Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any part of

the gastrointestinal tract from, from the mouth to the anus. It causes inflammation of your digestive
tract. Inflammation caused by Crohn's disease can involve different areas of the digestive tract
in different people. Bowel obstruction also commonly occurs and those with the disease are at
greater risk of bowel cancer

The inflammation caused by Crohn's disease often spreads deep into the layers of affected
bowel tissue. Crohn's disease can be both painful and debilitating, and sometimes may lead to
life-threatening complications.
Crohn's disease is caused by a combination of environmental, immune and bacterial factors in
genetically susceptible individuals.[7][8][9] It results in a chronic inflammatory disorder, in which the
body's immune system attacks the gastrointestinal tract possibly directed at microbial antigens.[8][10]
While Crohn's is an immune related disease, it does not appear to be an autoimmune disease . The
exact underlying immune problem is not clear; however, it may be an immunodeficiency state. It also
often begins after gastroenteritis. Diagnosis is based on a number of findings including biopsy and
appearance of the bowel wall, medical imaging and description of the disease.

Symptoms:
Gastrointestinal

Abdominal pain may be the initial symptom of Crohn's disease usually in the lower right area.[24] It is
often accompanied by diarrhoea, especially in those who have had surgery. The diarrhoea may or
may not be bloody. The nature of the diarrhoea in Crohn's disease depends on the part of the small
intestine or colon involved.
Faecal consistency may range from solid to watery. In severe cases, an individual may have more
than 20 bowel movements per day and may need to awaken at night to defecate. Flatulence and
bloating may also add to the intestinal discomfort.

Perianal discomfort may also be prominent in Crohn's disease. Itchiness or pain around
the anus may be suggestive of inflammation, fistulization or abscess around the anal area or anal
fissure. Perianal skin tags are also common in Crohn's disease and may appear with or without the
presence of colorectal polyps.

Extraintestinal

Sometimes, Crohns disease causes inflammation outside of the GI tract. These symptoms are
called extra-intestinal symptoms and can also be linked to inflammation.
Inflammatory manifestations of the skin, eyes, liver, and joints are considered primary manifestations.

Eye
Inflammation of the interior portion of the eye, known as uveitis, can cause blurred vision and eye
pain, especially when exposed to light. Inflammation may also involve the sclera, a condition
called episcleritis.[35] Both episcleritis and uveitis can lead to loss of vision if untreated.

Liver
About one in three people with Crohns develop gallstones. These are small stones made of
cholesterol which may get trapped in the gallbladder, just beneath the liver, and can be very painful.
Several factors linked with Crohns can make gallstones more likely for example, removal of the
end of the small intestine or severe inflammation in this area, which can lead to poor absorption of
bile salts (which help to digest fat in the gut).

Joints
Sometimes, the joints in the spine and pelvis become inflamed a condition called ankylosing
spondylitis (or sacroiliitis, in its less severe form). This can flare-up independently of IBD. It often
causes pain over the sacroiliac joints, on either side of the lower part of the spine. Stiffness and pain
in the spine itself may eventually lead to loss of flexibility.

Causes:
While the exact cause is unknown,[46] Crohn's disease seems to be due to a combination
of environmental factors and genetic predisposition. Crohn's is the first genetically complex disease
in which the relationship between genetic risk factors and the immune system is understood in
considerable detail.

Genetics

There's evidence to suggest genetics plays a role in the development of Crohn's disease.
The first mutation found to be associated with Crohn's was a frameshift in the NOD2 gene (also
known as the CARD15gene),[53] followed by the discovery of point mutations.[54] Over thirty genes
have been associated with Crohn's; a biological function is known for most of them.

Researchers have also discovered genetic variations in certain regions of chromosome

5 and chromosome 10 that appear to contribute to Crohn disease risk. One area
of chromosome 5, known as the IBD5 locus, contains several genetic changes that may
increase the risk of developing this condition

Immune System
Until recently, the prevailing wisdom concerning the pathophysiology of Crohn's disease contended that
the characteristic intestinal inflammation resulted from a T celldriven process initiated by usually
innocuous commensal bacteria or bacterial products. However, a newer theory hypothesizes that
Crohn's results from an impaired innate immunity.[64]

Different components of innate immunity in Crohn's disease have been suggested to be defective or
impaired, a seemingly paradoxical hypothesis, given the data documenting
The later hypothesis describes impaired cytokine secretion by macrophages, which contributes to
impaired innate immunity and leads to a sustained microbial-induced inflammatory response in the
colon, where the bacterial load is high.

