text: The 2018 Siena poll of 157 presidential scholars reported George Washington, Franklin D. Roosevelt, Abraham Lincoln, Theodore Roosevelt, and Thomas Jefferson as the top five US presidents, with SCRI director Don Levy stating, "The top five, Mount Rushmore plus FDR, is carved in granite with presidential historians..." Donald Trump—entering the SCRI survey for the first time—joined Andrew Johnson, James Buchanan, Warren G. Harding, and Franklin Pierce among the bottom five US presidents. George W. Bush, whom presidential scholars had rated among the bottom five in the previous 2010 survey, improved in position to the bottom of the third quartile. A 2021 C-SPAN poll continued a recent rehabilitation of Ulysses Grant, with Bush improving yet again, Obama remaining high and Trump near the bottom.


title: Historical rankings of presidents of the United States

text: Note: click the "sort" icon at the head of each column to view the rankings for each survey in numerical order.


text: The Murray–Blessing 1982 survey asked historians whether they were liberal or conservative on domestic, social, and economic issues. The table below shows that the two groups had only small differences in ranking the best and worst presidents. Both groups agreed on the composition of nine of the top ten presidents (and were split over the inclusion of either Lyndon B. Johnson or Dwight D. Eisenhower) and six of the worst seven (split over Jimmy Carter or Calvin Coolidge).


text: In September/October 2010, the United States Presidency Centre (USPC) of the Institute for the Study of the Americas at the University of London surveyed 47 British specialists on American history and politics. Presidents were rated from 1 to 10 in five categories:


text: William Henry Harrison (1841) and James Garfield (1881) were not rated because they died shortly after taking office. Barack Obama (2009–) ranked 8th in interim ranking as of January 2011, but was not counted in the final results (and thus did not affect the rankings of other presidents) because he had yet to complete a term.


text: Franklin D. Roosevelt (1933–1945) came in first overall and in the categories of vision/agenda, domestic leadership, and foreign policy leadership. Washington came in first for moral authority; Lincoln for his legacy. Morgan believes it is likely that Roosevelt's ranking (which only marginally surpassed Lincoln's) rose because the poll was conducted during the worst economic troubles since the 1930s.


text: Of presidents since 1960, only Ronald Reagan and (in interim results) Barack Obama placed in the top ten; Obama was the highest-ranked president since Harry Truman (1945–1953). Most of the other recent presidents held middling positions, though George W. Bush placed in the bottom ten, the lowest-ranked president since Warren Harding (1921–1923). Lyndon Johnson (1963–1969) "would have been placed much higher in recognition of his civil rights achievement but for the corrosive effect of Vietnam on his foreign policy and moral authority scores." As with US polls, the bottom five (other than Harding) were president before and after the Civil War.


text: One of the more significant differences from American polls is the relatively low ranking of John F. Kennedy (1961–1963), who placed fifteenth. British academics "seemingly faulted JFK for the gap between his rhetoric and his substantive achievements as president."


text: In 2016, the Presidential History Network surveyed 71 named British and Irish specialists. The questions were the same as in the USPC survey, which was directed by some of the same people. Some respondents did not rate presidents that they were not familiar with. The minimum number of responses (62) were for the rather obscure and inconsequential presidents Hayes, Arthur, Cleveland, and Benjamin Harrison. 69–70 rated all recent presidents, from FDR on.


text: The poll was initiated in 1982 and occurs one year into the term of each new president. It is currently a survey of 157 presidential scholars across a range of leadership parameters.


text: The ranking awarded the top five spots to George Washington, Franklin Roosevelt, Abraham Lincoln, Theodore Roosevelt, and Thomas Jefferson, in keeping with prior surveys. Washington had been ranked fourth in all previous surveys, and Franklin Roosevelt first.


text: The Siena College Research Institute released their seventh poll results on June 22, 2022. The best and worst 10% remain unchanged from their 2018 poll (top five: F. D. Roosevelt, Lincoln, Washington, T. Roosevelt, Jefferson; bottom five: Andrew Johnson, Buchanan, Trump, Harding, Pierce). 41% of the scholars polled said that if a president were to be added to Mount Rushmore, it should be FDR. 63% believed that the president should be elected by a national popular vote, versus 17% support for the Electoral College.


text: A year into his term, Joe Biden entered the ranking in the second quartile, at #19 out of 45. Among recent presidents, George H. W. Bush, Bill Clinton and Barack Obama moved up in the rankings, while George W. Bush and Donald Trump moved down, though part of the downward shift was due to the addition of a new president to the poll; counting from the other direction, Trump remained unchanged at third place from last. The changes were relatively small (one or two places), apart from Obama, who moved up six places (14%) to #11, in the first quartile. Notable shifts among earlier presidents included the continuing rehabilitation of Lyndon Johnson, up 8 places into the first quartile, and of Ulysses Grant, up 3 places (up 8 in the individual evaluations) into the second quartile; and the lessening appreciation of Andrew Jackson, down 4 places to the median (down 7, into the third quartile, in the individual evaluations); Ronald Reagan, down 5 places, remaining in the second quartile; and Zachary Taylor, down 6 places into the fourth quartile.


text: Professors Hanes Walton Jr. and Robert Smith conducted a poll in 2002 for their book "American Politics and the African American Quest for Universal Freedom", where 44 African-American political scientists and historians ranked presidents for their personal and institutional racism against their policies to counter racial subordination. The polls have been updated for subsequent editions of the book. The results (through Donald Trump) were as follows. Note that "white supremacist" refers to personal "belief"; the other categories refer to policy.


text: In May 2019, Dr. Alvin Tillery of the Center for the Study of Diversity and Democracy at Northwestern University and Dr. Christina Greer of Fordham University "conducted a poll of 113 academic researchers and asked them to rate the 14 modern presidents on both their overall leadership and rhetoric on diversity and inclusion using a scale ranging from 0 to 100." Survey respondents were significantly more liberal than the national average, "with only 13 percent of the respondents describing themselves as either moderate, slightly conservative, or conservative."


text: A Gallup poll taken on November 19–21, 2010, asked 1,037 Americans to say, based on what they know or remember about the nine most recent former presidents, whether they approve or disapprove of how each handled his job in office.


text: A Gallup poll about presidential greatness taken February 2–5, 2011, asked 1,015 American adults the following question: "Who do you regard as the greatest United States president?"


text: A Public Policy Polling poll taken between September 8–11, 2011, asked 665 American voters, based on what they know or remember about the nine then-most recent former presidents, whether they hold favorable or unfavorable views of how each handled his job in office.


text: A Vision Critical/Angus Reid Public Opinion poll taken on February 18–19, 2011, asked 1,010 respondents about 11 former presidents plus the current president and whether each was a good or bad president.


text: A Gallup poll taken November 7–10, 2013, asked 1,039 American adults the following question: "How do you think each of the following presidents will go down in history—as an outstanding president, above average, average, below average, or poor?".


text: A Quinnipiac University poll taken June 24–30, 2014, asked 1,446 American registered voters who they believed were the best and worst presidents since World War II.


text: Four years later, a Quinnipiac University poll taken January 20–25, 2017, asked 1,190 American voters who they believed were the best and worst presidents since World War II.


text: Including President Donald Trump for the first time, a Morning Consult poll taken February 9–10, 2017, asked 1,791 American registered voters who they believed were the best and worst presidents since World War II.


text: A Quinnipiac University poll taken March 3–5, 2018, asked 1,122 American voters who they believed were the best and worst presidents since World War II.


text: A Gallup poll taken January 4–15, 2021, asked 1,023 American adults the following question: "How do you think each of the following presidents will go down in history—as an outstanding president, above average, average, below average, or poor?"


text: In November 2014, Henry L. Roediger III and K. Andrew DeSoto published a study in the journal "Science" asking research subjects to name as many presidents as possible. They reported data from three generations as well as from an online survey conducted . The percentage of participants in the online survey sample who could name each president was the following:


text: David Herbert Donald, noted biographer of Abraham Lincoln, relates that when he met John F. Kennedy in 1961, Kennedy voiced his deep dissatisfaction and resentment with historians who had rated some of his predecessors. Kennedy remarked, "No one has a right to grade a president—even poor James Buchanan—who has not sat in his chair, examined the mail and information that came across his desk, and learned why he made his decisions." Historian and political scientist Julian E. Zelizer has argued that traditional presidential rankings explain little concerning actual presidential history and that they are "weak mechanisms for evaluating what has taken place in the White House." The broadly static nature of the rankings over multiple decades has also been called into question, particularly given the frequent exposure of previously unknown material about American government.


text: In 2002, Ron Walters, former director of the University of Maryland's African American Leadership Institute, stated that ranking based on the presidents' ability to balance the interests of the majority and those of excluded groups was practical in respect to American debate on racial politics. Presidents have traditionally been ranked on personal qualities and their leadership ability to solve problems that move the nation in a positive direction. Walters stated that there was a qualitative difference between presidential evaluations from white and African-American intellectuals. He gives as an example of this difference a comparison between two contemporary studies, a 1996 "New York Times" poll by Arthur M. Schlesinger Jr., where 31 white historians and one black historian ranked presidents as "Great", "Near Great", "High Average", "Average", "Below Average", or "Failure", and a survey performed by professors Hanes Walton Jr. and Robert Smith and featured in their book "American Politics and the African American Quest for Universal Freedom", where 44 African-American political scientists and historians ranked presidents as "White Supremacist", "Racist", "Racially Neutral", "Racially Ambivalent", or "Antiracist".


