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Definition:
Is a chronic transmural inflammatory disease that can involve the whole
GI-tract from the mouth to the perianal Area.
The transmural inflammatory nature of Crohn's disease often leads to
fibrosis and to obstructive clinical presentations. The transmural inflammation
can also result in sinus tracts that burrow through and penetrate the serosa,
giving rise to microperforations and fistulae.
Areas of involvement in percent:
-
Small bowl, usually distal
ileum 80%
-
Ileocolonic area 50%
-
Colon 20 %, with sparing the rectum in 50 % in
Patients
-
Perianal area 30%
-
Mouth, stomach and duodenum
5-15%
Epidemiology:
In America 3.1 to 20.2 cases per 100,000 person-years
Age between 15 and 40 years with second peak between 50 and 80
Female are slightly more than male
Approximately 10 to 25 percent of individuals with IBD have a first
degree relative with either Crohn's disease or ulcerative colitis
Etiology:
is unknown
Clinical
manifestations:
Symptoms of the disease:
-
diarrhea, usually chronic
without gross blood
-
Abdominal pain: crampy
pain, usually in lower right quadrant
-
Fatigue
-
Weight los
-
Fever
Symptoms of disease’s complications:
1-
Fistulas: are connection
between two organs with epithelial line.
45% of patients develop fistulas before the diagnosis, the cumulative
risk of developing a fistula in 10 years 33% and in 20 years is 50%:
There are many types of fistulas:
- enteroenteric fistula are usually symptomless and may
present as palpable mass
- enterovesical fistula present with recurrent urinary
tract infections, pneumaturia
- enterovaginal fistula: present with fecal or gas
passage through the vagina
- enterocotaneus fistula: bowel content drains to the
surface of the skin
- fistulas to the retroperitoneum: cause
Posoasabscesses, ureter obstruction with hydronephrosis.
2-
Abscesses cause abdominal
pain, fever, palpable mass, and tenderness by localized peritonitis. Penetration
with generalized peritonitis is rare but still can happen.
3-
Perianal disease: present
in 30% in patients and include anal fissure, perianal abscess, and anorectal
fistula.
4-
Constrictions and
obstructions with abdominal pain, vomiting.
5-
Malabsorption:
Causes deficiency manifestation: vitamin B12
deficiency
Bile salts malabsorption in terminal ileum
cause a compensatory high production in bile acid (ab 50-60 cm ileus
resection), this compensation will not be enough by 100 cm ileus resection, und
will lead to:
Watery diarrhea due to effect of bile acid on
the colon
Fatty diarrhea due to fat malabsorption
Gallen stones due to the reduction in bile
acid to cholesterol ratio in the bladder which make the bile more lithogen
6-
Symptoms of other
gastrointestinal involvement:
Aphthous in mouth, dysphagia in esophagus,
Magen-out obstruction.
Extraintestinal symptoms:
-
Arthritis: in 20% in
patients, usually large joints, central, such as sacroiliitis, ankylosing
spondylitis
-
Eye: 5% in Patients: episcleritis,
uveitis, iritis
-
Skin: 10 % in Patients: erythema nodosum, pyoderma
gangrenosum
-
Primary sclerosing cholangitis: 5%.
-
Venous and arterial thromboembolism
-
Renal Stones
-
Osteoporosis due to steroid
therapy and impaired Vit D and calcium absorption
-
Vit B12 Deficiency with
pernicious anemia
DDx:
-
Infectious colitis
-
Lactulose intolerance:
abdominal pain, diarrhea and flatulence after ingestion of milk or its products
-
Irritable bowel syndrome:
abdominal pain with altered bowel habits
-
Ulcerative colitis:
Suggestive for CD are:
Involvement of the small bowel
Sparing of the rectum
Perianal disease
Absence of the gross bleeding
Focality of the lesions.
Fistula formations
Granulomas presence
-
Another DDx vary due to the
location of the affected bowl segments:
Appendicitis, diverticulitis, ischemic
colitis, carcinoma etc.…
Diagnosis:
1-
Suggesting clinic
2-
Labor: CBC: anemia with leukocytosis
CRP and ESR are elevated
B12, Iron deficiency
3-
Fecal protectin may help
identify patients with intestinal inflammation and can be used to
monitor patients for postoperative recurrence after ileocolic resection for
Crohn's disease. Levels of >100 μg/g indicate endoscopic recurrence with a
sensitivity in the range of 89%. In patients with an infliximab-induced
remission, fecal calprotectin of >160 μg/g has a sensitivity of 91.7% and a
specificity of 82.9% to predict relapse
4-
Endoscopy:
-
Coloscopy with ileum
intubation:
Edema, skip lesions (focal ulcerations),
cobblestone appearance (polypoid changes)
Histologic: inflammation with ulcerations
(confirming but not diagnostic), granulomas in 30% (diagnostic but DDx for
granulomas must be excluded)
-
Gastroscopy
-
Wireless capsule endoscopy
-
enteroscopy
5-
Imaging studies:
CT-enterography and MRT-enterography to
evaluate the small bowel
Abdomen-CT by complications
MRT by perianal disease
Phenotypic
classification.
