur in autoimmune disease → may ✓ IgA EMA if concerned
If initial testing ⊖ but ↑ suspicion	Refer for EGD with SB bx
Borderline results:	✓  IgA EMA

Biopsy: If screening ⊕ → refer for confirmatory small bowel bx (villous atrophy, ↑ intraepithelial lymphocytes, crypt elongation); may obtain if screening ⊖ but ↑ suspicion

Management (Gastroenterology 2006;131:1977; Am J Gastroenterol 2013;108:656)

Diet: Lifelong gluten-free diet mainstay of therapy; no wheat, barley, or rye; pure oats may be introduced w/ caution; pts should be referred to experienced dietician when available

Counseling: Gluten-free diet helps improve sx & ↓ risk of complications; sx begin to improve in 2–4 wk & intestines heal by 6–24 mo; even minimal intake can → intestinal damage over time; gluten reintroduction typically → re-injury

Screen for complications: Screen for and treat nutritional deficiencies (✓ Fe, folate, vit D, vit B₁₂); consider DXA (see “Osteoporosis”)

When to refer: May refer if screening ⊖ but still ↑ suspicion; after dx confirmed, pts often followed by PCP but may need re-referral to GI if sx refractory despite confirmed adherence to gluten-free diet

 

Background (NEJM 2009;361:2066; Lancet 2012;380:9853)

Definition: Syndromes of chronic inflammation which primarily affect the GI tract

 

Crohn disease (CD): Systemic, often transmural, and granulomatous intestinal inflammation which can occur throughout the GI tract Ulcerative colitis (UC): Inflammatory disorder of the colonic mucosa

Pathophysiology: Both CD & UC are thought to result from dysregulation of immune system response to intestinal microbes; however, much of the genetic predispositions, clinical risk factors, presentation, complications, & tx are distinct

Epidemiology (Gastroenterology 2012;142:46)

CD: Bimodal, w/ peak incidence in 20s & 50s; ♀ > ♂; risk factors: smoking, ⊕ FHx, recent gastroenteritis, Ashkenazi Jewish heritage UC: Peak incidence in 20s, ♂ > ♀; risk factors: ⊕ FHx, Ashkenazi Jewish heritage, s/p bacterial colitis (e.g., Salmonella, Shigella), ? NSAIDs, OCPs; appendectomy + current smoking protective

Evaluation (Gut 2011;60:571)

General approach to diagnosis: Determine if IBD plausible explanation for sx, & if so, refer to GI for endoscopy; this can be done primarily w/ hx but impression can be honed w/ exam & selected lab studies

 

Initial Presentation of IBD
	Ulcerative Colitis	Crohn Disease
Distribution	Proctosigmoid (∼40–50%), left-sided colitis (∼30–40%), pancolitis (∼20%)	Small intestine (∼40%), ileocolitis (∼40%), colitis (∼20%)
History	May present as mild diarrhea, intermittent rectal bleeding, or as inflammatory diarrhea or proctitis (multiple loose stools, hematochezia, tenesmus) <10% p/w fulminant disease (appear systemically ill → ED)	Variable, can involve entire GI tract; indolent crampy abd pain ± fluctuating mucoid diarrhea, hematochezia, fatigue, fevers, wt loss, oral ulcers

History: Onset, severity, pattern of sx, bowel habits; systemic sx (fevers, chills, wt loss)

PMHx: Autoimmune disease, DVT, liver disease, recent gastroenteritis/colitis, gallstones or nephrolithiasis (CD) Other: FHx IBD, medications, smoking, travel hx

 

Assoc sx: Rashes, eye pain/irritation, arthritis, jaundice

Exam: VS, BMI, general appearance; HEENT: aphthous ulcers, episcleritis; derm: erythema nodosum, pyoderma gangrenosum; abd: RLQ mass/tenderness: ileocecal inflammation or phlegmon in CD; rectal exam: perineal exam for fissures, fistulas, or induration suggestive of abscess; rectal masses, presence of blood in stool Labs: CBC w/ diff, LFTs, ESR, CRP, Fe/B₁₂/folate, vit D

Stool studies: If diarrhea prominent, consider C. diff, stool culture, O+P, fecal leukocyte testing, fecal calprotectin (calprotectin released by activated neutrophils, ↑ in stool has Se/Sp 93/96% for IBD) or lactoferrin (BMJ 2010;341:c3369)

Imaging: KUB if ?obstruction, CT indicated if ?abscess, colitis, alt dx (diverticulitis)

Endoscopy: Flex sig (UC, distal CD) vs. colonoscopy to establish extent of disease

Differential diagnosis: Extensive: infectious colitis, diverticulitis, CRC, celiac disease, chronic pancreatitis, & IBS

Treatment (BMJ 2008;336:1062; Lancet 2012;380:1590)

When to refer: If severe disease (unstable VS, clinically ill, inadequate PO, ?abscess, obstruction) → ED; otherwise, if suspect IBD based on eval (above) → gastroenterology

Monitor for complications:

Stricture (CD or UC): Obstructive sx, usually in terminal ileum if 2/2 CD

Fistula (CD): Enterovesicular (recurrent polymicrobial UTIs), cutaneous, vaginal, enteric Abscess (CD): Fevers + peritonitis/abd pain (intra-abd) or perirectal pain/inflammation Perianal disease (CD): Seen in 1/3 of CD pts; perirectal abscess, fissures, fistulas

Health maintenance

Immunizations: Ensure up-to-date (flu, pneumococcal, HBV, ± HPV), caution w/ live vaccines if on or anticipating immunosuppresants in next ∼8 wk (see “Immunizations”) Colorectal CA screening: Overall risk of CRC higher in pts with PSC, early age at IBD dx, or long disease duration; consider screening after 8 y of disease in pts w/ colonic disease w/ surveillance q1y or as set by

 

gastroenterologist (Gastroenterology 2012;143:375) Other CA screening: Age-appropriate, also at ↑ risk of lymphoma, melanoma (Clin Gastroenterol Hepatol 2013;pii:S154) ID screening: Annual TB testing if on anti-TNF tx

Nonpharmacologic treatment (IBD 2008;14:1597)

Probiotics: Data incomplete but may ↓ risk of pouchitis (UC), no benefit proven in CD

Diet: No uniform modifications proven effective, but reasonable to trial eliminating foods pt assoc w/ sx Smoking cessation: Important in CD; likely overall health benefit in UC

Pharmacotherapy: Generally managed by gastroenterologists, divided into induction & maintenance Rx; drug classes below

 