text: A 2012 analysis by Mark Zachary Taylor faulted presidential surveys with "partisan bias and subjective judgments", suggesting an algorithm to rank of the presidents based on objectively measurable economic statistics. The results placed Franklin Roosevelt as the best president for the economy, followed by Harding, Hayes and McKinley tied for second. The worst-ranked presidents were Hoover and Van Buren, tied.


text: A common criticism of presidential surveys is that participants are "driven by liberal bias to give high ratings to presidents who expanded the role of government." The first British survey, published in 2011, places some small government advocates higher than recent US surveys have: Thomas Jefferson at 4, Ronald Reagan at 8, and Andrew Jackson at 9 (compare 7, 10 and 13 in C-SPAN 2009).


text: Alvin S. Felzenberg, a professor at both the Elliot School of International Affairs at George Washington University and the Annenberg School for Communication at the University of Pennsylvania, is one of those who has criticized what he sees as a liberal bias in presidential rankings. In particular, he ranks Ronald Reagan in third place, substantially higher than averaged rankings. In his 2010 review of Felzenberg's 2008 book "The Leaders We Deserved (and a Few We Didn't)", Genovese says, "Felzenberg is upset—with some justification—at the liberal bias he sees as so prevalent in the ranking of U.S. presidents by historians and political scientists. To remedy this, he has provided a counter to the liberal bias with a conservative bias. In doing so, he commits all the sins of which he accuses liberals. This book is a mirror image of the work he finds so troubling...It is unscientific, impressionistic, and highly subjective."


title: Thandiwe Newton

text: Melanie Thandiwe Newton ( ; born 6 November 1972), formerly credited as Thandie Newton, is a British actress. Newton has received various awards, including a Primetime Emmy Award and a British Academy Film Award, in addition to nominations for two Golden Globe Awards. She was appointed Officer of the Order of the British Empire (OBE) in the 2019 New Year Honours for services to film and charity.


title: Thandiwe Newton

text: Newton is known for starring roles such as the title character in "Beloved" (1998), Nyah Nordoff-Hall in "" (2000), Tiffany in "Shade" (2003), Dame Vaako in "The Chronicles of Riddick" (2004), Christine in "Crash" (2004), for which she received a BAFTA Award for Best Actress in a Supporting Role, Linda in "The Pursuit of Happyness" (2006), Libby in "Run Fatboy Run" (2007), Stella in "RockNRolla" (2008), Condoleezza Rice in "W." (2008), Laura Wilson in "2012" (2009), Tangie Adrose in "For Colored Girls" (2010), and Val in "" (2018).


title: Thandiwe Newton

text: Since 2016, Newton has played a sentient android, the madam Maeve Millay, in the HBO science fiction-western series "Westworld", for which she received a Primetime Emmy Award for Outstanding Supporting Actress in a Drama Series and two Critics Choice Awards, as well as nominations for a Golden Globe Award, Saturn Award, and Screen Actors Guild Award. In 2017, she portrayed DCI Roz Huntley in the BBC drama series "Line of Duty", which earned her a nomination for the British Academy Television Award for Best Actress.


title: Thandiwe Newton

text: Newton was born in Westminster, to Nyasha Jombe, a Zimbabwean member of a Shona chieftaincy family, and Nick Newton, an English laboratory technician and artist. Her family had been living in Zambia and later returned there, where her younger brother was born. Her birthplace has been incorrectly reported to be Zambia in some sources, but she has confirmed in interviews that she was born in London. "Thandiwe" is a name of Nguni origin, meaning "beloved".


title: Thandiwe Newton

text: When she was three years old, the family returned to the United Kingdom, settling in Penzance, Cornwall, so her father could help run his family's antiques business. She attended St Mary's Roman Catholic Primary School. Newton remarked at a TED conference, "From about the age of five, I was aware that I didn't fit. I was the black, atheist kid in the all-white Catholic school run by nuns. I was an anomaly." She began dropping the letter "w" in "Thandiwe", leaving it as "Thandie", pronounced in English.


title: Thandiwe Newton

text: Newton was raised in London and Penzance. She studied dance at the Tring Park School for the Performing Arts. Between 1992 and 1995, Newton studied at Downing College, Cambridge, where she obtained a degree in social anthropology.


title: Thandiwe Newton

text: Newton made her film debut in the coming of age comedy-drama "Flirting" (1991), filmed in 1989 but shelved for two years. She was credited as "Thandie Newton" and subsequently continued to use this name professionally. She then portrayed the slave "Yvette" in the Brad Pitt/Tom Cruise film "Interview with the Vampire" (1994). Newton appeared in the Merchant Ivory production of "Jefferson in Paris" as Sally Hemings. Next, she played in Jonathan Demme's drama "Beloved" (1998), based on Toni Morrison's novel, in which she played the title character, the ghost of a young slave girl whose mother kills her to save her from slavery. The film also starred Oprah Winfrey and Danny Glover. Newton starred as Nyah Nordoff-Hall, again opposite Cruise, in "". Her next role was in the low-budget film "It Was an Accident", written by her husband, screenwriter Ol Parker.


title: Thandiwe Newton

text: Between 2003 and 2005, Newton played Makemba "Kem" Likasu, love interest of John Carter on the American television series "ER". She reprised the role for the series finale in 2009. In 2004, she also appeared in "The Chronicles of Riddick" and "Crash". She won a BAFTA award for Best Supporting Actress in 2006 for her role in "Crash". She played Chris Gardner's wife, Linda Gardner, in "The Pursuit of Happyness". Also in 2006, Newton performed on radio in a pantomime version of "Cinderella".


title: Thandiwe Newton

text: In 2007, Newton co-starred with Eddie Murphy as his love interest in the comedy "Norbit". She played opposite Simon Pegg as his ex-girlfriend in the 2008 comedy "Run Fatboy Run". She next portrayed Condoleezza Rice, US National Security Advisor and then Secretary of State in "W.", Oliver Stone's biography of President George W. Bush. The film was released in October 2008.


title: Thandiwe Newton

text: Newton was an introducer at Wembley Stadium on 7 July 2007, for the UK leg of Live Earth. She was due to introduce former US Vice President Al Gore to the concert, but he was delayed, leaving Newton to tell jokes in an attempt to entertain the audience. Newton next portrayed fictional US First Daughter Laura Wilson in "2012", a disaster film directed by Roland Emmerich and released 13 November 2009.


title: Thandiwe Newton

text: In July 2011, Newton delivered a TED talk on "Embracing otherness, embracing myself." She discussed finding her "otherness" as a child growing up in two distinct cultures, and as an actress playing many different selves. In 2012, she starred alongside Tyler Perry in the romantic drama film "Good Deeds". She was also in Perry's movie "For Colored Girls" (2010), adapted from Ntozake Shange's 1975 original choreopoem "for colored girls who have considered suicide / when the rainbow is enuf". In 2013, Newton starred in "Rogue", the first original drama series for DirecTV's Audience Network. She left "Rogue" during the third season. In 2015, she starred in the US miniseries "The Slap".


title: Thandiwe Newton

text: In 2016, Newton began portraying Maeve Millay in HBO science fiction drama series "Westworld", for which she won the Primetime Emmy Award for Outstanding Supporting Actress in a Drama Series, among other accolades. In 2017, she served as a narrator for the documentary entitled "Bill Cosby: Fall of an American Icon", an exposé on the sexual assault charges laid against Cosby, which aired on BBC One. In the same year, Newton played DCI Roseanne "Roz" Huntley in the fourth season of BBC One's "Line of Duty", a role for which she received a BAFTA TV Award nomination for Best Actress.


title: Thandiwe Newton

text: In a 2021 interview, Newton announced that her professional name had been misspelled for 30 years and she was finally correcting this, and would henceforth be known and credited as "Thandiwe Newton", beginning with "Reminiscence" (2021), and would have corrections applied to her past performance credits.


title: Thandiwe Newton

text: Newton married English writer, director, and producer Ol Parker in 1998. They have three children: two daughters, including Nico, and a son born in 2014. All three were home births. She is vegan and was named PETA's "Sexiest Vegan of 2014" in the UK.


title: Thandiwe Newton

text: In 2006, Newton contributed a foreword to "We Wish: Hopes and Dreams of Cornwall's Children", a book of children's writing published in aid of the NSPCC. In it, she wrote about her childhood memories of growing up in Cornwall, and the way in which the county's cultural heritage made it easy for her to "enrich every situation with layers of magic and meaning".


title: Thandiwe Newton

text: In 2007, Newton sold her near-new BMW X5 and replaced it with a Toyota Prius after Greenpeace stuck a "This gas-guzzling 4x4 is causing climate change" sticker on her BMW. In 2008, Newton visited poverty-stricken Mali, describing it as a "humbling experience". She visited the village of Nampasso in the Ségou Region of the country. In 2013, Newton led the One Billion Rising flash mob in London, for an end to violence, and for justice and gender equality.


