Transcript Ulcerative Colitis : UPDATED

By
TARIK ZAHER , MD
Assistant professor of Tropical Medicine ,
Zagazig University ,Egypt
 In
general, there has been a distinct northsouth gradient in risk.
 In North America, incidence rates range from
6.0 to 15.6 cases per 100,000 person-years.
 In contrast, studies have reported
significantly lower incidence rates of 0.6 to 6
per 100,000 person-years in other parts of
the world, including Asia, Africa, and Latin
America.
The etiology of UC is currently unknown but is likely
multifactorial ; complex interaction of three elements: genetic
susceptibility, host immunity, and environmental factors.
 Family
history is one of the most important
risk factors for developing the disease.
 There are susceptibility genes for UC on
chromosomes 1, 2, 3, 5, 6, 7, 10, 12, and 17.
 The C3435T polymorphism for the human
multidrug resistance 1 (MDR1) gene is linked
to susceptibility for UC .
 Several centers have reported an association
between severe disease and a rare allele of
HLA-DR1 (DRB1*0103).
 Several
infectious organisms, including
mycobacteria and viruses, have been
implicated in the pathogenesis of IBD.
 Three studies have identified more than
45,000 bacterial small-subunit (SSU) rRNA
genes in UC patients.
 A breakdown in the balance between
protective and harmful intestinal bacteria,
termed dysbiosis, can lead to disease.
 Smoking ,intestinal parasites and
appendectomy are protective.
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Breaches in the well-regulated mucosal immune system
lead to the chronic, uncontrolled mucosal inflammation
observed in UC(increase TH1).
The concept that UC is an autoimmune disease is
supported by its increased association with other
autoimmune disorders, including thyroid disease, diabetes
mellitus, and pernicious anemia.
Studies have suggested that pANCA may be associated with
a more-aggressive disease course.
A novel T-cell–mediated inflammatory pathway, which
appears to be involved in the pathogenesis of both Crohn's
disease and UC, has been discovered and centers on the
Th17 cell lineage.
Th17 cells have been shown to produce a variety of
cytokines, most notably IL-6 and IL-17. IL-17 is a potent
proinflammatory cytokine that not only facilitates T-cell
activation but also stimulates a variety of cells.
45% of patients with UC have disease limited to the rectosigmoid,
35% have disease extending beyond the sigmoid but not involving
the entire colon, and 20% of patients have pancolitis.
 The
mucosa in UC appears hyperemic,
edematous, and granular in mild disease. As
disease progresses, the mucosa becomes
hemorrhagic, with visible punctate ulcers.
These ulcers can enlarge and extend into the
lamina propria.
 Epithelial regeneration with recurrent
attacks results in the formation of
pseudopolyps.
 Another characteristic appearance of longstanding disease is atrophic and featureless
colonic mucosa.
Neutrophilic infiltration of colonic crypts gives
rise to cryptitis and ultimately to crypt abscesses
with neutrophilic accumulations in crypt lumens.
This migration of neutrophils from the
circulation into the lamina propria occurs in
response to a variety of chemoattractants,
including chemotactic peptides of colonic
bacteria, IL-8, activated complement, plateletactivating factor, and leukotriene B4.
 Chronic inflammatory infiltrate.
 Inflammation in UC characteristically is confined
to the mucosa.
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Following the initial flare, 40% to 65% of patients have an intermittent
course, and 5% to 10% of patients have a chronic continuous course. Up to
10% of patients have a severe first attack ultimately requiring colectomy.
 Common
symptoms include diarrhea, rectal
bleeding, passage of mucus, tenesmus,
urgency, and abdominal pain. In more-severe
cases, fever and weight loss may be
prominent.
Patients with mild or even moderately severe
disease exhibit few abnormal physical signs.
 Patients with severe attacks also might appear
well, but most are ill with tachycardia, fever,
orthostasis, and weight loss.