Pharmacologic Agents Used in Treatment of IBD

5-ASA compounds: Often 1st-line for mild UC induction + maintenance; limited data in CD Route: PO for ileal or colonic; PR for distal disease (proctitis → suppository; proctosigmoiditis or L-sided colitis → enema) Specific agent: Mesalamine, Pentasa (small intestine + colon); Asacol (terminal ileum + R colon), Lialda (terminal ileum + delays to release throughout colon), sulfasalazine (colon), olsalazine/balsalazide (colon) Monitoring/SEs: Annual CBC, LFTs, U/A (risk of interstitial nephritis), BUN/Cr, small proportion (<5% of pts) experience idiosyncratic worsening of sx on tx

Escalated therapies (below) should be used in consultation with gastroenterology

Thiopurines: Used as maintenance in UC & CD ✓  TPMT genotype prior to tx to assess risk of toxicity (leukopenia, ↑ LFTs) Specific agents: 6-MP, AZA Monitoring/SEs: CBC w/ diff (BM suppression), LFTs, amylase/lipase (pancreatitis) every 2 wk, then q1–3 mo; metabolites also assessed if concerns for toxicity or nonadherence (6- TG, 6-MMP)

Corticosteroids: Typically used as induction, NOT maintenance Budesonide: High 1st-pass metabolism → ↓ systemic s/e; used in active ileitis or R-sided colon CD Prednisone: 40–60 mg/d used as induction, 60–80% of pts respond in 2–3 wk Monitoring/SEs: Multitude of risks related to immunosuppression and corticosteroid therapy/HPA axis suppression

Other: For mod—severe disease (frequently hospitalized), used if above tx fail for induction & as maintenance Anti-TNF (UC/CD): Infliximab, adalimumab, certolizumab pegol, golimumab (UC); anti-integrin: vedolizimab, natalizumab (CD); calcineurin inhibitors Monitoring/SEs: Related to immunosuppression, infusion reaction, lupus-like syndrome, annual TST or T- SPOT, reactivation HBV, contraindicated in heart failure

 

 

Background

Abnormal liver biochemical (“function”) tests (LFTs) extremely common; affect 10–20% of general population; usually mild; among these patients, <5% have severe liver disease (Eur J Gastroenterol Hepatol 2015;27:1) Testing obtained under variety of circumstances, ranging from severe illness to drug monitoring; correct interpretation requires considering clinical presentation and pattern of abnormalities

 

Tests Used in Assessing Liver Function (Clin Liver Dis 2009;13:167)
Aminotransferases (AST, ALT)	Intracellular enzymes released in hepatocyte damage; ALT more specific to liver than AST; also found in cardiac, skeletal muscle (↑ in rhabdo); levels do not always correlate w/ liver damage
Alkaline Phosphatase (Aφ)	Enzyme bound to hepatic canalicular membrane, also found in bone (mets, turnover), intestines, kidney, & placenta; ↑ enzyme synthesis in biliary obstruction, delayed peak/clearance after obstruction resolves
Gamma Glutamyl- Transpeptidase (GGT)	Enzyme on surface of hepatocytes & biliary epithelia, also in kidney, pancreas, heart, lung, brain, but NOT bone; used to confirm hepatic origin of Aφ; ↑ w/ EtOH, warfarin, phenytoin
Bilirubin (Bili)	Product of heme metabolism, conjugated in liver, excreted in bile; direct (conjugated) + indirect (unconjugated) = total bili
Albumin	Marker of liver synthetic function, delayed response to liver injury (t1/2 = 20 d); also ↓ w/ losses (nephrotic syndrome), turnover (glucocorticoids) or ↓ intake (malnutrition)
Prothrombin Time (PT & INR)	Marker of liver synthetic function (clotting factors except VIII made in liver); early marker of injury; correlates poorly w/ bleeding risk

Evaluation (NEJM 2000;342:1266)

General approach: Confirm persistence/severity; Ddx guided by pattern of elevation; full eval should include PMHx, meds (https://livertox.nih.gov/), EtOH use, & careful exam

Is it severe or is patient symptomatic? If asx & <2× ULN, recheck → LFTs will normalize in 30% of pts upon retesting (Ann Int Med 2008;148:348) What is pattern of elevation?

 

Patterns of LFT Abnormalities
Hepatocellular	↑↑ Aminotransferases, ± ↑ bili or Aφ
Cholestatic	↑↑ Aφ, ± ↑ aminotransferases, ↑ bili
Infiltrative	↑↑ Aφ, ± ↑ bili or aminotransferases
Isolated Hyperbilirubinemia	↑↑ bili

Differential Diagnosis

Hepatocellular pattern: Prevalence in US is 9%, likely driven by NAFLD (Am J Gastroenterol 2006;101:76); if AST:ALT > 2:1, consider EtOH, cirrhosis, rhabdo; if ALT <5× ULN, consider Ddx below; if these ⊖ or dx indicates → hepatology referral

 

Hepatocellular Injury Ddx When ALT <5× ULN
Meds, Toxins	EtOH most common cause; see medication table below
Viral Hepatitis	✓  HAV IgM, HBsAg, HBsAb, HBcAb, HCV Ab; see “HBV” & “HCV” If recent exposure, reasonable to check viral load
Hemochromatosis	Common in pts of Northern European descent ✓  Fe/TIBC ratio: If >45%, ✓ ferritin → if ferritin >400 ng/mL (♂) or >300 ng/mL (♀), ✓ HFE gene mutations Consider bx: Age >40, hepatosplenomegaly, abnl LFTs or ferritin >1000
NAFLD	Assoc w/ metabolic syndrome & insulin resistance; includes spectrum from steatosis to steatohepatitis (NASH) to cirrhosis; ✓   RUQ U/S, consider liver bx if age >50 y, BMI ≥30 or DM, any e/o liver synthetic dysfunction, or elevated NAFLD fibrosis score
Autoimmune Hepatitis	♀ > ♂ (4:1), bimodal age distribution; ✓ SPEP (80% have ↑ IgG), consider ANA, anti-SMA, soluble liver antigen (SLA), anti-LKM; refer for liver bx
Celiac Disease	Chronic diarrhea, symptoms of pancreatic insufficiency, long- standing IDA, wt loss, fatigue (see “Celiac Disease”)
Other	α-1 Antitrypsin deficiency: Assoc w/ panacinar emphysema; ✓ α1AT level (<80 mg/dL suggestive), SPEP Wilson disease: Usually age <40 y; ✓ceruloplasmin

Cholestatic/infiltrative pattern: Usually from intra/extrahepatic obstruction or infiltrative disease; if confirmed w/ ↑ GGT, obtain RUQ U/S

