GASTROINTESTINAL DILEMMAS
From the American Academy of Family Physicians’ 2008 Scientific Assembly, October 2008, San Diego, CA
John B. Pope, MD, Professor of Clinical Family Medicine, Louisiana State University Health Science Center,
Shreveport
Educational Objectives
| The goal of this program is to improve management of celiac disease (CD) and irritable bowel syndrome (IBS). After
hearing and assimilating this program, the clinician will be better able to:
|
 | 1. Recognize common presentations of CD.
|
| 2. Explain risks associated with CD.
|
| 3. Identify candidates for CD screening.
|
| 4. List symptoms characteristic of IBS.
|
| 5. Counsel patients about treatment of IBS based on clinical data.
|
Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee
to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest.
Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary
business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose.
Acknowledgements
Dr. Pope was recorded in San Diego, CA, at the 2008 Scientific Assembly, presented September 17-21, 2008, by the
American Academy of Family Physicians (AAFP). The Audio-Digest Foundation thanks Dr. Pope and the AAFP for
their cooperation in the production of this program.
| Celiac disease (CD): small-bowel disorder characterized by mucosal inflammation (can involve epithelium and extend
beyond lamina propria); results in villous atrophy of small bowel structure and hyperplasia of Lieberkühn’s
crypts; occurs after exposure to gluten; when gluten withdrawn from diet, changes reversed; difficult to diagnose
|
| Epidemiology: classically seen in whites (eg, Northern European ancestry), but also reported in those of Middle Eastern,
South American, Asian, and Saharan North African descent; recent studies show high prevalence (in at-risk populations,
1 in 100); incidence higher in people with positive family history of CD, IgA deficiency, autoimmune
diseases, type 1 diabetes, hypothyroidism, connective tissue diseases (eg, Sjögren’s syndrome), or Down syndrome;
diagnosis 3 times more common in women than in men
|
| Pathophysiology: gliadin component of gluten triggers complex inflammatory cascade; associated with HLA-DQ2
and HLA-DQ8 gene loci; adaptive immune response involves CD4 cells; innate immunity involves cytotoxic lymphocytes
and natural killer cells; changes predominantly in jejunum and duodenum
|
| Forms of CD: atypical—villous atrophy with milder or atypical symptoms (eg, iron deficiency anemia, osteoporosis,
short stature, infertility); more common; silent—villous atrophy with no symptoms; classical—villous atrophy; malabsorption
(eg, steatorrhea, weight loss, vitamin and mineral deficiency, anemia); resolution of symptoms and correction
of mucosal lesions after gluten withdrawn from diet; severity of disease does not necessarily correlate with
symptoms; increased intraepithelial lymphocytes with presence of preinfiltrative lesions; hyperplastic lesions lead to
shrinkage and destruction of villi; alterations can lead to other symptoms, eg, blood loss; latent—1) CD previously diagnosed
and improves after gluten-free diet; CD remains silent even after adoption of normal diet (≈20% of patients
remain asymptomatic and have normal villous architecture; atrophy recurs in some patients); can be transient; variable;
2) patients develop CD after normal mucosa diagnosed while on normal diet; potential—no evidence of CD on
biopsy, but patient has immunologic abnormalities characteristic of CD (eg, positive serology); patients often show
genetic predisposition (eg, DQ2 genetic marker); first-degree relatives with CD increase risk for active disease by 6%
to 20%
|
| Clinical manifestations: classic presentation (child with life-threatening malabsorption) rarely seen; presentation of
adult with, eg, diarrhea or weight loss, more common; shift from traditional presentation may be due to longer breast-
feeding or delayed (>4 mo) introduction of gluten into diet; classic signs—diarrhea; fatty stools; steatorrhea; increased
flatulence; explosive bowel movements; malabsorption; growth failure and weight loss in children; anemia; neurologic
disorders; osteopenia; osteoporosis; young infants—bloating; diarrhea; malabsorption; failure to thrive; children—
abdominal pain; mouth lesions; stomatitis; angular chelitis; aphthous ulcers; atopic dermatitis; seizure disorder; young
adults—dermatitis herpetiformis (DH); diarrhea; increased flatulence; floaty stools; mouth ulcers; alopecia; adults—
additional symptoms of osteopenia, osteoporosis, and anemia; patients with long-standing problems develop more serious
