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Inflammatory Bowel Disease

Lau Yi Ling
Lee Yi Ren
Inflammatory Bowel Disease (IBD)
• Inflammatory process that affect the large and small intestines
• Crohn’s disease
• Ulcerative colitis
• Coeliac Disease
(Burket’s Oral Medicine)
Crohn’s Disease
• Chronic, transmural inflammatory bowel disease
• May affect any part of the bowel system including the oral cavity
• Patchy distribution throughout the gut
• Transmural with inflammation extending the entire thickness of
intestinal wall
• Mucosal ulceration
• Aphthous ulcers within the mucosa that appear normal
• Deep ulcers within areas of swollen mucosa
• Long linear serpiginous ulcers
(Kornbluth et al, 2004)
• Two forms
• Non-perforating -> stenotic obstruction
• Aggressive or perforating -> prone to develop fistulae and abscesses
(Burket’s Oral Medicine)
• Classified based on the bowel segment it affects
• ileitis affecting ileum only
• colitis affecting colon only
• ileocolic affecting both ileum and colon.
(Ruthruff et al, 2007)
Epidemiology
• F>M
• More common between age 20-39 years old
• More common in Caucasian
• Most prevalent in North America, norther Europe and Australia
(Burket’s Oral Medicine)
Causes
• Genetic
• Risk of disease increases when there is an affected family member
• Mucosal immune responses
• Activation of mucosal immunity and suppression of immunoregulation
• Epithelial defects
• Defects in intestinal epithelial tight junction barrier function
• Barrier dysfunction can activate innate and adaptive mucosal immunity and sensitize
subjects to disease
• Microbiota
• Ongoing studies
• Smoking -> increases risk
(Robbins Basic Pathology)
Morphology
• Common sites
• Terminal ileum
• Ileocecal valve
• Cecum
• Skip lesion
• Multiple, separated, sharply delineated areas of disease

(Robbins Basic Pathology)


