Crohn's disease is a type of
inflammatory bowel disease
Inflammatory bowel disease (IBD) is a group of inflammation, inflammatory conditions of the colon (anatomy), colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine a ...
(IBD) that may affect any segment of the
gastrointestinal tract
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...
.
Symptoms often include
abdominal pain
Abdominal pain, also known as a stomach ache, is a symptom
Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than ...
,
diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
(which may be bloody if inflammation is severe),
fever
Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
,
abdominal distension, and
weight loss
Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...
.
Complications outside of the gastrointestinal tract may include
anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
,
skin rashes
A rash is a change of the human skin which affects its color, appearance, or texture.
A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cr ...
,
arthritis
Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...
,
inflammation of the eye, and
fatigue
Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
.
[ The skin rashes may be due to infections as well as pyoderma gangrenosum or erythema nodosum.][ ]Bowel obstruction
Bowel obstruction, also known as intestinal obstruction, is a mechanical or Ileus, functional obstruction of the Gastrointestinal tract#Lower gastrointestinal tract, intestines which prevents the normal movement of the products of digestion. Eith ...
may occur as a complication of chronic inflammation, and those with the disease are at greater risk of colon cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel mo ...
and small bowel cancer
Small intestine cancer is a cancer of the small intestine. It is relatively rare compared to other gastrointestinal malignancies such as gastric cancer (stomach cancer) and colorectal cancer.
Small intestine cancer can be subdivided into duodenal ...
.[
While the precise causes of Crohn's disease (CD) are unknown, it is believed to be caused by a combination of environmental, ]immune
In biology, immunity is the capability of multicellular organisms to resist harmful microorganisms. Immunity involves both specific and nonspecific components. The nonspecific components act as barriers or eliminators of a wide range of pathogens ...
, and bacterial factors in genetically susceptible individuals.[ It results in a chronic inflammatory disorder, in which the body's ]immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
defends the gastrointestinal tract, possibly targeting microbial
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
antigens
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
. While Crohn's is an immune-related disease, it does not appear to be an autoimmune disease
An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
(in that the immune system is not being triggered by the body itself). The exact underlying immune problem is not clear; however, it may be an immunodeficiency
Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
state.
About half of the overall risk is related to genetics, with more than 70 gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
s having been found to be involved. Tobacco smokers are twice as likely to develop Crohn's disease as nonsmokers. It also often begins after gastroenteritis
Gastroenteritis, also known as infectious diarrhea and gastro, is an inflammation of the gastrointestinal tract including the stomach and intestine. Symptoms may include diarrhea, vomiting, and abdominal pain. Fever, lack of energy, and dehydra ...
.[ Diagnosis is based on a number of findings, including ]biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
and appearance of the bowel wall, medical imaging
Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to rev ...
, and description of the disease.[ Other conditions that can present similarly include irritable bowel syndrome and Behçet's disease.][
There is no known cure for Crohn's disease.] Treatment options are intended to help with symptoms, maintain remission, and prevent relapse.[ In those newly diagnosed, a ]corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...
may be used for a brief period of time to rapidly improve symptoms, alongside another medication such as either methotrexate
Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...
or a thiopurine
The thiopurine drugs are purine antimetabolites widely used in the treatment of acute lymphoblastic leukemia, autoimmune disorders (e.g., Crohn's disease, rheumatoid arthritis), and organ transplant recipients.
Metabolism is catalyzed by S-methy ...
used to prevent recurrence.[ Stopping smoking is recommended in people with Crohn's disease.][ One in five people with the disease is admitted to the hospital each year, and half of those with the disease will require surgery for the disease at some point over a ten-year period.][ While surgery should be used as little as possible, it is necessary to address some ]abscess
An abscess is a collection of pus that has built up within the tissue of the body. Signs and symptoms of abscesses include redness, pain, warmth, and swelling. The swelling may feel fluid-filled when pressed. The area of redness often extends b ...
es, certain bowel obstructions, and cancers.[ Checking for bowel cancer via ]colonoscopy
Colonoscopy () or coloscopy () 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 can provide a visual diagnosis (''e. ...
is recommended every few years, starting eight years after the disease has begun.[
Crohn's disease affects about 3.2 per 1,000 people in Europe, North America,] and the UK. It is less common in Asia and Africa. It has historically been more common in the developed world.[ Rates have, however, been increasing, particularly in the developing world, since the 1970s.] Inflammatory bowel disease resulted in 47,400 deaths in 2015, and those with Crohn's disease have a slightly reduced life expectancy
Life expectancy is a statistical measure of the average time an organism is expected to live, based on the year of its birth, current age, and other demographic factors like sex. The most commonly used measure is life expectancy at birth ...
.[ It tends to start in young adulthood, though it can occur at any age.] Males and females are equally affected.
Name
The disease was named after gastroenterologist Burrill Bernard Crohn
Burrill Bernard Crohn (June 13, 1884 – July 29, 1983) was an American gastroenterologist who made the first major advance to identify the disease that now bears his name. Although the description of Crohn's disease is by far his most famous ac ...
, who in 1932, together with two colleagues at Mount Sinai Hospital in New York, described a series of patients with inflammation of the terminal ileum of the small intestine
The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through the p ...
, the area most commonly affected by the illness.
Signs and symptoms
Gastrointestinal
Many people with Crohn's disease have symptoms for years before the diagnosis. The usual onset is in the teens and twenties, 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. The symptoms experienced can change over time as inflammation increases and spreads. Symptoms can also be different depending on which organs are involved. It is generally thought that the presentation of Crohn's disease is different for each patient due to the high variability of symptoms, organ involvement, and initial presentation.
