Crohn's disease, also known as
regional enteritis, is a type of
inflammatory bowel diseaseIn medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
that may affect any part of the
gastrointestinal tractThe human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
from
mouthThe mouth is the first portion of the alimentary canal that receives food andsaliva. The oral mucosa is the mucous membrane epithelium lining the inside of the mouth....
to
anusThe anus is an opening at the opposite end of an animal's digestive tract from the mouth. Its function is to control the expulsion of feces, unwanted semi-solid matter produced during digestion, which, depending on the type of animal, may be one or more of: matter which the animal cannot digest,...
, causing a wide variety of
symptomA symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s. It primarily causes
abdominal painAbdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
,
diarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
(which may be bloody if inflammation is at its worst),
vomitingVomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
(can be continuous), or
weight lossWeight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...
, but may also cause complications outside the gastrointestinal tract such as skin rashes,
arthritisArthritis is a form of joint disorder that involves inflammation of one or more joints....
,
inflammation of the eyeUveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....
, tiredness, and lack of concentration.
Crohn's disease is caused by interactions between environmental, immunological and bacterial factors in genetically susceptible individuals. This results in a chronic inflammatory disorder, in which the body's
immune systemAn immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
attacks the gastrointestinal tract possibly directed at a microbial antigens. There is a
geneticGenetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
association with Crohn's disease, primarily with variations of the
NOD2Nucleotide-binding oligomerization domain-containing protein 2 also known as caspase recruitment domain-containing protein 15 or inflammatory bowel disease protein 1 is a protein that in humans is encoded by the NOD2 gene located on chromosome 16. NOD2 plays an important role in the immune system...
gene and its protein, which senses bacterial cell walls. Siblings of affected individuals are at higher risk. Males and females are equally affected. Smokers are two times more likely to develop Crohn's disease than nonsmokers. Crohn's disease affects between 400,000 and 600,000 people in
North AmericaNorth America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...
.
PrevalenceIn epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
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
pharmaceuticalA pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
or
surgicalSurgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
cure for Crohn's disease.
Treatment optionsManagement of Crohn's disease involves first treating the acute symptoms of the disease, then maintaining remission. Treatment initially involves the use of medications to eliminate infections, generally antibiotics, and reduce inflammation, generally aminosalicylate anti-inflammatory drugs and...
are restricted to controlling symptoms, maintaining remission, and preventing
relapseRelapse, in relation to drug misuse, is resuming the use of a drug or a dependent substance after one or more periods of abstinence. The term is a landmark feature of both substance dependence and substance abuse, which are learned behaviors, and is maintained by neuronal adaptations that mediate...
.
The disease was named after American
gastroenterologistGastroenterology is the branch of medicine whereby the digestive system and its disorders are studied. The name is a combination of three Ancient Greek words gaster , enteron , and logos...
Burrill Bernard Crohn, who, in 1932, together with two colleagues, described a series of patients with inflammation of the
terminal ileumThe terminal ileum is the most distal part of the small intestine. It connects to the cecum, the pouch between the small and the large intestine, via the ileocecal valve.-Pathology of the terminal ileum:...
, the area most commonly affected by the illness. For this reason, the disease has also been called regional ileitis or regional enteritis. The condition, however, had previously been independently described in medical literature by others. The most notable case was in 1904 by Polish surgeon
Antoni LeśniowskiAntoni Leśniowski was a Polish surgeon, credited with publishing what may have been the earliest reports of the condition which later became known as Crohn’s disease....
for whom the condition is alternatively named Leśniowski-Crohn's disease in Polish literature.
Classification
Crohn's disease is one type of
inflammatory bowel diseaseIn medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
(IBD). It typically manifests in the gastrointestinal tract and can be categorized by the specific tract region affected. A disease of both the
ileumThe ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum.The ileum follows the duodenum...
(the last part of the
small intestineThe small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
, which connects to the
large intestineThe large intestine is the third-to-last part of the digestive system — — in vertebrate animals. Its function is to absorb water from the remaining indigestible food matter, and then to pass useless waste material from the body...
), and the large intestine, Ileocolic Crohn's accounts for fifty percent of cases. Crohn's ileitis, manifest in the ileum only, accounts for thirty percent of cases, while Crohn's colitis, of the large intestine, accounts for the remaining twenty percent of cases and may be particularly difficult to distinguish from
ulcerative colitisUlcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...
. 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 (MedlinePlus 2010). The disease can attack any part of the digestive tract, from mouth to anus. However, individuals affected by the disease rarely fall outside these three classifications, with presentations in other areas.
Crohn's disease may also be categorized by the behavior of disease as it progresses. These categorizations formalized in the Vienna classification of the disease. There are three categories of disease presentation in Crohn's disease: stricturing, penetrating, and
inflammatoryInflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
. Stricturing disease causes narrowing of the bowel that may lead to
bowel obstructionBowel obstruction is a mechanical or functional obstruction of the intestines, preventing the normal transit of the products of digestion. It can occur at any level distal to the duodenum of the small intestine and is a medical emergency...
or changes in the caliber of the
fecesFeces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...
. Penetrating disease creates abnormal passageways (
fistulaIn medicine, a fistula is an abnormal connection or passageway between two epithelium-lined organs or vessels that normally do not connect. It is generally a disease condition, but a fistula may be surgically created for therapeutic reasons.-Locations:Fistulas can develop in various parts of the...
e) between the bowel and other structures, such as the skin. Inflammatory disease (or nonstricturing, nonpenetrating disease) causes inflammation without causing strictures or fistulae.
Gastrointestinal
Many people with Crohn's disease have symptoms for years prior to the diagnosis. The usual onset is between 15 and 30 years of age, but can occur at any age. Because of the 'patchy' nature of the gastrointestinal disease and the depth of tissue involvement, initial symptoms can be more subtle than those of ulcerative colitis. People with Crohn's disease experience chronic recurring periods of flare-ups and remission.
Abdominal pain may be the initial symptom of Crohn's disease. It is often accompanied by diarrhea, especially in those who have had surgery. The diarrhea may or may not be bloody. People who have had surgery or multiple surgeries often end up with
short bowel syndromeShort bowel syndrome is a malabsorption disorder caused by the surgical removal of the small intestine, or rarely due to the complete dysfunction of a large segment of bowel. Most cases are acquired, although some children are born with a congenital short bowel...
of the gastrointestinal tract. The nature of the diarrhea in Crohn's disease depends on the part of the small intestine or colon involved. Ileitis typically results in large-volume, watery feces. Colitis may result in a smaller volume of feces of higher frequency. Fecal consistency may range from solid to watery. In severe cases, an individual may have more than 20 bowel movements per day and may need to awaken at night to defecate. Visible bleeding in the feces is less common in Crohn's disease than in ulcerative colitis, but may be seen in the setting of Crohn's colitis. Bloody bowel movements are typically intermittent, and may be bright or dark red in color. In the setting of severe Crohn's colitis, bleeding may be copious.
FlatulenceFlatulence is the expulsion through the rectum of a mixture of gases that are byproducts of the digestion process of mammals and other animals. The medical term for the mixture of gases is flatus, informally known as a fart, or simply gas...
and bloating may also add to the intestinal discomfort.
Symptoms caused by
intestinal stenosisBowel obstruction is a mechanical or functional obstruction of the intestines, preventing the normal transit of the products of digestion. It can occur at any level distal to the duodenum of the small intestine and is a medical emergency...
are also common in Crohn's disease. Abdominal pain is often most severe in areas of the bowel with stenoses. In the setting of severe stenosis, vomiting and nausea may indicate the beginnings of small bowel obstruction. Although the association is greater in the context of
ulcerative colitisUlcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...
, Crohn's disease may also be associated with
primary sclerosing cholangitisPrimary sclerosing cholangitis is a chronic liver disease caused by progressive inflammation and scarring of the bile ducts of the liver. The inflammation impedes the flow of bile to the gut, which can ultimately lead to liver cirrhosis, liver failure and liver cancer...
, a type of inflammation of the bile ducts.
Perianal discomfort may also be prominent in Crohn's disease. Itchiness or pain around the
anusThe anus is an opening at the opposite end of an animal's digestive tract from the mouth. Its function is to control the expulsion of feces, unwanted semi-solid matter produced during digestion, which, depending on the type of animal, may be one or more of: matter which the animal cannot digest,...
may be suggestive of inflammation,
fistulizationIn medicine, a fistula is an abnormal connection or passageway between two epithelium-lined organs or vessels that normally do not connect. It is generally a disease condition, but a fistula may be surgically created for therapeutic reasons.-Locations:Fistulas can develop in various parts of the...
or
abscessAn abscess is a collection of pus that has accumulated in a cavity formed by the tissue in which the pus resides due to an infectious process or other foreign materials...
around the anal area or
anal fissureAn anal fissure is a break or tear in the skin of the anal canal. Anal fissures may be noticed by bright red anal bleeding on the toilet paper, sometimes in the toilet. If acute they may cause severe periodic pain after defecation but with chronic fissures pain intensity is often less...
. Perianal skin
tagsAn acrochordon An acrochordon An acrochordon (plural acrochorda, and also known as a (cutaneous) skin tag, or fibroepithelial polyp, is a small benign tumour that forms primarily in areas where the skin forms creases, such as the neck, armpit, and groin. They may also occur on the face, usually on...
are also common in Crohn's disease.
Fecal incontinenceFecal incontinence is the loss of regular control of the bowels. Involuntary excretion and leaking are common occurrences for those affected. Subjects relating to defecation are often socially unacceptable, thus those affected may be beset by feelings of shame and humiliation...
may accompany perianal Crohn's disease. At the opposite end of the gastrointestinal tract, the mouth may be affected by non-healing sores (
aphthous ulcerAn aphthous ulcer , also known as a canker sore, is a type of mouth ulcer which presents as a painful open sore inside the mouth or upper throat characterized by a break in the mucous membrane. Its cause is unknown, but they are not contagious...
s). Rarely, the
esophagusThe esophagus is an organ in vertebrates which consists of a muscular tube through which food passes from the pharynx to the stomach. During swallowing, food passes from the mouth through the pharynx into the esophagus and travels via peristalsis to the stomach...
, and
stomachThe stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
may be involved in Crohn's disease. These can cause symptoms including difficulty swallowing (
dysphagiaDysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, the term is sometimes used as a condition in its own right. Sufferers are sometimes unaware of their dysphagia....
), upper abdominal pain, and vomiting.
Systemic
Crohn's disease, like many other chronic, inflammatory diseases, can cause a variety of
systemic symptomsB symptoms refer to systemic symptoms of fever, night sweats, and weight loss which can be associated with both Hodgkin's lymphoma and non-Hodgkin's lymphoma...
. Among children, growth failure is common. Many children are first diagnosed with Crohn's disease based on
inability to maintain growthFailure to thrive is a medical term which is used in both pediatric and adult human medicine, as well as veterinary medicine ....
. As it may manifest at the time of the growth spurt in
pubertyPuberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
, up to 30% of children with Crohn's disease may have retardation of growth. Fever may also be present, though fevers greater than 38.5 ˚C (101.3 ˚F) are uncommon unless there is a complication such as an
abscessAn abscess is a collection of pus that has accumulated in a cavity formed by the tissue in which the pus resides due to an infectious process or other foreign materials...
. Among older individuals, Crohn's disease may manifest as weight loss, usually related to decreased food intake, since individuals with intestinal symptoms from Crohn's disease often feel better when they do not eat and might lose their appetite. People with extensive
small intestineThe small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
disease may also have
malabsorptionMalabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...
of
carbohydrateA carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
s or
lipidLipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
s, which can further exacerbate weight loss.
Extraintestinal
In addition to systemic and gastrointestinal involvement, Crohn's disease can affect many other organ systems. Inflammation of the interior portion of the eye, known as
uveitisUveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....
, can cause eye pain, especially when exposed to light (
photophobiaPhotophobia is a symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of actual physical photosensitivity of the eyes, though the term...
). Inflammation may also involve the white part of the eye (
scleraThe sclera , also known as the white or white of the eye, is the opaque , fibrous, protective, outer layer of the eye containing collagen and elastic fiber. In the development of the embryo, the sclera is derived from the neural crest...
), a condition called
episcleritisScleritis is a serious inflammatory disease that affects the white outer coating of the eye, known as the sclera. The disease is often contracted through association with other diseases of the body, such as Wegener's granulomatosis or rheumatoid arthritis; it can also be attained through disorders...
. Both episcleritis and uveitis can lead to loss of vision if untreated.
Crohn's disease is associated with a type of
rheumatologic diseaseRheumatology is a sub-specialty in internal medicine and pediatrics, devoted to diagnosis and therapy of rheumatic diseases. Clinicians who specialize in rheumatology are called rheumatologists...
known as
seronegative spondyloarthropathySpondyloarthropathy is any joint disease of the vertebral column. Spondyloarthropathy with inflammation is called spondylarthritis. In contrast, spondylopathy is a disease of the vertebra itself, but many conditions involve both spondylopathy and spondyloarthropathy...
. This group of diseases is characterized by inflammation of one or more
jointA joint is the location at which two or more bones make contact. They are constructed to allow movement and provide mechanical support, and are classified structurally and functionally.-Classification:...
s (
arthritisArthritis is a form of joint disorder that involves inflammation of one or more joints....
) or muscle insertions (
enthesitisEnthesitis is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. It is also called enthesopathy, or any pathologic condition involving the entheses. The entheses are any point of attachment of skeletal muscles to the bone, where recurring stress or...
). The arthritis can affect larger joints, such as the knee or shoulder, or may exclusively involve the small joints of the hands and feet. The arthritis may also involve the spine, leading to
ankylosing spondylitisAnkylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...
if the entire spine is involved or simply
sacroiliitisIn medicine, sacroiliitis is an inflammation of the sacroiliac joint. Sacroiliitis is a feature of spondylarthropathies .-External links:*...
if only the lower spine is involved. The symptoms of arthritis include painful, warm, swollen, stiff
jointsArthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
and loss of joint mobility or function.
Crohn's disease may also involve the skin, blood, and
endocrine systemIn physiology, the endocrine system is a system of glands, each of which secretes a type of hormone directly into the bloodstream to regulate the body. The endocrine system is in contrast to the exocrine system, which secretes its chemicals using ducts. It derives from the Greek words "endo"...
. One type of skin manifestation,
erythema nodosumErythema nodosum is an inflammation of the fat cells under the skin characterized by tender red nodules or lumps that are usually seen on both shins...
, presents as red nodules usually appearing on the shins. Erythema nodosum is due to inflammation of the underlying subcutaneous tissue, and is characterized by septal
panniculitisPanniculitis is a group of diseases whose hallmark is inflammation of subcutaneous adipose tissue...
. Another skin lesion,
pyoderma gangrenosumPyoderma gangrenosum is a disease that causes tissue to become necrotic, causing deep ulcers that usually occur on the legs. When they occur, they can lead to chronic wounds. Ulcers usually initially look like small bug bites or papules, and they progress to larger ulcers. Though the wounds...
, is typically a painful ulcerating nodule. Crohn's disease also increases the risk of blood clots; painful swelling of the lower legs can be a sign of deep venous thrombosis, while difficulty breathing may be a result of
pulmonary embolismPulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
.
Autoimmune hemolytic anemiaAutoimmune hemolytic anemia occurs when antibodies directed against the person's own red blood cells cause the RBCs to burst , leading to insufficient plasma concentration. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases...
, a condition in which the immune system attacks the red blood cells, is also more common in Crohn's disease and may cause fatigue, pallor, and other symptoms common in
anemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
. Clubbing, a deformity of the ends of the fingers, may also be a result of Crohn's disease. Finally, Crohn's disease may cause
osteoporosisOsteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
, or thinning of the bones. Individuals with osteoporosis are at increased risk of
bone fractureA bone fracture is a medical condition in which there is a break in the continuity of the bone...
s.