symptoms (eg, osteoporosis, lymphoma, chronic liver disease); older adults—diarrhea; bloating; belching; nonspecific
complaints
|
| Subclinical CD: mild; undetected for long time; symptoms (eg, fatigue, iron deficiency anemia) subtle; spectrum wide,
with variable severity; be aware that CD can account for unexplained symptomatology; risks associated with undiagnosed
CD—nutritional deficiency; osteoporosis; autoimmune disorders; risk for malignancy less than in patients with
diagnosed CD and malabsorption; malignancy risk decreases once patients in remission on gluten-free diet; diabetes; collagen
vascular disease; thyroiditis
|
| Nutritional deficiencies: iron; may lead to recurrent abdominal pain, mood changes, stomatitis, poor appetite, and
recurring diarrhea
|
| Nongastrointestinal (non-GI) manifestations: neuropsychiatric diseases—polyneuropathies; memory disturbances;
depression; anxiety; pathogenesis unclear; data suggest headache and ataxia could be sole manifestations of CD;
high prevalence of arthritis (untreated patients typically do worse); iron deficiency; osteopenia; osteoporosis (correcting
diet does not completely reduce risk for fracture or bone abnormality); hyposplenism (uncommon); kidney disease (IgA
deposition in ≈33% of cases of CD; typically, no clinical manifestations, but CD can cause renal failure); malignancy—
overall mortality in GI malignancies increased; 40- to 100-fold increased risk for non-Hodgkin’s lymphoma; decreased
risk for breast and lung cancers; effect of gluten-free diet uncertain; DH—papulovesicular rash; blisters rupture fairly
rapidly; usually on extensor surfaces of extremities, and on trunk, elbows, knees, and face; deposition of IgA in nonaffected
tissue; antibodies against tissue transglutaminase (tTG) elevated; 85% of patients with DH have CD; itching and
burning resolve after lesions rupture (resembles herpes); type 1 diabetes—uncertain whether affected by gluten-free
diet; selective IgA deficiency—look at IgG levels to diagnose CD; Down syndrome—24-fold increase in biopsy-proven
CD, compared to general population; liver disease—elevated aspartate aminotransferase (AST), alanine aminotransferase
(ALT), or γ-glutamyl transferase (GGT) levels; CD associated with congenital liver fibrosis, massive steatosis,
hepatitis, primary biliary cirrhosis, and autoimmune hepatitis; may improve on gluten-free diet; early detection important;
reproductive issues—infertility associated with untreated CD; menstrual abnormalities (eg, later menarche, earlier
menopause); abnormalities in sperm motility and morphology; myocarditis; cardiomyopathy; atrophic glossitis common
in young adults and adults; pancreatitis
|
| Candidates for screening: patients with chronic diarrhea, malabsorption, weight loss, abdominal distention, unexplained
elevated serum transferase levels, short stature, delayed puberty, iron deficiency anemia, miscarriages, or infertility;
symptomatic patients at high risk for CD—those with, eg, type 1 diabetes, autoimmune endocrinopathies,
first-degree relative with CD, Down syndrome, Turner’s syndrome, Williams syndrome; consider testing patients with
irritable bowel syndrome (IBS), aphthous stomatitis, autoimmune diseases, migraines, and dental enamel hyperplasia;
screening not recommended for general population or patients with osteoporosis; before testing, patients must be on
gluten-containing diet; look for clinical feature or complaint associated with CD
|
| Serologic testing: antigliadin antibodies (AGA) less sensitive and specific than IgA-based anti-tTG antibodies and antiendomysial
antibodies (AEMA); second-generation AGA testing with enhanced specificity “might make a comeback”;
AEMA—high sensitivity and specificity; more expensive; harder to perform; immunoassay test; must be done with tTG
test; normal results can be seen in patients on gluten-free diets (resume regular diet for several weeks before testing); consider
referral for malabsorption testing (eg, D-Xylose absorption testing, lactulose adherence testing); antibody levels remain
elevated for variable time after beginning gluten-free diet
|
| Small bowel biopsy: gold standard for diagnosis; identifies villous atrophy and crypt hyperplasia; perform in patients
with positive AEMA or anti-tTG test result; not necessary in patients with biopsy-proven DH; multiple (4-8) samples
in multiple areas required; look for characteristic changes (eg, scalloping of edges of duodenum, loss of plicae circularis,
mosaic pattern); diagnosis sometimes presumptively established based on concordance between serologic results
