Changing face of Crohn's Disease

1. CROHN’S DISEASE
DR. CHAYANIKA DAS
Ph.D
VETERINARY MICROBIOLOGY

2. Inflammatory bowel disease is a group of inflammatory
conditions of colon and small intestine
2 principle types: Crohn’s disease, Ulcerative colitis
Crohn’s Disease (CD)
Burrell B Crohn-1932

3. • A multisystem group of disorders
• Characterized by focal, asymmetric, transmural, and, occasionally,
granulomatous inflammation primarily affecting the gastrointestinal
(GI) tract
• Potential for systemic and extra-intestinal complications
About one third of patients with CD are expected to develop
extraintestinal inflammatory manifestations (Ramakrishna et al., 2015)
• Can affect any age group but more severe in adults
• CD more common in males with onset in third or fourth decade
The incidence and prevalence of CD in the Asia-Pacific region is reported
to be lower than that in North America or Europe
INTRODUCTION
Bandopadhyay, 2012; Gautam Ray, 2016

4. •CD started increasing from 1960 with plateauing after 1975 but recently have been
rising all over the world (Gaurav Ray, 2016)
• In India the first case of CD was reported about 23 years after UC
•First published report of CD in India was in 1970
•A multicentre study from northern and eastern regions of India indicated that there
was a cumulative rise in the number of patients with CD from fewer than 5,000 in
1987 to 21,061 in 2001, giving an indirect estimate of disease burden and its rise
over the years in India (Bandopadhyay, 2012)
•The IBD Task Force was set up in 2003-
Region wise distribution (UC:CD) in India were- North 220 (148:72), South 466
(235:231), Central 255 (227:28), East 159 (90:69), West 59 (50:9)
(Gaurav Ray, 2016)
The changing face of CD-
Survey of Inflammatory Bowel Disease in India (Makharia et al., 2012)-
Out of 1159 samples, 409(35.3%) samples positive for CD,

5. Estimate of IBD burden in India (2010)
The overall estimated IBD population in India in 2010 was about 1.4 million
Kedia and Ahuja, 2017

6. •CD results from a strong genetic predisposition on which environmental factors act
to produce dysregulated gut mucosal immune response to luminal antigens (the
intestinal microbiota, normal or abnormal)
•Childhood infections exposure to helminths, repeated use of drugs like antibiotics
and proton pump inhibitors, dietary and psychosocial factors have been implicated in
CD pathogenesis and may act by altering balance between the gut and microbiota
•Childhood infections by producing tolerance of immunoregulatory T cells to external
antigens early in life protects against CD in adult life
•Increasing incidence and earlier onset of CD in children of Indian diasporas settled in
cleaner and more hygienic environment of Europe and North America compared
to their parents and counterparts settled in India (Gautam Ray, 2016)
•Indian migrants in Western countries have shown increased incidence of IBD, more in
the second generation of immigrants (Amarapurkar et al., 2008)
•The increasing incidence of CD was first observed in Western countries, as the
sanitation - hygiene started improving with disappearance of helminthic infestations
(which promote Th2 response protective against CD) (Gautam Ray, 2016)
HYGIENE & CD

7. •In India the highest reporting of CD comes from Kerala with the
highest literacy rate and better hygiene (Gautam Ray, 2016)
•Main cause: Mycobacterium paratuberculosis
•Higher incidence of extraintestinal manifestations (EIM), higher use of 5ASA and
azathioprine (AZP), lower use of corticosteroids, no use of antibiotics for CD and a
possibility of medicine discontinuation
•Higher percentage of OGIB -
Capsule endoscopy, single and double balloon enteroscopy diagnosed CD as one of
the major causes of OGIB (Das et al., 2010; Goenka et al., 2014)
•Cigarette smoking and appendemectomy are classical risk factors associated with
a more aggressive course of CD (Ananthakrishnan, 2013)
•Serum 25(OH) vitamin D levels are significantly lower among patients with CD
(Bandopadhyay, 2012; Ananthakrishnan, 2013)
•Different exposure to sunlight and hence to vitamin D (which has an
antiinflammatory and immunomodulatory role) may account for a North-South
gradient in the West
CD is more commonly seen in Southern India as compared to Northern India
FACTORS RELATED TO OCCURENCE OF CD

8. •Genetic and immunological factors
Mutations in nucleotide-binding oligomerization domain 2 (NOD2) gene- 1st
genetic abnormality to be reported in patients with CD
Not reported in Indian patients (Kedia and Ahuja, 2017)
TNF alpha 863 AA genotype increased risk of both UC and CD in India
TNF SF15 gene polymorphism is associated with CD in Indian population
(Kedia and Ahuja, 2017)
Study from South India: T cell activation (increase in CD3, CD69 population)
and interferon-γ ELISPOT responses to hookworm antigens were significantly
lower in CD patients than in controls
ASCA is an antibody directed against mannan in the cell wall of
Saccharomyces cerevisiae, the baker's yeast that is found mainly when the
small bowel is involved in Crohn's disease (Dutta et al., 2011)
•Alteration of commensal flora following antibiotic use or disruption of the
intestinal barrier through agents such as nonsteroidal anti-inflammatory drugs
(NSAIDs) may increase the risk of disease (Ananthakrishnan, 2013)
•Use of oral contraceptives may cause hormonal imbalane, a risk factor for
occurence of CD in women (Ananthakrishnan, 2013)

