Week 10 GI (Moodle Version).pdf

ABDOMINAL PAIN & IRRITABLE BOWEL SYNDROME ASSESSMENT AND DIAGNOSIS CMS150 LEARNING OBJECTIVES Compare and contrast medical tests used in the evaluation of a patient with abdominal pain, based on evidence of accuracy Apply diagnostic evidence to clinical reasoning in the presence of abdominal pa...

ABDOMINAL PAIN & IRRITABLE BOWEL SYNDROME ASSESSMENT AND DIAGNOSIS CMS150 LEARNING OBJECTIVES Compare and contrast medical tests used in the evaluation of a patient with abdominal pain, based on evidence of accuracy Apply diagnostic evidence to clinical reasoning in the presence of abdominal pain Prioritize issues to be addressed in a patient encounter where there is abdominal pain Develop and refine a differential diagnosis based on new information related to abdominal pain Perform clinical examination and medical procedures safely in a patient with abdominal pain Identify appropriate strategic patient-centred interviewing skills to establish and sustain patient rapport in the context of abdominal pain ABDOMINAL PAIN: LOCATIONS ABDOMINAL PAIN: DIFFERENTIAL DIAGNOSES Location of Pain Possible diagnosis Biliary: cholecystitis, cholelithiasis, cholangitis Cardiac: myocardial infarction, pericarditis Epigastric Gastric: esophagitis, gastritis, peptic ulcer Pancreatic: mass, pancreatitis Vascular: aortic dissection, mesenteric ischemia Location of Pain Possible diagnosis Biliary: cholecystitis, cholelithiasis, cholangitis Colonic: colitis, diverticulitis Right Upper Quadrant Hepatic: abscess, hepatitis, mass Pulmonary: pneumonia, embolus Renal: nephrolithiasis, pyelonephritis ABDOMINAL PAIN: DIFFERENTIAL DIAGNOSES Location of Pain Possible diagnosis Gastric: esophagitis, gastritis, peptic ulcer Pancreatic: mass, pancreatitis Left Upper Quadrant Renal: nephrolithiasis, pyelonephritis Vascular: aortic dissection, mesenteric ischemia Colonic: early appendicitis Location of Pain Possible diagnosis Gastric: esophagitis, gastritis, peptic ulcer, small-bowel mass or obstruction Periumbilical Vascular: aortic dissection, mesenteric ischemia Colonic: appendicitis, colitis, diverticulitis, IBD, IBS ABDOMINAL PAIN: DIFFERENTIAL DIAGNOSES Location of Pain Possible diagnosis Gynecologic: ectopic pregnancy, fibroids, ovarian mass, torsion, PID Right Lower Renal: nephrolithiasis, pyelonephritis Quadrant Colonic: appendicitis, colitis, diverticulitis, IBD, IBS Location of Pain Possible diagnosis Gynecologic: ectopic pregnancy, fibroids, ovarian mass, Suprapubic torsion, PID Renal: cystitis, nephrolithiasis, pyelonephritis Colonic: colitis, diverticulitis, IBD, IBS ABDOMINAL PAIN: DIFFERENTIAL DIAGNOSES Location of Pain Possible diagnosis Gynecologic: ectopic pregnancy, fibroids, ovarian mass, torsion, PID Left Lower Renal: nephrolithiasis, pyelonephritis Quadrant Colonic: colitis, diverticulitis, IBD, IBS ABDOMINAL PAIN: DIFFERENTIAL DIAGNOSES Location of Pain Possible diagnosis Bowel obstruction Mesenteric ischemia Peritonitis Any Abdominal Narcotic withdrawal Location IBD Sickle cell crisis Porphyria Heavy metal poisoning ABDOMINAL PAIN: MUST NOT MISS CONDITIONS Based on the presence of abdominal pain: Appendicitis Bowel obstruction Abdominal malignancy Cardiovascular origins of abdominal pain Gynecological: PID, ectopic pregnancy, ovarian torsion APPENDICITIS Epidemiology 1.1% of adults presenting with abdominal pain to family practice clinic had appendicitis (Adelman 1987) 10-25% of children with abdominal pain presenting to emergency department had appendicitis (Bundy et al 2007) 40% of adult patients with abdominal pain who underwent abdominal CT and ultrasound had appendicitis (Doria et al 2006) APPENDICITIS Signs & symptoms LR + LR - Right lower quadrant pain 8.4 0.18 Migrating pain from periumbilical area to 3.6 0.4 right lower quadrant Fever 3.2 0.42 Psoas sign 3.2 0.88 Pain before vomiting 2.7 0.02 Rebound tenderness 2.03 0.28 Rigidity (abdominal) 1.59 0.88 Anorexia 1.1 0.9 APPENDICITIS Additional Signs and Symptoms Abdominal pain may be poorly localized initially Progressive inflammation eventually involves the parietal