Crohn's disease can also cause neurological complications (reportedly in up to 15% of patients). The most common of these are seizures,
strokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
,
myopathyIn medicine, a myopathy is a muscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness. "Myopathy" simply means muscle disease...
,
peripheral neuropathyPeripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of or trauma to the nerve or the side-effects of systemic illness....
,
headacheA headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
and
depressionDepression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
.
Crohn's patients often also have issues with
small bowel bacterial overgrowth syndromeSmall bowel bacterial overgrowth syndrome , or small intestinal bacterial overgrowth , also termed bacterial overgrowth; is a disorder of excessive bacterial growth in the small intestine. Unlike the colon , which is rich with bacteria, the small bowel usually has less than 104 organisms per...
, which has similar symptoms.
In the oral cavity crohn's patients may suffer from
cheilitis granulomatosaCheilitis granulomatosa is a condition characterized by a sudden onset and progressive course terminating in chronic enlargement of the lips....
and other forms of orofacial granulomatosis,
pyostomatitis vegetansPyostomatitis vegetans is an inflammatory stomatitis and most often seen in association with inflammatory bowel disease, namely ulcerative colitis and Crohn's disease.- See also :* Cheilitis* Cheilitis granulomatosa* Skin lesion...
, recurrent aphthous stomatitis,
geographic tongueGeographic tongue, an inflammatory condition of the tongue affecting approximately 2% of the population, is characterized by discolored regions of taste buds or sometimes even cracks in the tongue...
and
migratory stomatitisMigratory stomatitis is a benign condition on the oral soft tissue. This condition has two forms: the common form, which is consisted from red lesions with white borders on the tongue only. This form is called geographic tongue...
in higher prevalence than the general population.
Complications
Crohn's disease can lead to several mechanical complications within the intestines, including
obstructionBowel obstruction is a mechanical or functional obstruction of the intestines, preventing the normal transit of the products of digestion. It can occur at any level distal to the duodenum of the small intestine and is a medical emergency...
, fistulae, and abscesses. Obstruction typically occurs from strictures or adhesions that narrow the lumen, blocking the passage of the intestinal contents. Fistulae can develop between two loops of bowel, between the bowel and bladder, between the bowel and vagina, and between the bowel and skin. Abscesses are walled off collections of
infectionAn infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
, which can occur in the
abdomenIn vertebrates such as mammals the abdomen constitutes the part of the body between the thorax and pelvis. The region enclosed by the abdomen is termed the abdominal cavity...
or in the perianal area in Crohn's disease sufferers. Crohn's is responsible for 10% of vesicoenteric fistulae, and is the most common cause of ileovesical fistulae.
Crohn's disease also increases the risk of cancer in the area of inflammation. For example, individuals with Crohn's disease involving the small bowel are at higher risk for small intestinal cancer. Similarly, people with Crohn's colitis have a
relative riskIn statistics and mathematical epidemiology, relative risk is the risk of an event relative to exposure. Relative risk is a ratio of the probability of the event occurring in the exposed group versus a non-exposed group....
of 5.6 for developing colon cancer. Screening for colon cancer with
colonoscopyColonoscopy is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It may provide a visual diagnosis and grants the opportunity for biopsy or removal of suspected...
is recommended for anyone who has had Crohn's colitis for at least eight years. Some studies suggest there is a role for chemoprotection in the prevention of colorectal cancer in Crohn's involving the colon; two agents have been suggested, folate and mesalamine preparations.
Individuals with Crohn's disease are at risk of
malnutritionMalnutrition is the condition that results from taking an unbalanced diet in which certain nutrients are lacking, in excess , or in the wrong proportions....
for many reasons, including decreased food intake and
malabsorptionMalabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...
. The risk increases following resection of the small bowel. Such individuals may require oral supplements to increase their caloric intake, or in severe cases,
total parenteral nutritionParenteral nutrition is feeding a person intravenously, bypassing the usual process of eating and digestion. The person receives nutritional formulae that contain nutrients such as glucose, amino acids, lipids and added vitamins and dietary minerals...
(TPN). Most people with moderate or severe Crohn's disease are referred to a
dietitianDietitians supervise the preparation and service of food, develop modified diets, participate in research, and educate individuals and groups on good nutritional habits. The goals of dietitians are to provide medical nutritional intervention, and to obtain, safely prepare, serve and advise on...
for assistance in nutrition.
Crohn's disease can cause significant complications, including
bowel obstructionBowel obstruction is a mechanical or functional obstruction of the intestines, preventing the normal transit of the products of digestion. It can occur at any level distal to the duodenum of the small intestine and is a medical emergency...
, abscesses, free perforation and hemorrhage.
Crohn's disease can be problematic during
pregnancyPregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
, and some medications can cause adverse outcomes for the
fetusA fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
or mother. Consultation with an obstetrician and gastroenterologist about Crohn's disease and all medications allows preventative measures to be taken. In some cases, remission can occur during pregnancy. Certain medications can also impact sperm count or may otherwise adversely affect a man's ability to
conceiveFertilisation is the fusion of gametes to produce a new organism. In animals, the process involves the fusion of an ovum with a sperm, which eventually leads to the development of an embryo...
.
Cause
Crohn's disease seems to be caused by a combination of environmental factors and genetic predisposition. Crohn's is the first genetically complex disease in which the relationship between genetic risk factors and the immune system is understood in considerable detail. Each individual risk mutation makes a small contribution to the overall risk of Crohn's (approximately 1:200). The genetic data, and direct assessment of patient immunity, indicates a malfunction in the innate immune system. In this view, the chronic inflammation of Crohn's is caused when the adaptive immune system tries to compensate for a deficient innate immune system.
Genetics
Crohn's has a genetic component. The disease runs in families and siblings are 30 times more likely to develop Crohn's than the general population.
The first mutation found to be associated with Crohn's was a frameshift in the
NOD2Nucleotide-binding oligomerization domain-containing protein 2 also known as caspase recruitment domain-containing protein 15 or inflammatory bowel disease protein 1 is a protein that in humans is encoded by the NOD2 gene located on chromosome 16. NOD2 plays an important role in the immune system...
gene (also known as the CARD15 gene), followed by the discovery of point mutations. By now, over thirty genes have been associated. A biological function is known for most of them. For example, one association is with mutations in the
XBP1X-box binding protein 1, also known as XBP1, is a protein which in humans is encoded by the XBP1 gene. The XBP1 gene is located on chromosome 22 while a closely related pseudogene has been identified and localized to chromosome 5...
gene, which is involved in the
unfolded protein responseThe unfolded protein response is a cellular stress response related to the endoplasmic reticulum. It is a stress response that has been found to be conserved between all mammalian species, as well as yeast and worm organisms...
pathway of the endoplasmatic reticulum.
Environmental factors
The increased incidence of Crohn's in the industrialized world indicates an environmental component. Crohn's is associated with an increased intake of animal
proteinProteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
, milk protein and an increased ratio of
omega-6n−6 fatty acids are a family of unsaturated fatty acids that have in common a final carbon–carbon double bond in the n−6 position, that is, the sixth bond, counting from the methyl end.The biological effects of the n−6 fatty acids are largely mediated by their conversion to n-6 eicosanoids...
to
omega-3N−3 fatty acids are essential unsaturated fatty acids with a double bond starting after the third carbon atom from the end of the carbon chain....
polyunsaturated fatty acidsIn nutrition, polyunsaturated fat, or polyunsaturated fatty acid, are fatty acids in which more than one carbon–carbon double bond exists within the representative molecule. That is, the molecule has two or more points on its structure capable of supporting hydrogen atoms not currently part of the...
.
Crohn's is negatively associated with consumption of vegetable protein. Consumption of fish protein has no association.
SmokingTobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
increases the risk of the return of active disease (flares). The introduction of
hormonal contraceptionHormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive...
in the United States in the 1960s is associated with a dramatic increase in incidence, and one hypothesis is that these drugs work on the digestive system in ways similar to smoking.
IsotretinoinIsotretinoin, INN, is a medication used mostly for cystic acne. It was first developed for brain, pancreatic and other cancers. It is used to treat harlequin-type ichthyosis, a usually lethal skin disease, and lamellar ichthyosis. Its effects are systemic and nonselective...
is associated with Crohn's. Emotional stress is likely to exacerbate Crohn's.
Immune system
The prevailing view was that Crohn's disease is a primary T cell autoimmune disorder. A newer view is that Crohn's results from an impaired innate immunity.
In the newer view, impaired cytokine secretion by macrophages contributes to impaired innate immunity, and leads to a sustained microbial-induced inflammatory response in the colon, where the bacterial load is high.
One theory was that the inflammation of Crohn's was caused by an overactive T
h1
cytokineCytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
response. More recent studies argue that T
h17 is more important.
The most recent gene to be implicated in Crohn's disease is
ATG16L1Autophagy-related protein 16-1 is a protein that in humans is encoded by the ATG16L1 gene.-Function:Autophagy is the major intracellular degradation system delivering cytoplasmic components to lysosomes, and it accounts for degradation of most long-lived proteins and some organelles...
, which may induce autophagy and hinder the body's ability to attack invasive bacteria.
Microbes
Crohn's is not caused by infection by particular pathogenic bacteria. Current thinking is that microorganisms are taking advantage of their host's weakened mucosal layer and inability to clear bacteria from the intestinal walls, which are both symptoms of Crohn's. Some studies have suggested a role for
Mycobacterium avium subspecies paratuberculosisMycobacterium avium subspecies paratuberculosis is an obligate pathogenic bacterium in the genus Mycobacterium. It is often abbreviated M. paratuberculosis or M. avium ssp. paratuberculosis. It is the causative agent of Johne's disease, which affects ruminants such as cattle, and also perhaps...
(MAP), which causes a similar disease,
Johne's diseaseParatuberculosis or Johne's disease is a contagious, chronic and sometimes fatal infection that primarily affects the small intestine of ruminants. It is caused by the bacterium Mycobacterium avium subspecies paratuberculosis...
, in cattle. The
mannoseMannose is a sugar monomer of the aldohexose series of carbohydrates. Mannose is a C-2 epimer of glucose. It is not part of human metabolism, but is a component of microbial cell walls, and is therefore a target of the immune system and also of antibiotics....
-bearing antigens (mannins) from yeast may also cause an
antibodyAn antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
response. Other studies have linked specific strains of enteroadherent
E. coli to the disease. Still, this relationship between specific types of bacteria and Crohn's disease remains unclear.
Mouse studies have suggested some symptoms of Crohn's disease, ulcerative colitis and
irritable bowel syndromeIrritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...
have the same underlying cause. Biopsy samples taken from the colons of all three patient groups were found to produce elevated levels of a serine protease. Experimental introduction of the serine protease into mice has been found to produce widespread pain associated with irritable bowel syndrome, as well as colitis, which is associated with all three diseases. Regional and temporal variations in those illnesses follow those associated with infection with the protozoan
BlastocystisBlastocystis is a genus of single-celled protozoan parasites belonging to a group of organisms known as the Stramenopiles that includes algae, diatoms, and water molds...
.
The "cold-chain" hypothesis is that
psychrotrophic bacteriaPsychrotrophic bacteria are bacteria that are capable of surviving or even thriving in a cold environment. They can be found in soils, in surface and deep sea waters, in Antarctic ecosystems, and in foods....
such as
Yersinia and
Listeria species contribute to the disease. A statistical correlation was found between the advent of the use of refrigeration in the United States and various parts of Europe and the rise of the disease.
There is an apparent connection between Crohn's disease,
Mycobacterium, other pathogenic bacteria, and genetic markers. In many individuals, genetic factors predispose individuals to
Mycobacterium avium subsp.
paratuberculosis infection. This bacterium then produces mannins, which protect both itself and various bacteria from phagocytosis, which causes a variety of secondary infections.
Pathophysiology
During a
colonoscopyColonoscopy is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It may provide a visual diagnosis and grants the opportunity for biopsy or removal of suspected...
,
biopsiesA biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
of the colon are often taken to confirm the diagnosis. Certain characteristic features of the
pathologyPathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
seen point toward Crohn's disease; it shows a transmural pattern of
inflammationInflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
, meaning the inflammation may span the entire depth of the intestinal wall.
UlcerationA peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...
is an outcome seen in highly active disease. There is usually an abrupt transition between unaffected tissue and the ulcer. Under a microscope, biopsies of the affected colon may show mucosal inflammation, characterized by focal infiltration of neutrophils, a type of inflammatory cell, into the
epitheliumEpithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
. This typically occurs in the area overlying lymphoid aggregates. These neutrophils, along with
mononuclear cellsA lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
, may infiltrate the
cryptsIn histology, an intestinal crypt is a gland found in the epithelial lining of the small intestine and colon...
, leading to inflammation (crypititis) or abscess (crypt abscess).
GranulomaGranuloma is a medical term for a tiny collection of immune cells known as macrophages. Granulomas form when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate. Such substances include infectious organisms such as bacteria and fungi as well as...
s, aggregates of
macrophageMacrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
derivatives known as giant cells, are found in 50% of cases and are most specific for Crohn's disease. The granulomas of Crohn's disease do not show "caseation", a cheese-like appearance on microscopic examination characteristic of granulomas associated with infections, such as
tuberculosisTuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
. Biopsies may also show chronic mucosal damage, as evidenced by blunting of the intestinal villi, atypical branching of the crypts, and a change in the tissue type (
metaplasiaMetaplasia is the reversible replacement of one differentiated cell type with another mature differentiated cell type. The change from one type of cell to another may generally be a part of normal maturation process or caused by some sort of abnormal stimulus...
). One example of such metaplasia,
Paneth cell metaplasia, involves development of Paneth cells (typically found in the small intestine) in other parts of the gastrointestinal system.
Diagnosis
The diagnosis of Crohn's disease can sometimes be challenging, and a number of tests are often required to assist the physician in making the diagnosis. Even with a full battery of tests, it may not be possible to diagnose Crohn's with complete certainty; a colonoscopy is approximately 70% effective in diagnosing the disease, with further tests being less effective. Disease in the small bowel is particularly difficult to diagnose, as a traditional colonoscopy allows access to only the colon and lower portions of the small intestines; introduction of the
capsule endoscopyCapsule endoscopy is a way to record images of the digestive tract for use in medicine. The capsule is the size and shape of a pill and contains a tiny camera. After a patient swallows the capsule, it takes pictures of the inside of the gastrointestinal tract...
aids in endoscopic diagnosis. Multinucleated giant cells, a common finding in the lesions of Crohn's disease, are less common in the lesions of lichen nitidus.
Endoscopy
A
colonoscopyColonoscopy is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It may provide a visual diagnosis and grants the opportunity for biopsy or removal of suspected...
is the best test for making the diagnosis of Crohn's disease, as it allows direct visualization of the colon and the
terminal ileumThe terminal ileum is the most distal part of the small intestine. It connects to the cecum, the pouch between the small and the large intestine, via the ileocecal valve.-Pathology of the terminal ileum:...
, identifying the pattern of disease involvement. On occasion, the colonoscope can travel past the terminal ileum, but it varies from patient to patient. During the procedure, the gastroenterologist can also perform a
biopsyA biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
, taking small samples of tissue for laboratory analysis, which may help confirm a diagnosis. As 30% of Crohn's disease involves only the ileum,
cannulaA cannula or canula is a tube that can be inserted into the body, often for the delivery or removal of fluid or for the gathering of data...
tion of the terminal ileum is required in making the diagnosis. Finding a patchy distribution of disease, with involvement of the colon or ileum, but not the
rectumThe rectum is the final straight portion of the large intestine in some mammals, and the gut in others, terminating in the anus. The human rectum is about 12 cm long...
