title: Chick-fil-A

text: In 1961, after 15 years in the fast food business, Cathy found a pressure-fryer that could cook the chicken sandwich in the same amount of time it took to cook a fast-food hamburger. Following this discovery, he registered the name Chick-fil-A, Inc. The company's trademarked slogan, ""We Didn't Invent the Chicken, Just the Chicken Sandwich,"" refers to their flagship menu item, the Chick-fil-A chicken sandwich. Though Chick-Fil-A was the first national chain to make a quick-service, fried chicken sandwich its flagship item, several sources have demonstrated that Cathy's much broader claim to have "invented the chicken sandwich," which is referenced in the company's slogan and has been repeatedly featured in press materials, is untrue.


title: Chick-fil-A

text: From 1964 to 1967, the sandwich was licensed to over fifty eateries, including Waffle House and the concession stands of the new Houston Astrodome. The Chick-Fil-A sandwich was withdrawn from sale at other restaurants when the first standalone location opened in 1967, in the food court of the Greenbriar Mall in Atlanta.


title: Chick-fil-A

text: During the 1970s and early 1980s, the chain expanded by opening new locations in suburban malls' food courts. The first freestanding location was opened April 16, 1986, on North Druid Hills Road in Atlanta, Georgia, and the company began to focus more on this stand-alone type unit rather than on the food court type. Although it has expanded outward from its original geographic base, most new restaurants are located in Southern suburban areas.


title: Chick-fil-A

text: Since 1997, the Atlanta-based company has been the title sponsor of the Peach Bowl, an annual college football bowl game played in Atlanta on New Year's Eve. Chick-fil-A also is a key sponsor of the SEC and the ACC of college athletics.


title: Chick-fil-A

text: In October 2015, the company opened a three-story restaurant in Manhattan that became the largest free-standing Chick-fil-A in the country at that time.


title: Chick-fil-A

text: On December 17, 2017, Chick-fil-A broke their tradition and opened on a Sunday to prepare meals for passengers left stranded during the power outage at Atlanta Hartsfield-Jackson International Airport, and on January 13, 2019, a Chick-fil-A franchise in Mobile, Alabama, opened on Sunday to honor a birthday wish of a 14-year-old boy with cerebral palsy and autism.


title: Chick-fil-A

text: Chick-fil-A's business strategy involves a focus on a small menu and on customer service. While many fast food chains often expand their menu offerings to attempt to attract new customers, Chick-fil-A's business model is to remain focused on selling chicken sandwiches. The name capital A is meant to indicate that their chicken is "grade A top quality". In addition, an emphasis on customer service has allowed Chick-fil-A to consistently lead the fast food industry in customer satisfaction. These factors are seen as the reason for Chick-fil-A's massive growth in the United States.


title: Chick-fil-A

text: Chick-fil-A retains ownership of each restaurant. Chick-fil-A selects the restaurant location and builds it. Chick-fil-A franchisees need only a $10,000 initial investment to become an operator. Each operator is handpicked and goes through a rigorous training program; the interviews plus training can take months and is not an easy process. Chick-fil-A states on their site:


title: Chick-fil-A

text: Chick-fil-A grossed an average of $4.8 million per restaurant in 2016, despite opening only 6 days a week, the highest sales of all fast food restaurants in the United States. (Whataburger was second with $2.7 million per restaurant average).


title: Chick-fil-A

text: In 2019, Chick-fil-A reported $11.3 billion in sales in the United States, behind only McDonald's with $40.4 billion in sales in 2019.


title: Chick-fil-A

text: To respond to the aforementioned success and market dominance Chick-fil-A, competing fried chicken chain Popeyes introduced a fried chicken sandwich, starting the Chicken Sandwich Wars, with many more companies eventually following Popeyes.


title: Chick-fil-A

text: S. Truett Cathy was a devout Southern Baptist; his religious beliefs had a major impact on the company. The company's official statement of corporate purpose says that the business exists "To glorify God by being a faithful steward of all that is entrusted to us. To have a positive influence on all who come in contact with Chick-fil-A." Cathy opposed the company becoming public for religious and personal reasons.


title: Chick-fil-A

text: Their website states, "The Chick-fil-A culture and service tradition in our Restaurants is to treat every person with honor, dignity and respect –regardless of their belief, race, creed, sexual orientation or gender."


title: Chick-fil-A

text: The founder's beliefs are responsible for the chain's most well-known and distinctive feature: in accordance with the Christian doctrine of first-day Sabbatarianism, all Chick-fil-A locations (both corporate owned and franchised) are closed on Sundays, as well as on Thanksgiving and Christmas. Cathy states as the final step in his Five-Step recipe for Business Success "I was not so committed to financial success that I was willing to abandon my principles and priorities. One of the most visible examples of this is our decision to close on Sunday. Our decision to close on Sunday was our way of honoring God and of directing our attention to things that mattered more than our business."


title: Chick-fil-A

text: In an interview with ABC News's "Nightline", Truett's son Dan T. Cathy told reporter Vicki Mabrey that the company is also closed on Sundays because "by the time Sunday came, he was just worn out. And Sunday was not a big trading day, anyway, at the time. So he was closed that first Sunday and we've been closed ever since. He figured if he didn't like working on Sundays, that other people didn't either." The younger Cathy also quoted his father as saying, "I don't want to ask people to do that what I am not willing to do myself."


title: Chick-fil-A

text: Chick-fil-A's Sunday closures extend to non-traditional locations. In addition to countless shopping malls and airports, a Chick-fil-A location at Mercedes-Benz Stadium in Atlanta is closed on Sundays despite the fact that its main tenant, the Atlanta Falcons, plays most of their home games on Sundays. The location is open when the Falcons have a Monday night, Thursday night or Saturday home game, as well as non-Sunday home games of Atlanta United FC and other events at the stadium. The Chick-fil-A remained closed for Super Bowl LIII. On Sundays, the digital signs are flipped and concessionaire Levy Restaurants sells nonbranded food and drinks at the location.


title: Chick-fil-A

text: To honor the Western Christian liturgical season of Lent, Chick-fil-A promotes fish sandwiches in respect of the fact that this part of the Church Year is associated with the Friday Fast, with many practicing Christian vegetarianism throughout all the forty days of Lent.


title: Chick-fil-A

text: According to the Food and Drug Administration (FDA), antibiotics used in livestock, many of which are also used to treat humans, have contributed to the rise of dangerous bacteria. In December 2012, the FDA announced plans to phase out certain antibiotics in the food production industry.


title: Chick-fil-A

text: In February 2014, Chick-fil-A announced plans to serve chicken raised without antibiotics in its restaurants nationwide within five years. Chick-fil-A was the first quick service restaurant to set forth a plan and commit to serving only poultry raised without antibiotics. They achieved this goal in May 2019.


title: Chick-fil-A

text: In 2011, food blogger and activist Vani Hari wrote a post titled "Chick-fil-A or Chemical Fil-A?" on her website, FoodBabe.com. She asserted that Chick-fil-A sandwiches contained nearly 100 ingredients, including peanut oil with tert-butylhydroquinone (TBHQ), a preservative for unsaturated vegetable oils. In October 2012, Chick-fil-A invited Hari to meet with company executives at its headquarters. In December 2013, Chick-fil-A notified Hari that it had eliminated the dye Yellow No. 5 and had reduced the sodium content in its chicken soup. The company also said that it is testing a peanut oil that does not contain TBHQ and that it would start testing sauces and dressings made without high-fructose corn syrup in 2014.