peritoneum, resulting in pain localized to the right lower quadrant Nausea and vomiting Abdominal palpation is painful in periumbical and/or right lower quadrant McBurney’s point painful on palpation APPENDICITIS Investigations Abdominal CT scan (LR+, 24; LR−, 0.08) Ultrasound indicated in pregnancy Prognosis: EMERGENCY May progress to ischemia, necrosis, and perforation of bowel Perforation may lead to sepsis >50% of people with appendicitis who do not receive treatment (surgery and/or antibiotics) die  BOWEL OBSTRUCTION Epidemiology Accounts for 4% of abdominal pain cases Large bowel obstructions: 24% Small bowel obstructions: 76%  BOWEL OBSTRUCTION Etiology of Large Bowel Obstruction Cancer (53%) Sigmoid or cecal volvulus (17%) Diverticular disease (12%) Extrinsic compression from metastatic cancer (6%) Other (12%)  BOWEL OBSTRUCTION Etiology of Small Bowel Obstruction Postsurgical adhesions, 70% Malignant (usually metastatic) tumor, 10–20% Hernia (ventral, inguinal, or internal), 10% IBD (with stricture), 5% Radiation  BOWEL OBSTRUCTION At first, pain may be intermittent; later, pain often becomes more constant, bowel sounds may diminish and become absent In patients with abdominal pain, the absence of bowel movements or flatus suggests bowel obstruction Signs & symptoms (LBO) LR + LR - Constipation 8.8 0.6 Abdominal distention 5.7 0.4 Pain decreases after vomiting 4.5 0.8 Colic 2.8 0.8 Previous abdominal surgery 2.7 0.4  BOWEL OBSTRUCTION Combined signs & symptoms (LBO/SBO) LR + Distention associated with increased bowel sounds, ~10 vomiting, constipation, or prior surgery Increased bowel sounds with a history of prior 11 surgery Increased bowel sounds with vomiting 8 BOWEL OBSTRUCTION Investigations: LBO CT scan (LR+, 10.1; LR−, 0.1) Barium enema for large bowel obstruction (LR+, 48; LR−, 0.04) Investigations: SBO Radiograph (X-ray): LR+, 2.2; LR–, 0.37 Ultrasound: LR+, 14.1; LR–, 0.13 CT scan: LR+, 3.6; LR–, 0.18  BOWEL OBSTRUCTION Prognosis of Small Bowel Obstruction (SBO) Complete SBO: 20–40% progress to bowel strangulation and infarction Clinical signs do not allow for identification of strangulation prior to infarction: Fever, leukocytosis, and metabolic acidosis are late signs of strangulation and suggest infarction 50–75% of patients admitted for SBO require surgery Partial SBO: Rarely progresses to strangulation or infarction Characterized by continuing ability to pass stool or flatus (> 6–12 hours after symptom onset) or passage of contrast into cecum Resolves spontaneously (without surgery): 65–80%  BOWEL OBSTRUCTION Prognosis of Large Bowel Obstruction Most LBO will resolve with treatment Surgical emergency if bowel perforation or bowel ischemia occur  ABDOMINAL MALIGNANCY Colorectal cancer Gynecological cancers Pancreatic cancer Gall bladder/bile duct cancer Gastric cancer Liver cancer  ABDOMINAL MALIGNANCY Consider risk factors Personal or family history of cancer Lifestyle factors Age Consult cancer screening criteria Determine whether/when screening tests performed if applicable Consider systemic symptoms Unintentional weight loss (up to 36% of cancer diagnoses) Loss of appetite Significant night sweats Symptoms waking patient from sleep (diarrhea e.g.) Based on patient history and risk factors, further investigation may be indicated CARDIOVASCULAR ORIGINS OF ABDOMINAL PAIN Abdominal Aortic Aneurysm (AAA) Myocardial infarction (see Cardiovascular lecture) Pericarditis (see Cardiovascular lecture) Aortic dissection (see Cardiovascular lecture) Mesenteric ischemia CARDIOVASCULAR Abdominal Aortic Aneurysm (AAA) Epidemiology U.S. prevalence: 1.3% in women, 7.6% in men Strong family history of AAA increases prevalence to 8.3% in women Signs & Symptoms Pulsatile abdominal mass with ruptured AAA (LR+, 8.0; LR–, 0.6) Sensitivity severely limited in patients with rupture, large girth In patients without AAA rupture who are symptomatic: Abdominal pain: 83% Flank or back pain: 61–66% Syncope: 26% Abdominal mass on careful exam: 52% (only 18% had abdominal mass noted on routine abdominal exam) Hypotension or orthostasis: 48%  