Differential
diagnosis of the functional and organic diseases of intestine in children.
IRRITABLE
BOWEL SYNDROME IN CHILDREN
Irritable bowel syndrome (IBS) is
a digestive disorder that causes abdominal pain, bloating, gas, diarrhoea, and
constipation—or some combination of these problems. IBS affects people of all
ages, including children.
IBS is classified as a functional
disorder because it is caused by a problem in how the intestines, or bowels,
work. People with IBS tend to have overly sensitive intestines that have muscle
spasms in response to food, gas, and sometimes stress. These spasms may cause
pain, diarrhoea, and constipation.
Risk Factors for Irritable Bowel Syndrome
Symptoms of IBS cannot be
traced to a single organic cause. Research suggests that people with IBS seem
to have a colon that is more sensitive and reactive than usual to a variety of
things, including certain foods and stress. Some evidence indicates that the
immune system, which fights infection, is also involved. IBS symptoms can
result from the following:
·
The normal motility of the colon may
not work properly. It can be spasmodic or can even stop temporarily. Spasms are
sudden strong muscle contractions that come and go.
·
The lining of the colon (epithelium),
which is affected by the immune and nervous systems, regulates the passage of
fluids in and out of the colon. In IBS, the epithelium appears to work
properly. However, fast movement of the colon's contents can overcome the
absorptive capacity of the colon. The result is too much fluid in the stool. In
other patients, colonic movement is too slow, too much fluid is absorbed, and
constipation develops.
·
The colon responds strongly to
stimuli (for example, foods or stress) that would not bother most people.
Progression of Irritable Bowel Syndrome
The natural history of IBS is
unclear, and generally consists of repeated episodes of intestinal symptoms,
which makes initiation of treatment plans difficult.
Causes of IBS
The cause of IBS is
unknown. Research suggests people with IBS are more sensitive to gas or stool
in the colon. People with IBS can also have abnormalities in how their
intestines contract, called motility, which refers to the rate stool moves
through the intestines. Whereas a faster rate of movement may cause diarrhea, a slower rate may result in constipation.
Researchers have proposed
many explanations for the increased bowel sensitivity and abnormal bowel
motility associated with IBS, such as
Ø reactions
to certain foods
Ø overgrowth
of bacteria in the colon
Ø psychological
stress, including anxiety and depression
Ø problems
in the way the brain and the gastrointestinal tract communicate with each
other, called the brain-gut connection
IBS may be a cause of recurring
abdominal pain in children. The diagnosis of IBS is based on having abdominal
pain or discomfort plus any two of the following:
The
pain is relieved by having a bowel movement.
The onset of pain is associated with a
change in the frequency of stools.
The
onset of pain is associated with a change in stool consistency.
The symptoms must be present for at
least 12 weeks in the preceding 12 months, and there should be no diseases that
might cause the symptoms.
In children IBS affects girls and
boys equally and may be diarrhoea-predominant, constipation-predominant, or
have a variable stool pattern.
Children with IBS may also have headache,
nausea, or mucus in the stool. Weight loss may occur if a child eats less to
try to avoid pain. Some children first develop symptoms after a stressful
event, such as teething, a bout with the flu, or problems at school or at home.
Stress does not cause IBS, but it can trigger symptoms.
The frequency and severity of IBS symptoms vary widely and may include:
abdominal
pain or discomfort
intestinal
bloating
irregular
bowel habits, including diarrhea, constipation, or
both
a
change in the appearance of stool, including stools that are loose, hard, thin,
or pelletlike
mucus
in the stool
the
need to strain to have a bowel movement
a
sense of urgency when having a bowel movement
the
sensation of not completely emptying the bowels
Diagnostics
IBS is diagnosed based on
symptoms. A diagnostic manual called Rome III guides doctors in diagnosing and
treating functional gastrointestinal disorders, including IBS. According to
Rome III, for a child to be diagnosed with IBS, abdominal pain or discomfort
must be present at least 1 day per week for a period of 2 months or longer. Two
or more of the following must also occur at least 25 percent of the time:
Ø The
pain or discomfort is relieved by having a bowel movement.
