Presentation on theme: "Chronic Diarrhea: Differential, Diagnosis, and Treatment"— Presentation transcript:
1 Chronic Diarrhea: Differential, Diagnosis, and Treatment Alison Freeman, MD, MPHPrimary Care ConferenceJanuary 5, 2012
2 Case 161 yo M with no signif PMHx (although hasn’t been to MD in >10 yrs), presents w/ 3-4 years of watery diarrhea, now worse for last 1 mos. Endorses BMs, fairly large volume, daily. Denies hematochezia or melena, weight loss. For last 1 mos, has also developed N/V and dyspepsia. No travel, but does endorse occasional well water for the last 2 yrs.PHMx: noneMeds: nonePE: stlightly tachycardic to 105, normotensive, mild epigastric abd TTP, DRE: brown liquidy stool in vaultLabs: CBC normal, BMP notable only for BUN 30, Cr 1.8, Stool cx = neg; Stool Osm Gap = 23; Fecal leuks = neg
3 Definitions Derived from Greek “to flow through” Increased stool water content / fluidityIncreased stool weight> 200 gm/d3 or more BMs daily is generally abnormalRule out fecal incontinenceTimingAcute diarrhea: <2 weeksPersistent diarrhea: 2-4 weeksChronic diarrhea: > 4 weeks
4 Normal stool fluids processing 8-9 L/d enter GI systemIngest 1-2 L/dCreate approx 7 L/dsaliva, gastric, biliary, pancreatic secretionsSmall bowel reabsorbs 6-7 L/dLarge bowel absorbs 1-2 L/dgm/d stool createdReduction of water absorption, due to decrease in absorption or increase in secretion, by as little as 1% can lead to diarrhea
5 Types of Diarrhea Osmotic Diarrhea Secretory Diarrhea Caused by ingestion of poorly absorbed osmotically active substance (non-electrolytes) that retains fluid within the lumenIons = Magnesium, Sulfate, PhosphateSugars or Sugar Alcohols = Mannitol, Sorbitol, Lactase Deficiency, LactuloseSecretory DiarrheaDisordered electrolyte transportationNet secretion of anions (chloride or bicarbonate)Net inhibition of sodium absorption (and therefore water)
6 Causes of Diarrhea Osmotic Secretory Ingestion of poorly absorbed agent (eg, magnesium)Loss of nutrient transporter (eg, lactase deficiency)Exogenous secretagogues (eg, cholera toxin)Endogenous secretagogues (eg, NE tumor)Absence of ion transporter (eg, congenital chloridorrhea)Loss of intestinal surface area (eg, diffuse mucosal disease – IBD, celiac; surgical resection)Intestinal ischemiaRapid intestinal transit (eg, dumping syndrome)
7 Initial Evaluation: History Duration, pattern, epidemiologySeverity, dehydrationStool volume & frequencyStool characteristics (appearance, blood, mucus, oil droplets, undigested food particles)Nocturnal symptomsFecal urgency, incontinenceAssociated sx (abd pain, cramps, bloating, fever, weight loss, etc)Extra-intestinal symptomsRelationship to meals, specific foods, fasting, & stressMedical, surgical, travel, water exposure hxRecent hospitalizations, antibioticsHistory of radiationCurrent/recent medicationsDiet (including excessive fructose, sugar alcohols, caffeineSexual orientationPossibility of laxative abuse
8 Common medications and toxins associated with diarrhea Acid-reducing agents (H2 blockers, PPIs)Magnesium-containing antacidsAnti-arrhythmics (eg, digitalis, quinidine)AntibioticsAnti-neoplastic agentsAntiretroviralsBeta blockersColchicineLevothyroxineSSRIsFurosemideMetforminNSAIDs, ASAProstaglandin analogs (ie, misoprostil)TheophyllineAmphetaminesCaffeineAlcoholNarcotic/opioid withdrawal
9 Initial Evaluation: Physical Examination Most useful in determining severity of diarrheaOrthostatic changesFeverBowel sounds (or lack thereof)Abdominal distention, tenderness, masses, evidence of prior surgeriesHepatomegalyDRE including FOBTSkin, joints, thyroid, peripheral neuropathy, murmur, edema