CARDIOVASCULAR Mesenteric Ischemia Signs & Symptoms Acute: Abdominal pain intensity out of proportion to exam is a classic finding but is absent in 20–25% Vomiting (71%) Diarrhea (42%) Prior history of intestinal angina (50%) Chronic: Recurrent postprandial abdominal pain (often in first hour and diminishing 1–2 hours later) food fear, weight loss history of tobacco use (75%), peripheral vascular disease (55%) coronary artery disease (43%) hypertension (37%)  CARDIOVASCULAR Mesenteric Ischemia (chronic) Signs and Symptoms cont’d Abdominal pain: 94% Typically epigastric or periumbilical pain Postprandial pain: 88% Weight loss due to food aversion: 78% Diarrhea: 36% Investigations CT angiography for acute Ultrasonography for chronic GYNECOLOGICAL Urgent and Emergent Conditions Ectopic pregnancy Ovarian torsion Pelvic Inflammatory Disease (PID) GYNECOLOGICAL Urgent and Emergent Conditions: Ectopic (extrauterine) pregnancy Epidemiology Consider in patients of childbearing age with female reproductive organs Ectopic implantation occurs in approximately 2% of first trimester pregnancies Signs and Symptoms Severe lower quadrant pain occurs in almost every case. Pain sudden onset , stabbing, intermittent, does not radiate At least 2/3 patients have a history of abnormal menstruation Slight vaginal bleeding (spotting) Pelvic adnexal mass may be palpable GYNECOLOGICAL Urgent and Emergent Conditions: Ectopic pregnancy Prognosis Repeat tubal pregnancy occurs in about 10% of cases Mortality rare if treated before rupture ( 65 years High-dose NSAID therapy Concomitant use of aspirin (low or high dose), corticosteroids, or anticoagulants. Concurrent H pylori infection PEPTIC ULCER DISEASE Prevalence of PUD in patients with dyspepsia Dyspepsia = upper abdominal discomfort Age No NSAIDs or H. pylori Current NSAID use H. Pylori infection 40 years 1% 5% 20% 75 years 3% 20% 30% PEPTIC ULCER DISEASE Signs and Symptoms 60% of NSAID-associated ulcers are asymptomatic. 25% of non-NSAID ulcers are asymptomatic. Less than one-third of patients with epigastric discomfort have PUD. Unintentional weight loss 31–55% of patients with benign gastric ulcer noted weight loss. ~50% lost 10–20 lbs; 21% lost > 20 lb PEPTIC ULCER DISEASE Prognosis The first sign of PUD may be a life-threatening complication (hemorrhage or perforation): > 50% of patients with serious to life-threatening complication had no prior symptom Bleeding, which can vary from massive hemorrhage (with hematemesis and melena or hematochezia) to occult, chronic, subtle bleeding with iron deficiency anemia Perforation (EMERGENCY) PEPTIC ULCER DISEASE Investigations Screen for H. pylori infection Urea breath test Stool antigen test Blood test (antibodies): cannot distinguish between past and current H. pylori infection Imaging Esophagogastroduodenoscopy (EGD) (endoscopy) only recommended for >60 years old or if alarm features present  CHOLECYSTITIS Inflammation of the gall bladder and or bile ducts, secondary to cystic duct obstruction Epidemiology Accounts for 1/3 of patients older than 55 years presenting to emergency department with acute abdominal pain  CHOLECYSTITIS Signs & symptoms LR + LR - Murphy’s sign 5.0 0.4 Right upper quadrant pain 2.5 0.3 Fever 1.8 0.8 Jaundice 1.0 1.0 Nausea/vomiting may also be present  CHOLECYSTITIS Investigations Leukocytosis (elevated white blood cell count): (> 10,000/mcL) present in 52–63% of patients. Ultrasound Cholelithiasis is usually present (84–99%) Cholecystitis does not typically cause significant increases in lipase or liver biochemical tests Prognosis If left untreated necrosis, infection, and gangrene can occur NEPHROLITHIASIS Also known as kidney stones Epidemiology and risk factors 35–50% recurrence at 5 years Men affected 2–3 times more often than women Positive family history increases the risk (relative risk 2.6) NEPHROLITHIASIS Signs and Symptoms Rapid onset of excruciating back and flank pain, may radiate to the abdomen or groin Pain may be associated with nausea, vomiting, dysuria, or urinary frequency Abdominal tenderness unusual Hematuria (gross or