title: Chick-fil-A

text: In September 1994, Chick-fil-A opened its first location outside of the United States inside a student center food court at the University of Alberta in Edmonton, Alberta, Canada. This location did not perform very well and was closed within two or three years. The company returned to the province of Alberta by opening an outlet at the Calgary International Airport in Calgary in May 2014. This restaurant closed in 2019.


title: Chick-fil-A

text: In July 2018, Chick-fil-A announced plans to expand within Canada by opening a new restaurant in Toronto, Ontario, in 2019. That location opened on September 6, 2019 in the Yonge and Bloor Street area, marked by protests criticizing the company's violation of animal rights and "history of supporting anti-LGBTQ causes". Chick-fil-A announced that it would open two other locations in Toronto during 2019, and 12 additional stores in the Greater Toronto Area over the subsequent five years. The chain's second Toronto location opened at the Yorkdale Shopping Centre in January 2020.


title: Chick-fil-A

text: The company expanded to other areas of Ontario in 2021, opening standalone locations with drive-thrus in Kitchener and Windsor, in August and October respectively.


title: Chick-fil-A

text: In August 1996, Chick-fil-A opened its first location outside of North America by building a restaurant in Durban, South Africa. A second location was opened in Johannesburg in November 1997. Since neither of the South African locations was profitable, both of these locations were closed in 2001.


title: Chick-fil-A

text: A Chick-fil-A operated in Edinburgh during Spring 2018. On October 10, 2019, Chick-fil-A returned to Europe, with the opening of a store at The Oracle shopping centre in Reading, UK. The store closed in March 2020 after The Oracle opted not to continue the lease of the location beyond the six-month pilot period in the face of continued protests over the chain's anti-LGBTQ stance.


title: Chick-fil-A

text: In February 2019, Chick-fil-A opened a store on a 12-month pilot scheme in Aviemore, Scotland. The store was closed in January 2020 amidst protest and controversy from locals and customers regarding the chain's former donations to charities supporting anti-LGBT rights causes. The reason for closing however was not the controversy (only 1,000 signatures were gained in a petition) but the pop-up nature of the experiment and the competition from more established outlets.


title: Chick-fil-A

text: In July 2018, Chick-fil-A announced it would be opening its first location in Hawaii in Kahului in early 2022, with additional locations in Honolulu and Kapoleo to follow. In December 2020, it was announced the company would open a new location in Puerto Rico. The first Puerto Rican location opened on March 3, 2022 in Bayamón.


title: Chick-fil-A

text: "Eat Mor Chikin" is the chain's most prominent advertising slogan, created by The Richards Group in 1995. The slogan is often seen in advertisements, featuring Holstein dairy cows that are often seen wearing (or holding) signs that (usually) read "Eat Mor Chikin" in all capital letters. The ad campaign was temporarily halted on January 1, 2004 during a mad cow disease scare, so as not to make the chain seem insensitive or appear to be taking advantage of the scare to increase its sales. Two months later, the cows were put up again. The cows replaced the chain's old mascot, Doodles, an anthropomorphized chicken who still appears as the C on the logo.


title: Chick-fil-A

text: Chick-fil-A vigorously protects its intellectual property, sending cease and desist letters to those they think have infringed on their trademarks. The corporation has successfully protested at least 30 instances of the use of an "eat more" phrase, saying that the use would cause confusion of the public, dilute the distinctiveness of their intellectual property, and diminish its value.


title: Chick-fil-A

text: A 2011 letter to Vermont artist Bo Muller-Moore who screen prints T-shirts reading: "Eat More Kale" demanded that he cease printing the shirts and turn over his website. The incident drew criticism from Vermont governor Peter Shumlin, and created backlash against what he termed Chick-fil-A's "corporate bullying." On December 11, 2014, Bo Muller-Moore announced that the U.S. Patent Office granted his application to trademark his "Eat More Kale" phrase. A formal announcement of his victory took place on December 12, 2014, with Shumlin and other supporters on the Statehouse steps. His public fight drew regional and national attention, the support of Shumlin, and a team of pro-bono law students from the University of New Hampshire legal clinic.


title: Chick-fil-A

text: After 22 years with The Richards Group, Chick-fil-A switched to McCann New York in 2016. Along with the cows, ads included famous people in history in a campaign called "Chicken for Breakfast. It's not as crazy as you think."


title: Chick-fil-A

text: Chick-fil-A has donated over $5 million, via the WinShape Foundation, to groups that oppose same-sex marriage. In response, students at several colleges and universities worked to ban or remove the company's restaurants from their campuses.


title: Chick-fil-A

text: In June and July 2012, Chick-fil-A's chief operating officer Dan T. Cathy made several public statements about same-sex marriage, saying that those who "have the audacity to define what marriage is about" were "inviting God's judgment on our nation". Several prominent politicians expressed disapproval. Boston Mayor Thomas Menino and Chicago Alderman Proco "Joe" Moreno said they hoped to block franchise expansion into their areas. The proposed bans drew criticism from liberal pundits, legal experts, and the American Civil Liberties Union. The Jim Henson Company, which had a "Pajanimals" kids' meal toy licensing arrangement with Chick-fil-A, said it would cease its business relationship, and donate the payment to the Gay & Lesbian Alliance Against Defamation. Chick-fil-A stopped distributing the toys, claiming that unrelated safety concerns had arisen prior to the controversy. Chick-fil-A released a statement on July 31, 2012, saying, "We are a restaurant company focused on food, service, and hospitality; our intent is to leave the policy debate over same-sex marriage to the government and political arena."


title: Chick-fil-A

text: In response to the controversy, former Arkansas Governor Mike Huckabee initiated a Chick-fil-A Appreciation Day movement to counter a boycott of Chick-fil-A launched by same-sex marriage activists. Many of the chain's stores reported record levels of customers that day. The United States Federal Aviation Administration also responded to two cities that were preventing Chick-fil-A from opening in their international airport, citing "Federal requirements prohibit airport operators from excluding persons on the basis of religious creed from participating in airport activities that receive or benefit from FAA grant funding."


title: Chick-fil-A

text: In April 2018, Chick-fil-A reportedly continued to donate to the Fellowship of Christian Athletes, which opposes gay marriage. In a November 18, 2019 interview, Chick-fil-A president Tim Tassopoulos said the company would stop donating to The Salvation Army and the Fellowship of Christian Athletes.


title: Chick-fil-A

text: The popularity of Chick-fil-A's drive-throughs in the United States has led to traffic problems, police interventions, and complaints by neighboring businesses in more than 20 states. The long drive-through lines have been reported to cause traffic backups, blocking emergency vehicles and city buses and increasing the risk of collisions and pedestrian injuries.


title: Chick-fil-A

text: Truett Cathy opened his first restaurant in 1946, The Dwarf Grill – later renamed the Dwarf House – in Hapeville, Georgia, and developed the pressure-cooked chicken breast sandwich there. At the original Chick-fil-A Dwarf Grill, in addition to the full-size entrances, there is also an extra small-sized front door. The original Dwarf House in Hapeville, Georgia is open 24 hours a day, six days a week, except on Sundays, Thanksgiving, and Christmas. The store closes at 10:00 p.m. on Saturday nights, and the day before Thanksgiving and Christmas and reopens at 6 a.m. on Monday mornings and the day after Thanksgiving and Christmas. It has a larger dine-in menu than the other Dwarf House locations as well as an animated seven dwarfs display in the back of the restaurant. It was across the street from the former Ford Motor Company factory called Atlanta Assembly.


