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Friday, January 24, 2025

Astroturfing

From Wikipedia, the free encyclopedia

Astroturfing is the deceptive practice of hiding the sponsors of an orchestrated message or organization (e.g., political, economic, advertising, religious, or public relations) to make it appear as though it originates from, and is supported by, unsolicited grassroots participants. It is a practice intended to give the statements or organizations credibility by withholding information about the source's financial backers.

The implication behind the use of the term is that instead of a "true" or "natural" grassroots effort behind the activity in question, there is a "fake" or "artificial" appearance of support.

Definition

Artificial grass produced by AstroTurf, which inspired the name "astroturfing" for creating a false impression of grassroots support

In political science, it is defined as the process of seeking electoral victory or legislative relief for grievances by helping political actors find and mobilize a sympathetic public, and is designed to create the image of public consensus where there is none. Astroturfing is the use of fake grassroots efforts that primarily focus on influencing public opinion and typically are funded by corporations and political entities to form opinions.

On the internet, astroturfers use software to hide their identity. Sometimes one individual operates through many personas to give the impression of widespread support for their client's agenda. Some studies suggest astroturfing can alter public viewpoints and create enough doubt to inhibit action. In the first systematic study of astroturfing in the United States, Oxford Professor Philip N. Howard argued that the internet was making it much easier for powerful lobbyists and political movements to activate small groups of aggrieved citizens to have an exaggerated importance in public policy debates. Astroturfed accounts on social media do not always require humans to write their posts; one January 2021 study detailed a "set of human-looking bot accounts" used to post political content, which was able to operate automatically for fourteen days (and make 1,586 posts) before being detected and suspended by Twitter. Twitter trends are often targeted by astroturfing as they are used as a proxy for popularity. A study conducted by researchers at EPFL reported that 20% of the global Twitter trends in 2019 were fake, created automatically using fake and compromised accounts which tweet in a coordinated way to mimic grassroots organizing of regular Twitter users.

Policies and enforcement

Many countries have laws that prohibit more overt astroturfing practices. In the United States, the Federal Trade Commission (FTC) may send cease-and-desist orders or require a fine of $16,000 per day for those that violate its "Guides Concerning the Use of Endorsements and Testimonials in Advertising". The FTC's guides were updated in 2009 to address social media and word-of-mouth marketing. According to an article in the Journal of Consumer Policy, the FTC's guides holds advertisers responsible for ensuring bloggers or product endorsers comply with the guides, and any product endorsers with a material connection are required to provide honest reviews.

In the European Union, the Unfair Commercial Practices Directive requires that paid-for editorial content in the media provide a clear disclosure that the content is a sponsored advertisement. Additionally, it prohibits those with a material connection from misleading readers into thinking they are a regular consumer.

The United Kingdom has the Consumer Protection from Unfair Trading Regulations, which prohibits "Falsely representing oneself as a consumer." They allow for up to two years in prison and unlimited fines for breaches. Additionally, the advertising industry in the UK has adopted many voluntary policies, such as the Code of Non-Broadcast Advertising, Sale, Promotion and Direct Marketing. A trade association, the Advertising Standards Authority, investigates complaints of breaches. The policy requires that marketing professionals not mislead their audience, including by omitting a disclosure of their material connection.

In Australia, astroturfing is regulated by Section 18 of the Australian Consumer Law, which broadly prohibits "misleading and deceptive conduct". According to the Journal of Consumer Policy, Australia's laws, which were introduced in 1975, are more vague. In most cases, they are enforced through lawsuits from competitors, rather than the regulatory body, the Australian Competition & Consumer Commission. There is also an International Consumer Protection and Enforcement Network (ICPEN).

Legal regulations are primarily targeted towards testimonials, endorsements and statements as to the performance or quality of a product. Employees of an organization may be considered acting as customers if their actions are not guided by authority within the company.

In October 2018, after denying that they had paid for people to show up in support of a controversial power plant development project in New Orleans, Entergy was fined five million dollars for using astroturf firm The Hawthorn Group to provide actors to prevent real community members' voices from being counted at city council meetings and show false grassroots support.

Debate

Effectiveness

In the book Grassroots for Hire: Public Affairs Consultants in American Democracy, Edward Walker defines "astroturfing" as public participation that is perceived as heavily incented, as fraudulent (claims are attributed to those who did not make such statements), or as an elite campaign masquerading as a mass movement. Although not all campaigns by professional grassroots lobbying consultants meet this definition, the book finds that the elite-sponsored grassroots campaigns often fail when they are not transparent about their sources of sponsorship and/or fail to develop partnerships with constituencies that have an independent interest in the issue. Walker highlights the case of Working Families for Wal-Mart, in which the campaign's lack of transparency led to its demise.

A study published in the Journal of Business Ethics examined the effects of websites operated by front groups on students. It found that astroturfing was effective at creating uncertainty and lowering trust about claims, thereby changing perceptions that tend to favor the business interests behind the astroturfing effort. The New York Times reported that "consumer" reviews are more effective, because "they purport to be testimonials of real people, even though some are bought and sold just like everything else on the commercial Internet." Some organizations feel that their business is threatened by negative comments, so they may engage in astroturfing to drown them out. Online comments from astroturfing employees can also sway the discussion through the influence of groupthink.

Justification

Some astroturfing operatives defend their practice. Regarding "movements that have organized aggressively to exaggerate their sway", author Ryan Sager said that this "isn't cheating. Doing everything in your power to get your people to show up is basic politics." According to a Porter/Novelli executive, "There will be times when the position you advocate, no matter how well framed and supported, will not be accepted by the public simply because you are who you are."

Impact on society

Data-mining expert Bing Liu (University of Illinois Chicago) estimated that one-third of all consumer reviews on the Internet are fake. According to The New York Times, this has made it hard to tell the difference between "popular sentiment" and "manufactured public opinion". According to an article in the Journal of Business Ethics, astroturfing threatens the legitimacy of genuine grassroots movements. The authors argued that astroturfing that is "purposefully designed to fulfill corporate agendas, manipulate public opinion and harm scientific research represents a serious lapse in ethical conduct." A 2011 report found that often paid posters from competing companies are attacking each other in forums and overwhelming regular participants in the process. George Monbiot said that persona-management software supporting astroturfing "could destroy the Internet as a forum for constructive debate". An article in the Journal of Consumer Policy said that regulators and policy makers needed to be more aggressive about astroturfing. The author said that it undermines the public's ability to inform potential customers of sub-standard products or inappropriate business practices, but also noted that fake reviews were difficult to detect.

Techniques

Use of one or more front groups is one astroturfing technique. These groups typically present themselves as serving the public interest, while actually working on behalf of a corporate or political sponsor. Front groups may resist legislation and scientific consensus that is damaging to the sponsor's business by emphasizing minority viewpoints, instilling doubt and publishing counterclaims by corporate-sponsored experts. Fake blogs can also be created that appear to be written by consumers, while actually being operated by a commercial or political interest. Some political movements have provided incentives for members of the public to send a letter to the editor at their local paper, often using a copy and paste form letter that is published in dozens of newspapers verbatim.

Another technique is the use of sockpuppets, where a single person creates multiple identities online to give the appearance of grassroots support. Sockpuppets may post positive reviews about a product, attack participants that criticize the organization, or post negative reviews and comments about competitors, under fake identities. Astroturfing businesses may pay staff based on the number of posts they make that are not flagged by moderators. Persona management software may be used so that each paid poster can manage five to seventy convincing online personas without getting them confused. Online astroturfing using sockpuppets is a form of Sybil attack against distributed systems.