 In fulminant colitis, the abdomen often becomes
distended and firm, with absent bowel sounds
and signs of peritoneal inflammation.
 There may be aphthoid ulceration of the oral
mucosa. Clubbing of the fingernails is a
manifestation of chronic disease. Peripheral
edema can occur secondary to
hypoalbuminemia.
 Signs of extraintestinal manifestations
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Hematologic changes, including anemia,
leukocytosis, and thrombocytosis, reflect active
disease.
 Iron deficiency anemia may be present because
of chronic blood loss. Anemia also may be
present secondary to bone marrow suppression
resulting from chronic inflammation or
medications, including azathioprine, 6mercaptopurine (6-MP), and sulfasalazine.
 Serum inflammatory markers including
erythrocyte sedimentation rate (ESR) and Creactive protein (CRP) may be elevated in active
disease.
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 Colonoscopy
is not recommended in patients
with severely active disease for fear of
perforation; care must be taken to avoid
excessive distention.
A
plain film can give considerable
information with respect to the extent of
disease. The presence of marked colonic
dilatation suggests fulminant colitis or toxic
megacolon.
 Barium enema provides information on their
location, length, and diameter and allows
visualization of the entire colon when the
presence of strictures precludes
advancement of the colonoscope.
Mild
<4 stools/day, without or with only small amounts of blood
No fever
No tachycardia
Mild anemia
ESR < 30 mm/hr
Moderate
Intermediate between mild and severe
Severe
>6 stools/day, with blood
Fever > 37.5°C
Heart rate > 90 beats/min
Anemia with hemoglobin level < 75% of normal
ESR > 30 mm/hr
The goals of therapy of UC are to induce remission, to maintain remission,
to maintain adequate nutrition, to minimize disease- and treatmentrelated complications, and to improve the patient's quality of life.
Mild Disease
5-Aminosalicylates (Sulfasalazine , Olsalazine , Balsalazide , Mesalamine ):>2gm/d
-Topical (distal colitis)
-Oral (distal/extensive colitis)
-Combination
Moderate Disease
5-Aminosalicylates :
-Topical (distal colitis)
-Oral (distal/extensive colitis)
- Combination
Glucocorticoids:
-Topical (distal colitis):
-Oral (distal/extensive colitis): 1 mg/kg /day predinisolon
-Combination
Azathioprine or 6-mercaptopurine : 1 mg/kg /day
Severe Disease
IV glucocorticoids
IV cyclosporine : 2 mg/kg/day(blood level 200 - 300 ng/ml)
IV infliximab: 5 mg/kg/day ; 0,2,6 weeks
5-Aminosalicylates
-Topical (distal colitis)
-Oral (distal/extensive colitis):1.5 gm /day
Azathioprine or 6mercaptopurine:1mg/kg/day
Infliximab:5mg/kg every 2 monthes
Dose-Related
Alopecia
Anorexia
Back pain
Folate malabsorption (with sulfasalazine)
Headache
Nausea, vomiting, dyspepsia
Non–Dose-Related
Agranulocytosis, aplastic anemia
Arthralgia
Colitis
Fever
Fibrosing alveolitis, pulmonary eosinophilia
Hemolytic anemia (Heinz bodies)
Hepatitis
Hypersensitivity skin rashes (occasionally with photosensitivity)
Male infertility (with sulfasalazine)
Pancreatitis
Pericarditis, myocarditis
Acne
Impaired wound healing
Purpura, ecchymoses, petechiae
Striae
Adrenal insufficiency
Cushingoid appearance
Dyspepsia
Dysphagia/odynophagia (candidiasis)
Numerous pathogens
Growth retardation
Hyperglycemia, secondary diabetes mellitus
Hyperlipidemia, altered fat distribution
Hypertension
Myopathy
Osteonecrosis
Osteoporosis
Anxiety, mood swings
Depression
Insomnia
Psychosis
Cataracts
Glaucoma
Abnormal liver biochemical test results
Bone marrow suppression
Hypersensitivity reactions (fever, rash,
arthralgia)
Infections
Lymphoma
Nausea, abdominal pain, diarrhea
Pancreatitis
Anaphylaxis
Diarrhea
Electrolyte abnormalities
Gingival hyperplasia
Headache
Hepatotoxicity
Hirsutism
Hypertension
Infections
Nausea, vomiting
Opportunistic infections
Paresthesia
Renal insufficiency
Seizure
Tremor
Prophylaxis against Pneumocystis pneumonia (PCP) during
therapy is required.