The international standard of phenotypic classification
is currently the 2005 Montreal revision of the Vienna classification. This
classification system includes age of onset, disease location, and disease
behavior.
-
A1 refers to disease onset
at 16 years of age or younger, A2 disease onset between 17 and 40 years of age,
and A3 over 40 years.
-
Disease location is divided
into L1 (terminal ileum), L2 (colon), L3 (ileocolonic), and L4 (upper GI
involvement).
-
Disease behavior is divided
into B1 (nonstricturing, nonpenetrating), B2 (structuring), and B3
(penetrating). The letter “p” is appended to the B subtype if there is the
presence of perianal fistulizing disease.
-
Location tends to remain
stable and behavior tends to progress from B1 to B2 or B3 over the course of
disease
Therapy:
General principles:
Clinical evidence of improvement should be taken within 2-4 weeks of
Therapy, maximal improvement should happen in 12-16 Weeks.
Goal of the therapy to induce remission and maintain it
Therapy differs due to disease’s activity:
1- Mild to moderate Crohn disease:
Patient can eat and drink well, weight loss <10%, no complications
such as fever, dehydration, abdominal mass, or obstruction: CDAI 150-220:
-
5 ASA (aminosalicylates):
sulfasalazine and mesalazine:
Sulfalazine 6-9 g/Day: in colonic/ileocolonic
disease BUT NOT in small bowel CD
Mesalazine: its use has no prove of efficacy
and shouldn’t be used in active CD
-
Antibiotics: ciprofloxacin
and metronidazole;
its use has no prove of efficacy and
shouldn’t be used in active CD
-
Glucocorticoids:
prednisolone, budesonide
Budisonide 9 mg /day by ileocecal disease
(less Corticosteroid Side effects)
2- Moderate to severe disease
Patient with sig. weight loss, failure to therapy of mild to moderate
disease or complications such as fever, dehydration, abdominal mass, intermittent
nausea or vomiting without obstruction. CDAI > 220-450
3- Refractory disease:
-
Repeatedly relapse after
achieving remission with first-line agents
-
Remain symptomatic despite
adequate doses of glucocorticoids (steroid-resistant), antibiotics
-
Flare when glucocorticoids
are decreased or stopped (steroid-dependent)
To be treated like moderate to severe disease
-
Oral corticosteroids:
As short-term therapy to relive the symptoms
Prednisolon 40-60 mg/day over 1-2 weeks then reduce
successive within no more 3 months
-
Immunomodulators:
A response to these medications will usually
be seen within three to six months. During this period, patients often require
concomitant steroid therapy with a gradual reduction in the steroid dose after
one to two months of treatment with azathioprine or 6-MP.
Azatioprin 1.5-2.5 mg/Kg/day for
maintenance of remission AND NOT as remission induction
6 Mercaptopurin: 0.75-1.5 mg/kg/day
for maintenance of remission AND NOT as remission induction
TPMT (mercaptopurine methyltransferase)
should be tested before initial use of Azatiopron/6 MP
SE: Bone marrow suppression, Malignancy
Methotrixat:
A response should be seen within three
months. For patients on steroid therapy, the steroid should be continued during
this period with a gradual lowering of the dose.
25 mg i.m . /Week: as remission maintenance,
when response achieved, dosage of 15 to 12.5 mg/week s.c. , p.o. or i.m. could
be enough.
SE: hepatotoxicity, bone marrow suppression
Concomitant therapy with folic
acid 1 mg/day may diminish adverse effects to methotrexate
-
Anti TNF Agents: Infliximab
i.v., adalimumab s.c. /2weeks, certolizumab s.c. / 4 weeks (not approved in
Europe)):
By corticosteroid resistance/Thiopurine or
MTX refractory
Assessment of latent or active infections
should be initiated before beginning with therapy (Tuberculosis, Hepatitis B)
Vaccination status should IDEALY be reviewed
and updated before initiated therapy,
for induction of remission and remission
maintenance
Combination therapy of infliximab with
immunomodulators (thiopurines) is more effective than treatment with either
immunomodulators alone or infliximab alone
Infliximab: 5-10 mg/kg/ 8 Weeks.