Pharmaceutical companies may sponsor patient support groups and simultaneously push them to help market their products. Bloggers who receive free products, paid travel or other accommodations may also be considered astroturfing if those gifts are not disclosed to the reader. Analysts could be considered astroturfing, since they often cover their own clients without disclosing their financial connection. To avoid astroturfing, many organizations and press have policies about gifts, accommodations and disclosures.

Detection

Persona management software can age accounts and simulate the activity of attending a conference automatically to make it more convincing that they are genuine. At HBGary, employees were given separate thumb drives that contain online accounts for individual identities and visual cues to remind the employee which identity they are using at the time.

Mass letters may be printed on personalized stationery using different typefaces, colors and words to make them appear personal.

According to an article in The New York Times, the Federal Trade Commission rarely enforces its astroturfing laws. Operations are frequently detected if their profile images are recognized or if they are identified through the usage patterns of their accounts. Filippo Menczer's group at Indiana University developed software in 2010 that detects astroturfing on Twitter by recognizing behavioral patterns.

Business and adoption

According to an article in the Journal of Consumer Policy, academics disagree on how prolific astroturfing is.

According to Nancy Clark from Precision Communications, grass-roots specialists charge $25 to $75 for each constituent they convince to send a letter to a politician. Paid online commentators in China are purportedly paid 50 cents for each online post that is not removed by moderators, leading to the nickname of the "50-cent party". The New York Times reported that a business selling fake online book reviews charged $999 for 50 reviews and made $28,000 a month shortly after opening.

According to the Financial Times, astroturfing is "commonplace" in American politics, but was "revolutionary" in Europe when it was exposed that the European Privacy Association, an anti-privacy "think-tank", was actually sponsored by technology companies.

History of incidents

Origins

Although the term "astroturfing" was not yet developed, an early example of the practice was in Act 1, Scene 2 of Shakespeare's play Julius Caesar. In the play, Gaius Cassius Longinus writes fake letters from "the public" to convince Brutus to assassinate Julius Caesar.

The term "astroturfing" was first coined in 1985 by Texas Democratic Party senator Lloyd Bentsen when he said, "a fellow from Texas can tell the difference between grass roots and AstroTurf... this is generated mail." Bentsen was describing a "mountain of cards and letters" sent to his office to promote insurance industry interests.

Pharmaceuticals

Patient advocacy groups funded by biopharmaceutical companies are common. In 1997, Schering Plough paid a P/R firm Schandwick International, to create a national coalition of patient advocacy groups promoting Schering's Rebotron, a treatment for Hepatitis C. The groups pushed increased testing as a way to manufacture cases and lobbied state legislatures to cover the $18,000 treatment. The groups also hosted telephone "information lines" with scripts written by the drug company and distributed "patient information" pamphlets promoting drug therapies over other alternatives and overstating the danger of the medical condition. Manufacturers of AIDS drugs commonly fund LGBTQ organizations, which in turn, lobby to advance policies that increase AIDS drug sales. In 2019, the communications director of AIDS United, a Washington DC–based coalition of AIDS service organizations, resigned, stating such funding creates conflicts of interest among gay rights activists.

Tobacco

In response to the passage of tobacco control legislation in the US, Philip Morris, Burson-Marsteller and other tobacco interests created the National Smokers Alliance (NSA) in 1993. The NSA and other tobacco interests initiated an aggressive public relations campaign from 1994 to 1999 in an effort to exaggerate the appearance of grassroots support for smoker's rights. According to an article in the Journal of Health Communication, the NSA had mixed success at defeating bills that were damaging revenues of tobacco interests.

Internet

Email, automated phone calls, form letters, and the Internet made astroturfing more economical and prolific in the late 1990s. In 2001, as Microsoft was defending itself against an antitrust lawsuit, Americans for Technology Leadership (ATL), a group heavily funded by Microsoft, initiated a letter-writing campaign. ATL contacted constituents under the guise of conducting a poll and sent pro-Microsoft consumers form and sample letters to send to involved lawmakers. The effort was designed to make it appear as though there was public support for a sympathetic ruling in the antitrust lawsuit.

In January 2018, YouTube user Isaac Protiva uploaded a video alleging that internet service provider Fidelity Communications was behind an initiative called "Stop City-Funded Internet", based on how some images on the Stop City-Funded Internet website had "Fidelity" in their file names. The campaign appeared to be in response to the city of West Plains expanding their broadband network, and advocated for the end of municipal broadband on the basis that it was too risky. Days later, Fidelity released a letter admitting to sponsoring the campaign.

Politics

In 2009–2010, an Indiana University research study developed a software system to detect astroturfing on Twitter due to the sensitivity of the topic in the run up to the 2010 U.S. midterm elections and account suspensions on the social media platform. The study cited a limited number of examples, all promoting conservative policies and candidates.

In 2003, GOPTeamLeader.com offered the site's users "points" that could be redeemed for products if they signed a form letter promoting George Bush and got a local paper to publish it as a letter to the editor. More than 100 newspapers published an identical letter to the editor from the site with different signatures on it. Similar campaigns were used by GeorgeWBush.com, and by MoveOn.org to promote Michael Moore's film Fahrenheit 9/11. The Committee for a Responsible Federal Budget's "Fix the Debt" campaign advocated to reduce government debt without disclosing that its members were lobbyists or high-ranking employees at corporations that aim to reduce federal spending. It also sent op-eds to various students that were published as-is.

Some organizations in the Tea Party movement have been accused of being astroturfed.

In October and November 2018, conservative marketing firm Rally Forge created what The New Yorker described as "a phony left-wing front group, America Progress Now, which promoted Green Party candidates online in 2018, apparently to hurt Democrats in several races." Its ads on Facebook used socialist memes and slogans to attack Democrats and urge third-party protest voting in several tight races, including the 2018 Wisconsin gubernatorial election.

In 2018, a website called "Jexodus" claiming to be by "proud Jewish Millennials tired of living in bondage to leftist politics" was set up by Jeff Ballabon, a Republican operative in his mid-50s. The website was denounced as "likely a clumsy astroturf effort rather than an actual grassroots movement". The website was registered November 5, 2018, before the congressional election, and before those representatives accused of antisemitism had even been voted in. This website was later cited by Donald Trump as though it were an authentic movement.

In January 2021, a team led by Mohsen Mosleh conducted a politically oriented astroturfing campaign on Twitter, using "a set of human-looking bot accounts"; each bot would search for users posting links the researchers considered to be fake news, and "tweet a public reply message to the user's tweet that contained the link to the false story". 1,586 spam replies were made over the course of fourteen days, until Twitter detected and suspended all of the bot accounts.

Environment

The Koch brothers started a public advocacy group to prevent the development of wind turbines offshore in Massachusetts. The Kennedy family was also involved.

Corporate efforts to mobilize the public against environmental regulation accelerated in the US following the election of president Barack Obama.

In 2014, the Toronto Sun conservative media organization has published an article accusing Russia of using astroturf tactics to drum up anti-fracking sentiment across Europe and the West, supposedly in order to maintain dominance in oil exports through Ukraine.

In Canada, a coalition of oil and gas company executives grouped under the Canadian Association of Petroleum Producers also initiated a series of Canadian actions to advocate for the oil and gas industry in Canada through mainstream and social media, and using online campaigning to generate public support for fossil fuel energy projects.

Commercial

In 2006, two Edelman employees created a blog called "Wal-Marting Across America" about two people traveling to Wal-Marts across the country. The blog gave the appearance of being operated by spontaneous consumers, but was actually operated on behalf of Working Families for Walmart, a group funded by Wal-Mart. In 2007, Ask.com deployed an anti-Google advertising campaign portraying Google as an "information monopoly" that was damaging the Internet. The ad was designed to give the appearance of a popular movement and did not disclose it was funded by a competitor.

