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Ulcerative colitis Dr.Shi-neng Zhang Professor Department of Gastroenterology Sun Yat-sen University BY

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Page 1: 21 ulcerative colitis

Ulcerative colitis

Dr.Shi-neng ZhangProfessorDepartment of GastroenterologySun Yat-sen University

BY

Page 2: 21 ulcerative colitis

Ulcerative colitisUlcerative colitis (UC) is a chronic disease of unknown (UC) is a chronic disease of unknown

etiology characterized by inflammation of the mucosa and etiology characterized by inflammation of the mucosa and

submucosa of the large intestine.submucosa of the large intestine.

The inflammation usually involves the rectum down to the The inflammation usually involves the rectum down to the

anal margin and extends proximally in the colon for a anal margin and extends proximally in the colon for a

variable distance.variable distance.

There is no difference between men and women.There is no difference between men and women.

The worldwide incidence is 0.5~24 new cases per 100 000 The worldwide incidence is 0.5~24 new cases per 100 000

individuals, and prevalence is 100~200 cases per 100 000.individuals, and prevalence is 100~200 cases per 100 000.

Ulcerative colitisUlcerative colitis (UC) is a chronic disease of unknown (UC) is a chronic disease of unknown

etiology characterized by inflammation of the mucosa and etiology characterized by inflammation of the mucosa and

submucosa of the large intestine.submucosa of the large intestine.

The inflammation usually involves the rectum down to the The inflammation usually involves the rectum down to the

anal margin and extends proximally in the colon for a anal margin and extends proximally in the colon for a

variable distance.variable distance.

There is no difference between men and women.There is no difference between men and women.

The worldwide incidence is 0.5~24 new cases per 100 000 The worldwide incidence is 0.5~24 new cases per 100 000

individuals, and prevalence is 100~200 cases per 100 000.individuals, and prevalence is 100~200 cases per 100 000.

Introduction

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UC: is a form of (IBD). It is a form of colitis, of that includes UC: is a form of (IBD). It is a form of colitis, of that includes

characteristic ulcers, or open sores, in the colon.characteristic ulcers, or open sores, in the colon.

The main symptom of active disease is usually diarrhea The main symptom of active disease is usually diarrhea

mixed with blood, of gradual onset. mixed with blood, of gradual onset.

UC is, however, a systemic disease that affects many parts UC is, however, a systemic disease that affects many parts

of the body outside the intestine. Because of the name, IBD of the body outside the intestine. Because of the name, IBD

is often confused with irritable bowel syndrome ("IBS"), a is often confused with irritable bowel syndrome ("IBS"), a

troublesome, but much less serious condition.troublesome, but much less serious condition.

UC: is a form of (IBD). It is a form of colitis, of that includes UC: is a form of (IBD). It is a form of colitis, of that includes

characteristic ulcers, or open sores, in the colon.characteristic ulcers, or open sores, in the colon.

The main symptom of active disease is usually diarrhea The main symptom of active disease is usually diarrhea

mixed with blood, of gradual onset. mixed with blood, of gradual onset.

UC is, however, a systemic disease that affects many parts UC is, however, a systemic disease that affects many parts

of the body outside the intestine. Because of the name, IBD of the body outside the intestine. Because of the name, IBD

is often confused with irritable bowel syndrome ("IBS"), a is often confused with irritable bowel syndrome ("IBS"), a

troublesome, but much less serious condition.troublesome, but much less serious condition.

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External environmentExternal environment

It is indisputable that the emergence of IBD in various parts It is indisputable that the emergence of IBD in various parts

of the world is associated with social and economical of the world is associated with social and economical

progress, as initially observed in Northern Europe and progress, as initially observed in Northern Europe and

North America, then the rest of Europe, South America and North America, then the rest of Europe, South America and

Japan, and further the Asian Pacific region, as we are now Japan, and further the Asian Pacific region, as we are now

witnessing.witnessing.

A large number of unrelated environmental factors are A large number of unrelated environmental factors are

considered risk factors for IBD, including considered risk factors for IBD, including smokingsmoking, diet, , diet,

drugs (oral contraceptive and NSAIDs). drugs (oral contraceptive and NSAIDs).

External environmentExternal environment

It is indisputable that the emergence of IBD in various parts It is indisputable that the emergence of IBD in various parts

of the world is associated with social and economical of the world is associated with social and economical

progress, as initially observed in Northern Europe and progress, as initially observed in Northern Europe and

North America, then the rest of Europe, South America and North America, then the rest of Europe, South America and

Japan, and further the Asian Pacific region, as we are now Japan, and further the Asian Pacific region, as we are now

witnessing.witnessing.

A large number of unrelated environmental factors are A large number of unrelated environmental factors are

considered risk factors for IBD, including considered risk factors for IBD, including smokingsmoking, diet, , diet,

drugs (oral contraceptive and NSAIDs). drugs (oral contraceptive and NSAIDs).

Current concept of etiopathogenesis

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GeneticsGenetics

There is an increased familial incidence of IBD, both for There is an increased familial incidence of IBD, both for

Crohn’s disease and ulcerative colitis.Crohn’s disease and ulcerative colitis.

This is due in large part to technological advances in DNA This is due in large part to technological advances in DNA

analsis and sequencing, such as genome-wide analsis and sequencing, such as genome-wide

associational, and the use of huge multicenter or associational, and the use of huge multicenter or

multinational databases.multinational databases.

The era modern IBD genetics began in 2001 with the The era modern IBD genetics began in 2001 with the

discovery of mutations in the NOD2/CARD15 gene, the first discovery of mutations in the NOD2/CARD15 gene, the first

susceptibility gene in CD.susceptibility gene in CD.

Polymorphisms of TLR4 have been associated with an Polymorphisms of TLR4 have been associated with an

increased risk for UC as well as CD.increased risk for UC as well as CD.

GeneticsGenetics

There is an increased familial incidence of IBD, both for There is an increased familial incidence of IBD, both for

Crohn’s disease and ulcerative colitis.Crohn’s disease and ulcerative colitis.

This is due in large part to technological advances in DNA This is due in large part to technological advances in DNA

analsis and sequencing, such as genome-wide analsis and sequencing, such as genome-wide

associational, and the use of huge multicenter or associational, and the use of huge multicenter or

multinational databases.multinational databases.

The era modern IBD genetics began in 2001 with the The era modern IBD genetics began in 2001 with the

discovery of mutations in the NOD2/CARD15 gene, the first discovery of mutations in the NOD2/CARD15 gene, the first

susceptibility gene in CD.susceptibility gene in CD.

Polymorphisms of TLR4 have been associated with an Polymorphisms of TLR4 have been associated with an

increased risk for UC as well as CD.increased risk for UC as well as CD.

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Microbial factorsMicrobial factors

Among the components of IBD pathogenesis, the Among the components of IBD pathogenesis, the

investigation of role of infectious agents and the gut investigation of role of infectious agents and the gut

commensal flora is an area in which relatively less commensal flora is an area in which relatively less

progress has occurred.progress has occurred.

There are two main reasons for this There are two main reasons for this

(1) Only isolated reports on new infectious agents with an (1) Only isolated reports on new infectious agents with an

etiologic potential for IBD have been published in several etiologic potential for IBD have been published in several

years, and (2) major methodological difficuties are years, and (2) major methodological difficuties are

encountered in the study of the flora in the human gut.encountered in the study of the flora in the human gut.

Microbial factorsMicrobial factors

Among the components of IBD pathogenesis, the Among the components of IBD pathogenesis, the

investigation of role of infectious agents and the gut investigation of role of infectious agents and the gut

commensal flora is an area in which relatively less commensal flora is an area in which relatively less

progress has occurred.progress has occurred.

There are two main reasons for this There are two main reasons for this

(1) Only isolated reports on new infectious agents with an (1) Only isolated reports on new infectious agents with an

etiologic potential for IBD have been published in several etiologic potential for IBD have been published in several

years, and (2) major methodological difficuties are years, and (2) major methodological difficuties are

encountered in the study of the flora in the human gut.encountered in the study of the flora in the human gut.

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Immunological factorsImmunological factors

The investigation of IBD pathogenesis has been dominated The investigation of IBD pathogenesis has been dominated

for a long time by studies of mucosal immunity and, in for a long time by studies of mucosal immunity and, in

particular, studies of the function of local T cells in Cd and particular, studies of the function of local T cells in Cd and

UC tissues.UC tissues.

CD4+CD25- T cells(Tr1 cells)CD4+CD25- T cells(Tr1 cells)

CD4+CD25+Foxp3+ T cells(T regs)CD4+CD25+Foxp3+ T cells(T regs)

IL-23, IFN-r,TNF-aIL-23, IFN-r,TNF-a

Immunological factorsImmunological factors

The investigation of IBD pathogenesis has been dominated The investigation of IBD pathogenesis has been dominated

for a long time by studies of mucosal immunity and, in for a long time by studies of mucosal immunity and, in

particular, studies of the function of local T cells in Cd and particular, studies of the function of local T cells in Cd and

UC tissues.UC tissues.