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Antibiotics(metronidazole, ciprofloxacine,
refaximin).
Probiotics (Lactobacillus or Bifidobacterium),
Prebiotics(food constituents increasing,
probiotics and Synbiotics( both).
Nicotine patches.
Heparin: anti-inflammatory.
Biological Therapy:
-Anti-Tumor Necrosis Factor Antibodies:
infliximab and adalimumab
-Anti-Adhesion Molecules: Alicaforsen
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Cytapheresis: decrease WBCs.
Peroxisome Proliferator Receptor
Agonists(rosiglitazon)
Budesonide-MMX : decrease the rate of
steroid side effects.
Tofacitinib:oral Janus kinase 3 (JAK3)
inhibitor
Fish oil: protecting the integrity of colonic
mucosa
Trichuris suis : increase TH2.
Daclizumab : humanized monoclonal
antibody against the IL-2 receptor .
1- Risk of infection
Serious infections have happened in patients
Receiving TNFblocking; infections include
tuberculosis (TB) and infections caused by
viruses, fungi or bacteria that have spread
throughout the body.
2- Risk of Cancer
There have been cases of unusual
cancers(lymphomas) in children and teenage
patients using TNFblocking agents.
Indications for Surgery in Patients with
Ulcerative Colitis
-Colonic dysplasia or carcinoma
-Colonic hemorrhage, uncontrollable
-Colonic perforation
-Growth retardation
-Intolerable or unacceptable side effects of
medical therapy
-Medically refractory disease
-Systemic complications that are recurrent or
unmanageable
-Toxic megacolon
Acute colonic dilatation with a transverse
colon diameter of greater than 6 cm (on
radiologic examination) and loss of
haustration in a patient with a severe attack
of colitis.
 Colonic
strictures complicate UC in
approximately 5% of patients, most
commonly in those with extensive and longstanding colitis.
 Patients with colonic strictures usually
present with alterations in bowel habits,
both constipation and diarrhea.
 One series reported malignancy in 24% of
colonic strictures in patients with UC.
 In
general, the risk of colorectal cancer may
be estimated to increase within the range of
0.5% to 1.0% per year after 8 to 10 years of
disease in patients with extensive UC.
 Surveillance by colonoscopy every year after
8 years of UC ( biopsy every 10 cm).
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Pouchitis is said to occur when there is
nonspecific inflammation of the ileal
reservoir, resulting in variable clinical
symptoms resembling those of UC.
The mainstay of therapy for pouchitis is
antibiotics.
Angular stomatitis
Aphthous stomatitis
Erythema nodosum
Oral ulcerations
Psoriasis
Pyoderma gangrenosum
Pyostomatitis vegetans
Sweet's syndrome (acute febrile neutrophilic
dermatosis)
Conjunctivitis
Episcleritis
Retinal vascular disease
Scleritis
Uveitis, iritis
Ankylosing spondylitis
Osteomalacia
Osteonecrosis
Osteopenia
Osteoporosis
Peripheral arthropathy
Sacroiliitis
Autoimmune hepatitis
Cholangiocarcinoma
Pericholangitis
Primary sclerosing cholangitis
Hepatic steatosis
Anemia of chronic disease
Autoimmune hemolytic anemia
Hypercoagulable state
Iron deficiency anemia
Leukocytosis or thrombocytosis
Leukopenia or thrombocytopenia