10 Initial Evaluation: Testing CBC w/ differential (Hct, MCV, WBC count)CMP (electrolytes, BUN /Cr, glucose, LFTs, Ca, albumin)TSH, B12, folate, INR/PTT, Vit D, iron, ESR, CRP, Amoeba Ab, anti-transglutaminase IgA Ab, anti-endomyseal IgA Ab, HIVStool studiesCulture (more useful only for acute), O&P, Giardia Ag, C diff, Coccidia, Microsporidia, CryptosporidiosisFecal leukocytes (or marker for neutrophils: lactoferrin or calprotectin)Fecal occult bloodStool electolytes for osmolar gap = 290 – 2[Na + K]Stool pH (<6 suggests CHO malabsorption due to colonic bacterial fermentation to CO2, H2, and short chain FA)Fat content (48h or 72h quantitative or Sudan stain)Laxative screen (if positive, repeat before approaching pt)
11 Clinical classification FattyBloating, flatulence, greasy malodorous stools that can be difficult to flush, weight loss, s/s of vitamin deficiencies (periph neuropathy, easy bruising)Anemia, coagulopathy, hypoalbuminemia, osteopeniaWateryLarge volume, variable presentationInflammatoryBlood, mucus, pus, abd pain, fever, small volumePositive fecal leukocytes, gross or occult blood, ESR/CRP, leukocytosis
13 Differential Diagnosis: Fatty Diarrhea Maldigestion = inadequate breakdown of triglyceridesMalabsorption = inadequate mucosal transport of digestion productsPancreatic exocrine insufficiency (eg, chronic pancreatitis)Inadequate luminal bile acid concentration (eg, advanced primary biliary cirrhosis)Mucosal diseases (eg, Celiac sprue, Whipple’s disease)Mesenteric ischemiaStructural disease (eg, short bowel syndrome)Small intestinal bacterial overgrowth (bile salt deconjugation)
14 Signs and Sx of Malabsorption (1) Malabsorption ofClinical featuresLab findingsCaloriesWt loss w/ normal appetiteFatPale voluminous stool, steatorrheaStool fat >6 g dailyProteinEdema, muscle atrophy, amenorrheaLow albumin, low proteinCarbohydratesWatery diarrhea, flatulence, milk intoleranceStool pH < 6; stool osmotic gap >100; increased breath hydrogenVitamin B12Anemia, subacute combined degeneration of spinal cord (paresthesias, ataxia, loss of position/ vibratory sense)Macrocytic anemia; low B12 level; increased MMA and homocysteine levels; abnormal Schilling testFolic acidAnemiaMacrocytic anemia; decreased serum/RBC folate; increased homocysteine level
15 Signs and Sx of Malabsorption (2) Malabsorption ofClinical featuresLab findingsIronAnemia, glossitis, pagophagiaMicrocytic anemia; decreased serum iron and ferritin levels; increased TIBCCalcium and Vitamin DParesthesia, tetany, pathologic fractures, positive Chvostek and Trusseau signsLow serum calcium; abnormal DEXA; elevated Alk PhosVitamin AFollicular hyperkeratosis, night blindnessDecreased serum caroteneVitamin KEasy bruising, bleeding disordersElevated INR; decreased Vitamin K-dependent coagulation factors (2, 7, 9, 10)Vitamin B (general)Cheilosis, painless glossitis, angular stmatitis, acrodermatitis
16 Review of Nutrient/Vitamin Absorption Duodenum/JejunumIleumColonCarbohydrates / simple sugarsVitamin B12Short-chain fatty acidsFatsBile saltsVitamin K**Amino acidsMagnesiumBiotin**IronFat-soluble vitamins (A, D, E, K)CalciumOther VitaminsMinerals** In part produced by bacterial gut flora
17 Differential Diagnosis: Watery Diarrhea Osmotic (poorly absorbable substance in lumen)Secretory (malabsorption or secretion of electrolytes, H2O)Carbohydrate malabsorption (eg, lactase deficiency, diet high in fructose or sugar alcohols)Osmotic laxatives (Mg, PO4, SO4)Very broad differential – see next slide