CD4+CD25- T cells(Tr1 cells)CD4+CD25- T cells(Tr1 cells)

CD4+CD25+Foxp3+ T cells(T regs)CD4+CD25+Foxp3+ T cells(T regs)

IL-23, IFN-r,TNF-aIL-23, IFN-r,TNF-a

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GeneticsGeneticsGeneticsGenetics

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Additional factorsAdditional factors

In addition to the environmental, genes, microbes, and the In addition to the environmental, genes, microbes, and the

immune system, other factors also participate in IBD immune system, other factors also participate in IBD

pathogenesis, and two in particular are worth mentioning:pathogenesis, and two in particular are worth mentioning:

FibrosisFibrosis::

AngiogenesisAngiogenesis :: It has recently been shown to be a novel It has recently been shown to be a novel

and important component of IBD pathogenesis, and one and important component of IBD pathogenesis, and one

likely to contribute to the chronicity of the disease. likely to contribute to the chronicity of the disease.

Angiogenesis blockage is effective in decreasing Angiogenesis blockage is effective in decreasing

inflammation in experimental colitis.inflammation in experimental colitis.

Additional factorsAdditional factors

In addition to the environmental, genes, microbes, and the In addition to the environmental, genes, microbes, and the

immune system, other factors also participate in IBD immune system, other factors also participate in IBD

pathogenesis, and two in particular are worth mentioning:pathogenesis, and two in particular are worth mentioning:

FibrosisFibrosis::

AngiogenesisAngiogenesis :: It has recently been shown to be a novel It has recently been shown to be a novel

and important component of IBD pathogenesis, and one and important component of IBD pathogenesis, and one

likely to contribute to the chronicity of the disease. likely to contribute to the chronicity of the disease.

Angiogenesis blockage is effective in decreasing Angiogenesis blockage is effective in decreasing

inflammation in experimental colitis.inflammation in experimental colitis.

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Although UC has no known cause, there is a presumed Although UC has no known cause, there is a presumed

genetic component to susceptibility.genetic component to susceptibility.

The disease may be triggered in a susceptible person by The disease may be triggered in a susceptible person by

environmental factors. Although dietary modification may environmental factors. Although dietary modification may

reduce the discomfort of a person with the disease, UC is reduce the discomfort of a person with the disease, UC is

not thought to be caused by dietary factors.not thought to be caused by dietary factors.

Although UC is treated as though it were an autoimmune Although UC is treated as though it were an autoimmune

disease, there is no consensus that it is such.disease, there is no consensus that it is such.

Although UC has no known cause, there is a presumed Although UC has no known cause, there is a presumed

genetic component to susceptibility.genetic component to susceptibility.

The disease may be triggered in a susceptible person by The disease may be triggered in a susceptible person by

environmental factors. Although dietary modification may environmental factors. Although dietary modification may

reduce the discomfort of a person with the disease, UC is reduce the discomfort of a person with the disease, UC is

not thought to be caused by dietary factors.not thought to be caused by dietary factors.

Although UC is treated as though it were an autoimmune Although UC is treated as though it were an autoimmune

disease, there is no consensus that it is such.disease, there is no consensus that it is such.

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Pathologic changes in the colon in UC readily predict the Pathologic changes in the colon in UC readily predict the

clinical features of the disease.clinical features of the disease.

Unlike the segmental lesions of CD, UC involves primarily Unlike the segmental lesions of CD, UC involves primarily

the mucosa of the colon, the mucosa is inflamed the mucosa of the colon, the mucosa is inflamed

continuously.continuously.

The involved mucosa is red and granular and bleeds The involved mucosa is red and granular and bleeds

diffusely. The macroscopic lesions may progress from diffusely. The macroscopic lesions may progress from

small, petechial ulcerations to deeper, linear ulcers small, petechial ulcerations to deeper, linear ulcers

separated by islands of inflamed but intact mucosa.separated by islands of inflamed but intact mucosa.

In severe cases, large areas of the colon may be denuded.In severe cases, large areas of the colon may be denuded.

Pathologic changes in the colon in UC readily predict the Pathologic changes in the colon in UC readily predict the

clinical features of the disease.clinical features of the disease.

Unlike the segmental lesions of CD, UC involves primarily Unlike the segmental lesions of CD, UC involves primarily

the mucosa of the colon, the mucosa is inflamed the mucosa of the colon, the mucosa is inflamed

continuously.continuously.

The involved mucosa is red and granular and bleeds The involved mucosa is red and granular and bleeds

diffusely. The macroscopic lesions may progress from diffusely. The macroscopic lesions may progress from

small, petechial ulcerations to deeper, linear ulcers small, petechial ulcerations to deeper, linear ulcers

separated by islands of inflamed but intact mucosa.separated by islands of inflamed but intact mucosa.

In severe cases, large areas of the colon may be denuded.In severe cases, large areas of the colon may be denuded.

Pathology

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The characteristic pathology is one of chronic inflammation The characteristic pathology is one of chronic inflammation

characterized by large numbers of lymphocytes and characterized by large numbers of lymphocytes and

histocytes in the diseased mucosa and submucosa with an histocytes in the diseased mucosa and submucosa with an

acute inflammatory infiltrate composed of neutrophils acute inflammatory infiltrate composed of neutrophils

variably present. variably present.

The alterating processes of superfical ulceration and The alterating processes of superfical ulceration and

granulation followed by re-epithelialization can lead to the granulation followed by re-epithelialization can lead to the

development of polypoid excrescences. These are development of polypoid excrescences. These are

inflammatory polyps(pseudopolyps) that are not inflammatory polyps(pseudopolyps) that are not

neoplastic.neoplastic.

The characteristic pathology is one of chronic inflammation The characteristic pathology is one of chronic inflammation

characterized by large numbers of lymphocytes and characterized by large numbers of lymphocytes and

histocytes in the diseased mucosa and submucosa with an histocytes in the diseased mucosa and submucosa with an

acute inflammatory infiltrate composed of neutrophils acute inflammatory infiltrate composed of neutrophils

variably present. variably present.

The alterating processes of superfical ulceration and The alterating processes of superfical ulceration and

granulation followed by re-epithelialization can lead to the granulation followed by re-epithelialization can lead to the

development of polypoid excrescences. These are development of polypoid excrescences. These are

inflammatory polyps(pseudopolyps) that are not inflammatory polyps(pseudopolyps) that are not

neoplastic.neoplastic.

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UC is an intermittent disease, with periods of exacerbated UC is an intermittent disease, with periods of exacerbated

symptoms, and periods that are relatively symptom-free.symptoms, and periods that are relatively symptom-free.

Although the symptoms of UC can sometimes diminish on Although the symptoms of UC can sometimes diminish on

their own, the disease usually requires treatment to go into their own, the disease usually requires treatment to go into

remission. remission.

UC is an intermittent disease, with periods of exacerbated UC is an intermittent disease, with periods of exacerbated

symptoms, and periods that are relatively symptom-free.symptoms, and periods that are relatively symptom-free.

Although the symptoms of UC can sometimes diminish on Although the symptoms of UC can sometimes diminish on

their own, the disease usually requires treatment to go into their own, the disease usually requires treatment to go into

remission. remission.

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UC is a systemic disease that affects many parts of the body.UC is a systemic disease that affects many parts of the body.

Sometimes the extra-intestinal manifestations of the disease Sometimes the extra-intestinal manifestations of the disease

are the initial signs, such as painful, arthritic knees in a are the initial signs, such as painful, arthritic knees in a

teenager. It is, however, unlikely that the disease will be teenager. It is, however, unlikely that the disease will be

correctly diagnosed until the onset of the intestinal correctly diagnosed until the onset of the intestinal

manifestations.manifestations.

UC is a systemic disease that affects many parts of the body.UC is a systemic disease that affects many parts of the body.

Sometimes the extra-intestinal manifestations of the disease Sometimes the extra-intestinal manifestations of the disease

are the initial signs, such as painful, arthritic knees in a are the initial signs, such as painful, arthritic knees in a

teenager. It is, however, unlikely that the disease will be teenager. It is, however, unlikely that the disease will be

correctly diagnosed until the onset of the intestinal correctly diagnosed until the onset of the intestinal

manifestations.manifestations.

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The five most common symptoms of UC are rectal bleeding, The five most common symptoms of UC are rectal bleeding,

diarrhea, abdominal pain, weight loss, and fever.diarrhea, abdominal pain, weight loss, and fever.

The clinical presentationThe clinical presentation of UC depends on the extent of the of UC depends on the extent of the

disease process. Patients usually present with diarrhea disease process. Patients usually present with diarrhea

mixed with blood and mucus, of gradual onset.mixed with blood and mucus, of gradual onset.

They also may have signs of weight loss, and blood on They also may have signs of weight loss, and blood on

rectal examination.rectal examination.