]
Perianal
Perianal
The anus (Latin, 'ring' or 'circle') 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, the residual semi-solid waste that remains after food digestion, which, d ...
discomfort may also be prominent in Crohn's disease. Itchiness or pain around the anus
The anus (Latin, 'ring' or 'circle') 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, the residual semi-solid waste that remains after food digestion, which, d ...
may be suggestive of inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
of the anus, or perianal complications such as anal fissure
An 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 toilet paper and undergarments, or sometimes in the toilet. If acute they are painful after defecation, but with chronic ...
s, fistulae, or abscess
An abscess is a collection of pus that has built up within the tissue of the body. Signs and symptoms of abscesses include redness, pain, warmth, and swelling. The swelling may feel fluid-filled when pressed. The area of redness often extends b ...
es around the anal area. Perianal skin tags
A skin tag, or acrochordon (pl. acrochorda), is a small benign tumor that forms primarily in areas where the skin forms creases (or rubs together), such as the neck, armpit and groin. They may also occur on the face, usually on the eyelids. Th ...
are also common in Crohn's disease, and may appear with or without the presence of colorectal polyp
A colorectal polyp is a polyp (fleshy growth) occurring on the lining of the colon or rectum. Untreated colorectal polyps can develop into colorectal cancer.
Colorectal polyps are often classified by their behaviour (i.e. benign vs. malignant) ...
s. Fecal incontinence may accompany perianal Crohn's disease.
Intestines
The intestines, especially the colon and terminal ileum, are the most commonly affected areas of the body. Abdominal pain
Abdominal pain, also known as a stomach ache, is a symptom
Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than ...
is a common initial symptom of Crohn's disease, especially in the lower right abdomen. Flatulence, bloating, and abdominal distension are additional symptoms and may also add to the intestinal discomfort. Pain is often accompanied by diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
, which may or may not be bloody. Inflammation in different areas of the intestinal tract
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
can affect the quality of the feces
Feces ( or faeces), known colloquially and in slang as poo and poop, are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the large intestine. Feces contain a relati ...
. Ileitis
Ileitis is an inflammation of the ileum, a portion of the small intestine. Crohn's ileitis is a type of Crohn's disease affecting the ileum. Ileitis is caused by the bacterium ''Lawsonia intracellularis
''Lawsonia intracellularis'' is a speci ...
typically results in large-volume, watery feces, while 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 is not unusual. Bloody bowel movements are usually intermittent, and may be bright red, dark maroon, or even black in color. The color of bloody stool depends on the location of the bleed. In severe Crohn's colitis, bleeding may be copious.
Stomach and esophagus
The stomach is rarely the sole or predominant site of CD. To date there are only a few documented case reports of adults with isolated gastric CD and no reports in the pediatric population. Isolated stomach involvement is very unusual presentation accounting for less than 0.07% of all gastrointestinal CD. Rarely, the esophagus
The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to the ...
and stomach may be involved in Crohn's disease. These can cause symptoms including difficulty swallowing (dysphagia
Dysphagia is difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, in some contexts it is classified as a disease#Terminology, condition in its own right.
It may be a sensation that suggests difficulty in the passag ...
), upper abdominal pain, and vomiting.
Oropharynx (mouth)
The mouth may be affected by recurrent sores ( aphthous ulcers). Recurrent aphthous ulcers are common; however, it is not clear whether this is due to Crohn's disease or simply that they are common in the general population. Other findings may include diffuse or nodular swelling of the mouth, a cobblestone appearance inside the mouth, granulomatous ulcers, or pyostomatitis vegetans. Medications that are commonly prescribed to treat CD, such as anti-inflammatory and sulfa-containing drugs, may cause lichenoid drug reactions in the mouth. Fungal infection such as candidiasis is also common due to the immunosuppression required in the treatment of the disease. Signs of anemia such as pallor and angular cheilitis or glossitis are also common due to nutritional malabsorption.
People with Crohn's disease are also susceptible to angular stomatitis
Angular cheilitis (AC) is inflammation of one or both corners of the mouth. Often the corners are red with skin breakdown and crusting. It can also be itchy or painful. The condition can last for days to years. Angular cheilitis is a type of chei ...
, an inflammation of the corners of the mouth, and pyostomatitis vegetans Pyostomatitis vegetans is an inflammatory stomatitis and most often seen in association with inflammatory bowel disease, namely ulcerative colitis and Crohn's disease. Uncommonly, it may be one of the features of orofacial granulomatosis.
See also ...
.
Systemic
Like many other chronic, inflammatory diseases, Crohn's disease can cause a variety of systemic symptoms
Systemic fundamental to a predominant social, economic, or political practice. This refers to:
In medicine
In medicine, ''systemic'' means affecting the whole body, or at least multiple organ systems. It is in contrast with ''topical'' or ''loc ...
.[ Among children, ]growth failure
Failure to thrive (FTT), also known as weight faltering or faltering growth, indicates insufficient weight gain or absence of appropriate physical growth in children. FTT is usually defined in terms of weight, and can be evaluated either by a low ...
is common. Many children are first diagnosed with Crohn's disease based on inability to maintain growth.[ As it may manifest at the time of the growth spurt in ]puberty
Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is 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 abscess.[ 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 intestine
The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through the p ...
disease may also have malabsorption of carbohydrate
In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or ma ...
s or lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
s, which can further exacerbate weight loss.
Extraintestinal
Crohn's disease can affect many organ systems beyond the gastrointestinal tract
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...
.
Visual
Inflammation of the interior portion of the eye, known as uveitis, can cause blurred vision and eye pain, especially when exposed to light ( photophobia). Uveitis can lead to loss of vision if untreated.
Inflammation may also involve the white part of the eye (sclera
The sclera, also known as the white of the eye or, in older literature, as the tunica albuginea oculi, is the opaque, fibrous, protective, outer layer of the human eye containing mainly collagen and some crucial elastic fiber. In humans, and som ...
) or the overlying connective tissue ( episclera), which causes conditions called scleritis
Scleritis 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 granulomatosis with polyangiitis or ...
and episcleritis
Episcleritis is a benign, self-limiting inflammatory disease affecting part of the eye called the episclera. The episclera is a thin layer of tissue that lies between the conjunctiva and the connective tissue layer that forms the white of the ey ...
, respectively.
Other very rare ophthalmological manifestations include: conjunctivitis
Conjunctivitis, also known as pink eye, is inflammation of the conjunctiva, outermost layer of the white part of the eye and the inner surface of the eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness, or itchiness may ...
, glaucoma
Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...
, and retinal vascular disease.