If no ductal dilatation on ultrasound: consider

Medications: See chart below: D/c potential offenders & monitor for

 

response (recalling that bili “lags”; expect some delay of bili peak after injury) PBC (primary biliary cholangitis, formerly primary biliary cirrhosis): ♀ > ♂, onset 40–50 y; fatigue, pruritus; ✓AMA (Se/Sp 95/98%) & SPEP (↑ IgM); if ⊕, refer for liver bx (NEJM 2005;353:1261; Clin Liver Dis 2008;12:261) Other: Biliary epithelial damage from hepatitis (↑ ALT) or cirrhosis (↑ PT, ↓ albumin); infiltrative process, e.g., liver abscess, amyloidosis, fungal infection, HCC (check AFP), lymphoma, metastatic CA, sarcoidosis, TB; consider MRI or CT, hepatology referral

If ductal dilatation present: Consider

Choledocholithiasis: Referral for MRCP or EUS (intermediate probability) vs. ERCP (if ↑ probability) (Gastrointest Endosc 2010;71:1) Cholangiocarcinoma or pancreatic CA: MRI or CT → referral for bx vs. ERCP

Primary sclerosing cholangitis: ♀ > ♂, age 30–40, assoc w/ IBD, always involves common bile duct; MRCP & hepatology referral

Isolated hyperbilirubinemia (see “Jaundice”)

 

Common Medications Causing Liver Injury, By Pattern (NEJM 2006;354:731)
Hepatocellular		Mixed	Cholestatic
Acarbose APAP Allopurinol Amiodarone Baclofen Bupropion Fluoxetine HAART Rx Herbals: Kava kava, Germander INH Ketoconazole Lisinopril	Losartan MTX NSAIDs Omeprazole Paroxetine PZA Rifampin Risperidone Sertraline Statins Tetracyclines Trazodone VPA	Amitriptyline AZA Captopril Carbamazepine Clindamycin Enalapril Nitrofurantoin Phenobarbital Phenytoin Sulfonamides Trazodone TMP–SMX Verapamil	Amoxicillin– clavulanate Anabolic steroids Chlorpromazine Clopidogrel Oral contraceptives Erythromycins Estrogens Irbesartan Mirtazapine Phenothiazines Terbinafine Tricyclics

EVALUATION OF JAUNDICE

 

Background (BMJ 2001;322:33)

Definitions: Jaundice: Yellowish discoloration of the skin, sclera, &

 

mucous membranes due to hyperbilirubinemia (usually appears when total bili >3 mg/dL)

Hyperbilirubinemia: Accumulation of bili above nl limits (>1.5 mg/dL)

Etiologies range from benign to life-threatening; full evaluation needed for management

Physiology:

 

 

 

1. Hgb (from RBCs) broken down in RES → unconjugated (“indirect”) bili
2. Unconjugated bilirubin (UCB) bound to albumin in blood & transported to liver UCB then conjugated w/ glucuronic acid → water-soluble conjugated (“direct”) bili
3. Conjugated bilirubin (CB) then excreted in bile into intestines

Pathophysiology: Excess heme breakdown or defective conjugation

→ ↑ unconjugated (“indirect”) bili; impaired excretion, biliary obstruction, or epithelial damage → ↑ conjugated (“direct”) bili

Evaluation (AFP 2004;69:299)

General approach: Characterize type of bilirubinemia (predominantly indirect or mixed?) to guide Ddx; consider ED referral/admission for anyone clinically ill w/ new jaundice

History: Determine any assoc sx: fatigue, fevers, confusion, bleeding; SOB, DOE; RUQ pain, pruritus; epigastric pain, wt loss; any recent illness, travel, injection drug hx

Meds/toxins: EtOH, medications (see “above”)

 

PMHx: Liver disease, HIV, gallstones, wt loss, autoimmune disease, abd surgery (e.g., CCY), FHx liver disease

Exam: Jaundice (conjunctival, sublingual), stigmata of ESLD (ascites, spider angiomata, splenomegaly, gynecomastia), xanthomas, hyperpigmentation

Initial diagnostics:

Labs: TB + DB, CBC for all jaundiced pts, along w/ ALT, AST, Aφ, PT/INR, alb Imaging: If conjugated, RUQ U/S often next step

Differential Diagnosis (Best Pract Res Clin Gastroenterol 2010;24:555)

 

Selected Causes of Indirect Hyperbilirubinemia
Overproduction	Hemolytic, ineffective erythropoiesis, hematoma reabsorption, large PE
Defective Conjugation	Gilbert’s: Conjugation enzyme insufficiency, affects 5% of US; often detected incidentally when TB slightly ↑ despite nl LFTs; can present w/ jaundice during stress/illness/fasting but resolves w/ sx; clinical dx; benign; can offer reassurance Crigler–Najjar: Conjugation enzyme deficiency, rare
Selected Causes of Direct Hyperbilirubinemia
Obstruction	Intrahepatic: PBC, medications (OCPs, erythromycin) Extrahepatic: Choledocholithiasis, stricture, cholangioCA, pancreatic CA, PSC
Epithelial Damage	Hepatitis (viral, EtOH, autoimmune), cirrhosis
Defective Excretion	Genetic d/o: Dubin–Johnson, Rotor syndrome, abnl biliary transport proteins

Background (Am J Gastroenterol 2009;104:1802)

Definition: Cirrhosis: End stage of chronic liver disease from any cause; histologic diagnosis of liver fibrosis & nodular regeneration from hepatocellular injury; clinically classified as compensated or decompensated

Decompensated cirrhosis: Cirrhosis which is complicated by portal HTN (ascites, variceal bleeding) and/or hepatic insufficiency

 

(jaundice, encephalopathy)

Epidemiology: Compensated cirrhosis often clinically silent & thus underdiagnosed; estimated at 1% prevalence, but may ↑ in US in next decade, 2/2 progression of chronic HCV acquired during peak of 1970/80s and rising burden of NAFLD (Gastroenterology 2010;138:513; Hepatology 2016;64(1):73)

Etiology: EtOH (60%), HCV (10–20%), NAFLD (10–15%) (Curr Opin

Gastroenterol 2011;27:204)

Natural history: 58% of pts w/ compensated cirrhosis → decompensation over a 10-y period; median survival w/ compensated cirrhosis ∼9 y, median survival w/ decompensated cirrhosis 1.6 y

(Hepatology 1987;7:122)

Risk factors for decompensation: (Hepatology 2011;54:555; 2012;56:1983)

Clinical: Obesity, EtOH use, smoking, new viral hepatitis, other hepatic insult incl DILI Biochemical: MELD >10, albumin <4 g/dL, HVPG >10 mmHg (Gastroenterol 2007;133:481)

Evaluation (JAMA 2012;307:832)

All pts w/ chronic liver disease should be evaluated for cirrhosis; this includes history, exam, & diagnostic testing; pts w/ known cirrhosis should be routinely assessed for evidence of/risk factors for progression and undergo regular HCC surveillance