The disease is usually accompanied with different degrees The disease is usually accompanied with different degrees

of abdominal pain, from mild discomfort to severely painful of abdominal pain, from mild discomfort to severely painful

cramps.cramps.

The five most common symptoms of UC are rectal bleeding, The five most common symptoms of UC are rectal bleeding,

diarrhea, abdominal pain, weight loss, and fever.diarrhea, abdominal pain, weight loss, and fever.

The clinical presentationThe clinical presentation of UC depends on the extent of the of UC depends on the extent of the

disease process. Patients usually present with diarrhea disease process. Patients usually present with diarrhea

mixed with blood and mucus, of gradual onset.mixed with blood and mucus, of gradual onset.

They also may have signs of weight loss, and blood on They also may have signs of weight loss, and blood on

rectal examination.rectal examination.

The disease is usually accompanied with different degrees The disease is usually accompanied with different degrees

of abdominal pain, from mild discomfort to severely painful of abdominal pain, from mild discomfort to severely painful

cramps.cramps.

Clinical manifestations

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Extent of involvement Extent of involvement UC UC is normally continuous from the rectum up the colon. is normally continuous from the rectum up the colon. The disease is classified by the extent of involvement, The disease is classified by the extent of involvement, depending on how far up the colon the disease extends:depending on how far up the colon the disease extends:

Distal colitis, potentially treatable with enemas:Distal colitis, potentially treatable with enemas:

Proctitis:Proctitis:

Involvement limited to the rectum. Involvement limited to the rectum.

Proctosigmoiditis:Proctosigmoiditis:

Involvement of the rectosigmoid colon, the portion of the Involvement of the rectosigmoid colon, the portion of the colon adjacent to the rectum. colon adjacent to the rectum.

Left-sided colitis:Left-sided colitis:

Involvement of the descending colon, which runs along Involvement of the descending colon, which runs along the patient's left side, up to the splenic flexure and the the patient's left side, up to the splenic flexure and the beginning of the transverse colon. beginning of the transverse colon.

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Extensive colitisExtensive colitis, inflammation extending beyond the reach , inflammation extending beyond the reach of enemas:of enemas:

Pancolitis:Pancolitis: Involvement of the entire colon, extending from Involvement of the entire colon, extending from the rectum to the cecum, beyond which the small intestine the rectum to the cecum, beyond which the small intestine begins.begins.

Extensive colitisExtensive colitis, inflammation extending beyond the reach , inflammation extending beyond the reach of enemas:of enemas:

Pancolitis:Pancolitis: Involvement of the entire colon, extending from Involvement of the entire colon, extending from the rectum to the cecum, beyond which the small intestine the rectum to the cecum, beyond which the small intestine begins.begins.

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Severity of diseaseSeverity of disease

In addition to the extent of involvement, UC patients may also In addition to the extent of involvement, UC patients may also

be characterized by the severity of their disease.be characterized by the severity of their disease.

Mild diseaseMild disease correlates with fewer than four stools daily, with correlates with fewer than four stools daily, with

or without blood, no systemic signs of toxicity, and a normal or without blood, no systemic signs of toxicity, and a normal

erythrocyte sedimentation rate (ESR). There may be mild erythrocyte sedimentation rate (ESR). There may be mild

abdominal pain or cramping. Patients may believe they are abdominal pain or cramping. Patients may believe they are

constipated when in fact they are experiencing tenesmus, constipated when in fact they are experiencing tenesmus,

which is a constant feeling of the need to empty the bowel which is a constant feeling of the need to empty the bowel

accompanied by involuntary straining efforts, pain, and accompanied by involuntary straining efforts, pain, and

cramping with little or no fecal output. Rectal pain is cramping with little or no fecal output. Rectal pain is

uncommon.uncommon.

Severity of diseaseSeverity of disease

In addition to the extent of involvement, UC patients may also In addition to the extent of involvement, UC patients may also

be characterized by the severity of their disease.be characterized by the severity of their disease.

Mild diseaseMild disease correlates with fewer than four stools daily, with correlates with fewer than four stools daily, with

or without blood, no systemic signs of toxicity, and a normal or without blood, no systemic signs of toxicity, and a normal

erythrocyte sedimentation rate (ESR). There may be mild erythrocyte sedimentation rate (ESR). There may be mild

abdominal pain or cramping. Patients may believe they are abdominal pain or cramping. Patients may believe they are

constipated when in fact they are experiencing tenesmus, constipated when in fact they are experiencing tenesmus,

which is a constant feeling of the need to empty the bowel which is a constant feeling of the need to empty the bowel

accompanied by involuntary straining efforts, pain, and accompanied by involuntary straining efforts, pain, and

cramping with little or no fecal output. Rectal pain is cramping with little or no fecal output. Rectal pain is

uncommon.uncommon.

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Moderate diseaseModerate disease correlates with more than four stools daily, correlates with more than four stools daily,

but with minimal signs of toxicity. Patients may display but with minimal signs of toxicity. Patients may display

anemia (not requiring transfusions), moderate abdominal anemia (not requiring transfusions), moderate abdominal

pain, and low grade fever, 38 to 39 °C pain, and low grade fever, 38 to 39 °C

Severe disease,Severe disease, correlates with more than six bloody stools a correlates with more than six bloody stools a

day, and evidence of toxicity as demonstrated by fever, day, and evidence of toxicity as demonstrated by fever,

tachycardia, anemia or an elevated ESR.tachycardia, anemia or an elevated ESR.

Moderate diseaseModerate disease correlates with more than four stools daily, correlates with more than four stools daily,

but with minimal signs of toxicity. Patients may display but with minimal signs of toxicity. Patients may display

anemia (not requiring transfusions), moderate abdominal anemia (not requiring transfusions), moderate abdominal

pain, and low grade fever, 38 to 39 °C pain, and low grade fever, 38 to 39 °C

Severe disease,Severe disease, correlates with more than six bloody stools a correlates with more than six bloody stools a

day, and evidence of toxicity as demonstrated by fever, day, and evidence of toxicity as demonstrated by fever,

tachycardia, anemia or an elevated ESR.tachycardia, anemia or an elevated ESR.

Page 23: 21 ulcerative colitis

Fulminant Fulminant disease correlates with more than ten bowel disease correlates with more than ten bowel

movements daily, continuous bleeding, toxicity, abdominal movements daily, continuous bleeding, toxicity, abdominal

tenderness and distension, blood transfusion requirement tenderness and distension, blood transfusion requirement

and colonic dilation. Patients in this category may have and colonic dilation. Patients in this category may have

severe inflammation extending beyond just the mucosal severe inflammation extending beyond just the mucosal

layer, causing impaired colonic motility and leading to toxic layer, causing impaired colonic motility and leading to toxic

megacolon.megacolon. If the serous membrane is involved, colonic If the serous membrane is involved, colonic

perforation may ensue. Unless treated, fulminant disease will perforation may ensue. Unless treated, fulminant disease will

soon lead to death. soon lead to death.

Fulminant Fulminant disease correlates with more than ten bowel disease correlates with more than ten bowel

movements daily, continuous bleeding, toxicity, abdominal movements daily, continuous bleeding, toxicity, abdominal

tenderness and distension, blood transfusion requirement tenderness and distension, blood transfusion requirement

and colonic dilation. Patients in this category may have and colonic dilation. Patients in this category may have

severe inflammation extending beyond just the mucosal severe inflammation extending beyond just the mucosal

layer, causing impaired colonic motility and leading to toxic layer, causing impaired colonic motility and leading to toxic

megacolon.megacolon. If the serous membrane is involved, colonic If the serous membrane is involved, colonic

perforation may ensue. Unless treated, fulminant disease will perforation may ensue. Unless treated, fulminant disease will

soon lead to death. soon lead to death.

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Extraintestinal features Extraintestinal features

As UC is a systemic disease, patients may present with As UC is a systemic disease, patients may present with

symptoms and complications outside the colon. These symptoms and complications outside the colon. These

include the following:include the following:

aphthousaphthous ulcers of the mouth . ulcers of the mouth .

Ophthalmic .Ophthalmic .

Iritis or uveit.Iritis or uveit.

Episcleritis.Episcleritis.

Extraintestinal features Extraintestinal features

As UC is a systemic disease, patients may present with As UC is a systemic disease, patients may present with

symptoms and complications outside the colon. These symptoms and complications outside the colon. These

include the following:include the following:

aphthousaphthous ulcers of the mouth . ulcers of the mouth .

Ophthalmic .Ophthalmic .

Iritis or uveit.Iritis or uveit.

Episcleritis.Episcleritis.