Gallbladder and liver
Crohn's disease that affects the ileum may result in an increased risk of gallstones. This is due to a decrease in bile acid resorption in the ileum, and the bile
Bile (from Latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver (liver bile ...
gets excreted in the stool. As a result, the cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
/bile ratio increases in the gallbladder, resulting in an increased risk for gallstones. Although the association is greater in the context of ulcerative colitis, Crohn's disease may also be associated with primary sclerosing cholangitis
Primary sclerosing cholangitis (PSC) is a long-term progressive disease of the liver and gallbladder characterized by inflammation and scarring of the bile ducts, which normally allow bile to drain from the gallbladder. Affected individuals may ha ...
, a type of inflammation of the bile duct
A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates.
Bile is required for the digestion of food and is secreted by the liver into passages that carry bile toward the hepatic duct. It ...
s.
Liver involvement of Crohn's disease can include cirrhosis
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...
and steatosis. Nonalcoholic fatty liver disease
Non-alcoholic fatty liver disease (NAFLD), also known as metabolic (dysfunction) associated fatty liver disease (MAFLD), is excessive fat build-up in the liver without another clear cause such as alcohol use. There are two types; non-alcoholic f ...
(Nonalcoholic Steatohepatitis, NAFLD) are relatively common and can slowly progress to end-stage liver disease. NAFLD sensitizes the liver to injury and increases the risk of developing acute or chronic liver failure following another liver injury.
Other rare hepatobiliary manifestations of Crohn's disease include: cholangiocarcinoma
Cholangiocarcinoma, also known as bile duct cancer, is a type of cancer that forms in the bile ducts. Symptoms of cholangiocarcinoma may include abdominal pain, yellowish skin, weight loss, generalized itching, and fever. Light colored stool ...
, granulomatous hepatitis, cholelithiasis, autoimmune hepatitis
Autoimmune hepatitis, formerly known as lupoid hepatitis, plasma cell hepatitis, or autoimmune chronic active hepatitis, is a chronic, autoimmune disease of the liver that occurs when the body's immune system attacks liver cells, causing the liv ...
, hepatic abscess, and pericholangitis.
Renal and urological
Nephrolithiasis
Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the body in the urine s ...
, obstructive uropathy
Obstructive uropathy is a structural or functional hindrance of normal urine flow, sometimes leading to renal dysfunction (obstructive nephropathy).
It is a very broad term, and does not imply a location or cause.
Presentation
Symptoms, less lik ...
, and fistulization
A fistula (plural: fistulas or fistulae ; from Latin ''fistula'', "tube, pipe") in anatomy is an abnormal connection between two hollow spaces (technically, two epithelialized surfaces), such as blood vessels, intestines, or other hollow org ...
of the urinary tract directly result from the underlying disease process. Nephrolithiasis is due to calcium oxalate or uric acid stones. Calcium oxalate is due to hyperoxaluria typically associated with either distal ileal CD or ileal resection. Oxalate absorption increases in the presence of unabsorbed fatty acids in the colon. The fatty acids compete with oxalate to bind calcium, displacing the oxalate, which can then be absorbed as unbound sodium oxalate across colonocytes and excreted into the urine. Because sodium oxalate only is absorbed in the colon, calcium-oxalate stones form only in patients with an intact colon. Patients with an ileostomy are prone to formation of uric-acid stones because of frequent dehydration. The sudden onset of severe abdominal, back, or flank pain in patients with IBD, particularly if different from the usual discomfort, should lead to inclusion of a renal stone in the differential diagnosis.
Urological manifestations in patients with IBD may include ureteral calculi, enterovesical fistula, perivesical infection, perinephric abscess, and obstructive uropathy with hydronephrosis. Ureteral compression is associated with retroperitoneal extension of the phlegmonous inflammatory process involving the terminal ileum and cecum, and may result in hydronephrosis severe enough to cause hypertension
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
.
Immune complex glomerulonephritis presenting with proteinuria and hematuria has been described in children and adults with CD or UC. Diagnosis is by renal biopsy, and treatment parallels the underlying IBD.
Amyloidosis
Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weight ...
(see endocrinological involvement) secondary to Crohn's disease has been described and is known to affect the kidneys.
Pancreatic
Pancreatitis
Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic pancr ...
may be associated with both UC and CD. The most common cause is iatrogenic and involves sensitivity to medications used to treat IBD (3% of patients), including sulfasalazine, mesalamine, 6-mercaptopurine
Mercaptopurine (6-MP), sold under the brand name Purinethol among others, is a medication used for cancer and autoimmune diseases. Specifically it is used to treat acute lymphocytic leukemia (ALL), acute promyelocytic leukemia (APL), Crohn's dise ...
, and azathioprine. Pancreatitis may present as symptomatic (in 2%) or more commonly asymptomatic (8–21%) disease in adults with IBD.
Cardiovascular and circulatory
Children and adults with IBD have been rarely (<1%) reported developing pleuropericarditis either at initial presentation or during active or quiescent disease. The pathogenesis of pleuropericarditis is unknown, although certain medications (e.g., sulfasalazine and mesalamine derivatives) have been implicated in some cases. The clinical presentation may include chest pain, dyspnea, or in severe cases pericardial tamponade
Cardiac tamponade, also known as pericardial tamponade (), is the buildup of fluid in the pericardium (the sac around the heart), resulting in compression of the heart. Onset may be rapid or gradual. Symptoms typically include those of obstruct ...
requiring rapid drainage. Nonsteroidal anti-inflammatory drug
Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
s have been used as therapy, although this should be weighed against the hypothetical risk of exacerbating the underlying IBD.
In rare cases, cardiomyopathy
Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...
, endocarditis
Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or the ...
, and myocarditis
Myocarditis, also known as inflammatory cardiomyopathy, is an acquired cardiomyopathy due to inflammation of the heart muscle. Symptoms can include shortness of breath, chest pain, decreased ability to exercise, and an irregular heartbeat. The ...
have been described.
Crohn's disease also increases the risk of blood clot
A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of c ...
s; painful swelling of the lower legs can be a sign of deep venous thrombosis
Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and enla ...
, while difficulty breathing may be a result of pulmonary embolism.