title: Thandiwe Newton

text: David Schwimmer (who directed "Run Fatboy Run") called the actress "the queen of practical jokes". Newton has expressed an affinity for Buddhism.


title: Thandiwe Newton

text: In 2016, Newton stated she had been the victim of a director who repeatedly showed his friends a video of her in a sexually graphic audition which she made as a teenager. Newton cited this experience as being a part of why she had taken the "Westworld" role, which involved substantial nudity. This role reflected experiences of survivors of sexual abuse while also asking moral questions about the meaning of humanity and what it means to be humane. In 2018, Newton said she was disappointed not to have been invited to participate in Time's Up, a movement against sexual harassment, considering that she had been "ostracised" for having spoken out about alleged sexual abuse by a director.


title: Thandiwe Newton

text: Newton was ranked one of the best-dressed women in 2018 by fashion website Net-a-Porter. Later that year, it was announced that Newton was included in the 2019 edition of the "Powerlist", ranking the 100 most influential Black Britons.


title: Oleksandr Usyk

text: Oleksandr Oleksandrovych Usyk (; born 17 January 1987) is a Ukrainian professional boxer. He is a world champion in two weight classes, having held the unified WBA (Super), IBF, WBO and IBO heavyweight titles since 2021, "The Ring" magazine heavyweight title since 2022, and the undisputed cruiserweight title from 2018 to 2019, being the first cruiserweight champion to hold all four major world titles. He is widely regarded as one of the greatest Ukrainian boxers of all time. With his victory over Joshua, Usyk became one of only three boxers to have unified the cruiserweight world titles and become a world heavyweight champion, joining Evander Holyfield and David Haye.


title: Oleksandr Usyk

text: As an amateur, Usyk won gold medals at the 2011 World Championships and 2012 Olympics, both in the heavyweight division. He turned professional in 2013 and won the undisputed cruiserweight championship in his 15th professional fight in 2018. Three of his titles were won during the inaugural World Boxing Super Series, in which he won the Muhammad Ali Trophy, as well as "The Ring" magazine and lineal cruiserweight titles. For his achievements, Usyk was named the 2018 Fighter of the Year by "Sports Illustrated", ESPN, "The Ring" and the Boxing Writers Association of America (BWAA).


title: Oleksandr Usyk

text: In 2018 Usyk became the fourth male boxer in history to simultaneously hold the WBA, WBC, IBF and WBO titles, after Jermain Taylor, Bernard Hopkins and Terence Crawford. He was the first Ukrainian undisputed champion. He is particularly notable for the speed of his accomplishments, winning his first world title in his tenth fight, and becoming the undisputed champion of his weight class by his fifteenth fight. Usyk vacated his cruiserweight titles in 2019 to move up to heavyweight. By that point, in sixteen fights he had defeated five current or former world champions.


title: Oleksandr Usyk

text: As of August 2022, Usyk is ranked as the world's best active boxer, pound for pound, by "The Ring", second by the Transnational Boxing Rankings Board (TBRB), third by BWAA, fifth by BoxRec and sixth by ESPN. He is also ranked as the best heavyweight by TBRB, BoxRec and ESPN.


title: Oleksandr Usyk

text: Usyk was born in Simferopol, Crimean Oblast, Ukrainian SSR, Soviet Union on 17 January 1987, to parents originally from northern Ukraine. His mother was born in the Chernihiv region (in the village of Rybotyn, Korop Raion), while his father was a native of Sumy. His mother worked in construction and moved to Simferopol to study. His father was a military man who passed through Afghanistan, working as a security guard in Crimea, and the two met there. He is the first born of his family and he has two siblings. Until age 15, he played football and was trained at the SC Tavriya Simferopol specialized sports school of Olympic reserve (club's football academy). In 2002 Usyk switched to boxing. He is a graduate of Lviv State University of Physical Culture.


title: Oleksandr Usyk

text: At the 2006 European Championships he won his first three matches but lost in the semi-final to Matvey Korobov.


title: Oleksandr Usyk

text: In February 2008, he moved up another weight class and was sent to the Olympic qualifier in Roseto degli Abruzzi replacing European Champion Denys Poyatsyka. There he defeated world class Azeri Elchin Alizade and Daniel Price.


title: Oleksandr Usyk

text: At the 2008 Olympic Games, Usyk outpointed Yushan Nijiati by 23–4, but lost to Clemente Russo by 4–7 in the quarter-final.


title: Oleksandr Usyk

text: He dropped down to light-heavyweight and won gold at the 2008 European Championships, but later moved back up to heavyweight. At the 2011 World Amateur Boxing Championships he defeated Artur Beterbiev and Teymur Mammadov to win the heavyweight title and qualify for the 2012 Summer Olympics.


title: Oleksandr Usyk

text: At the 2012 Olympic Games in London, Usyk won the gold medal, outpointing Artur Beterbiev, Tervel Pulev and Italy's Clemente Russo, outscoring him by 6–3 in the final.


title: Oleksandr Usyk

text: Prior to turning professional, he competed in the heavyweight division (91+ kg) of the 2012–13 World Series of Boxing (WSB), as part of team Ukraine Otamans, winning all six of his bouts with two by stoppage (Junior Fa by UD, Eric Brechlin by 3rd round TKO, Joe Joyce by UD, Magomedrasul Majidov by UD, Matteo Modugno by 2nd round TKO and Mihai Nistor by UD).


title: Oleksandr Usyk

text: Usyk turned pro in late 2013 at the age of 26 and signed a promotional deal with the Klitschko brothers' K2 Promotions, fighting in the cruiserweight division.


title: Oleksandr Usyk

text: On 9 November 2013 Usyk made his professional debut by defeating Mexican fighter Felipe Romero via a fifth-round knockout. The following month he stopped 38 year old Epifanio Mendoza in four rounds. In his third professional fight on 26 April 2014, Usyk made his debut in Germany on the undercard of Klitschko-Leapai at the Koenig Pilsener Arena, defeating Ben Nsafoah via third-round knockout. A month later, Usyk returned home and scored a fourth-round knockout-victory over Argentine Cesar David Crenz.


title: Oleksandr Usyk

text: Usyk won his first title on 4 October 2014, after beating South African boxer Daniel Bruwer via seventh-round technical knockout (TKO) for the interim WBO Inter-Continental cruiserweight title. Usyk defended the title two months later, stopping 35 year old Danie Venter in the ninth-round. Usyk was ahead on all three judges' scorecards at the time of stoppage.


title: Oleksandr Usyk

text: Usyk made another defence on 18 April 2015, against former Russian cruiserweight champion Andrey Knyazev (11-1, 6 KOs) in Kyiv. After seven one-sided rounds, referee Mickey Vann finally stopped the fight in round eight after deciding Knyazev had taken too much punishment. This win kept Usyk on course to a WBO title fight against then champion Marco Huck.


title: Oleksandr Usyk

text: In 29 August 2015, Usyk defeated former South African light heavyweight champion Johnny Muller via third-round TKO at the Sport Palace in Kyiv, which saw Usyk control the fight with a jab. Usyk knocked down Muller twice in round three and although Muller protested, the referee waved the fight off with one second of the round left.


title: Oleksandr Usyk

text: Usyk made a fourth and final defense against unknown Cuban boxer Pedro Rodriguez in a scheduled 12-round fight on 12 December at the Sport Palace. Usyk won the fight scoring, his ninth straight knockout in as many fights, first dropping Rodriguez in round six with an uppercut before the fight was stopped in round seven, being knocked down again, although he beat the count. This win put Usyk at the WBO's number 1 position, with a World title fight on the cards for 2016.


title: Oleksandr Usyk

text: In June 2016, it was announced that Usyk would challenge undefeated Polish boxer Krzysztof Głowacki (26-0, 16 KOs) for his WBO cruiserweight title on 17 September, at the Ergo Arena, Gdansk, Poland. It was reported that Usyk's trainer James Ali Bashir wanted to recruit former world champion Antonio Tarver as a sparring partner. It was said that Tarver not only requested too much money, but also wanted to appear on the card as a co-featured main event. Głowacki weighed 199.3 pounds, with Usyk coming in slightly lighter at 198.75 pounds. The fight was shown live on Sky Sports in the UK. On the night, Usyk outpointed Głowacki after an exciting 12-round fight with the judges scoring it 119–109, 117–111, and 117–111 all in Usyk's favour. The decision win also ended Usyk's knockout streak. Usyk dominated the fight with his footwork, superior hand speed and spearing jab, injuring Głowacki's eye early in the fight, causing a cut that continued to bleed for the remainder of the contest.


title: Oleksandr Usyk

text: Usyk announced he would be making his American debut on the Bernard Hopkins vs. Joe Smith Jr. undercard on 17 December 2016. The fight would take place at the Forum in Inglewood, California. On 11 November K2 Promotions announced Usyk would be defending his WBO title against 28 year old South African boxer Thabiso Mchunu (17-2, 11 KOs). Mchunu previously lost to Ilunga Makabu via eleventh-round stoppage, although being ahead on the scorecards at the time. The fight started out slow, causing the fans in attendance to boo with displeasure. The pace picked up after the first couple of rounds when Usyk began breaking down Mchunu with his trademark, accurate combinations. Usyk scored a knockdown in the sixth round, and a further two more in the ninth, causing referee Lou Moret to wave off the fight at 2:53 of round 9. CompuBox statistics showed that Usyk landed 163 of 517 punches thrown (32%), and Mchunu landed 76 of his 278 (27%).