, is suggestive of Crohn's disease, as are other endoscopic stigmata.
The utility of capsule endoscopy for this, however, is still uncertain.
A "
cobblestoneCobblestones are stones that were frequently used in the pavement of early streets. "Cobblestone" is derived from the very old English word "cob", which had a wide range of meanings, one of which was "rounded lump" with overtones of large size...
"-like appearance is seen in approximately 40% of cases of Crohn's disease upon colonoscopy, representing areas of ulceration separated by narrow areas of healthy tissue.
Radiologic tests
A
small bowel follow-throughA barium follow-through procedure is a type of medical imaging technique. It is used to evaluate the presence of disease in a person's small intestine.-Examination:...
may suggest the diagnosis of Crohn's disease and is useful when the disease involves only the small intestine. Because colonoscopy and
gastroscopyFor other expansions of the initialism "OGD", see the disambiguation page.In medicine , esophagogastroduodenoscopy is a diagnostic endoscopic procedure that visualizes the upper part of the gastrointestinal tract up to the duodenum...
allow direct visualization of only the terminal ileum and beginning of the
duodenumThe duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...
, they cannot be used to evaluate the remainder of the small intestine. As a result, a
barium follow-throughA barium follow-through procedure is a type of medical imaging technique. It is used to evaluate the presence of disease in a person's small intestine.-Examination:...
X-ray, wherein
barium sulfateBarium sulfate is the inorganic compound with the chemical formula BaSO4. It is a white crystalline solid that is odorless and insoluble in water. It occurs as the mineral barite, which is the main commercial source of barium and materials prepared from it...
suspension is ingested and
fluoroscopicFluoroscopy is an imaging technique commonly used by physicians to obtain real-time moving images of the internal structures of a patient through the use of a fluoroscope. In its simplest form, a fluoroscope consists of an X-ray source and fluorescent screen between which a patient is placed...
images of the bowel are taken over time, is useful for looking for inflammation and narrowing of the small bowel. Barium enemas, in which barium is inserted into the rectum and fluoroscopy is used to image the bowel, are rarely used in the work-up of Crohn's disease due to the advent of colonoscopy. They remain useful for identifying anatomical abnormalities when strictures of the colon are too small for a colonoscope to pass through, or in the detection of colonic fistulae (in this case contrast should be performed with iodate substances).
CTX-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
and MRI scans are useful for evaluating the small bowel with
enteroclysisEnteroclysis is a fluoroscopic X-ray of the small intestine. Radiocontrast is infused through a tube inserted through the nose to the duodenum, and images are taken in real time as the contrast moves through aided by administration of methyl cellulose. Enteroclysis is also known by the confusing...
protocols.They are also useful for looking for intra-abdominal complications of Crohn's disease, such as abscesses, small bowel obstructions, or fistulae.
Magnetic resonance imagingMagnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(MRI) is another option for imaging the small bowel as well as looking for complications, though it is more expensive and less readily available
Nuclear scans
Multiphase
white blood cell scansThe indium white blood cell scan, also called "indium leukocyte imaging," "indium-111 scan," or simply "indium scan," is a nuclear medicine procedure in which white blood cells are removed from the patient, tagged with the radioisotope Indium-111, and then injected intravenously into the patient...
have been shown to be effective in detecting the locations of active Crohn's disease, particularly in hard to diagnose patients suffering with the early stages or a mild form of the disease with negative endoscopic and radiologic findings. The procedure, a type of
nuclear medicineIn nuclear medicine procedures, elemental radionuclides are combined with other elements to form chemical compounds, or else combined with existing pharmaceutical compounds, to form radiopharmaceuticals. These radiopharmaceuticals, once administered to the patient, can localize to specific organs...
, uses white blood cells removed from the patient; they are tagged with a radioisotope, and then injected intravenously into the patient, and later scanned at several intervals to detect any abnormal white blood cell accumulation, such as pooling in the intestinal tract. Studies have also suggested such scans are useful to monitor the disease and evaluate the effectiveness of therapy.
Blood tests
A
complete blood countA complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...
may reveal
anemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, which may be caused by blood loss, by
vitamin B
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel diseaseIn medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
that may affect any part of the
gastrointestinal tractThe human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
from
mouthThe mouth is the first portion of the alimentary canal that receives food andsaliva. The oral mucosa is the mucous membrane epithelium lining the inside of the mouth....
to
anusThe anus is an opening at the opposite end of an animal's digestive tract from the mouth. Its function is to control the expulsion of feces, unwanted semi-solid matter produced during digestion, which, depending on the type of animal, may be one or more of: matter which the animal cannot digest,...
, causing a wide variety of
symptomA symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s. It primarily causes
abdominal painAbdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
,
diarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
(which may be bloody if inflammation is at its worst),
vomitingVomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
(can be continuous), or
weight lossWeight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...
, but may also cause complications outside the gastrointestinal tract such as skin rashes,
arthritisArthritis is a form of joint disorder that involves inflammation of one or more joints....
,
inflammation of the eyeUveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....
, tiredness, and lack of concentration.
Crohn's disease is caused by interactions between environmental, immunological and bacterial factors in genetically susceptible individuals. This results in a chronic inflammatory disorder, in which the body's
immune systemAn immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
attacks the gastrointestinal tract possibly directed at a microbial antigens. There is a
geneticGenetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
association with Crohn's disease, primarily with variations of the
NOD2Nucleotide-binding oligomerization domain-containing protein 2 also known as caspase recruitment domain-containing protein 15 or inflammatory bowel disease protein 1 is a protein that in humans is encoded by the NOD2 gene located on chromosome 16. NOD2 plays an important role in the immune system...
gene and its protein, which senses bacterial cell walls. Siblings of affected individuals are at higher risk. Males and females are equally affected. Smokers are two times more likely to develop Crohn's disease than nonsmokers. Crohn's disease affects between 400,000 and 600,000 people in
North AmericaNorth America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...
.
PrevalenceIn epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
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
pharmaceuticalA pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
or
surgicalSurgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
cure for Crohn's disease.
Treatment optionsManagement of Crohn's disease involves first treating the acute symptoms of the disease, then maintaining remission. Treatment initially involves the use of medications to eliminate infections, generally antibiotics, and reduce inflammation, generally aminosalicylate anti-inflammatory drugs and...
are restricted to controlling symptoms, maintaining remission, and preventing
relapseRelapse, in relation to drug misuse, is resuming the use of a drug or a dependent substance after one or more periods of abstinence. The term is a landmark feature of both substance dependence and substance abuse, which are learned behaviors, and is maintained by neuronal adaptations that mediate...
.
The disease was named after American
gastroenterologistGastroenterology is the branch of medicine whereby the digestive system and its disorders are studied. The name is a combination of three Ancient Greek words gaster , enteron , and logos...
Burrill Bernard Crohn, who, in 1932, together with two colleagues, described a series of patients with inflammation of the
terminal ileumThe terminal ileum is the most distal part of the small intestine. It connects to the cecum, the pouch between the small and the large intestine, via the ileocecal valve.-Pathology of the terminal ileum:...
, the area most commonly affected by the illness. For this reason, the disease has also been called regional ileitis or regional enteritis. The condition, however, had previously been independently described in medical literature by others. The most notable case was in 1904 by Polish surgeon
Antoni LeśniowskiAntoni Leśniowski was a Polish surgeon, credited with publishing what may have been the earliest reports of the condition which later became known as Crohn’s disease....
for whom the condition is alternatively named Leśniowski-Crohn's disease in Polish literature.
Classification
Crohn's disease is one type of
inflammatory bowel diseaseIn medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
(IBD). It typically manifests in the gastrointestinal tract and can be categorized by the specific tract region affected. A disease of both the
ileumThe ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum.The ileum follows the duodenum...
(the last part of the
small intestineThe small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
, which connects to the
large intestineThe large intestine is the third-to-last part of the digestive system — — in vertebrate animals. Its function is to absorb water from the remaining indigestible food matter, and then to pass useless waste material from the body...
), and the large intestine, Ileocolic Crohn's accounts for fifty percent of cases. Crohn's ileitis, manifest in the ileum only, accounts for thirty percent of cases, while Crohn's colitis, of the large intestine, accounts for the remaining twenty percent of cases and may be particularly difficult to distinguish from
ulcerative colitisUlcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...
. 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 (MedlinePlus 2010). The disease can attack any part of the digestive tract, from mouth to anus. However, individuals affected by the disease rarely fall outside these three classifications, with presentations in other areas.
Crohn's disease may also be categorized by the behavior of disease as it progresses. These categorizations formalized in the Vienna classification of the disease. There are three categories of disease presentation in Crohn's disease: stricturing, penetrating, and
inflammatoryInflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
. Stricturing disease causes narrowing of the bowel that may lead to
bowel obstructionBowel obstruction is a mechanical or functional obstruction of the intestines, preventing the normal transit of the products of digestion. It can occur at any level distal to the duodenum of the small intestine and is a medical emergency...
or changes in the caliber of the
fecesFeces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...
. Penetrating disease creates abnormal passageways (
fistulaIn medicine, a fistula is an abnormal connection or passageway between two epithelium-lined organs or vessels that normally do not connect. It is generally a disease condition, but a fistula may be surgically created for therapeutic reasons.-Locations:Fistulas can develop in various parts of the...
e) between the bowel and other structures, such as the skin. Inflammatory disease (or nonstricturing, nonpenetrating disease) causes inflammation without causing strictures or fistulae.
Gastrointestinal
Many people with Crohn's disease have symptoms for years prior to the diagnosis. The usual onset is between 15 and 30 years of age, but can occur at any age. Because of the 'patchy' nature of the gastrointestinal disease and the depth of tissue involvement, initial symptoms can be more subtle than those of ulcerative colitis. People with Crohn's disease experience chronic recurring periods of flare-ups and remission.
Abdominal pain may be the initial symptom of Crohn's disease. It is often accompanied by diarrhea, especially in those who have had surgery. The diarrhea may or may not be bloody. People who have had surgery or multiple surgeries often end up with
short bowel syndromeShort bowel syndrome is a malabsorption disorder caused by the surgical removal of the small intestine, or rarely due to the complete dysfunction of a large segment of bowel. Most cases are acquired, although some children are born with a congenital short bowel...
of the gastrointestinal tract. The nature of the diarrhea in Crohn's disease depends on the part of the small intestine or colon involved. Ileitis typically results in large-volume, watery feces. Colitis may result in a smaller volume of feces of higher frequency. Fecal consistency may range from solid to watery. In severe cases, an individual may have more than 20 bowel movements per day and may need to awaken at night to defecate. Visible bleeding in the feces is less common in Crohn's disease than in ulcerative colitis, but may be seen in the setting of Crohn's colitis. Bloody bowel movements are typically intermittent, and may be bright or dark red in color. In the setting of severe Crohn's colitis, bleeding may be copious.
FlatulenceFlatulence is the expulsion through the rectum of a mixture of gases that are byproducts of the digestion process of mammals and other animals. The medical term for the mixture of gases is flatus, informally known as a fart, or simply gas...
and bloating may also add to the intestinal discomfort.
Symptoms caused by
intestinal stenosisBowel obstruction is a mechanical or functional obstruction of the intestines, preventing the normal transit of the products of digestion. It can occur at any level distal to the duodenum of the small intestine and is a medical emergency...
are also common in Crohn's disease. Abdominal pain is often most severe in areas of the bowel with stenoses. In the setting of severe stenosis, vomiting and nausea may indicate the beginnings of small bowel obstruction. Although the association is greater in the context of
ulcerative colitisUlcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...
, Crohn's disease may also be associated with
primary sclerosing cholangitisPrimary sclerosing cholangitis is a chronic liver disease caused by progressive inflammation and scarring of the bile ducts of the liver. The inflammation impedes the flow of bile to the gut, which can ultimately lead to liver cirrhosis, liver failure and liver cancer...
, a type of inflammation of the bile ducts.
Perianal discomfort may also be prominent in Crohn's disease. Itchiness or pain around the
anusThe anus is an opening at the opposite end of an animal's digestive tract from the mouth. Its function is to control the expulsion of feces, unwanted semi-solid matter produced during digestion, which, depending on the type of animal, may be one or more of: matter which the animal cannot digest,...
may be suggestive of inflammation,
fistulizationIn medicine, a fistula is an abnormal connection or passageway between two epithelium-lined organs or vessels that normally do not connect. It is generally a disease condition, but a fistula may be surgically created for therapeutic reasons.-Locations:Fistulas can develop in various parts of the...
or
abscessAn abscess is a collection of pus that has accumulated in a cavity formed by the tissue in which the pus resides due to an infectious process or other foreign materials...
around the anal area or
anal fissureAn anal fissure is a break or tear in the skin of the anal canal. Anal fissures may be noticed by bright red anal bleeding on the toilet paper, sometimes in the toilet. If acute they may cause severe periodic pain after defecation but with chronic fissures pain intensity is often less...
. Perianal skin
tagsAn acrochordon An acrochordon An acrochordon (plural acrochorda, and also known as a (cutaneous) skin tag, or fibroepithelial polyp, is a small benign tumour that forms primarily in areas where the skin forms creases, such as the neck, armpit, and groin. They may also occur on the face, usually on...
are also common in Crohn's disease.
Fecal incontinenceFecal incontinence is the loss of regular control of the bowels. Involuntary excretion and leaking are common occurrences for those affected. Subjects relating to defecation are often socially unacceptable, thus those affected may be beset by feelings of shame and humiliation...
may accompany perianal Crohn's disease. At the opposite end of the gastrointestinal tract, the mouth may be affected by non-healing sores (
aphthous ulcerAn aphthous ulcer , also known as a canker sore, is a type of mouth ulcer which presents as a painful open sore inside the mouth or upper throat characterized by a break in the mucous membrane. Its cause is unknown, but they are not contagious...
s). Rarely, the
esophagusThe esophagus is an organ in vertebrates which consists of a muscular tube through which food passes from the pharynx to the stomach. During swallowing, food passes from the mouth through the pharynx into the esophagus and travels via peristalsis to the stomach...
, and
stomachThe stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
may be involved in Crohn's disease. These can cause symptoms including difficulty swallowing (
dysphagiaDysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, the term is sometimes used as a condition in its own right. Sufferers are sometimes unaware of their dysphagia....
), upper abdominal pain, and vomiting.
Systemic
Crohn's disease, like many other chronic, inflammatory diseases, can cause a variety of
systemic symptomsB symptoms refer to systemic symptoms of fever, night sweats, and weight loss which can be associated with both Hodgkin's lymphoma and non-Hodgkin's lymphoma...
. Among children, growth failure is common. Many children are first diagnosed with Crohn's disease based on
inability to maintain growthFailure to thrive is a medical term which is used in both pediatric and adult human medicine, as well as veterinary medicine ....
. As it may manifest at the time of the growth spurt in
pubertyPuberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
, up to 30% of children with Crohn's disease may have retardation of growth. Fever may also be present, though fevers greater than 38.5 ˚C (101.3 ˚F) are uncommon unless there is a complication such as an
abscessAn abscess is a collection of pus that has accumulated in a cavity formed by the tissue in which the pus resides due to an infectious process or other foreign materials...
. Among older individuals, Crohn's disease may manifest as weight loss, usually related to decreased food intake, since individuals with intestinal symptoms from Crohn's disease often feel better when they do not eat and might lose their appetite. People with extensive
small intestineThe small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
disease may also have
malabsorptionMalabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...
of
carbohydrateA carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
s or
lipidLipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
s, which can further exacerbate weight loss.