Clinical Features
• Intermittent attacks of mild diarrhea, fever and abdominal pain
• Right lower quadrant pain, fever and bloody diarrhea that mimics
acute appendicitis or bowel perforation
• Periods of active disease will be interrupted by asymptomatic
intervals that last for weeks to months
• Disease reactivated by external triggers such as physical or emotional
stress, specific dietary items and cigarette smoking
(Robbins Basic Pathology)
• Abdominal cramps
• Diarrhoea
• Melena
• Rectal bleeding
• Vomiting
• Poor appetite
• Fatigue
• Weight loss
• Fever
• Joint pain
• Mucocutaneous and ocular problems
(Bernstein et al, 2001)
• Impaired absorption of fat, fat-soluble vitamins, salt, water, protein and
iron
• Inflammation of duodenum -> Malabsorption of vital nutrients such as
Calcium, Iron and folate
• Inflammation of terminal ileum -> Malabsorption of bile salts & vitamin
B12
• Electrolyte abnormalities and low albumin levels can occur in cases of
severe diarrhea
• Anemia -> iron or folate deficiency
• Leukocytosis -> if abscess or perforation is present
(Burket’s Oral Medicine)
Diagnosis
• Hematological screening
• complete blood count
• renal functional test
• liver function tests
• erythrocyte sedimentation rate
• C-reactive protein to check for anemia, thrombocytopenia, electrolyte
abnormalities, bile duct problems, and inflammatory processes throughout
the body.
• Serum testing for the presence of anti-Saccharomyces cerevisiae antibodies
(ASCA) and antineutrophil cytoplasmic antibodies (ANCA) in serum (detection
of intestinal inflammation and differentiating CD from UC)
(Kornbluth et al, 2004)
• Endoscopy
• mucosal edema
• thickening
• frank ulceration
• Cobblestoning
• Psuedopolyps
• Histological features of CD include infiltration of intestinal mucosa with neutrophils,
lymphocytes, and mononuclear cells. Clusters of giant cells or noncaseating granulomas have
been found in up to 60% of resected gut specimens and are highly specific for CD.
• Ileocolic location of the disease with rectal sparing, patchy rather than
continuous disease distribution throughout the intestine, transmural
inflammation, and characteristic granulomatous histology are highly suggestive
of CD
(Karlinger et al, 2000)
Inflammatory polyposis in the transverse colon
(http://www.gastrolab.info/gall109.htm)
Lower endoscopy in Crohn's disease demonstrates the characteristic patchy erythema
(left panel) and ulceration (right panel) that occur next to areas of normal mucosa.
Courtesy of James B McGee, MD, UpToDate
• Colonscopy
• Less informative
• Capsule Endoscopy
• In non-stricturing Crohn’s disease
• Barium contrast enemas
• detect anatomical abnormalities and colonic fistulas when colonoscopy is difficult, as in the case of
stricturing
• fluoroscopic imaging
• locating intestinal inflammation and narrowing at the small bowel.
• Computerized tomography (CT), magnetic resonance imaging (MRI), ultrasonography
• to detect intra-abdominal complications such as fistulas, abscesses, and obstructions.
• Patients with long-standing, advanced IBD are at risk for colorectal carcinoma and should
undergo regular colonoscopy, biopsies, and follow-up care
(Fatahzadeh, 2009)
Extraintestinal Manifestation
• Mucocutaneous manifestations in the head and neck region.
• Granulomatous changes of oral cavity caused by direct extension of
intestinal inflammation or those of metastatic CD affecting a distant
cutaneous site noncontiguous with the bowel
• oral findings may precede onset of intestinal disease in up to 60% of
patients
• macrocheilia with or without fissuring, cobblestoning of oral mucosa,
deep linear ulcers of buccal vestibules, and polypoid mucosal tags are
considered specific and pathognomic for CD
(Fatahzadeh, 2009)
Clinical photo illustrating macrocheilia and fissuring affecting lower lip, mild perioral dermatitis, and
exfoliative cheilitis.
(Fatahzadeh, 2009)
Clinical photo illustrating edematous, hyperplastic tissues affecting right maxillary and mandibular gingiva,
punctate erosions on upper right vestibule, and folding/cobblestoning of right buccal mucosa.
(Fatahzadeh, 2009)
Clinical photo illustrating multiple superficial aphthous ulcers on right buccal and vestibular
mucosa, and linear ulceration of lower labial vestibule. (Fatahzadeh, 2009)
Clinical photo illustrating an ulcer with associated hyperplastic folds on lower labial vestibule.
(Fatahzadeh, 2009)
Clinical photo illustrating hyperplastic folds resembling epulis fissuratum affecting lingual
vestibules and floor of the mouth. (Fatahzadeh, 2009)
• Certain mucocutaneous changes in IBD may be the result of reactive
disorders associated with it
• Stomatitis, glossitis, aphthous ulceration, cheilitis, or perioral
dermatitis
• deficiencies of albumin, zinc, folic acid, niacin, vitamin B, and other essential
nutrients.
• corticosteroid or immunosuppressive therapy
• Mucocutaneous opportunistic infections and acne
• Extraintestinal manifestations of IBDs often respond to systemic
therapy with anti-inflammatory drugs, immunomodulators, and
biological agents directed at the underlying disease.

(Fatahzadeh, 2009)
Oral Manifestation
• Recurrent aphthous ulcer
• Diffuse soft or tense swelling of the lips, or mucosal thickening
• Cobblestone thickening of the buccal muscosa, with fissuring and
hyperplastic folds
• Gingivae may be erythematous and swollen
• Mucosal tags in sulcus sometimes present
• Glossitis due to iron, folate or vitamin B12 deficiency can result from
malabsorption
• Rupture of salivary ducts and localized mucocele formation with
granulomatous lesion in salivary glands
(Cawson’s Essentials of Oral Pathology and Oral Medicine)
(Odell, 2017)
As a dental practitioner,
• Recognize the orofacial manifestations of patients undergoing
corticosteroid or immunosuppressive therapy
• A complete gastrointestinal work-up is indicated for patients with oral
manifestations suggestive of IBDs and gastrointestinal complaints.
• Even in the absence of intestinal signs and symptoms, pathognomonic
orofacial manifestations should prompt an astute clinician to perform
a tissue biopsy with appropriate staining and closely follow the
patient for potential development of intestinal disease over time.
(Fatahzadeh, 2009)
Management
• Palliation of intestinal symptoms
• Controlling the inflammatory process
• Improving patient's quality of life
• Correction of nutritional deficiencies
• Prevention of complications.
• Medical therapy of IBD is individualized, requires time to work, and is often
associated with serious side effects. In CD, a number of factors including
intestinal location of disease, its phenotypic behavior, and patient's age
also affect decisions on therapeutic approach.
• A variety of anti-inflammatory, immunosuppressive, and biological agents
have been used to induce and/or maintain remission in IBDs.
(Fatahzadeh, 2009)
Ulcerative Colitis
• Disease that causes ulcers and irritation in the inner
lining of the colon and rectum.
• Ulcerative: sores or ulcers
• Colitis: inflammation of the colon