History: Assess for risk factors of liver injury: PMHx: HCV, HBV, obesity, HLD, DM; social hx: EtOH use, lifetime or ongoing hx of IDU; Meds: APAP, NSAIDs (see “Abnormal LFTs”)

Exam: Examine for evidence of portal HTN & hepatic insufficiency

HEENT: Scleral icterus; chest: gynecomastia; GI: firm, nodular liver, hepatosplenomegaly, ascites (⊕ LR 7.2), caput medusa (⊕ LR 10, dilated veins flow away from umbilicus); GU: testicular atrophy; derm: jaundice, ↓ body hair, spider angiomata (⊕ LR 4.3), palmar erythema; ext: clubbing, edema, Terry’s nails (⊕ LR 16), silver- white discoloration of proximal nail bed; neuro: asterixis (⊕ LR 10)

Labs: Hallmarks of cirrhosis are synthetic dysfunction, evidenced by ↓ alb (⊕ LR 3.5 in alb <3.5 g/dL) and ↑ INR (⊕ LR 5 if abnl); other findings below

CBC: Neutropenia, anemia, ↓ PLT (due to splenomegaly; ⊕ LR for

 

cirrhosis of 6.8 if PLT <160 K) BMP: ↓ Na, Cr assoc w/ prognosis (MELD score)

LFTs: Conjugated hyperbilirubinemia (↑ total bilirubin, ⊕ LR 2.7 if TB

>1.2), ↑ Aφ/GGT, often ↑ AST/ALT but correlates poorly w/ disease severity

 

MELD Score                                                       3 Mo Mortality
>40	>70%
30–39	50%
20–29	20%
10–19	6%
<9	2%

Diagnosis: If cirrhosis suspected → liver bx (transjugular > percutaneous if ascites/coagulopathy) or noninvasive measures (Fibroscan or FibroSURE, strongly validated in chronic HBV and HCV), hepatology referral

Prognosis: MELD (Model for End-Stage Liver Disease) score: TB, Cr, INR → predicts survival & stratifies transplant list (Gastroenterology 2003;124:91); www.mayoclinic.org/meld/mayomodel6.html

Treatment (Am J Gastroenterol 2009;104:1802)

General approach: Cirrhosis often co-managed by hepatologist & PCP, with routine visits to screen for decompensation & encourage appropriate tx of underlying cause; some cases of compensated cirrhosis may stabilize/reverse w/ appropriate tx

Treatment underlying/contributing cause: HBV tx, HCV tx, EtOH tx, wt loss; with established cirrhosis, HCV treatment should only be undertaken in consultation with hepatologist given evolving and controversial implications

Immunizations: HAV, HBV, influenza, pneumococcus

Counseling

Lifestyle: EtOH abstinence, tobacco cessation; limited data suggest coffee linked to improved outcomes (i.e., okay to continue); obesity/DM assoc w/ worse outcomes but limited data re: wt loss, glycemic control Medications: Limit APAP to <2 g/d, avoid NSAIDs, BZDs, & opioids; discuss med changes or herbal

 

supplements w/ provider, avoid PPI in pts w/ ascites if possible (↑ risk SBP) (Hepatology 2013;57:1651) Diet: 50–90% of cirrhotic pts are malnourished, which predicts morbidity/mortality; protein requirement nearly 2x that of healthy adults (1–1.5 g/kg/d vs. 0.8 g/kg/d); supplement vit A, D, E, & K, selenium, zinc; no CHO restriction (Clin Gastroenterol Hepatol 2012;10:117)

Screening for Complications of Cirrhosis: See table below

 

Screening in Compensated Cirrhosis
Complication	Screening Modality
HCC	RUQ U/S or MRI ± AFP q6–12 mo → ↓ mortality (Clin Gastroenterol Hepatol 2007;5:508)
Varices	EGD at time of dx, then q3y if no varices or at new decompensation
Decompensation	Hx/PE at routine visits, CBC, BMP, LFTs, INR q3–6 mo

Referral for Transplant: After 1st episode of decompensation, HCC, MELD ≥14

Decompensated Cirrhosis

Acute complications typically managed as inpt or by hepatologists; given ↑ morbidity/mortality in this group; all decompensated pts should be evaluated for transplant; discussion of goals of care for all in this group (see “Advance Care Planning”)

General approach: Any new decompensation → inpt eval, e.g., new ascites → ED for dx para, further w/u

 

Decompensated Cirrhosis Management
Complication	Indications & Rx
Variceal Bleed	Ppx: Nonselective βB (e.g., nadolol, carvedilol, propranolol, goal HR 60) 1° prevention: Pts w/ varices 2° prevention: βB as above + endoscopic band ligation (↓ mortality > EBL alone) (Hepatology 2000;32:461) Refractory/recurrent: Consider TIPS When to discontinue: History of SBP, refractory volume issues, hepatorenal syndrome
SBP	Concern for current SBP: Refer to ED Ppx: Cipro 500 mg QD or TMP–SMX 1° prevention: Pts w/ ascitic TP <1.5 g/dL and altered renal function (≥1.2 mg/dL, BUN ≥25 mg/dL, Na ≤130 mEq/L) or liver failure (Child–Pugh score ≥9 and a bilirubin ≥3 mg/dL) 2° prevention: Indicated in all pts w/ hx

 

	SBP
Ascites	New/worsening ascites: Refer to ED Stable: Restrict Na <2 g/d; if Cr stable, spironolactone 50–100 mg QD (max 400 mg); add furosemide 20–40 mg (max 160 mg) (preferred ratio for K+ balance: 50-mg spironolactone:20-mg furosemide), goal loss 2 lb/wk; monitor BUN/Cr, K, Na; reduce/hold diuretics if Cr incr. Refractory: Serial LVP + albumin, TIPS
Encephalopathy	New/worsening encephalopathy: Refer to ED Stable: Diet: at least 1–1.5 g/kg/d protein (no restriction); lactulose 30 mL titrated to 2–3 loose BMs/d; consider adding rifaximin 550 mg BID, can ↓ hospitalizations (NEJM 2010;362:1071) Refractory: Add rifaximin
Hepatorenal Syndrome	Typically in pts w/ refractory ascites—HRS1 rapidly progressive, ↑ Cr (median survival 2 wk), HRS2 gradual (med survival 6 mo) Hold diuretics in any pt w/ ↑ Cr to >1.5 mg/dL or ↑ 1.5× baseline & discuss w/ hepatology/nephrology (Transp 1995;59:361) Acute ↑ Cr → ED for albumin challenge & r/o other causes
Transplant eval	1st episode of decompensation, HCC, or MELD ≥14

 

