Inflammatory Bowel Disease

Georgia Allen, DO
Internal Medicine
Assistant Professor, Primary Care Dept.
January 14, 2021
Objectives
 Explain the etiology and pathology of Ulcerative
Colitis and Crohn’s disease.
Understand the differences between UC and CD
Describe the clinical presentation of IBD
Recognize extraintestinal manifestations of IBD
Describe the basic work-up for a patient with
suspected IBD
Understand different modes of therapy for both UC
and CD
Understand complications from these diseases
Definition
Inflammatory bowel
disease is simply
Ulcerative colitis- chronic inflammatory
inflammation of the condition characterized by relapsing and
bowel, and is
comprised of two remitting episodes of inflammation on
major disorders: the mucosal layer of the colon that starts
ulcerative colitis
and Crohn’s disease at the colon and extends proximally in a
continuous fashion.
Crohn’s Disease- transmural
inflammation that may involve the entire
GI tract from mouth to perianal area and
typically consists of “skip lesions”.
Epidemiology
Incidence of IBD varies geographically, by region and
even by season, leading many to believe there are both
genetic and environmental components to these
diseases.
In one of the largest studies in the US, the prevalence
of UC was 238/100,000 adults, and the prevalence of
CD was 201/100,000 adults.
Incidence of both of these diseases has been changing
over time. At one point ulcerative colitis was more
common, now ulcerative colitis and Crohn disease is
roughly equivalent in North America and Europe.
Risk Factors
 Age of onset 15-40 years
Pathogenesis of  Incidence of IBD lower in black and Hispanic
IBD remains
populations compared to whites
unclear, some risk
factors have been  ~10-25% of patients with IBD have first degree
identified. relative with IBD as well
 Smoking increases risk of Crohn’s disease
 “Western” diet increases risk of CD and possibly UC
 Increased physical activity decreases risk of CD,
obesity may alter course of disease
 Some infections may be a risk factor for developing
IBD
 Breastfeeding is protective against CD
 Other questionable risk factors: antibiotic use,
NSAID’s, oral contraceptives, stress, sleep deprivation
Ulcerative Colitis
Pathology, Presentation, Diagnosis, Management
Pathophysiology
Recurring episodes of inflammation limited to the
mucosal layer of the colon. Commonly involving the
rectum and extending proximally in continuous fashion.
Not yet fully understood…
Believed to be a dysregulated proinflammatory response
to gut flora.
Also, may have MUC2 gene mutation which codes for a
protective mucin that coats the gut epithelium. HLA
alleles may play a role as well.
Patient Presentation

Diarrhea, usually associated with blood

Other symptoms include: coliky abdominal pain, tenesmus,
incontinence. May also have constipation in patients with
distal disease
Onset is gradual and symptoms are progressive over weeks
Severity ranges from mild (4 or less stools/day with or
without blood) to severe (>10 stools/day with severe
cramps and continuous bleeding)
Other systemic symptoms include: fever, fatigue, weight
loss, dyspnea and palpitations (due to anemia)
Physical Exam
Mostly benign
May have fever,
tachycardia, hypotension
May have abdominal
tenderness
May have rectal bleeding
on exam
Extraintestinal Manifestations
Musculoskeletal: arthritis, akylosing spondylitis,
osteoporosis
Eye: uveitis and episcleritis
Skin: erythema nodosum and pyoderma gangrenosum

GI: primary sclerosing cholangitis, fatty liver, autoimmune

liver disease
Hemetologic: increased risk of thromboembolism,
autoimmune hemolytic anemia
Pulmonary: airway inflammation, parenchymal lung disease
Differential Diagnoses
Any causes of Crohn’s disease
colitis or proctitis
can mimic Infectious colitis- bacterial, parasitic,
Ulcerative Colitis
amebic, C diff
Radiation colitis
Medication induced colitis (NSAID)
Graft vs host disease
Diverticular colitis
Gonorrhea or HSV proctitis
Work-up
Lab tests: CBC, ESR, metabolic panel, stool studies
Anemia- chronic disease and blood loss
Elevated ESR- non-specific inflammatory marker
Low albumin- PLE
Electrolyte abnormalities- chronic diarrhea
 Stool tests: stool culture, C. diff toxin, O&P, Giarida, fecal calprotectin
Imaging: most images will be normal in mild UC
Abdominal xray, ultrasound, CT and MRI may show non-specific
thickening of the bowel wall
Barium enema may show abnormal collections of barium as well as
areas of ulceration
Endoscopy and colon biopsy
“Lead pipe
colon”
Diagnosis
Chronic diarrhea (>4 Severity classified by
weeks) and evidence of extent of disease:
active inflammation on
endoscopy as well as Ulcerative proctitis
chronic changes on Proctosigmoiditis
biopsy
Left-sided or distal UC
Plus, exclusion of other
Extensive colitis
causes of colitis by
history, lab studies, Pancolitis
endoscopy and biopsy
Endoscopy & Biopsy
Endoscopy shows
erythematous and
edematous mucosa
with erosions,
friability and
bleeding based on
severity of disease.