microscopic) may be present, but absence does not rule out (LR+, 1.4; LR–, 0.49) NEPHROLITHIASIS Investigations Non-contrast renal CT is most accurate: (LR+, 48; LR−, 0.05) Determine composition of stones to prevent recurrence Urine culture, pH, and chemical analysis of retrieved stones Serum Calcium Multiple 24-hour urine analysis Types of kidney stones: Calcium oxalate stones 75% Calcium phosphate stones (CaPO4) 5% Uric acid stones 5–10% Struvite stones (MgNH4PO4) 5–15% Other: cystine and indinavir stones NEPHROLITHIASIS Prognosis Ureteral obstruction Pyelonephritis Sepsis Acute kidney injury is rare, occurring in patients with bilateral obstruction or obstruction of a solitary functioning kidney ACUTE PANCREATITIS Epidemiology Alcohol abuse (typically binge drinking) and choledocholithiasis (obstruction of common bile duct) cause 80% of acute pancreatitis cases 15–25% of cases are idiopathic, many of which may be due to microlithiasis or sphincter of Oddi dysfunction 34–67% of patients with idiopathic pancreatitis were found to have small gallstones ACUTE PANCREATITIS Signs & Symptoms Low-grade fevers (< 38.3°C) are common (60%). Pain may radiate to the back (50%) and may be exacerbated in the supine position. Nausea and vomiting are usually present (75%). Rebound is rare on presentation; guarding is common (50%). Periumbilical bruising (Cullen sign) is rare. Pancreatitis (and other diseases) can lead to retroperitoneal bleeding and flank bruising (Grey Turner sign), which is a rare but valuable clue if present. ACUTE PANCREATITIS (AP) Investigations Blood tests Lipase > 3 times the upper limit of normal Elevated amylase ALT or AST elevations > 100 international units/L suggest AP (sensitivity ≈ 55%, specificity ≈ 93%; LR+ 8–9) AST levels < 50 international units/L make AP unlikely (sensitivity, 90%; specificity, 68%; LR−, 0.15). 10% of patients with AP have normal levels of alkaline phosphatase, bilirubin, AST, and ALT. Imaging Transabdominal ultrasound in all patients to determine whether gallstones or common bile duct dilation present CHRONIC PANCREATITIS Epidemiology and Etiology Usually secondary to recurrent acute pancreatitis, primarily from alcohol abuse (70% of adult cases). CHRONIC PANCREATITIS Signs & Symptoms Chronic, disabling, mid-epigastric postprandial pain (80–100% of patients) Pain may radiate to the back and be relieved by sitting forward Abdominal bloating (30% of cases) Unintentional weight loss and diarrhea (68% of patients) Weight loss secondary to anorexia and malabsorption with steatorrhea Steatorrhea Manifestations include difficult to flush oily stools and weight loss Floating stools are not specific for steatorrhea. Bacterial gas may also cause stools to float. CHRONIC PANCREATITIS Investigations CT scan Prognosis Pancreatic cancer develops in 4% of patients Diabetes may develop due to concomitant destruction of pancreatic islet cells (28% of cases) DIVERTICULAR DISEASE Acute inflammation of outpouching of large intestine = diverticulitis Presence of outpouching = diverticulosis Epidemiology Develops in 5–10% of patients aged > 45 years, 50% in persons aged > 60 years, and 80% in those aged > 85 years Mean age of onset is 63 years DIVERTICULAR DISEASE Diverticulitis Signs and Symptoms Left lower quadrant tenderness: (LR+, 3.4; LR–, 0.41) May present with fever (45% of cases) Investigations Abdominal CT scan DIVERTICULAR DISEASE Prognosis Potential complications of diverticulitis: Abscess Peritonitis Sepsis Colonic obstruction Fistula formation DIFFERENTIAL DIAGNOSES Autoimmune & inflammatory conditions Inflammatory bowel disease (IBD) Ulcerative Colitis Crohn’s disease Celiac disease These conditions should be evaluated in the presence of chronic diarrhea and abdominal pain ABDOMINAL PAIN W/ DIARRHEA Potential causes of diarrhea Infectious Bacterial, viral, parasitic Antibiotic Side Effect Autoimmune/inflammatory Ulcerative colitis Crohn’s disease Celiac disease Endocrine Hyperthyroid Bile acid malabsorption Dietary Food intolerances Food sensitivities Functional GI conditions ABDOMINAL PAIN: KEY TAKEAWAYS