Ø The
pain or discomfort is associated with an increase or decrease in the number of
bowel movements.
Ø The
pain or discomfort is associated with a change in the appearance of stool.
No test can show if a person
has IBS; however, a doctor may run tests to rule out diseases with symptoms
similar to IBS. Signs and symptoms that suggest a problem other than IBS
include:
·
persistent pain in the upper right or
lower right area of the abdomen
·
difficulty swallowing
·
persistent vomiting
·
gastrointestinal bleeding
·
waking up during the night with diarrhea or because of abdominal pain
·
a family history of IBD, celiac
disease, or peptic ulcer disease
·
arthritis
·
inflamed, pus-filled masses around
the rectum, also called perirectal disease
·
involuntary weight loss
·
a sudden stop in height growth
·
delayed puberty
·
unexplained fever
To diagnose IBS, the doctor
will ask questions about symptoms and examine the child to rule out more
serious problems or diseases. IBS is not a disease—it is a syndrome, or group
of symptoms that occur together. It does not damage the intestine, so if the
physical exam and other tests show no sign of disease or damage, the doctor may
diagnose IBS.
Treatment
No cure for
IBS exists; however, treatment can reduce symptoms. Treatment is guided by the
symptoms present, their severity, and the child’s response to treatment.
Treatment includes dietary changes, medication, and stress management.
Dietary Changes
Being
a chronic gastrointestinal disorder, irritable bowel syndrome (IBS) is closely
connected with the food we eat, and the way we eat it. This is why diet plays a
very important role in alleviating or aggravating IBS. For the gut to properly
function in digesting and moving waste material, a diet, modified according to
the needs of the sufferer must be followed. Several food categories and methods
of eating are more beneficial and are included in any recommended diet for
irritable bowel syndrome sufferers.
Reducing
or eliminating certain foods may improve symptoms. Common trigger foods include
fatty foods, dairy products, carbonated beverages, and caffeine. Keeping a
diary of symptoms, bowel habits, and diet may help identify foods that trigger
IBS symptoms.
Eating high-fiber foods, such as fruits, vegetables, and whole grain
breads and cereals, may also help. Fiber helps
relieve constipation and promotes regular bowel movements.
Eating several small
meals throughout the day instead of a few large ones may reduce symptoms.
Medications to Control
Constipation and Diarrhea
Fiber
supplements, such as Metamucil or Citrucil, help
control constipation.
Laxatives,
such as PEG 3350 (MiraLax, GlycoLax),
mineral oil, or bisacodyl (Dulcolax),
relieve moderate to severe constipation.
Loperamide (Imodium)
and bismuth subsalicylate (Pepto-Bismol) help relieve diarrhea.
Restores the physiological balance of bowel
movements through:
Þ lowering
the risk of constipation
Þ improvement
of intestinal microflora
Þ improvement
of the condition of intestinal epithelium
Þ improvement
of the intestinal function
Antispasmodics,
such as dycyclomine (Bentyl),
relax smooth muscle contractions in the bowel and can, theoretically, lessen
pain related to IBS but should be used with caution due to potentially serious
side effects.
Antidepressants, including
selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants
(TCAs), are used to treat IBS, although their effectiveness in children is not
well documented.
Before taking any of these
medications, children and their parents should seek the advice of a health care
provider to help weigh the potential benefits against the risk of possible side
effects.
Stress
Management
Understanding
that IBS is not a life-threatening disease can help reduce a child’s anxiety,
which may in turn lessen IBS symptoms. Certain types of counseling,
including cognitive behavior therapy and
hypnotherapy, have been shown to help manage IBS symptoms. Parents can help
reduce a child’s stress by discussing potential IBS-related issues with school
personnel—for example, the need for ready access to a private restroom.