In 2010, the Federal Trade Commission settled a complaint with Reverb Communications, who was using interns to post favorable product reviews in Apple's iTunes store for clients. In September 2012, one of the first major identified cases of astroturfing in Finland involved criticisms about the cost of a €1.8 billion patient information system, which was defended by fake online identities operated by involved vendors.

In September 2013, New York Attorney General Eric T. Schneiderman announced a settlement with 19 companies to prevent astroturfing. "'Astroturfing' is the 21st century's version of false advertising, and prosecutors have many tools at their disposal to put an end to it," said Scheiderman. The companies paid $350,000 to settle the matter, but the settlement opened the way for private suits as well. "Every state has some version of the statutes New York used," according to lawyer Kelly H. Kolb. "What the New York attorney general has done is, perhaps, to have given private lawyers a road map to file suit."

State-sponsored

An Al Jazeera TV series The Lobby documented Israel's attempt to promote more friendly, pro-Israel rhetoric to influence the attitudes of British youth, partly through influencing already established political bodies, such as the National Union of Students and the Labour Party, but also by creating new pro-Israel groups whose affiliation with the Israeli administration was kept secret.

In 2008, an expert on Chinese affairs, Rebecca MacKinnon, estimated the Chinese government employed 280,000 people in a government-sponsored astroturfing operation to post pro-government propaganda on social media and drown out voices of dissent.

In June 2010, the United States Air Force solicited for "persona management" software that would "enable an operator to exercise a number of different online persons from the same workstation and without fear of being discovered by sophisticated adversaries. Personas must be able to appear to originate in nearly any part of the world and can interact through conventional online services and social media platforms..." The $2.6 million contract was awarded to Ntrepid for astroturfing software the military would use to spread pro-American propaganda in the Middle East, and disrupt extremist propaganda and recruitment. The contract is thought to have been awarded as part of a program called Operation Earnest Voice, which was first developed as a psychological warfare weapon against the online presence of groups ranged against coalition forces.

On April 11, 2022, seven weeks into the 2022 Russian invasion of Ukraine, BBC published the results of investigation of a network of Facebook groups with the overall aim to promote the Russian president Vladimir Putin as a hero standing up to the West with overwhelming international support. Members, activities, and interrelations in 10 pro-Putin public groups with more than 650,000 members between them in the time of writing, boasting names such as Vladimir Putin - Leader of the Free World, were analyzed. Over a month, researchers counted 16,500 posts, receiving more than 3.6 million interactions. The campaign "creates the appearance of widespread support for Putin and the Kremlin in the shadow of the invasion and relies on... inauthentic accounts to accomplish its goal", according to a report. Lead researcher Moustafa Ayad described the network and its practice of using tens of duplicate accounts in potential violation of Facebook's rules on inauthentic behavior as an example of astroturfing.

Proavis

From Wikipedia, the free encyclopedia
Hypothetical restoration of "one of the Pro-Aves", as shown at the British Museum by William Plane Pycraft in 1906 (here extracted from Pycraft 1910 book A History of Birds).

Proavis refers to a hypothetical extinct species or hypothetical extinct taxon and was coined in the early 20th century in an attempt to support and explain the hypothetical evolutionary steps and anatomical adaptations leading from non-avian theropod dinosaurs to birds. The term has also been used by defenders of the thecodontian origin of birds.

History

The term "Proavis" was first coined, although under the form "Pro-Aves", by English osteologist and zoologist William Plane Pycraft in "The Origin of Birds", a 1906 article published in the magazine Knowledge and Scientific News. Pycraft added to his article his own drawn depiction of the hypothetical animal, a restoration entitled "One of the Pro-Aves". Pycraft's "Pro-Avis" (singular of "Pro-Aves") was arboreal, as suggested Professor Osborn six years before, in 1900, in an article dealing with the hypothetical common ancestors of dinosaurs and birds. Pycraft assumed that birds had developed as tree-dwelling dinosaurs, gliding on membranes between the limbs and the trunk. These membranes would gradually have been covered by increasingly more elongated scales, which eventually would have evolved into feathers.

A year after Pycraft's article, the Hungarian aristocrat and paleontologist Franz Nopcsa, who, while residing at London, had seen Pycraft's restoration, drew his own vision of the animal, a picture and article published in a 1907 issue of the Proceedings of the Zoological Society of London (an English science publication nowadays known as Journal of Zoology). But this time, for his own "Pro-Avis" restoration, Nopcsa suggested a cursorial origin, not arboreal. The "Pro-Avis" would thus have been a running animal, accelerating and prolonging its jumps by flapping with feathered forelimbs. There is a model of Nopcsa's restoration, still preserved, and recently restored, in the Grant Museum of Zoology, the only remaining university zoological museum in London.

When Pycraft published his book A History of Birds, in 1910, he reinserted his 1906 restoration One of the Pro-Aves (in page 39). In the following years, as of 1913, Danish artist and amateur zoologist Gerhard Heilmann also used and popularised the term Proavis, this time presenting the public with more accurate and anatomically probable drawings. Heilmann favoured a scientific model in which the assumed Proavis was arboreal and of thecodontian descent, thus not a dinosaur.

In 1961, Czech paleontologist Josef Augusta included "Proavis" in his book Prehistoric Birds and Reptiles. The animal illustration, as were all illustrations in the book, was painted by Zdeněk Burian.

During the 1970s the work of John Ostrom, breathing new life into the hypothesis that birds were dinosaurs, revived the interest in the direct ancestors of birds. Ostrom assumed these were cursorial. An illustration of a running dinosaur explicitly indicated as a "Proavis" was in 1976 published by Dieter Stefan Peters.

In 1991 and 1996 "proavis" or "protoavis" models were proposed by respectively Samuel Tarsitano and Alan Feduccia, both adherents of the "thecodont" hypothesis about the origins of birds. These "proaves" were supposed to be arboreal, with short necks, long trunks, sprawling legs, non-elongated hindlimbs, small hands and feet, small general size, and gliding on membranes. Feduccia's "protoavis" had membranes on the forelimbs only and was fashioned on the model of Megalancosaurus.

The term Proavis was used again in 1999, when Joseph Garner, Graham Taylor, and Adrian Thomas proposed their "pouncing proavis model", an hypothesis entailing that the origin of avian flight rested in a predatory behaviour, the "proavis" jumping on its prey from trees (see pouncing proavis model in Origin of avian flight).

In his 2002 book Dinosaurs of the Air, Gregory S. Paul tried to conceptually model a "pro-avian". In his view the direct ancestors of birds cannot have been completely arboreal, because in that case they would probably have used membranes to fly. He thought they must have represented an intermediate ecological stage, in which the hindlimbs still had largely cursorial adaptations whereas the arms had been elongated in order to climb. Feathers, originally serving the insulation of an already warm-blooded animal, would by elongation have turned the arms into wings in order to fly. More generally, the proavians would, in view of their basal theropod forebears and bird descendants, have been typified by long necks, a short trunk, long fingers with opposable digits, a decoupling of the locomotor functions of the forelimbs and hindlimbs, a lack of a propatagium, a shallow tail, and a weight of about one kilogramme. Paul illustrated his analysis with a skeletal diagram, accompanied by a life illustration of a "proavis". When in 2013 Aurornis was described, at the time the most basal known member of the Avialae, the group consisting of birds and their closest relatives, the Italian paleontologist Andrea Cau remarked it bore an uncanny resemblance to Paul's "proavis".

