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ulcerative colitis
INTRODUCTION
• recurring episodes of inflammation limited
to the mucosal layer of the colon
• commonly involves the rectum and may
extend in a proximal and continuous
fashion
CLINICAL MANIFESTATIONS
• Colitis
– diarrhea+blood
– frequent and small in volume
– colicky abdominal pain, urgency, tenesmus, and incontinence
– mainly distal disease may have constipation accompanied by frequent
discharge of blood and mucus.
– onset: gradual
– progressive over several weeks
– self-limited
– severity: from mild disease with four or fewer stools per day with or
without blood to severe disease with more than 10 stools per day with
severe cramps and continuous bleeding
– systemic symptoms: fever, fatigue, and weight loss. Dyspnea, and
palpitations due to anemia secondary to iron deficiency from blood
loss, anemia of chronic disease, or autoimmune hemolytic anemia
(AIHA).
• Physical examination is often normal
• Patients with moderate to severe ulcerative
colitis may have abdominal tenderness to
palpation, fever, hypotension, tachycardia, and
pallor.
• Rectal examination may reveal evidence of
blood.
• Patients with prolonged diarrhea symptoms may
have evidence of muscle wasting, loss of
subcutaneous fat, and peripheral edema due to
weight loss and malnutrition.
Disease severity
• Montreal classification
– frequency and severity of diarrhea, and the presence of systemic
symptoms and laboratory abnormalities
• Mild: four or fewer stools per day with or without blood, no signs of
systemic toxicity, and a normal erythrocyte sedimentation rate
(ESR).
• Moderate: frequent loose, bloody stools (>4 per day), mild anemia
not requiring blood transfusions, and abdominal pain that is not
severe
• Severe: frequent loose bloody stools (≥6 per day) with severe
cramps and evidence of systemic toxicity as demonstrated by a
fever (temperature ≥37.5ºC), tachycardia (HR ≥90 beats/minute),
anemia (hemoglobin <10.5 g/dL), or an elevated ESR (≥30
mm/hour).
• Mayo score
– Stool pattern, Most severe rectal bleeding of the day, Enoscopic
findings, Global assessment by physician
Acute complications
• Severe bleeding
– up to 10 percent of patients
• Fulminant colitis and toxic megacolon
– fulminant colitis with more than 10 stools per day, continuous
bleeding, abdominal pain, distension, and acute, severe toxic
symptoms including fever and anorexia
– Toxic megacolon is characterized by colonic diameter ≥6 cm or
cecal diameter >9 cm and the presence of systemic toxicity
• Perforation
– most commonly occurs as a consequence of toxic megacolon
– may also occur in the absence of toxic megacolon in patients
with the first episode of ulcerative colitis due to lack of scarring
from prior attacks of colitis
– 50 percent mortality
Extraintestinal manifestations
• less than 10 percent at initial presentation
• 25 percent in their lifetime
– Musculoskeletal (most frequent)
• nondestructive peripheral arthritis (large joints) and ankylosing spondylitis
• osteoporosis, osteopenia, and osteonecrosis
– Eye
• uveitis and episcleritis
• Scleritis, iritis, and conjunctivitis
– Skin
• erythema nodosum and pyoderma gangrenosum
– Hepatobiliary
• Primary sclerosing cholangitis (Alkp↑), fatty liver, and autoimmune liver disease
• fatigue, pruritus, fevers, chills, night sweats, and right upper quadrant pain
– Hematopoietic/coagulation
• venous and arterial thromboembolism
• Autoimmune hemolytic anemia (AIHA)
– Pulmonary (rare)
• parenchymal lung disease, serositis, thromboembolic disease, and drug-induced lung toxicity
LABORATORY FINDINGS
• anemia, an elevated erythrocyte
sedimentation rate (ESR) (≥30mm/hour),
low albumin, and electrolyte abnormalities
due to diarrhea and dehydration
• primary sclerosing cholangitis may have
an elevation in serum alkaline
phosphatase concentration
• Fecal calprotectin or lactoferrin may be
elevated due to intestinal inflammation
IMAGING
• not required for the diagnosis of ulcerative
colitis
• may identify proximal constipation,
mucosal thickening or “thumbprinting”
secondary to edema, and colonic dilation
in patients with severe or fulminant
ulcerative colitis.