Environment
The increased incidence of Crohn's in the industrialized world indicates an environmental
component. Crohn's is associated with an increased intake of animal protein, milk protein and an
increased ratio of omega-6 to omega-3 polyunsaturated fatty acids. Those who consume vegetable
proteins appear to have a lower incidence of Crohn's disease. Consumption of fish protein has no
association.[96] Smoking increases the risk of the return of active disease (flares). Although stress is
sometimes claimed to exacerbate Crohn's disease, there is no concrete evidence to support such
claim.

Pathophysiology:
Chronic inflammation from T-cell activation
leading to tissue injury is implicated in the
pathogenesis of Crohn disease.

After activation by antigen presentation,

unrestrained responses of type 1 T helper (Th1)
cells predominate in Crohn disease as a
consequence of defective regulation. Th1
cytokines such as interleukin (IL)-12 and TNF-
stimulate the inflammatory response.
Inflammatory cells recruited by these cytokines
release nonspecific inflammatory substances,
including arachidonic acid metabolites,
proteases, platelet activating factor, and free
radicals, which result in direct injury to the
intestine.

Microscopically, the initial lesion starts as a focal

inflammatory infiltrate around the crypts,
followed by ulceration of superficial mucosa.
Later, inflammatory cells invade the deep
Figure 1Figure 1Colonic granuloma in patient with Crohn disease.
mucosal layers and, in that process, begin to
Hematoxylin-eosin staining.
organize into noncaseating granulomas (see the
image below). The granulomas extend through
all layers of the intestinal wall and into the mesentery and the regional lymph nodes.

Neutrophil infiltration into the crypts forms crypt abscesses, leading to destruction of the crypt
and atrophy of the colon. Chronic damage may be seen in the form of villous blunting in the
small intestine as well. Ulcerations are common and are often seen on a background of normal
mucosa.

Transmural inflammation results in thickening of the bowel wall and narrowing of the lumen.
As Crohn disease progresses, it is complicated by obstruction or deep ulceration leading to
fistulization by way of the sinus tracts penetrating the serosa, microperforation, abscess
formation, adhesions, and malabsorption.

Diagnosis:

The diagnosis of Crohn's disease can sometimes be challenging,[21] and a number of tests are often
required to assist the physician in making the diagnosis.[25] Even with a full battery of tests, it may not
be possible to diagnose Crohn's with complete certainty; a colonoscopy is approximately 70%
effective in diagnosing the disease, with further tests being less effective.

Although laboratory results for Crohn disease are nonspecific and are of value
principally for facilitating disease management, they may also be used as surrogate
markers for inflammation and nutritional status and to screen for deficiencies of vitamins
and minerals.
Routine laboratory studies include the following:
CBC count
Chemistry panel
Liver function tests
Inflammatory markers (ESR w/ CRP)
Stool studies (Faecal Calprotectin)
Serologic tests

Imaging modalities used for Crohn disease include the following:

Plain abdominal radiography
Barium contrast studies (eg, small bowel follow-through, barium enema, enteroclysis)
CT scanning of the abdomen
CT enterography or magnetic resonance enterography: Replacing small bowel follow-
through studies
MRI of the pelvis
Abdominal and/or endoscopic ultrasonography
Nuclear imaging (eg, technetium-99m hexamethyl propylene amine oxime, indium-111)
Fluorine-18-2-fluoro-2-deoxy-D-glucose scanning combined with positron emission
tomography or CT scanning

Management:

There is no cure for Crohn's disease and remission may not be possible or prolonged if achieved. In
cases where remission is possible, relapse can be prevented and symptoms controlled with
medication, lifestyle and dietary changes, changes to eating habits (eating smaller amounts more
often), reduction of stress, moderate activity and exercise. Surgery is generally contraindicated and
has not been shown to prevent remission. Adequately controlled, Crohn's disease may not
significantly restrict daily living.[139] Treatment for Crohn's disease is only when symptoms are active
and involve first treating the acute problem, then maintaining remission.
Lifestyle:

Certain lifestyle changes can reduce symptoms, including dietary adjustments, elemental diet,
proper hydration, and smoking cessation. Diets that include higher levels of fiber and fruit are
associated with reduced risk, while diets rich in total fats, polyunsaturated fatty acids, meat, and
omega-6 fatty acids may increase the risk of Crohn's.