Respiratory
Laryngeal involvement in inflammatory bowel disease is extremely rare. Only 12 cases of laryngeal involvement in Crohn disease have been reported until now. Moreover, only one case of laryngeal manifestations in ulcerative colitis has been reported so far. 9 patients complained of difficulty in breathing due to edema
Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...
and ulceration from the larynx
The larynx (), commonly called the voice box, is an organ in the top of the neck involved in breathing, producing sound and protecting the trachea against food aspiration. The opening of larynx into pharynx known as the laryngeal inlet is about ...
to the hypopharynx
The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its struct ...
Hoarseness, sore throat, and odynophagia are other symptoms of laryngeal involvement of Crohn's disease.
Considering extraintestinal manifestations of CD, those involving the lung
The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
are relatively rare. However, there is a wide array of lung manifestations, ranging from subclinical alterations, airway diseases and lung parenchyma
Parenchyma () is the bulk of functional substance in an animal organ or structure such as a tumour. In zoology it is the name for the tissue that fills the interior of flatworms.
Etymology
The term ''parenchyma'' is New Latin from the word π ...
l diseases to pleural
The pleural cavity, pleural space, or interpleural space is the potential space between the pleurae of the pleural sac that surrounds each lung. A small amount of serous pleural fluid is maintained in the pleural cavity to enable lubrication bet ...
diseases and drug-related diseases. The most frequent manifestation is bronchial inflammation and suppuration with or without bronchiectasis. There are a number of mechanisms by which the lungs may become involved in CD. These include the same embryological origin of the lung and gastrointestinal tract by ancestral intestine, similar immune systems in the pulmonary and intestinal mucosa, the presence of circulating immune complexes and auto-antibodies, and the adverse pulmonary effects of some drugs. A complete list of known pulmonary manifestations include: Fibrosing alveolitis, Pulmonary vasculitis
Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily caused b ...
, Apical fibrosis, Bronchiectasis
Bronchiectasis is a disease in which there is permanent enlargement of parts of the bronchi, airways of the lung. Symptoms typically include a chronic cough with sputum, mucus production. Other symptoms include shortness of breath, hemoptysis, co ...
, Bronchitis, Bronchiolitis
Bronchiolitis is inflammation of the small airways in the lungs. Acute bronchiolitis is due to a viral infection usually affecting children younger than two years of age. Symptoms may include fever, cough, runny nose, wheezing, and breathing ...
, Tracheal stenosis
Laryngotracheal stenosis refers to abnormal narrowing of the central air passageways. This can occur at the level of the larynx, trachea, carina or main bronchi.
In a small number of patients narrowing may be present in more than one anatomical l ...
, Granuloma
A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such substances include infectious ...
tous lung disease, and Abnormal pulmonary function.
Musculoskeletal
Crohn's disease is associated with a type of rheumatologic disease
Rheumatism or rheumatic disorders are conditions causing chronic, often intermittent pain affecting the joints or connective tissue. Rheumatism does not designate any specific disorder, but covers at least 200 different conditions, including a ...
known as seronegative spondyloarthropathy. This group of diseases is characterized by inflammation of one or more joints (arthritis
Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...
) or muscle insertions (enthesitis
Enthesitis is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. It is an enthesopathy, a pathologic condition of the entheses. Early clinical manifestations are an aching sensation akin to "working out too ...
). The arthritis in Crohn's disease can be divided into two types. The first type affects larger weight-bearing joints such as the knee (most common), hips, shoulders, wrists, or elbows. The second type symmetrically involves five or more of the small joints of the hands and feet. The arthritis may also involve the spine
Spine or spinal may refer to:
Science Biology
* Vertebral column, also known as the backbone
* Dendritic spine, a small membranous protrusion from a neuron's dendrite
* Thorns, spines, and prickles, needle-like structures in plants
* Spine (zoolog ...
, leading to ankylosing spondylitis
Ankylosing spondylitis (AS) is a type of arthritis characterized by long-term inflammation of the joints of the spine typically where the spine joins the pelvis. Occasionally areas affected may include other joints such as the shoulders or hip ...
if the entire spine is involved, or simply sacroiliitis if only the sacroiliac joint
The sacroiliac joint or SI joint (SIJ) is the joint between the sacrum and the ilium bones of the pelvis, which are connected by strong ligaments. In humans, the sacrum supports the spine and is supported in turn by an ilium on each side. The ...
is involved. The symptoms of arthritis include painful, warm, swollen, stiff joints, and loss of joint mobility or function.
Crohn's disease increases the risk of osteoporosis
Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...
or thinning of the bones. Individuals with osteoporosis are at increased risk of bone fracture
A bone fracture (abbreviated FRX or Fx, Fx, or #) is a medical condition in which there is a partial or complete break in the continuity of any bone in the body. In more severe cases, the bone may be broken into several fragments, known as a '' ...
s.
Dermatological
Crohn's disease may also involve the skin, blood, and endocrine system
The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...
. Erythema nodosum is the most common type of skin problem, occurring in around 8% of people with Crohn's disease, producing raised, tender red nodules usually appearing on the shin
Shin may refer to:
Biology
* The front part of the human leg below the knee
* Shinbone, the tibia, the larger of the two bones in the leg below the knee in vertebrates
Names
* Shin (given name) (Katakana: シン, Hiragana: しん), a Japanese ...
s. Erythema nodosum is due to inflammation of the underlying subcutaneous tissue
The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and macr ...
, and is characterized by septal
In biology, a septum (Latin for ''something that encloses''; plural septa) is a wall, dividing a cavity or structure into smaller ones. A cavity or structure divided in this way may be referred to as septate.
Examples
Human anatomy
* Interatri ...
panniculitis
Panniculitis is a group of diseases whose hallmark is inflammation of subcutaneous adipose tissue (the fatty layer under the skin – panniculus adiposus). Symptoms include tender skin nodules, and systemic signs such as weight loss and fatigue. ...
.
Pyoderma gangrenosum is a less common skin problem, occurring in under 2%, and is typically a painful ulcerating nodule.
Clubbing, a deformity of the ends of the fingers, may also be a result of Crohn's disease.
Other very rare dermatological manifestations include: Pyostomatitis vegetans Pyostomatitis vegetans is an inflammatory stomatitis and most often seen in association with inflammatory bowel disease, namely ulcerative colitis and Crohn's disease. Uncommonly, it may be one of the features of orofacial granulomatosis.
See also ...
, Psoriasis
Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...