title: Oleksandr Usyk

text: Prior to the fight, Usyk spoke of his desire to fight other cruiserweight titlists as well as fighting Anthony Joshua at heavyweight. The fight averaged 560,000 viewers on HBO: this was considered good numbers, considering it was Usyk's HBO debut and on the undercard.


title: Oleksandr Usyk

text: K2 Promotions announced that Usyk would be returning to regular HBO to defend his cruiserweight world title in April 2017. He was originally planned to appear on the undercard of the Golovkin-Jacobs HBO PPV in March at Madison Square Garden; however, since Román González and Carlos Cuadras were scheduled to appear in separate fights and not fight each other, Usyk was pulled from the card.


title: Oleksandr Usyk

text: On 12 February 2017, Usyk announced that he had parted ways with long time trainer James Ali Bashir and replaced him with Vasiliy Lomachenko's father and trainer, Anatoly Lomachenko. Bob Arum announced that Usyk would be part of a triple header including Vasiliy Lomachenko at the MGM National Harbor in Oxon Hill, Maryland on 8 April 2017 against Michael Hunter (12-0, 8 KOs). Usyk weighed 199.4 whilst Hunter came in at 199 pounds. In front of a sold-out crowd of 2,828, where there was majority Ukrainian fans in attendance, Usyk was taken the distance for the second time in his career and won a rather one-sided unanimous decision to retain his WBO title. Hunter unexpectedly controlled the first three rounds behind the jab. It wasn't until the fourth round, when Usyk took control of the bout using his left and connecting well to the body to win the majority of the remaining rounds. Pundits thought Hunter was gifted going the distance and the fight should have been stopped by referee Bill Clancy in the championship rounds. In the last minute of round 12, it appeared Hunter, while taking punches, was only standing because the ropes where holding him up. The referee halted the action and gave Hunter a standing eight count, ruling it a knockdown for Usyk. All three judges scored the fight unanimously 117–110 for Usyk. Although it took him a few rounds to get into the fight, Usyk was happy with his performance and called out other titleholders, "I'm very happy with my performance. I did what I wanted to do. He took a lot of punches. I thought maybe they would stop the fight (in the 12th round). I'd love to fight any of the titleholders, any time, any place."


title: Oleksandr Usyk

text: According to CompuBox punch stats, Usyk landed 321 of his 905 punches thrown, 36%. Hunter managed to land 24% of his punches, connecting 190 of 794. The fight drew an average of 679,000 viewers on HBO and peaked at 774,000 viewers.


title: Oleksandr Usyk

text: On 1 July 2015, Usyk finally announced that he would join fellow cruiserweights Mairis Briedis, Murat Gassiev, Yuniel Dorticos, Marco Huck and Krzysztof Włodarczyk in the eight-man bracket style tournament, due to start in September 2017. He said, "I feel happy and inspired with the idea of such a tournament. I've been dreaming of putting together all the champs to see who is the strongest and becomes the undisputed king of the division." The draw was to take place on 8 July in Monte Carlo. The winner of the tournament would receive a grand money prize and the Muhammad Ali trophy.


title: Oleksandr Usyk

text: At the Draft Gala, Usyk, who had first pick, chose to fight former WBO champion Marco Huck (40–4–1, 27 KOs). When asked why he chose Huck, Usyk said, "Because of my fans." Huck, who was equally excited, replied that Usyk was his 'wish opponent'. On 26 July it was announced that the fight would take place at the Max-Schmeling-Halle in Berlin on 9 September 2017. This would mark the second time Usyk would fight in Germany as a professional, having fought there in his third professional bout in April 2014. It would also mark the first fight of the tournament.


title: Oleksandr Usyk

text: On 6 September 2017, at the final press-conference, Huck pushed Usyk in the face-off. In regards to the shove, Huck said, "I wanted to show Usyk that he is in my hometown and that he should be prepared for the battle of his life on Saturday." Usyk, who remained professional and calm, replied, "If you want to be a great champion, you have to beat the best and Huck is one of the best. I chose to enter this tournament because it is a path to achieve my dream of unifying all the belts. There’s a prestigious trophy at stake too, the Muhammad Ali Trophy. We were born on the same day and I admire Ali because he is the biggest role model in boxing and I will thank God if I win a trophy with his name on it." As he was leaving the building, Usyk claimed he would 'bury' Huck.


title: Oleksandr Usyk

text: On fight night, Usyk used his footwork and combination punching to cruise to a TKO win. On top of his dominant performance, Usyk taunted Huck throughout the fight. In round 8, Usyk tripped on Huck's feet and Huck lost a point on the scorecards as he threw a punch at Usyk when the latter was down. Usyk continued to land combinations with little to no response from Huck until referee Robert Byrd stopped the fight in the tenth-round. With the win, Usyk progressed to the semi-final stage of the Super Series and was to face the winner of the Mairis Briedis vs. Mike Perez, scheduled for 30 September.


title: Oleksandr Usyk

text: Usyk would next fight Mairis Briedis (23–0, 18 KOs) following the latter's win over Perez via unanimous decision. In November 2017, it was reported the fight would take place on 27 January 2018 in Riga, Latvia, a week before Gassiev vs. Dorticos takes place. Arēna Rīga was confirmed as the location by Comosa's Chief Boxing Officer Kalle Sauerland. Usyk came in at 199.5 pounds and Briedis weighed 199.1 pounds. Usyk moved on to the final of the tournament after defeating Briedis via majority decision. With a high work rate, Usyk controlled most of the fight with his jab, applying pressure when needed. Briedis was credited with landing the harder punches. The opening four rounds were closely contested, with Usyk receiving a cut over his right eye from an accidental clash of heads in the third round. From round five, Usyk became busier and took control of the fight, although he was still hit with some hard shots to the head from Briedis. One judge scored the fight 114–114, whilst the remaining two judges scored the fight 115–113 in favour of Usyk, giving him the win. After the fight, Usyk stated it was the hardest fight of his career. According to CompuBox Stats, Usyk landed 212 of 848 punches thrown (25%) and Briedis was more accurate, landing 195 of his 579 thrown (33.7%). Usyk landed 40% of his power punches. Many boxers and pundits praised the fight.


title: Oleksandr Usyk

text: After Usyk defeated Briedis, it was announced in the post-fight press conference that the final would take place in Jeddah, Saudi Arabia, on 11 May 2018. However, once Murat Gassiev (26-0, 19 KOs) stopped Yuniel Dorticos, setting up the final, the secretary general of the Russian Boxing Federation, Umar Kremlev, stated that he would push forward in order to outbid Saudi Arabia and have the final of the tournament take place in Russia on the Day of Russian Boxing on 22 July. On 16 April, it was reported that Usyk had suffered an elbow injury during training, pushing the final to possibly June or July 2018. On 18 June, at a press conference, Kremlev announced the final would take place on 21 July at the Olympic Stadium, Moscow, Russia. On 29 June, the final was officially confirmed. On the release date, 7,000 tickets were sold. Both boxers came in at 198.45 pounds at the weigh-in.


title: Oleksandr Usyk

text: Usyk quickly took control of the fight, moving rapidly and using his "beautiful, commandeering jab". Usyk controlled the fight, not allowing Gassiev to use his power. Gassiev did not land a solid punch until the end of round 2. According to many reports, Usyk outclassed, outboxed, and dominated Gassiev. The result was never in question as Usyk was declared the winner by unanimous decision, with the judges’ scorecards reading 120–108, 119–109, and 119–109. Muhammad Ali's widow, Lonnie Ali, presented the trophy to Usyk. After the fight, both combatants were exemplars of good sportsmanship, embracing, with Gassiev saying "I had the best opponent of my professional career ... today is Oleksandr's day". Usyk humbly adding "My team made me look like I looked in the ring. This is our victory". The win made Usyk the first ever four-belt undisputed cruiserweight champion. Usyk dominated throughout, landing 252 of 939 thrown punches (27%), compared to Gassiev's 91 landed of 313 thrown (29%). Usyk used his superior conditioning to finish the fight, also increasing his output by landing 47 of 117 punches thrown in round 12. Usyk managed to withstand the 32 power body shots he received and continued to move around the ring.


title: Oleksandr Usyk

text: When asked whom he would like to fight next, Usyk said, "At this time I have heard that Tony Bellew wants to fight the winner of the Muhammad Ali Trophy. I hope he will see me talking... 'hey Tony Bellew, are you ready?' If he doesn't want to go down [in weight], I will go up [in weight] for him. I will eat more spaghetti for my dinner!" Also after the fight Usyk said: "Olympic [stadium], thanks. People, countrymen and those who supported. Moscow 2018. Bang! Daddy's in the building!".