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Patients with ulcerative colitis can occasionally have Patients with ulcerative colitis can occasionally have aphthous ulcers involving the tongue, lips, palate and aphthous ulcers involving the tongue, lips, palate and pharynx pharynx

Patients with ulcerative colitis can occasionally have Patients with ulcerative colitis can occasionally have aphthous ulcers involving the tongue, lips, palate and aphthous ulcers involving the tongue, lips, palate and pharynx pharynx

Page 26: 21 ulcerative colitis

Musculoskeletal:Musculoskeletal:

Seronegative arthritis, which can be a large-joint Seronegative arthritis, which can be a large-joint

oligoa rthritis (affecting one or two joints), or may affect oligoa rthritis (affecting one or two joints), or may affect many small joints of the hands and feet many small joints of the hands and feet

Ankylosing spondylitis, arthritis of the spine Ankylosing spondylitis, arthritis of the spine

Sacroiliitis, arthritis of the lower spine Sacroiliitis, arthritis of the lower spine

CutaneousCutaneous

Erythemanodosum, which is a panniculitis, or Erythemanodosum, which is a panniculitis, or inflammation of subcutaneous tissue involving the lower inflammation of subcutaneous tissue involving the lower extremities extremities

Pyoderma gangrenosum, which is a painful ulcerating Pyoderma gangrenosum, which is a painful ulcerating lesion involving the skin lesion involving the skin

Musculoskeletal:Musculoskeletal:

Seronegative arthritis, which can be a large-joint Seronegative arthritis, which can be a large-joint

oligoa rthritis (affecting one or two joints), or may affect oligoa rthritis (affecting one or two joints), or may affect many small joints of the hands and feet many small joints of the hands and feet

Ankylosing spondylitis, arthritis of the spine Ankylosing spondylitis, arthritis of the spine

Sacroiliitis, arthritis of the lower spine Sacroiliitis, arthritis of the lower spine

CutaneousCutaneous

Erythemanodosum, which is a panniculitis, or Erythemanodosum, which is a panniculitis, or inflammation of subcutaneous tissue involving the lower inflammation of subcutaneous tissue involving the lower extremities extremities

Pyoderma gangrenosum, which is a painful ulcerating Pyoderma gangrenosum, which is a painful ulcerating lesion involving the skin lesion involving the skin

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Deep venous thrombosisDeep venous thrombosis and pulmonary embolism and pulmonary embolism

Autoimmune hemolytic anemia Autoimmune hemolytic anemia

clubbingclubbing, ,

Primary sclerosingPrimary sclerosing cholangitis, or inflammation of the cholangitis, or inflammation of the

bile ducts bile ducts

Deep venous thrombosisDeep venous thrombosis and pulmonary embolism and pulmonary embolism

Autoimmune hemolytic anemia Autoimmune hemolytic anemia

clubbingclubbing, ,

Primary sclerosingPrimary sclerosing cholangitis, or inflammation of the cholangitis, or inflammation of the

bile ducts bile ducts

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CLINICAL FEATURESCLINICAL FEATURES

Clinical typesClinical types ☆ ☆ Initial attackInitial attack ☆ ☆ Chronic relapseChronic relapse ☆ ☆ Chronic continuanceChronic continuance ☆ ☆ Acute fulminateAcute fulminate The degree of severityThe degree of severity ☆ ☆ MildMild ☆ ☆ ModerateModerate ☆ ☆ SevereSevere

Page 29: 21 ulcerative colitis

COMLICATIONCOMLICATION

Toxic megacolonToxic megacolon Carcinoma of the rectum and colonCarcinoma of the rectum and colon Others: massive bleeding,Others: massive bleeding,

perforation,perforation,

stricturestricture

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COMPLICATIONCOMPLICATION

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Course and complications Course and complications

Progression or remissionProgression or remission

Patients with UC usually have an intermittent course, with Patients with UC usually have an intermittent course, with

periods of disease inactivity alternating with "flares" of periods of disease inactivity alternating with "flares" of

disease. Patients with proctitis or left-sided colitis usually disease. Patients with proctitis or left-sided colitis usually

have a more benign course: only 15% progress proximally have a more benign course: only 15% progress proximally

with their disease, and up to 20% can have sustained with their disease, and up to 20% can have sustained

remission in the absence of any therapy. Patients with remission in the absence of any therapy. Patients with

more extensive disease are less likely to sustain remission, more extensive disease are less likely to sustain remission,

but the rate of remission is independent of the severity of but the rate of remission is independent of the severity of

diseasedisease

Course and complications Course and complications

Progression or remissionProgression or remission

Patients with UC usually have an intermittent course, with Patients with UC usually have an intermittent course, with

periods of disease inactivity alternating with "flares" of periods of disease inactivity alternating with "flares" of

disease. Patients with proctitis or left-sided colitis usually disease. Patients with proctitis or left-sided colitis usually

have a more benign course: only 15% progress proximally have a more benign course: only 15% progress proximally

with their disease, and up to 20% can have sustained with their disease, and up to 20% can have sustained

remission in the absence of any therapy. Patients with remission in the absence of any therapy. Patients with

more extensive disease are less likely to sustain remission, more extensive disease are less likely to sustain remission,

but the rate of remission is independent of the severity of but the rate of remission is independent of the severity of

diseasedisease

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UC and colorectal cancerUC and colorectal cancer

There is a significantly increased risk of colorectal cancer There is a significantly increased risk of colorectal cancer

in patients with UC after 10 years if involvement is beyond in patients with UC after 10 years if involvement is beyond

the splenicflexure. Those with only proctitis or the splenicflexure. Those with only proctitis or

rectosigmoiditis usually have no increased risk. rectosigmoiditis usually have no increased risk.

It is recommended that patients have screening It is recommended that patients have screening

colonoscopies with random biopsies to look for dysplasia colonoscopies with random biopsies to look for dysplasia

after eight years of disease after eight years of disease

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Invasive Invasive adenocarcinoma is adenocarcinoma is diagnosed when diagnosed when neoplastic epithelium neoplastic epithelium traverses the traverses the muscularis mucosaemuscularis mucosae

Stromal desmoplasia Stromal desmoplasia is prominent (compare is prominent (compare with lamina propria)with lamina propria)

IBD: Ulcerative Colitis - IBD: Ulcerative Colitis - DysplasiaDysplasiaAdenocarcinoma in Ulcerative Adenocarcinoma in Ulcerative

ColitisColitis

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Primary sclerosing cholangitis (PSC)Primary sclerosing cholangitis (PSC)

UC has a significant association with (PSC), a progressive UC has a significant association with (PSC), a progressive

inflammatory disorder of small and large bile ducts. As inflammatory disorder of small and large bile ducts. As

many as 5% of patients with UC may progress to develop many as 5% of patients with UC may progress to develop

(PSC). (PSC).

MortalityMortality

The effect of UC on mortality is unclear, but it is thought that The effect of UC on mortality is unclear, but it is thought that

the disease primarily affects quality of life, and not lifespan.the disease primarily affects quality of life, and not lifespan.

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LABORATORY FINDINGSLABORATORY FINDINGS

Blood: anemia, leukocytosis, Blood: anemia, leukocytosis,

ESR ESR ↑↑, ,

CRP CRP ↑↑,,

hypoalbuminemiahypoalbuminemia Stool: no identifiable pathogenic bacteria,Stool: no identifiable pathogenic bacteria,

no parasitesno parasites Antibodis: p-ANCA, ASCAAntibodis: p-ANCA, ASCA

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LABORATORY FINDINGSLABORATORY FINDINGS

ColonscopyColonscopy ☆ ☆ Loss of the fine vascular patternLoss of the fine vascular pattern

☆ ☆ AA geanular appearancegeanular appearance

☆ ☆ Superfical ulcerationsSuperfical ulcerations

☆ ☆ MucopusMucopus

☆ ☆ Postinflammatory polypsPostinflammatory polyps

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EndoscopicEndoscopic

The best test for diagnosis of UC remains endoscopy. The best test for diagnosis of UC remains endoscopy. Full colonoscopy to the cecum and entry into the Full colonoscopy to the cecum and entry into the terminal ileum is attempted only if diagnosis of UC is terminal ileum is attempted only if diagnosis of UC is unclear.unclear.

Otherwise, a flexible sigmoidoscopy is sufficient to Otherwise, a flexible sigmoidoscopy is sufficient to support the diagnosis. The physician may elect to limit support the diagnosis. The physician may elect to limit the extent of the exam if severe colitis is encountered to the extent of the exam if severe colitis is encountered to minimize the risk of perforation of the colon. Endoscopic minimize the risk of perforation of the colon. Endoscopic findings in UC include the following:findings in UC include the following:

Loss of the vascular appearance of the colon, Erythema Loss of the vascular appearance of the colon, Erythema (or redness of the mucosa) and friability of the mucosa (or redness of the mucosa) and friability of the mucosa Superficial ulceration, which may be confluent, and Superficial ulceration, which may be confluent, and Pseudopolyps. Pseudopolyps.