Functional abdominal pains
Chronic functional
abdominal pain (CFAP) is the ongoing presence of abdominal pain for which there
is no known medical explanation. It is quite similar to, but less common than,
irritable bowel syndrome (IBS), and many of the same treatments for IBS can
also be of benefit to those with CFAP. The fundamental difference between IBS
and CFAP is that in CFAP, unlike in IBS, there is no change in bowel habits
such as constipation or diarrhea. Bowel dysfunction
is a necessary diagnostic criteria of IBS.
CFAP is characterized by chronic
pain with no physical explanation or findings (no structural, infectious, or
mechanical causes can be found). It is theorized that CFAP is a disorder of the
nervous system where normal nociceptive nerve impulses are amplified "like
a stereo system turned up too loud" resulting in pain. Alternately it is
hypothesized that there exists in the intestine a protozoan (namely blastocystis) which is interacting with the sympathetic
nervous system and causing the pain. Newer semi-synthetic antibiotics such as rifaximin have been used in treatment. This visceral
hypersensitivity may be a stand-alone cause of CFAP, or CFAP may result from
the same type of brain-gut nervous system disorder that underlies IBS. As with
IBS, low doses of antidepressants have been found useful in controlling the
pain of CFAP.
Abdominal pain that cannot be
explained by any visible or detectable abnormality, after a thorough physical
examination and appropriate further testing if needed, is known as functional
abdominal pain. Functional abdominal pain can be intermittent (recurrent
abdominal pain or RAP) or continuous. Although the exact cause is not known,
nerve signals or chemicals secreted by the gut or brain, may cause the gut to
be more sensitive to triggers that normally do not cause significant pain (such
as stretching or gas bloating). Because of this change in bowel function, this
type of abdominal pain is often referred to as “functional abdominal pain.”
Parents and children need to be reassured that functional abdominal
pain is not life threatening. However, functional abdominal pain may have
negative effects on the child’s physical and psychological state. The pain may
interfere with school attendance, participation in sports and other
extra-curricular activities. Infrequently, it may affect appetite and sleep.
The changes in the daily routine may affect the child’s mood and emotions, and
in turn cause depression and anxiety. In some cases, children previously
suffering from anxiety, depression and other psychiatric disorders may show an
exaggerated pain response. Sometimes, the parent and the child may not be
consciously aware of any stress or emotional disturbances.
Most young children will
point to the umbilicus (belly button) when asked to describe the location of
abdominal pain. However, pain centered around the belly button could be due to a number of causes
that should be considered w hen evaluating a child
with chronic abdominal pain. Some of those causes are not very serious while
other causes require close and long term care. Possible causes that should be
considered based on the history, physical examination and testing, are acid
reflux, constipation, lactose intolerance, parasitic infections of the small
and large intestines, infections of the stomach with a germ called Helicobacter
pylori (that is associated with ulcers in the first portion of the small bowel),
inflammatory bowel diseases (IBD) such as Crohn’s
disease and ulcerous colitis, celiac disease which is a sensitivity to cereal
grains, food allergies, inflammation of the liver (hepatitis), gall bladder
problems, an inflamed pancreas, an
intestinal obstruction (blockage), appendicitis, and many more rare disorders.
It must be emphasized that typically, none of these more severe problems cause
abdominal pain in most children with chronic or recurrent bellyaches. Instead,
the pain is usually “functional”.
Diagnosis
The diagnosis of
functional abdominal pain is often based on the report of symptoms and normal
physical examination. It is also quite possible that the doctor may obtain some
tests. The reason for these tests is to look for signs of any serious disease.
These screening tests may initially include blood and stool tests. The results
of screening tests often guide the doctor in deciding whether further tests are
needed or whether a trial of diet changes, stress management or medication may
be started. Testing should be limited if the history is typical for functional
abdominal pain and the child’s physical examination is normal. In that case, many doctors prefer to treat
without testing in order to avoid the discomfort of testing or the slight risk
associated with testing. Of course, if
the history, the physical examination, or the results of screening tests are
abnormal, further testing may be required.