title: Chick-fil-A

text: Opened in 1986, Truett's original, full-service restaurants offer a substantial menu and provide customers a choice of table service, walk-up counter service or a drive-thru window. There are currently five of the original eleven Chick-fil-A Dwarf House restaurants still operating in the metro Atlanta area, including Duluth, Riverdale, Jonesboro, Forest Park and Fayetteville.


title: Chick-fil-A

text: In 1996, the first Truett's Grill was opened in Morrow, Georgia. The second location opened in 2003 in McDonough, Georgia, and a third location opened in 2006 in Griffin, Georgia. Similar to the Chick-fil-A Dwarf Houses, these independently owned restaurants offer traditional, sit-down dining and expanded menu selections in a diner-themed restaurant. In 2017, Chick-fil-A demolished several Dwarf House locations to replace them with Truett's Grill locations.


title: Chick-fil-A

text: Truett's Chick-fil-A is designed in honor of founder S. Truett Cathy. The restaurant is decorated with family photos and favorite quotes of the restaurant founder. The restaurant offers drive-thru, counter, and sit-down service. The restaurant offers breakfast, lunch and dinner. There are four locations including Newnan, Rome, Stockbridge, and Woodstock, Georgia.


title: Chick-fil-A

text: Truett Cathy visited Hawaii and loved the experience so much that he wanted to bring Hawaii to Fayetteville Georgia. At the age of 92 he opened Truett's Luau in 2013. The menu includes island favorites with a southern spin. The restaurant offers sit down, counter and drive-thru service.


title: Chick-fil-A

text: Chick-fil-A has been run by the Cathy family since the restaurant chain's founding in 1946; it is currently being led by the third-generation of the Cathy family.


title: Chick-fil-A

text: Based on data from 2018, the most popular (most ordered) item was the waffle fries followed by soft drinks, chicken nuggets, and the original chicken sandwich. These items should be available at every franchise location with some locations offering the full menu or close to the full menu. The full list of menu items and nutrition information can be found on Chick-fil-A's website.


title: Ruud van Nistelrooy

text: Rutgerus Johannes Martinus van Nistelrooij (anglicised to Van Nistelrooy; born 1 July 1976) is a Dutch professional football coach and former player. He is currently the coach of PSV Eindhoven.


title: Ruud van Nistelrooy

text: A former footballer, Van Nistelrooy is often considered one of the best strikers of all time. He has been the top scorer in three separate UEFA Champions League seasons, and is the sixth-highest goalscorer in the competition's history with 56 goals. He has also been the top scorer in three different European domestic leagues. In 2004, he was listed in the FIFA 100 of the world's greatest living players.


title: Ruud van Nistelrooy

text: Van Nistelrooy began his career with Den Bosch, before moving onto Heerenveen, eventually making a name for himself at PSV Eindhoven, where he won two Eredivisie titles. His goalscoring record at PSV attracted attention from Manchester United; a deal was in place in the summer of 2000, but because of injury problems, his move was secured a year later for a then British record fee of £19 million. His time at United was successful, winning the Premier League, FA Cup, Football League Cup, and FA Community Shield, along with winning the Sir Matt Busby Player of the Year twice. Van Nistelrooy scored 150 goals in just 219 games for United, as well as becoming at the time their all-time European record goalscorer, but fell out of favour towards the end of his tenure. Real Madrid then secured his services in 2006. Although an injury blighted the end of his days with Madrid, he won La Liga twice and the Supercopa de España before signing for Hamburger SV during the January transfer window in 2010. After one-and-a-half seasons with Hamburg, he moved back to Spain with Málaga in the summer of 2011. His retirement from football was announced on 14 May 2012.


title: Ruud van Nistelrooy

text: Internationally, Van Nistelrooy represented the Netherlands on 70 occasions, netting 35 times. He was part of the Euro 2004, 2006 World Cup, and Euro 2008 squads.


title: Ruud van Nistelrooy

text: Born in Oss, North Brabant, Van Nistelrooy started his career in 1993, aged 17, with Dutch Eerste Divisie side Den Bosch, where he was converted from a central midfielder to centre-forward, after playing for local clubs Nooit Gedacht and RKSV Margriet. After netting 12 goals in 31 games in the 1996–97 campaign, he transferred for €360,000 to Heerenveen the next year, and scored 13 goals in 31 matches in his only season with the club. He was then signed by PSV Eindhoven the next season for €6.3 million, a then-record transfer sum between two Dutch teams.


title: Ruud van Nistelrooy

text: He scored 31 goals in 34 matches, the highest season total in the Eredivisie and second-highest in Europe overall, in addition to scoring all three of PSV's goals in a Champions League match against HJK Helsinki on 25 November 1998. Van Nistelrooy capped off the year by winning the Dutch Player of the Year award. The following season, he won his second Eredivisie scoring title with 29 goals. According to a 2001 interview with "The Daily Telegraph," Manchester United coach Sir Alex Ferguson said that his son, Darren, who was at try-outs for Eredivisie rival Heerenveen at the time, begged his father, "You've got to sign Van Nistelrooy right away, he's fantastic. We've been watching him." Ferguson sent team representatives to PSV's next league game and signed Van Nistelrooy the next day.


title: Ruud van Nistelrooy

text: Van Nistelrooy looked set to complete a club record £18.5 million transfer to Manchester United in the summer of 2000. He was to be unveiled at a press conference four days later, but this was instead used to announce that the transfer had been postponed over concerns about his fitness, having not played for a month due to problems with his knee. The transfer was then cancelled after PSV refused to agree to further medical tests, and the next day he suffered a rupture to his anterior cruciate knee ligaments during a training session, leaving him injured for a year.


title: Ruud van Nistelrooy

text: A year later, Van Nistelrooy signed a five-year contract after passing his medical. He downplayed United's £19 million investment to reporters, saying, "The price is not heavy for me – it lifts me up because it means United have big confidence in me."


title: Ruud van Nistelrooy

text: Van Nistelrooy made his debut in the Charity Shield against Liverpool, scoring in a 2–1 loss. On 19 August, Van Nistelrooy made his Premier League debut against Fulham at Old Trafford, and scored two goals to help United to a 3–2 win. He scored his first Champions League goals on 17 October in a 3–2 loss to Deportivo La Coruña.


title: Ruud van Nistelrooy

text: On 22 December, Van Nistelrooy scored his first Premier League hat-trick in a 6–1 win against Southampton. In the FA Cup, Van Nistelrooy started on the bench for the third round tie against Aston Villa due to a groin strain, but was substituted on for Luke Chadwick in the second-half with United 2–0 down and scored two "sublime" goals in three minutes to help United advance to the fourth round with a 3–2 win.


title: Ruud van Nistelrooy

text: In total during his first season, Van Nistelrooy scored 23 goals in 32 league games. He broke the record he shared with Mark Stein, Alan Shearer and Thierry Henry, by scoring in eight consecutive league games. He also scored ten Champions League goals, and was named the PFA Players' Player of the Year.


title: Ruud van Nistelrooy

text: The following season, he finished as the top Premier League scorer with 25 goals in 34 games, with a goal on the final day against Everton earning him the Golden Boot ahead of Arsenal's Thierry Henry. His tally included three hat-tricks against Newcastle United, Fulham, and Charlton Athletic. He also scored in each of the final eight games of the season as United won the title. Van Nistelrooy won the Premier League Player of the Season in 2003. He was accredited with spearheading the title win for United with a goal tally that was described as "astonishing". After scoring 12 Champions League goals in nine consecutive matches, he was named by UEFA as the best striker in Europe.