20 Additional studies Imaging Small bowel seriesCT/MRI or CT/MR enterographyEndoscopy vs Push Enteroscopy with small bowel biopsy and aspirate for quantitative cultureColonoscopy vs Flexible Sigmoidoscopy, including random biopsies
21 Treatment Correct dehydration and electrolyte deficits Oral rehydration therapy (cereal-based best)Sports drinks + crackers/pretzelsGenerally, empiric course of antibiotics is not useful for chronic diarrheaEmpiric trials of (in appropriate clinical setting):Dietary restrictionsPancreatic enzyme supplementationOpiates (codeine, morphine, loperamide, tincture of opium)Bile acid binding resinsClonidine (diabetic diarrhea)Octreotide (for carcinoid syndrome, other endocrinopathies, dumping syndrome, chemotherapy-induced diarrhea, AIDS-related diarrhea)Fiber supplements (psyllium) and pectin
22 Case 1 (a reminder)61 yo M with no signif PMHx (although hasn’t been to MD in >10 yrs), presents w/ 3-4 years of watery diarrhea, now worse for last 1 mos. Endorses BMs, fairly large volume, daily. Denies hematochezia or melena, weight loss. For last 1 mos, has also developed N/V and dyspepsia. No travel, but does endorse occasional well water for the last 2 yrs.PHMx: noneMeds: nonePE: stlightly tachycardic to 105, normotensive, mild epigastric abd TTP, DRE: brown liquidy stool in vaultLabs: CBC normal, BMP notable only for BUN 30, Cr 1.8, Stool cx = neg; Stool Osm Gap = 23; Fecal leuks = neg
23 Case 1 (con’t)EGD – Erosive esophagitis, hypertrophied gastric rugae w/ edema, multiple diffuse small gastric nodules w/o active bleeding, mutliple deep non-bleeding ulcers in first and second portion of duodenum, some w/ eschar-like base and more ulcers visible when looking down-stream in duodenum. Bx = normal.Colonoscopy – Few diverticuli, otherwise normal to ileum.
24 Case 1 (con’t)EGD w/ hypertrophic rugal folds and multiple duodenal ulcers is highly suggestive of Zollinger-Ellison syndrome (ie, gastrinoma).Gastrin level = 184 (normal , >1000 diagnostic of ZE)CT abd = normalOctreotide scan = normalSecretin stim test = diagnostic for ZEEUS = pendingTx: started on high-dose PPI and diarrhea now resolved
25 Case 223 yo F administrative assistant, reported 6 months of diarrhoea. She had been passing up to 4 loose stools each day, although there were periods of up to a week when her bowel habit was normal.What further information do you want?What is on your differential diagnosis?
26 Etiologies to consider Lactose intoleranceFlatulence, bloating, soft stools with lactose ingestionAcquired lactase deficiencyAfrican Americans (70%), Asians (85%)Irritable bowel syndromeAlternating constipation, diarrhoea, mucus in stoolRelief with defecation, worse with stressNo night-time symptomsGiardia infectionFoul smelling stool, steatorrhea, flatulence, crampingExposure to contaminated waterThyrotoxicosisPalpitations, wt loss, tremor, heat intoleranceTrouble sleeping, anxietyMedications/substancesSSRI, metformin, NSAIDs, allopurinol, chemotherapy, antibiotics, etcAmphetamines, narcotic withdrawal
27 Case 2 (continued)She had colicky lower abdominal pain, relieved by defecation. She also had abdominal bloating.She had not had any diarrhea at night. There was no blood in the stools. Her weight had not altered over this time. She did notice occasional mucus in the stools, but denied joint pains.She had been under considerable stress at work. Her firm was undergoing restructuring and she was concerned that she would lose her job.