, Erythema multiforme
Erythema multiforme (EM) is a skin condition that appears with red patches evolving into target lesions, typically on both hands.
It is a type of erythema possibly mediated by deposition of immune complexes (mostly IgM-bound complexes) in the s ...
, Epidermolysis bullosa acquista (described in a case report), and Metastatic CD (the spread of Crohn's inflammation to the skin). It is unknown if Sweet's Syndrome is connected to Crohn's disease.
Neurological
Crohn's disease can also cause neurological
Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal ...
complications (reportedly in up to 15%).[Crohn's disease](_blank)
. professionals.epilepsy.com. Retrieved July 13, 2007. The most common of these are seizures
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
, stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
, myopathy
In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. ''Myopathy'' means muscle disease (Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meani ...
, peripheral neuropathy, headache
Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Headaches can occur as a result ...
, and depression.
Central and peripheral neurological disorders are described in patients with IBD and include peripheral neuropathies
Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...
, myopathies
In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. ''Myopathy'' means muscle disease (Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meani ...
, focal central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
defects, convulsion
A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a s ...
s, confusional episodes, meningitis
Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...
, syncope, optic neuritis, and sensorineural
Sensorineural hearing loss (SNHL) is a type of hearing loss in which the root cause lies in the inner ear or sensory organ (cochlea and associated structures) or the vestibulocochlear nerve ( cranial nerve VIII). SNHL accounts for about 90% of r ...
loss. Autoimmune mechanisms are proposed for involvement with IBD. Nutritional deficiencies associated with neurological manifestations, such as vitamin B12 deficiency
Vitamin B12 deficiency, also known as cobalamin deficiency, is the medical condition in which the blood and tissue have a lower than normal level of vitamin B12. Symptoms can vary from none to severe. Mild deficiency may have few or absent symp ...
, should be investigated. Spinal abscess
An abscess is a collection of pus that has built up within the tissue of the body. Signs and symptoms of abscesses include redness, pain, warmth, and swelling. The swelling may feel fluid-filled when pressed. The area of redness often extends b ...
has been reported in both a child and an adult with initial complaints of severe back pain due to extension of a psoas abscess from the epidural space to the subarachnoid space.
Psychiatric and psychological
Crohn's disease is linked to many psychological disorders, including depression and anxiety
Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
, denial of your disease, the need for dependence or dependent behaviors, feeling overwhelmed, and having a poor self-image.
Endocrinological or hematological
Autoimmune hemolytic anemia
Autoimmune hemolytic anemia (AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to an insufficient number of oxygen-carrying red blood cells in the circulation. The lifetime of ...
, a condition in which the immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
attacks the red blood cells
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek language, Greek ''erythros'' for "red" and ''k ...
, is also more common in Crohn's disease and may cause fatigue
Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
, a pale appearance, and other symptoms common in anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
.
Secondary amyloidosis
Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weight ...
(AA) is another rare but serious complication of inflammatory bowel disease
Inflammatory bowel disease (IBD) is a group of inflammation, inflammatory conditions of the colon (anatomy), colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine a ...
(IBD), generally seen in Crohn's disease. At least 1% of patients with Crohn's disease develop amyloidosis. In the literature, the time lapse between the onset of Crohn's disease and the diagnosis of amyloidosis has been reported to range from one to 21 years.
Leukocytosis and thrombocytopenia
Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...
are usually due to immunosuppressant
Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system.
Classification
Immunosuppressive drugs can be classified in ...
treatments or sulfasalazine. Plasma erythropoietin
Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production (erythropoiesis) in the bo ...
levels often are lower in patients with IBD than expected, in conjunction with severe anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
.
Thrombocytosis
Thrombocythemia is a condition of high platelet (thrombocyte) count in the blood. Normal count is in the range of 150x109 to 450x109 platelets per liter of blood, but investigation is typically only considered if the upper limit exceeds 750x109/L. ...
and thromboembolic events resulting from a hypercoagulable state in patients with IBD can lead to pulmonary embolism or thrombosis
Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thro ...
elsewhere in the body. Thrombosis has been reported in 1.8% of patients with UC and 3.1% of patients with CD. Thromboembolism and thrombosis are less frequently reported among pediatric patients, with 3 patients with UC and 1 with CD described in case reports.
In rare cases, hypercoagulation disorders and portal vein thrombosis
Portal vein thrombosis (PVT) is a vascular disease of the liver that occurs when a blood clot occurs in the hepatic portal vein, which can lead to increased pressure in the portal vein system and reduced blood supply to the liver. The mortality ...
have been described.
Malnutrition symptoms
People with Crohn's disease may develop anemia due to vitamin B12, folate, iron deficiency, or due to anemia of chronic disease
Anemia of chronic disease (ACD) or anemia of chronic inflammation is a form of anemia seen in chronic infection, chronic immune activation, and malignancy. These conditions all produce elevation of interleukin-6, which stimulates hepcidin product ...
. The most common is iron deficiency anemia
Iron-deficiency anemia is anemia caused by a lack of iron. Anemia is defined as a decrease in the number of red blood cells or the amount of hemoglobin in the blood. When onset is slow, symptoms are often vague such as feeling tired, weak, shor ...
from chronic blood loss
Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...
, reduced dietary intake, and persistent inflammation leading to increased hepcidin
Hepcidin is a protein that in humans is encoded by the ''HAMP'' gene. Hepcidin is a key regulator of the entry of iron into the circulation in mammals.
During conditions in which the hepcidin level is abnormally high, such as inflammation, se ...
levels, restricting iron
Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in f ...
absorption in the duodenum. As Crohn's disease most commonly affects the terminal ileum where the vitamin B12/intrinsic factor
Intrinsic factor (IF), cobalamin binding intrinsic factor, also known as gastric intrinsic factor (GIF), is a glycoprotein produced by the parietal cells (in humans) or chief cells (in rodents) of the stomach. It is necessary for the absorption o ...
complex is absorbed, B12 deficiency may be seen. This is particularly common after surgery to remove the ileum. Involvement of the duodenum and jejunum can impair the absorption of many other nutrients including folate. People with Crohn's often also have issues with small bowel bacterial overgrowth syndrome
Small intestinal bacterial overgrowth (SIBO), also termed bacterial overgrowth, or small bowel bacterial overgrowth syndrome (SBBOS), is a disorder of excessive bacterial growth in the small intestine. Unlike the colon (or large bowel), which is r ...