Extraintestinal
In addition to systemic and gastrointestinal involvement, Crohn's disease can affect many other organ systems. Inflammation of the interior portion of the eye, known as
uveitisUveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....
, can cause eye pain, especially when exposed to light (
photophobiaPhotophobia is a symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of actual physical photosensitivity of the eyes, though the term...
). Inflammation may also involve the white part of the eye (
scleraThe sclera , also known as the white or white of the eye, is the opaque , fibrous, protective, outer layer of the eye containing collagen and elastic fiber. In the development of the embryo, the sclera is derived from the neural crest...
), a condition called
episcleritisScleritis is a serious inflammatory disease that affects the white outer coating of the eye, known as the sclera. The disease is often contracted through association with other diseases of the body, such as Wegener's granulomatosis or rheumatoid arthritis; it can also be attained through disorders...
. Both episcleritis and uveitis can lead to loss of vision if untreated.
Crohn's disease is associated with a type of
rheumatologic diseaseRheumatology is a sub-specialty in internal medicine and pediatrics, devoted to diagnosis and therapy of rheumatic diseases. Clinicians who specialize in rheumatology are called rheumatologists...
known as
seronegative spondyloarthropathySpondyloarthropathy is any joint disease of the vertebral column. Spondyloarthropathy with inflammation is called spondylarthritis. In contrast, spondylopathy is a disease of the vertebra itself, but many conditions involve both spondylopathy and spondyloarthropathy...
. This group of diseases is characterized by inflammation of one or more
jointA joint is the location at which two or more bones make contact. They are constructed to allow movement and provide mechanical support, and are classified structurally and functionally.-Classification:...
s (
arthritisArthritis is a form of joint disorder that involves inflammation of one or more joints....
) or muscle insertions (
enthesitisEnthesitis is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. It is also called enthesopathy, or any pathologic condition involving the entheses. The entheses are any point of attachment of skeletal muscles to the bone, where recurring stress or...
). The arthritis can affect larger joints, such as the knee or shoulder, or may exclusively involve the small joints of the hands and feet. The arthritis may also involve the spine, leading to
ankylosing spondylitisAnkylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...
if the entire spine is involved or simply
sacroiliitisIn medicine, sacroiliitis is an inflammation of the sacroiliac joint. Sacroiliitis is a feature of spondylarthropathies .-External links:*...
if only the lower spine is involved. The symptoms of arthritis include painful, warm, swollen, stiff
jointsArthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
and loss of joint mobility or function.
Crohn's disease may also involve the skin, blood, and
endocrine systemIn physiology, the endocrine system is a system of glands, each of which secretes a type of hormone directly into the bloodstream to regulate the body. The endocrine system is in contrast to the exocrine system, which secretes its chemicals using ducts. It derives from the Greek words "endo"...
. One type of skin manifestation,
erythema nodosumErythema nodosum is an inflammation of the fat cells under the skin characterized by tender red nodules or lumps that are usually seen on both shins...
, presents as red nodules usually appearing on the shins. Erythema nodosum is due to inflammation of the underlying subcutaneous tissue, and is characterized by septal
panniculitisPanniculitis is a group of diseases whose hallmark is inflammation of subcutaneous adipose tissue...
. Another skin lesion,
pyoderma gangrenosumPyoderma gangrenosum is a disease that causes tissue to become necrotic, causing deep ulcers that usually occur on the legs. When they occur, they can lead to chronic wounds. Ulcers usually initially look like small bug bites or papules, and they progress to larger ulcers. Though the wounds...
, is typically a painful ulcerating nodule. Crohn's disease also increases the risk of blood clots; painful swelling of the lower legs can be a sign of deep venous thrombosis, while difficulty breathing may be a result of
pulmonary embolismPulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
.
Autoimmune hemolytic anemiaAutoimmune hemolytic anemia occurs when antibodies directed against the person's own red blood cells cause the RBCs to burst , leading to insufficient plasma concentration. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases...
, a condition in which the immune system attacks the red blood cells, is also more common in Crohn's disease and may cause fatigue, pallor, and other symptoms common in
anemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
. Clubbing, a deformity of the ends of the fingers, may also be a result of Crohn's disease. Finally, Crohn's disease may cause
osteoporosisOsteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
, or thinning of the bones. Individuals with osteoporosis are at increased risk of
bone fractureA bone fracture is a medical condition in which there is a break in the continuity of the bone...
s.
Crohn's disease can also cause neurological complications (reportedly in up to 15% of patients). The most common of these are seizures,
strokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
,
myopathyIn medicine, a myopathy is a muscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness. "Myopathy" simply means muscle disease...
,
peripheral neuropathyPeripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of or trauma to the nerve or the side-effects of systemic illness....
,
headacheA headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
and
depressionDepression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
.
Crohn's patients often also have issues with
small bowel bacterial overgrowth syndromeSmall bowel bacterial overgrowth syndrome , or small intestinal bacterial overgrowth , also termed bacterial overgrowth; is a disorder of excessive bacterial growth in the small intestine. Unlike the colon , which is rich with bacteria, the small bowel usually has less than 104 organisms per...
, which has similar symptoms.
In the oral cavity crohn's patients may suffer from
cheilitis granulomatosaCheilitis granulomatosa is a condition characterized by a sudden onset and progressive course terminating in chronic enlargement of the lips....
and other forms of orofacial granulomatosis,
pyostomatitis vegetansPyostomatitis vegetans is an inflammatory stomatitis and most often seen in association with inflammatory bowel disease, namely ulcerative colitis and Crohn's disease.- See also :* Cheilitis* Cheilitis granulomatosa* Skin lesion...
, recurrent aphthous stomatitis,
geographic tongueGeographic tongue, an inflammatory condition of the tongue affecting approximately 2% of the population, is characterized by discolored regions of taste buds or sometimes even cracks in the tongue...
and
migratory stomatitisMigratory stomatitis is a benign condition on the oral soft tissue. This condition has two forms: the common form, which is consisted from red lesions with white borders on the tongue only. This form is called geographic tongue...
in higher prevalence than the general population.
Complications
{{Complications of CD vs. UC}}
Crohn's disease can lead to several mechanical complications within the intestines, including
obstructionBowel obstruction is a mechanical or functional obstruction of the intestines, preventing the normal transit of the products of digestion. It can occur at any level distal to the duodenum of the small intestine and is a medical emergency...
, fistulae, and abscesses. Obstruction typically occurs from strictures or adhesions that narrow the lumen, blocking the passage of the intestinal contents. Fistulae can develop between two loops of bowel, between the bowel and bladder, between the bowel and vagina, and between the bowel and skin. Abscesses are walled off collections of
infectionAn infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
, which can occur in the
abdomenIn vertebrates such as mammals the abdomen constitutes the part of the body between the thorax and pelvis. The region enclosed by the abdomen is termed the abdominal cavity...
or in the perianal area in Crohn's disease sufferers. Crohn's is responsible for 10% of vesicoenteric fistulae, and is the most common cause of ileovesical fistulae.
Crohn's disease also increases the risk of cancer in the area of inflammation. For example, individuals with Crohn's disease involving the small bowel are at higher risk for small intestinal cancer. Similarly, people with Crohn's colitis have a
relative riskIn statistics and mathematical epidemiology, relative risk is the risk of an event relative to exposure. Relative risk is a ratio of the probability of the event occurring in the exposed group versus a non-exposed group....
of 5.6 for developing colon cancer. Screening for colon cancer with
colonoscopyColonoscopy is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It may provide a visual diagnosis and grants the opportunity for biopsy or removal of suspected...
is recommended for anyone who has had Crohn's colitis for at least eight years. Some studies suggest there is a role for chemoprotection in the prevention of colorectal cancer in Crohn's involving the colon; two agents have been suggested, folate and mesalamine preparations.
Individuals with Crohn's disease are at risk of
malnutritionMalnutrition is the condition that results from taking an unbalanced diet in which certain nutrients are lacking, in excess , or in the wrong proportions....
for many reasons, including decreased food intake and
malabsorptionMalabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...
. The risk increases following resection of the small bowel. Such individuals may require oral supplements to increase their caloric intake, or in severe cases,
total parenteral nutritionParenteral nutrition is feeding a person intravenously, bypassing the usual process of eating and digestion. The person receives nutritional formulae that contain nutrients such as glucose, amino acids, lipids and added vitamins and dietary minerals...
(TPN). Most people with moderate or severe Crohn's disease are referred to a
dietitianDietitians supervise the preparation and service of food, develop modified diets, participate in research, and educate individuals and groups on good nutritional habits. The goals of dietitians are to provide medical nutritional intervention, and to obtain, safely prepare, serve and advise on...
for assistance in nutrition.
Crohn's disease can cause significant complications, including
bowel obstructionBowel obstruction is a mechanical or functional obstruction of the intestines, preventing the normal transit of the products of digestion. It can occur at any level distal to the duodenum of the small intestine and is a medical emergency...
, abscesses, free perforation and hemorrhage.
Crohn's disease can be problematic during
pregnancyPregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
, and some medications can cause adverse outcomes for the
fetusA fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
or mother. Consultation with an obstetrician and gastroenterologist about Crohn's disease and all medications allows preventative measures to be taken. In some cases, remission can occur during pregnancy. Certain medications can also impact sperm count or may otherwise adversely affect a man's ability to
conceiveFertilisation is the fusion of gametes to produce a new organism. In animals, the process involves the fusion of an ovum with a sperm, which eventually leads to the development of an embryo...
.
Cause
{{Risk factors in CD vs. UC}}
Crohn's disease seems to be caused by a combination of environmental factors and genetic predisposition. Crohn's is the first genetically complex disease in which the relationship between genetic risk factors and the immune system is understood in considerable detail. Each individual risk mutation makes a small contribution to the overall risk of Crohn's (approximately 1:200). The genetic data, and direct assessment of patient immunity, indicates a malfunction in the innate immune system. In this view, the chronic inflammation of Crohn's is caused when the adaptive immune system tries to compensate for a deficient innate immune system.
Genetics
Crohn's has a genetic component. The disease runs in families and siblings are 30 times more likely to develop Crohn's than the general population.
The first mutation found to be associated with Crohn's was a frameshift in the
NOD2Nucleotide-binding oligomerization domain-containing protein 2 also known as caspase recruitment domain-containing protein 15 or inflammatory bowel disease protein 1 is a protein that in humans is encoded by the NOD2 gene located on chromosome 16. NOD2 plays an important role in the immune system...
gene (also known as the CARD15 gene), followed by the discovery of point mutations. By now, over thirty genes have been associated. A biological function is known for most of them. For example, one association is with mutations in the
XBP1X-box binding protein 1, also known as XBP1, is a protein which in humans is encoded by the XBP1 gene. The XBP1 gene is located on chromosome 22 while a closely related pseudogene has been identified and localized to chromosome 5...
gene, which is involved in the
unfolded protein responseThe unfolded protein response is a cellular stress response related to the endoplasmic reticulum. It is a stress response that has been found to be conserved between all mammalian species, as well as yeast and worm organisms...
pathway of the endoplasmatic reticulum.
Environmental factors
The increased incidence of Crohn's in the industrialized world indicates an environmental component. Crohn's is associated with an increased intake of animal
proteinProteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
, milk protein and an increased ratio of
omega-6n−6 fatty acids are a family of unsaturated fatty acids that have in common a final carbon–carbon double bond in the n−6 position, that is, the sixth bond, counting from the methyl end.The biological effects of the n−6 fatty acids are largely mediated by their conversion to n-6 eicosanoids...
to
omega-3N−3 fatty acids are essential unsaturated fatty acids with a double bond starting after the third carbon atom from the end of the carbon chain....
polyunsaturated fatty acidsIn nutrition, polyunsaturated fat, or polyunsaturated fatty acid, are fatty acids in which more than one carbon–carbon double bond exists within the representative molecule. That is, the molecule has two or more points on its structure capable of supporting hydrogen atoms not currently part of the...
.
Crohn's is negatively associated with consumption of vegetable protein. Consumption of fish protein has no association.
SmokingTobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
increases the risk of the return of active disease (flares). The introduction of
hormonal contraceptionHormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive...
in the United States in the 1960s is associated with a dramatic increase in incidence, and one hypothesis is that these drugs work on the digestive system in ways similar to smoking.
IsotretinoinIsotretinoin, INN, is a medication used mostly for cystic acne. It was first developed for brain, pancreatic and other cancers. It is used to treat harlequin-type ichthyosis, a usually lethal skin disease, and lamellar ichthyosis. Its effects are systemic and nonselective...
is associated with Crohn's. Emotional stress is likely to exacerbate Crohn's.
Immune system
The prevailing view was that Crohn's disease is a primary T cell autoimmune disorder. A newer view is that Crohn's results from an impaired innate immunity.
In the newer view, impaired cytokine secretion by macrophages contributes to impaired innate immunity, and leads to a sustained microbial-induced inflammatory response in the colon, where the bacterial load is high.
One theory was that the inflammation of Crohn's was caused by an overactive T
h1
cytokineCytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
response. More recent studies argue that T
h17 is more important.
The most recent gene to be implicated in Crohn's disease is
ATG16L1Autophagy-related protein 16-1 is a protein that in humans is encoded by the ATG16L1 gene.-Function:Autophagy is the major intracellular degradation system delivering cytoplasmic components to lysosomes, and it accounts for degradation of most long-lived proteins and some organelles...
, which may induce autophagy and hinder the body's ability to attack invasive bacteria.
Microbes
Crohn's is not caused by infection by particular pathogenic bacteria. Current thinking is that microorganisms are taking advantage of their host's weakened mucosal layer and inability to clear bacteria from the intestinal walls, which are both symptoms of Crohn's. Some studies have suggested a role for
Mycobacterium avium subspecies paratuberculosisMycobacterium avium subspecies paratuberculosis is an obligate pathogenic bacterium in the genus Mycobacterium. It is often abbreviated M. paratuberculosis or M. avium ssp. paratuberculosis. It is the causative agent of Johne's disease, which affects ruminants such as cattle, and also perhaps...
(MAP), which causes a similar disease,
Johne's diseaseParatuberculosis or Johne's disease is a contagious, chronic and sometimes fatal infection that primarily affects the small intestine of ruminants. It is caused by the bacterium Mycobacterium avium subspecies paratuberculosis...
, in cattle. The
mannoseMannose is a sugar monomer of the aldohexose series of carbohydrates. Mannose is a C-2 epimer of glucose. It is not part of human metabolism, but is a component of microbial cell walls, and is therefore a target of the immune system and also of antibiotics....
-bearing antigens (mannins) from yeast may also cause an
antibodyAn antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
response. Other studies have linked specific strains of enteroadherent
E. coli to the disease. Still, this relationship between specific types of bacteria and Crohn's disease remains unclear.
Mouse studies have suggested some symptoms of Crohn's disease, ulcerative colitis and
irritable bowel syndromeIrritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...
have the same underlying cause. Biopsy samples taken from the colons of all three patient groups were found to produce elevated levels of a serine protease. Experimental introduction of the serine protease into mice has been found to produce widespread pain associated with irritable bowel syndrome, as well as colitis, which is associated with all three diseases. Regional and temporal variations in those illnesses follow those associated with infection with the protozoan
BlastocystisBlastocystis is a genus of single-celled protozoan parasites belonging to a group of organisms known as the Stramenopiles that includes algae, diatoms, and water molds...
.
The "cold-chain" hypothesis is that
psychrotrophic bacteriaPsychrotrophic bacteria are bacteria that are capable of surviving or even thriving in a cold environment. They can be found in soils, in surface and deep sea waters, in Antarctic ecosystems, and in foods....
such as
Yersinia and
Listeria species contribute to the disease. A statistical correlation was found between the advent of the use of refrigeration in the United States and various parts of Europe and the rise of the disease.