This further testing may include a test to confirm lactose intolerance,
ultrasound of the abdomen, a CT of the abdomen, and upper GI series (radiology
test), and possibly an endoscopy (scope). The scope allows the doctor to use a
special camera on the scope to look at the inner lining of the food pipe,
stomach, first and last portion of the small intestine and the large intestine.
At the time of the scope, biopsies (small pinches of the lining) are also
obtained and examined under the microscope for signs of certain infections and
disorders like IBD and celiac disease. Normal test results in a child without
alarm signs or red flags strongly suggest RAP or one of the other types of
functional abdominal pain, such as irritable bowel syndrome or functional
dyspepsia.
Treatment
If a specific cause for
abdominal pain is discovered during the evaluation, the physician will discuss
specific management of conditions like constipation, lactose intolerance,
infections, IBD, celiac disease, and food allergies. If no specific cause is
found and functional abdominal pain is suspected, the child needs to be
reassured that his or her abdominal pain is accepted as a real disorder and not
something that is “just in the head”. The goal of managing functional abdominal
pain is to provide a satisfactory quality of life through support, education,
medicines and better coping skills.
Reassurance about the good outcome of functional abdominal pain and the
positive aspects of the child’s health are crucial. Addressing the parents’ and
child’s concerns and fears and identifying emotional or psychological stressors
are also important. As noted before, some tests may be needed during the
evaluation of functional abdominal pain, but it is also important for parents and
children to know that doing too many unnecessary tests may be frustrating to
the family and child. If functional abdominal pain is strongly suspected as the
likely diagnosis, testing should be limited to the most useful, simple and
relatively non-invasive tests.
The child may benefit from
certain dietary changes depending on his/her history. These are recommended on
a case-by-case basis. The physician may advise avoidance of greasy and spicy
foods, caffeine, juices, and carbonated drinks. Eliminating lactose (a natural
sugar in milk and other dairy products) from the diet may benefit those who
suffer from lactose intolerance in addition to functional abdominal pain. Some
children with abdominal pain who also experience “gas” may improve by eating
food slowly and by avoiding carbonated drinks, and gas forming foods such as
cabbage, or beans. In addition, fruit drinks, sugar-free chewing gum, and sugar
free candy sweetened with an alcohol called sorbitol should be avoided. Sorbitol, which tastes sweet, cannot be
properly digested, and when taken in large amounts, it can cause cramping,
bloating, and even diarrhea.
Some children may be candidates
for medications, if functional abdominal pain is significantly limiting the daily
routine. These medications include anti-spasmodic medicines for those with crampy pain in relation to bowel movements, laxatives for
those with constipation, and acid-suppressing medicines for those with pain and
dyspepsia. If the child does not respond to any of these treatments, he or she
may benefit from low doses of medicines called tricyclic antidepressants (used
at much higher doses to treat depression). At low doses, these medicines can be
excellent pain relievers for some children. A fearful, anxious, or depressed
child however should be fully assessed by a psychiatrist or psychologist. Some
psychological treatments that help children cope with functional abdominal pain
and other stressors , include behavioral
therapy, relaxation exercises and hypnosis. It is very important that the
physician, parents, and school encourage the child resume a normal
routine.
Prognosis
Fortunately, the
diagnosis of functional abdominal pain has a good outcome overall, with almost
half of these children getting better on their own or with treatment within a
few weeks to months. A supportive and understanding environment at home and
school is important to keep the child physically and mentally healthy.
Functional constipation
Constipation has been
defined as “a delay or difficulty in defecation, present for two or more weeks,
sufficient to cause significant distress to the patient. This condition is
responsible for an estimated 3 to 5 percent of physician visits by children.
Constipation often causes more distress to parents and other caregivers than to
the affected child. Many caregivers worry that a child’s constipation is the
sign of a serious medical problem.
Constipation is responsible for
up to 5% of pediatric office visits. It is defined as
delay or difficulty in the passing of hard, sometimes large stools for ≥
2 wk.