, which can produce micronutrient deficiencies.[ ]
Text was copied from this source, which is available under
Creative Commons Attribution 2.0 Generic (CC BY 2.0)
license.
Complications
Intestinal damage
Crohn's disease can lead to several mechanical complications within the intestine
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...
s, including obstruction
Obstruction may refer to:
Places
* Obstruction Island, in Washington state
* Obstruction Islands, east of New Guinea
Medicine
* Obstructive jaundice
* Obstructive sleep apnea
* Airway obstruction, a respiratory problem
** Recurrent airway obst ...
, fistulae, and abscess
An abscess is a collection of pus that has built up within the tissue of the body. Signs and symptoms of abscesses include redness, pain, warmth, and swelling. The swelling may feel fluid-filled when pressed. The area of redness often extends b ...
es. Obstruction typically occurs from strictures
A stenosis (from Ancient Greek στενός, "narrow") is an abnormal narrowing in a blood vessel or other tubular organ or structure such as foramina and canals. It is also sometimes called a stricture (as in urethral stricture).
''Stricture' ...
or adhesions that narrow the lumen, blocking the passage of the intestinal contents. A fistula can develop between two loops of bowel, between the bowel and bladder
The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine enters ...
, between the bowel and vagina
In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hymen ...
, and between the bowel and skin. Abscesses are walled-off concentrations of infection
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
, which can occur in the abdomen
The abdomen (colloquially called the belly, tummy, midriff, tucky or stomach) is the part of the body between the thorax (chest) and pelvis, in humans and in other vertebrates. The abdomen is the front part of the abdominal segment of the torso. ...
or in the perianal
The anus (Latin, 'ring' or 'circle') 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, the residual semi-solid waste that remains after food digestion, which, d ...
area. Crohn's is responsible for 10% of vesicoenteric fistulae, and is the most common cause of ileovesical fistulae.
Symptoms caused by intestinal stenosis, or the tightening and narrowing of the bowel, are also common in Crohn's disease. Abdominal pain is often most severe in areas of the bowel with stenosis
A stenosis (from Ancient Greek στενός, "narrow") is an abnormal narrowing in a blood vessel or other tubular organ or structure such as foramina and canals. It is also sometimes called a stricture (as in urethral stricture).
''Stricture'' ...
. Persistent vomiting and nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
may indicate stenosis from small bowel obstruction
Bowel obstruction, also known as intestinal obstruction, is a mechanical or functional obstruction of the intestines which prevents the normal movement of the products of digestion. Either the small bowel or large bowel may be affected. Signs an ...
or disease involving the stomach, pylorus, or duodenum
The 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 m ...
.
Intestinal granuloma
A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such substances include infectious ...
s are a walled-off portions of the intestine by macrophages in order to isolate infections. Granuloma formation is more often seen in younger patients, and mainly in the severe, active penetrating disease. Granuloma is considered the hallmark of microscopic diagnosis in Crohn's disease (CD), but granulomas can be detected in only 21-60% of CD patients.
Cancer
Crohn's disease also increases the risk of cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
in the area of inflammation. For example, individuals with Crohn's disease involving the small bowel
The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through the pa ...
are at higher risk for small intestinal cancer. Similarly, people with Crohn's colitis
Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension, ...
have a relative risk
The relative risk (RR) or risk ratio is the ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group. Together with risk difference and odds ratio, relative risk measures the association bet ...
of 5.6 for developing colon cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel mo ...
. Screening for colon cancer with colonoscopy
Colonoscopy () or coloscopy () 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 can provide a visual diagnosis (''e. ...
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. Also, immunomodulators
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
and biologic agents used to treat this disease may promote developing extra-intestinal cancers.
Some cancers, such as Acute Myelocytic Leukaemia have been described in cases of Crohn's disease. Hepatosplenic T-cell lymphoma
Hepatosplenic T-cell lymphoma is a rare form of lymphoma that is generally incurable, except in the case of an allogeneic stem cell transplant.
It is a systemic neoplasm comprising medium-sized cytotoxic T-cells that show significant sinusoidal in ...
(HSTCL) is a rare, lethal disease generally seen in young male patients with inflammatory bowel disease. TNF-α Inhibitor treatments ( infliximab, adalimumab, certolizumab, natalizumab, and etanercept) are thought to be the cause of this rare disease.
Major complications
Major complications of Crohn's disease include bowel obstruction
Bowel obstruction, also known as intestinal obstruction, is a mechanical or Ileus, functional obstruction of the Gastrointestinal tract#Lower gastrointestinal tract, intestines which prevents the normal movement of the products of digestion. Eith ...
, abscesses, free perforation, and hemorrhage
Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...
, which in rare cases may be fatal.
Other complications
Individuals with Crohn's disease are at risk of malnutrition
Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues a ...
for many reasons, including decreased food intake and malabsorption. The risk increases following resection of the small bowel
The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through the pa ...
. Such individuals may require oral supplements to increase their caloric intake
The calorie is a unit of energy. For historical reasons, two main definitions of "calorie" are in wide use. The large calorie, food calorie, or kilogram calorie was originally defined as the amount of heat needed to raise the temperature of on ...
, or in severe cases, total parenteral nutrition (TPN). Most people with moderate or severe Crohn's disease are referred to a dietitian
A dietitian, medical dietitian, or dietician is an expert in identifying and treating disease-related malnutrition and in conducting medical nutrition therapy, for example designing an enteral tube feeding regimen or mitigating the effects of ca ...
for assistance in nutrition.
Small intestinal bacterial overgrowth
Small intestinal bacterial overgrowth (SIBO), also termed bacterial overgrowth, or small bowel bacterial overgrowth syndrome (SBBOS), is a disorder of excessive bacterial growth in the small intestine. Unlike the colon (or large bowel), which is r ...
(SIBO) is characterized by excessive proliferation of colonic bacterial species in the small bowel. Potential causes of SIBO include fistulae, strictures, or motility disturbances. Hence, patients with Crohn's disease are especially predisposed to develop SIBO. As result, CD patients may experience malabsorption and report symptoms such as weight loss, watery diarrhea, meteorism, flatulence, and abdominal pain, mimicking acute flare in these patients.