Crohn's disease

From Wikipedia, the free encyclopedia
 
Crohn's disease
Other namesCrohn disease, Crohn syndrome, granulomatous enteritis, regional enteritis, Leśniowski-Crohn disease
Endoscopic image of severe Crohn's colitis showing diffuse loss of mucosal architecture, friability of mucosa in sigmoid colon and exudate on wall.
SpecialtyGastroenterology
SymptomsDiarrhea, abdominal pain, fatigue, weight loss, fever
ComplicationsAnemia, bowel cancer, bowel obstruction, strictures, fistulas, abscesses, anal fissure
Usual onset20–30 years
DurationLifelong
CausesUncertain
Risk factorsGenetic predisposition, living in a developed country, smoking, diet, antibiotics, oral contraceptives, aspirin, NSAIDS
Diagnostic methodColonoscopy, capsule endoscopy, medical imaging, histopathology
Differential diagnosisUlcerative colitis, Behçet's disease, intestinal lymphoma, intestinal tuberculosis, ischaemic colitis, irritable bowel syndrome
MedicationBiologics (especially TNF blockers), immunosuppressants (thiopurines and methotrexate), corticosteroids,
PrognosisSlightly reduced life expectancy
Frequency~300 in 100,000 (North America and Western Europe)
Named after

Crohn's disease is a chronic inflammatory bowel disease characterized by recurrent episodes of intestinal inflammation, primarily manifesting as diarrhea and abdominal pain. Unlike ulcerative colitis, inflammation can occur anywhere in the gastrointestinal tract, though it most frequently affects the ileum and colon, involving all layers of the intestinal wall. Symptoms may be non-specific and progress gradually, often delaying diagnosis. About one-third of patients have colonic disease, another third have ileocolic disease, and the remaining third have isolated ileal disease. Systemic symptoms such as chronic fatigue, weight loss, and low-grade fevers are common. Organs such as the skin and joints can also be affected. Complications can include bowel obstructions, fistulas, nutrition problems, and an increased risk of intestinal cancers.

Crohn's disease is influenced by genetic, environmental, and immunological factors. Smoking is a major modifiable risk factor, especially in Western countries, where it doubles the likelihood of developing the disease. Dietary shifts from high-fiber to processed foods may reduce microbiota diversity and increase risk, while high-fiber diets can offer some protection. Genetic predisposition plays a significant role, with first-degree relatives facing a five-fold increased risk, particularly due to mutations in genes like NOD2 that affect immune response. The condition results from a dysregulated immune response to gut bacteria and increased intestinal permeability, alongside changes in the gut microbiome.

Diagnosing Crohn's disease can be complex due to symptom overlap with other gastrointestinal disorders. It typically involves a combination of clinical history, physical examination, and various diagnostic tests. Key methods include ileocolonoscopy, which identifies the disease in about 90% of cases, and imaging techniques like CT and MRI enterography, which help assess the extent of the disease and its complications. Histological examination of biopsy samples is the most reliable method for confirming diagnosis.

Management of Crohn's disease is individualized, focusing on disease severity and location to achieve mucosal healing and improve long-term outcomes. Treatment may include corticosteroids for quick symptom relief, immunosuppressants for maintaining remission, and biologics like anti-TNF therapies, which are effective for both induction and maintenance. Surgery may be necessary for complications such as blockages. Despite ongoing treatment, Crohn's disease is a chronic condition with no cure, often leading to a higher risk of related health issues and reduced life expectancy.

The disease is most prevalent in North America and Western Europe, particularly among Ashkenazi Jews, with prevalence rates of 322 per 100,000 in Germany, 319 in Canada, and 300 in the United States. There is also a rising prevalence in newly industrialized countries, such as 18.6 per 100,000 in Hong Kong and 3.9 in Taiwan. The typical age of onset is between 20 and 30 years, with an increasing number of cases among children.

Signs and symptoms

Diagram of the three most common sites of intestinal involvement in Crohn's disease.
The three most common sites of intestinal involvement in Crohn's disease are ileal, ileocolic and colonic.

Crohn's disease is characterized by recurring flares of intestinal inflammation, with diarrhea and abdominal pain as the primary symptoms. Symptoms may be non-specific and progress gradually, and many people have symptoms for years before diagnosis. Unlike ulcerative colitis, inflammation can occur anywhere in the gastrointestinal tract, most often in the ileum and colon, and can involve all layers of the intestine. Disease location tends to be stable, with a third of patients having colonic disease, a third having ileocolic disease, and a third having ileal disease. The disease may also involve perianal, upper gastrointestinal, and extraintestinal organs.

Gastrointestinal

  • Diarrhea affects 82% of people at the onset of Crohn's disease, with severity ranging from mild to severe enough to require substitution of water and electrolytes. With Crohn's disease, diarrhea is frequent and urgent rather than voluminous.
  • Abdominal pain affects at least 70% of people during the course of Crohn's disease. It can result directly from intestinal inflammation, or from complications such as strictures and fistulas. Pain most commonly occurs in the lower right abdomen.
  • Rectal bleeding is less common than in ulcerative colitis, and is more likely to occur with inflammation in the colon or rectum. Bleeding in the colon or rectum is bright red, whereas bleeding in higher segments causes dark or black stools.
  • Bloating, flatus, and other symptoms of irritable bowel syndrome occur in 41% of people in remission.
  • Perianal involvement occurs in 18–43% of cases, more frequently if the colon and rectum are inflamed, and can cause fistulas, skin tags, hemorrhoids, fissures, ulcers, and strictures.
  • Upper gastrointestinal involvement is rare, occurring in 0.5-16% of cases, and may cause symptoms such as pain while swallowing, difficulty swallowing, vomiting, and nausea.

Systemic

Crohn's disease often presents with systemic symptoms, including:

  • Chronic fatigue, which lasts for at least 6 months and cannot be cured by rest, occurs in 80% of people with Crohn's disease, including 30% of people who are in remission.
  • Fevers, typically low-grade, are often reported as initial symptoms of Crohn's disease. High-grade fevers are often a result of abscesses.
  • Weight loss often occurs due to diarrhea and reduced appetite.

Extraintestinal

Extraintestinal manifestations occur in 21–47% of cases, and include symptoms such as:

Complications

Image of colon cancer identified during a colonoscopy in Crohn's disease.
Image of colon cancer identified in the sigmoid colon of a person with Crohn's disease during a colonoscopy.

Bowel damage due to inflammation occurs in half of cases within 10 years of diagnosis, and can lead to stricturing or penetrating disease forms. This can cause complications such as:

Malnutrition occurs in 38.9% of people in remission and 82.8% of people with active disease due to malabsorption in the small intestine, reduced appetite, and drug interactions. This can cause complications such as:

Intestinal cancers may develop as a result of prolonged or severe inflammation. This includes:

  • Colorectal cancer has a prevalence of 7% at 30 years after diagnosis and accounts for 15% of deaths in people with Crohn's. Risk is higher if the disease occurs in most of the colon. Endoscopic surveillance is performed to detect and remove polyps, while surgery is required for dysplasia beyond the mucosal surface.
  • Small bowel cancer has a prevalence of 1.6%, at least 12-times greater in people with Crohn's disease. Unlike colorectal cancer, endoscopic surveillance is ineffective and not recommended for small bowel cancer.