and biopsy findings; diagnosis confirmed by improvement of symptoms with gluten-free diet
|
| Diagnostic approach for low-risk patients: negative serologic test results—consider selective IgA deficiency
(test for IgG antibodies); rate for false-negative test results, ≤15% (repeat test or perform small bowel biopsy); consider
other conditions, eg, bacterial overgrowth, Crohn’s disease, cow milk intolerance, eosinophilic gastroenteritis,
Giardia infection, Whipple’s disease, tuberculosis, radiation exposure, autoimmune enteropathies; negative predictive
value of HLA-DQ2 and -DQ8 markers high; positive serologic test results and negative small bowel biopsy—
consider sampling error; false-positive serologic test results rare, but possible; consider high-gluten diet and repeat biopsy;
negative serologic test results and negative biopsy—unclear why some patients with IBS-type symptomatology
respond to gluten-free diet (“it’s not absolutely cut and dry”); in most low-risk patients, small bowel biopsy not necessary
(in moderate or high-risk patients, diagnosis based on serology and small bowel biopsy before dietary treatment)
|
| Adherence and follow-up: antibody levels correlate with compliance with gluten-free diet; baseline usually reached
in 3 to 12 mo; persistently elevated levels indicate intentional or inadvertent exposure to gluten; gluten-free diet expensive
and adherence difficult; if antibody levels not initially elevated, follow-up difficult; possible variation between
laboratory tests (use same manufacturers); minor dietary infractions can increase risk for associated diseases
|
| More about screening: no demonstrated benefit to screening asymptomatic patients; screening may be appropriate
in subclinical group with minor laboratory abnormalities and symptoms; other tests—small bowel radiography and
capsule endoscopy do not provide specific diagnosis
|
| Management: consult dietitian; educate patient about disease process; lifelong adherence to gluten-free diet required;
treat nutritional deficiencies; patients need support; continuous long-term follow-up by multidisciplinary team most
beneficial; gluten-free diet—elimination of dietary wheat, rye, and barley; oats may be acceptable, but often contaminated
in collection process; benefits of rigid gluten avoidance not proven; most authorities advocate strict adherence,
due to associated risks; supplement nutritional deficiencies; prevent bone loss (perform dual-energy x-ray absorptiometry
[DEXA]); pneumococcal vaccine, polyvalent (Pneumovax 23); monitor response; gluten rechallenge not recommended
unless diagnosis uncertain (gliadin shock phenomenon of intense inflammatory response can occur);
persistent symptoms usually due to poor compliance or inadvertent gluten ingestion (also, consider, eg, IBS or lactose
intolerance); refractory sprue—can be severe; progressive malabsorption can lead to death; typically treated with immunosuppression
or corticosteroids; risk for ulcerative jejunitis or intestinal lymphoma can be predicted by performing
biopsy and looking for aberrant T-cell monoclonality
|
Irritable Bowel Syndrome
| Background: chronic abdominal pain and altered bowel habits in absence of organic cause; most commonly diagnosed
GI condition; highly prevalent in women and younger patients; 2:1 female predominance
|
| Causes: GI motility; visceral hypersensitivity; microscopic inflammation; undiagnosed infection; bile acid malabsorption;
studies conflict; uncertain
|
| Psychosocial dysfunction: anxiety, depression, phobias, and somatization; patients rarely meet criteria for major
psychiatric disorder, and those who do not seek care psychologically indistinguishable from healthy controls; consider
possible history of sexual or physical abuse
|
| Clinical manifestations: abdominal pain—cramping; periodic exacerbations; in left lower quadrant or other areas;
typically with eating or emotional distress; symptoms improve with defecation; be concerned about patients with anorexia,
malnutrition, and weight loss (rare unless psychiatric problem present); typically not nocturnal; progressive pain
alarming; altered bowel habits—diarrhea and/or constipation; large-volume, bloody, or nocturnal (ie, awakens patient
at night) diarrhea and greasy stools not characteristic of IBS (consider other organic causes); constipation can be
periodic; upper GI tract symptoms—gastroesophageal reflux disease (GERD); dysphagia; early satiety; dyspepsia;
nausea; noncardiac chest pain; other—impaired sexual function; dysmenorrhea; dyspareunia
|