Biopsy shows:
distortion of crypt
architecture, mucin Pseudopoly
cell depletion in ps
epithelium, Paneth
cell metaplasia,
increased lamina
propria,
inflammatory cells
Management
Management is 5-aminosalicylic acid (5-ASA)
based on disease
extent and clinical suppositories/enemas. Preferred over
severity. Different topical corticosteroid preparations.
management to
induce remission Oral 5-ASA preparations if fail topical
and maintain
remission as well.
or unable to tolerate.
Combination of oral/topical 5-ASA and
corticosteroid preparations.
Oral steroids for flares and to induce
remission.
Management of severe disease
IV or oral steroids for extended periods used to induce remission
If the patient has fever and/or any other toxic symptoms, IV
antibiotics should be started
Maintenance therapy: oral 5-ASA, azathioprine (AZA), 6-
mercaptopurine (6-MP), or anti-TNF (infliximab/adalimumab)
If the symptoms are severe (fulminant)- progressing to toxic
megacolon/perforation
NPO, IV fluids, IV antibiotics
Refractory cases
Cyclosporine
Infliximab
Colectomy
Acute complications
Severe bleeding- massive
hemorrhage may necessitate
transfusions and urgent
colectomy
Toxic megacolon- severe colitis
may progress to enlarged colon
and signs of systemic toxicity as
inflammatory process extends
into muscle layers of the colon
Perforation- commonly occurs
with above, is a surgical
emergency. Perforation with
peritonitis has about a 50%
mortality rate.
Chronic Complications
Strictures
Caused by repeated episodes of inflammation
Most common in the rectosigmoid colon
Cause symptoms of obstruction
Colorectal cancer- risk based on severity and duration
of disease
Incidence ~ 2.5% after 20yrs and 7.6% after 30yrs of
disease
Mortality- slightly higher mortality rate than the
general population
This number is decreasing over time!
Crohn’s Disease
Pathology, Presentation, Diagnosis, Management
Pathophysiology

Transmural inflammation that can affect the entire GI tract

from mouth to anus in segmental fashion (skip lesions)
Rectum is usually spared (unlike UC)
Believed to be caused by dysregulated immune system,
genetic and environmental factors.
Studies showing increased rate of DR5 DQ1 HLA
haplotype in CD patients.
Patient Presentation
More varied presentation than patients with UC. Can be
asymptomatic, and many have symptoms years before
diagnosis.
Diarrhea is most common symptom. May have microscopic
bleeding, rarely present with gross hematochezia.
Other symptoms: crampy abdominal pain, perianal drainage,
steatorrhea, fatigue, weight loss
More common to have extraintestial manifestations than UC
Physical Exam
Exam will be varied depending on severity and
location of disease
Abdominal pain, possible abdominal mass palpable
Apthous ulcers in the mouth
Perirectal fistulas, fissures, abscesses
What are fistulas?
Tracts caused by
transmural inflammation
that connect two
epithelial-lined organs.
Enterovesical (bladder)
Enterocutaneous (skin)
Enteroenteric (bowel)
Enterovaginal (vagina)
Extraintestinal Manifestations
Skeletal- arthritis (large joints), ankylosing spondylitis,
osteopenia/porosis (steroid use)
Eye- uveitis, iritis, episcleritis

Skin- erythema nodosum and pyoderma gangrenosum

Pumonary- chronic inflammatory processes
GI- Primay sclerosing cholangitis
Heme- Thromboembolism
Differential Diagnoses
Differential can
vary with site of
involvement and
chronicity of Irritable bowel syndrome
symptoms.
Lactose intolerance
Early symptoms Infectious colitis
of CD may be
mild and non- Ulcerative colitis
specific, therefore
diagnosis may not
Depending on location of disease:
be made until appendicitis, diverticulitis, ischemic
more severe
disease. colitis, endometriosis
Work-up
Laboratory: CBC, CMP, ESR, CRP, serum iron, vit B12
Anemia (chronic disease/iron deficiency), elevated
inflammatory markers and Vit B12 deficiency
Stool: routine culture, O&P, C diff toxin
Stool would be negative in CD
Imaging- barium enema, upper GI with SBFT, CT and MRE
Looking for inflammation, strictures, length of colon
Wireless capsule endoscopy- swallow capsule and takes
video throughout GI tract
Can visualize lesions, no radiation exposure
Colonoscopy and biopsy
Xray showing
ileus

MRE
image
Cobblestoning
seen with barium
study
Diagnosis
Clinical history and
laboratory studies
suggestive of Crohn’s
disease and ruling out
other disease processes.