Double contrast barium enema
• diffusely reticulated
pattern with
superimposed
punctate collections
of barium in
microulcerations
• Barium enema
should be avoided
in patients who are
severely ill since it
may precipitate
ileus with toxic
megacolon
EVALUATION
• exclude other causes of colitis > establish
the diagnosis of ulcerative colitis >
determine the extent and severity of the
disease
Diagnosis
• based on
– presence of chronic diarrhea for more than
four weeks
– evidence of active inflammation on
endoscopy
– chronic changes on biopsy
History
• risk factors for other causes of colitis
• recent travel to areas endemic for parasitic infections including
amebiasis
• recent antibiotic use that might predispose to an infection with
Clostridium difficile,
• history of or risk factors for sexually transmitted diseases (eg,
Neisseria gonorrhea and herpes simplex virus (HSV)) that are
associated with proctitis.
• Atherosclerotic disease or prior ischemic episodes are suggestive of
chronic colonic ischemia.
• A history of abdominal/pelvic radiation and NSAID/medication
exposure should be sought as these may also be associated with
colitis.
• In an immunocompromised patient, cytomegalovirus (CMV) can
mimic ulcerative colitis.
Laboratory studies
• Stool Clostridium difficile toxin
• routine stool cultures (Salmonella, Shigella,
Campylobacter, Yersinia),
• specific testing for E. coli O157:H7. Microscopy for ova
and parasites (three samples) and a Giardia stool
antigen test
• specific serologic testing for sexually transmitted
diseases including Neisseria gonorrhea, HSV, and
Treponema pallidum should be consider
• complete blood count, electrolytes, albumin, and
markers of inflammation erythrocyte sedimentation rate
and C-reactive protein (CRP)
Endoscopy
• are nonspecific. Biopsies of the colon obtained on endoscopy are
necessary to establish the chronicity of inflammation and to exclude
other causes of colitis
• a colonoscopy should be avoided in hospitalized patients with
severe colitis because of the potential to precipitate toxic
megacolon.
• loss of vascular markings due to engorgement of the mucosa, giving
it an erythematous appearance
• In addition, granularity of the mucosa, petechiae, exudates, edema,
erosions, touch friability, and spontaneous bleeding may be present
• severe cases may be associated with macroulcerations, profuse
bleeding, and copious exudates
• Nonneoplastic pseudopolyps may be present in areas of disease
involvement due to prior inflammation
Biopsy
• Biopsy features suggestive of ulcerative colitis
include crypt abscesses, crypt branching,
shortening and disarray, and crypt atrophy
• increased lamina propria cellularity, basal
plasmacytosis, basal lymphoid aggregates, and
lamina propria eosinophils
• Although none of these features are specific for
ulcerative colitis, the presence of two or more
histologic features is highly suggestive of
ulcerative colitis
DIFFERENTIAL DIAGNOSIS
• Crohn disease
– absence of gross bleeding, presence of
perianal disease (eg, anal fissures, anorectal
abscess), and fistulas.
– The absence of rectal inflammation and the
presence of ileitis, focal inflammation, and
granulomas on endoscopy and biopsy
• Infectious colitis
– be excluded with stool and tissue cultures,
stool studies, and on biopsies of the colon
DIFFERENTIAL DIAGNOSIS
• Solitary rectal ulcer syndrome
– histology with a thickened mucosal layer and distortion of crypt
architecture
– lamina propria is replaced with smooth muscle and collagen
leading to hypertrophy and disorganization of the muscularis
mucosa
• Graft versus host disease
– bone marrow transplantation pt: chronic diarrhea
– proximal gastrointestinal tract (eg, dysphagia, painful ulcers) or
other organs (eg, liver involvement as suggested by elevated
liver tests, skin involvement resembling lichen planus or
scleroderma)
– histologic examination in chronic GVHD is characterized by the
presence of crypt cell necrosis with the accumulation of
degenerative material in the dead crypts
DIFFERENTIAL DIAGNOSIS
• Diverticular colitis
– inflammation in the interdiverticular mucosa
without involvement of the diverticular orifices
– limitation to a segment of diverticular disease,
sparing the rectum, terminal ileum, and other
portions of the colon)
• Medication associated colitis
– NSAIDs can cause chronic diarrhea and
bleeding. Other drugs that may cause a
similar clinical presentation include retinoic
acid, ipilimumab, and gold.