title: Ruud van Nistelrooy

text: Van Nistelrooy started the 2003–04 season by scoring twice in his first two league matches. This meant he had scored in 10 consecutive league games, then a Premier League record, which stood until 2015 when Jamie Vardy scored in 11 consecutive matches. In the 0–0 draw on 21 September 2003, later dubbed the Battle of Old Trafford, Van Nistelrooy was at the centre of one of the most infamous incidents of the Arsenal–Manchester United rivalry. After missing a last-minute penalty that would have won the game for United, Van Nistelrooy was attacked by Martin Keown, prompting a melee involving several players from both sides; five Arsenal players including Keown received various bans and fines, while the club itself received a record fine of £175,000. Earlier in the game, he had been fouled by Patrick Vieira, who was sent off for a second bookable offence. Vieira and his manager Arsène Wenger both accused Van Nistelrooy of cheating and stamping on Vieira, prompting a vociferous defence by Alex Ferguson.


title: Ruud van Nistelrooy

text: On 27 September, he scored a hat-trick against Leicester City in a 4–1 victory. He scored his 100th goal for the club in a dramatic 4–3 victory over Everton on 7 February 2004.


title: Ruud van Nistelrooy

text: In the FA Cup fifth round derby against Manchester City, Van Nistelrooy scored twice to help ten-man United win 4–2, and again scored twice in the quarter-final against Fulham as United came from behind to win 2–1. He scored a further two goals, including one penalty, in United's victory over Millwall in the 2004 FA Cup Final.


title: Ruud van Nistelrooy

text: Van Nistelrooy missed a large part of the 2004–05 season due to injury, but nonetheless scored a Champions League-best eight goals. One of them was his 30th career European goal, which he scored in a 2–2 Champions League group stage draw with Lyon on 15 September 2004, overtaking Denis Law's previous club record of 28 goals. Law later said to reporters, "I'm delighted for Ruud. It could not happen to a nicer guy."


title: Ruud van Nistelrooy

text: On 24 October, Arsenal returned to Old Trafford for another dramatic fixture. Arsenal entered the fixture with 49-game unbeaten run and had been dubbed "The Invincibles", but United won the game 2–0. Van Nistelrooy scored the opening goal from the penalty spot, atoning for the penalty miss the previous year, with Wayne Rooney scoring a second. Van Nistelrooy was later banned for three games for a foul on Ashley Cole that the referee had missed. On 3 November, Van Nistelrooy scored all four goals in a 4–1 win against Sparta Prague. On 17 April 2005, he scored two goals in the FA Cup semi-final in a 4–1 win against Newcastle, but United lost the final on penalties to Arsenal.


title: Ruud van Nistelrooy

text: At the start of the 2005–06 season, Van Nistelrooy scored in United's first four Premier League games. He finished as the second-highest league scorer with 21 goals, behind Arsenal's Thierry Henry. However, he was benched for the League Cup Final against Wigan Athletic, fuelling speculation of a rift between him and Alex Ferguson, which Van Nistelrooy denied. He was nonetheless left on the bench for six consecutive league matches, and though he then returned to the starting line-up and scored match-winners against West Ham United and Bolton Wanderers, fresh doubt spread over Van Nistelrooy's future when he was benched for United's season finale win over Charlton Athletic. Ferguson claimed that Van Nistelrooy was angry at the decision and left the stadium three hours before kick-off. On 9 May 2006, it was reported that Van Nistelrooy's exclusion from the squad was due to a training session fight between him and teammate Cristiano Ronaldo. Van Nistelrooy allegedly criticised Ronaldo's tendency to hold onto the ball instead of passing to his teammates, which sparked the fight, after which Van Nistelrooy remarked, "What are you going to do? Complain to your daddy?" This was in reference to United's Portuguese assistant manager, Carlos Queiroz, but Ronaldo took the statement literally and allegedly broke into tears since his father, José had died eight months previously. Van Nistelrooy later apologised to Ferguson for his behaviour in the previous few months.


title: Ruud van Nistelrooy

text: Van Nistelrooy signed with Spanish La Liga side Real Madrid on 28 July, departing Old Trafford after five seasons with a total of 150 goals in 219 appearances, with his final goal coming on 1 April against Bolton, scoring what proved to be the winning goal. With 38 goals, he is also the club's second all-time European goalscorer, behind Wayne Rooney.


title: Ruud van Nistelrooy

text: On 15 July 2006, Ferguson confirmed that Van Nistelrooy wanted to leave Manchester United and Real Madrid announced two weeks later that he had signed a three-year contract after being purchased for €14 million.


title: Ruud van Nistelrooy

text: Van Nistelrooy made his debut for the Spanish club in a 1–0 friendly win over Reggina on 4 August 2006. Van Nistelrooy scored a hat-trick in his second league match against Levante and, on 12 November 2006, he scored all four of Real Madrid's goals in a 4–1 victory over Osasuna. For the first six months he was a teammate of Ronaldo, a player whom Van Nistelrooy regards as the best he ever played with. Van Nistelrooy won the league's Pichichi award with 25 goals as Real Madrid took home the 2006–07 title, and he also equalled the longest consecutive scoring streak in La Liga history with seven straight matches, tying a league record shared by Hugo Sánchez.


title: Ruud van Nistelrooy

text: In January 2008, Van Nistelrooy signed a contract extension keeping him with Madrid until 2010, with the expiration date one day shy of his 34th birthday. He underwent ankle surgery in March, and returned for the El Clásico derby against Barcelona on 7 May, in which he netted a penalty two minutes after coming on as a substitute. He finished the season with 20 goals in 33 appearances.


title: Ruud van Nistelrooy

text: In November 2008, Real Madrid announced that Van Nistelrooy would miss the remainder of the 2008–09 season after exploratory arthroscopic surgery revealed a partially torn meniscus in his right knee, with an expected recovery time of six to nine months following a second operation to repair the damage. Van Nistelrooy travelled to the United States to see specialist Richard Steadman, who had previously operated on the same knee back in 2000. At the time of his injury, he had 10 goals in 12 club appearances for the season. Following the injury, he was de-registered by Real Madrid for the rest of the 2008–09 season, and his shirt number was given to Dani Parejo. On 24 August 2009, in the last pre-season match before the start of La Liga, Van Nistelrooy stepped on the pitch for the first time since his injury and played the last 15 minutes of the game against Rosenborg, substituting Kaká. Van Nistelrooy came on for Cristiano Ronaldo in the 80th minute against Xerez in his first La Liga match since recovering from his injury. In the 81st minute, he provided the assist for a Karim Benzema goal, following it with his own 88th-minute goal. During his strike, however, he picked up a thigh injury, where it was later revealed by Real Madrid that he would be out from first team action for up to six weeks. On 27 October, Van Nistelrooy made his second comeback of the season coming on as a substitute for Raúl in the 71st minute against Alcorcón in the Copa del Rey.


title: Ruud van Nistelrooy

text: On 23 January 2010, Van Nistelrooy signed an 18-month contract with the German club Hamburger SV until June 2011. He made his first appearance for the club after coming off the bench in the last two minutes of Hamburg's 3–3 draw with 1. FC Köln on 6 February. Van Nistelrooy scored his first two goals for Hamburg on 13 February 2010 against VfB Stuttgart in the 75th and 77th minutes of a 3–1 win, after entering the game just a few minutes prior. On 11 March 2010, he scored his first UEFA Europa League goal in the 40th minute of Hamburg's match against Anderlecht.