(Francis A. Farraye, MD, MSc: Questions and Answers About Ulcerative


Colitis)
Symptoms of ulcerative colitis
• Bloody diarrhoea
• Abdominal discomfort
• Loose stool contain blood and mucus
• Fatigue
• Fever
• Chills
• Loss of appetite
• Weight loss

(Francis A. Farraye, MD, MSc: Questions and Answers About Ulcerative Colitis)
Severity of ulcerative colitis
• Number of factors: frequency of diarrhoea
• Systemic signs of toxicity: fever, rapid heart rate, abnormal lab tests
1. Mild: having fewer than four diarrhoea daily, with or without blood,
no systemic signs of toxicity (normal temperature and pulse), and a
normal erythrocyte sedimentation rate (ESR)
2. Moderate: having more than four diarrhoea daily but with minimal
signs of toxicity
3. Severe: more than six bleeding diarrhoea daily and evidence of
systemic toxicity as shown by fever (>37.5̊̊C), tachycardia
(>90beats/min), anemia and an elevated ESR and abdominal
tenderness.
(Francis A. Farraye, MD, MSc: Questions and Answers About Ulcerative Colitis)
Pathophysiology
• Cause is unknown
• Autoimmunity may have indirect effect
• Antibodies to epithelial cells in the colon have been found in some
individuals with ulcerative colitis
• Inflammation always starts in rectum and extend upward into the
colon
• Most probably involves the entire colon along the way

(Carie Ann Braun, Cindy Miller Anderson: Pathophysiology: Functinal Alterations in Human Halth pp:
65)
Pathophysiology
• Inflammation invades superficial mucosa
• Mucosa friable, becomes a state where tissue readily bleeds
• Mucosa becomes erythematous and granular
• Lesion in the crypts of Lieberkühn can form into abscesses
• Extensive exudates present in the abscess and ulceration is common
• Overtime, epithelial cells of the mucosa begin to atrophy

(Carie Ann Braun, Cindy Miller Anderson: Pathophysiology: Functinal Alterations in Human Halth pp:
65)
Complications
• Higher risk for colorectal cancer- epithelial cells metaplasia
• Obstruction- granular, abscessess
• Perforation- epithelial mucosal atrophy
• Massive haemorrhage- mucosal friable

(Carie Ann Braun, Cindy Miller Anderson: Pathophysiology: Functinal Alterations in Human Halth pp:
65)
Diagnostic significance in regular dental practice
: Oral and Skin Manifestation
• Pyostomatitis vegetans
-Broad based milliary abscess in area of intense erythema
-Pustular lesion
• Erosion Ulceration
• Fissuring
Common on labial buccal mucosa, labial attached gingiva and hard palate
• Pyoderma vegetans on skin
-Asymmetrical rash most commonly in skin folds (armpit, groin, scalp)
-less common in trunk, face and finger
(Dr. Ayu’s lecture notes: Oral Manifestations of Systemic disease)
Investigation of Ulcerative Colitis
• Plain abdominal X-ray film
• Full blood count
• Liver function tests
• BUSE
• Barium enema (rarely used)-contraindicate for very active colitis and with
toxic megacolon, perforation
• Colonoscopy (most useful)
• Antibody testing