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EndoscopicEndoscopic

UC is usually continuous from the rectum, with the UC is usually continuous from the rectum, with the

rectum almost universally being involved. There is rarely rectum almost universally being involved. There is rarely

peri-anal disease, but cases have been reported. The peri-anal disease, but cases have been reported. The

degree of involvement endoscopically ranges from degree of involvement endoscopically ranges from

proctitis or inflammation of the rectum, to left sided proctitis or inflammation of the rectum, to left sided

colitis, to pancolitis, which is inflammation involving the colitis, to pancolitis, which is inflammation involving the

ascending colon ascending colon

EndoscopicEndoscopic

UC is usually continuous from the rectum, with the UC is usually continuous from the rectum, with the

rectum almost universally being involved. There is rarely rectum almost universally being involved. There is rarely

peri-anal disease, but cases have been reported. The peri-anal disease, but cases have been reported. The

degree of involvement endoscopically ranges from degree of involvement endoscopically ranges from

proctitis or inflammation of the rectum, to left sided proctitis or inflammation of the rectum, to left sided

colitis, to pancolitis, which is inflammation involving the colitis, to pancolitis, which is inflammation involving the

ascending colon ascending colon

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Polyps In Colitis

Page 45: 21 ulcerative colitis

PseudopolypsPseudopolyps

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Endoscopic image of ulcerative colitis affecting the left side Endoscopic image of ulcerative colitis affecting the left side of the colon. The image shows confluent superficial of the colon. The image shows confluent superficial ulceration and loss of mucosal architecture. Crohn's disease ulceration and loss of mucosal architecture. Crohn's disease may be similar in appearance, a fact that can make may be similar in appearance, a fact that can make diagnosing UC a challenge.diagnosing UC a challenge.

Endoscopic image of ulcerative colitis affecting the left side Endoscopic image of ulcerative colitis affecting the left side of the colon. The image shows confluent superficial of the colon. The image shows confluent superficial ulceration and loss of mucosal architecture. Crohn's disease ulceration and loss of mucosal architecture. Crohn's disease may be similar in appearance, a fact that can make may be similar in appearance, a fact that can make diagnosing UC a challenge.diagnosing UC a challenge.

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Colonic pseudopolyps of a patient with intractable ulcerative colitis. Colectomy specimen.

Colonic pseudopolyps of a patient with intractable ulcerative colitis. Colectomy specimen.

Page 48: 21 ulcerative colitis

HistologicHistologic

Biopsies of the mucosa are taken to definitively diagnose Biopsies of the mucosa are taken to definitively diagnose

UC and differentiate it from Crohn's diseas, Microbiological UC and differentiate it from Crohn's diseas, Microbiological

samples are typically taken at the time of endoscopy. samples are typically taken at the time of endoscopy.

The pathology in UC typically involves distortion of crypt The pathology in UC typically involves distortion of crypt

architecture, inflammation of crypts (cryptitis), frank crypt architecture, inflammation of crypts (cryptitis), frank crypt

abscesses, and hemorrhage or inflammatory cells in the abscesses, and hemorrhage or inflammatory cells in the

lamina propria. In cases where the clinical picture is lamina propria. In cases where the clinical picture is

unclear, the histomorphologic analysis often plays a unclear, the histomorphologic analysis often plays a

pivotal role in determining the management.pivotal role in determining the management.

HistologicHistologic

Biopsies of the mucosa are taken to definitively diagnose Biopsies of the mucosa are taken to definitively diagnose

UC and differentiate it from Crohn's diseas, Microbiological UC and differentiate it from Crohn's diseas, Microbiological

samples are typically taken at the time of endoscopy. samples are typically taken at the time of endoscopy.

The pathology in UC typically involves distortion of crypt The pathology in UC typically involves distortion of crypt

architecture, inflammation of crypts (cryptitis), frank crypt architecture, inflammation of crypts (cryptitis), frank crypt

abscesses, and hemorrhage or inflammatory cells in the abscesses, and hemorrhage or inflammatory cells in the

lamina propria. In cases where the clinical picture is lamina propria. In cases where the clinical picture is

unclear, the histomorphologic analysis often plays a unclear, the histomorphologic analysis often plays a

pivotal role in determining the management.pivotal role in determining the management.

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Diagnosis

The diagnosis of UC is usually made on the basis of its

clinical features, the demonstration of inflammation of the

rectal and sigmoidal mucosa on proctosigmoidosocpy,

and the exclusion of specific infectious by appropriate

stool culture and examination for parasites.

The diagnosis may be supported by radiologic

examination, colooscopy, and rectal biopsy.

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Differential diagnosisDifferential diagnosis

The following conditions may present in a similar manner The following conditions may present in a similar manner and should be excluded:and should be excluded:

Crohn's diseaseCrohn's disease

Infectious colitisInfectious colitis, which is typically detected on stool cultures, which is typically detected on stool cultures

Pseudom embranousPseudom embranous colitis, or Clostridium difficile- colitis, or Clostridium difficile-associated colitis, bacterial upsets often seen following associated colitis, bacterial upsets often seen following administration of antibiotics administration of antibiotics

Ischemic colitisIschemic colitis, inadequate blood supply to the intestine, , inadequate blood supply to the intestine, which typically affects the elderlywhich typically affects the elderly

Radiation colitisRadiation colitis in patients with previous pelvic in patients with previous pelvic radiotherapy radiotherapy

Chemical colitisChemical colitis resulting from introduction of harsh resulting from introduction of harsh chemicals into the colon from an enema or other procedure. chemicals into the colon from an enema or other procedure.

Differential diagnosisDifferential diagnosis

The following conditions may present in a similar manner The following conditions may present in a similar manner and should be excluded:and should be excluded:

Crohn's diseaseCrohn's disease

Infectious colitisInfectious colitis, which is typically detected on stool cultures, which is typically detected on stool cultures

Pseudom embranousPseudom embranous colitis, or Clostridium difficile- colitis, or Clostridium difficile-associated colitis, bacterial upsets often seen following associated colitis, bacterial upsets often seen following administration of antibiotics administration of antibiotics

Ischemic colitisIschemic colitis, inadequate blood supply to the intestine, , inadequate blood supply to the intestine, which typically affects the elderlywhich typically affects the elderly

Radiation colitisRadiation colitis in patients with previous pelvic in patients with previous pelvic radiotherapy radiotherapy

Chemical colitisChemical colitis resulting from introduction of harsh resulting from introduction of harsh chemicals into the colon from an enema or other procedure. chemicals into the colon from an enema or other procedure.

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Comparison to Crohn's Disease Comparison to Crohn's Disease

The most common disease that mimics the symptoms of UC The most common disease that mimics the symptoms of UC

is Crohn's disease, as both are IBD that can affect the colon is Crohn's disease, as both are IBD that can affect the colon

with similar symptoms. with similar symptoms.

It is important to differentiate these diseases, since the It is important to differentiate these diseases, since the

course of the diseases and treatments may be different. course of the diseases and treatments may be different.

In some cases, however, it may not be possible to tell the In some cases, however, it may not be possible to tell the

difference, in which case the disease is classified as difference, in which case the disease is classified as

indeterminate colitis.indeterminate colitis.

Comparison to Crohn's Disease Comparison to Crohn's Disease

The most common disease that mimics the symptoms of UC The most common disease that mimics the symptoms of UC

is Crohn's disease, as both are IBD that can affect the colon is Crohn's disease, as both are IBD that can affect the colon

with similar symptoms. with similar symptoms.

It is important to differentiate these diseases, since the It is important to differentiate these diseases, since the

course of the diseases and treatments may be different. course of the diseases and treatments may be different.

In some cases, however, it may not be possible to tell the In some cases, however, it may not be possible to tell the

difference, in which case the disease is classified as difference, in which case the disease is classified as

indeterminate colitis.indeterminate colitis.

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Comparisons of various factors in Crohn's disease and ulcerative colitis

Crohn's Disease Crohn's Disease Ulcerative Colitis Ulcerative Colitis

Involves terminal ileum Involves terminal ileum Commonly Commonly Seldom Seldom

Involves colon? Involves colon?

Involves rectum? Involves rectum?

Usually Usually

Seldom Seldom

Always Always

Usually Usually

Peri-anal involvement Peri-anal involvement Commonl Commonl Seldom Seldom

Bile duct involvement? Bile duct involvement? Not associated Not associated Higher rate of Primary Higher rate of Primary sclerosing cholangitis sclerosing cholangitis

Distribution of Disease Distribution of Disease Patchy areas of Patchy areas of inflammation inflammation

Continuous area of Continuous area of inflammation inflammation

Endoscopy Endoscopy Linear and serpiginous Linear and serpiginous (snake-like) ulcers (snake-like) ulcers

Continuous ulcer Continuous ulcer

Depth of inflammation Depth of inflammation May be transmural, deep May be transmural, deep into tissues into tissues

Shallow, mucosal Shallow, mucosal

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Fistulae, abnormal Fistulae, abnormal passageways between passageways between

organs organs

Commonly Commonly Seldom Seldom

Biopsy Biopsy Can have granulomata Can have granulomata Crypt abscesses and Crypt abscesses and cryptitis cryptitis

Surgical cure ?Surgical cure ?