Location, location, location? Location of pain, while relevant, is not necessarily highly predictive of diagnosis Assess severity of pain Determine timing and progression of symptoms Identify associated symptoms Determine patient history and risk factors FUNCTIONAL GI DISORDERS FUNCTIONAL GI DISORDERS Definition and evolving terminology Disorders of the Gut-Brain Interaction (DGBI) Limited abnormalities on diagnostic testing Symptom clusters Potential processes involved: Impaired GI motility Altered microbiome Visceral hypersensitivity Mucosal layer alterations FUNCTIONAL GI DISORDERS Difference between Functional Diarrhea (FD) or Constipation (FC) and IBS: IBS includes pain/visceral hypersensitivity, whereas FD and FC do not In both cases there is no clear cause that can be reliably tested IRRITABLE BOWEL SYNDROME (IBS) Epidemiology More than 1 in 4 adults in the general population meet the Rome IV criteria for Functional Bowel Disorders Adult Canada prevalence of IBS: 4.5% (3.6–5.4)(based on Rome IV) Based on Rome III: 9.5% (8.2–10.8) (Palsson 2020, UK, US, Canada)  IRRITABLE BOWEL SYNDROME (IBS) IBS Diagnostic Criteria: Rome IV Recurrent abdominal pain on average at least 1 day/week in the last 3 months, associated with two or more of the following criteria: 1. Related to defecation 2. Associated with a change in frequency of stool 3. Associated with a change in form (appearance) of stool * Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis https://theromefoundation.org/rome-iv/rome-iv-criteria/ ASSESSING STOOL CONSISTENCY Aliment Pharmacol Ther, Volume: 44, Issue: 7, Pages: 693-703, First published: 05 August 2016, DOI: (10.1111/apt.13746) ROME IV IBS SUBTYPES IBS-C (Constipation dominant) >25% of bowel movements with Bristol stool types 1 and 2 and 25% of bowel movements with Bristol stool types 6 and 7 and 25% of bowel movements with Bristol stool types 1 and 2 and >25% Bristol stool charts type 6 or 7. IBS-U (Unclassified) Patients who meet IBS criteria but whose bowel habits do not fall into the above categories. https://theromefoundation.org/rome-iv/rome-iv-criteria/ IBS-DIARRHEA Investigations: When is testing recommended? United European Gastroenterology and European Society for Neurogastroenterology and Motility Guidelines (2022): Recommends FOR limited blood testing in patients with suspected IBS‐D or Functional Diarrhea in the absence of alarm features* Complete blood count, C‐reactive protein, celiac disease (Moderate level evidence; recommendation strong) IBS-DIARRHEA Investigations: When is testing recommended? *Alarm features*: Unintentional weight loss Nocturnal diarrhea Tenesmus Passing of bright red blood in stool (haematochezia) High‐volume diarrhea, or very high number of bowel movements Suspicion of malnutrition Family history of colorectal cancer IBS-DIARRHEA Investigations: When is testing recommended? United European Gastroenterology and European Society for Neurogastroenterology and Motility Guidelines (2022): Recommends FOR fecal calprotectin evaluation in patients with suspected IBS‐D or Functional Diarrhea in order to exclude inflammatory bowel disease (moderate evidence; recommendation strong) IBS-DIARRHEA Investigations: When is testing recommended? United European Gastroenterology and European Society for Neurogastroenterology and Motility Guidelines (2022): Recommends FOR colonoscopy in patients with suspected IBS‐D or Functional Diarrhea older than 50 years, and in those with alarm features (moderate evidence; recommendation strong) Recommends FOR considering the diagnosis of bile acid diarrhea, and testing with SeHCAT or other biomarkers if available, or if not, a trial of treatment, in all patients with unexplained chronic diarrhea (High evidence; strong recommendation) IBS-DIARRHEA Investigations for IBS-D or Functional Diarrhea (FD) United European Gastroenterology and European Society for Neurogastroenterology and Motility Guidelines (2022): Recommends AGAINST routine diagnostic testing for small intestinal bacterial overgrowth (SIBO) in all patients with suspected IBS‐D or FD SIBO testing should