The
frequency of normal bowel movements varies for infants. In the first year, the
average number of bowel movements ranges from 2 to 4/day. This number also
varies depending on whether infants are breastfed or formula-fed (breastfed
infants have more frequent bowel movements). In general, signs of effort (eg, straining) do not signify constipation; infants only
gradually develop the muscles to assist a bowel movement. After age 1 yr, children average 1 bowel movement/day.
Etiology
Constipation in children is divided
into 2 main types:
·
Organic (5%)
·
Functional (95%)
Organic: Organic causes involve
specific structural, neurologic, toxic/metabolic, or intestinal disorders. They
are rare but important to recognize. The most common cause is Hirschsprung's disease.
Other organic causes that may
manifest in the neonatal period or later include:
Ø Anorectal
malformations
Ø Cystic
fibrosis
Ø Metabolic
disorders (eg, hypothyroidism, hypercalcemia,
hyperkalemia)
Ø Spinal
cord abnormalities
Functional: Functional
constipation is difficulty passing stools for reasons other than organic
causes.
In infants, the use of formula
can lead to small, hard stools.
Causes of constipation in babies
§ Babies
who are bottle fed often suffer from constipation due to lack of water in their
diet.
§ Even
breastfed babies may suffer from constipation if their mothers follow improper
diet.
§ When
a baby is introduced to solids, frequent change in their diet may cause
constipation.
§ If
the baby takes more of fat or protein but less of fiber
then they may suffer from constipation.
§ If
a child has infant rickets then also he/she may have constipation.
§ If
a child suffers from anemia which is induced by iron
deficiency then there are chances of constipation.
§ Hypothyroidism
causes constipation.
§ Sometimes
allergy to certain food like cow’s milk, eggs or fish may cause inflammation
which in turn causes constipation.
§ Sometimes
toddlers avoid toilet. They may avoid their toilet trips when her environment
changes like when she joins preschool or when she is too busy with playing.
Often presence of anal fissures may make defecation painful for which she may
avoid defecating.
§ Long
term use of medicines like antibiotics and anticonvulsants often result in
constipation.
Baby constipation effects on a baby’s body
Þ Constipation
often makes babies cranky, lethargic and she may lose appetite also.
Þ Malabsorption
of essential vitamins and minerals in the body create imbalance which may
finally lead to iron deficiency.
Þ Constipation
in babies may cause inflammation of the intestine which results in abdominal
pain.
Þ Chronic
constipation often leads to certain medical complications. Blood circulation in
the intestine of the baby may be hampered and inflammation in colon can also
occur.
Þ Cracks
may develop in the babies’ rectum due to constipation. Appearance of blood in
stool may follow which requires immediate medical attention.
In older children, diets
low in fiber and high in dairy lead to hard stools
that are uncomfortable to pass and can cause anal fissures. Children sometimes
put off having bowel movements because they have discomfort caused by fissures
or because they do not want to interrupt play. To avoid having a bowel
movement, children may tighten the external sphincter muscles, pushing the
stool higher in the rectal vault.
If this behavior
is repeated, the rectum stretches to accommodate the retained stool. The urge
to defecate is then decreased, and the stool becomes harder, leading to a
vicious circle of painful defecation and worsened constipation. Occasionally,
soft stool passes around the impacted stool and leads to stool incontinence.
Stress, toilet training, desire
for control, and sexual abuse are also some of the functional causes of stool
retention and subsequent constipation.
Evaluation
Evaluation should focus on
differentiating functional constipation from constipation with an organic
cause.
History
History of present illness in
neonates should determine whether meconium has been passed at all and, if so,
when. For older infants and children, history should note onset and duration of
constipation, frequency and consistency of stools, and timing of
symptoms—whether they began after a specific event, such as introduction of
certain foods or a stressor that could lead to stool retention (eg, introduction of toilet training). Important associated
symptoms include soiling (stool incontinence), discomfort during defecation,
and blood on or in the stool. The composition of the diet, especially the
amount of fluids and fiber, should be noted.