title: Ruud van Nistelrooy

text: Van Nistelrooy scored his only competitive hat-trick with Hamburg on 15 August 2010, in a 5–1 win over Torgelower SV Greif in the first round of the 2010–11 DFB-Pokal. On 21 August 2010, he scored a brace in Hamburg's season opener against Schalke 04, which HSV won 2–1. During that match, he played against his friend and former Real Madrid teammate Raúl, who was making his Bundesliga debut. In the January transfer window, Van Nistelrooy was linked a return move back to Real Madrid and could be used for a short-term basis to cover, following injuries of Gonzalo Higuaín and Karim Benzema as manager José Mourinho would be happy for Van Nistelrooy to join the club as Mourinho left the door for him. Van Nistelrooy admitted he seriously considered moving back to the club if the bid happened. The club, however, rejected Madrid's bid for Van Nistelrooy, giving the club a warning as Hamburg wants to keep hold of him until the transfer window ended. Despite being angered over his move to Real Madrid rejected, Van Nistelrooy said he would remain committed at Hamburg. During a match between Hamburg and Hannover 96 on 16 April 2011, Van Nistelrooy suffered a calf injury that kept him out until the last matchday.


title: Ruud van Nistelrooy

text: Van Nistelrooy netted seven goals and made two assists in 25 appearances in his only full season with Hamburg.


title: Ruud van Nistelrooy

text: On 1 June 2011, Van Nistelrooy returned to Spain to pen a one-year deal with La Liga side Málaga, on a free transfer. Van Nistelrooy was presented at La Rosaleda Stadium as he was welcomed by 15,000 Málaga fans. He made his debut in a 2–1 loss against Sevilla on the opening game of the 2011–12 season.


title: Ruud van Nistelrooy

text: Van Nistelrooy registered his first goal on 1 October 2011 against Getafe. On 21 December, against the same club, he opened the scoring with a volley as Málaga won 3–2 on aggregate in the Copa del Rey. Later on in the season, Van Nistelrooy scored two more goals in the league against Espanyol and Racing Santander, with the latter being his final goal of his career. Just one day before his retirement, Van Nistelrooy made his last appearance of his career, coming on as a substitute in the 75th minute for goalscorer Salomón Rondón, who scored the only goal in Málaga's league match against Sporting Gijón.


title: Ruud van Nistelrooy

text: On 14 May 2012, Van Nistelrooy announced his retirement from football at the age of 35. He told Sport1 he previously made hints that his football career was coming to an end after insisting Málaga would be his last club.


title: Ruud van Nistelrooy

text: Van Nistelrooy earned 70 caps and scored 35 goals for the Netherlands. He made his debut for the national team in a friendly match against Germany on 18 November 1998. However, the cruciate ligament injury which postponed his transfer to Manchester United also ruled Van Nistelrooy out of Euro 2000.


title: Ruud van Nistelrooy

text: As the Dutch failed to qualify for the 2002 World Cup, Van Nistelrooy did not make his tournament debut for the Netherlands until Euro 2004, where he and the Czech Republic's Milan Baroš were the only players to score in all three group stage matches. The Netherlands reached the semi-finals where they were defeated by hosts Portugal 2–1. Van Nistelrooy was named in the tournament all-star team.


title: Ruud van Nistelrooy

text: During a 2006 World Cup qualifying match, he scored in the Dutch's 4–0 win over bottom-placed Andorra and was yellow-carded for going to Andorra player Antoni Lima and celebrating in front of him, following an incident six minutes before when Van Nistelrooy missed a penalty and Lima laughed at him. He was a part of coach Marco van Basten's squad for the 2006 World Cup finals, for which he served as the official FIFA/SOS ambassador. He started, and was substituted, in all of the Netherlands' group stage matches, and scored his lone goal against the Ivory Coast. Van Nistelrooy was dropped to the bench by Van Basten without an explanation for the Netherlands' second round match, which saw them again eliminated by Portugal.


title: Ruud van Nistelrooy

text: Van Basten left the striker out of the squad for a friendly against the Republic of Ireland on 16 August 2006. Dirk Kuyt replaced Van Nistelrooy in their next match against Portugal in September. After Klaas-Jan Huntelaar was unavailable for Euro 2008 qualifiers against Bulgaria and Belarus due to injury, Van Nistelrooy refused Van Basten's request to take his place on the roster.


title: Ruud van Nistelrooy

text: On 23 January 2007, Van Nistelrooy announced his retirement from international football following continued disputes with Van Basten, which had started back in 2006 during the course of the World Cup finals matches. After several phone conversations and at the persuasion of veteran goalkeeper Edwin van der Sar, however, both player and coach put aside their differences. Van Basten announced four months later that Van Nistelrooy was returning to the "Oranje". On 8 September, Van Nistelrooy filled Huntelaar's spot, as previously requested, for the qualifier against Bulgaria, scoring in a 2–0 victory, and scored the winning goal four days later in injury time of the Netherlands' win over Albania.


title: Ruud van Nistelrooy

text: At Euro 2008, Van Nistelrooy scored for the Netherlands in their decisive 3–0 victory over Italy in the group stage, and scored the equaliser in their eventual 3–1 loss to Russia in the quarter-finals. On 4 August, he again announced his retirement from international competition.


title: Ruud van Nistelrooy

text: During the buildup to the 2010 World Cup, Van Nistelrooy again made himself available, but was left out by the Netherlands' new coach Bert van Marwijk. After being left out for the World Cup, Van Nistelrooy said he had no choice but to face the fact that his international career is finished.


title: Ruud van Nistelrooy

text: After main striker Robin van Persie suffered an injury during a match with his club Arsenal, Van Marwijk gave Van Nistelrooy a chance to reclaim his position as the main striker of the Netherlands' national team. Van Nistelrooy was invited to two Netherlands' Group E qualification matches for Euro 2012 against San Marino and Finland. He scored in the 5–0 victory against San Marino on 3 September 2010.


title: Ruud van Nistelrooy

text: Van Nistelrooy was again recalled to the squad in March 2011 for two Euro 2012 qualification games with Hungary, after injuries to strikers Klaas-Jan Huntelaar, Arjen Robben and Theo Janssen. In the away game on 25 March, he appeared as a late substitute for Dirk Kuyt while in the return game in Amsterdam four days later, he came off the bench to score his 35th international goal. adding it is "wonderful to be able to add something to this Oranje team", as he told Berend Scholten.


title: Ruud van Nistelrooy

text: A highly prolific goalscorer, Van Nistelrooy was known for being extremely clinical and opportunistic in front of goal, and stood out throughout his career for his outstanding striking ability and finishing ability with either foot as well as his head, which earned him a reputation as one of the best strikers of his generation. Due to his excellent positional sense, quick reactions, and intelligent offensive movement, he excelled at finding space in the penalty area and at anticipating his opponents to the ball, and was also known for his ability to time his runs to lose his markers, beat the offside trap, and get on the end of his teammates' passes; his tendency to be in the right place at the right time in the box saw him occasionally labelled as a "poacher" in the media.


title: Ruud van Nistelrooy

text: A well-rounded centre-forward, in addition to his eye for goal, Van Nistelrooy was gifted with pace, physical strength, and shooting power, as well as excellent technical skills, and an ability to hold up the ball with his back to goal and link-up with his teammates or provide them with assists, due to his ability to read the game. He was also an accurate penalty taker. In spite of his talent and goalscoring ability, however, at times he drew criticism from managers, players and pundits for his controversial behaviour, as well as for having a tendency to be selfish, overly flamboyant, or for his penchant for simulation.


title: Ruud van Nistelrooy

text: On 22 June 2013, Van Nistelrooy joined PSV as a coaching intern working with the under-17s. He was revealed as the new striker coach of the under-17s, 19s and the reserve team in February 2016.