Background (NEJM 2008;358:2804; https://www.niddk.nih.gov/; BMJ 2007;335:295)

Definitions: Gallstones: Small, crystallized concretions of bile which form in the gallbladder; cholelithiasis (biliary colic): development of symptomatic disease due to temporary blockage of biliary tree by gallstones; cholecystitis: infection or ischemia of gallbladder (GB); 90% of cases due to obstructing gallstone = surgical emergency; other complications include choledocholithiasis & gallstone pancreatitis Pathophysiology: Thought that bile salts precipitate into gallstones when bile has altered ratio of components (↑ cholesterol, ↑ bili, ↓ bile salts) or incomplete/infrequent gallbladder emptying

Epidemiology: Majority of US adults have gallstones; 10–15% lifetime prevalence of symptomatic disease

Natural history: Asx gallstones: 10% of these pts develop sx w/in 5 y; 25% develop sx w/in 10 y (1–4% annual risk); biliary colic: 20% of pts w/ biliary colic develop acute cholecystitis if left untreated

Risk factors: Women (esp if pregnant, using HRT or OCPs; estrogen may ↑ cholesterol excretion & ↓ GB emptying); obesity, rapid wt loss, Native American or Hispanic ethnicity, ⊕ FHx, DM (↑ risk of gallstones

 

& ↑ risk of sx disease/complications), age >60; also TPN, sickle cell, cirrhosis, Crohn disease

Pts at increased risk of complications from gallstones: DM, sickle cell, hereditary spherocytosis, s/p gastric bypass

Evaluation

Varies by clinical scenario; for those w/ incidentally discovered gallstones, assess for sx or presence of complication risk factors (above); for those in whom etiology of abdominal pain uncertain, see “Abdominal Pain”

 

Classic Presentation of Gallstone Disease
Cholelithiasis	Episodic RUQ or epigastric pain, can be poorly localized, w/ abrupt onset that typically resolves within hours, often after meals or in the evening; may radiate to scapula, R shoulder/back, ±N/V
Acute Cholecystitis	Often w/ hx of episodes as above; similar sx but persistent, localizes to RUQ, accompanied by fever/systemic sx

Exam: May be normal in pt w/cholelithiasis; in acute cholecystitis, evaluate for fever, RUQ pain, and Murphy sign (pain w/ deep inspiration during palpation of RUQ); should have full abdominal exam; look for jaundice

Right upper quadrant ultrasound: Se/Sp >95% for detecting stones

>5 mm (Se highest when pt has been fasting, as GB then distended w/ bile); sonographic Murphy sign (pain when probe pressed against GB)

+ stones has high PPV of acute cholecystitis

Differential diagnosis: Dyspepsia, hepatic abscess, duodenal ulcer, angina, sphincter of Oddi dysfunction, biliary dyskinesia

Management

Suspected acute cholecystitis (fever, acute RUQ pain): send to ED for treatment

History consistent with biliary colic + stones on ultrasound: Surgical referral; select pts (stone <1 cm, mild sxs, minimal calcification) who are unable to tolerate surgery may benefit from indefinite ursodiol (Gastroenterol Clin North Am 2010;39:245)

History consistent with biliary colic but no stones on ultrasound: Consider other etiologies (see Ddx, “Abdominal Pain”), consider GI referral or advanced/functional GB imaging, e.g., HIDA scan

 

Asymptomatic with incidentally discovered stones → expectant mgmt; discuss natural hx & nature of sx w/ pts; no randomized trials of elective CCY in this group but may be considered in pts w/ features which ↑ risk of GB cancer (GB polyps, porcelain GB); these pts and those with increased risk of complications from GB disease may benefit from discussion w/ surgeon re: risks/benefits (Cochrane Database Syst Rev 2007;1:CD006230)

 

ACUTE PANCREATITIS

 

Background (Lancet 2008;371:143; NEJM 2016;375:1972)

Definition: Pancreatic inflammation, ranging from mild/interstitial to extensive necrosis

Epidemiology: Overall incidence increasing in US; higher incidence w/

↑ age, African–Americans; majority of cases mild but 20% severe (assoc w/ ↑ morbidity/mortality)

Risk factors: Smoking (↑ risk of EtOH-induced & idiopathic pancreatitis); obesity (↑ severity & incidence); DM2 (2–3× ↑ risk), EtOH

→ 4× ↑ risk of acute pancreatitis and ↑ risk of progression to chronic pancreatitis

 

Selected Etiologies for Pancreatitis
Obstructive	Gallstones (40% of all cases), cysts, ?pancreatic divisum
Meds/Toxic	EtOH (30%; often >5 y heavy consumption), organophosphates Meds: Usually mild; many implicated but most commonly azathioprine, 6-MP, valproic acid, ACEI, and mesalamine; also HAART (lamivudine, nelfinavir); ?DPP-4 inhibitors; evidence suggests GLP-4 not assoc w/ pancreatitis
Metabolic	Hyperlipidemia (2–5%; fasting TG >1000 mg/dL), hypercalcemia
Genetic, Autoimmune	Autoimmune (IgG4 disease; more commonly presents as pancreatic mass), SLE, Sjögren
Other	Post-procedural: ERCP, abdominal, or cardiac surgery Infection: Viral (mumps, CMV, VZV), parasitic (Ascaris, Clonorchis)

 

Complications: Systemic (AKI, ARDS, DIC), metabolic (↓ Ca, hyperglycemia), acute fluid collection, necrosis with resultant superinfection, pseudocyst

Evaluation (Ann Intern Med 2010;153:ITC51; Gut 2013;62:102)

General approach: Most pts who p/w acute pancreatitis require inpt tx; dx and etiology can often be made in clinic setting

Diagnosis: based on ≥2 of the following: (1) typical presentation, (2) serum lipase or amylase >3x ULN, and (3) evidence of pancreatitis on imaging (CT or MR)

 

Typical Presentation for Acute Pancreatitis
History	Abd pain (upper abdomen radiating to back, often w/o alleviators), nausea, vomiting, aggravated by PO intake
Exam	Epigastric and/or periumbilical pain w/ or w/o palpation; may radiate to chest, back, flank ± ↓ bowel sounds; pt may bend forward (“knee–chest” position) to ↓ pain if peritonitis present

PMHx & risk factors: Known gallstones, EtOH use, smoking, prior CCY (↑ gallstone pancreatitis), ↑ TG, DM, prior pancreatitis or similar episodes, prior ERCP Meds: Rare, but possible

Labs: Lipase or amylase (combo doesn’t ↑ diagnostic accuracy), LFTs, TG, CBC, BMP

Lipase: More specific than amylase & ↑ for longer time; also ↑ in head trauma, intracranial masses, CKD, & in pts on heparin Amylase: ↑ Se/↓ Sp; also ↑ in CKD, salivary gland or fallopian tube d/o, intestinal ischemia, perforated peptic ulcer

