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Inflammatory bowel disease
Taming the painful lesions into
remission
BY Robert Penner, MD and Karen Madsen,
PhD
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What
is inflammatory bowel disease?
Inflammatory bowel disease (IBD) refers primarily to two chronic
inflammatory disorders: ulcerative colitis (UC) and Crohn's disease
(CD). Ulcerative colitis is an inflammatory disease of the colon,
while CD can involve the entire intestinal tract from the mouth
to the anus. Although these are generally thought of as two clinically
distinct conditions, with different clinical, anatomical and histological
findings, it's likely that these disorders represent a continuum
of diseases, with UC and CD at opposite ends. While significant
morbidity is associated with IBD, mortality isn't increased significantly.
There is currently no known cure for IBD.
The highest incidence rates and prevalence
for CD and UC are seen in northern Europe, the United Kingdom and
North America. In North America, incidence rates for IBD range from
2.2 to 14.3 cases per 100,000 person-years for UC and from 3.1 to
14.6 cases per 100,000 person-years for CD.1
Prevalence ranges from 37 to 246 cases per 100,000 for UC and from
26 to 199 cases per 100,000 persons for CD.1
The peak age of onset for IBD occurs in late adolescence and early
adulthood.2 CD occurs slightly
more often in women, and more frequently among groups who have a
socioeconomic advantage. Higher rates of CD occur in people of Caucasian
and Ashkenazi Jewish origin, although recently, an increased incidence
has been seen in African-Americans and in second-generation South
Asians who have migrated to developed countries.
Do
environmental factors play a role in IBD?
IBD is most prevalent in developed regions of the world. In addition,
a gradient of decreasing prevalence from north to south is seen,
and a higher frequency occurs more often in urban than rural communities.
This high incidence in industrialized countries, and the dramatic
increase in frequency noted during the second half of the 20th
century lends credence to the idea that environmental factors contribute
to disease onset.3
It has been suggested that changes in diet,
smoking, sanitation, and altered exposure to sunlight, pollution,
and various chemicals also play a role. In particular, events in
early childhood are thought to influence the development of IBD.
These include, perinatal infections, length of breastfeeding, domestic
crowding and hygiene, and type of water exposure.1
The occurrence of IBD has an inverse relationship with the degree
of sanitation, with poor sanitation appearing to protect against
the occurrence of IBD. Both UC and CD are more prevalent in individuals
involved in sedentary or indoor occupations, compared with individuals
who work outdoors and do more physical activity.4
An inverse relationship between cigarette
smoking and UC is seen, that is, those who smoke appear to have
a significantly lower risk of developing UC.1
Cigarette smoking may also alter the disease — active smokers
with UC are less likely to be hospitalized for this disease compared
to non-smokers; those who quit smoking have more active disease,
require more hospitalizations, and have a greater need for drug
therapy compared to UC patients who continue to smoke.1
In contrast, cigarette smoking is a significant risk factor for
the development of CD. Smokers with CD also have more frequent recurrences
and a worse response to therapy, leading to more frequent surgical
interventions and a greater need for immunosuppressive treatment.1
Appendectomy appears to protect against the development of UC, and
some studies have shown that this procedure raises the risk for
CD.1
What
is the etiology of IBD?
It's believed that IBD results from a complex interaction between
genetic, environmental, and immunological factors, with luminal
microflora appearing to be a significant factor in the onset and
chronicity of inflammation. In humans, the lumen of the colon contains
approximately 1014 organisms comprising
greater than 500 species, with a large number of these species unculturable
and unidentifiable. In healthy individuals, these luminal bacteria
are tolerated and don't result in neutrophilic infiltration into
the gut mucosa. It seems, however, that patients with IBD have lost
this tolerance, and mount an aggressive inflammatory response against
bacteria in the gut. This activation of lymphocytes and over-expression
of pro-inflammatory cytokines seen in the gut mucosa of IBD patients
has led to the development of several novel therapeutic agents that
act to specifically block production of key inflammatory cytokines
in patients. The dysregulated immune reactivity to specific gut
bacteria is thought to involve both the innate and adaptive immune
system, and has been hypothesized to occur as a result of several
contributing factors, including alterations in regulatory T-cell
function, defects in bacterial antigen recognition, a breakdown
in gut barrier function, and an imbalance between beneficial and
inflammatory microbes within the lumen of the gut.
In UC patients, the primary triggers of disease
appear to be epithelial antigens or altered aerobic bacteria, while
in CD, the reactive antigens are more commonly anaerobic bacteria
and bacterial components.5 To
date, no single infectious or pathogenic microbe has demonstrated
causality or is associated conclusively with IBD. The concept that
IBD develops in response to certain gut bacteria has led to the
idea that altering the gut microflora by administering nonpathogenic
probiotic organisms (Lactobacillus and Bifidobacterium) may
be therapeutic in the treatment or prevention of IBD relapse. Current
trials with probiotics are showing promise in pouchitis and UC treatment.6
What
are the clinical features and presentation of IBD?
Crohn's disease
The typical patient with CD is a young adult who develops right
lower quadrant pain, diarrhea, and a low-grade fever (Table
1). The clinical presentation is often insidious. The patient
may have recurrent episodes of mild diarrhea, abdominal pain, and
fever lasting from days to weeks, followed by spontaneous improvement
in symptoms. The abdominal pain is often localized to the right
lower quadrant. If the colon is involved, crampy pain may occur
in one or both lower abdominal quadrants, and urgency, incontinence
and rectal bleeding may occur.
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