title: Oleksandr Usyk

text: After calling out Tony Bellew (30-2-1, 20 KOs) after winning the tournament, Bellew responded via social media that he would accept the fight; however, he stated the fight would need to take place in 2018 and be for the undisputed cruiserweight championship. Bellew believed a fight at heavyweight would not be as appealing as he would not gain much with a win. Bellew also stated it would be his last fight as a professional. By the end of July, it was said the fight would likely take place in November 2018 in London. After positive meetings between Bellew's promoter Eddie Hearn and K2's Alexander Krassyuk, on 20 August, Boxing Scene reported the fight was likely to take place on 10 November 2018. A week later, K2 Promotions confirmed the date of the fight. On 5 September, the WBA ordered Usyk to start negotiating with Denis Lebedev (30-2, 22 KO), who was their 'champion in recess' and gave them until the first week of October 2018 to complete negotiations. There was said to be a stumbling block for the potential Usyk vs. Bellew fight. According to Hearn, the fight was likely to be pushed back to 2019. Prior to negotiations, Bellew stated the fight must happen in 2018.


title: Oleksandr Usyk

text: On 7 September, Usyk signed a multi-fight deal with Matchroom Boxing, which meant he would fight exclusively on Sky Sports in the UK and DAZN in USA. The agreement meant Matchroom would co-promote Usyk alongside K2 Promotions. Usyk's next fight would be confirmed 'in the very near future', according to Hearn. A week after signing with Matchroom, the Usyk vs. Bellew fight was announced to take place on 10 November at the Manchester Arena, live and exclusive on Sky Box Office. Experienced British referee Terry O'Connor was named as the official. Bellew weighed 199¼ pounds, just over 2 years since he last made the cruiserweight limit and Usyk weighed 198¼ pounds.


title: Oleksandr Usyk

text: On fight night, Usyk, who is usually a slow starter, eventually took full control of the bout and stopped Bellew in round 8 to retain all the cruiserweight belts. The official time of the stoppage was at 2:00 of round 8. There was very little action in round 1 as both boxers showed each other respect. It was a feeling out round. Due to the lack of action, the crowd began to boo towards the end of the first. Overall, Usyk landed just 3 jabs and Bellew landed 1 power shot. Round 2 was similar, however Bellew stepped on the gas, managed to land some clean shots along with some showboating. Bellew took control in round 3, landing two straight right hands. Usyk began using his jab more and after landing an overhand left, Bellew was left slightly shaken. By the end of round 4, Bellew was backed up against the ropes and looked to tire. Bellew aimed most of his shots to Usyk's body and by round 7, was missing a lot of shots, mostly due to Usyk's foot movement, and ended the round with a bloody nose. In round 8, whilst in a neutral corner, Usyk landed a hard left, again buzzing Bellew, forcing him to move away against the ropes. Another left hand wobbled Bellew before Usyk finished him off with another left, dropping Bellew backwards with his head landing on the bottom rope. A brave Bellew tried to get up slowly and beat the count but referee Terry O'Connor stopped the fight. Bellew's 10-fight winning streak came to an end. Judges Alejandro Cid and Steve Gray scored the first seven rounds 68–65 and 67–66 respectively in favour of Bellew and Yury Koptsev had the fight 67–67 entering round 8.


title: Oleksandr Usyk

text: Afterwards, Bellew paid tribute to Usyk and announced his retirement from boxing, saying; "I have been doing this for 20 years, and it is over." Usyk stated 2018 was the most difficult year of his career, but most successful. "We need to put goals in front of us and move towards them," Usyk later stated. There was a small concern during Bellew's post-fight interview as many felt he was clearly concussed. According to compubox stats, Usyk landed 112 of his 424 punches thrown (26%) and Bellew landed 61 of his 268 thrown (23%). Both landed 47 power shots each.


title: Oleksandr Usyk

text: After defeating Bellew, Usyk declared his intention to move up to heavyweight. Carlos Takam (36-5-1, 28 KO) was announced as his opponent, with the fight scheduled for 25 May 2019. On 7 May, it was reported that Usyk had suffered a bicep injury. The bout was rescheduled for a date in September, to be featured on DAZN. On 22 August, following the Golovkin vs. Derevyanchenko press conference, promoter Eddie Hearn revealed in an interview that Carlos Takam is "out of the fight" and "will not be taking the fight". Usyk also had the option to challenge the winner of the rematch between Andy Ruiz Jr. and Anthony Joshua for the WBA (Super), IBF, WBO and IBO heavyweight titles as the mandatory for the WBO belt, as per WBO regulations, which allow a 'super champion' of a weight class to become an immediate mandatory challenger when moving up or down in weight.


title: Oleksandr Usyk

text: In September, Usyk's heavyweight debut was announced to be on 12 October 2019, at the Wintrust Arena, Chicago, Illinois, against Tyrone Spong (14-0, 13 KOs). A few days before the fight, Spong tested positive for a banned substance, clomiphene, and the fight was thrown into disarray. Promoter Eddie Hearn said there were several backup fighters being considered. Spong's replacement was then announced as Chazz Witherspoon (38-3, 29 KOs). Usyk won the fight as Witherspoon retired in his corner after round 7.


title: Oleksandr Usyk

text: On 11 March 2020 it was announced that Usyk would fight former world title challenger Derek Chisora (32-9, 23 KOs) on 23 May 2020 at The O2 Arena in London. If successful, Usyk would be first in line to fight for the WBO heavyweight title held by Anthony Joshua. As part of his preparation for his bouts, Usyk sparred occasionally with former unified heavyweight champion Wladimir Klitschko. The fight was pushed back to 31 October 2020 due to the COVID-19 pandemic, and the venue was moved to the SSE Arena. On the night, Usyk used his superior footwork and stamina to wear down his opponent and win a unanimous decision victory with scores of 117–112, 115–113, 115–113. Chisora had become worn and exhausted later on in the fight, struggling to keep up with Usyk. In his post-fight interview, Usyk reiterated his desire to fight Joshua, saying "Anthony, how are you? I'm coming for you, Anthony."


title: Oleksandr Usyk

text: Unified heavyweight champion Anthony Joshua, for whom Usyk was the WBO mandatory challenger, had been in negotiations to fight undefeated WBC and "The Ring" champion Tyson Fury. However, when it appeared that Fury would instead be forced to face former WBC champion Deontay Wilder in a trilogy bout due to an arbitration ruling, the WBO gave Joshua's camp 48 hours to come to an agreement for the fight with Fury on 21 May 2021, or they would instead order Joshua to face Usyk. Joshua and Fury's camps could not reach an agreement, and thus on 22 May the WBO issued the instruction that Joshua would have to fight Usyk, with an agreement for the bout to be in place by 31 May. Usyk reacted to these developments with a video message directed to Joshua's promoter Eddie Hearn, telling him, "Eddie, I want money, more money."


title: Oleksandr Usyk

text: On 20 July, an official announcement was made, confirming that the fight between Usyk and Joshua would be taking place on 25 September at Tottenham Hotspur Stadium. Although many fans and pundits doubted Usyk would have the size or power to trouble Joshua, Usyk produced an upset, outboxing the champion and rocking him several times over 12 rounds to claim a unanimous decision victory, with scores of 117–112, 116–112 and 115–113, and retained his undefeated record. Reflecting upon his performance in his post-fight interview, Usyk said, "This means a lot for me. The fight went the way I expected it to go. There were moments when Anthony pushed me hard but it was nothing special. I had no objective to knock him out because my corner pushed me not to do that. In the beginning, I tried to hit him hard, but then I stuck to my job." On 22 June, it was announced that a rematch was scheduled to take place in Jeddah, Saudi Arabia on 20 August with Usyk defending the WBA, WBO and IBF championship belts, and Joshua, as the challenger.


title: Oleksandr Usyk

text: On 29 September 2021, four days after Usyk defeated Anthony Joshua to become unified world heavyweight champion, it was announced by his promoter Alexander Krassyuk that a one-sided rematch clause which had been specified in the fight contract had "already been activated in principle, from the side of Joshua." Krassyuk noted that Usyk relished the prospect of squaring off against Joshua twice: "So I remember when we discussed with Oleksandr the issue of rematch, he was delighted and said 'Wow, cool, I will beat Antokha [sic] twice.'" Regarding the venue of the rematch, Usyk made it known that he hoped it would take place in his native country of Ukraine, saying, "I would love to have the rematch at Olimpiyskiy Stadium in Kyiv." However, Joshua's promoter, Eddie Hearn, stated that Ukraine was a "very unlikely" venue, as he wanted to maximise income: "I think it will be international or the UK, I would think it would be in the UK."


title: Oleksandr Usyk

text: With the Russian invasion of Ukraine on 24 February 2022, a potential Usyk–Joshua rematch was thrown into doubt. In the days following the start of the invasion, Usyk posted on his social media channels to confirm that he had returned to Ukraine, and to plead with Russian President Vladimir Putin to stop the invasion, with one video captioned "NO WAR". On 2 March, Usyk confirmed in a video interview with American news network CNN that he had taken up arms and joined a territorial defence battalion in Ukraine. Regarding his professional boxing career, Usyk said, "I really don't know when I'm going to be stepping back in the ring. My country and my honour are more important to me than a championship belt." In late March, it was reported that Usyk would be leaving Ukraine to begin preparations for the rematch with Joshua. Usyk revealed his decision to leave his homeland and refocus his efforts on boxing was supported by Mayor of Kyiv and former heavyweight champion Vitali Klitschko, as well as his younger brother Wladimir Klitschko, also a former heavyweight champion who had been defeated by Anthony Joshua in 2017.