Smoking Smoking

Often returns following Often returns following removal of affected removal of affected

part part

Higher risk for smokers Higher risk for smokers

Usually cured by Usually cured by removal of colon, can removal of colon, can

be followed by be followed by

po uchitis po uchitis

Lower risk for smokers Lower risk for smokers

Autoimmune disease Autoimmune disease Generally regarded as Generally regarded as an autoimmune an autoimmune

disease disease

No consensus No consensus

Cancer risk? Cancer risk? Lower than ulcerative Lower than ulcerative colitis colitis

Higher than Crohn's Higher than Crohn's

Comparisons of various factors in Crohn's disease and UC (Cont.)

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Standard treatment for UC depends on Standard treatment for UC depends on extentextent of involvement of involvement and disease and disease severityseverity..

The goal is to induce remission initially with medications, The goal is to induce remission initially with medications, followed by the administration of maintenance medications followed by the administration of maintenance medications to prevent a relapse of the disease.to prevent a relapse of the disease.

The concept of induction of remission and maintenance of The concept of induction of remission and maintenance of remission is very important.remission is very important.

Standard treatment for UC depends on Standard treatment for UC depends on extentextent of involvement of involvement and disease and disease severityseverity..

The goal is to induce remission initially with medications, The goal is to induce remission initially with medications, followed by the administration of maintenance medications followed by the administration of maintenance medications to prevent a relapse of the disease.to prevent a relapse of the disease.

The concept of induction of remission and maintenance of The concept of induction of remission and maintenance of remission is very important.remission is very important.

Treatment

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The medications used to induce and maintain a remission The medications used to induce and maintain a remission

somewhat overlap, but the treatments are different. somewhat overlap, but the treatments are different.

Physicians first direct treatment to inducing a remission Physicians first direct treatment to inducing a remission

which involves relief of symptoms and mucosal healing of which involves relief of symptoms and mucosal healing of

the lining of the colon and then longer term treatment to the lining of the colon and then longer term treatment to

maintain the remission.maintain the remission.

Current treatments have been effective for many patients Current treatments have been effective for many patients

with UC but have numerous limitations for patients with with UC but have numerous limitations for patients with

moderate to severe disease. moderate to severe disease.

The medications used to induce and maintain a remission The medications used to induce and maintain a remission

somewhat overlap, but the treatments are different. somewhat overlap, but the treatments are different.

Physicians first direct treatment to inducing a remission Physicians first direct treatment to inducing a remission

which involves relief of symptoms and mucosal healing of which involves relief of symptoms and mucosal healing of

the lining of the colon and then longer term treatment to the lining of the colon and then longer term treatment to

maintain the remission.maintain the remission.

Current treatments have been effective for many patients Current treatments have been effective for many patients

with UC but have numerous limitations for patients with with UC but have numerous limitations for patients with

moderate to severe disease. moderate to severe disease.

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Drugs used Drugs used Aminosalicylates Aminosalicylates

are the mainstay of UC pharmacotherapy for induction and are the mainstay of UC pharmacotherapy for induction and

maintenance of remission for patients with mild to maintenance of remission for patients with mild to

moderate disease.moderate disease.

Sulfasalazine Sulfasalazine has been a major agent in the therapy of has been a major agent in the therapy of

mild to moderate UC for over 50 years. In 1977 Mastan mild to moderate UC for over 50 years. In 1977 Mastan

S.Kalsi et al determined that 5-aminosalicyclic acid (5-ASA S.Kalsi et al determined that 5-aminosalicyclic acid (5-ASA

and mesalazine) was the therapeutically active compound and mesalazine) was the therapeutically active compound

in sulfasalazine. Since then many 5-ASA compounds have in sulfasalazine. Since then many 5-ASA compounds have

been developed with the aim of maintaining efficacy but been developed with the aim of maintaining efficacy but

reducing the common side effects associated with the reducing the common side effects associated with the

sulfapyridine moiety in sulfasalazine.sulfapyridine moiety in sulfasalazine.

Drugs used Drugs used Aminosalicylates Aminosalicylates

are the mainstay of UC pharmacotherapy for induction and are the mainstay of UC pharmacotherapy for induction and

maintenance of remission for patients with mild to maintenance of remission for patients with mild to

moderate disease.moderate disease.

Sulfasalazine Sulfasalazine has been a major agent in the therapy of has been a major agent in the therapy of

mild to moderate UC for over 50 years. In 1977 Mastan mild to moderate UC for over 50 years. In 1977 Mastan

S.Kalsi et al determined that 5-aminosalicyclic acid (5-ASA S.Kalsi et al determined that 5-aminosalicyclic acid (5-ASA

and mesalazine) was the therapeutically active compound and mesalazine) was the therapeutically active compound

in sulfasalazine. Since then many 5-ASA compounds have in sulfasalazine. Since then many 5-ASA compounds have

been developed with the aim of maintaining efficacy but been developed with the aim of maintaining efficacy but

reducing the common side effects associated with the reducing the common side effects associated with the

sulfapyridine moiety in sulfasalazine.sulfapyridine moiety in sulfasalazine.

Page 58: 21 ulcerative colitis

MesalazineMesalazine, also known as 5-aminosalicylic acid, , also known as 5-aminosalicylic acid,

mesalamine, or 5-ASA. (Asacol, Pentasa, Mezavant, Lialda, mesalamine, or 5-ASA. (Asacol, Pentasa, Mezavant, Lialda,

and Salofalk).and Salofalk).

SulfasalazineSulfasalazine, also known as Azulfidine., also known as Azulfidine.

BalsalazideBalsalazide - Disodium , also known as Colazal. - Disodium , also known as Colazal.

OlsalazineOlsalazine, also known as Dipentum., also known as Dipentum.

MesalazineMesalazine, also known as 5-aminosalicylic acid, , also known as 5-aminosalicylic acid,

mesalamine, or 5-ASA. (Asacol, Pentasa, Mezavant, Lialda, mesalamine, or 5-ASA. (Asacol, Pentasa, Mezavant, Lialda,

and Salofalk).and Salofalk).

SulfasalazineSulfasalazine, also known as Azulfidine., also known as Azulfidine.

BalsalazideBalsalazide - Disodium , also known as Colazal. - Disodium , also known as Colazal.

OlsalazineOlsalazine, also known as Dipentum., also known as Dipentum.

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Adverse effects of salicylatesAdverse effects of salicylates SulfasalazineSulfasalazine

Dose dependentDose dependent Anorexia, nausea, dyspepsia, Anorexia, nausea, dyspepsia,

headache, folate headache, folate malabsorption, sperm malabsorption, sperm abnormalitiesabnormalities

IdiosyncraticIdiosyncratic Hypersensitivity reaction, Hypersensitivity reaction,

bone marrow bone marrow , hepatitis, , hepatitis, pancreatitis,pneumonitis & pancreatitis,pneumonitis & eosinophilia, colitiseosinophilia, colitis

5-ASA5-ASA

Headache, dyspepsiaHeadache, dyspepsia

Hypersensitivity colitis, Hypersensitivity colitis, nephrotoxicity, myocarditis, nephrotoxicity, myocarditis, pneomonitis, hepatitis, pancreatitispneomonitis, hepatitis, pancreatitis

Niraj Jani et al. Gastro Clin North America 2002, Katz S. J Clin Gastro 2002,

Page 60: 21 ulcerative colitis

CorticosteroidsCorticosteroids

It is often required for the one-third of patients who fail to It is often required for the one-third of patients who fail to

respond to 5-ASAs, But it is not useful for maintenance respond to 5-ASAs, But it is not useful for maintenance

of remission and carry significant undesirable side of remission and carry significant undesirable side

effects, as osteoporosis, glucose intolerance, and effects, as osteoporosis, glucose intolerance, and

increased risk of infection. increased risk of infection.

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Corticosteroid toxicityCorticosteroid toxicity

Adrenal suppressionAdrenal suppression OsteoporosisOsteoporosis

Hypertension ( x 4 of controls)Hypertension ( x 4 of controls) Glucose intolerance ( x 4 of controls)Glucose intolerance ( x 4 of controls)

Infections ( relative risk 1.6%)Infections ( relative risk 1.6%) CushingoidCushingoid

Psychiatric effectsPsychiatric effects Posterior subcapsular cataract (9%)Posterior subcapsular cataract (9%)

Cutaneous effectsCutaneous effects

Page 62: 21 ulcerative colitis

Immunosupressive drugsImmunosupressive drugs

It have a role in maintenance of remission in moderate to It have a role in maintenance of remission in moderate to

severe UC. Their relatively slow onset of action precludes severe UC. Their relatively slow onset of action precludes

their use during flares of the disease, and the use of these their use during flares of the disease, and the use of these

agents has been reported to potentially increase the risk of agents has been reported to potentially increase the risk of

lymphoma in patients with IBD. It requires intense lymphoma in patients with IBD. It requires intense

monitoring, and may cause irreversible nephrotoxicity, all monitoring, and may cause irreversible nephrotoxicity, all

of which limit its use to severe cases only. of which limit its use to severe cases only.