There is an apparent connection between Crohn's disease,
Mycobacterium, other pathogenic bacteria, and genetic markers. In many individuals, genetic factors predispose individuals to
Mycobacterium avium subsp.
paratuberculosis infection. This bacterium then produces mannins, which protect both itself and various bacteria from phagocytosis, which causes a variety of secondary infections.
Pathophysiology
{{Pathophysiology in CD vs. UC}}
During a
colonoscopyColonoscopy is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It may provide a visual diagnosis and grants the opportunity for biopsy or removal of suspected...
,
biopsiesA biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
of the colon are often taken to confirm the diagnosis. Certain characteristic features of the
pathologyPathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
seen point toward Crohn's disease; it shows a transmural pattern of
inflammationInflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
, meaning the inflammation may span the entire depth of the intestinal wall.
UlcerationA peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...
is an outcome seen in highly active disease. There is usually an abrupt transition between unaffected tissue and the ulcer. Under a microscope, biopsies of the affected colon may show mucosal inflammation, characterized by focal infiltration of neutrophils, a type of inflammatory cell, into the
epitheliumEpithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
. This typically occurs in the area overlying lymphoid aggregates. These neutrophils, along with
mononuclear cellsA lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
, may infiltrate the
cryptsIn histology, an intestinal crypt is a gland found in the epithelial lining of the small intestine and colon...
, leading to inflammation (crypititis) or abscess (crypt abscess).
GranulomaGranuloma is a medical term for a tiny collection of immune cells known as macrophages. Granulomas form when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate. Such substances include infectious organisms such as bacteria and fungi as well as...
s, aggregates of
macrophageMacrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
derivatives known as giant cells, are found in 50% of cases and are most specific for Crohn's disease. The granulomas of Crohn's disease do not show "caseation", a cheese-like appearance on microscopic examination characteristic of granulomas associated with infections, such as
tuberculosisTuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
. Biopsies may also show chronic mucosal damage, as evidenced by blunting of the intestinal villi, atypical branching of the crypts, and a change in the tissue type (
metaplasiaMetaplasia is the reversible replacement of one differentiated cell type with another mature differentiated cell type. The change from one type of cell to another may generally be a part of normal maturation process or caused by some sort of abnormal stimulus...
). One example of such metaplasia,
Paneth cell metaplasia, involves development of Paneth cells (typically found in the small intestine) in other parts of the gastrointestinal system.
{{-}}
Diagnosis
The diagnosis of Crohn's disease can sometimes be challenging, and a number of tests are often required to assist the physician in making the diagnosis. Even with a full battery of tests, it may not be possible to diagnose Crohn's with complete certainty; a colonoscopy is approximately 70% effective in diagnosing the disease, with further tests being less effective. Disease in the small bowel is particularly difficult to diagnose, as a traditional colonoscopy allows access to only the colon and lower portions of the small intestines; introduction of the
capsule endoscopyCapsule endoscopy is a way to record images of the digestive tract for use in medicine. The capsule is the size and shape of a pill and contains a tiny camera. After a patient swallows the capsule, it takes pictures of the inside of the gastrointestinal tract...
aids in endoscopic diagnosis. Multinucleated giant cells, a common finding in the lesions of Crohn's disease, are less common in the lesions of lichen nitidus.
Endoscopy
A
colonoscopyColonoscopy is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It may provide a visual diagnosis and grants the opportunity for biopsy or removal of suspected...
is the best test for making the diagnosis of Crohn's disease, as it allows direct visualization of the colon and the
terminal ileumThe terminal ileum is the most distal part of the small intestine. It connects to the cecum, the pouch between the small and the large intestine, via the ileocecal valve.-Pathology of the terminal ileum:...
, identifying the pattern of disease involvement. On occasion, the colonoscope can travel past the terminal ileum, but it varies from patient to patient. During the procedure, the gastroenterologist can also perform a
biopsyA biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
, taking small samples of tissue for laboratory analysis, which may help confirm a diagnosis. As 30% of Crohn's disease involves only the ileum,
cannulaA cannula or canula is a tube that can be inserted into the body, often for the delivery or removal of fluid or for the gathering of data...
tion of the terminal ileum is required in making the diagnosis. Finding a patchy distribution of disease, with involvement of the colon or ileum, but not the
rectumThe rectum is the final straight portion of the large intestine in some mammals, and the gut in others, terminating in the anus. The human rectum is about 12 cm long...
, is suggestive of Crohn's disease, as are other endoscopic stigmata.
The utility of capsule endoscopy for this, however, is still uncertain.
A "
cobblestoneCobblestones are stones that were frequently used in the pavement of early streets. "Cobblestone" is derived from the very old English word "cob", which had a wide range of meanings, one of which was "rounded lump" with overtones of large size...
"-like appearance is seen in approximately 40% of cases of Crohn's disease upon colonoscopy, representing areas of ulceration separated by narrow areas of healthy tissue.
Radiologic tests
A
small bowel follow-throughA barium follow-through procedure is a type of medical imaging technique. It is used to evaluate the presence of disease in a person's small intestine.-Examination:...
may suggest the diagnosis of Crohn's disease and is useful when the disease involves only the small intestine. Because colonoscopy and
gastroscopyFor other expansions of the initialism "OGD", see the disambiguation page.In medicine , esophagogastroduodenoscopy is a diagnostic endoscopic procedure that visualizes the upper part of the gastrointestinal tract up to the duodenum...
allow direct visualization of only the terminal ileum and beginning of the
duodenumThe duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...
, they cannot be used to evaluate the remainder of the small intestine. As a result, a
barium follow-throughA barium follow-through procedure is a type of medical imaging technique. It is used to evaluate the presence of disease in a person's small intestine.-Examination:...
X-ray, wherein
barium sulfateBarium sulfate is the inorganic compound with the chemical formula BaSO4. It is a white crystalline solid that is odorless and insoluble in water. It occurs as the mineral barite, which is the main commercial source of barium and materials prepared from it...
suspension is ingested and
fluoroscopicFluoroscopy is an imaging technique commonly used by physicians to obtain real-time moving images of the internal structures of a patient through the use of a fluoroscope. In its simplest form, a fluoroscope consists of an X-ray source and fluorescent screen between which a patient is placed...
images of the bowel are taken over time, is useful for looking for inflammation and narrowing of the small bowel. Barium enemas, in which barium is inserted into the rectum and fluoroscopy is used to image the bowel, are rarely used in the work-up of Crohn's disease due to the advent of colonoscopy. They remain useful for identifying anatomical abnormalities when strictures of the colon are too small for a colonoscope to pass through, or in the detection of colonic fistulae (in this case contrast should be performed with iodate substances).
CTX-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
and MRI scans are useful for evaluating the small bowel with
enteroclysisEnteroclysis is a fluoroscopic X-ray of the small intestine. Radiocontrast is infused through a tube inserted through the nose to the duodenum, and images are taken in real time as the contrast moves through aided by administration of methyl cellulose. Enteroclysis is also known by the confusing...
protocols.They are also useful for looking for intra-abdominal complications of Crohn's disease, such as abscesses, small bowel obstructions, or fistulae.
Magnetic resonance imagingMagnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(MRI) is another option for imaging the small bowel as well as looking for complications, though it is more expensive and less readily available
Nuclear scans
Multiphase
white blood cell scansThe indium white blood cell scan, also called "indium leukocyte imaging," "indium-111 scan," or simply "indium scan," is a nuclear medicine procedure in which white blood cells are removed from the patient, tagged with the radioisotope Indium-111, and then injected intravenously into the patient...
have been shown to be effective in detecting the locations of active Crohn's disease, particularly in hard to diagnose patients suffering with the early stages or a mild form of the disease with negative endoscopic and radiologic findings. The procedure, a type of
nuclear medicineIn nuclear medicine procedures, elemental radionuclides are combined with other elements to form chemical compounds, or else combined with existing pharmaceutical compounds, to form radiopharmaceuticals. These radiopharmaceuticals, once administered to the patient, can localize to specific organs...
, uses white blood cells removed from the patient; they are tagged with a radioisotope, and then injected intravenously into the patient, and later scanned at several intervals to detect any abnormal white blood cell accumulation, such as pooling in the intestinal tract. Studies have also suggested such scans are useful to monitor the disease and evaluate the effectiveness of therapy.
Blood tests
A
complete blood countA complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...
may reveal
anemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, which may be caused by blood loss, by
vitamin B
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel diseaseIn medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
that may affect any part of the
gastrointestinal tractThe human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
from
mouthThe mouth is the first portion of the alimentary canal that receives food andsaliva. The oral mucosa is the mucous membrane epithelium lining the inside of the mouth....
to
anusThe anus is an opening at the opposite end of an animal's digestive tract from the mouth. Its function is to control the expulsion of feces, unwanted semi-solid matter produced during digestion, which, depending on the type of animal, may be one or more of: matter which the animal cannot digest,...
, causing a wide variety of
symptomA symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s. It primarily causes
abdominal painAbdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
,
diarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
(which may be bloody if inflammation is at its worst),
vomitingVomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
(can be continuous), or
weight lossWeight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...
, but may also cause complications outside the gastrointestinal tract such as skin rashes,
arthritisArthritis is a form of joint disorder that involves inflammation of one or more joints....
,
inflammation of the eyeUveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....
, tiredness, and lack of concentration.
Crohn's disease is caused by interactions between environmental, immunological and bacterial factors in genetically susceptible individuals. This results in a chronic inflammatory disorder, in which the body's
immune systemAn immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
attacks the gastrointestinal tract possibly directed at a microbial antigens. There is a
geneticGenetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
association with Crohn's disease, primarily with variations of the
NOD2Nucleotide-binding oligomerization domain-containing protein 2 also known as caspase recruitment domain-containing protein 15 or inflammatory bowel disease protein 1 is a protein that in humans is encoded by the NOD2 gene located on chromosome 16. NOD2 plays an important role in the immune system...
gene and its protein, which senses bacterial cell walls. Siblings of affected individuals are at higher risk. Males and females are equally affected. Smokers are two times more likely to develop Crohn's disease than nonsmokers. Crohn's disease affects between 400,000 and 600,000 people in
North AmericaNorth America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...
.
PrevalenceIn epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
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
pharmaceuticalA pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
or
surgicalSurgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
cure for Crohn's disease.
Treatment optionsManagement of Crohn's disease involves first treating the acute symptoms of the disease, then maintaining remission. Treatment initially involves the use of medications to eliminate infections, generally antibiotics, and reduce inflammation, generally aminosalicylate anti-inflammatory drugs and...
are restricted to controlling symptoms, maintaining remission, and preventing
relapseRelapse, in relation to drug misuse, is resuming the use of a drug or a dependent substance after one or more periods of abstinence. The term is a landmark feature of both substance dependence and substance abuse, which are learned behaviors, and is maintained by neuronal adaptations that mediate...
.
The disease was named after American
gastroenterologistGastroenterology is the branch of medicine whereby the digestive system and its disorders are studied. The name is a combination of three Ancient Greek words gaster , enteron , and logos...
Burrill Bernard Crohn, who, in 1932, together with two colleagues, described a series of patients with inflammation of the
terminal ileumThe terminal ileum is the most distal part of the small intestine. It connects to the cecum, the pouch between the small and the large intestine, via the ileocecal valve.-Pathology of the terminal ileum:...
, the area most commonly affected by the illness. For this reason, the disease has also been called regional ileitis or regional enteritis. The condition, however, had previously been independently described in medical literature by others. The most notable case was in 1904 by Polish surgeon
Antoni LeśniowskiAntoni Leśniowski was a Polish surgeon, credited with publishing what may have been the earliest reports of the condition which later became known as Crohn’s disease....
for whom the condition is alternatively named Leśniowski-Crohn's disease in Polish literature.
Classification
Crohn's disease is one type of
inflammatory bowel diseaseIn medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
(IBD). It typically manifests in the gastrointestinal tract and can be categorized by the specific tract region affected. A disease of both the
ileumThe ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum.The ileum follows the duodenum...
(the last part of the
small intestineThe small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
, which connects to the
large intestineThe large intestine is the third-to-last part of the digestive system — — in vertebrate animals. Its function is to absorb water from the remaining indigestible food matter, and then to pass useless waste material from the body...
), and the large intestine, Ileocolic Crohn's accounts for fifty percent of cases. Crohn's ileitis, manifest in the ileum only, accounts for thirty percent of cases, while Crohn's colitis, of the large intestine, accounts for the remaining twenty percent of cases and may be particularly difficult to distinguish from
ulcerative colitisUlcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...
. 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 (MedlinePlus 2010). The disease can attack any part of the digestive tract, from mouth to anus. However, individuals affected by the disease rarely fall outside these three classifications, with presentations in other areas.
Crohn's disease may also be categorized by the behavior of disease as it progresses. These categorizations formalized in the Vienna classification of the disease. There are three categories of disease presentation in Crohn's disease: stricturing, penetrating, and
inflammatoryInflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
. Stricturing disease causes narrowing of the bowel that may lead to
bowel obstructionBowel obstruction is a mechanical or functional obstruction of the intestines, preventing the normal transit of the products of digestion. It can occur at any level distal to the duodenum of the small intestine and is a medical emergency...
or changes in the caliber of the
fecesFeces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...
. Penetrating disease creates abnormal passageways (
fistulaIn medicine, a fistula is an abnormal connection or passageway between two epithelium-lined organs or vessels that normally do not connect. It is generally a disease condition, but a fistula may be surgically created for therapeutic reasons.-Locations:Fistulas can develop in various parts of the...
e) between the bowel and other structures, such as the skin. Inflammatory disease (or nonstricturing, nonpenetrating disease) causes inflammation without causing strictures or fistulae.
Gastrointestinal
Many people with Crohn's disease have symptoms for years prior to the diagnosis. The usual onset is between 15 and 30 years of age, but can occur at any age. Because of the 'patchy' nature of the gastrointestinal disease and the depth of tissue involvement, initial symptoms can be more subtle than those of ulcerative colitis. People with Crohn's disease experience chronic recurring periods of flare-ups and remission.
Abdominal pain may be the initial symptom of Crohn's disease. It is often accompanied by diarrhea, especially in those who have had surgery. The diarrhea may or may not be bloody. People who have had surgery or multiple surgeries often end up with
short bowel syndromeShort bowel syndrome is a malabsorption disorder caused by the surgical removal of the small intestine, or rarely due to the complete dysfunction of a large segment of bowel. Most cases are acquired, although some children are born with a congenital short bowel...
of the gastrointestinal tract. The nature of the diarrhea in Crohn's disease depends on the part of the small intestine or colon involved. Ileitis typically results in large-volume, watery feces. Colitis may result in a smaller volume of feces of higher frequency. Fecal consistency may range from solid to watery. In severe cases, an individual may have more than 20 bowel movements per day and may need to awaken at night to defecate. Visible bleeding in the feces is less common in Crohn's disease than in ulcerative colitis, but may be seen in the setting of Crohn's colitis. Bloody bowel movements are typically intermittent, and may be bright or dark red in color. In the setting of severe Crohn's colitis, bleeding may be copious.
FlatulenceFlatulence is the expulsion through the rectum of a mixture of gases that are byproducts of the digestion process of mammals and other animals. The medical term for the mixture of gases is flatus, informally known as a fart, or simply gas...
and bloating may also add to the intestinal discomfort.