Pregnancy
Crohn's disease can be problematic during pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ca ...
, and some medications can cause adverse outcomes for the fetus
A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal deve ...
or mother. Consultation with an obstetrician and gastroenterologist about Crohn's disease and all medications facilitates preventive measures. In some cases, remission occurs during pregnancy. Certain medications can also lower sperm count or otherwise adversely affect a man's fertility
Fertility is the capability to produce offspring through reproduction following the onset of sexual maturity. The fertility rate is the average number of children born by a female during her lifetime and is quantified demographically. Fertili ...
.
Ostomy-related complications
Common complications of an ostomy In anatomy, a stoma (plural stomata or stomas) is any opening in the body. For example, a mouth, a nose, and an anus are natural stomata. Any hollow organ can be manipulated into an artificial stoma as necessary. This includes the esophagus, stoma ...
(a common surgery in Crohn's disease) are: Mucosal edema, Peristomal dermatitis, Retraction, Ostomy prolapse, Mucosal/skin detachment, Hematoma, Necrosis, Parastomal hernia, and Stenosis.
Etiology
The etiology
Etiology (pronounced ; alternatively: aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek (''aitiología'') "giving a reason for" (, ''aitía'', "cause"); and ('' -logía''). More completely, e ...
of Crohn's disease is unknown. Many theories have been disputed, with four main theories hypothesized to be the primary mechanism of Crohn's disease. In autoimmune diseases
An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
, antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
and T lymphocytes are the primary mode of inflammation. These cells and bodies are part of the adaptive immune system
The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...
, or the part of the immune system that learns to fight foreign bodies when first identified. Autoinflammatory disease
Periodic fever syndromes are a set of disorders characterized by recurrent episodes of systemic and organ-specific inflammation. Unlike autoimmune disorders such as systemic lupus erythematosus, in which the disease is caused by abnormalities of ...
s are diseases where the innate immune system
The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...
, or the immune system we are genetically coded with, is designed to attack our own cells. Crohn's disease likely has involvement of both the adaptive and innate immune systems.
Autoinflammatory theory
Crohn's disease can be described as a multifactorial autoinflammatory disease. The etiopathogenesis of Crohn's disease is still unknown. In any event, a loss of the regulatory capacity of the immune apparatus would be implicated in the onset of the disease. In this respect interestingly enough, as for Blau's disease (a monogenic autoinflammatory disease), the NOD2
Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), also known as caspase recruitment domain-containing protein 15 (CARD15) or inflammatory bowel disease protein 1 (IBD1), is a protein that in humans is encoded by the ''NOD2'' g ...
gene mutations have been linked to Crohn's disease. However, in Crohn's disease, NOD2 mutations act as a risk factor, being more common among Crohn's disease patients than the background population, while in Blau's disease NOD2 mutations are linked directly to this syndrome, as it is an autosomal-dominant disease. All this new knowledge in the pathogenesis of Crohn's disease allows us to put this multifactorial disease in the group of autoinflammatory
Periodic fever syndromes are a set of disorders characterized by recurrent episodes of systemic and organ-specific inflammation. Unlike autoimmune disorders such as systemic lupus erythematosus, in which the disease is caused by abnormalities of ...
syndromes.
Some examples of how the innate immune system affects bowel inflammation have been described. A meta-analysis of CD genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
-wide association studies revealed 71 distinct CD-susceptibility loci. Interestingly, three very important CD-susceptibility genes (the intracellular pathogen-recognition receptor, NOD2; the autophagy-related 16-like 1, ATG16L1
Autophagy related 16 like 1 is a protein that in humans is encoded by the ''ATG16L1'' gene. This protein is characterized as a subunit of the autophagy-related ATG12-ATG5/ATG16 complex and is essentially important for the LC3 (ATG8) lipidation and ...
and the immunity-related GTPase M, IRGM
Immunity-related GTPase family M protein (IRGM), also known as interferon-inducible protein 1 (IFI1), is an enzyme that in humans is ''IRGM'' gene.
IRGM is a member of the interferon-inducible GTPase family. The encoded protein may play a role i ...
) are involved in innate immune responses against gut microbiota, while one (the X-box binding protein 1) is involved in regulation of the daptiveimmune pathway via MHC class II
MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, ...
, resulting in autoinflammatory inflammation. Studies have also found that increased ILC3
Type 3 innate lymphoid cells (ILC3) are immune cells from the lymphoid lineage that are part of the innate immune system. These cells participate in innate mechanisms on mucous membranes, contributing to tissue homeostasis, host-commensal mutualis ...
can overexpress major histocompatibility complex (MHC) II. MHC class II can induce CD4+ T cell apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
, thus avoiding the T cell
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
response to normal bowel micro bacteria. Further studies of IBD patients compared with non-IBD patients found that the expression of MHC II by ILC3 was significantly reduced in IBD patients, thus causing an immune reaction against intestinal cells or normal bowel bacteria and damaging the intestines. This can also make the intestines more susceptible to environmental factors, such as food or bacteria.
The thinking is, that because Crohn's disease has strong innate immune system involvement and has NOD2 mutations as a predisposition, Crohn's disease is more likely an autoinflammatory disease than an autoimmune disease.
Immunodeficiency theory
A substantial body of data has emerged in recent years to suggest that the primary defect in Crohn's disease is actually one of relative immunodeficiency
Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
. This view has been bolstered recently by novel immunological and clinical studies that have confirmed gross aberrations in this early response, consistent with subsequent genetic studies that highlighted molecules important for innate immune function. The suggestion therefore is that Crohn's pathogenesis actually results from partial immunodeficiency, a theory that coincides with the frequent recognition of a virtually identical, non-infectious inflammatory bowel disease arising in patients with congenital
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...
monogenic disorders impairing phagocyte function.
Causes
While the exact cause or causes are unknown, Crohn's disease seems to be due to a combination of environmental factors and genetic predisposition
A genetic predisposition is a genetic characteristic which influences the possible phenotypic development of an individual organism within a species or population under the influence of environmental conditions. In medicine, genetic susceptibilit ...
. Crohn's is the first genetically complex disease in which the relationship between genetic risk factor
In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection.
Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often use ...
s and the immune system is understood in considerable detail. Each individual risk mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
makes a small contribution to the overall risk of Crohn's (approximately 1:200). The genetic data, and direct assessment of immunity, indicates a malfunction in the innate immune system
The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...
.[
] In this view, the chronic inflammation of Crohn's is caused when the adaptive immune system
The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...
tries to compensate for a deficient innate immune system.
Genetics
Crohn's has a genetic component. Because of this, siblings of known people with Crohn's 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
Ribosomal frameshifting, also known as translational frameshifting or translational recoding, is a biological phenomenon that occurs during translation that results in the production of multiple, unique proteins from a single mRNA. The process can ...
in the NOD2
Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), also known as caspase recruitment domain-containing protein 15 (CARD15) or inflammatory bowel disease protein 1 (IBD1), is a protein that in humans is encoded by the ''NOD2'' g ...
gene (also known as the CARD15 gene), followed by the discovery of point mutations. Over 30 genes have been associated with Crohn's; a biological function is known for most of them. For example, one association is with mutations in the XBP1
X-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. The XBP ...
gene, which is involved in the unfolded protein response pathway of the endoplasmic reticulum
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
. The gene variants of NOD2/CARD15 seem to be related with small-bowel involvement. Other well documented genes which increase the risk of developing Crohn's disease are ATG16L1
Autophagy related 16 like 1 is a protein that in humans is encoded by the ''ATG16L1'' gene. This protein is characterized as a subunit of the autophagy-related ATG12-ATG5/ATG16 complex and is essentially important for the LC3 (ATG8) lipidation and ...
, IL23R
The interleukin-23 receptor is a type I cytokine receptor. It is encoded in human by the ''IL23R'' gene. In complex with the interleukin-12 receptor β1 subunit ( IL-12Rβ1), it is activated by the cytokine interleukin 23 (IL-23). The ''IL23R'' mR ...
, IRGM
Immunity-related GTPase family M protein (IRGM), also known as interferon-inducible protein 1 (IFI1), is an enzyme that in humans is ''IRGM'' gene.
IRGM is a member of the interferon-inducible GTPase family. The encoded protein may play a role i ...
, and SLC11A1
Natural resistance-associated macrophage protein 1 is a protein that in humans is encoded by the ''SLC11A1'' gene.
Function
This gene is a member of the solute carrier family 11 (proton-coupled divalent metal ion transporters) family and encode ...
.
There is considerable overlap between susceptibility loci for IBD and mycobacterial
''Mycobacterium'' is a genus of over 190 species in the phylum Actinomycetota, assigned its own family, Mycobacteriaceae. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis ('' M. tuberculosis'') and ...
infections. Genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
-wide association studies have shown that Crohn's disease is genetically linked to coeliac disease.
Crohn's has been linked to the gene LRRK2
Leucine-rich repeat kinase 2 (LRRK2), also known as dardarin (from the Basque word "dardara" which means trembling) and PARK8 (from early identified association with Parkinson's disease), is a large, multifunctional kinase enzyme that in humans i ...
with one variant potentially increasing the risk of developing the disease by 70%, while another lowers it by 25%. The gene is responsible for making a protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
, which collects and eliminates waste product
Waste (or wastes) are unwanted or unusable materials. Waste is any substance discarded after primary use, or is worthless, defective and of no use. A by-product, by contrast is a joint product of relatively minor economic value. A waste pro ...
in cells, and is also associated with Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
.
Immune system
There was a prevailing view that Crohn's disease is a primary T cell
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
autoimmune disorder; however, a newer theory hypothesizes that Crohn's results from an impaired innate immunity. The later hypothesis describes impaired cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
secretion by macrophage
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
s, which contributes to impaired innate immunity and leads to a sustained microbial-induced inflammatory response in the colon, where the bacterial load is high. Another theory is that the inflammation of Crohn's was caused by an overactive Th1 and Th17 cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
response.
In 2007, the ATG16L1 gene was implicated in Crohn's disease, which may induce autophagy
Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
and hinder the body's ability to attack invasive bacteria. Another study theorized that the human immune system traditionally evolved with the presence of parasite
Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson has ...
s inside the body and that the lack thereof due to modern hygiene standards has weakened the immune system. Test subjects were reintroduced to harmless parasites, with positive responses.
Microbes
It is hypothesized that maintenance of commensal microorganism
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
growth in the GI tract
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
is dysregulated, either as a result or cause of immune dysregulation Immune dysregulation is any proposed or confirmed breakdown or maladaptive change in molecular control of immune system processes. For example, dysregulation is a component in the pathogenesis of autoimmune diseases and some cancers. Immune system d ...
.
There is an apparent connection between Crohn's disease, ''Mycobacterium
''Mycobacterium'' is a genus of over 190 species in the phylum Actinomycetota, assigned its own family, Mycobacteriaceae. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis ('' M. tuberculosis'') and ...
'', other pathogenic bacteria, and genetic markers. A number of studies have suggested a causal role for ''Mycobacterium avium'' subspecies ''paratuberculosis'' (MAP), which causes a similar disease, Johne's disease
Paratuberculosis 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''. Infections normally affect ru ...
, in cattle. In many individuals, genetic factors predispose individuals to ''Mycobacterium avium
''Mycobacterium avium ''complex is a group of mycobacteria comprising ''Mycobacterium intracellulare'' and ''Mycobacterium avium'' that are commonly grouped because they infect humans together; this group, in turn, is part of the group of nontub ...
'' subsp.'' paratuberculosis
Paratuberculosis 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''. Infections normally affect ru ...
'' infection. This bacterium may produce certain compounds containing mannose
Mannose is a sugar monomer of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylation ...
, which may protect both itself and various other bacteria from phagocytosis, thereby possibly causing a variety of secondary infections.
NOD2 is a gene involved in Crohn's genetic susceptibility. It is associated with macrophage
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
s' diminished ability to phagocytize
Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is ca ...
MAP. This same gene may reduce innate and adaptive immunity in gastrointestinal tissue and impair the ability to resist infection by the MAP bacterium. Macrophages that ingest the MAP bacterium are associated with high production of TNF-α
Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...
.
Other studies have linked specific strains of