Imaging: CT in most pts to confirm dx and assess complications (fluid collection, necrosis) RUQ U/S in all pts w/ first episode (visualizes gallstones, not pancreatitis itself)

Urgent ERCP (inpt) indicated for e/o sepsis with gallstone pancreatitis or comorbid biliary obstruction (e/o cholangitis, ↑ TB, worsening pain in setting of biliary dilatation)

Red flags: Unstable VS (fever, HoTN), peritonitis (guarding), inability to take adequate PO, multiple comorbidities, elderly, severe pain → ED Ddx (see “Abdominal Pain”): PUD, chronic pancreatitis, biliary colic, cholecystitis, biliary colic, renal colic, appendicitis, ectopic pregnancy

 

Predicting severity: No rebound tenderness, nl HCT, & nl serum Cr predicts a nonsevere course w/ 98% accuracy

Treatment (Gastroenterology 2007;132:2022)

Most acute pancreatitis managed in inpt setting (see Red Flags above); mild cases rarely managed as outpt if fluid status, nutrition, & analgesia can be managed on PO basis

Prevention of future episodes:

Counseling: ↑ Likelihood of recurrence w/ EtOH (even if pancreatitis felt to be 2/2 another cause) → EtOH cessation/reduction (see “Alcohol Use Disorder”); smoking cessation; adherence to diet, lipid-lowering medication if ↑ TG

CHRONIC PANCREATITIS

 

Background (Gastroenterology 1998;115:763; Pancreas 2014;43:1143, AFP 2007;76:1679)

Definition: Chronic inflammation which leads to progressive fibrosis & destruction of pancreatic cells; can → pain (80–90%), endocrine (>40%) and/or exocrine (10%) insufficiency & ↑ risk of pancreatic CA Etiology: Toxic-metabolic: EtOH (45–65% of cases, risk greatest at

>4–5 drinks/d), smoking; smoking + EtOH → ↑↑ risk); idiopathic, genetic, recurrent/severe acute pancreatitis, autoimmune (hypergammaglobulinemia, ↑ IgG4), obstructive, idiopathic Epidemiology: ♂ > ♀, age at dx typically 35–55 y Pathophysiology: Recurrent acute pancreatitis necessary but not sufficient; “two-hit hypothesis” of preexisting acute pancreatitis RF +

initial acute pancreatitis → immune system activation → progression to chronic pancreatitis

Complications: Pseudocyst/abscess, pancreatic CA (13.3x ↑ risk, up to 4% incidence over 20 y) (Best Pract Res Clin Gastroenterol 2010;24:349), pseudoaneurysm of adjacent arteries, portal vein thrombosis, CBD stricture, duodenal stenosis

Evaluation (Clin Gastroenterol Hepatol 2012;10:108; Pancreas 2014;43:1143)

General approach: Sx develop over years; diagnosed based on imaging + lab findings

 

History: Intermittent → chronic epigastric pain, often postprandial; e/o pancreatic insufficiency (steatorrhea, weight loss, hyperglycemia), risk factors (alcohol, tobacco, family history)

Labs: Amylase/lipase often nl; may have ↑ AΦ, TB, ↑ glucose, ↑ fecal fat, vit D; consider fecal elastase (↓) or serum trypsin (↓) if ? of exocrine insufficiency

Imaging: CT initial test; classic findings = calcification in combination w/ atrophy or dilated duct; if inconclusive or nondiagnostic → additional testing (below)

Additional testing: Done by specialist; if CT inconclusive or nondiagnostic → EUS, MRI w/ MRCP; if this is unrevealing → pancreatic function testing, ERCP

Differential diagnosis: Pancreatic CA, IPMN, BD/duodenal obstruction

Treatment (Gastroenterology 2013;144:1282; Lancet 2016;387:1957)

General approach: Management based on slowing progression, managing pain, endocrine/exocrine insufficiency, and potential complications (biliary obstruction, bleeding, malignancy); most pts managed w/ help of GI specialist (below)

When to refer: Consider GI referral in all cases; refer if dx unclear, no clear etiology, or suspect an etiology other than EtOH; if sx persistent/severe, refer for evaluation & consideration of endoscopic/surgical tx; low threshold for inpatient admission (new fever, new jaundice, major change in sx all merit further eval) Lifestyle treatment: All pts w/ chronic pancreatitis should be counseled re: low-fat diet, EtOH & tobacco abstinence, Ca/Vit D supplementation (consider BMD testing)

Analgesia: Consider APAP/NSAID, then tramadol, pregabalin/gabapentin, SSRI/SNRI/TCA (see “Chronic Pain”) Exocrine/endocrine treatment: If insufficient, pancreatic supplementation (e.g., pancrelipase w/ meals; can add PPI, H2RA to ↑ activity); for DM, may use metformin but often poorly tolerated; particularly prone to hypoglycemia when on insulin (see “Diabetes”)

PANCREATIC CYSTS

 

Background (Gastroenterology 2015;148:819; JAMA 2016;315:1882)

Asymptomatic (“incidental”) pancreatic cysts diagnosed with ↑ frequency 2/2 ↑ frequency of cross-sectional imaging; detected in 2– 20% of pts who undergo advanced imaging for unrelated reasons, incidence ↑ w/ age

Classification: Multiple types of cysts; 2 types are precursors for pancreatic adenoCA

Premalignant (30%): Mucinous cystic neoplasms and intraductal papillary mucinous neoplasms (IPMNs) Benign: Serous cystic neoplasms (20%)

Pseudocysts (30%): Not malignant: assoc w/ pancreatitis (often 4–6 wk after acute attack); “pseudo” b/c lining w/o epithelium; if suspected → GI referral given risk of complications

Natural history: Incidental MRI lesions unlikely to be malignant: (∼1 in 10,000 chance of mucinous cystadenoCA, 1.7 in 10,000 chance of ductal adenoCA); malignant transformation rate also very low,

∼0.24% annually; even among lower-risk patients with higher-risk features, mortality from nonpancreatic CA > pancreatic CA (Am J Gastroenterol 2017;112:1330)

Higher-risk features: Cyst size >3 cm (3x ↑ risk of malignancy), solid component (8x ↑ risk), dilated pancreatic duct

Evaluation  (Gastroenterology 2015;148:819)

Before embarking on surveillance strategy, consider pt’s wishes, risk tolerance, life-expectancy, and pt willingness to consider/appropriateness of surgery if the cyst has/develops high-risk features (still relatively low absolute CA risk and ∼2% mortality rate w/ surgery) (see “Disease Screening”)