Symptoms of constipation
·
painful bowel movements
·
stomach pain/abdominal distention
·
rectal bleeding from tears (fissures)
·
poor appetite
·
irritability/crankiness
·
urine
problems (recurrent infections, bedwetting).
Review of systems should
ask about symptoms that suggest an organic cause, including new onset of poor
suck, hypotonia, and ingestion of honey before age 12
mo (infantile botulism); cold intolerance, dry skin,
fatigue, hypotonia, prolonged neonatal hyperbilirubinemia, urinary frequency, and excessive thirst
(endocrinopathies); change in gait, pain or weakness
in lower extremities, and urinary incontinence (spinal cord defects); night
sweats, fever, and weight loss and vomiting, abdominal pain, poor growth,
intermittent diarrhea, and constipation (intestinal
disorders).
Past medical history should ask about
known disorders that can cause constipation, including cystic fibrosis and
celiac sprue. Exposure to constipating drugs or lead
paint dust should be noted. Clinicians should ask about delayed passage of
meconium within the first 24 to 48 h of life, as well as previous episodes of
constipation and family history of constipation.
Physical examination
The physical examination begins
with general assessment of the child's level of comfort or distress and overall
appearance (including skin and hair condition). Height and weight should be
measured and plotted on growth charts.
Examination should focus on the
abdomen and anus and on the neurologic examination.
The abdomen is inspected for
distention, auscultated for bowel sounds, and palpated for masses and
tenderness. The anus is inspected for a fissure (taking care not to spread the
buttocks so forcefully as to cause one). A digital rectal examination is done
gently to check stool consistency and to obtain a sample for occult blood
testing. Rectal examination should note the tightness of the rectal opening and
presence or absence of stool in the rectal vault. Examination includes
placement of the anus and presence of any hair tuft or pit superior to the
sacrum.
Auscultation
for bowel sounds
In infants, neurologic examination
focuses on tone and muscle strength. In older children, the focus is on gait,
deep tendon reflexes, and signs of weakness in the lower extremities.
Interpretation of findings
A primary finding that
suggests an organic cause in neonates is constipation from birth; those who
have had a normal bowel movement are unlikely to have a significant structural
disorder.
In older children, clues to
an organic cause include constitutional symptoms (particularly weight loss,
fever, vomiting), poor growth (decreasing percentile on growth charts), an
overall ill appearance, and any focal abnormalities detected during
examination. A well-appearing child who has no other complaints besides
constipation, who is not on any constipating drugs, and who has a normal
examination likely has a functional disorder.
A distended rectum
filled with stool or the presence of an anal fissure is consistent with
functional constipation in an otherwise normal child. Constipation that began
after starting a constipating drug or that coincides with a dietary change can
be attributed to that drug or food. Foods that are known to be constipating
include dairy (eg, milk, cheese, yogurt)
and starches and processed foods that do not contain fiber.
However, if constipation complaints begin after ingestion of wheat, celiac sprue should be considered. History of a new stress (eg, a new sibling) or other potential causes of stool
retention behavior, with normal physical findings,
support a functional etiology.
The following findings are of particular
concern:
ü Delayed
passage of meconium (> 24 to 48 h after birth)
ü Hypotonia and poor
suck (suggesting infant botulism)
ü Abnormal
gait and deep tendon reflexes (suggesting spinal cord involvement)
Testing
For patients whose
histories are consistent with functional constipation, no tests are needed unless
there is no response to conventional treatment. An abdominal x-ray should be
done if patients have been unresponsive to treatment or an organic cause is
suspected. Tests for organic causes should be done based on the history and
physical examination.