title: Ruud van Nistelrooy

text: In March 2014, it was announced that Van Nistelrooy would be assisting Guus Hiddink after the 2014 World Cup.


title: Ruud van Nistelrooy

text: On 25 June 2018, Van Nistelrooy became the new manager of the PSV under-19s, taking over Mark van Bommel, who left his role for the senior team.


title: Ruud van Nistelrooy

text: In December 2019 it was confirmed, that Van Nistelrooy beside his position at PSV, also had been added to Ronald Koeman's backroom staff as an assistant manager together with Maarten Stekelenburg ahead of the Euro 2020, after Kees van Wonderen recently had left the position.


title: Ruud van Nistelrooy

text: In March 2022, Van Nistelrooy was appointed as the replacement for the outgoing Roger Schmidt as PSV's head coach. He signed a three-year contract beginning with the 2022–23 season.


title: Ruud van Nistelrooy

text: Van Nistelrooy married his girlfriend, Leontien Slaats, in July 2004. The couple had their first child, a girl named Moa Annette, in September 2006, and a son named Liam in March 2008. Van Nistelrooy is a Roman Catholic Christian.


title: Ruud van Nistelrooy

text: Van Nistelrooy and his wife are both heavily involved with the charity organization SOS Children's Villages. The organization has been around since 1949 and is an international development charity which serves to protect the interests and rights of children. Van Nistelrooy was officially appointed "FIFA for SOS Children's Villages" Ambassador in the Netherlands on 1 September 2001.


title: Ruud van Nistelrooy

text: On 17 November 2009, Van Nistelrooy and his wife hosted SOS at Ciudad Real Madrid. The purpose of the event was to help create a calendar which would be sold to benefit the organization.


title: Ruud van Nistelrooy

text: Van Nistelrooy was sponsored by sportswear company Nike and appeared in Nike commercials. In a global Nike advertising campaign in the run-up to the 2002 World Cup in Korea and Japan, he starred in a "Secret Tournament" commercial (branded "Scorpion KO") directed by Terry Gilliam, appearing alongside football players such as Thierry Henry, Ronaldo, Edgar Davids, Fabio Cannavaro, Francesco Totti, Ronaldinho, Luís Figo and Hidetoshi Nakata, with former player Eric Cantona as the tournament "referee".


title: Sarcoidosis

text: Sarcoidosis (also known as "Besnier-Boeck-Schaumann disease") is a disease involving abnormal collections of inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph nodes. Less commonly affected are the eyes, liver, heart, and brain. Any organ can be affected though. The signs and symptoms depend on the organ involved. Often, no, or only mild, symptoms are seen. When it affects the lungs, wheezing, coughing, shortness of breath, or chest pain may occur. Some may have Löfgren syndrome with fever, large lymph nodes, arthritis, and a rash known as erythema nodosum.


title: Sarcoidosis

text: The cause of sarcoidosis is unknown. Some believe it may be due to an immune reaction to a trigger such as an infection or chemicals in those who are genetically predisposed. Those with affected family members are at greater risk. Diagnosis is partly based on signs and symptoms, which may be supported by biopsy. Findings that make it likely include large lymph nodes at the root of the lung on both sides, high blood calcium with a normal parathyroid hormone level, or elevated levels of angiotensin-converting enzyme in the blood. The diagnosis should only be made after excluding other possible causes of similar symptoms such as tuberculosis.


title: Sarcoidosis

text: Sarcoidosis may resolve without any treatment within a few years. However, some people may have long-term or severe disease. Some symptoms may be improved with the use of anti-inflammatory drugs such as ibuprofen. In cases where the condition causes significant health problems, steroids such as prednisone are indicated. Medications such as methotrexate, chloroquine, or azathioprine may occasionally be used in an effort to decrease the side effects of steroids. The risk of death is 1–7%. The chance of the disease returning in someone who has had it previously is less than 5%.


title: Sarcoidosis

text: In 2015, pulmonary sarcoidosis and interstitial lung disease affected 1.9 million people globally and they resulted in 122,000 deaths. It is most common in Scandinavians, but occurs in all parts of the world. In the United States, risk is greater among black people as opposed to white people. It usually begins between the ages of 20 and 50. It occurs more often in women than men. Sarcoidosis was first described in 1877 by the English doctor Jonathan Hutchinson as a non-painful skin disease.


title: Sarcoidosis

text: Sarcoidosis is a systemic inflammatory disease that can affect any organ, although it can be asymptomatic and is discovered by accident in about 5% of cases. Common symptoms, which tend to be vague, include fatigue (unrelieved by sleep; occurs in up to 85% of cases ), lack of energy, weight loss, joint aches and pains (which occur in about 70% of cases), arthritis (14–38% of cases), dry eyes, swelling of the knees, blurry vision, shortness of breath, a dry, hacking cough, or skin lesions. Less commonly, people may cough up blood. Sarcoidosis is also accompanied by psychological distress and symptoms of anxiety and depression, which are also associated with fatigue. The cutaneous symptoms vary, and range from rashes and noduli (small bumps) to erythema nodosum, granuloma annulare, or lupus pernio. Sarcoidosis and cancer may mimic one another, making the distinction difficult.


title: Sarcoidosis

text: The combination of erythema nodosum, bilateral hilar lymphadenopathy, and joint pain is called Löfgren syndrome, which has a relatively good prognosis. This form of the disease occurs significantly more often in Scandinavian patients than in those of non-Scandinavian origin.


title: Sarcoidosis

text: Localization to the lungs is by far the most common manifestation of sarcoidosis. At least 90% of those affected experience lung involvement. Overall, about 50% develop permanent pulmonary abnormalities, and 5 to 15% have progressive fibrosis of the lung parenchyma. Sarcoidosis of the lung is primarily an interstitial lung disease in which the inflammatory process involves the alveoli, small bronchi, and small blood vessels. In acute and subacute cases, physical examination usually reveals dry crackles. At least 5% of cases include pulmonary arterial hypertension. The upper respiratory tract (including the larynx, pharynx, and sinuses) may be affected, which occurs in between 5 and 10% of cases.


title: Sarcoidosis

text: The four stages of pulmonary involvement are based on radiological stage of the disease, which is helpful in prognosis:


title: Sarcoidosis

text: Use of the Scadding scale only provides general information regarding the prognosis of the pulmonary disease over time. Caution is recommended, as it only shows a general relation with physiological markers of the disease and the variation is such that it has limited applicability in individual assessments, including treatment decisions.


title: Sarcoidosis

text: Sarcoidosis involves the skin in between 9 and 37% of cases and is more common in African Americans than in European Americans. The skin is the second-most commonly affected organ after the lungs. The most common lesions are erythema nodosum, plaques, maculopapular eruptions, subcutaneous nodules, and lupus pernio. Treatment is not required, since the lesions usually resolve spontaneously in 2–4 weeks. Although it may be disfiguring, cutaneous sarcoidosis rarely causes major problems. Sarcoidosis of the scalp presents with diffuse or patchy hair loss.


title: Sarcoidosis

text: Histologically, sarcoidosis of the heart is an active granulomatous inflammation surrounded by reactive oedema. The distribution of affected areas is patchy with localised enlargement of heart muscles. This causes scarring and remodelling of the heart, which leads to dilatation of heart cavities and thinning of heart muscles. As the situation progresses, it leads to aneurysm of heart chambers. When the distribution is diffuse, there would be dilatation of both ventricles of the heart, causing heart failure and arrhythmia. When the conduction system in the intraventricular septum is affected, it would lead to heart block, ventricular tachycardia and ventricular arrhythmia, causing sudden death. Nevertheless, the involvement of pericardium and heart valves are uncommon.