Symptomatic cysts, those w/ higher-risk features (see above) or main-duct IPMNs: GI referral for EUS w/ FNA; high-grade dysplasia or concerning features then → surgery referral

Asymptomatic cysts: Per 2015 AGA guidelines, dedicated MRI/MRCP: if no worrisome/higher-risk features, repeat MRI in 1 y; if stable, repeat MRI in 1–2 y; if stable then, generally d/c surveillance, although may consider extended surveillance in pts at ↑ risk or w/ certain imaging features (Am J Gastroenterol 2017;112:1153)

 

                                GI BLEEDING

 

Background (Essentials of Gastroenterology 2012:317)

Hemodynamically significant or acute bleeding episodes warrant ED visit ± admission; however, mild or chronic GIB may be managed as outpatients

Definition: GI bleeding (GIB): May occur anywhere in the alimentary tract; hx & risk factors guide localization for purposes of evaluation; ligament of Treitz separates upper GIB (proximal) from lower GIB (distal); occult bleeding: not evident to pt but evidenced by ⊕ FOBT or Fe-deficiency anemia

Risk factors: ↑ Age, liver disease, prior hx, NSAID, or anticoagulant/antiplatelet use

In general, acuity of blood loss determines severity of sx

Evaluation (AFP 2013;87:430; Gastroenterology 2007;133:1697)

General approach: In pts w/ suspected bleed, first determine if admission warranted (any red flags); if not, proceed w/ evaluation Indications for urgent evaluation: Concern for hemodynamically significant bleed (HoTN, tachycardia, orthostasis), comorbidities (ESLD, CHF, CAD), or symptomatic anemia → ED

Bleeding symptoms: Hematemesis, “coffee-ground emesis”—dark 2/2 exposure of heme to gastric contents; melena (black, tarry, malodorous stool from digested blood), hematochezia (maroon-colored stool assoc w/ brisk UGIB vs. LGIB), BRBPR

History: Onset, duration (acute or chronic/intermittent)

Assoc sx: Abd pain, wt loss, change in bowel habits, fever, sx of volume depletion (orthostasis, syncope), or symptomatic anemia (DOE/SOB, fatigue) Alt source of blood: Epistaxis, hemoptysis, menses, hematuria

PMHx: Liver disease, malignancy, coagulopathy, GI or aortic surgery, IBD, prior GIB, PUD, diverticulosis, hemorrhoids, celiac disease Meds/toxins: EtOH, ASA, NSAID, anti-PLT, anticoagulant, herbal supplements

Exam: VS, general appearance; e/o volume depletion, anemia, liver disease; abd exam; rectal exam: masses, hemorrhoids, fissures, stool

 

appearance, color (melena, bright red blood, brown stool); guaiac if no overt bleeding

 

Selected Causes of Mild or Occult Lower GI Bleeding
Colon Cancer	Wt loss, elderly, w/o recent colonoscopy, anemia, change in bowel habits (Br J Cancer 2010;102:48)
Colonic Polyps	Hx polyps, no recent colonoscopy, ↑ age
Diverticular Bleeding	Painless BRBPR or hematochezia, typically >50 y (see “Diverticular Disease”)
IBD	Episodes of tenesmus, urgency, fatigue, fevers, diarrhea w/ blood or hematochezia (see “IBD”)
Hemorrhoids	Constipation, blood on toilet paper or in bowl, can coat exterior of stool; hemorrhoids on PE (see “Hemorrhoids & Anal Fissures”)
Anal Fissure	Visible on PE, hx constipation/straining, pain w/ defecation (see “Hemorrhoids & Anal Fissures”)
Mesenteric Ischemia	Postprandial pain, weight loss, vasculopathy (see “Diarrhea”)
Selected Causes of Mild or Occult Upper GI Bleeding
Esophagitis/Ulcer	Dysphagia, odynophagia; infection, pill-induced, GERD, immunosuppression
Gastritis/GU Duodenitis/DU	Epigastric pain, NSAID use, ASA, EtOH (see “PUD”), positive H. pylori
Gastric Cancer	Early satiety, abd pain, dyspepsia (Gut 1997;41:142)
Angiodysplasia	CKD/ESRD; HHT, GAVE, AS, assoc w/ ASA/NSAID use
Esophageal CA	Wt loss, older ♂, dysphagia, hx of smoking/EtOH use
Celiac	⊕ FHx, steatorrhea, bloating (see “Celiac”)

Lab studies: Hgb/HCT (↓ often “delayed” during acute bleed due to hemoconcentration), MCV, Fe studies; consider BMP, coags, LFTs; further labs as directed by hx/PE

Management

Occult bleeding: Referral for colonoscopy ± EGD (dependent on presentation; upper GI source more common in pts w/o Fe-deficiency anemia or those with upper GI sx [heartburn, dysphagia, odynophagia, N/V, dyspepsia]) (NEJM 1998;339:153); these 2 studies will determine bleeding source in 48–71% of pts (AFP 2013;87:430); further studies

 

(capsule study, push enteroscopy) as determined by gastroenterology Positive FOBT obtained for colorectal cancer screening: colonoscopy

All pts w/ upper GI or alarm symptoms (e.g., abd pain, dysphagia, wt loss): EGD

If hx/PE consistent w/ LGIB of known cause (e.g., hemorrhoids), no e/o iron-deficiency anemia and recent colonoscopy, reasonable to treat underlying cause; GI referral if bleeding persists/recurs

 

Background (Dis Colon Rectum 2011;54:1059; JSTCR 2011;3:68; AFP 2011;84:204)

Definition: Swollen and/or inflamed veins of the anus & lower rectum Classification: Internal hemorrhoids: above dentate line, viscerally innervated → painless; external hemorrhoids: below dentate line, somatic innervation → pain

Pathophysiology: ↑ Intra-abdominal pressure (straining, constipation, pregnancy, ascites) → dilation of submucosal vascular tissue + weakening of supporting connective tissue → descent/prolapse of hemorrhoid

Epidemiology: Prevalence: 4–30%; variable estimates due to wide range in severity & whether mild and/or unreported disease included; one of the 3 most common outpatient GI diagnoses; peak prevalence

∼45–65 y

Differential diagnosis: Skin tags (may be hemorrhoidal remnant), anal warts, fistula or perirectal abscess (Crohn’s), anal fissure, perianal dermatitis, tumor, polyp, rectal prolapse, rectal ulceration, rectal STI (GC/CT)

Evaluation (NEJM 2014;371:944)

History: Ask about onset, bowel habits, straining, fiber and fluid intake, if c/o bleeding, assess severity (see “GI Bleeding”); classical sx of hemorrhoids include:

Bleeding: BRBPR w/ or after defecation, blood on toilet tissue or drops in bowl (60%) Pruritus: 2/2 inflammation/hygiene difficulties (55%)