Symptoms caused by
intestinal stenosisBowel obstruction is a mechanical or functional obstruction of the intestines, preventing the normal transit of the products of digestion. It can occur at any level distal to the duodenum of the small intestine and is a medical emergency...
are also common in Crohn's disease. Abdominal pain is often most severe in areas of the bowel with stenoses. In the setting of severe stenosis, vomiting and nausea may indicate the beginnings of small bowel obstruction. Although the association is greater in the context of
ulcerative colitisUlcerative colitis is a form of inflammatory bowel disease . Ulcerative colitis is a form of colitis, a disease of the colon , that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset...
, Crohn's disease may also be associated with
primary sclerosing cholangitisPrimary sclerosing cholangitis is a chronic liver disease caused by progressive inflammation and scarring of the bile ducts of the liver. The inflammation impedes the flow of bile to the gut, which can ultimately lead to liver cirrhosis, liver failure and liver cancer...
, a type of inflammation of the bile ducts.
Perianal discomfort may also be prominent in Crohn's disease. Itchiness or pain around the
anusThe anus is an opening at the opposite end of an animal's digestive tract from the mouth. Its function is to control the expulsion of feces, unwanted semi-solid matter produced during digestion, which, depending on the type of animal, may be one or more of: matter which the animal cannot digest,...
may be suggestive of inflammation,
fistulizationIn medicine, a fistula is an abnormal connection or passageway between two epithelium-lined organs or vessels that normally do not connect. It is generally a disease condition, but a fistula may be surgically created for therapeutic reasons.-Locations:Fistulas can develop in various parts of the...
or
abscessAn abscess is a collection of pus that has accumulated in a cavity formed by the tissue in which the pus resides due to an infectious process or other foreign materials...
around the anal area or
anal fissureAn anal fissure is a break or tear in the skin of the anal canal. Anal fissures may be noticed by bright red anal bleeding on the toilet paper, sometimes in the toilet. If acute they may cause severe periodic pain after defecation but with chronic fissures pain intensity is often less...
. Perianal skin
tagsAn acrochordon An acrochordon An acrochordon (plural acrochorda, and also known as a (cutaneous) skin tag, or fibroepithelial polyp, is a small benign tumour that forms primarily in areas where the skin forms creases, such as the neck, armpit, and groin. They may also occur on the face, usually on...
are also common in Crohn's disease.
Fecal incontinenceFecal incontinence is the loss of regular control of the bowels. Involuntary excretion and leaking are common occurrences for those affected. Subjects relating to defecation are often socially unacceptable, thus those affected may be beset by feelings of shame and humiliation...
may accompany perianal Crohn's disease. At the opposite end of the gastrointestinal tract, the mouth may be affected by non-healing sores (
aphthous ulcerAn aphthous ulcer , also known as a canker sore, is a type of mouth ulcer which presents as a painful open sore inside the mouth or upper throat characterized by a break in the mucous membrane. Its cause is unknown, but they are not contagious...
s). Rarely, the
esophagusThe esophagus is an organ in vertebrates which consists of a muscular tube through which food passes from the pharynx to the stomach. During swallowing, food passes from the mouth through the pharynx into the esophagus and travels via peristalsis to the stomach...
, and
stomachThe stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
may be involved in Crohn's disease. These can cause symptoms including difficulty swallowing (
dysphagiaDysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, the term is sometimes used as a condition in its own right. Sufferers are sometimes unaware of their dysphagia....
), upper abdominal pain, and vomiting.
Systemic
Crohn's disease, like many other chronic, inflammatory diseases, can cause a variety of
systemic symptomsB symptoms refer to systemic symptoms of fever, night sweats, and weight loss which can be associated with both Hodgkin's lymphoma and non-Hodgkin's lymphoma...
. Among children, growth failure is common. Many children are first diagnosed with Crohn's disease based on
inability to maintain growthFailure to thrive is a medical term which is used in both pediatric and adult human medicine, as well as veterinary medicine ....
. As it may manifest at the time of the growth spurt in
pubertyPuberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
, up to 30% of children with Crohn's disease may have retardation of growth. Fever may also be present, though fevers greater than 38.5 ˚C (101.3 ˚F) are uncommon unless there is a complication such as an
abscessAn abscess is a collection of pus that has accumulated in a cavity formed by the tissue in which the pus resides due to an infectious process or other foreign materials...
. Among older individuals, Crohn's disease may manifest as weight loss, usually related to decreased food intake, since individuals with intestinal symptoms from Crohn's disease often feel better when they do not eat and might lose their appetite. People with extensive
small intestineThe small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
disease may also have
malabsorptionMalabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...
of
carbohydrateA carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
s or
lipidLipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
s, which can further exacerbate weight loss.
Extraintestinal
In addition to systemic and gastrointestinal involvement, Crohn's disease can affect many other organ systems. Inflammation of the interior portion of the eye, known as
uveitisUveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....
, can cause eye pain, especially when exposed to light (
photophobiaPhotophobia is a symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of actual physical photosensitivity of the eyes, though the term...
). Inflammation may also involve the white part of the eye (
scleraThe sclera , also known as the white or white of the eye, is the opaque , fibrous, protective, outer layer of the eye containing collagen and elastic fiber. In the development of the embryo, the sclera is derived from the neural crest...
), a condition called
episcleritisScleritis is a serious inflammatory disease that affects the white outer coating of the eye, known as the sclera. The disease is often contracted through association with other diseases of the body, such as Wegener's granulomatosis or rheumatoid arthritis; it can also be attained through disorders...
. Both episcleritis and uveitis can lead to loss of vision if untreated.
Crohn's disease is associated with a type of
rheumatologic diseaseRheumatology is a sub-specialty in internal medicine and pediatrics, devoted to diagnosis and therapy of rheumatic diseases. Clinicians who specialize in rheumatology are called rheumatologists...
known as
seronegative spondyloarthropathySpondyloarthropathy is any joint disease of the vertebral column. Spondyloarthropathy with inflammation is called spondylarthritis. In contrast, spondylopathy is a disease of the vertebra itself, but many conditions involve both spondylopathy and spondyloarthropathy...
. This group of diseases is characterized by inflammation of one or more
jointA joint is the location at which two or more bones make contact. They are constructed to allow movement and provide mechanical support, and are classified structurally and functionally.-Classification:...
s (
arthritisArthritis is a form of joint disorder that involves inflammation of one or more joints....
) or muscle insertions (
enthesitisEnthesitis is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. It is also called enthesopathy, or any pathologic condition involving the entheses. The entheses are any point of attachment of skeletal muscles to the bone, where recurring stress or...
). The arthritis can affect larger joints, such as the knee or shoulder, or may exclusively involve the small joints of the hands and feet. The arthritis may also involve the spine, leading to
ankylosing spondylitisAnkylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...
if the entire spine is involved or simply
sacroiliitisIn medicine, sacroiliitis is an inflammation of the sacroiliac joint. Sacroiliitis is a feature of spondylarthropathies .-External links:*...
if only the lower spine is involved. The symptoms of arthritis include painful, warm, swollen, stiff
jointsArthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
and loss of joint mobility or function.
Crohn's disease may also involve the skin, blood, and
endocrine systemIn physiology, the endocrine system is a system of glands, each of which secretes a type of hormone directly into the bloodstream to regulate the body. The endocrine system is in contrast to the exocrine system, which secretes its chemicals using ducts. It derives from the Greek words "endo"...
. One type of skin manifestation,
erythema nodosumErythema nodosum is an inflammation of the fat cells under the skin characterized by tender red nodules or lumps that are usually seen on both shins...
, presents as red nodules usually appearing on the shins. Erythema nodosum is due to inflammation of the underlying subcutaneous tissue, and is characterized by septal
panniculitisPanniculitis is a group of diseases whose hallmark is inflammation of subcutaneous adipose tissue...
. Another skin lesion,
pyoderma gangrenosumPyoderma gangrenosum is a disease that causes tissue to become necrotic, causing deep ulcers that usually occur on the legs. When they occur, they can lead to chronic wounds. Ulcers usually initially look like small bug bites or papules, and they progress to larger ulcers. Though the wounds...
, is typically a painful ulcerating nodule. Crohn's disease also increases the risk of blood clots; painful swelling of the lower legs can be a sign of deep venous thrombosis, while difficulty breathing may be a result of
pulmonary embolismPulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
.
Autoimmune hemolytic anemiaAutoimmune hemolytic anemia occurs when antibodies directed against the person's own red blood cells cause the RBCs to burst , leading to insufficient plasma concentration. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases...
, a condition in which the immune system attacks the red blood cells, is also more common in Crohn's disease and may cause fatigue, pallor, and other symptoms common in
anemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
. Clubbing, a deformity of the ends of the fingers, may also be a result of Crohn's disease. Finally, Crohn's disease may cause
osteoporosisOsteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
, or thinning of the bones. Individuals with osteoporosis are at increased risk of
bone fractureA bone fracture is a medical condition in which there is a break in the continuity of the bone...
s.
Crohn's disease can also cause neurological complications (reportedly in up to 15% of patients). The most common of these are seizures,
strokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
,
myopathyIn medicine, a myopathy is a muscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness. "Myopathy" simply means muscle disease...
,
peripheral neuropathyPeripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of or trauma to the nerve or the side-effects of systemic illness....
,
headacheA headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
and
depressionDepression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
.
Crohn's patients often also have issues with
small bowel bacterial overgrowth syndromeSmall bowel bacterial overgrowth syndrome , or small intestinal bacterial overgrowth , also termed bacterial overgrowth; is a disorder of excessive bacterial growth in the small intestine. Unlike the colon , which is rich with bacteria, the small bowel usually has less than 104 organisms per...
, which has similar symptoms.
In the oral cavity crohn's patients may suffer from
cheilitis granulomatosaCheilitis granulomatosa is a condition characterized by a sudden onset and progressive course terminating in chronic enlargement of the lips....
and other forms of orofacial granulomatosis,
pyostomatitis vegetansPyostomatitis vegetans is an inflammatory stomatitis and most often seen in association with inflammatory bowel disease, namely ulcerative colitis and Crohn's disease.- See also :* Cheilitis* Cheilitis granulomatosa* Skin lesion...
, recurrent aphthous stomatitis,
geographic tongueGeographic tongue, an inflammatory condition of the tongue affecting approximately 2% of the population, is characterized by discolored regions of taste buds or sometimes even cracks in the tongue...
and
migratory stomatitisMigratory stomatitis is a benign condition on the oral soft tissue. This condition has two forms: the common form, which is consisted from red lesions with white borders on the tongue only. This form is called geographic tongue...
in higher prevalence than the general population.
Complications
{{Complications of CD vs. UC}}
Crohn's disease can lead to several mechanical complications within the intestines, including
obstructionBowel obstruction is a mechanical or functional obstruction of the intestines, preventing the normal transit of the products of digestion. It can occur at any level distal to the duodenum of the small intestine and is a medical emergency...
, fistulae, and abscesses. Obstruction typically occurs from strictures or adhesions that narrow the lumen, blocking the passage of the intestinal contents. Fistulae can develop between two loops of bowel, between the bowel and bladder, between the bowel and vagina, and between the bowel and skin. Abscesses are walled off collections of
infectionAn infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
, which can occur in the
abdomenIn vertebrates such as mammals the abdomen constitutes the part of the body between the thorax and pelvis. The region enclosed by the abdomen is termed the abdominal cavity...
or in the perianal area in Crohn's disease sufferers. Crohn's is responsible for 10% of vesicoenteric fistulae, and is the most common cause of ileovesical fistulae.
Crohn's disease also increases the risk of cancer in the area of inflammation. For example, individuals with Crohn's disease involving the small bowel are at higher risk for small intestinal cancer. Similarly, people with Crohn's colitis have a
relative riskIn statistics and mathematical epidemiology, relative risk is the risk of an event relative to exposure. Relative risk is a ratio of the probability of the event occurring in the exposed group versus a non-exposed group....
of 5.6 for developing colon cancer. Screening for colon cancer with
colonoscopyColonoscopy is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It may provide a visual diagnosis and grants the opportunity for biopsy or removal of suspected...
is recommended for anyone who has had Crohn's colitis for at least eight years. Some studies suggest there is a role for chemoprotection in the prevention of colorectal cancer in Crohn's involving the colon; two agents have been suggested, folate and mesalamine preparations.
Individuals with Crohn's disease are at risk of
malnutritionMalnutrition is the condition that results from taking an unbalanced diet in which certain nutrients are lacking, in excess , or in the wrong proportions....
for many reasons, including decreased food intake and
malabsorptionMalabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...
. The risk increases following resection of the small bowel. Such individuals may require oral supplements to increase their caloric intake, or in severe cases,
total parenteral nutritionParenteral nutrition is feeding a person intravenously, bypassing the usual process of eating and digestion. The person receives nutritional formulae that contain nutrients such as glucose, amino acids, lipids and added vitamins and dietary minerals...
(TPN). Most people with moderate or severe Crohn's disease are referred to a
dietitianDietitians supervise the preparation and service of food, develop modified diets, participate in research, and educate individuals and groups on good nutritional habits. The goals of dietitians are to provide medical nutritional intervention, and to obtain, safely prepare, serve and advise on...
for assistance in nutrition.
Crohn's disease can cause significant complications, including
bowel obstructionBowel obstruction is a mechanical or functional obstruction of the intestines, preventing the normal transit of the products of digestion. It can occur at any level distal to the duodenum of the small intestine and is a medical emergency...
, abscesses, free perforation and hemorrhage.
Crohn's disease can be problematic during
pregnancyPregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
, and some medications can cause adverse outcomes for the
fetusA fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
or mother. Consultation with an obstetrician and gastroenterologist about Crohn's disease and all medications allows preventative measures to be taken. In some cases, remission can occur during pregnancy. Certain medications can also impact sperm count or may otherwise adversely affect a man's ability to
conceiveFertilisation is the fusion of gametes to produce a new organism. In animals, the process involves the fusion of an ovum with a sperm, which eventually leads to the development of an embryo...
.
Cause
{{Risk factors in CD vs. UC}}
Crohn's disease seems to be caused by a combination of environmental factors and genetic predisposition. Crohn's is the first genetically complex disease in which the relationship between genetic risk factors and the immune system is understood in considerable detail. Each individual risk mutation makes a small contribution to the overall risk of Crohn's (approximately 1:200). The genetic data, and direct assessment of patient immunity, indicates a malfunction in the innate immune system. In this view, the chronic inflammation of Crohn's is caused when the adaptive immune system tries to compensate for a deficient innate immune system.
Genetics
Crohn's has a genetic component. The disease runs in families and siblings are 30 times more likely to develop Crohn's than the general population.
The first mutation found to be associated with Crohn's was a frameshift in the
NOD2Nucleotide-binding oligomerization domain-containing protein 2 also known as caspase recruitment domain-containing protein 15 or inflammatory bowel disease protein 1 is a protein that in humans is encoded by the NOD2 gene located on chromosome 16. NOD2 plays an important role in the immune system...
gene (also known as the CARD15 gene), followed by the discovery of point mutations. By now, over thirty genes have been associated. A biological function is known for most of them. For example, one association is with mutations in the
XBP1X-box binding protein 1, also known as XBP1, is a protein which in humans is encoded by the XBP1 gene. The XBP1 gene is located on chromosome 22 while a closely related pseudogene has been identified and localized to chromosome 5...
gene, which is involved in the
unfolded protein responseThe unfolded protein response is a cellular stress response related to the endoplasmic reticulum. It is a stress response that has been found to be conserved between all mammalian species, as well as yeast and worm organisms...
pathway of the endoplasmatic reticulum.