(Nicholas Joseph Tally, Simon O’Connor: Examination Medicine: A guide to Physician Training pp
135)
Management: Mild to Moderate
First line treatment
(Anti-inflammatory, antidiarrheal medication, corticosteroids, fluid for
rehydration)
• Anti-inflammatory drugs: Sulfasalazine, Mesalazine
- Most common using in inflammatory bowel disease
- Effective for both Crohn’s and ulcerative colitis
- Side effect of Sulfasalazine more than Mesalazine
- Allergic skin rash, nausea, headache, folate deficiency, reversible male
infertility
- Decrease relapsed rate but should be administered continuously

(Nicholas Joseph Tally, Simon O’Connor: Examination Medicine: A guide to Physician Training pp
135)
Management: Mild to Moderate
• Corticosteroids
- Budesonide (Entocort, Uceris)
- Orally tablet or capsule or rectally
- Anti-inflammation
- Budesonide less side effects than others corticosteroids
- Weight gain, high blood sugar, acne, increase hair growth, high BP
- Once remission is achieved, reduced gradually and ultimately stop
- Ineffective as maintenance therapy, does not reduce relapse rate

(Ulcerative colitis Guide medication-https://www.everydayhealth.com/ulcerative-


colitis/guide/medications)
(Nicholas Joseph Tally, Simon O’Connor: Examination Medicine: A guide to Physician Training pp
135)
Management: Mild to Moderate
• Antidiarrheal medication
- Loperamide: Imodium (without prescription)
- Diphenoxylate: Lomotil (with prescription)
- Slows down painful spasm in intestines
- Contraindicate in moderate to severe colon inflammation
- Complications: Toxic megacolon

(Antidiarrheal Medicines for Inflammatory Bowel Disease - Topic Overview WebMD)


Management: Acute, moderate to severe
• IV broad spectrum antibiotics
- usually Metronidazole and Ciprofloxacin
- Achieving and maintaining remission
- Control symptoms, reduce intestinal bacteria, suppress intestine immune
system
- More useful in Crohn’s disease than ulcerative colitis
- Complication: toxic megacolon
(www.crohnscolitisfoundation.org/info/treatment/antibiotics)

• IV corticosteroid therapy
Management: Acute, moderate to severe
• IV immune suppressors
- Acute UC
- IV corticosteroids not effective
- IV cyclosporine, infliximab, azathioprine
- Cyclosporine and azathioprine: suppress immune system activity
- Infliximab- TNF-alpha inhibitor, blocking inflammatory action
- Raise risk of infection and cancer

(Ulcerative colitis Guide medication-https://www.everydayhealth.com/ulcerative-


colitis/guide/medications)
Nicholas Joseph Tally, Simon O’Connor: Examination Medicine: A guide to Physician Training pp 135)
Management: Acute, moderate to severe
• Colectomy
- Curative
- Indicates for chronic ill health and severe disease
- Indicates when complications occur and not responding to medical
treatment in 7-10 days
- High risk of carcinoma
- Standard Brooke ileostomy, ileal pouch anal anastomosis

(Nicholas Joseph Tally, Simon O’Connor: Examination Medicine: A guide to Physician Training pp
135)
Crohn’s disease vs Ulcerative Colitis
• Involvement of small intestine or upper part of the alimentary canal
• Segmental disease of the colon with ‘skip’ areas of normal rectum
• The appearance of fissures or sinus tracts
• Presence of well-formed sarcoid type granulomas
• In CD, chronic inflammation may affect any part of the
gastrointestinal tract, whereas in UC, mucosal inflammatory changes
are confined to colon.
• UC is twice more prevalent than CD and the incidence of both
diseases appears to follow a bimodal age distribution with signs and
symptoms frequently manifesting in early adulthood as well as 50 to
70 years of age.
• The involvement of colonic mucosa is possible with both UC and CD
giving rise to similar symptoms. In this context, differentiation
between the 2 diseases is often difficult leading to a less specific
diagnosis known as indeterminate colitis.
Feature Crohn's disease Ulcerative colitis
Involvement of terminal ileum Commonly Rare
Involvement of colon Usually Always
Rectum involvement Rare Often
Perianal disease Common Rare
Disease distribution Patchy inflammation Continuous inflammation
Depth of mucosal inflammation Deep or transmural Shallow
Presence of fistulae Common Rare
Stenotic complication Common Rare
Etiology Possibly autoimmune Not known
Risk of colorectal cancer Lower than ulcerative colitis Higher than Crohn's disease
Presence of granulomas on biopsy May be present Not present