28 Irritable bowel syndrome: diagnosis of exclusion R/O “red flags” for inflammation &/or malabsorptionFever, night sweatswt loss, inability to gain wtbloody stooljoint painsnight-time symptomsreactive arthritis syndrome with genital infections, bacterial diarrhoea (eye, skin, joints, GU)nutritional deficits: Hb, Ca, INR, albuminExclude other common thingsGiardiaLactose intolerance, wheat allergyLaxative abuseHyperthyroidismMedicationsIBS vs functional diarrhea
29 Case 329 yo F, reported several months of diarrhea and general malaise. She has had 6 – 8 loose to watery stools daily. She denies hematochezia or melena. She endorses increased fatigue and lethargy. Her appetite had been poor and she thought she had lost lb. She also reports intermittent joint pains, particularly in her knees. She denies fever, but has had night sweats on several occasions. She denies palpitations, increased hunger or tremor. On exam temperature was 37.8oC. Abd exam noteable for RLQ tenderness. Examination of her knees was normal. Stool tests: WBC seen, positive FOBT, no ova, cysts or parasites, neg bacterial cx Labs: Hct 32, WBC 13.5, ESR 38, CRP 21.2 What diagnosis is most likely?
30 IBD Key Features Crohn’s disease Ulcerative colitis skip lesions from mouth to anusperianal abscesses and fistulasbloody stool may not be as obviousfrequently involves terminal ileum (RLQ)Ulcerative colitisTenesmus, bloody stoolInvolves rectum, and contiguous section of colonDiagnose by colonoscopy w/ biopsyUC: crypt abscesses, crypt branching, atrophy of glands, loss of mucin in goblet cellsCrohn’s: transmural inflammation, granulomas
31 Systemic manifestations of IBD JointsReactive arthritisEyesUveitis, iritis, episcleritisSkin / Mucus MembranesErythema nodosumPyoderma gangrenosumAphthous stomatitisLiver/GIPrimary sclerosing cholangitis with elevated GGT, ALPCholelithiasisPancreatitisHeme/OncHypercoagulabilityIncreased risk for colorectal cancerAnnals of Medicine. 2010; 42: 97–114
32 Case 424 yo M p/w 4 months of diarrhea, 5-6 loose stools each day, which he said were pale and difficult to flush. He endorses abdominal bloating, 8 lb weight loss without dieting, and intermittent itchy rash. He travelled to Africa 9 mos ago. He denies reactive arthritis and hyperthyroid symptoms.Physical examination was normal.Notable labs/testing:Stool cultures, ova and parasites all negative; Giardia Ag negative; FOBT negative.Hb 31, MCV 75, Ferritin 10Colonoscopy -- negative, including terminal ileumWhat additional testing would you like?
33 Further investigations Small bowel biopsyBlunting of intestinal villi, crypt hypertrophyLamina propria infiltration with excess lymphocytes and plasma cellsAuto-antibodiesAnti-endomyseal IgA AbAnti-transglutamase IgA AbAntigliadin IgG and IgA AbIgA deficiency can occur in 10% and give false negative results for the IgA AbIgA antibodies disappear on gluten-free dietMelissa P. Upton (2008) “Give Us This Day Our Daily Bread”—Evolving Concepts in Celiac Sprue. Archives of Pathology & Laboratory Medicine: October 2008, Vol. 132, No. 10, pp
34 Celiac sprue 1:250 Caucasians Gluten sensitive enteropathy Usually resolves on gluten-free dietAffects distal duodenum, proximal jejunumCauses malabsorption of multiple nutrients
36 ReferencesLR Schiller, JH Selin (2010). Chpt 15, Diarrhea. In M Feldman, LS Friedman, and LJ Brandt (Eds.), Sleisenger and Fordtran’s Gastrointestinal and Liver Disease (pg ). Elsevier.PA Bons, JT LaMont. Approach to the adult with chronic diarrhea in developed countries. Up-To-Date, May 2011.