Eating small meals frequently instead of big meals may also help with a low appetite. To manage
symptoms, have a balanced diet with proper portion control. Fatigue can be helped with regular
exercise, a healthy diet, and enough sleep.

A food diary may help with identifying foods that trigger symptoms. Some people should follow a low
fiber diet to control acute symptoms especially if fibrous foods cause symptoms.

Medication:

Acute treatment uses medications to treat any infection (normally antibiotics) and to reduce
inflammation (normally aminosalicylate anti-inflammatory drugs and corticosteroids). When
symptoms are in remission, treatment enters maintenance, with a goal of avoiding the recurrence of
symptoms.

Prolonged use of corticosteroids has significant side-effects; as a result, they are, in general, not
used for long-term treatment. Alternatives include aminosalicylates alone, though only a minority can
maintain the treatment, and many require immunomodulators.

Immunomodulators change the way the immune system behaves. Immunosuppressants decrease
the activity of the immune system. Immunostimulators increase the activity. Immunosuppressants
prescribed for Crohn's disease include:

azathioprine ( Azasan, Imuran)

cyclosporine
6-mercaptopurine (6MP, Purinethol)
tacrolimus (Prograf)
Methotrexate (MTX, Rheumatrex, Trexall)

Biologic drugs such as infliximab (Remicade) or infliximab-dyyb (Inflectra), a biosimilar to Remicade,

are often prescribed when a person with Crohn's disease does not respond to the standard
treatments of 5 ASA-containing drugs, corticosteroids, and immunosuppressants. Infliximab is an
antibody that attaches itself to the inflammation-promoting protein, tumor-necrosis factor-alpha
(TNF-alpha). Other anti-TNF medications are adalimumab (Humira) and adalimumab-atto
(Amjevita).

Other substances that may be prescribed to treat Crohn's include:

Antibiotics to treat bacterial infections and overgrowth of bacteria in the small intestine; types
of antibiotics commonly prescribed include:
 o ampicillin (Omnipen)
o cephalosporins
o fluoroquinolones (Ciprofloxacin)
o metronidazole (Flagyl)
o sulfonamides
o tetracycline
Antidiarrheal agents to stop diarrhea
Fluid replacements to counteract dehydration
Nutritional supplements to provide the nutrients that may not be absorbing properly

Surgery
Crohn's cannot be cured by surgery, as the disease eventually recurs, though it is used in the case
of partial or full blockage of the intestine. Surgery may also be required for complications such as
obstructions, fistulas, or abscesses, or if the disease does not respond to drugs.

After the first surgery, Crohn's usually comes back at the site where the diseased intestine was
removed and the healthy ends were re-joined, however it can come back in other locations.

After a resection, scar tissue builds up, which can cause strictures, which form when the intestines
become too small to allow excrement to pass through easily, which can lead to a blockage. After the
first resection, another resection may be necessary within five years.

Prognosis:
Crohn's disease can lead to several mechanical complications within the intestines,
including obstruction,[171]fistulae,[172] and abscesses.[173] Obstruction typically occurs
from strictures or adhesions that narrow the lumen, blocking the passage of the intestinal contents.

Crohn's disease also increases the risk of cancer in the area of inflammation. For example,
individuals with Crohn's disease involving the small bowel are at higher risk for small intestinal
cancer. Similarly, people with Crohn's colitis have a relative risk of 5.6 for developing colon
cancer.[175] Screening for colon cancer with colonoscopy is recommended for anyone who has had
Crohn's colitis for at least eight years.