 

Soiling: (10%)

Pain: Distention from engorged vein (20%); thrombosis can → acute discomfort

Red flags: Change in bowel habits, abd pain/bloating, weight loss, blood in stool, ⊕ FHx colorectal CA, overdue for CRC screening Exam: Abdominal, perineal, digital rectal, and anoscopy exam; classical findings: venous dilation w/ distortion of anal architecture; external: often dull pink; internal: dilated purple–blue veins; seen on anoscopy or at anus if prolapsed

Diagnostics: FOBT; referral for colonoscopy if: (1) Pt >50 y & has not had colonoscopy in last 10 y; (2) pts >40 y w/o recent colonoscopy but

⊕ FHx colorectal CA dx before age 60; (3) pts w/ iron-deficiency anemia, ⊕ FOBT, or red flag sx

Treatment (Dis Colon Rectum 2011;54:1060; BMJ 2008;336:380; AFP 2011;84:209)

Nonsurgical management: Best for mild disease (e.g., bleeding but no prolapse)

↑ Fiber shown to ↓ overall sx (Cochrane Data System Rev 2005;19:CD004649), trial of sitz baths, limit time on commode; use of laxatives & stool softeners to avoid straining (see “Constipation”); more research needed on PO bioflavonoids Rx: Topical steroids (avoid prolonged use, limited efficacy data), anesthetics, astringents, and/or antiseptics; thrombosed veins: topical lidocaine cream

Surgical management: Indicated for mod–severe sx (primarily with internal hemorrhoids) or acute thrombosis (if w/in 72 h of sx onset); offers definitive tx for existing hemorrhoids but does not prevent recurrence; frequently an office-based procedure; tx include rubber band ligation, infrared coagulation, stapled hemorrhoidopexy, & hemorrhoidectomy

Gastroenterology referral: Young pts w/ chronic constipation assoc w/ hemorrhoids; consider obstructive defecation & referral for anorectal manometry

ANAL FISSURES (Gastroenterol Clin North Am 2008;37:627)

 

Definition: Tear in distal anal canal, often painful; may be acute or

 

chronic

History: Pain w/ defecation, bright red blood on tissue or streaking stool surface

Exam: Perineal exam ± anoscopy → visible tear, posterior midline > anterior midline, off midline may suggest alternative dx, e.g., anal CA or IBD; in chronic fissures, may see indurated edges, hypertrophied anal papillae, or sphincter fibers visible at fissure base

Etiology: Not clearly understood, thought 2/2 anal canal trauma from hard stool → pain w/ defecation → ↑ involuntary resting internal anal sphincter tone→ more trauma

Treatment: Stool softeners (see “Constipation”); for chronic/refractory sx → GI/colorectal surgery for consideration of alt tx (can include topical CCB, botulinum injection); no role for manual sphincter dilatation (sphincter damage → incontinence)

When to refer: Chronic, refractory to stool softeners

 

Background (NEJM 2007;357:2057; J Clin Gastroenterol 1999;94:3110)

Definitions: Diverticula: Pouch-like external protrusions of the colonic wall, predominantly found in the sigmoid & descending colon; diverticulosis: phenomenon of having diverticula; diverticulitis: clinical syndrome resulting from inflammation of diverticula Pathophysiology: Diverticulosis thought to arise 2/2 ↑ intraluminal pressure & herniation of colonic mucosa through weakened areas of the bowel wall (adjacent to vasa recta); diverticulitis thought to be 2/2 stasis/obstruction at neck of individual diverticulum → local infection/ischemia

Natural history: Most pts w/ diverticulosis are asx, but some develop diverticular disease: Diverticular hemorrhage (∼3–5%): responsible for

∼23% of all LGIB cases (see “GI Bleeding”) Diverticulitis (∼10–25%):

10–33% of this group will have recurrent episode

Epidemiology: Prevalence ↑ w/ age; found in <10% of pts <40 y,

∼70% of pts >80 y (Gastroenterology 2009;136:1134); initial presentation typically after age 50

Risk factors: For diverticular disease: Low-fiber diet (↑ colonic transit

 

time & ↑ colonic pressure), ⊕ FHx (2.9× ↑ risk), obesity (∼1.5× ↑ risk), smoking, NSAIDs, constipation; for diverticular bleeding: ASA/NSAID use (Gastroenterology 2013;144:736; 2011;140:1427; 2009;136:115)

Treatment (Nat Rev Gastroenterol Hepatol 2015;12:629)

Diet: Fiber data somewhat conflicting but intake may improve sx & ↓ diverticulitis risk; red meat intake may ↑ diverticulitis sx/complications; not assoc w/ nuts & popcorn intake

Lifestyle: ↑ Physical activity can ↓ risk of diverticular bleeding & diverticulitis; wt loss & smoking cessation interventions not well-studied; moderate EtOH intake recommended

DIVERTICULITIS

 

Evaluation

General approach: Diverticulitis primarily a clinical dx; obtain complete hx & perform thorough exam on all pts (see “Abdominal Pain”); those w/ severe sx or atypical features require further testing

Classic presentation: Hx: Low-grade fever, obstipation, LLQ abd pain, no vomiting; PE: may have abd or perirectal “fullness” on exam, trace

⊕ FOBT; LLQ localized tenderness has ⊕ LR 10 (Dis Colon Rectum

2010;53:896)

Differential diagnosis: IBD, PID, ectopic pregnancy, cystitis, infectious colitis, colon CA

Labs: CBC, BMP; consider U/A, β-hCG

Imaging: Indicated if dx uncertain, presentation severe, or refractory; CT preferred

Endoscopy: Not performed in acute setting 2/2 ↑ risk perforation, performed 6–8 weeks after treatment to r/o malignancy or IBD

Red flags: Severe pain, peritonitis on exam, unable to tolerate POs, hx complicated diverticular disease in the past → ED

Treatment (AFP 2013;87:612; Aliment Pharmacol Ther 2015;42(6):664)

Mild disease: 7–10 d course of PO abx (1 RCT suggests may not have benefit in uncomplicated disease (Br J Surg 2012;99:532) but not confirmed w/ other studies)

Clear liquid diet, pain mgmt; arrange f/u (phone/in-person) at 72 h & if

 

not improving → imaging (or re-imaging) & consider inpt mgmt

All patients: Colonoscopy at 6–8 wk unless negative CRC screening within past year; begin high-fiber diet 6–8 wk after resolution of acute sx

When to refer: If red flags (above), e/o complications on imaging, advanced age or multiple comorbidities, PO or outpatient medication intolerance → ED/hospital admission; pts w/ recurrent disease (>2 episodes), complications, or younger age should have surgical eval