Causes

Risk factors

Smoking is a major modifiable risk factor for Crohn's disease, particularly in Western countries, where it doubles the risk. This risk is higher in females and varies with age. Smoking is also linked to earlier disease onset, increased need for immunosuppression, more surgeries, and higher recurrence rates. Ethnic differences have been noted, with studies in Japan linking passive smoking to the disease. Proposed mechanisms for smoking's effects include impaired autophagy, direct toxicity to immune cells, and changes in the microbiome.

Diet may influence the development of Crohn's disease by affecting the gut microbiome. The shift from high-fiber, low-fat foods to processed foods reduces microbiota diversity, increasing the risk of Crohn's disease. Conversely, high-fiber diets may reduce risk by up to 40%, likely due to the production of anti-inflammatory short-chain fatty acids from fiber metabolism by gut bacteria. The Mediterranean diet is also linked to a lower risk of later-onset Crohn's disease. Since diet's effect on the microbiome is temporary, its role in gut dysbiosis is controversial.

Childhood antibiotic exposure is linked to a higher risk of Crohn's disease due to changes in the intestinal microbiome, which shapes the immune system in early life. Other medications, like oral contraceptives, aspirin, and NSAIDs, may also increase risk by up to two-fold. Conversely, breastfeeding and statin use may reduce risk, though breastfeeding's effects are inconsistent. Early life factors such as mode of delivery, pet exposure, and infections—related to the hygiene hypothesis—also significantly influence risk, likely due to influences on the microbiome.

Genetics

Genetics significantly influences the risk of Crohn's disease. First-degree relatives of affected individuals have a five-fold increased risk, while identical twins have a 38–50% risk if one twin is affected. Genome-wide association studies have identified around 200 loci linked to Crohn's, most found in non-coding regions that regulate gene expression and overlap with other immune-related conditions, such as ankylosing spondylitis and psoriasis. While genetics can predict disease location, it does not determine complications like stricturing. A substantial portion of inherited risk is attributed to a few key polymorphisms.

  • NOD2 mutations are the primary genetic risk factor for ileal Crohn's disease, impairing the function of immune cells, particularly Paneth cells. These mutations are found in 10–27% of individuals with Crohn's disease, predominantly in Caucasian populations. Heterozygotes (one mutated copy) have a three-fold risk, while homozygotes (two copies) have a 20–40 fold risk.
  • ATG16L1 mutations impair autophagy and immune defense, and are more common in Caucasians.
  • IL23R mutations increase inflammatory signaling of the interleukin-23 pathway, and are more common in Caucasians.
  • TNFSF15 mutations are the primary genetic risk factor in Asian populations.
  • IL10RA mutations impair the anti-inflammatory signaling of interleukin-10, causing early-onset Crohn's disease with high penetrance.

Mechanism

diagram of mechanism of Crohn's disease
The intestinal barrier and immune system in health and during Crohn's disease. In health, immune cells secrete TGFβ and retinoic acid to promote the differentiation of Tregs, which regulate the inflammatory behavior of effector T cells. During Crohn's disease, microbiome alterations, intestinal barrier permeability, and deficient innate immunity enable pathogens to enter the gut tissue. This causes antigen-presenting cells to upregulate IL-12, IL-18, and IL-23, increasing the differentiation of Th1 and Th17 cells. These cells secrete inflammatory cytokines such as IL-17, IFNγ, and TNF to perpetuate inflammation.

Crohn's disease is believed to be caused by a dysregulated immune response to gut bacteria, though the exact mechanism is unknown. This is evidenced by the disease's links to genes involved in bacteria defense and its occurrence in the ileum and colon, the most bacteria-dense segments of the intestine. In Crohn's disease, a permeable intestinal barrier and a deficient innate immune response enable bacteria to enter intestinal tissue, causing an excessive inflammatory response from T helper 1 (Th1) and T helper 17 (Th17) cells. An altered microbiome may also be causatory and serve as the link to environmental factors.

Intestinal barrier

The epithelial barrier is a single layer of epithelial cells covered in antimicrobial mucus that protects the intestine from gut bacteria. Epithelial cells are joined by tight junction proteins, which are reduced by Crohn's-linked polymorphisms. In particular, claudin-5 and claudin-8 are reduced, while pore-forming claudin-2 is increased, causing intestinal permeability. Epithelial cells under stress emit inflammatory signals such as the unfolded protein response to stimulate the immune system, and Crohn's-linked polymorphisms to the ATG16L1 gene lower the threshold at which this response is triggered.

In a functional state, the intestinal epithelium and IgA dimers work together to manage and keep the luminal microflora distinct from the mucosal immune system. Paneth cells exist in the epithelial barrier of the small intestine and secrete α-defensins to prevent bacteria from entering gut tissue. Genetic polymorphisms associated with Crohn's disease can impair this ability and lead to Crohn's disease in the ileum. NOD2 is a receptor produced by Paneth cells to sense bacteria, and mutations to NOD2 can inhibit the antimicrobial activity of Paneth cells. ATG16L1, IRGM, and LRRK2 are proteins involved in selective autophagy, the mechanism by which Paneth cells secrete α-defensins, and mutations to these genes also impair the antimicrobial activity of Paneth cells.

Intraepithelial lymphocytes (IELs) are immune cells that exist in the epithelial barrier, consisting mostly of activated T cells. They interact with gut bacteria directly and emit signals to regulate the intestinal immune system. IELs in Crohn's disease produce increased levels of inflammatory cytokines IL-17, IFNγ, and TNF. It is hypothesized that inflammatory signals from the immune system and alterations to the gut microbiome influence IELs to produce inflammatory signals, contributing to Crohn's disease.

Immune system

Normally, intestinal macrophages have reduced inflammatory behavior while retaining their ability to consume and destroy pathogens. In Crohn's disease, the number and activity of macrophages is reduced, enabling the entrance of pathogens into intestinal tissue. Macrophages degrade internal pathogens through autophagy, which is impaired by Crohn's-linked polymorphisms in genes such as NOD2 and ATG16L1. Additionally, people with Crohn's tend to have a separate abnormal population of macrophages that secrete proinflammatory cytokines such as TNF and IL-6.

Neutrophils are recruited from the bloodstream in response to inflammatory signals, and defend tissue by secreting antimicrobial substances and consuming pathogens. In Crohn's disease, neutrophil recruitment is delayed and autophagy is impaired, allowing bacteria to survive in intestinal tissue. Dysfunction in neutrophil secretion of reactive oxygen species, which are toxic to bacteria, is associated with very early onset Crohn's disease. Although neutrophils are important in bacterial defense, their subsequent accumulation in Crohn's disease damages the epithelial barrier and perpetuates inflammation.

Innate lymphoid cells (ILCs) consist of subtypes including ILC1s, ILC2s, and ILC3s. ILC3s are particularly important for regenerating the epithelial barrier through secretion of IL-17 by NCR- ILC3s and IL-22 by NCR+ ILC3s. During Crohn's disease, inflammatory signals from antigen-presenting cells, such as IL-23, cause excessive IL-17 and IL-22 secretion. Although these cytokines protect the intestinal barrier, excessive production damages the barrier through increased inflammation and neutrophil recruitment. Additionally, IL-12 from activated dendritic cells influence NCR+ ILC3s to transform into inflammatory IFNγ-producing ILC1s.

Naive T cells are activated primarily by dendritic cells, which then differentiate into anti-inflammatory T regulatory cells (Tregs) or inflammatory T helper cells to maintain balance. In Crohn's disease, macrophages and antigen-presenting cells secrete IL-12, IL-18, and IL-23 in response to pathogens, increasing Th1 and T17 differentiation and promoting inflammation via IL-17, IFNγ and TNF. IL-23 is particularly important, and IL-23 receptor polymorphisms that increase activity are linked with Crohn's disease. Tregs suppress inflammation via IL-10, and mutations to IL-10 and its receptor cause very early onset Crohn's disease.