Some studies suggest there is a role for chemoprotection in the prevention of colorectal cancer in
Crohn's involving the colon; two agents have been
suggested, folate and mesalamine preparations.[177] Also, immunomodulators and biologic
agents used to treat this disease may promote developing extra-intestinal cancers.

Individuals with Crohn's disease are at risk of malnutrition for many reasons, including decreased
food intake and malabsorption. The risk increases following resection of the small bowel. Such
individuals may require oral supplements to increase their caloric intake, or in severe cases, total
parenteral nutrition (TPN). Most people with moderate or severe Crohn's disease are referred to
a dietitian for assistance in nutrition.
 Epidemiology:
Crohns Disease may not be rare in India. Because of the high prevalence of intestinal tuberculosis there
is a possibility that Crohns Disease may be under-recognized in India.

m It is estimated that 1.4 million Americans suffer from Crohn's disease. American Jews of European
descent are four to five times more likely to develop IBD than the general population. Crohns disease has
long been considered a predominantly white disease. The prevalence rate among whites is 149 per
100,000.

Among African Americans, however, there has been a steady increase in reported cases of both Crohn's
disease and ulcerative colitis. An HMO with two million members reported hospitalization rates per
100,000 by race, over a six-year period, as:

o 10.2 - Whites
o 10.2 - African Americans
According to this study, prevalence rates among Hispanics and Asians were lower than those for whites
and African Americans.
The incidence of Crohn's disease is increasing in Europe.

Crohn's disease begins most commonly in people in their teens and 20s, and people in their 50s
through to their 70s. It is rarely diagnosed in early childhood. It usually affects female children more
severely than males.[188] However, only slightly more women than men have Crohn's disease.
CASE STUDY
10 yr old Indian male had been complaining of low grade fever, abdominal cramps, body ache and
increased bowel movement for 1 month. The routine stool test revealed mucous and 10-15 pus cells.
CRP was positive at 42mg/l. Initially treated for gastroenteritis with cefixime for 10 days. However, no
significant results were achieved.

The patient has one sibling who is healthy. Both parents are health. There is no family history of IBD.

Patient was referred for CT of the chest, abdomen and pelvis with Barium contrast. Following were the
results:

Both lungs are clear.

No significant hilar or mediastinal lymphadenopathy seen
Stricturing and thickening of terminal ileum, causing narrowing of the lumen suggesting
Crohns Disease.

Esophagogastroduodenoscopy (EGD) and colonoscopy was conducted to confirm suspicion of

Crohns disease. Bowel-cleansing was done pre-op. Biopsies was also collected from the
following:
Duodenum
Stomach
Terminal ileum
Ascending colon
Descending colon

The following were the observations:

Ileocecal valve inflamed and narrow. Surgeon couldnt enter despite several attempts.
Mild gastritis
Mild duodenitis in the first part only, rest of the duodenum is normal.

Following the EGD and colonoscopy, patient was prescribed on 1.5g of sulfasalazine and 25mg
of 6-mercaptopourine.

Patient was doing fine in terms of GI tract. However, because of immunosuppression and
asthma, patient had recurrent chest infections. Was referred to pulmonologist.

Seven years later, patient complains of stomach pain, anorexia, nausea. X-ray revealed chronic
constipation. Patient was prescribed bisacodyl and polyethylene glycol for relieving constipation.
Blood levels revealed positive CRP at 54 mg/l. Faecal calprotectin test was positive at 2100
mg/kg, all indicative of intestinal inflammation.

Patient was admitted and an MRE with barium contrast was conducted. Following were the
observations:
Distal ileum failed to adequately distend with reqd. oral suspension throughout study,
most likely due to and luminal narrowing
Significant bowel wall thickening measuring appr 7mm, involving ileocecal valve region
and distal 10-15 cm of ileum.
Distal ileum surrounded by fat stranding and minimal traces of free fluid.
 Active inflammatory process involving the ileocecal junction, distal ileum and proximal
caecum with luminal narrowing of the distal ileum.
No signs of acute bowel obstruction.

Following the MRE, the patient was prescribed 40mg prednisolone to ease intestinal
inflammation. Dosage of 6-mercaptopourine was increased to 50mg. Dosage of sulfasalazine
was increased to 2mg.