Immunosupressive drugsImmunosupressive drugs

It have a role in maintenance of remission in moderate to It have a role in maintenance of remission in moderate to

severe UC. Their relatively slow onset of action precludes severe UC. Their relatively slow onset of action precludes

their use during flares of the disease, and the use of these their use during flares of the disease, and the use of these

agents has been reported to potentially increase the risk of agents has been reported to potentially increase the risk of

lymphoma in patients with IBD. It requires intense lymphoma in patients with IBD. It requires intense

monitoring, and may cause irreversible nephrotoxicity, all monitoring, and may cause irreversible nephrotoxicity, all

of which limit its use to severe cases only. of which limit its use to severe cases only.

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Mercaptopurine, also known as 6-Mercaptopurine, 6-MP Mercaptopurine, also known as 6-Mercaptopurine, 6-MP

and Purinethol.and Purinethol.

Azathioprine, also known as Imuran, Azasan or Azamun, Azathioprine, also known as Imuran, Azasan or Azamun,

which metabolises to 6-MP.which metabolises to 6-MP.

Methotrexate.Methotrexate.

Tacrolimus.Tacrolimus.

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Adverse effects of immunomodulatorsAdverse effects of immunomodulators

AZA / 6 MP are metabolized AZA / 6 MP are metabolized Metabolites : 6TG & 6MMP Metabolites : 6TG & 6MMP Crucial enzyme : Thiopurine methyl transferase Crucial enzyme : Thiopurine methyl transferase

(TPMT)(TPMT) Homozygous : 89 %Homozygous : 89 % Heterozygous : 11 %Heterozygous : 11 % Absent enzyme : 0.3 %Absent enzyme : 0.3 %

Adverse effects : bone marrow Adverse effects : bone marrow , hepatitis, , hepatitis, pancreatitispancreatitis

Niraj Jani et al. Gastro Clin North America 2002, Katz S. J Clin Gastro 2002, Farrell RJ et al Lancet 2002, Chinyu Su et al, Gastro Clin North America 2002

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Biological treatmentBiological treatment

It refers to the use of medication that is tailored to It refers to the use of medication that is tailored to

specifically target an immune or genetic mediator of specifically target an immune or genetic mediator of

disease. The, molecules that are involved in the disease disease. The, molecules that are involved in the disease

process have been identified, and can be targeted for process have been identified, and can be targeted for

biological therapy; many of these molecules, which are biological therapy; many of these molecules, which are

mainly cytokines, are directly involved in the immune mainly cytokines, are directly involved in the immune

system.system.

Biological therapy has found a niche in the management of Biological therapy has found a niche in the management of

cancer, autoimmune diseases, and diseases of unknown cancer, autoimmune diseases, and diseases of unknown

cause that result in symptoms due to immune related cause that result in symptoms due to immune related

mechanisms .mechanisms .

(Infliximab ,Visilizumab) (Infliximab ,Visilizumab)

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InfliximabInfliximab is known as a "chimeric monoclonal antibody" is known as a "chimeric monoclonal antibody"

(the term "chimeric" refers to the use of both mouse (the term "chimeric" refers to the use of both mouse

(murine) and human components of the drug. (murine) and human components of the drug.

The drug blocks the action of TNFα (tumor necrosis factor The drug blocks the action of TNFα (tumor necrosis factor

alpha) by binding to it and preventing it from signaling the alpha) by binding to it and preventing it from signaling the

receptors for TNFα on the surface of cells. TNFα is one of receptors for TNFα on the surface of cells. TNFα is one of

the key cytokines that triggers and sustains the the key cytokines that triggers and sustains the

inflammation respone.inflammation respone.

InfliximabInfliximab is known as a "chimeric monoclonal antibody" is known as a "chimeric monoclonal antibody"

(the term "chimeric" refers to the use of both mouse (the term "chimeric" refers to the use of both mouse

(murine) and human components of the drug. (murine) and human components of the drug.

The drug blocks the action of TNFα (tumor necrosis factor The drug blocks the action of TNFα (tumor necrosis factor

alpha) by binding to it and preventing it from signaling the alpha) by binding to it and preventing it from signaling the

receptors for TNFα on the surface of cells. TNFα is one of receptors for TNFα on the surface of cells. TNFα is one of

the key cytokines that triggers and sustains the the key cytokines that triggers and sustains the

inflammation respone.inflammation respone.

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VisilizumabVisilizumab is a humanized monoclonal antibody. It is is a humanized monoclonal antibody. It is

being investigated for use as an immunosuppressive drug being investigated for use as an immunosuppressive drug

in patients with UC and Crohn's disease. Visilizumab binds in patients with UC and Crohn's disease. Visilizumab binds

to the CD3 receptor on certain activated T cells without to the CD3 receptor on certain activated T cells without

effecting resting T cells. It is currently under clinical effecting resting T cells. It is currently under clinical

studies.studies.

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The The αα447 integrin7 integrin is a heterodimeric cell surface is a heterodimeric cell surface

glycoprotein present on the surface of subsets of glycoprotein present on the surface of subsets of

circulating memory CD4+ and CD8+T cells and most B circulating memory CD4+ and CD8+T cells and most B

cells. cells.

It has received particular attention in the context of It has received particular attention in the context of

mucosal immune responses because of its intimate mucosal immune responses because of its intimate

involvement in lymphocyte recruitment to normal involvement in lymphocyte recruitment to normal

gastrointestinal (GI) mucosa and associated lymphoid gastrointestinal (GI) mucosa and associated lymphoid

tissue. tissue.

The The αα447 integrin7 integrin is a heterodimeric cell surface is a heterodimeric cell surface

glycoprotein present on the surface of subsets of glycoprotein present on the surface of subsets of

circulating memory CD4+ and CD8+T cells and most B circulating memory CD4+ and CD8+T cells and most B

cells. cells.

It has received particular attention in the context of It has received particular attention in the context of

mucosal immune responses because of its intimate mucosal immune responses because of its intimate

involvement in lymphocyte recruitment to normal involvement in lymphocyte recruitment to normal

gastrointestinal (GI) mucosa and associated lymphoid gastrointestinal (GI) mucosa and associated lymphoid

tissue. tissue.

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This agent inhibits the binding of This agent inhibits the binding of αα447 integrin to its 7 integrin to its

ligand, the mucosal addressin cell adhesion molecule-1 ligand, the mucosal addressin cell adhesion molecule-1

(MAdCAM-1) which is highly expressed on GI mucosa-(MAdCAM-1) which is highly expressed on GI mucosa-

associaetd endothelium and high endothelial venules of associaetd endothelium and high endothelial venules of

mesenteric lymph nodes.mesenteric lymph nodes.

Binding of integrin antagnosit to Binding of integrin antagnosit to αα447 on lymphocytes 7 on lymphocytes

disrupts lymphocyte migration into inflamed GI mucosa, disrupts lymphocyte migration into inflamed GI mucosa,

thus providing a potential therapeutic option for patients thus providing a potential therapeutic option for patients

with UC. with UC.

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SurgerySurgery

Failure of medical therapy leads to colectomy in (9% - 35%) of Failure of medical therapy leads to colectomy in (9% - 35%) of

patients with UC within 5 years. Colectomy is considered to patients with UC within 5 years. Colectomy is considered to

be an important adjunct treatment for refractory UC; be an important adjunct treatment for refractory UC;

however, colectomy with ileal pouch anal anastomosis (the however, colectomy with ileal pouch anal anastomosis (the

standard surgical therapy) has many limitations and is standard surgical therapy) has many limitations and is

associated with its own set of complications, including high associated with its own set of complications, including high

stool frequency, female infertility, and a cumulative incidence stool frequency, female infertility, and a cumulative incidence

of chronic pouchitis of 50% at 10 years. of chronic pouchitis of 50% at 10 years.

SurgerySurgery

Failure of medical therapy leads to colectomy in (9% - 35%) of Failure of medical therapy leads to colectomy in (9% - 35%) of

patients with UC within 5 years. Colectomy is considered to patients with UC within 5 years. Colectomy is considered to

be an important adjunct treatment for refractory UC; be an important adjunct treatment for refractory UC;

however, colectomy with ileal pouch anal anastomosis (the however, colectomy with ileal pouch anal anastomosis (the

standard surgical therapy) has many limitations and is standard surgical therapy) has many limitations and is

associated with its own set of complications, including high associated with its own set of complications, including high

stool frequency, female infertility, and a cumulative incidence stool frequency, female infertility, and a cumulative incidence

of chronic pouchitis of 50% at 10 years. of chronic pouchitis of 50% at 10 years.