Diagnosis is usually
established with
endoscopic or imaging
findings
Endoscopy & Biopsy
Endoscopy:
Ulcerations, may be
large enough to
demaracate islands
of mucosa
(“cobblestoning”),
fistulas, strictures,
thickened mesentary
encasing bowel
(“creeping fat”)

Biopsy: transmural
inflammation,
fistulas, crypt
abscesses,
noncaseating
granulomas
Management of mild to moderate CD
Many therapies exist for Crohn’s disease. Choice of
medication is based on location and severity of
disease, as well as induction/maintenance medication.
5-aminosalicylates (5-ASA) – oral
Antibiotics (Ciprofloxacin, Metronidazole)
Glucocorticoids – oral
Non-systemic glucocorticoids (Budesonide)
Immunomodulators (Azathioprine, 6-mercaptopurine,
methotrexate)
Biologics (Inflixamab, Adalimumab)
Other therapies
Probiotics have been shown to be helpful in some
patients
Dietary modifications: lactose avoidance, low carb
diet, fiber?, other elimination diets based on individual
triggers
Remember your viscerosomatic reflexes!
Management of severe CD
For patients who fail outpatient management,
hospitalize for IV steroids to induce remission
If not responding, patient may need bowel rest (NPO)
and total parenteral nutrition (TPN)

Total enteral nutrition of amino based formulas is

being used in some centers.
Complications
Varied based on extent of disease: strictures, fistulas,
obstruction, perforation
Conflicted data exist about risk of colorectal cancer.
Some studies say about the same risk as UC, but
depends on extent and duration of disease.
Mortality risk is varied, ranging from no increased risk
to a fivefold increased risk of death.
UC vs CD
Is there a lab test Antibody tests are showing promise in
to aid in the
diagnosis of distinguishing Ulcerative Colitis from
IBD??? Crohn’s disease!
Perinuclear antineutrophil cytoplasmic
antibody (pANCA) may be + in UC
Anti-Saccharomyces cerevisiae
antibodies (ASCA) may be + in CD
The only problem is the tests are only
about 40-60% sensitive, so not yet
useful in diagnosis.
Ulcerative Colitis vs Crohn’s Disease
References
Harrison’s Principles of Internal Medicine, 18th
Edition, 2012. Chapter 295. Inflammatory Bowel
Disease.
www.uptodate.com
Sections on Ulcerative Colitis and Crohn’s Disease
An Osteopathic Approach to Diagnosis and Treatment,
3rd Edition. Chapter 114. Gastrointestinal
Applications.
www.naspghan.org
Sections on IBD
Break?
Irritable Bowel Syndrome