Surgical cure Not possible Possible


Association with smoking Higher risk for smokers Lower risk for smoker
Effect of bowel rest Improves symptoms Worsens symptoms
Celiac Disease
• Celiac disease is a lifelong genetically conditioned autoimmune disease.
(Textbook: Gerontorheumatology by Josef Rovensky)
• It is an immune-mediated enteropathy triggered by ingestion of gluten-
containing grains (including wheat, rye and barley) in genetically
susceptible individuals. (Textbook: Frontiers in Celiac Disease by Alessio Fasano)
• Genetically susceptible individuals associated with HLA-DQ2 and HLA-DQ8
• Its affect more women than men, with M:F ration of about 1:2
• Strong hereditary component, prevalence of first degree relatives is 8-18%
• Concordance in monozygotic twins approaches 70%
Clinical features of coeliac disease
• Depends largely on patient’s age, duration of gluten exposure, genetic
deposition
• More common in affecting children, with symptoms of
- Diarrhoea
- Weight loss
- Anaemia
• In adulthood (mostly between 30th and 40th):
- GIT symptoms less intensive
- Trigger by stressful situation (infection, surgery, long term stress)
- Minor GIT problem such as flatulence, LOA
- Fatigue
- Atypical extra-intestinal symptoms such as
1. Osteoporosis (not correlate with age and anaemia)
2. Glossitis
3. Aphthous stomatitis
4. Muscle weakness
5. Alopecia
6. Infertility
7. Amenorrhea
8. Dermatitis herpeformis
Oral and non-oral manifestation
Pathophysiology of Celiac disease
• Gluten is degraded in the intestinal
lumen to give a resistant fragment
• Gluten fragments enter intestinal
tissue and is deaminated by
transglutaminase
• Deaminated peptides engulf by APC
(Macrophage) and presented by HLA-
DQ (specific HLA molecules in the
lamina propria of small intestine)
• T-helper cells response by activated T-
cells and induce B-cells maturation to
plasma cells.
• Activated T-cells: produce pro-
inflammatory cytokines
• Plasma cells: produce antibodies to
gluten peptides as well as tissue
transglutaminase
Pathophysiology of Celiac disease
• The delivery of gliadin peptides (fraction of gluten) to HLA-DQ1- and
HLA-DQ8-positive cells provokes an excessive immune response in the
small intestine mucosa, mediated by T-cells
• At the same time, a high amount of highly specific antibodies (against
tissue transglutaminase) is being generated.
• Ultimately, reaction to gluten results in damage of intestinal mucosa
(mostly duodenal and jejunal) with varying degree of atrophy and
inflammatory mucosal changes.
• Damage to the intestinal mucosa inhibits ingestion because of
damage to the villi that produce and secrete digestive hormones and
enzymes.
• Inadequate secretion of hormones and enzymes inhibits gallbladder
and pancreatic function.
• This further restricts the digestive process.
• Absorption is also impaired because these villi undergo atrophy,
which disallows the effective passage of nutrients across the mucosa.
• Absorption is further disrupted with a loss of carrier substances
needed to transport nutrients across the mucosa.
• Impaired in nutrients absorption causes complications such as
osteoporosis, anaemia, infertility, muscle weakness to occur.
Complications
• Osteoporosis
- Deficient of calcium
• Anaemia
- Glossitis, aphthous stomatits
- Deficiency of iron, folate, pyridoxine and vitamin B12
• Gynaecological disorder
- Infertility (malnutrition), dysmenorrhea (prostaglandin-uterine contractions)
• Neurological disorder
- Muscle weakness (lack of protein, glucose, lipids), epileptic seizures (lack of folic acid)
• Dermatitis herpetiformis (cutaneous manifestation of coeliac disease)
- Vesiculobullous disease with intense pruritus
- Associated with IgA deposits
- Abnormal presentation of epidermal transglutaminase
Classification of Coeliac disease
Classic (Typical) form • Serological and histological markers are present.
• Clinical features: GIT symptoms.
Subclinical (Atypical) form • Serological and histological findings are positive.
• Clinical features: Atypical extra-intestinal symptoms
(anaemia, osteoporosis, neurological and
gynaecological disorders)
Silent form • Histological and serological findings are positive.
• Clinical symptoms are absent.
Latent form • Serological findings are positive.
• Histological findings: only increase in lymphocytes
numbers, without atrophy
• Clinical symptoms are absent.
• Early stages of disease
Potential form • Serological findings: may be negative or partially
positive
• Histological findings: negative/ increase in
intraepithelial lymphocytes
• Clinical symptoms are absent
• Genetic examination recommended
• At risk of developing CD in future
Investigation
1. FBC and blood smear – Low Hb and microcytic red cells
2. immunoglobulin A-tissue transglutaminase (IgA-tTG) test – titre above normal
range
3. Endomysial antibody (EMA) – elevated titre
4. Skin Biopsy - granular deposits of IgA at the dermal papillae of lesional and
perilesional skin by direct immunofluorescence
5. IgG DGP or IgA/IgG DGP (deamidated gliadin peptide) – elevated
6. HLA Typing - positive HLA-DQ2 or -DQ8
7. Small bowel histology - presence of intra-epithelial lymphocytes, villous
atrophy, and crypt hyperplasia