title: Oleksandr Usyk

text: On 19 June 2022, it was officially announced that Usyk would be facing Joshua in a rematch in Jeddah, Saudi Arabia on 20 August. The fight marked the first defense of Usyk's world heavyweight titles, whilst it was Joshua's twelfth consecutive world heavyweight title fight. The fight was also an attempt by Joshua to become a three-time world heavyweight champion.


title: Oleksandr Usyk

text: Despite Joshua's much improved performance compared to his first loss to Usyk, the latter successfully defended his belts by a split decision with one judge scoring the fight 115–113 to Joshua, while the other two judges scoring it 115–113 and 116–112 in Usyk's favour. The split decision was controversial and surprised the majority of viewers. "The Ring" magazine called Glenn Feldman's scorecard "horrible". Among those criticizing his judging were promoter Lou DiBella and boxing trainer Teddy Atlas.


title: Oleksandr Usyk

text: According to "New York Times" statistics, Joshua landed 37 body punches compared to 15 in their first fight. Overall, however, Usyk outperformed Joshua, landing 170 of 712 punches, compared with 124 of 492 for Joshua. According to CompuBox, Usyk established new records for punches landed by an Anthony Joshua opponent (170) and most punches landed on Joshua in a single round (39 punches in the 10th round).


title: Oleksandr Usyk

text: His wife has Russian citizenship and the boxer uses Russian as his first language. On 28 April 2014, after the annexation of Crimea by the Russian Federation, Usyk declared he would never exchange his Ukrainian citizenship for Russian citizenship. In 2016, responding to a question if he can still enter Crimea, he stated that he often visits his family in the peninsula; that he does not like to talk politics due to the fact that people like to take words out of context, that in Russia he has many fans and that he does not divide "our peoples because we are Slavs". Afterwards, whenever pressed on the question, Usyk would often reply "Crimea belongs to God"; however in September 2022 Usyk stated that Crimea "was, is and will be" Ukrainian and that is had been taken away forcefully from Ukraine. In November, after Ukrainian Armed Forces recaptured Kherson, Usyk posted a message on his Instagram account: "Donetsk is Ukraine. Luhansk is Ukraine. Zaporizhzhia is Ukraine. Crimea is Ukraine. Kherson is Ukraine. Glory to Ukraine. Glory to ZSU".


title: Oleksandr Usyk

text: Usyk is an Orthodox Christian. After his fight against Anthony Joshua, he said in an interview, "The only thing I wanted to do with this fight is to give praise to my Lord Jesus Christ and to say that all comes from him."


title: Oleksandr Usyk

text: On 26 February 2022, Usyk urged Russian President Vladimir Putin to call off Russia's invasion of Ukraine that had begun on 24 February. A few days later, Usyk, fellow boxer Vasiliy Lomachenko and Bellator MMA Welterweight Champion Yaroslav Amosov travelled to Ukraine to join the country's territorial defense forces, although in late March, Usyk left Ukraine to train for his rematch with Anthony Joshua.


title: Crohn's disease

text: 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, and weight loss. Complications outside of the gastrointestinal tract may include anemia, skin rashes, arthritis, inflammation of the eye, and fatigue. The skin rashes may be due to infections as well as pyoderma gangrenosum or erythema nodosum. Bowel obstruction may occur as a complication of chronic inflammation, and those with the disease are at greater risk of colon cancer and small bowel cancer.


title: Crohn's disease

text: While the precise causes of Crohn's disease (CD) are unknown, it is believed to be caused by a combination of environmental, immune, and bacterial factors in genetically susceptible individuals. It results in a chronic inflammatory disorder, in which the body's immune system defends the gastrointestinal tract, possibly targeting microbial antigens. While Crohn's is an immune-related disease, it does not appear to be an autoimmune disease (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 state.


title: Crohn's disease

text: About half of the overall risk is related to genetics, with more than 70 genes 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. Diagnosis is based on a number of findings, including biopsy and appearance of the bowel wall, medical imaging, and description of the disease. Other conditions that can present similarly include irritable bowel syndrome and Behçet's disease.


title: Crohn's disease

text: 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 may be used for a brief period of time to rapidly improve symptoms, alongside another medication such as either methotrexate or a thiopurine 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 abscesses, certain bowel obstructions, and cancers. Checking for bowel cancer via colonoscopy is recommended every few years, starting eight years after the disease has begun.


title: Crohn's disease

text: 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. It tends to start in young adulthood, though it can occur at any age. Males and females are equally affected.


title: Crohn's disease

text: The disease was named after gastroenterologist Burrill Bernard Crohn, 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 area most commonly affected by the illness.


title: Crohn's disease

text: 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.


title: Crohn's disease

text: Perianal discomfort may also be prominent in Crohn's disease. Itchiness or pain around the anus may be suggestive of inflammation of the anus, or perianal complications such as anal fissures, fistulae, or abscesses around the anal area. Perianal skin tags are also common in Crohn's disease, and may appear with or without the presence of colorectal polyps. Fecal incontinence may accompany perianal Crohn's disease.


title: Crohn's disease

text: The intestines, especially the colon and terminal ileum, are the most commonly affected areas of the body. Abdominal pain 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, which may or may not be bloody. Inflammation in different areas of the intestinal tract can affect the quality of the feces. Ileitis 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.


title: Crohn's disease

text: 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 and stomach may be involved in Crohn's disease. These can cause symptoms including difficulty swallowing (dysphagia), upper abdominal pain, and vomiting.


title: Crohn's disease

text: 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.


title: Crohn's disease

text: People with Crohn's disease are also susceptible to angular stomatitis, an inflammation of the corners of the mouth, and pyostomatitis vegetans.


title: Crohn's disease

text: Like many other chronic, inflammatory diseases, Crohn's disease can cause a variety of systemic symptoms. Among children, growth failure 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, 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 disease may also have malabsorption of carbohydrates or lipids, which can further exacerbate weight loss.


title: Crohn's disease

text: 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.


title: Crohn's disease

text: Inflammation may also involve the white part of the eye (sclera) or the overlying connective tissue (episclera), which causes conditions called scleritis and episcleritis, respectively.


title: Crohn's disease

text: Other very rare ophthalmological manifestations include: conjunctivitis, glaucoma, and retinal vascular disease.


title: Crohn's disease

text: 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 gets excreted in the stool. As a result, the cholesterol/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, a type of inflammation of the bile ducts.


title: Crohn's disease

text: Liver involvement of Crohn's disease can include cirrhosis and steatosis. Nonalcoholic fatty liver disease (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.


title: Crohn's disease

text: Other rare hepatobiliary manifestations of Crohn's disease include: cholangiocarcinoma, granulomatous hepatitis, cholelithiasis, autoimmune hepatitis, hepatic abscess, and pericholangitis.


title: Crohn's disease

text: Nephrolithiasis, obstructive uropathy, and fistulization 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.


title: Crohn's disease

text: 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.


title: Crohn's disease

text: 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.


title: Crohn's disease

text: Amyloidosis (see endocrinological involvement) secondary to Crohn's disease has been described and is known to affect the kidneys.


title: Crohn's disease

text: Pancreatitis 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, and azathioprine. Pancreatitis may present as symptomatic (in 2%) or more commonly asymptomatic (8–21%) disease in adults with IBD.


title: Crohn's disease

text: 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 requiring rapid drainage. Nonsteroidal anti-inflammatory drugs have been used as therapy, although this should be weighed against the hypothetical risk of exacerbating the underlying IBD.


title: Crohn's disease

text: Crohn's disease also increases the risk of blood clots; painful swelling of the lower legs can be a sign of deep venous thrombosis, while difficulty breathing may be a result of pulmonary embolism.


title: Crohn's disease

text: 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 and ulceration from the larynx to the hypopharynx Hoarseness, sore throat, and odynophagia are other symptoms of laryngeal involvement of Crohn's disease.


title: Crohn's disease

text: Considering extraintestinal manifestations of CD, those involving the lung are relatively rare. However, there is a wide array of lung manifestations, ranging from subclinical alterations, airway diseases and lung parenchymal diseases to pleural 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, Apical fibrosis, Bronchiectasis, Bronchitis, Bronchiolitis, Tracheal stenosis, Granulomatous lung disease, and Abnormal pulmonary function.


title: Crohn's disease

text: Crohn's disease is associated with a type of rheumatologic disease known as seronegative spondyloarthropathy. This group of diseases is characterized by inflammation of one or more joints (arthritis) or muscle insertions (enthesitis). 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, leading to ankylosing spondylitis if the entire spine is involved, or simply sacroiliitis if only the sacroiliac joint is involved. The symptoms of arthritis include painful, warm, swollen, stiff joints, and loss of joint mobility or function.


title: Crohn's disease

text: Crohn's disease increases the risk of osteoporosis or thinning of the bones. Individuals with osteoporosis are at increased risk of bone fractures.


title: Crohn's disease

text: Crohn's disease may also involve the skin, blood, and endocrine system. 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 shins. Erythema nodosum is due to inflammation of the underlying subcutaneous tissue, and is characterized by septal panniculitis.