Georgia Allen, DO
Internal Medicine
Assistant Professor, Primary Care Dept.
Objectives
Recognize the epidemiology of irritable bowel
syndrome
Be able to define IBS using the Rome III criteria
Understand key factors that play a role in the
pathogenesis of IBS
Know how a patient with IBS may present and what a
basic work-up would entail
Recognize different management modalities for IBS
Definition
GI disorder
characterized by chronic
abdominal pain and
altered bowel habits in
the absence of structural
abnormalities or any
organic cause.
Previously thought of as
solely a somatic
manifestation of
psychological stress
Epidemiology
Most commonly diagnosed GI condition
25-50% of all GI referrals
Most patients diagnosed before age 45
Women are 2 times more likely than men to be
diagnosed with IBS
Prevalence of IBS in the US is 10-15% of the
population
Pathophysiology
Still remains unclear
Thought to be due to number of factors, including
genetic and environmental
Factors that play a role in IBS
Alteration in GI motility
Prolonged colonic transit time in some patients with
constipation-predominant IBS
Exaggerated response in diarrhea-dominant patients
Visceral hypersensitivity
Stimulation of receptors in the gut wall transmit signals
that eventually signal pain to the brain (sensitivity in GI
vs brain?)
Studies have shown that patients with IBS have
increased sensitivity to intestinal balloon distension than
controls
Other studies show that patients with IBS who complain
of bloating have similar volumes of gas to controls, but
More factors
Intestinal inflammation
Some IBS patients have increased levels of inflammatory
cells in their GI tract
Infectious
Two meta-analyses showed increased risk of IBS in patients
with an episode of gastroenteritis
More specific risks: young age, prolonged fever, anxiety,
depression
Alteration of fecal flora and bacterial overgrowth
Fecal microbiota differs between individuals with IBS vs
healthy controls
Conflicting evidence in association of IBS with abnormal
hydrogen breath tests
Food sensitivities
Some patients with IBS report sensitivities to certain foods,
but this is all individualized
Food allergies
Improved symptoms with elimination diets if a patient had
elevated IgG levels to certain foods
Carbohydrate malabsorption
No current evidence to suggest that patients with IBS have
impaired carbohydrate absorption
Gluten sensitivity
Some studies suggest some overlap, especially with +IgG
antigliadin antibodies and HLA-DQ2/8+ without vilious
atrophy
Psychosocial factors
Some studies show increased anxiety and depression
in patients with IBS vs controls
One interesting study:
Corticotropin releasing factor (CRF) is a peptide that is
released during a stress response
Increased CRF contributes to anxiety and depression
Administration of CRF (IV) induced abdominal pain and
diarrhea to a higher degree in IBS patients vs controls
Patient Presentation
Varied presentation between
patients
Most commonly: abdominal
pain and altered bowel habits
Abdominal pain is varied in
location, crampy and can be
mild to severe
Red flags: anorexia,
malnutrition, weight loss,
prevents sleep
Combination of diarrhea,
constipation, or both. Can also
have intermittent normal
stooling as well
GI symptoms
 Diarrhea- frequent loose stools
during the day, usually after a
meal, feeling of incomplete
evacuation, urgency and
incontinence
 Red flags: large volume, bloody stools,
nocturnal diarrhea, greasy stools
 Constipation- hard, pellet shaped
stools. May have feelings of
incomplete evacuation
 Other patients may complain of:
gastroesophageal reflux,
dysphagia, early satiety, dyspepsia,
nausea, abdominal bloating,
increased gas production
Differential Diagnosis
Dependent on symptom and location of abdominal pain
Parasitic/bacterial infections Hypothyroidism,
GERD, PUD, pancreatic hypoparathyroidism
disease, biliary tract dx Side effect of
IBD, diverticular disease,
medications
colon cancer
Acute intermittent
Gastroparesis, partial
obstruction porphyria, lead
Lactase deficiency, poisoning
malabsorption,
hyperthyroidism
Work-up
CBC, CMP, ESR, ?thyroid studies
Should be normal
If patient has symptoms suggestive of IBS, no red flag
symptoms, no family hx of IBD or colorectal cancer,
then no further testing is warranted.
If they have any alarming symptoms, further imaging
and/or colonoscopy is needed.
Further work-up
Diarrhea-predominant Constipation-predominant
Stool cultures and O&P Xray
Celiac screening Colonoscopy
TTG IgA and serum
IgA
24 hour stool collection
Looking for
malabsorption
Colonoscopy and
biopsy
Diagnosis
Chronic abdominal pain and altered bowel habits
IBS is diagnosis of exclusion
Rome criteria developed to standardize a definition of
IBS
Management
Dependent on symptoms and severity of disease
First step is developing a healthy physician-patient
relationship
Discuss diagnosis, validate symptoms, reassurance,
establish realistic expectations
Next is dietary modification
Exclude gas producing foods
Trial of Lactose-free diet
Next…low FODMAP diet
Low FODMAP diet
This should be done under guidance of trained
dietician to avoid over-restriction
This is done for 6-8 weeks until symptom resolution
Then start adding back these foods to determine
individual intolerance to specific foods
If that doesn’t work…
Trial of gluten-free diet for 2 weeks
Limited evidence to support this
Fiber supplementation
Controversial evidence, but very low
side-effect profile
Physical activity has shown some
benefit!
20-60 min of moderate to vigorous
exercise 3-5 times per week
Pharmacologic therapy
Laxative- polyethylene Loperamide-
glycol (PEG), lactulose, antidiarrheal
milk of magnesia Cholestyramine- bile
Lubiprostone and acid sequestrant
Linactolide are newer Dicyclomine and
medications that Hyoscyamine-
increase intestinal fluid antispasmodics
secretion Tricyclic
antidepressants- slow
intestinal transit time
Rifixamin- antibiotic
Probiotics can be tried
Other therapies
Behavior modification
Anxiolytics (short term)
Accupuncture
OMM
Viscerosomatic reflexes
References
Harrison’s Principles of Internal Medicine, 19 th Edition.
Irritable Bowel Syndrome.
www.uptodate.com
Pathophysiology of irritable bowel syndrome
Clinical manifestations and diagnosis of irritable bowel
syndrome in adults
Treatment of irritable bowel syndrome in adults
Weinberg, DS, et al. “American Gastroenterological
Association Institution Guideline on the
Pharmacological Management of Irritable Bowel
Syndrome.” Gastroenterology 2014; 147:1146-1148.
Questions?