Environmental factors
The increased incidence of Crohn's in the industrialized world indicates an environmental component. Crohn's is associated with an increased intake of animal
proteinProteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
, milk protein and an increased ratio of
omega-6n−6 fatty acids are a family of unsaturated fatty acids that have in common a final carbon–carbon double bond in the n−6 position, that is, the sixth bond, counting from the methyl end.The biological effects of the n−6 fatty acids are largely mediated by their conversion to n-6 eicosanoids...
to
omega-3N−3 fatty acids are essential unsaturated fatty acids with a double bond starting after the third carbon atom from the end of the carbon chain....
polyunsaturated fatty acidsIn nutrition, polyunsaturated fat, or polyunsaturated fatty acid, are fatty acids in which more than one carbon–carbon double bond exists within the representative molecule. That is, the molecule has two or more points on its structure capable of supporting hydrogen atoms not currently part of the...
.
Crohn's is negatively associated with consumption of vegetable protein. Consumption of fish protein has no association.
SmokingTobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
increases the risk of the return of active disease (flares). The introduction of
hormonal contraceptionHormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive...
in the United States in the 1960s is associated with a dramatic increase in incidence, and one hypothesis is that these drugs work on the digestive system in ways similar to smoking.
IsotretinoinIsotretinoin, INN, is a medication used mostly for cystic acne. It was first developed for brain, pancreatic and other cancers. It is used to treat harlequin-type ichthyosis, a usually lethal skin disease, and lamellar ichthyosis. Its effects are systemic and nonselective...
is associated with Crohn's. Emotional stress is likely to exacerbate Crohn's.
Immune system
The prevailing view was that Crohn's disease is a primary T cell autoimmune disorder. A newer view is that Crohn's results from an impaired innate immunity.
In the newer view, impaired cytokine secretion by macrophages contributes to impaired innate immunity, and leads to a sustained microbial-induced inflammatory response in the colon, where the bacterial load is high.
One theory was that the inflammation of Crohn's was caused by an overactive T
h1
cytokineCytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
response. More recent studies argue that T
h17 is more important.
The most recent gene to be implicated in Crohn's disease is
ATG16L1Autophagy-related protein 16-1 is a protein that in humans is encoded by the ATG16L1 gene.-Function:Autophagy is the major intracellular degradation system delivering cytoplasmic components to lysosomes, and it accounts for degradation of most long-lived proteins and some organelles...
, which may induce autophagy and hinder the body's ability to attack invasive bacteria.
Microbes
Crohn's is not caused by infection by particular pathogenic bacteria. Current thinking is that microorganisms are taking advantage of their host's weakened mucosal layer and inability to clear bacteria from the intestinal walls, which are both symptoms of Crohn's. Some studies have suggested a role for
Mycobacterium avium subspecies paratuberculosisMycobacterium avium subspecies paratuberculosis is an obligate pathogenic bacterium in the genus Mycobacterium. It is often abbreviated M. paratuberculosis or M. avium ssp. paratuberculosis. It is the causative agent of Johne's disease, which affects ruminants such as cattle, and also perhaps...
(MAP), which causes a similar disease,
Johne's diseaseParatuberculosis or Johne's disease is a contagious, chronic and sometimes fatal infection that primarily affects the small intestine of ruminants. It is caused by the bacterium Mycobacterium avium subspecies paratuberculosis...
, in cattle. The
mannoseMannose is a sugar monomer of the aldohexose series of carbohydrates. Mannose is a C-2 epimer of glucose. It is not part of human metabolism, but is a component of microbial cell walls, and is therefore a target of the immune system and also of antibiotics....
-bearing antigens (mannins) from yeast may also cause an
antibodyAn antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
response. Other studies have linked specific strains of enteroadherent
E. coli to the disease. Still, this relationship between specific types of bacteria and Crohn's disease remains unclear.
Mouse studies have suggested some symptoms of Crohn's disease, ulcerative colitis and
irritable bowel syndromeIrritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...
have the same underlying cause. Biopsy samples taken from the colons of all three patient groups were found to produce elevated levels of a serine protease. Experimental introduction of the serine protease into mice has been found to produce widespread pain associated with irritable bowel syndrome, as well as colitis, which is associated with all three diseases. Regional and temporal variations in those illnesses follow those associated with infection with the protozoan
BlastocystisBlastocystis is a genus of single-celled protozoan parasites belonging to a group of organisms known as the Stramenopiles that includes algae, diatoms, and water molds...
.
The "cold-chain" hypothesis is that
psychrotrophic bacteriaPsychrotrophic bacteria are bacteria that are capable of surviving or even thriving in a cold environment. They can be found in soils, in surface and deep sea waters, in Antarctic ecosystems, and in foods....
such as
Yersinia and
Listeria species contribute to the disease. A statistical correlation was found between the advent of the use of refrigeration in the United States and various parts of Europe and the rise of the disease.
There is an apparent connection between Crohn's disease,
Mycobacterium, other pathogenic bacteria, and genetic markers. In many individuals, genetic factors predispose individuals to
Mycobacterium avium subsp.
paratuberculosis infection. This bacterium then produces mannins, which protect both itself and various bacteria from phagocytosis, which causes a variety of secondary infections.
Pathophysiology
{{Pathophysiology in CD vs. UC}}
During a
colonoscopyColonoscopy is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It may provide a visual diagnosis and grants the opportunity for biopsy or removal of suspected...
,
biopsiesA biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
of the colon are often taken to confirm the diagnosis. Certain characteristic features of the
pathologyPathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
seen point toward Crohn's disease; it shows a transmural pattern of
inflammationInflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
, meaning the inflammation may span the entire depth of the intestinal wall.
UlcerationA peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...
is an outcome seen in highly active disease. There is usually an abrupt transition between unaffected tissue and the ulcer. Under a microscope, biopsies of the affected colon may show mucosal inflammation, characterized by focal infiltration of neutrophils, a type of inflammatory cell, into the
epitheliumEpithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
. This typically occurs in the area overlying lymphoid aggregates. These neutrophils, along with
mononuclear cellsA lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
, may infiltrate the
cryptsIn histology, an intestinal crypt is a gland found in the epithelial lining of the small intestine and colon...
, leading to inflammation (crypititis) or abscess (crypt abscess).
GranulomaGranuloma is a medical term for a tiny collection of immune cells known as macrophages. Granulomas form when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate. Such substances include infectious organisms such as bacteria and fungi as well as...
s, aggregates of
macrophageMacrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
derivatives known as giant cells, are found in 50% of cases and are most specific for Crohn's disease. The granulomas of Crohn's disease do not show "caseation", a cheese-like appearance on microscopic examination characteristic of granulomas associated with infections, such as
tuberculosisTuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
. Biopsies may also show chronic mucosal damage, as evidenced by blunting of the intestinal villi, atypical branching of the crypts, and a change in the tissue type (
metaplasiaMetaplasia is the reversible replacement of one differentiated cell type with another mature differentiated cell type. The change from one type of cell to another may generally be a part of normal maturation process or caused by some sort of abnormal stimulus...
). One example of such metaplasia,
Paneth cell metaplasia, involves development of Paneth cells (typically found in the small intestine) in other parts of the gastrointestinal system.
{{-}}
Diagnosis
The diagnosis of Crohn's disease can sometimes be challenging, and a number of tests are often required to assist the physician in making the diagnosis. Even with a full battery of tests, it may not be possible to diagnose Crohn's with complete certainty; a colonoscopy is approximately 70% effective in diagnosing the disease, with further tests being less effective. Disease in the small bowel is particularly difficult to diagnose, as a traditional colonoscopy allows access to only the colon and lower portions of the small intestines; introduction of the
capsule endoscopyCapsule endoscopy is a way to record images of the digestive tract for use in medicine. The capsule is the size and shape of a pill and contains a tiny camera. After a patient swallows the capsule, it takes pictures of the inside of the gastrointestinal tract...
aids in endoscopic diagnosis. Multinucleated giant cells, a common finding in the lesions of Crohn's disease, are less common in the lesions of lichen nitidus.
Endoscopy
A
colonoscopyColonoscopy is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It may provide a visual diagnosis and grants the opportunity for biopsy or removal of suspected...
is the best test for making the diagnosis of Crohn's disease, as it allows direct visualization of the colon and the
terminal ileumThe terminal ileum is the most distal part of the small intestine. It connects to the cecum, the pouch between the small and the large intestine, via the ileocecal valve.-Pathology of the terminal ileum:...
, identifying the pattern of disease involvement. On occasion, the colonoscope can travel past the terminal ileum, but it varies from patient to patient. During the procedure, the gastroenterologist can also perform a
biopsyA biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
, taking small samples of tissue for laboratory analysis, which may help confirm a diagnosis. As 30% of Crohn's disease involves only the ileum,
cannulaA cannula or canula is a tube that can be inserted into the body, often for the delivery or removal of fluid or for the gathering of data...
tion of the terminal ileum is required in making the diagnosis. Finding a patchy distribution of disease, with involvement of the colon or ileum, but not the
rectumThe rectum is the final straight portion of the large intestine in some mammals, and the gut in others, terminating in the anus. The human rectum is about 12 cm long...
, is suggestive of Crohn's disease, as are other endoscopic stigmata.
The utility of capsule endoscopy for this, however, is still uncertain.
A "
cobblestoneCobblestones are stones that were frequently used in the pavement of early streets. "Cobblestone" is derived from the very old English word "cob", which had a wide range of meanings, one of which was "rounded lump" with overtones of large size...
"-like appearance is seen in approximately 40% of cases of Crohn's disease upon colonoscopy, representing areas of ulceration separated by narrow areas of healthy tissue.
Radiologic tests
A
small bowel follow-throughA barium follow-through procedure is a type of medical imaging technique. It is used to evaluate the presence of disease in a person's small intestine.-Examination:...
may suggest the diagnosis of Crohn's disease and is useful when the disease involves only the small intestine. Because colonoscopy and
gastroscopyFor other expansions of the initialism "OGD", see the disambiguation page.In medicine , esophagogastroduodenoscopy is a diagnostic endoscopic procedure that visualizes the upper part of the gastrointestinal tract up to the duodenum...
allow direct visualization of only the terminal ileum and beginning of the
duodenumThe duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...
, they cannot be used to evaluate the remainder of the small intestine. As a result, a
barium follow-throughA barium follow-through procedure is a type of medical imaging technique. It is used to evaluate the presence of disease in a person's small intestine.-Examination:...
X-ray, wherein
barium sulfateBarium sulfate is the inorganic compound with the chemical formula BaSO4. It is a white crystalline solid that is odorless and insoluble in water. It occurs as the mineral barite, which is the main commercial source of barium and materials prepared from it...
suspension is ingested and
fluoroscopicFluoroscopy is an imaging technique commonly used by physicians to obtain real-time moving images of the internal structures of a patient through the use of a fluoroscope. In its simplest form, a fluoroscope consists of an X-ray source and fluorescent screen between which a patient is placed...
images of the bowel are taken over time, is useful for looking for inflammation and narrowing of the small bowel. Barium enemas, in which barium is inserted into the rectum and fluoroscopy is used to image the bowel, are rarely used in the work-up of Crohn's disease due to the advent of colonoscopy. They remain useful for identifying anatomical abnormalities when strictures of the colon are too small for a colonoscope to pass through, or in the detection of colonic fistulae (in this case contrast should be performed with iodate substances).
CTX-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
and MRI scans are useful for evaluating the small bowel with
enteroclysisEnteroclysis is a fluoroscopic X-ray of the small intestine. Radiocontrast is infused through a tube inserted through the nose to the duodenum, and images are taken in real time as the contrast moves through aided by administration of methyl cellulose. Enteroclysis is also known by the confusing...
protocols.They are also useful for looking for intra-abdominal complications of Crohn's disease, such as abscesses, small bowel obstructions, or fistulae.
Magnetic resonance imagingMagnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(MRI) is another option for imaging the small bowel as well as looking for complications, though it is more expensive and less readily available
Nuclear scans
Multiphase
white blood cell scansThe indium white blood cell scan, also called "indium leukocyte imaging," "indium-111 scan," or simply "indium scan," is a nuclear medicine procedure in which white blood cells are removed from the patient, tagged with the radioisotope Indium-111, and then injected intravenously into the patient...
have been shown to be effective in detecting the locations of active Crohn's disease, particularly in hard to diagnose patients suffering with the early stages or a mild form of the disease with negative endoscopic and radiologic findings. The procedure, a type of
nuclear medicineIn nuclear medicine procedures, elemental radionuclides are combined with other elements to form chemical compounds, or else combined with existing pharmaceutical compounds, to form radiopharmaceuticals. These radiopharmaceuticals, once administered to the patient, can localize to specific organs...
, uses white blood cells removed from the patient; they are tagged with a radioisotope, and then injected intravenously into the patient, and later scanned at several intervals to detect any abnormal white blood cell accumulation, such as pooling in the intestinal tract. Studies have also suggested such scans are useful to monitor the disease and evaluate the effectiveness of therapy.
Blood tests
A
complete blood countA complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...
may reveal
anemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, which may be caused by blood loss, by
vitamin B{{ssubCyanocobalamin is an especially common vitamer of the vitamin B12 family. It is the most famous vitamer of the family, because it is, in chemical terms, the most air-stable...
deficiency or, possibly,
autoimmune hemolysisAutoimmune hemolytic anemia occurs when antibodies directed against the person's own red blood cells cause the RBCs to burst , leading to insufficient plasma concentration. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases...
. The latter may be seen with ileitis because vitamin B{{ssub|12}} is absorbed in the
ileumThe ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum.The ileum follows the duodenum...
.
Erythrocyte sedimentation rateThe erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...
, or ESR, and
C-reactive proteinC-reactive protein is a protein found in the blood, the levels of which rise in response to inflammation...
measurements can also be useful to gauge the degree of inflammation. It is also true in patients with an ilectomy done in response to the complication. Another cause of anemia is anemia of chronic disease, characterized by its microcytic and hypochromic anemia. There can be various reasons for it, including medication used in treatment of inflammatory bowel disease, like azathioprine, which can lead to cytopenia, and sulfasalazine, which can also result in folate malabsorption, etc. Testing for
Saccharomyces cerevisiaeSaccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...
antibodies (ASCA) and
antineutrophil cytoplasmic antibodiesAnti-neutrophil cytoplasmic antibodies are a group of autoantibodies, mainly of the IgG type, against antigens in the cytoplasm of neutrophil granulocytes and monocytes...
(ANCA) has been evaluated to identify inflammatory diseases of the intestine and to differentiate Crohn's disease from ulcerative colitis. Furthermore, increasing amounts and levels of serological antibodies such as ASCA, antilaminaribioside [Glc(β1,3)Glb(β); ALCA], antichitobioside (GlcNAc(β1,4)GlcNAc(β); ACCA], antimannobioside [Man(α1,3)Man(α)AMCA], antiLaminarin [Glc(β1,3))3n(Glc(β1,6))n; anti-L] and antichitin [(GlcNAc(β1,4)n; anti-C] associate with disease behavior and surgery, and may aid in the prognosis of Crohn's disease.
Comparison with ulcerative colitis
The most common disease that mimics the symptoms of Crohn's disease is ulcerative colitis, as both are inflammatory bowel diseases that can affect the
colonThe colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
with similar symptoms. It is important to differentiate these diseases, since the course of the diseases and treatments may be different. In some cases, however, it may not be possible to tell the difference, in which case the disease is classified as indeterminate colitis.