title: Crohn's disease

text: Pyoderma gangrenosum is a less common skin problem, occurring in under 2%, and is typically a painful ulcerating nodule.


title: Crohn's disease

text: Other very rare dermatological manifestations include: Pyostomatitis vegetans, Psoriasis, Erythema multiforme, 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.


title: Crohn's disease

text: Crohn's disease can also cause neurological complications (reportedly in up to 15%). The most common of these are seizures, stroke, myopathy, peripheral neuropathy, headache, and depression.


title: Crohn's disease

text: Central and peripheral neurological disorders are described in patients with IBD and include peripheral neuropathies, myopathies, focal central nervous system defects, convulsions, confusional episodes, meningitis, syncope, optic neuritis, and sensorineural loss. Autoimmune mechanisms are proposed for involvement with IBD. Nutritional deficiencies associated with neurological manifestations, such as vitamin B12 deficiency, should be investigated. Spinal abscess 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.


title: Crohn's disease

text: Crohn's disease is linked to many psychological disorders, including depression and anxiety, denial of your disease, the need for dependence or dependent behaviors, feeling overwhelmed, and having a poor self-image.


title: Crohn's disease

text: Autoimmune hemolytic anemia, a condition in which the immune system attacks the red blood cells, is also more common in Crohn's disease and may cause fatigue, a pale appearance, and other symptoms common in anemia.


title: Crohn's disease

text: Secondary amyloidosis (AA) is another rare but serious complication of inflammatory bowel disease (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.


title: Crohn's disease

text: Leukocytosis and thrombocytopenia are usually due to immunosuppressant treatments or sulfasalazine. Plasma erythropoietin levels often are lower in patients with IBD than expected, in conjunction with severe anemia.


title: Crohn's disease

text: Thrombocytosis and thromboembolic events resulting from a hypercoagulable state in patients with IBD can lead to pulmonary embolism or thrombosis 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.


title: Crohn's disease

text: People with Crohn's disease may develop anemia due to vitamin B, folate, iron deficiency, or due to anemia of chronic disease. The most common is iron deficiency anemia from chronic blood loss, reduced dietary intake, and persistent inflammation leading to increased hepcidin levels, restricting iron absorption in the duodenum. As Crohn's disease most commonly affects the terminal ileum where the vitamin B12/intrinsic factor 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, which can produce micronutrient deficiencies.


title: Crohn's disease

text: Crohn's disease can lead to several mechanical complications within the intestines, including obstruction, fistulae, and abscesses. Obstruction typically occurs from strictures 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, between the bowel and vagina, and between the bowel and skin. Abscesses are walled-off concentrations of infection, which can occur in the abdomen or in the perianal area. Crohn's is responsible for 10% of vesicoenteric fistulae, and is the most common cause of ileovesical fistulae.


title: Crohn's disease

text: 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. Persistent vomiting and nausea may indicate stenosis from small bowel obstruction or disease involving the stomach, pylorus, or duodenum.


title: Crohn's disease

text: Intestinal granulomas 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.


title: Crohn's disease

text: Crohn's disease also increases the risk of cancer in the area of inflammation. For example, individuals with Crohn's disease involving the small bowel are at higher risk for small intestinal cancer. Similarly, people with Crohn's colitis have a relative risk of 5.6 for developing colon cancer. Screening for colon cancer with colonoscopy is recommended for anyone who has had Crohn's colitis for at least eight years.


title: Crohn's disease

text: 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 and biologic agents used to treat this disease may promote developing extra-intestinal cancers.


title: Crohn's disease

text: Some cancers, such as Acute Myelocytic Leukaemia have been described in cases of Crohn's disease. Hepatosplenic T-cell lymphoma (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.


title: Crohn's disease

text: Major complications of Crohn's disease include bowel obstruction, abscesses, free perforation, and hemorrhage, which in rare cases may be fatal.


title: Crohn's disease

text: Individuals with Crohn's disease are at risk of malnutrition for many reasons, including decreased food intake and malabsorption. The risk increases following resection of the small bowel. Such individuals may require oral supplements to increase their caloric intake, or in severe cases, total parenteral nutrition (TPN). Most people with moderate or severe Crohn's disease are referred to a dietitian for assistance in nutrition.


title: Crohn's disease

text: Small intestinal bacterial overgrowth (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.


title: Crohn's disease

text: Crohn's disease can be problematic during pregnancy, and some medications can cause adverse outcomes for the fetus 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.


title: Crohn's disease

text: Common complications of an ostomy (a common surgery in Crohn's disease) are: Mucosal edema, Peristomal dermatitis, Retraction, Ostomy prolapse, Mucosal/skin detachment, Hematoma, Necrosis, Parastomal hernia, and Stenosis.


title: Crohn's disease

text: The etiology 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, antibodies and T lymphocytes are the primary mode of inflammation. These cells and bodies are part of the adaptive immune system, or the part of the immune system that learns to fight foreign bodies when first identified. Autoinflammatory diseases are diseases where the innate immune system, 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.


title: Crohn's disease

text: 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 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 syndromes.


title: Crohn's disease

text: Some examples of how the innate immune system affects bowel inflammation have been described. A meta-analysis of CD genome-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 and the immunity-related GTPase M, IRGM) are involved in innate immune responses against gut microbiota, while one (the X-box binding protein 1) is involved in regulation of the [adaptive] immune pathway via MHC class II, resulting in autoinflammatory inflammation. Studies have also found that increased ILC3 can overexpress major histocompatibility complex (MHC) II. MHC class II can induce CD4+ T cell apoptosis, thus avoiding the T cell 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.


title: Crohn's disease

text: 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.


title: Crohn's disease

text: 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. 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 monogenic disorders impairing phagocyte function.


title: Crohn's disease

text: While the exact cause or causes are unknown, Crohn's disease seems to be due to a combination of environmental factors and genetic predisposition. Crohn's is the first genetically complex disease in which the relationship between genetic risk factors and the immune system is understood in considerable detail. Each individual risk mutation makes a small contribution to the overall risk of Crohn's (approximately 1:200). The genetic data, and direct assessment of immunity, indicates a malfunction in the innate immune system. In this view, the chronic inflammation of Crohn's is caused when the adaptive immune system tries to compensate for a deficient innate immune system.


title: Crohn's disease

text: 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.


title: Crohn's disease

text: The first mutation found to be associated with Crohn's was a frameshift in the NOD2 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 gene, which is involved in the unfolded protein response pathway of the 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, IL23R, IRGM, and SLC11A1.


title: Crohn's disease

text: There is considerable overlap between susceptibility loci for IBD and mycobacterial infections. Genome-wide association studies have shown that Crohn's disease is genetically linked to coeliac disease.


title: Crohn's disease

text: Crohn's has been linked to the gene LRRK2 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, which collects and eliminates waste product in cells, and is also associated with Parkinson's disease.


title: Crohn's disease

text: There was a prevailing view that Crohn's disease is a primary T cell autoimmune disorder; however, a newer theory hypothesizes that Crohn's results from an impaired innate immunity. The later hypothesis describes impaired cytokine secretion by macrophages, 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 T1 and T17 cytokine response.


title: Crohn's disease

text: In 2007, the ATG16L1 gene was implicated in Crohn's disease, which may induce autophagy and hinder the body's ability to attack invasive bacteria. Another study theorized that the human immune system traditionally evolved with the presence of parasites 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.


title: Crohn's disease

text: It is hypothesized that maintenance of commensal microorganism growth in the GI tract is dysregulated, either as a result or cause of immune dysregulation.


title: Crohn's disease

text: There is an apparent connection between Crohn's disease, "Mycobacterium", 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, in cattle. In many individuals, genetic factors predispose individuals to "Mycobacterium avium" subsp." paratuberculosis" infection. This bacterium may produce certain compounds containing mannose, which may protect both itself and various other bacteria from phagocytosis, thereby possibly causing a variety of secondary infections.


title: Crohn's disease

text: NOD2 is a gene involved in Crohn's genetic susceptibility. It is associated with macrophages' diminished ability to phagocytize 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.


title: Crohn's disease

text: Other studies have linked specific strains of enteroadherent "E. coli" to the disease. Adherent-invasive Escherichia coli (AIEC), more common in people with CD, have the ability to make strong biofilms compared to non-AIEC strains correlating with high adhesion and invasion indices of neutrophils and the ability to block autophagy at the autolysosomal step, which allows for intracellular survival of the bacteria and induction of inflammation. Inflammation drives the proliferation of AIEC and dysbiosis in the ileum, irrespective of genotype. AIEC strains replicate extensively inside macrophages inducing the secretion of very large amounts of TNF-α.


title: Crohn's disease

text: Mouse studies have suggested some symptoms of Crohn's disease, ulcerative colitis, and irritable bowel syndrome have the same underlying cause. Biopsy samples taken from the colons of all three patient groups were found to produce elevated levels of a serine protease. Experimental introduction of the serine protease into mice has been found to produce widespread pain associated with irritable bowel syndrome, as well as colitis, which is associated with all three diseases. Regional and temporal variations in those illnesses follow those associated with infection with the protozoan "Blastocystis".