Microbiome

People with Crohn's disease tend to have altered microbiomes, although no disease-specific microorganisms have been identified. An altered microbiome may link environmental factors with Crohn's, though causality is uncertain. Firmicutes tend to be reduced, particularly Faecalibacterium prausnitzii, which produces short-chain fatty acids that reduce inflammation. Bacteroidetes and proteobacteria tend to be increased, particularly adherent-invasive E. coli, which attaches to intestinal epithelial cells. Additionally, mucolytic and sulfate-reducing bacteria are elevated, contributing to damage to the intestinal barrier.

Alterations in gut viral and fungal communities may contribute to Crohn's disease. Caudovirales bacteriophage sequences found in children with Crohn's suggest a potential biomarker for early-onset disease. A meta-analysis showed lower viral diversity in Crohn's patients compared to healthy individuals, with increased Synechococcus phage S CBS1 and Retroviridae viruses. Additionally, a Japanese study found that the fungal microbiota in Crohn's patients differs significantly from that of healthy individuals, particularly with an abundance of Candida.

Diagnosis

Diagnosis of Crohn's disease may be challenging since its symptoms overlap with other gastrointestinal diseases. An accurate diagnosis requires a combined assessment of clinical history, physical examination, and diagnostic tests.

Endoscopy

Image of deep ulcers in the colon of a person with Crohn's colitis.
Image of a colon showing deep ulceration due to Crohn's disease.
Image of a serpiginous ulcer due to Crohn's disease found during a colonoscopy.
Image of a serpiginous ulcer in the colon, a classic finding in Crohn's disease

Ileocolonoscopy is the primary procedure for diagnosing Crohn's disease in the ileum and colon, accurately identifying it in about 90% of cases. During this exam, doctors closely examine the intestinal lining and take small tissue samples for further testing. Signs of Crohn's disease include uneven inflammation and 'skip lesions', which are patches of inflammation separated by healthy tissue. The ulcers can be small (less than 5 mm) or larger (over 5 mm), often appearing cobblestone-like. Their depth helps determine disease severity. Unlike ulcerative colitis, Crohn's disease usually does not affect the rectum or cause continuous inflammation around the bowel.

In certain cases, such as disease in the upper small bowel, standard colonoscopy may be ineffective. Physicians may then opt for device-assisted enteroscopy or capsule endoscopy. While capsule endoscopy is effective in detecting abnormalities, it may not reliably diagnose Crohn's disease and carries a risk of retention, which is about 1.6% when Crohn's disease is suspected and increases to 13% if already diagnosed. To reduce this risk, physicians typically perform small-bowel imaging and use a patency capsule that disintegrates within 48 to 72 hours. Once the patency capsule has passed through the intestine, capsule endoscopy may be performed.

Device-assisted enteroscopy is not typically the first choice for diagnosing small-bowel Crohn's disease due to its invasiveness and higher costs. The procedure closely examines the small intestine using specialized tools, such as longer endoscopes or balloon-assisted devices, making it easier for doctors to visualize and treat issues. It often requires sedation and is generally reserved for patients needing a tissue sample or immediate treatment.

Cross-sectional Imaging

CT scan of Crohn's disease in the fundus of the stomach.
CT scan showing Crohn's disease in the stomach

Cross-sectional imaging techniques, like bowel ultrasonography (BUS), CT enterography (CTE), and MRI enterography (MRE), are essential for understanding how extensive Crohn's disease is and whether there are any complications, like blockages or abnormal connections between organs. All three methods are quite accurate for diagnosing Crohn's disease and spotting these complications.

  • CTE involves radiation and requires the use of contrast agents (substances that help show details in images). Despite this, CTE is very effective, with over 80% accuracy in diagnosing the disease and its complications, including blockages and fistulas (abnormal connections).
  • MRE is particularly good for detecting intestinal narrowing, with 89% sensitivity and 94% specificity. It is the preferred option for examining fistulas and abscesses in the pelvic area.
  • BUS is a non-invasive method that doesn't involve radiation and is effective for assessing the intestinal wall and related issues, such as fistulas and abscesses. Despite its limitations, it can accurately identify signs of Crohn's disease when the bowel wall thickens to more than 3 mm, achieving high accuracy rates (88–100%) when also considering factors like fistulas and abscesses.

Histology

Tissue stain of a granuloma due to Crohn's disease.
Tissue stain of a granuloma in the colonic mucosa due to Crohn's disease, consisting of an aggregate of histiocytes in the center of the image.
Tissue stain of colon showing deep inflammation across all layers.
Tissue stain of colon showing deep inflammation across all layers.

The most reliable way to confirm a diagnosis of Crohn's disease is through a histological examination of biopsy samples or tissue removed during surgery. This process helps distinguish Crohn's disease from ulcerative colitis and other types of colitis, particularly infections. While no features are unique to Crohn's disease, typical signs include patchy chronic inflammation, irregularities in the intestinal lining, granulomas (not related to tissue injury), and abnormal villi structure in the terminal ileum. A pathologist specializing in inflammatory bowel disease is important for accurate Crohn's disease diagnoses. Even if biopsy results are unclear, doctors can still suggest a Crohn's disease diagnosis based on clinical symptoms, endoscopic findings, and imaging results.

Disease activity indexes

The Crohn's Disease Activity Index (CDAI) is a scoring system to assess the symptoms associated with Crohn's disease. It assigns a score based on eight clinical factors, including overall well-being, frequency of loose stools, abdominal pain, presence of abdominal masses, changes in weight, low hemoglobin levels, and use of opiates for diarrhea. The CDAI is primarily used in clinical trials to evaluate the effectiveness of treatments and to determine whether the disease is in remission. This is particularly significant, as approximately 50% of patients who report feeling well may still exhibit signs of active disease in the intestine, while some patients with symptoms may present with normal intestinal findings.

The Harvey–Bradshaw Index (HBI) provides a more streamlined approach by assessing only clinical factors, thus eliminating the need for laboratory tests. Neither the CDAI nor the HBI incorporates diagnostic procedures such as endoscopies or imaging studies; instead, they focus exclusively on symptom tracking. The HBI is generally considered easier to apply than the CDAI and may be more suitable for certain clinical trials and routine practice due to its simplicity in calculation and reduced reliance on patient recall of symptoms.

The Crohn's Disease Endoscopic Index of Severity (CDEIS) is a scoring system used during endoscopy to evaluate Crohn's disease severity. It assesses six factors: deep and shallow ulcers, nonulcerated and ulcerated stenosis, the area covered by ulcers, and the overall disease-affected area across five intestinal sections. Scores range from 0 to 44, with higher scores indicating more severe disease. While often seen as the standard for measuring severity, CDEIS can be complex to calculate and may underestimate severity if only one segment, particularly the ileum, is affected. There are also no clear score cutoffs for specific outcomes or treatment responses, limiting its effectiveness in determining remission.

The Simple Endoscopic Score for Crohn's Disease (SES-CD) offers a more straightforward approach than the CDEIS scoring system, using four key factors to evaluate Crohn's disease during an endoscopy. These factors include the presence and size of ulcers, the area affected by ulcers, the overall extent of the disease, and any narrowing of the intestine (stenosis). The first three factors are scored from 0 to 3 in each of the five sections of the intestine, with a maximum score of 15 for each section. Stenosis is scored separately, ranging from 0 to 11. This results in a total SES-CD score that can range from 0 to 56, with higher scores indicating more severe disease.