NATURAL HISTORY
• usually present with attacks of bloody
diarrhea that last for weeks to months
• intermittent exacerbations alternating with
long periods of complete symptomatic
remission
• a small percentage of patients have
continuing symptoms and are unable to
achieve complete remission
Disease course
• 67 percent of patients have at least one
relapse 10 years following the diagnosis
• late-onset ulcerative colitis (diagnosed at
age 50 years or older) -> higher likelihood
of steroid free clinical remission (64 versus
49 percent) at one year as compared with
those with early onset ulcerative colitis
(diagnosed between ages 18 and 30
years)
Disease course
• Extension of colonic disease is seen in up to 20 percent
of patients within five years [42,46-48]. Patients with
proctitis have a 50 percent chance of extension and
those with disease proximal to the sigmoid colon have a
9 percent chance of progression to pancolitis.
• Approximately 20 to 30 percent of patients with
ulcerative colitis will require colectomy for acute
complications or for medically intractable disease.
• for patients with pancolitis, the rate of colectomy is
approximately 19 percent after 10 years [42]. In contrast,
5 percent of patients who present with proctitis alone
have undergone colectomy after 10 years
• Mucosal healing in response to treatment is also
important in predicting long-term clinical outcomes
Chronic complications
• Stricture
– due to repeated episodes of inflammation and
muscle hypertrophy in about 10 percent of cases with
ulcerative colitis
– most frequently seen in the rectosigmoid colon
– should be considered malignant until proven
otherwise by endoscopic evaluation with biopsy
– Surgery is indicated for strictures that cause
continued symptoms of obstruction or that cannot be
fully evaluated to exclude malignancy.
Chronic complications
• Dysplasia or colorectal cancer
– increased risk for colorectal cancer (CRC)
– extent of colitis and duration of disease are the two
most important risk factors for CRC
– proctitis and proctosigmoiditis are probably not an
increased risk of CRC
– risk begins to increase 8 to 10 years following the
onset of symptoms in patients with pancolitis
• 2.5 percent after 20 years and 7.6 percent after 30 years
• left-sided colitis have almost the same risk of CRC and
dysplasia as those with pancolitis but the risk of CRC
increases only after 15 to 20 years
Chronic complications
• Mortality
– slightly higher overall mortality compared with
the general population (HR 1.2, 95% CI 1.22-
1.28)
– The overall mortality appears to be highest in
the first year after ulcerative colitis diagnosis
(HR 2.4, 95% CI 2.3-2.6).
– mortality rates appear to have decreased over
time

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Understanding ulcerative colitis: causes, symptoms & treatment

  • 2. INTRODUCTION • recurring episodes of inflammation limited to the mucosal layer of the colon • commonly involves the rectum and may extend in a proximal and continuous fashion
  • 3. CLINICAL MANIFESTATIONS • Colitis – diarrhea+blood – frequent and small in volume – colicky abdominal pain, urgency, tenesmus, and incontinence – mainly distal disease may have constipation accompanied by frequent discharge of blood and mucus. – onset: gradual – progressive over several weeks – self-limited – severity: from mild disease with four or fewer stools per day with or without blood to severe disease with more than 10 stools per day with severe cramps and continuous bleeding – systemic symptoms: fever, fatigue, and weight loss. Dyspnea, and palpitations due to anemia secondary to iron deficiency from blood loss, anemia of chronic disease, or autoimmune hemolytic anemia (AIHA).
  • 4. • Physical examination is often normal • Patients with moderate to severe ulcerative colitis may have abdominal tenderness to palpation, fever, hypotension, tachycardia, and pallor. • Rectal examination may reveal evidence of blood. • Patients with prolonged diarrhea symptoms may have evidence of muscle wasting, loss of subcutaneous fat, and peripheral edema due to weight loss and malnutrition.