Barium
enema, rectal manometry, and biopsy (Hirschsprung's disease)
Plain
x-rays of lumbosacral spine; MRI considered (tethered spinal cord or tumor)
Thyroid-stimulating
hormone and thyroxine (hypothyroidism)
Blood
lead level (lead poisoning)
Stool
for botulinum toxin (infant botulism)
Sweat
test and genetic testing (cystic fibrosis)
Ca
and electrolytes (metabolic derangement)
IgA
and IgG anti-gliadin
antibodies, IgA anti-endomysium antibodies, IgA
anti-tissue glutaminase (celiac disease)
Treatment
Specific organic causes
should be treated. Functional constipation is ideally initially treated with
dietary changes and behavior modification.
Diets high in protein and fiber give the body the essential fuels needed to build
muscle, increase energy and exercise to lose fat, rather than muscle. Purify
the digestive tract by eating large amounts of roughage like spinach, romaine
lettuce, fruit and whole grains and oats. Protein-rich diets help keep
everybody full, while fiber-rich.
Dietary changes include
adding prune juice to formula for infants, increasing fruits and vegetables for
older infants and children, increasing water intake, and decreasing the amount
of constipating foods (eg, milk, cheese).
Behavior
modification for older children involves encouraging regular stool passage
after meals if they are toilet trained and providing a reinforcement chart and
encouragement to them. For children who are in the process of toilet training,
it is sometimes worthwhile to give them a break from training until the
constipation concern has passed.
Unresponsive constipation
is treated by disimpacting the bowel and maintaining
a regular diet and stool routine. Disimpaction can
occur through oral or rectal agents. Oral agents require consumption of large
volumes of liquid. Rectal agents can feel invasive and can be difficult to
give. Both methods can be done by parents under medical supervision; however, disimpaction sometimes requires hospitalization if
outpatient management is unsuccessful. Usually, infants do not require extreme
measures, but if intervention is required, a glycerin
suppository is typically adequate.
For
maintenance of healthy bowels, some children may require OTC dietary fiber supplements. These supplements require consuming 32
to
Organic bowel disease
The inflammatory bowel disease (IBD)
include Crohn's disease and ulcerous colitis.
Crohn's
disease (also known as granulomatous, and colitis) is an inflammatory disease
of the intestines that may affect any part of the gastrointestinal tract from
mouth to anus, causing a wide variety of symptoms. It primarily causes
abdominal pain, diarrhea (which may be bloody),
vomiting, or weight loss, but may also cause complications outside of the
gastrointestinal tract such as skin rashes, arthritis, inflammation of the eye,
tiredness, and lack of concentration.
Crohn's
disease is thought to be an autoimmune disease, in which the body's immune
system attacks the gastrointestinal tract, causing inflammation; it is
classified as a type of inflammatory bowel disease. There has been evidence of
a genetic link to
Crohn's disease, putting individuals with
siblings afflicted with the disease at higher risk. It is understood to have a
large environmental component as evidenced by the higher number of cases in
western industrialized nations.
Males and females are equally
affected. Smokers are three times more likely to develop Crohn's
disease. Crohn's
disease affects between 400,000 and 600,000 people in North America. Prevalence
estimates for Northern Europe have ranged from 27–48 per 100,000. Crohn's disease tends to present initially in the teens and
twenties, with another peak incidence in the fifties to seventies, although the
disease can occur at any age.
There is no known pharmaceutical or
surgical cure for Crohn's disease.Treatment
options are restricted to controlling symptoms, maintaining remission and
preventing relapse.
The disease was named for
American gastroenterologist Burrill Bernard Crohn, who in 1932, along with two colleagues, described a
series of patients with inflammation of the terminal ileum, the area most
commonly affected by the illness.
Classification
Distribution of
gastrointestinal Crohn's disease. Based on data from
American Gastroenterological Association.