be considered in cases with strong clinical suspicion based on the presence of predisposing conditions (e.g. gastrointestinalmotility diseases, gastrointestinal anatomical abnormalities, hypochlorhydria, various immune deficiency conditions, signs of malabsorption). (Moderate evidence; strong recommendation) Recommends AGAINST microbiota testing in patients with IBS‐D or FD, as the clinical relevance of its testing remains unclear (Low evidence; strong recommendation). CHRONIC CONSTIPATION Constipation is defined as difficult, unsatisfactory, or infrequent defecation (ESNM) Epidemiology More prevalent in females than males Prevalence increases with age Genetic predisposition CHRONIC CONSTIPATION Signs and Symptoms The most frequent symptoms of chronic constipation are straining and hard stools (ESNM guidelines) Chronic/functional constipation vs. IBS-C: symptoms with absence of pain/visceral hypersensitivity Digital rectal exam: detect stool in the rectal vault, anorectal masses, hemorrhoids, anal fissures, rectal prolapse, and rectoceles that may cause constipation CHRONIC CONSTIPATION Rome IV Functional Constipation Criteria: Straining with bowel movement Hard stools (Bristol 1‐2) Sensation of incomplete evacuation Sensation of anorectal obstruction Need for manual maneuvers to facilitate evacuation Less than 3 spontaneous bowel movements per week *present in 25% of bowel movements (ESNM 2022) *NB: absence of abdominal pain CHRONIC CONSTIPATION *Red Flag/Alarm features in Constipation* Blood in stool Weight loss Anemia Family history of colon cancer, celiac disease or inflammatory bowel disease Acute onset at age older than 50 Significant pain Vomiting, especially if recurrent Fever IRRITABLE BOWEL SYNDROME (IBS) Prognosis Not at increased risk for colorectal cancer Small increased risk of developing celiac and IBD 5 years post-diagnosis Quality of life an important factor to consider IRRITABLE BOWEL SYNDROME (IBS) Additional laboratory investigations? IgG food sensitivity testing SIBO testing SMALL INTESTINAL BACTERIAL OVERGROWTH (SIBO) Epidemiology & Etiology Patients with IBS 2.6 (95% CI 1.3–6.9) and 8.3 (95% CI 3.0–5.9) times more likely to have a positive SIBO test compared with healthy controls, using Glucose Hydrogen Breath Test (GHBT) and jejunal aspirate culture, respectively. Patients with diarrhea-predominant IBS more likely to have positive GHBT as compared with the other subtypes. (Ghosal et al 2020) SMALL INTESTINAL BACTERIAL OVERGROWTH (SIBO) Risk Factors Dysmotility (impaired motility of small intestine) Proton Pump Inhibitor (PPI) use Surgeries (gastric bypass) Conditions reducing acid secretion (H. pylori e.g.) Connective tissue disorders (Not significant based on Bohm 2020 study) SMALL INTESTINAL BACTERIAL OVERGROWTH (SIBO) Signs and Symptoms Limited research suggests that the most common symptom is diarrhea, followed by abdominal pain, and then bloating (Grace et al 2013) May also be asymptomatic A broader set of symptoms has been associated with SIBO: Diarrhea and/or constipation Esophageal reflux Dyspepsia Belching and/or flatulence Nausea Fatigue SIBO TESTING Duodenal aspirate via endoscopy is considered most accurate, however has limitations: Lack of standardization of procedure and interpretation of results No established cut-off value for defining the abnormal levels of bacterial growth, especially in different parts of the small intestine Invasive and very expensive Breath tests more commonly used Still relatively expensive: ~$200-$350 Lactulose breath test: sensitivity 42%; specificity 70.6% LR+ 1.43; LR- 0.82 Glucose breath test: sensitivity: 54.5% specificity: 83.2% LR+ 3.24; LR- 0.55 FOOD SENSITIVITY TESTING IMMUNE MEDIATED REACTIONS Food allergies, intolerances, and sensitivities (review) Allergy IgE mediated (Type I reaction) Short reaction time (minutes to hours) Sxs: Anaphylaxis, urticaria, vomiting Intolerance Lacking enzyme for digestion (lactose e.g.) Sxs: abdominal bloating, gas, diarrhea, constipation… Delayed sensitivity IgG-mediated? Delayed reaction: up to 72 hours Symptoms are varied FOOD