| Diagnostic approach: use selective testing to identify symptom complex compatible with IBS; if no alarm symptoms
(eg, weight loss, bleeding, dysphagia, waking at night) present, then routine use of endoscopy, radiography, fecal occult
blood test (FOBT), and stool studies not recommended; since patients ≥50 yr of age at higher risk for, eg, colorectal
cancer, additional testing may be performed; if alarm signs or symptoms present, nonjudgmental assessment of symptoms
(ask open-ended questions about, eg, dietary exposures) required; complete blood cell count (CBC) and chemistry
panel should be normal (if abnormal, consider other condition); if diarrhea predominates, consider CD, parasite, or infectious
origin; 24-hr stool studies may be helpful in certain cases; diagnostic yield low with routine flexible sigmoidoscopy;
colonoscopy recommended for patients ≥50 yr of age with IBS symptom complex; if patients worsen after
symptomatic therapy, consider other testing; consider physical or sexual abuse or other psychologic or social factors in
refractory or severe IBS; consider referral for, eg, motility studies, fecal colonic transit studies, manometry
|
| Treatment: no known cure for chronic IBS; symptomatic relief possible; address patient concerns; consider exacerbating
factors; therapeutic patient-physician relationship critical (be nonjudgmental and understanding; recognize IBS as
actual debilitating entity); dietary modification—consider lactose intolerance and exclusion of flatulence-inducing
foods; role of food allergies unclear; encourage dietary fiber (bulking agents recommended, but evidence of effectiveness
poor); psychosocial therapy helpful for motivating patients who associate symptoms with stressors; data about
hypnosis, biofeedback, and psychotherapy show some benefits in reducing stress and promoting healthy behaviors; in
some reviews, behavioral therapy shown more effective than placebo
|
| Medications: specific symptoms determine choices; avoid long-term use; no good evidence of long-term effectiveness;
antispasmodics (eg, dicyclomine) frequently used, but benefits unclear; effectiveness variable; placebo effect high; antidepressants
and selective serotonin reuptake inhibitors (SSRIs) may modulate pain; tricyclic antidepressants (TCAs)
slow transit time (may help diarrhea-predominant IBS); conflicting data; antidiarrheal agents (eg, loperamide) fairly effective,
but do not improve global IBS symptoms; limited usefulness of benzodiazepines (may lead to habituation and
rebound); alosetron may help with abdominal pain, but associated with ischemic colitis; data show 5-hydroxytryptamine
4 receptor agonists increase colonic motility in constipation-predominant IBS, but under investigational
drug protocol, due to cardiovascular effects; some reports of antibiotics used for bloating; limited evidence for herbal
and psychologic therapy; consider herbal therapy and probiotics; some data (but nondefinitive) on psychotherapy and
acupuncture
|
| Approach: mild symptoms—education; reassurance; dietary modification; moderate symptoms—monitor symptoms;
look for precipitating factors; modify diet and behavior; consider psychotherapy; use drugs for constipation or diarrhea;
severe—consider underlying psychiatric impairment; behavioral modification; psychoactive drugs
|
Suggested Reading
Burgin-Wolff A et al: Two-step approach for diagnosing celiac disease. Clin Gastroenterol Hepatol 6:1173; author reply
1173, 2008; Curtiss FR: Irritable bowel syndrome and antidepressants. J Manag Care Pharm 14:882, 2008; Faresjo A et
al: Self-reported use of pharmaceuticals among patients with irritable bowel syndrome in primary care. J Manag Care Pharm
14:870, 2008; Ford AC et al: Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome:
systematic review and meta-analysis. BMJ 337:a2313, 2008; Freeman HJ: Neurological disorders in adult celiac disease. Can J
Gastroenterol 22:909, 2008; Jones R: Treatment of irritable bowel syndrome in primary care. BMJ 337:a2213, 2008; Kurppa
K et al: Changing phenotype of celiac disease after long-term gluten exposure. J Pediatr Gastroenterol Nutr 47:500, 2008;
O'Shea U et al: Investigation of molecular markers in the diagnosis of refractory coeliac disease in a large patient cohort. J Clin
Pathol 61:1200, 2008; Raivio T et al: Comparison of a novel whole blood transglutaminase-based ELISA with a whole blood
rapid antibody test and established conventional serological celiac disease assays. J Pediatr Gastroenterol Nutr 47:562, 2008;
Shekhar C et al: Tailor treatment to the patient in irritable bowel syndrome. Practitioner 252:23, 2008.
|