title: Sarcoidosis

text: The frequency of cardiac involvement varies and is significantly influenced by race; in Japan, more than 25% of those with sarcoidosis have symptomatic cardiac involvement, whereas in the US and Europe, only about 5% of cases present with cardiac involvement. Autopsy studies in the US have revealed a frequency of cardiac involvement of about 20–30%, whereas autopsy studies in Japan have shown a frequency of 60%. The presentation of cardiac sarcoidosis can range from asymptomatic conduction abnormalities to fatal ventricular arrhythmia.


title: Sarcoidosis

text: Conduction abnormalities are the most common cardiac manifestations of sarcoidosis in humans and can include complete heart block. Second to conduction abnormalities, in frequency, are ventricular arrhythmias, which occurs in about 23% of cases with cardiac involvement. Sudden cardiac death, either due to ventricular arrhythmias or complete heart block is a rare complication of cardiac sarcoidosis. Cardiac sarcoidosis can cause fibrosis, granuloma formation, or the accumulation of fluid in the interstitium of the heart, or a combination of the former two. Cardiac sarcoidosis may also cause congestive heart failure when granulomas cause myocardial fibrosis and scarring. Congestive heart failure affects 25-75% of those with cardiac sarcoidosis. Diabetes mellitus and sarcoidosis-related arrhythmias are believed to be strong risk factors of heart failure in sarcoidosis. A small (20-40%) increased risk of acute myocardial infarction has also been described. Pulmonary arterial hypertension occurs by two mechanisms in cardiac sarcoidosis: reduced left heart function due to granulomas weakening the heart muscle or from impaired blood flow.


title: Sarcoidosis

text: Eye involvement occurs in about 10–90% of cases. Manifestations in the eye include uveitis, uveoparotitis, and retinal inflammation, which may result in loss of visual acuity or blindness. The most common ophthalmologic manifestation of sarcoidosis is uveitis. The combination of anterior uveitis, parotitis, VII cranial nerve paralysis and fever is called uveoparotid fever or Heerfordt syndrome (). Development of scleral nodule associated with sarcoidosis has been observed.


title: Sarcoidosis

text: Any of the components of the nervous system can be involved. Sarcoidosis affecting the nervous system is known as neurosarcoidosis. Cranial nerves are most commonly affected, accounting for about 5–30% of neurosarcoidosis cases, and peripheral facial nerve palsy, often bilateral, is the most common neurological manifestation of sarcoidosis. It occurs suddenly and is usually transient. The central nervous system involvement is present in 10–25% of sarcoidosis cases. Other common manifestations of neurosarcoidosis include optic nerve dysfunction, papilledema, palate dysfunction, neuroendocrine changes, hearing abnormalities, hypothalamic and pituitary abnormalities, chronic meningitis, and peripheral neuropathy. Myelopathy, that is spinal cord involvement, occurs in about 16–43% of neurosarcoidosis cases and is often associated with the poorest prognosis of the neurosarcoidosis subtypes. Whereas facial nerve palsies and acute meningitis due to sarcoidosis tend to have the most favourable prognosis, another common finding in sarcoidosis with neurological involvement is autonomic or sensory small-fiber neuropathy. Neuroendocrine sarcoidosis accounts for about 5–10% of neurosarcoidosis cases and can lead to diabetes insipidus, changes in menstrual cycle and hypothalamic dysfunction. The latter can lead to changes in body temperature, mood, and prolactin (see the endocrine and exocrine section for details).


title: Sarcoidosis

text: Prolactin is frequently increased in sarcoidosis, between 3 and 32% of cases have hyperprolactinemia this frequently leads to amenorrhea, galactorrhea, or nonpuerperal mastitis in women. It also frequently causes an increase in 1,25-dihydroxy vitamin D, the active metabolite of vitamin D, which is usually hydroxylated within the kidney, but in sarcoidosis patients, hydroxylation of vitamin D can occur outside the kidneys, namely inside the immune cells found in the granulomas the condition produces. 1,25-dihydroxy vitamin D is the main cause for hypercalcemia in sarcoidosis and is overproduced by sarcoid granulomata. Gamma-interferon produced by activated lymphocytes and macrophages plays a major role in the synthesis of 1 alpha, 25(OH)2D3. Hypercalciuria (excessive secretion of calcium in one's urine) and hypercalcemia (an excessively high amount of calcium in the blood) are seen in <10% of individuals and likely results from the increased 1,25-dihydroxy vitamin D production.


title: Sarcoidosis

text: Parotid enlargement occurs in about 5–10% of cases. Bilateral involvement is the rule. The gland is usually not tender, but firm and smooth. Dry mouth can occur; other exocrine glands are affected only rarely. The eyes, their glands, or the parotid glands are affected in 20–50% of cases.


title: Sarcoidosis

text: Symptomatic gastrointestinal (GI) involvement occurs in less than 1% of cases (if one excludes the liver), and most commonly the stomach is affected, although the small or large intestine may also be affected in a small portion of cases. Studies at autopsy have revealed GI involvement in less than 10% of people. These cases would likely mimic Crohn's disease, which is a more commonly intestine-affecting granulomatous disease. About 1–3% of people have evidence of pancreatic involvement at autopsy. Symptomatic kidney involvement occurs in just 0.7% of cases, although evidence of kidney involvement at autopsy has been reported in up to 22% of people and occurs exclusively in cases of chronic disease. Symptomatic kidney involvement is usually nephrocalcinosis, although granulomatous interstitial nephritis that presents with reduced creatinine clearance and little proteinuria is a close second. Less commonly, the epididymis, testicles, prostate, ovaries, fallopian tubes, uterus, or the vulva may be affected, the latter may cause vulva itchiness. Testicular involvement has been reported in about 5% of people at autopsy. In males, sarcoidosis may lead to infertility.


title: Sarcoidosis

text: Around 70% of people have granulomas in their livers, although only in about 20–30% of cases, liver function test anomalies reflecting this fact are seen. About 5–15% of patients exhibit hepatomegaly. Only 5–30% of cases of liver involvement are symptomatic. Usually, these changes reflect a cholestatic pattern and include raised levels of alkaline phosphatase (which is the most common liver function test anomaly seen in those with sarcoidosis), while bilirubin and aminotransferases are only mildly elevated. Jaundice is rare.


title: Sarcoidosis

text: Abnormal blood tests are frequent, accounting for over 50% of cases, but are not diagnostic. Lymphopenia is the most common blood anomaly in sarcoidosis. Anemia occurs in about 20% of people with sarcoidosis. Leukopenia is less common and occurs in even fewer cases but is rarely severe. Thrombocytopenia and hemolytic anemia are fairly rare. In the absence of splenomegaly, leukopenia may reflect bone marrow involvement, but the most common mechanism is a redistribution of blood T cells to sites of disease. Other nonspecific findings include monocytosis, occurring in the majority of sarcoidosis cases, increased hepatic enzymes or alkaline phosphatase. People with sarcoidosis often have immunologic anomalies like allergies to test antigens such as "Candida" or purified protein derivative. Polyclonal hypergammaglobulinemia is also a fairly common immunologic anomaly seen in sarcoidosis.