SENSITIVITY TESTING Serum IgG sensitivity testing Theory Levels of serum IgG antibodies reflect the reactivity of a person’s immune system to specific food antigens Higher levels of antigen-specific serum IgG antibodies correspond to immune hyperreactivity to said antigens Elevated IgG levels correspond to a range of clinical symptoms Testing these levels will identify food sensitivities and inform dietary interventions (elimination and/or avoidance) to resolve these symptoms IGG FOOD SENSITIVITY TESTING Are elevated IgG antibody levels pathological? “In patients with IgE-mediated food allergy, increased production of allergen-specific IgE antibodies is observed as well as low production or lack of allergen-specific IgG1 and IgG4 antibodies.” “[…] the presence of specific IgG antibodies directed against food allergens reflects natural defence reactions of a body to allergens penetrating due to the damage of the epithelial barrier.” Gocki J, Bartuzi Z. Role of immunoglobulin G antibodies in diagnosis of food allergy. Advances in Dermatology and Allergology/Postȩpy Dermatologii i Alergologii. 2016 Aug;33(4):253. IGG FOOD SENSITIVITY TESTING Do elevated IgG antibody levels correspond to symptoms? “Forty-five patients (62%) were IgG4 positive for a number of foods, mainly egg, milk, casein and wheat. None of the patients with IgG4-positive testing showed adverse reactions, neither immediate nor delayed, to the corresponding food.” (Antico et al. 2011) IGG FOOD SENSITIVITY TESTING Do elevated IgG antibody levels correspond to symptoms? n=21 000 Results: The levels of food-specific IgGs were variable both in healthy and in symptomatic Chinese adults. Author conclusion: Demographic factors, the type of food and specific chronic symptoms should be considered before food elimination treatment based on IgG testing in patients with chronic symptoms is used in clinical practice. Zeng Q, Dong SY, Wu LX, Li H, Sun ZJ, Li JB, Jiang HX, Chen ZH, Wang QB, Chen WW. Variable food- specific IgG antibody levels in healthy and symptomatic Chinese adults. PloS one. 2013 Jan 3;8(1):e53612. IGG FOOD SENSITIVITY TESTING Do IgG antibody levels correspond to symptoms? Participants: 37 patients with IBS, 28 patients with functional dyspepsia Control: 20 healthy controls Outcomes: Serum IgG levels Results: Serum IgG antibody titres to some common foods increased in IBS and FD patients compared to controls. But there is no significant correlation between symptom severity and elevated serum food antigen-specific IgG antibodies in these patients. Zuo, X.L., Li, Y.Q., Li, W.J., Guo, Y.T., Lu, X.F., Li, J.M. and Desmond, P.V. (2007), Alterations of food antigen-specific serum immunoglobulins G and E antibodies in patients with irritable bowel syndrome and functional dyspepsia. Clinical & Experimental Allergy, 37: 823- 830. https://doi.org/10.1111/j.1365-2222.2007.02727.x IGG FOOD SENSITIVITY TESTING Do IgG antibody levels correspond to symptoms? “In the light of current scientific knowledge, the IgG-specific antibody-mediated reactions are a body's natural and normal defensive reactions to infiltrating food antigens, which are considered as pathogens. On the other hand, specific IgG antibodies against food allergens play a crucial role in the induction and maintaining of immunological tolerance to food antigens” (Gocki and Bartuzi 2012) FOOD SENSITIVITY TESTING Do elimination diets based on IgG testing have clinical benefit for IBS? Participants: 150 adults diagnosed with IBS Intervention: An elimination diet based on foods elevated in IgG testing Control: Sham diet Outcomes: IBS symptom severity and global rating scores Results: Patients in the true diet group experienced a 10% greater reduction in symptom severity than those allocated to the sham diet Atkinson W, Sheldon TA, Shaath N, Whorwell PJ. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Gut. 2004 Oct 1;53(10):1459-64. FOOD SENSITIVITY TESTING Do elimination diets based on IgG testing have clinical benefit for IBS? Participants: 21 adults diagnosed with migraine and IBS Intervention: Crossover trial of baseline diet, IgG-based elimination or provocation diet, interchange of elimination and provocation diets Outcomes: IBS symptom severity score and headache parameters Results: Statistically significant improvements in some items of IBS symptom severity score, quality of life score, and some headache parameters. Aydinlar EI, Dikmen PY, Tiftikci A, Saruc M, Aksu M, Gunsoy HG, Tozun N. IgG-based elimination diet in migraine plus irritable bowel syndrome. Headache: The Journal of Head and Face Pain. 2013 Mar;53(3):514-25. FOOD SENSITIVITY TESTING Do elimination diets based on IgG testing have clinical benefit for IBS? Participants: 77 adults with diagnosed IBS-D, 26 healthy controls Intervention: Elimination diet based on elevated serum IgG antibodies Control: No control intervention Outcomes: IBS symptom questionnaire Results: 39 out of 77 patients diagnosed with IBS-D had elevated IgG antibodies for the 14 food antigens tested. 4 of the healthy controls had elevated levels. 35 of the IBS-d patients followed an elimination diet and had statistically significant reductions in their IBS questionnaire scores. Guo H, Jiang T, Wang J, Chang Y, Guo H, Zhang W. The value of eliminating foods according to food-specific immunoglobulin G antibodies in irritable bowel syndrome with diarrhoea. Journal of International Medical Research. 2012 Feb;40(1):204-10. FOOD SENSITIVITY TESTING Summary Lack of published research to suggest a clear association between elevated serum IgG levels and clinical symptoms Mixed data suggests some improvement in IBS (and other) symptoms following an IgG-based elimination diet However: Studies are few and sample sizes are generally small Symptom improvements may be due to elimination of commonly aggravating foods in IBS, such as dairy and wheat (Hunter 2005) FOOD SENSITIVITY TESTING Important considerations before testing Cost of testing Potential harms Depending on results, subsequent elimination diet can be very restricted Risk of malnutrition Risk of disordered eating PATIENT CENTERED CONSIDERATIONS  PATIENT-CENTERED APPROACHES Understand impact of symptoms on quality of life Validate symptoms and impact Asking about symptom-specific anxiety can help understand and address patient concerns Question patients with chronic diarrhoea about fecal incontinence using appropriate phrasing (UEG/USNM 2022) PATIENT-CENTERED APPROACHES Educate patient on pathogenesis of pain, including role of gut- brain axis, and psychosocial factors contributing to pain Chronic Disorders of Gut-Brain Interaction pain is real Pain is perceived from sensory signals that are processed and modulated in the brain Peripheral factors can drive increased pain Pain is modifiable  PATIENT-CENTERED APPROACHES Approach to patient dialogue around testing Reinforce the importance of ruling out potentially threatening structural etiologies Talk about Disorders of Gut-Brain Interaction before testing, explaining that negative test results are evidence of DGBI Set shared goals and expectations for pain management “Phrase the diagnosis as “You have IBS”. This use of qualified language increases patient acceptance, reduces apprehension, and provides a framework to build upon for treatment recommendations, medication adherence, and a positive patient- provider relationship. 12 Linedale EC, Chur-Hansen A, Mikocka-Walus A, Gibson PR, Andrews JM. Uncertain diagnostic language affects further studies, endoscopies, and repeat consultations for patients with functional gastrointestinal disorders. Clin Gastroenterol Hepatol 2016; 14:1735-41.e1.  PATIENT-CENTERED APPROACHES Approach to patient dialogue around diagnosis Set shared goals and expectations for pain management “Phrase the diagnosis as “You have IBS” instead of “We think you have IBS”. This use of qualified language increases patient acceptance, reduces apprehension, and provides a framework to build upon for treatment recommendations, medication adherence, and a positive patient-provider relationship Linedale EC, Chur-Hansen A, Mikocka-Walus A, Gibson PR, Andrews JM. 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