  • 5. Disease severity • Montreal classification – frequency and severity of diarrhea, and the presence of systemic symptoms and laboratory abnormalities • Mild: four or fewer stools per day with or without blood, no signs of systemic toxicity, and a normal erythrocyte sedimentation rate (ESR). • Moderate: frequent loose, bloody stools (>4 per day), mild anemia not requiring blood transfusions, and abdominal pain that is not severe • Severe: frequent loose bloody stools (≥6 per day) with severe cramps and evidence of systemic toxicity as demonstrated by a fever (temperature ≥37.5ºC), tachycardia (HR ≥90 beats/minute), anemia (hemoglobin <10.5 g/dL), or an elevated ESR (≥30 mm/hour). • Mayo score – Stool pattern, Most severe rectal bleeding of the day, Enoscopic findings, Global assessment by physician
  • 6. Acute complications • Severe bleeding – up to 10 percent of patients • Fulminant colitis and toxic megacolon – fulminant colitis with more than 10 stools per day, continuous bleeding, abdominal pain, distension, and acute, severe toxic symptoms including fever and anorexia – Toxic megacolon is characterized by colonic diameter ≥6 cm or cecal diameter >9 cm and the presence of systemic toxicity • Perforation – most commonly occurs as a consequence of toxic megacolon – may also occur in the absence of toxic megacolon in patients with the first episode of ulcerative colitis due to lack of scarring from prior attacks of colitis – 50 percent mortality
  • 7. Extraintestinal manifestations • less than 10 percent at initial presentation • 25 percent in their lifetime – Musculoskeletal (most frequent) • nondestructive peripheral arthritis (large joints) and ankylosing spondylitis • osteoporosis, osteopenia, and osteonecrosis – Eye • uveitis and episcleritis • Scleritis, iritis, and conjunctivitis – Skin • erythema nodosum and pyoderma gangrenosum – Hepatobiliary • Primary sclerosing cholangitis (Alkp↑), fatty liver, and autoimmune liver disease • fatigue, pruritus, fevers, chills, night sweats, and right upper quadrant pain – Hematopoietic/coagulation • venous and arterial thromboembolism • Autoimmune hemolytic anemia (AIHA) – Pulmonary (rare) • parenchymal lung disease, serositis, thromboembolic disease, and drug-induced lung toxicity
  • 8.
  • 9. LABORATORY FINDINGS • anemia, an elevated erythrocyte sedimentation rate (ESR) (≥30mm/hour), low albumin, and electrolyte abnormalities due to diarrhea and dehydration • primary sclerosing cholangitis may have an elevation in serum alkaline phosphatase concentration • Fecal calprotectin or lactoferrin may be elevated due to intestinal inflammation
  • 10. IMAGING • not required for the diagnosis of ulcerative colitis • may identify proximal constipation, mucosal thickening or “thumbprinting” secondary to edema, and colonic dilation in patients with severe or fulminant ulcerative colitis.
  • 11. Double contrast barium enema • diffusely reticulated pattern with superimposed punctate collections of barium in microulcerations • Barium enema should be avoided in patients who are severely ill since it may precipitate ileus with toxic megacolon
  • 12. EVALUATION • exclude other causes of colitis > establish the diagnosis of ulcerative colitis > determine the extent and severity of the disease
  • 13. Diagnosis • based on – presence of chronic diarrhea for more than four weeks – evidence of active inflammation on endoscopy – chronic changes on biopsy
  • 14. History • risk factors for other causes of colitis • recent travel to areas endemic for parasitic infections including amebiasis • recent antibiotic use that might predispose to an infection with Clostridium difficile, • history of or risk factors for sexually transmitted diseases (eg, Neisseria gonorrhea and herpes simplex virus (HSV)) that are associated with proctitis. • Atherosclerotic disease or prior ischemic episodes are suggestive of chronic colonic ischemia. • A history of abdominal/pelvic radiation and NSAID/medication exposure should be sought as these may also be associated with colitis. • In an immunocompromised patient, cytomegalovirus (CMV) can mimic ulcerative colitis.