Laboratory testing

While no lab test can definitively confirm or rule out Crohn's disease, results from serum and stool tests can help support the diagnosis:

  • The antimicrobial antibody ASCA is a well-known blood test marker used in the diagnosis of Crohn's disease. Approximately 60–70% of individuals with Crohn's disease test positive for ASCA, while only 10–15% of those with ulcerative colitis and less than 5% of patients with other types of colitis have positive results.
  • The autoantibody pANCA is found in 10–15% of Crohn's disease cases, in 60–70% of ulcerative colitis cases, and in less than 5% of patients with other types of colitis that aren't inflammatory bowel disease. Additionally, patients with Crohn's disease who test positive for pANCA often show symptoms similar to those of ulcerative colitis.
  • C-reactive protein (CRP) is a blood marker that indicates inflammation and can help monitor Crohn's disease activity. However, about one third of patients with active disease may have normal CRP levels, while one third with high levels of CRP have inactive disease. Moreover, CRP's ability to predict disease progression is not well established.
  • Fecal calprotectin is a stool test used to differentiate inflammatory bowel disease, like Crohn's disease, from irritable bowel syndrome. While there are no official cut-off values, it is commonly used to assess disease activity in Crohn's. Elevated levels may also indicate other intestinal infections or inflammatory conditions, not just Crohn's disease.

Differential diagnosis

Crohn's disease has similar endoscopic, radiographic and histological features with other inflammatory or infectious diseases. 10% of people with Crohn's disease are initially diagnosed with indeterminate colitis.

  • Behçet’s disease can cause intestinal inflammation, primarily featuring single ulcers and symptoms outside the intestines, which differ from Crohn's disease. Recurrent sores in the mouth and genitals raise suspicion for Behçet's. A pathergy test, where the skin is lightly pricked to check for a red bump or ulcer, can help confirm the diagnosis. Eye inflammation (uveitis) and skin issues are also common in Behçet's disease.
  • Intestinal lymphoma lacks symptoms that differentiate it from other conditions; diagnosis can only be confirmed through histological examination of tissue samples.
  • Intestinal tuberculosis can cause symptoms such as fever, night sweats, and ulcers in the transverse colon, along with a swollen ileocecal valve. Key tissue changes include granulomas, which may be caseating, confluent, or large. A positive smear test for acid-fast bacillus and imaging that detects necrotic lymph nodes are also important indicators of the disease.
  • Ischemic colitis is also a possible alternative diagnosis to Crohn's disease. It often shows swelling and redness of the inner lining of the colon, while the rectum usually remains unaffected.

Classification

The Montreal classification system is a widely used framework for categorizing the phenotypes of Crohn's disease. It considers three primary factors: the age at diagnosis (divided into three groups: less than 16 years, 17 to 40 years, and over 40 years), the location of the disease (which can be ileal, colonic, ileocolonic, or isolated upper), and the behavior of the disease (including non-stricturing/non-penetrating, stricturing, penetrating, and perianal types).

Management

The management of Crohn's disease is customized based on the severity, location, and behavior of the disease. Providers also assess the risk of aggressive disease to determine the need for more intensive treatment. Risk factors include diagnosis before age 30, extensive disease involvement, perianal complications, deep ulcers, and history of surgery. A key goal of treatment is to achieve mucosal healing, which restores the intestinal lining. Mucosal healing is linked to better outcomes, such as fewer flare-ups, reduced hospitalizations, steroid-free remission, and a longer interval without surgery.

Corticosteroids

Steroids are often used to quickly induce remission and relieve symptoms in Crohn's disease, but they are ineffective for maintaining remission. Options include intravenous steroids, prednisone, and budesonide, with budesonide preferred for its safety, though it's limited to mild to moderate cases in the ileum and right colon. Patients on systemic steroids should switch to other medications for long-term remission, as prolonged use can cause adrenal issues, weight gain, cataracts, hypertension, and diabetes. Additionally, systemic steroids may increase the risk of serious infections and mortality in moderate to severe Crohn's disease.

Conventional immunosuppressants

Thiopurines, like azathioprine and 6-mercaptopurine, maintain remission in Crohn's disease but do not induce it initially. Since thiopurines take 6 to 12 weeks to work, steroids are often used to manage symptoms during this time. Before starting thiopurines, liver metabolism is assessed and Epstein-Barr virus is tested in patients under 25. Around 15% to 20% of patients stop thiopurines due to side effects, including low blood cell counts, liver problems, nausea, vomiting, allergic reactions, and acute pancreatitis. Thiopurines also raise the risk of certain cancers and serious conditions, necessitating regular lab monitoring.

Methotrexate is used to induce and maintain remission in Crohn's disease, being slightly more effective than thiopurines and taking 8 to 16 weeks to work. About 17% of patients stop taking it due to side effects like nausea, vomiting, headaches, and fatigue. It can affect liver health and, rarely, lower blood cell counts, requiring regular blood tests. Methotrexate may also cause anemia and mouth sores, so daily folic acid is recommended. Additionally, it may increase the risk of certain skin cancers and lymphoma. Methotrexate is discontinued during pregnancy due to the risks of miscarriage and birth defects.

Biologics

Anti-TNF therapy is the most effective treatment for inducing and maintaining remission, with FDA-approved agents including infliximab, adalimumab, and certolizumab pegol. It blocks the inflammatory protein TNF and induces cell death in activated T cells. Responses may occur within a week, but full effects can take up to six weeks. Loss of response can happen due to the development of antidrug antibodies, necessitating a switch in agents or drug classes. Anti-TNF agents are often combined with thiopurines or methotrexate to minimize antibody development. Side effects include injection-site reactions, a higher risk of infection, a slight increase in melanoma risk, and rare cases of cytopenias and liver toxicity.

Vedolizumab is the first treatment designed specifically for the gut in moderate to severe Crohn's disease. It blocks the molecule α4β7 that helps white blood cells enter the gut, reducing inflammation. Unlike natalizumab, it does not carry a risk of the serious brain infection PML. While vedolizumab can induce remission, it works slowly, taking about 12 weeks to show effects, and its overall effectiveness is limited. However, patients who respond well can maintain remission for up to a year. Since it specifically targets the gut, it does not significantly increase the risk of serious side effects or infections, except for mild nasal infections.

Ustekinumab, approved for moderate to severe Crohn's disease in October 2016, has been FDA-approved for psoriasis since 2009. It appears to be comparable to anti-TNF therapy in both the induction and maintenance of remission, functioning by blocking the inflammatory molecules IL-12 and IL-23. The onset of action is similar to that of anti-TNF treatments, with responses typically observed within six weeks. Notably, Ustekinumab does not seem to increase the risk of serious infections, although the studies conducted in Crohn's disease have been relatively short-term.

The JAK inhibitor such as upadacitinib is approved for treatment of moderate to severe Crohn's disease, with a large multi-centre randomized control trial demonstrating its effectiveness in induction and maintenance of disease.

Surgery

Resected ileum from a person with Crohn's disease

Many individuals with Crohn's disease may require a bowel resection to remove part of the intestine due to blockages, lesions, infections, or ineffective medications. Since surgery is not a cure, the goal is to preserve as much of the small bowel as possible, and extensive resections can lead to short bowel syndrome. In cases with widespread strictures, only the most prominent stricture is typically resected, while minor strictures may be dilated through strictureplasty. After a resection, the healthy ends of the intestine are rejoined in a primary anastomosis.

Approximately six to twelve months after surgery, patients usually undergo a colonoscopy to check for inflammation, using the Rutgeerts scoring system to assess the likelihood of recurrence. About 50% may experience a return of symptoms within five years, and nearly 40% may need a second surgery within ten years, often due to inflammation near the anastomosis. While drug therapy aims to prevent recurrences, its effectiveness remains uncertain.