title: Crohn's disease

text: The "cold-chain" hypothesis is that psychrotrophic bacteria such as "Yersinia" and "Listeria" species contribute to the disease. A statistical correlation was found between the advent of the use of refrigeration in the United States and various parts of Europe and the rise of the disease.


title: Crohn's disease

text: The increased incidence of Crohn's in the industrialized world indicates an environmental component. Crohn's is associated with an increased intake of animal protein, milk protein, and an increased ratio of omega-6 to omega-3 polyunsaturated fatty acids.


title: Crohn's disease

text: Those who consume vegetable proteins appear to have a lower incidence of Crohn's disease. Consumption of fish protein has no association.


title: Crohn's disease

text: Smoking increases the risk of the return of active disease (flares). The introduction of hormonal contraception in the United States in the 1960s is associated with a dramatic increase in incidence, and one hypothesis is that these drugs work on the digestive system in ways similar to smoking. Isotretinoin is associated with Crohn's.


title: Crohn's disease

text: Although stress is sometimes claimed to exacerbate Crohn's disease, there is no concrete evidence to support such claim. Still, it is well known that immune function is related to stress. Dietary microparticles, such as those found in toothpaste, have been studied as they produce effects on immunity, but they were not consumed in greater amounts in patients with Crohn's. The use of doxycycline has also been associated with increased risk of developing inflammatory bowel diseases. In one large retrospective study, patients who were prescribed doxycycline for their acne had a 2.25-fold greater risk of developing Crohn's disease.


title: Crohn's disease

text: During a colonoscopy, biopsies of the colon are often taken to confirm the diagnosis. Certain characteristic features of the pathology seen point toward Crohn's disease; it shows a transmural pattern of inflammation, meaning the inflammation may span the entire depth of the intestinal wall. Ulceration is an outcome seen in highly active disease. There is usually an abrupt transition between unaffected tissue and the ulcer—a characteristic sign known as skip lesions. Under a microscope, biopsies of the affected colon may show mucosal inflammation, characterized by focal infiltration of neutrophils, a type of inflammatory cell, into the epithelium. This typically occurs in the area overlying lymphoid aggregates. These neutrophils, along with mononuclear cells, may infiltrate the crypts, leading to inflammation (crypititis) or abscess (crypt abscess).


title: Crohn's disease

text: Granulomas, aggregates of macrophage derivatives known as giant cells, are found in 50% of cases and are most specific for Crohn's disease. The granulomas of Crohn's disease do not show "caseation", a cheese-like appearance on microscopic examination characteristic of granulomas associated with infections, such as tuberculosis. Biopsies may also show chronic mucosal damage, as evidenced by blunting of the intestinal villi, atypical branching of the crypts, and a change in the tissue type (metaplasia). One example of such metaplasia, "Paneth cell metaplasia", involves the development of Paneth cells (typically found in the small intestine and a key regulator of intestinal microbiota) in other parts of the gastrointestinal system.


title: Crohn's disease

text: The diagnosis of Crohn's disease can sometimes be challenging, and many tests are often required to assist the physician in making the diagnosis. Even with a full battery of tests, it may not be possible to diagnose Crohn's with complete certainty; a colonoscopy is approximately 70% effective in diagnosing the disease, with further tests being less effective. Disease in the small bowel is particularly difficult to diagnose, as a traditional colonoscopy allows access to only the colon and lower portions of the small intestines; introduction of the capsule endoscopy aids in endoscopic diagnosis. Giant (multinucleate) cells, a common finding in the lesions of Crohn's disease, are less common in the lesions of lichen nitidus.


title: Crohn's disease

text: Crohn's disease is one type of inflammatory bowel disease (IBD). It typically manifests in the gastrointestinal tract and can be categorized by the specific tract region affected. A disease of both the ileum (the last part of the small intestine that connects to the large intestine), and the large intestine, Ileocolic Crohn's accounts for fifty percent of cases. Crohn's ileitis, manifest in the ileum only, accounts for thirty percent of cases, while Crohn's colitis, of the large intestine, accounts for the remaining twenty percent of cases and may be particularly difficult to distinguish from ulcerative colitis.


title: Crohn's disease

text: Gastroduodenal Crohn's disease causes inflammation in the stomach and the first part of the small intestine called the duodenum. Jejunoileitis causes spotty patches of inflammation in the top half of the small intestine, called the jejunum. The disease can attack any part of the digestive tract, from mouth to anus. However, individuals affected by the disease rarely fall outside these three classifications, with presentations in other areas.


title: Crohn's disease

text: Crohn's disease may also be categorized by the behavior of disease as it progresses. These categorizations formalized in the Vienna classification of the disease. There are three categories of disease presentation in Crohn's disease: stricturing, penetrating, and inflammatory. Stricturing disease causes narrowing of the bowel that may lead to bowel obstruction or changes in the caliber of the feces. Penetrating disease creates abnormal passageways (fistulae) between the bowel and other structures, such as the skin. Inflammatory disease (or nonstricturing, nonpenetrating disease) causes inflammation without causing strictures or fistulae.


title: Crohn's disease

text: A colonoscopy is the best test for making the diagnosis of Crohn's disease, as it allows direct visualization of the colon and the terminal ileum, identifying the pattern of disease involvement. On occasion, the colonoscope can travel past the terminal ileum, but it varies from person to person. During the procedure, the gastroenterologist can also perform a biopsy, taking small samples of tissue for laboratory analysis, which may help confirm a diagnosis. As 30% of Crohn's disease involves only the ileum, cannulation of the terminal ileum is required in making the diagnosis. Finding a patchy distribution of disease, with involvement of the colon or ileum, but not the rectum, is suggestive of Crohn's disease, as are other endoscopic stigmata.


title: Crohn's disease

text: The utility of capsule endoscopy for this, however, is still uncertain. A "cobblestone"-like appearance is seen in approximately 40% of cases of Crohn's disease upon colonoscopy, representing areas of ulceration separated by narrow areas of healthy tissue.


title: Crohn's disease

text: A small bowel follow-through may suggest the diagnosis of Crohn's disease and is useful when the disease involves only the small intestine. Because colonoscopy and gastroscopy allow direct visualization of only the terminal ileum and beginning of the duodenum, they cannot be used to evaluate the remainder of the small intestine. As a result, a barium follow-through X-ray, wherein barium sulfate suspension is ingested and fluoroscopic images of the bowel are taken over time, is useful for looking for inflammation and narrowing of the small bowel. Barium enemas, in which barium is inserted into the rectum and fluoroscopy is used to image the bowel, are rarely used in the work-up of Crohn's disease due to the advent of colonoscopy. They remain useful for identifying anatomical abnormalities when strictures of the colon are too small for a colonoscope to pass through, or in the detection of colonic fistulae (in this case contrast should be performed with iodate substances).


title: Crohn's disease

text: CT and MRI scans are useful for evaluating the small bowel with enteroclysis protocols. They are also useful for looking for intra-abdominal complications of Crohn's disease, such as abscesses, small bowel obstructions, or fistulae. Magnetic resonance imaging (MRI) is another option for imaging the small bowel as well as looking for complications, though it is more expensive and less readily available. MRI techniques such as diffusion-weighted imaging and high-resolution imaging are more sensitive in detecting ulceration and inflammation compared to CT.


title: Crohn's disease

text: A complete blood count may reveal anemia, which commonly is caused by blood loss leading to iron deficiency or by vitamin B deficiency, usually caused by ileal disease impairing vitamin B absorption. Rarely autoimmune hemolysis may occur. Ferritin levels help assess if iron deficiency is contributing to the anemia. Erythrocyte sedimentation rate (ESR) and C-reactive protein help assess the degree of inflammation, which is important as ferritin can also be raised in inflammation. Serum iron, total iron binding capacity and transferrin saturation may be more easily interpreted in inflammation. Anemia of chronic disease results in a normocytic anemia.


title: Crohn's disease

text: Other causes of anemia include medication used in treatment of inflammatory bowel disease, like azathioprine, which can lead to cytopenia, and sulfasalazine, which can also result in folate deficiency. Testing for "Saccharomyces cerevisiae" antibodies (ASCA) and antineutrophil cytoplasmic antibodies (ANCA) has been evaluated to identify inflammatory diseases of the intestine and to differentiate Crohn's disease from ulcerative colitis. Furthermore, increasing amounts and levels of serological antibodies such as ASCA, antilaminaribioside [Glc(β1,3)Glb(β); ALCA], antichitobioside [GlcNAc(β1,4)GlcNAc(β); ACCA], antimannobioside [Man(α1,3)Man(α)AMCA], antiLaminarin [(Glc(β1,3))3n(Glc(β1,6))n; anti-L] and antichitin [GlcNAc(β1,4)n; anti-C] associate with disease behavior and surgery, and may aid in the prognosis of Crohn's disease.


title: Crohn's disease

text: Low serum levels of vitamin D are associated with Crohn's disease. Further studies are required to determine the significance of this association.


title: Crohn's disease

text: The most common disease that mimics the symptoms of Crohn's disease is ulcerative colitis, as both are inflammatory bowel diseases that can affect the colon with similar symptoms. It is important to differentiate these diseases, since the course of the diseases and treatments may be different. In some cases, however, it may not be possible to tell the difference, in which case the disease is classified as indeterminate colitis.