9. •Enteric microbial Infections
 Altered number, type and location of colonic bacterial flora in IBD-
Mucosal adherence of E. coli in the colon of CD patients
 The occurrence of Crostridium difficile infection (CDI) in patients with IBD
has steadily increased over the past decade
 Hospitalized patients with CDI-IBD have a 4-fold greater mortality risk than
patients who do not have IBD-CDI
 Enteric infection with Salmonella and Campylobacter, may increase the risk
of development of CDI
Ananthakrishnan, 2013

10. CLINICAL SIGNS & SYMPTOMS
•Chronic diarrhoea
•Hematochezia
•Fever, weight loss
•Severe abdominal pain
•Growth retardation
•Anaemia
•Ascites
LESIONS
Oedematous wall
•May affect any part of the GIT from mouth to anus
•Anal lesions
•Terminal ileum and ascending colon(70% cases)
•Transmural inflammation (whole lumen of bowel
wall)
•Hard, rubbery bowel wall with small lumen
(String sing)
•Fibrosed

11. The histological features :
•Presence of granuloma,
• Characteristics of granuloma-
Ulceration of surface epithelium,
Appearance of crypts,
Presence of lymphoid aggregates and site and type of
inflammatory infiltrate

12. Malik et al., 2014 reported a case of sudden death due to peritonitis followed by
Crohn’s Disease in a 26 years old man from Haryana travelling to Guwahati
• Historical report: fever and abdominal pain
•Autopsy findings showed multiple perforation and oedematous large intestine
Histopathological findings-
Small intestine showed diffuse mixed inflammatory infiltrates, focal collections
of polymorphs (micro abscesses), inflammatory necrosis and vascular
proliferation in serosal layer
Large intestine showed the involvement of inflammatory cell infiltrate in all
layers and focal collection of polymorphs in serosal layer with granulation tissue
reaction

13. Treatment
-through medication or surgery
Medication:
• Anti-inflammatory drugs such as aminosalicylates (5ASA),
corticosteroids
• Immunomodulators such as azathioprine, cyclosporine,
vedolizumab and/or infliximab
• Iron supplements, pain relievers
• Anti-diarrhoeal drugs
• Antibiotics
• Vitamin D supplements
Surgery:
• Proctocolectomy (removal of the colon)
TREATMENT
www.apollohospitals.com

14. Aminosalicylates (asa): They work at the level of gastrointestinal lining and reduce
inflammation
Corticosteroids: They nonspecifically suppress the immune system and used to treat
moderate to severe episodes
Antibiotics: may be used when infections—such as abscesses—occur in Crohn’s disease. They
can also be helpful with fistulas around the anal canal and vagina
Immunomodulators: modulates or suppresses the body’s immune system response to
suppress inflammation
Surgery for Crohn’s disease
Proctocolectomy and ileostomy
Bowel resection
Intestinal transplant
www.wellinghomeopathy.com

15. DIAGNOSIS
•The diagnosis of CD should be based on a combination of clinical, endoscopic, histological,
and radiological features and with satisfactory exclusion of tuberculosis
Clinical approach to patients with chronic large bowel diarrhoea
Ghoshal, 2012

16. DIFFERENTIAL DIAGNOSIS
•In India, the major differential diagnostic condition that has clinical, endoscopic,
colonoscopy, imaging, and histological similarities to CD is intestinal tuberculosis
Tendon and Prakash, 1972
•Expression of mesenchymal
cell marker CD73 and
increased IL17 only in ITB
granuloma
•Increased IL1, IL6, IL8 in
PBMC and increased γ-INF,
TLR-5, TLR-9 in biopsy
specimen of CD

17. Ulcerative Colitis and Crohns Disease (Ghoshal, 2012)

18. Serology tests
• Anti-neutrophil cytoplasmic antibody (ANCA) specific ELISA
•Anti Saccharomyces Cerevisiae antibody (ASCA) specific ELISA
Molecular tests
•Tissue polymerase chain reaction (PCR) for Mycobacterium
tuberculosis (TB PCR)
•Faecal sample PCR (Dutta et al., 2011)

19. The diagnostic confusion of CD with ITB is still prevalent and in spite of multiple
investigations for differentiation, about a third of CD patients still get anti-
tuberculosis drugs
•In case of misdiagnosis of GITB, unnecessary anti-tuberculosis therapy (ATT)
poses a risk of toxicity and treatment of CD is delayed
•In contrast, treatment with steroids alone (for CD) can be disastrous, if diagnosis
of GITB is missed
•Emergence of multi-drug resistant TB can further complicate the issue by
decreasing the therapeutic response even in presence of TB
•All these situations highlight the need to establish the diagnosis of either CD or
GITB, before starting any form of empirical treatment
Amarapurkar et al., 2008; Moka et al., 2017