{{Findings in CD vs. UC}}
Management
{{Main|Management of Crohn's disease}}
{{Treatment in CD vs. UC}}
At the present time, there is no cure for Crohn's disease and remission may not be possible or prolonged if achieved. In cases where remission is possible,
relapseRelapse, in relation to drug misuse, is resuming the use of a drug or a dependent substance after one or more periods of abstinence. The term is a landmark feature of both substance dependence and substance abuse, which are learned behaviors, and is maintained by neuronal adaptations that mediate...
can be prevented and
symptomA symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s controlled with medication, lifestyle changes, and, in some cases, surgery. Adequately controlled, Crohn's disease may not significantly restrict daily living. Treatment for Crohn's disease is only when symptoms are active and involve first treating the acute problem, then maintaining remission.
Lifestyle changes
Certain lifestyle changes can reduce symptoms, including
dietaryIn nutrition, diet is the sum of food consumed by a person or other organism. Dietary habits are the habitual decisions an individual or culture makes when choosing what foods to eat. With the word diet, it is often implied the use of specific intake of nutrition for health or weight-management...
adjustments
Elemental dietAn elemental diet is a diet that proposes the ingestion or in more severe cases, use of a gastric feeding tube or intravenous feeding of liquid nutrients in an easily assimilated form. It is usually composed of amino acids, fats, sugars, vitamins, and minerals...
, proper
hydrationDrinking water or potable water is water pure enough to be consumed or used with low risk of immediate or long term harm. In most developed countries, the water supplied to households, commerce and industry is all of drinking water standard, even though only a very small proportion is actually...
, and
smoking cessationSmoking cessation is the process of discontinuing the practice of inhaling a smoked substance. This article focuses exclusively on cessation of tobacco smoking; however, the methods described may apply to cessation of smoking other substances that can be difficult to stop using due to the...
. Smoking may increase Crohn's disease; stopping is recommended. Eating small meals frequently instead of big meals may also help with a low appetite. To manage symptoms have a balanced diet with proper portion control. Fatigue can be helped with regular exercise, a healthy diet, and enough sleep. A food diary may help with identifying foods that trigger symptoms. Some patients should follow a low
dietary fiberDietary fiber, dietary fibre, or sometimes roughage is the indigestible portion of plant foods having two main components:* soluble fiber that is readily fermented in the colon into gases and physiologically active byproducts, and* insoluble fiber that is metabolically inert, absorbing water as it...
diet to control symptoms especially if fibrous foods cause symptoms. Patients should avoid milk or dairy products as they have been shown in recent research (2007) to contribute to or even cause Crohn's disease.
Medication
Acute treatment uses medications to treat any infection (normally
antibioticAn antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s) and to reduce inflammation (normally
aminosalicylate4-aminosalicylic acid, commonly known as PAS, is an antibiotic used to treat tuberculosis. This organic compound has been use since the 1940s for the treatment of inflammatory bowel diseases , where it has shown greater potency in ulcerative colitis and Crohn's disease. It is thought to act via...
anti-inflammatory drugs and
corticosteroidCorticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s). When symptoms are in remission, treatment enters maintenance, with a goal of avoiding the recurrence of symptoms. Prolonged use of corticosteroids has significant
side-effectsIn medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
; as a result, they are, in general, not used for long-term treatment. Alternatives include aminosalicylates alone, though only a minority are able to maintain the treatment, and many require immunosuppressive drugs. It has been also suggested that antibiotics change the enteric flora, and their continuous use may pose the risk of overgrowth with pathogens such as
Clostridium difficileClostridium difficile , also known as "CDF/cdf", or "C...
.
Medications used to treat the symptoms of Crohn's disease include
5-aminosalicylic acidMesalazine , also known as Mesalamine or 5-aminosalicylic acid , is an anti-inflammatory drug used to treat inflammation of the digestive tract ulcerative colitis and mild-to-moderate Crohn's disease...
(5-ASA) formulations,
prednisonePrednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...
, immunomodulators such as
azathioprineAzathioprine is a purine analogue immunosuppressive drug. It is used to prevent organ rejection following organ transplantation and to treat a vast array of autoimmune diseases, including rheumatoid arthritis, pemphigus, inflammatory bowel disease , multiple sclerosis, autoimmune hepatitis, atopic...
,
mercaptopurineMercaptopurine is an immunosuppressive drug.It is a thiopurine.-Uses:...
,
methotrexateMethotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
,
infliximabInfliximab is a monoclonal antibody against tumour necrosis factor alpha . It is used to treat autoimmune diseases. Remicade is marketed by Janssen Biotech, Inc...
,
adalimumabAdalimumab is the third TNF inhibitor, after infliximab and etanercept, to be approved in the United States. Like infliximab and etanercept, adalimumab binds to TNFα, preventing it from activating TNF receptors; adalimumab was constructed from a fully human monoclonal antibody, while infliximab...
, certolizumab and
natalizumabNatalizumab is a humanized monoclonal antibody against the cellular adhesion molecule α4-integrin. Natalizumab is used in the treatment of multiple sclerosis and Crohn's disease. It is co-marketed by Biogen Idec and Élan as Tysabri, and was previously named Antegren. Natalizumab is administered by...
. Hydrocortisone should be used in severe attacks of Crohn's disease.
Surgery
Crohn's cannot be cured by
surgerySurgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
, though it is used when partial or a full blockage of the intestine occurs. Surgery may also be required for complications such as obstructions, fistulas and/or abscesses, or if the disease does not respond to drugs. After the first surgery, Crohn's usually shows up at the site of the resection, however it can appear in other locations. After a resection, scar tissue builds up, which can cause
stricturesA stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure.It is also sometimes called a stricture ....
, which form when the intestines become too small to allow excrement to pass through easily, which can lead to a blockage. After the first resection, another resection may be necessary within five years. For patients with an obstruction due to a stricture, two options for treatment are
strictureplastyStrictureplasty is a surgical procedure performed in response to scar tissue that has built up in the intestinal wall from inflammatory bowel conditions such as Crohn's disease. The scar tissue accumulates as a result of repeated damage and healing, with the scarring causing a stricture...
and resection of that portion of bowel. There is no
statistical significanceIn statistics, a result is called statistically significant if it is unlikely to have occurred by chance. The phrase test of significance was coined by Ronald Fisher....
between strictureplasty alone versus strictureplasty and resection in cases of
duodenalThe duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...
involvement. In these cases, re-operation rates were 31% and 27%, respectively, indicating that strictureplasty is a safe and effective treatment for selected patients with duodenal involvement.
Short bowel syndromeShort bowel syndrome is a malabsorption disorder caused by the surgical removal of the small intestine, or rarely due to the complete dysfunction of a large segment of bowel. Most cases are acquired, although some children are born with a congenital short bowel...
(SBS, also short gut syndrome or simply short gut) can be caused by the surgical removal of the small intestines. It usually develops in those having had half or more of their small intestines removed. Diarrhea is the main symptom of short bowel syndrome, however other symptoms may include cramping, bloating, and heartburn. Short bowel syndrome is treated with changes in diet, intravenous feeding, vitamin and mineral supplements, and treatment with medications. Another complication following surgery for Crohn's disease in which the terminal ileum has been removed is the development of excessive watery diarrhea. This is due to an inability of the ileum to reabsorb bile acids after resection of the terminal ileum. {{Citation needed|date=March 2009}}
In some cases of SBS, intestinal transplant surgery may be considered; though the number of transplant centres offering this procedure is quite small and it comes with a high risk due to the chance of infection and rejection of the transplanted intestine.
Alternative medicine
More than half of people with Crohn's disease have tried complementary or alternative therapy. These include diets, probiotics, fish oil and other
herbalHerbalism is a traditional medicinal or folk medicine practice based on the use of plants and plant extracts. Herbalism is also known as botanical medicine, medical herbalism, herbal medicine, herbology, herblore, and phytotherapy...
and nutritional supplements. The benefit of these medications is uncertain.
- Acupuncture
Acupuncture is a type of alternative medicine that treats patients by insertion and manipulation of solid, generally thin needles in the body....
is used to treat inflammatory bowel disease in ChinaChinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
, and is being used more frequently in Western societyThe Western world, also known as the West and the Occident , is a term referring to the countries of Western Europe , the countries of the Americas, as well all countries of Northern and Central Europe, Australia and New Zealand...
. There is insufficient evidence to recommend the use of acupuncture, though further studies are warranted.
- Homeopathy
Homeopathy is a form of alternative medicine in which practitioners claim to treat patients using highly diluted preparations that are believed to cause healthy people to exhibit symptoms that are similar to those exhibited by the patient...
is frequently used in GermanyGermany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
as a treatment for Crohn's disease, though no clinical trialClinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s exist that demonstrate it is effective.
Prognosis
{{Expand section|date=October 2009}}
Crohn's disease is a
chronicA chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
condition for which there is currently no cure. It is characterised by periods of improvement followed by episodes when symptoms flare up. With treatment, most people achieve a healthy weight, and the mortality rate for the disease is relatively low. However, Crohn's disease is associated with an increased risk of small bowel and colorectal carcinoma, including bowel cancer.
Epidemiology
The incidence of Crohn's disease has been ascertained from population studies in
NorwayNorway , officially the Kingdom of Norway, is a Nordic unitary constitutional monarchy whose territory comprises the western portion of the Scandinavian Peninsula, Jan Mayen, and the Arctic archipelago of Svalbard and Bouvet Island. Norway has a total area of and a population of about 4.9 million...
and the
United StatesThe United States of America is a federal constitutional republic comprising fifty states and a federal district...
and is similar at 6 to 7.1:100,000. The Crohn's and Colitis Foundation of America cites this number as approx 149:100,000; NIH cites 28 to 199 per 100,000. Crohn's disease is more common in northern countries, and shows a higher preponderance in northern areas of the same country. The incidence of Crohn's disease is thought to be similar in
EuropeEurope is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
but lower in
AsiaAsia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
and
AfricaAfrica is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
. It also has a higher incidence in
Ashkenazi JewsAshkenazi Jews, also known as Ashkenazic Jews or Ashkenazim , are the Jews descended from the medieval Jewish communities along the Rhine in Germany from Alsace in the south to the Rhineland in the north. Ashkenaz is the medieval Hebrew name for this region and thus for Germany...
and smokers.
Crohn's disease has a
bimodal distributionIn statistics, a bimodal distribution is a continuous probability distribution with two different modes. These appear as distinct peaks in the probability density function, as shown in Figure 1....
in
incidenceIncidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
as a function of age: the disease tends to strike people in their teens and 20s, and people in their 50s through to their 70s, and ages in between due to not being diagnosed with Crohn's and being diagnosed instead with
irritable bowel syndromeIrritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...
(IBS). It is rarely diagnosed in early childhood. It usually strikes females who are pediatric patients more severely than males. However, only slightly more women than men have Crohn's disease. Parents, siblings or children of people with Crohn's disease are 3 to 20 times more likely to develop the disease. Twin studies show a concordance of greater than 55% for Crohn's disease.
History
{{Expand section|date=October 2009}}
Inflammatory bowel diseases were described by
Giovanni Battista MorgagniGiovanni Battista Morgagni was an Italian anatomist, celebrated as the father of modern anatomical pathology.-Education:...
(1682–1771) and by
ScottishScotland is a country that is part of the United Kingdom. Occupying the northern third of the island of Great Britain, it shares a border with England to the south and is bounded by the North Sea to the east, the Atlantic Ocean to the north and west, and the North Channel and Irish Sea to the...
physician T. Kennedy Dalziel in 1913.
Ileitis terminalis was first described by Polish surgeon
Antoni LeśniowskiAntoni Leśniowski was a Polish surgeon, credited with publishing what may have been the earliest reports of the condition which later became known as Crohn’s disease....
in 1904, however, due to the precedence of Crohn's name in the alphabet, it became later to be known in the worldwide literature as Crohn’s disease.{{Citation needed|date=August 2010}} Only in
PolandPoland , officially the Republic of Poland , is a country in Central Europe bordered by Germany to the west; the Czech Republic and Slovakia to the south; Ukraine, Belarus and Lithuania to the east; and the Baltic Sea and Kaliningrad Oblast, a Russian exclave, to the north...
it continues to be named Leśniowski-Crohn’s disease.
Burrill Bernard Crohn, an American gastroenterologist at
New York CityNew York is the most populous city in the United States and the center of the New York Metropolitan Area, one of the most populous metropolitan areas in the world. New York exerts a significant impact upon global commerce, finance, media, art, fashion, research, technology, education, and...
's
Mount Sinai HospitalMount Sinai Hospital, founded in 1852, is one of the oldest and largest teaching hospitals in the United States. In 2011-2012, Mount Sinai Hospital was ranked as one of America's best hospitals by U.S...
, described fourteen cases in 1932, and submitted them to the
American Medical AssociationThe American Medical Association , founded in 1847 and incorporated in 1897, is the largest association of medical doctors and medical students in the United States.-Scope and operations:...
under the rubric of "Terminal ileitis: A new clinical entity". Later that year, he, along with colleagues Leon Ginzburg and Gordon Oppenheimer published the case series as "Regional ileitis: a pathologic and clinical entity".
Research
Researchers at
University College LondonUniversity College London is a public research university located in London, United Kingdom and the oldest and largest constituent college of the federal University of London...
have questioned the wisdom of suppressing the immune system in Crohn's, as the problem may be an underactive rather than an overactive immune system: Their study found that Crohn's patients showed an abnormally low response to an introduced infection, marked by a poor flow of blood to the wound, and the response improved when the patients were given
sildenafil citrateSildenafil citrate, sold as Viagra, Revatio and under various other trade names, is a drug used to treat erectile dysfunction and pulmonary arterial hypertension . It was originally developed by British scientists and then brought to market by the US-based pharmaceutical company Pfizer...
.
Recent studies using
helminthic therapyHelminthic therapy, a type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the ova of a helminth. Helminths are parasitic worms such as hookworms and whipworms....
or hookworms to treat Crohn's Disease and other (non-viral) auto-immune diseases seem to yield promising results.
Numerous preclinical studies demonstrate that activation of the CB1 and CB2 cannabinoid receptors exert biological functions on the gastrointestinal tract. Activation of CB1 and CB2 receptors in animals has shown a strong anti-inflammatory effect.
CannabinoidsCannabinoids are a class of chemical compounds that include the phytocannabinoids , and chemical compounds that mimic the actions of phytocannabinoids or have a similar structure...
and/or modulation of the endocannabinoid system is a novel therapeutic means for the treatment of numerous GI disorders, including inflammatory bowel diseases like Crohn's disease.
- Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
is a folate anti-metabolite drug that is also used for chemotherapyChemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
. It is useful in maintenance of remission for those no longer taking corticosteroids.
- Metronidazole
Metronidazole is a nitroimidazole antibiotic medication used particularly for anaerobic bacteria and protozoa. Metronidazole is an antibiotic, amebicide, and antiprotozoal....
and ciprofloxacinCiprofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class.It is a second-generation fluoroquinolone antibacterial. It kills bacteria by interfering with the enzymes that cause DNA to rewind after being copied, which stops synthesis of DNA and of...
are antibiotics used to treat Crohn's that have colonic or perianal involvement, although, in the United States, this use has not been approved by the Food and Drug AdministrationThe Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
. They are also used for treatment of complications, including abscesses and other infections accompanying Crohn's disease.
- Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
has shown response in reversing endoscopicEndoscopy means looking inside and typically refers to looking inside the body for medical reasons using an endoscope , an instrument used to examine the interior of a hollow organ or cavity of the body. Unlike most other medical imaging devices, endoscopes are inserted directly into the organ...
evidence of disease.
- Cannabis
Medical cannabis refers to the use of parts of the herb cannabis as a physician-recommended form of medicine or herbal therapy, or to synthetic forms of specific cannabinoids such as THC as a physician-recommended form of medicine...
-derived drugs may be used to treat Crohn's Disease with their anti-inflammatory properties. Cannabis-derived drugs may also help to heal the gut lining.
External links
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