(http://bestpractice.bmj.com/topics/en-gb/636/investigations#firstOrder)
Dental Aspects
• Patient usually has short stature associated with diarrhea and enamel
defects
• Anemia – glossitis, burning mouth, angular cheilitis and ulcers
• Untreated patients may have bleeding tendency
• Anemia may complicate GA
• Information on oral manifestations of celiac disease helps prepare
dentists for the opportunity to contribute to early diagnosis of celiac
disease and in so doing, may help avoid disease complications.
References
• Francis A. Farraye, MD, MSc: Questions and Answers About Ulcerative Colitis
• Carie Ann Braun, Cindy Miller Anderson: Pathophysiology: Functinal Alterations in
Human Halth pp: 65
• Dr. Ayu’s lecture notes: Oral Manifestation of Systemic disease
• Nicholas Joseph Tally, Simon O’Connor: Examination Medicine: A guide to
Physician Training pp 135
• www.crohnscolitisfoundation.org/info/treatment/antibiotics
• Ulcerative colitis Guide medication-https://www.everydayhealth.com/ulcerative-
colitis/guide/medications
• Antidiarrheal Medicines for Inflammatory Bowel Disease - Topic Overview
WebMD
• Types of ileostomy: MedlinePlus Medical Encyclopedia
• Greenberg, M.S., Burket, L.W. and Glick, M., 2003. Burket's oral medicine:
Diagnosis & Treatment. BC Decker.
• Kumar, V., Abbas, A.K. and Aster, J.C., 2017. Robbins Basic Pathology E-Book.
Elsevier Health Sciences.
• Kornbluth, A. and Sachar, D.B., 2004. Ulcerative colitis practice guidelines in
adults (update): American College of Gastroenterology, Practice Parameters
Committee. The American journal of gastroenterology, 99(7), pp.1371-1385.
• Bernstein, C.N., Blanchard, J.F., Rawsthorne, P. and Yu, N., 2001. The prevalence
of extraintestinal diseases in inflammatory bowel disease: a population-based
study. The American journal of gastroenterology, 96(4), pp.1116-1122.
• Fatahzadeh, M. (2009). Inflammatory bowel disease. Oral Surgery, Oral Medicine,
Oral Pathology, Oral Radiology, and Endodontology, 108(5), pp.e1-e10.
• Odell, E. (2017). Cawson's essentials of oral pathology and oral medicine,
international edition. [Place of publication not identified]: Churchill Livingstone.