  • 15. Laboratory studies • Stool Clostridium difficile toxin • routine stool cultures (Salmonella, Shigella, Campylobacter, Yersinia), • specific testing for E. coli O157:H7. Microscopy for ova and parasites (three samples) and a Giardia stool antigen test • specific serologic testing for sexually transmitted diseases including Neisseria gonorrhea, HSV, and Treponema pallidum should be consider • complete blood count, electrolytes, albumin, and markers of inflammation erythrocyte sedimentation rate and C-reactive protein (CRP)
  • 16. Endoscopy • are nonspecific. Biopsies of the colon obtained on endoscopy are necessary to establish the chronicity of inflammation and to exclude other causes of colitis • a colonoscopy should be avoided in hospitalized patients with severe colitis because of the potential to precipitate toxic megacolon. • loss of vascular markings due to engorgement of the mucosa, giving it an erythematous appearance • In addition, granularity of the mucosa, petechiae, exudates, edema, erosions, touch friability, and spontaneous bleeding may be present • severe cases may be associated with macroulcerations, profuse bleeding, and copious exudates • Nonneoplastic pseudopolyps may be present in areas of disease involvement due to prior inflammation
  • 17. Biopsy • Biopsy features suggestive of ulcerative colitis include crypt abscesses, crypt branching, shortening and disarray, and crypt atrophy • increased lamina propria cellularity, basal plasmacytosis, basal lymphoid aggregates, and lamina propria eosinophils • Although none of these features are specific for ulcerative colitis, the presence of two or more histologic features is highly suggestive of ulcerative colitis
  • 18. DIFFERENTIAL DIAGNOSIS • Crohn disease – absence of gross bleeding, presence of perianal disease (eg, anal fissures, anorectal abscess), and fistulas. – The absence of rectal inflammation and the presence of ileitis, focal inflammation, and granulomas on endoscopy and biopsy • Infectious colitis – be excluded with stool and tissue cultures, stool studies, and on biopsies of the colon
  • 19. DIFFERENTIAL DIAGNOSIS • Solitary rectal ulcer syndrome – histology with a thickened mucosal layer and distortion of crypt architecture – lamina propria is replaced with smooth muscle and collagen leading to hypertrophy and disorganization of the muscularis mucosa • Graft versus host disease – bone marrow transplantation pt: chronic diarrhea – proximal gastrointestinal tract (eg, dysphagia, painful ulcers) or other organs (eg, liver involvement as suggested by elevated liver tests, skin involvement resembling lichen planus or scleroderma) – histologic examination in chronic GVHD is characterized by the presence of crypt cell necrosis with the accumulation of degenerative material in the dead crypts
  • 20. DIFFERENTIAL DIAGNOSIS • Diverticular colitis – inflammation in the interdiverticular mucosa without involvement of the diverticular orifices – limitation to a segment of diverticular disease, sparing the rectum, terminal ileum, and other portions of the colon) • Medication associated colitis – NSAIDs can cause chronic diarrhea and bleeding. Other drugs that may cause a similar clinical presentation include retinoic acid, ipilimumab, and gold.
  • 21. NATURAL HISTORY • usually present with attacks of bloody diarrhea that last for weeks to months • intermittent exacerbations alternating with long periods of complete symptomatic remission • a small percentage of patients have continuing symptoms and are unable to achieve complete remission
  • 22. Disease course • 67 percent of patients have at least one relapse 10 years following the diagnosis • late-onset ulcerative colitis (diagnosed at age 50 years or older) -> higher likelihood of steroid free clinical remission (64 versus 49 percent) at one year as compared with those with early onset ulcerative colitis (diagnosed between ages 18 and 30 years)
  • 23. Disease course • Extension of colonic disease is seen in up to 20 percent of patients within five years [42,46-48]. Patients with proctitis have a 50 percent chance of extension and those with disease proximal to the sigmoid colon have a 9 percent chance of progression to pancolitis. • Approximately 20 to 30 percent of patients with ulcerative colitis will require colectomy for acute complications or for medically intractable disease. • for patients with pancolitis, the rate of colectomy is approximately 19 percent after 10 years [42]. In contrast, 5 percent of patients who present with proctitis alone have undergone colectomy after 10 years • Mucosal healing in response to treatment is also important in predicting long-term clinical outcomes
  • 24. Chronic complications • Stricture – due to repeated episodes of inflammation and muscle hypertrophy in about 10 percent of cases with ulcerative colitis – most frequently seen in the rectosigmoid colon – should be considered malignant until proven otherwise by endoscopic evaluation with biopsy – Surgery is indicated for strictures that cause continued symptoms of obstruction or that cannot be fully evaluated to exclude malignancy.
  • 25. Chronic complications • Dysplasia or colorectal cancer – increased risk for colorectal cancer (CRC) – extent of colitis and duration of disease are the two most important risk factors for CRC – proctitis and proctosigmoiditis are probably not an increased risk of CRC – risk begins to increase 8 to 10 years following the onset of symptoms in patients with pancolitis • 2.5 percent after 20 years and 7.6 percent after 30 years • left-sided colitis have almost the same risk of CRC and dysplasia as those with pancolitis but the risk of CRC increases only after 15 to 20 years
  • 26. Chronic complications • Mortality – slightly higher overall mortality compared with the general population (HR 1.2, 95% CI 1.22- 1.28) – The overall mortality appears to be highest in the first year after ulcerative colitis diagnosis (HR 2.4, 95% CI 2.3-2.6). – mortality rates appear to have decreased over time