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SurgerySurgery

Absolute indications for subtotal or total colectomy are:Absolute indications for subtotal or total colectomy are:

(1)(1) perforation, with or without abscess formationperforation, with or without abscess formation

(2)(2) colonic carcinoma, for which total protocolectomy and lymph colonic carcinoma, for which total protocolectomy and lymph

node dissection are requirednode dissection are required

(3)(3) massive hemorrhage massive hemorrhage

Relative indications are as follow:Relative indications are as follow:

(1)(1) Severe acute colitis with or without toxic dilatation of the colon, Severe acute colitis with or without toxic dilatation of the colon,

with failure to respond to maximal therapywith failure to respond to maximal therapy

(2)(2) Failure to medical managementFailure to medical management

(3)(3) Suspicion of cancerSuspicion of cancer

SurgerySurgery

Absolute indications for subtotal or total colectomy are:Absolute indications for subtotal or total colectomy are:

(1)(1) perforation, with or without abscess formationperforation, with or without abscess formation

(2)(2) colonic carcinoma, for which total protocolectomy and lymph colonic carcinoma, for which total protocolectomy and lymph

node dissection are requirednode dissection are required

(3)(3) massive hemorrhage massive hemorrhage

Relative indications are as follow:Relative indications are as follow:

(1)(1) Severe acute colitis with or without toxic dilatation of the colon, Severe acute colitis with or without toxic dilatation of the colon,

with failure to respond to maximal therapywith failure to respond to maximal therapy

(2)(2) Failure to medical managementFailure to medical management

(3)(3) Suspicion of cancerSuspicion of cancer

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Unlike Crohn's disease, UC can generally be cured by Unlike Crohn's disease, UC can generally be cured by

surgical removal of the large intestine. This procedure is surgical removal of the large intestine. This procedure is

necessary in the event of: exsanguinating hemorrhage, frank necessary in the event of: exsanguinating hemorrhage, frank

perforation or documented or strongly suspected carcinoma. perforation or documented or strongly suspected carcinoma.

Surgery is also indicated for patients with severe colitis or Surgery is also indicated for patients with severe colitis or

toxic megacolon.toxic megacolon.

Patients with symptoms that are disabling and do not Patients with symptoms that are disabling and do not

respond to drugs may wish to consider whether surgery respond to drugs may wish to consider whether surgery

would improve the quality of life.would improve the quality of life.

In rare cases the extra-intestinal manifestations of the In rare cases the extra-intestinal manifestations of the

disease may require removal of the colon.disease may require removal of the colon.

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Moderate

High dose 5-ASA

High dosemaintenance

Steroids

Severe Extensive

Colitis

5-ASA

CsA

AZA / 6-MP

AZA/6-MPmaintenance Colectomy

RemissionRemission

NORemissionRemission

NO RemissioRemissionn

RemissionRemission RemissionRemission

FailurFailuree

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Alternative treatments Alternative treatments

Smoking :Smoking :

Unlike Crohn's disease, UC has a lesser prevalence in Unlike Crohn's disease, UC has a lesser prevalence in

smokers than non-smokers .smokers than non-smokers .

Dietary modification :Dietary modification :

Dietary modification may reduce the symptoms of the Dietary modification may reduce the symptoms of the

disease.disease.

Lactose intolerance is noted in many ulcerative colitis Lactose intolerance is noted in many ulcerative colitis

patients. Those with suspicious symptoms should get a patients. Those with suspicious symptoms should get a

lactose breath hydrogen test. lactose breath hydrogen test.

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Patients with abdominal cramping or diarrhea may find relief Patients with abdominal cramping or diarrhea may find relief

or a reduction in symptoms by avoiding fresh fruits and or a reduction in symptoms by avoiding fresh fruits and

vegetables, caffeine, carbonated drinks and sorbitol-vegetables, caffeine, carbonated drinks and sorbitol-

containing foods. containing foods.

Many dietary approaches have purported to treat UC, Many dietary approaches have purported to treat UC,

including the ElaineGottschall's specific carbohydrate diet including the ElaineGottschall's specific carbohydrate diet

and the "anti-fungal diet" (Holland/Kaufmann).and the "anti-fungal diet" (Holland/Kaufmann).

The use of elemental and semi-elemental formula has been The use of elemental and semi-elemental formula has been

successful in pediatric patientssuccessful in pediatric patients

Patients with abdominal cramping or diarrhea may find relief Patients with abdominal cramping or diarrhea may find relief

or a reduction in symptoms by avoiding fresh fruits and or a reduction in symptoms by avoiding fresh fruits and

vegetables, caffeine, carbonated drinks and sorbitol-vegetables, caffeine, carbonated drinks and sorbitol-

containing foods. containing foods.

Many dietary approaches have purported to treat UC, Many dietary approaches have purported to treat UC,

including the ElaineGottschall's specific carbohydrate diet including the ElaineGottschall's specific carbohydrate diet

and the "anti-fungal diet" (Holland/Kaufmann).and the "anti-fungal diet" (Holland/Kaufmann).

The use of elemental and semi-elemental formula has been The use of elemental and semi-elemental formula has been

successful in pediatric patientssuccessful in pediatric patients

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Bacterial recolonization Bacterial recolonization

Probiotics may have benefit. And promise for people with Probiotics may have benefit. And promise for people with UC.UC.

Fecalbacteriotherapy involves the infusion of human Fecalbacteriotherapy involves the infusion of human probiotics through fecal enemas. It suggests that the cause probiotics through fecal enemas. It suggests that the cause of UC may be a previous infection by a still unknown of UC may be a previous infection by a still unknown pathogen. pathogen.

This initial infection resolves itself naturally, but somehow This initial infection resolves itself naturally, but somehow causes an imbalance in the colonic bacterial flora, leading causes an imbalance in the colonic bacterial flora, leading to a cycle of inflammation which can be broken by to a cycle of inflammation which can be broken by "recolonizing" the colon with bacteria from a healthy "recolonizing" the colon with bacteria from a healthy bowel. There have been several reported cases of patients bowel. There have been several reported cases of patients who have remained in remission for up to 13 years. who have remained in remission for up to 13 years.

Bacterial recolonization Bacterial recolonization

Probiotics may have benefit. And promise for people with Probiotics may have benefit. And promise for people with UC.UC.

Fecalbacteriotherapy involves the infusion of human Fecalbacteriotherapy involves the infusion of human probiotics through fecal enemas. It suggests that the cause probiotics through fecal enemas. It suggests that the cause of UC may be a previous infection by a still unknown of UC may be a previous infection by a still unknown pathogen. pathogen.

This initial infection resolves itself naturally, but somehow This initial infection resolves itself naturally, but somehow causes an imbalance in the colonic bacterial flora, leading causes an imbalance in the colonic bacterial flora, leading to a cycle of inflammation which can be broken by to a cycle of inflammation which can be broken by "recolonizing" the colon with bacteria from a healthy "recolonizing" the colon with bacteria from a healthy bowel. There have been several reported cases of patients bowel. There have been several reported cases of patients who have remained in remission for up to 13 years. who have remained in remission for up to 13 years.

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Intestinal parasites Intestinal parasites

IBD is less common in the developing world. Some have IBD is less common in the developing world. Some have

suggested that this may be because intestinal parasites are suggested that this may be because intestinal parasites are

more common in underdeveloped countries. Some parasites more common in underdeveloped countries. Some parasites

are able to reduce the immune response of the intestine, an are able to reduce the immune response of the intestine, an

adaptation that helps the parasite colonize the intestine. The adaptation that helps the parasite colonize the intestine. The

decrease in immune response could reduce or eliminate the decrease in immune response could reduce or eliminate the

IBD.IBD.

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PrognosisPrognosisThe outlook for recovery from a first attack of UC is very The outlook for recovery from a first attack of UC is very

good. good.

Mortality, which is about 5%, occurs almost exclusively in Mortality, which is about 5%, occurs almost exclusively in

those who have a severe form of the disease involving the those who have a severe form of the disease involving the

entire colon. entire colon.

The mortality is higher in patients over 60 years,

approximately 17%, compared to 2% in patients between

ages 20 and 59.

Toxic megacolon has a mortality rate of about 20 percent.

Death generally results from the complications of massive

hemorrhage, systemic infections, pulmonary embolism, or

associated cardiac disorders.

PrognosisPrognosisThe outlook for recovery from a first attack of UC is very The outlook for recovery from a first attack of UC is very

good. good.

Mortality, which is about 5%, occurs almost exclusively in Mortality, which is about 5%, occurs almost exclusively in

those who have a severe form of the disease involving the those who have a severe form of the disease involving the

entire colon. entire colon.

The mortality is higher in patients over 60 years,

approximately 17%, compared to 2% in patients between

ages 20 and 59.

Toxic megacolon has a mortality rate of about 20 percent.

Death generally results from the complications of massive

hemorrhage, systemic infections, pulmonary embolism, or

associated cardiac disorders.

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