Diet

  • Enteral nutrition, which administers nutrients as a powder or liquid, is the primary method for inducing remission in children with Crohn's disease. It can induce remission in up to 80% of cases. Outside of Japan, it is not used to treat Crohn's disease in adults due to unpalatable formulations.
  • Parenteral nutrition, which administers nutrients directly into the bloodstream, may be used to supply nutrients to patients when there is extensive inflammation that impairs absorption. Parenteral nutrition has the same effectiveness as enteral nutrition in inducing remission.
  • The Mediterranean diet, rich in fruits, vegetables, unsaturated fats, and lean protein, is beneficial to general health but has not been found to reduce the rate of flares in Crohn's disease.
  • Cooking and processing fruits and vegetables to reduce fibrousness increases tolerance of those foods in people with intestinal strictures.

Other treatments

  • Mesalamine is not effective for inducing or maintaining remission in Crohn's disease, but is nevertheless commonly used as a treatment due to its perceived benefits and low risk of side effects.
  • Antibiotics are not effective in inducing or maintaining remission in Crohn's disease. However, they are effective in treating perianal fistulas and inflammation when used alongside anti-TNF therapy.
  • Fecal microbiota transplants have shown potential effectiveness in preliminary studies. However, larger studies are needed to verify its efficacy.
  • Acupuncture influences the immune system by stimulating the vagus nerve. Early studies have shown efficacy in improving clinical symptoms, but larger studies are needed.
  • Cannabis is a potential therapy for Crohn's disease by targeting the endocannabinoid system. Although it has shown benefits in animal models, its efficacy as a treatment is uncertain.
  • Cognitive behavioral therapy has shown short-term positive psychological effects in people with Crohn's disease, but it has no long-term effect on physical or psychological health.

Outlook

Crohn's disease is a chronic condition requiring ongoing management, as there is currently no cure. Inflammation is typically controlled through medications such as steroids and immunosuppressants, and in severe cases, surgery may be necessary. The clinical course of the disease is classified into four patterns:

  • Remission: Severity decreases in response to treatment, leading to sustained remission.
  • Improved and Stable: Severity lessens, but mild inflammation persists.
  • Relapsing: The disease fluctuates between periods of remission and severe inflammation.
  • Refractory: Severe inflammation continues without respite.

Approximately 40% to 56% of individuals with Crohn's disease achieve clinical remission after one year of infliximab treatment, increasing to 56% to 58% when combined with an immunosuppressant. Furthermore, 16% to 39% attain both clinical and endoscopic remission, showing no signs of inflammation in the intestine. Once in remission, individuals have an 80% chance of maintaining this state for the following year. Conversely, 10% to 15% of individuals may experience ongoing active disease without remission.

Chronic inflammation from Crohn's disease increases the risk of heart problems, cancers, arthritis, osteoporosis (weakened bones), and mental health issues. Some medications can also raise the chances of infections and cancers. Because of these combined risks, people with Crohn's disease tend to have a shorter lifespan compared to those who are healthy. In Canada, studies show that women affected with Crohn's disease live about 7.7 years less than unaffected women, and affected men live about 7.7 years less than otherwise expected.

Epidemiology

Crohn's disease is most prevalent in North America and Western Europe, particularly among Ashkenazi jews and possibly more common in women. The annual incidence in North America is 0–20.2 new cases per 100,000 people, while incidence in Europe is 0.3–12.7 per 100,000. The prevalence of Crohn's disease is 322 per 100,000 in Germany, 319 per 100,000 in Canada, and 300 per 100,000 in the United States. The prevalence of Crohn's disease has risen in newly industrialized countries, with rates of 18.6 per 100,000 in Hong Kong and 3.9 per 100,000 in Taiwan.

The typical age of onset is between 20 and 30 years, with a smaller peak around 50 years, leading to a median onset age of 30. About 20 to 25% of patients presenting with inflammatory bowel disease are children under 18 years old, while 80% are adolescents. Additionally, the incidence of Crohn's disease in children is on the rise, with 2.5–11.4 new cases per 100,000 and a prevalence of 58 per 100,000.

History

Giovanni Battista Morgagni, often referred to as the father of anatomic pathology, provided one of the earliest detailed accounts of the disease in his 1761 treatise, noting specific autopsy findings in a young patient who suffered from severe gastrointestinal symptoms.

The first notable series of cases of Crohn's disease was reported by Polish surgeon Antoni Leśniowski in 1903, followed by Scottish surgeon Thomas Kennedy Dalziel in 1913, who described nine patients exhibiting significant pathological features treated by surgical resection. However, the disease only gained widespread recognition with a landmark 1932 article by Burrill B. Crohn, Leon Ginzburg, and Gordon D. Oppenheimer. In this publication, they introduced the term "regional ileitis" based on their observations of chronic inflammation in the terminal ileum of 14 patients.

Over the following decades, Crohn's disease was recognized as affecting various parts of the gastrointestinal tract, with reports of involvement from the esophagus to the colon. This period also marked the identification of skip lesions—areas of healthy bowel between diseased sections—adding to the understanding of the disease's pathology. Public awareness of Crohn's disease increased significantly after President Eisenhower underwent surgery for the condition in 1956, which highlighted its impact on quality of life and encouraged discussions about the disease.

In 1960, ulcerative colitis and Crohn's colitis were officially classified as distinct diseases, despite lingering beliefs that Crohn's disease could not manifest in the colon. During this decade, advancements such as fiberoptic colonoscopy and the capability to perform biopsies significantly enhanced the diagnosis and management of Crohn's disease, facilitating improved visualization of the gastrointestinal tract and more accurate assessments of disease severity. Subsequent decades saw the testing of various medications for Crohn's disease in clinical trials, including the identification of methotrexate's efficacy in 1989.

In the 1990s, the focus of treatment for Crohn's disease began to shift towards biologic therapies, particularly anti-TNF agents. Concurrently, nutritional therapy gained prominence in managing pediatric cases and instances of malnutrition. The introduction of MRI enterography emerged as a safe and effective method for monitoring disease activity. This was further augmented by the FDA's approval of capsule endoscopy in 2001, which allowed for improved imaging of the small intestine. Since the inception of genome-wide association studies in 2005, several genetic markers associated with Crohn's disease have been identified, contributing to a deeper understanding of the condition.

Support organizations such as the Crohn's & Colitis Foundation have also emerged, providing resources and community for patients, helping to raise awareness and funding for research initiatives. Today, Crohn's disease continues to be a focus of extensive research, aiming to improve treatment outcomes and enhance the quality of life for those affected.

Etymology

Crohn's disease is named after Dr. Burrill Crohn, though its eponymous association arose from complex circumstances. Initially, researchers Ginzburg and Oppenheimer identified a pattern of the disease and compiled 12 cases, all linked to surgeon A. A. Berg. However, Berg declined authorship due to his lack of prior involvement. Ginzburg and Oppenheimer then connected with Crohn, who received the manuscript, which was later published with his name listed first and two additional cases included.

Originally, the disease was referred to as "regional ileitis," reflecting the findings of the time, but subsequent reports revealed its presence throughout the gastrointestinal tract, leading to the adoption of the eponym. In Poland, it was historically called “Lesniowski-Crohn's disease.” There has been growing criticism of medical eponyms for their inaccuracies, prompting a movement towards using non-possessive forms, such as "Crohn disease," which has gained traction in recent years among academic and medical publications.

Anti-art

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