4- Severe-fulminant disease persistent symptoms despite
therapy with i.v. corticosteroid or biologic agents, obstruction, abscess,
peritonitis signs, cachexia, CDAI > 450:
-
Intravenous corticosteroids
should be used to treat severe or fulminant Crohn's disease 40-60 mg/day
-
Infliximab may be
administered to treat fulminant Crohn's disease
MAINTENANCE
THERAPY OF LUMINAL CROHN'S DISEASE
-
Once remission is induced
with corticosteroids, a thiopurine 50 mg/day or methotrexate 25 to 12.5 mg/Week
should be considered
-
Patients who are steroid
dependent should be started on thiopurines or methotrexate with or without
anti-TNF therapy
-
Oral 5-aminosalicylic acid
is not recommended for long-term treatment
-
Corticosteroids are not
effective for maintenance of medically induced remission in Crohn's disease and
should not be used for long-term treatment
-
Anti-TNF therapy,
specifically infliximab 5-10 mg/kg/ 8 Weeks, adalimumab, and certolizumab
pegol, should be used to maintain remission of anti-TNF-induced remission,
Combination with thiopurine or Methotrexate is more effective BUT at higher
risk of malignancy and should be considered individually
-
There is no higher risk of
opportunistic infections with the combination of thiopurines and anti-TNFs
compared with either medication alone
POSTOPERATIVE
CROHN'S DISEASE: MAINTENANCE, PREVENTION, AND TREATMENT
-
Postoperative recurrence of
Crohn's disease can be defined by endoscopic findings or clinical symptoms
-
Patients at low risk for
postoperative CD recurrence are: nonsmokers, do not have penetrating disease,
and have never had a prior surgical resection.
No treatment after surgery in this population
with subsequently performing a 6-month postoperative colonoscopy to assess for
the presence of CD recurrence would be reasonable.
-
Patients who are
nonsmokers, who have penetrating disease without a prior history of surgical
resection, and who have received no prior medication should receive thiopurines
with or without metronidazole (no more than 3 months), and subsequently undergo
a colonoscopy at 6 months. If there is evidence of CD on the colonoscopy, then
anti-TNF therapy should be added.
-
Patients who have had a
prior resection within a 10-year period should receive (ab week 4
postoperative) anti-TNF therapy with or
without an immunomodulator and undergo a subsequent colonoscopy at 6 months
postoperatively.
MEDICAL MANAGEMENT
OF CROHN'S DISEASE COMPLICATIONS:
1.
Fistulae:
-
30% of Patients would have
fistulae
-
infliximab 5 mg/kg administered
at weeks 0, 2, and 6 and then every 8 weeks as maintenance therapy. Combination
therapy with azathioprine has
superior efficacy than monotherapy, but should NOT be done as long term therapy
due to malignancy risk
Drainage of abscesses (surgically or
percutaneously) should be undertaken before treatment of fistulizing Crohn's
disease with anti-TNF agents
-
Antibiotics may be
effective and should be considered in treating simple perianal fistulas
Metronidazol 400 mg x2 for 8 weeks/
Ciprofloxacin 500 mg x2 for 8 Weeks
-
Steroids and sulfasalazine have
not been successful for inducing fistula closure
2.
Localized peritonitis:
-
bowel rest and
broad-spectrum antibiotics i.v. for 7-10 days, followed be two- to four-week
course of outpatient oral therapy with ciprofloxacin and metronidazole should
be considered.
-
Intestinal resection should
be considered in nonresponders.
-
If patient on
corticosteroid, then a small increase in the dose may be required. for those
not previously on steroids, withholding steroids to avoid masking any further
sepsis is to be advised.
3.
Abscesses:
-
medical management with
antibiotics
-
percutaneous drainage,
-
surgery with resection of
involved intestinal segments.
4.
Small bowl obstruction:
-
Conservative therapy with
intravenous hydration, nasogastric suction, and parenteral nutrition is often
successful, with a response seen within 24 to 48 hours.
-
Parenteral glucocorticoids
should be considered in nonresponders.
-
Surgery is reserved for
those patients who do not respond to these noninvasive measures OR who have
evidence of small bowel ischemia.
Written by: Ayman Zoaa
I’m a resident doctor living in Bremerhaven-Germany, my goal here is to explain medical stuff as easy and practical as possible. My second purpose is to help those who are trying to begin specializing in Germany.About my profession, I’m 30 years old, was born in Syria on 1989, I studied medicine at the University of Aleppo between 2007 and 2013, then I traveled to Germany and began my actual work before about 3 Years. I have got my medicine certificate recognized in Germany after I had made the recognition test and the medical language test.I’m specializing in internal medicine, and then I’ll proceed to gastroenterology, and hopefully endocrinology.I find writing interesting, and it also helps me to keep my information up to date, what we- medical people - need.Let us keep in touch through singing up, and through the contact-from, i will answer your Questions gladly
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