Crohn's
disease is one type of inflammatory bowel disease (IBD). It affects the
gastrointestinal tract and can be categorized by the area of the
gastrointestinal tract which it affects. Ileocolic Crohn's disease, which affects both the ileum (the last
part of the small intestine that connects to the large intestine) and the large
intestine, accounts for fifty percent of cases. Crohn's
ileitis, affecting the ileum only, accounts for thirty percent of cases, and Crohn's colitis, affecting the large intestine, accounts
for the remaining twenty percent of cases and may be particularly difficult to
distinguish from ulcerous colitis. Gastroduodenal Crohn's disease causes inflammation in the stomach and
first part of the small intestine, called the duodenum. Jejunoileitis
causes spotty patches of inflammation in the top half of the small intestine,
called the jejunum. The disease can attack any part of the digestive tract,
from mouth to anus. However, individuals affected by the disease fall these
three classifications rarely, being affected in other parts of the
gastrointestinal tract such as the stomach and esophagus.
Crohn's
disease may also be categorized by the behavior of
disease as it progresses. This was formalized in the Vienna classification of Crohn's disease.
There are three categories of
disease presentation in Crohn's disease: stricturing, penetrating, and inflammatory. Stricturing disease causes narrowing of the bowel that may
lead to bowel obstruction or changes in the caliber
of the feces. Penetrating disease creates abnormal
passageways (fistulae) between the bowel and other structures such as the skin.
Inflammatory disease (or non-stricturing,
non-penetrating disease) causes inflammation without causing strictures or
fistulae.
Crohn's Disease - Affected Areas
Causes
Although the exact cause of Crohn's disease is still unknown, a combination of
environmental factors and genetic predisposition seems to cause the disease.
The genetic risk factors have now more or less been comprehensively elucidated,
making Crohn's disease the first genetically complex
disease of which the genetic background has been resolved. The relative risks
of contracting the disease when one has a mutation in one of the risk genes,
however, are actually very low (approximately 1:200). Broadly speaking, the
genetic data indicate that innate immune systems in patients with Crohn's disease malfunction, and direct assessment of
patient immunity confirms this notion. This had led to the notion that Crohn's disease should be viewed as innate immune
deficiency, chronic inflammation being caused by adaptive immunity trying to
compensate for the reduced function of the innate immune system.
Genetics
Schematic of NOD2 CARD15
gene, which is associated with certain disease patterns in Crohn's
disease.
Some research has indicated
that Crohn's disease may have a genetic link. The
disease runs in families and those with a sibling with the disease are 30 times
more likely to develop it than the general population.
Mutations in the CARD15 gene
(also known as the NOD2 gene) are associated with Crohn's
disease and with susceptibility to certain phenotypes of disease location and
activity. In earlier studies, only two genes were linked to Crohn's,
but scientists now believe there are over thirty genes that show genetics play
a role in the disease, either directly through causation or indirectly as with
a mediator variable. Anomalies in the XBP1 gene have recently been identified
as a factor, pointing towards a role for the unfolded protein response pathway
of the endoplasmatic reticulum in inflammatory bowel
diseases.
Environmental factors
Diet is believed to
be linked to its higher prevalence in industrialized parts of the world. A positive
correlation has been found between the incidence of the disease and an
increased intake of animal protein, milk protein and an increased ratio of n-6
to n-3 polyunsaturated fatty acids. Negative correlation of the disease
incidence was found to the increased consumption of vegetable protein, and no
correlation to fish protein. Smoking has been shown to increase the risk of the
return of active disease, or "flares".
Immune system
Abnormalities in the
immune system have often been invoked as being causes of Crohn's
disease. Crohn's disease is thought to be an
autoimmune disease, with inflammation stimulated by an over-active Th1 cytokine
response. However, more recent evidence has shown that Th17 is of greater
importance in the disease.
The most recent gene
to be implicated in Crohn's disease is ATG16L1, which
may induce autophagy and hinder the body's ability to attack invasive bacteria.
Contrary to the
prevailing view that Crohn's disease is a primary T
cell autoimmune disorder, there is an increasing body of evidence in favor of the hypothesis that Crohn's
disease results from an impaired innate immunity. The immunodeficiency, which
has been shown to be due to (at least in part) impaired cytokine secretion by
macrophages, is thought to lead to a sustained microbial-induced inflammatory
response, particularly in the colon where the bacterial load is especially
high.