title: Sarcoidosis

text: Lymphadenopathy (swollen glands) is common in sarcoidosis and occurs in 15% of cases. Intrathoracic nodes are enlarged in 75 to 90% of all people; usually this involves the hilar nodes, but the paratracheal nodes are commonly involved. Peripheral lymphadenopathy is very common, particularly involving the cervical (the most common head and neck manifestation of the disease), axillary, epitrochlear, and inguinal nodes. Approximately 75% of cases show microscopic involvement of the spleen, although only in about 5–10% of cases does splenomegaly appear.


title: Sarcoidosis

text: Sarcoidosis can be involved with the joints, bones, and muscles. This causes a wide variety of musculoskeletal complaints that act through different mechanisms.


title: Sarcoidosis

text: Sarcoidosis patients with acute arthritis often also have bilateral hilar lymphadenopathy and erythema nodosum. These three associated syndromes often occur together in Löfgren syndrome. The arthritis symptoms of Löfgren syndrome occur most frequently in the ankles, followed by the knees, wrists, elbows, and metacarpophalangeal joints. Usually, true arthritis is not present, but instead, periarthritis appears as a swelling in the soft tissue around the joints that can be seen by ultrasonographic methods.


title: Sarcoidosis

text: These joint symptoms tend to precede or occur at the same time as erythema nodosum develops. Even when erythema nodosum is absent, it is believed that the combination of hilar lymphadenopathy and ankle periarthritis can be considered as a variant of Löfgren syndrome.


title: Sarcoidosis

text: Enthesitis also occurs in about one-third of patients with acute sarcoid arthritis, mainly affecting the Achilles tendon and heels. Soft-tissue swelling of the ankles can be prominent, and biopsy of this soft tissue reveals no granulomas, but does show panniculitis similar to erythema nodosum.


title: Sarcoidosis

text: Chronic sarcoid arthritis usually occurs in the setting of more diffuse organ involvement. The ankles, knees, wrists, elbows, and hands may all be affected in the chronic form and often this presents itself in a polyarticular pattern. Dactylitis similar to that seen in psoriatic arthritis, that is associated with pain, swelling, overlying skin erythema, and underlying bony changes may also occur. Development of Jaccoud arthropathy (a nonerosive deformity) is very rarely seen.


title: Sarcoidosis

text: Bone involvement in sarcoidosis has been reported in 1–13% of cases. The most frequent sites of involvement are the hands and feet, whereas the spine is less commonly affected. Half of the patients with bony lesions experience pain and stiffness, whereas the other half remain asymptomatic.


title: Sarcoidosis

text: The exact cause of sarcoidosis is not known. The current working hypothesis is, in genetically susceptible individuals, sarcoidosis is caused through alteration to the immune response after exposure to an environmental, occupational, or infectious agent. Some cases may be caused by treatment with tumor necrosis factor (TNF) inhibitors like etanercept.


title: Sarcoidosis

text: The heritability of sarcoidosis varies according to ethnicity. About 20% of African Americans with sarcoidosis have a family member with the condition, whereas the same figure for European Americans is about 5%. Additionally, in African Americans, who seem to experience more severe and chronic disease, siblings and parents of sarcoidosis cases have about a 2.5-fold increased risk for developing the disease. In Swedish individuals heritability was found to be 39%. In this group, if a first-degree family member was affected, a person has a four-fold greater risk of being affected.


title: Sarcoidosis

text: Investigations of genetic susceptibility yielded many candidate genes, but only few were confirmed by further investigations and no reliable genetic markers are known. Currently, the most interesting candidate gene is "BTNL2"; several "HLA-DR" risk alleles are also being investigated. In persistent sarcoidosis, the HLA haplotype "HLA-B7-DR15" is either cooperating in disease or another gene between these two loci is associated. In nonpersistent disease, a strong genetic association exists with "HLA DR3-DQ2". Cardiac sarcoid has been connected to tumor necrosis factor alpha (TNFA) variants.


title: Sarcoidosis

text: Several infectious agents appear to be significantly associated with sarcoidosis, but none of the known associations is specific enough to suggest a direct causative role. The major implicated infectious agents include: mycobacteria, fungi, borrelia, and rickettsia. A meta-analysis investigating the role of mycobacteria in sarcoidosis found it was present in 26.4% of cases, but they also detected a possible publication bias, so the results need further confirmation. "Mycobacterium tuberculosis" catalase-peroxidase has been identified as a possible antigen catalyst of sarcoidosis. The disease has also been reported by transmission via organ transplants. A large epidemiological study found little evidence that infectious diseases spanning years before sarcoidosis diagnosis could confer measurable risks for sarcoidosis diagnosis in the future.


title: Sarcoidosis

text: Association of autoimmune disorders has been frequently observed. The exact mechanism of this relation is not known, but some evidence supports the hypothesis that this is a consequence of Th1 lymphokine prevalence. Tests of delayed cutaneous hypersensitivity have been used to measure progression.


title: Sarcoidosis

text: Granulomatous inflammation is characterized primarily by the accumulation of macrophages and activated T-lymphocytes, with increased production of key inflammatory mediators, tumor necrosis factor alpha (TNF), interferon gamma, interleukin 2 (IL-2), IL-8, IL-10, IL-12, IL-18, IL-23 and transforming growth factor beta (TGF-β), indicative of a T helper cell-mediated immune response.


title: Sarcoidosis

text: Sarcoidosis has paradoxical effects on inflammatory processes; it is characterized by increased macrophage and CD4 helper T-cell activation, resulting in accelerated inflammation, but immune response to antigen challenges such as tuberculin is suppressed. This paradoxic state of simultaneous hyper- and hypoactivity is suggestive of a state of anergy. The anergy may also be responsible for the increased risk of infections and cancer. The regulatory T-lymphocytes in the periphery of sarcoid granulomas appear to suppress IL-2 secretion, which is hypothesized to cause the state of anergy by preventing antigen-specific memory responses.


title: Sarcoidosis

text: While TNF is widely believed to play an important role in the formation of granulomas (this is further supported by the finding that in animal models of mycobacterial granuloma formation inhibition of either TNF or IFN-γ production inhibits granuloma formation), sarcoidosis can and does still develop in those being treated with TNF antagonists like etanercept.


title: Sarcoidosis

text: B cells also likely play a role in the pathophysiology of sarcoidosis. Serum levels of soluble human leukocyte antigen (HLA) class I antigens and angiotensin converting enzyme (ACE) are higher in people with sarcoidosis. Likewise the ratio of CD4/CD8 T cells in bronchoalveolar lavage is usually higher in people with pulmonary sarcoidosis (usually >3.5), although it can be normal or even abnormally low in some cases. Serum ACE levels have been found to usually correlate with total granuloma load.


title: Sarcoidosis

text: Cases of sarcoidosis have also been reported as part of the immune reconstitution syndrome of HIV, that is, when people receive treatment for HIV, their immune system rebounds and the result is that it starts to attack the antigens of opportunistic infections caught prior to said rebound and the resulting immune response starts to damage healthy tissue.


title: Sarcoidosis

text: Sarcoidosis is characterized by the formation of non-necrotizing ("non-caseating") granulomas in various organs and tissues. Giant cells, specifically Langhans giant cells, are often seen in sarcoidosis. Schaumann bodies seen in sarcoidosis are calcium and protein inclusions inside of giant cells as part of a granuloma. Asteroid bodies can be seen in sarcoidosis. Hamazaki–Wesenberg bodies can be seen in lymph nodes and more rarely in lung biopsies with sarcoidosis and are inclusion bodies of lysosomes with protein, glycoprotein and iron.


title: Sarcoidosis

text: Diagnosis of sarcoidosis is a matter of exclusion, as there is no specific test for the condition. To exclude sarcoidosis in a case presenting with pulmonary symptoms might involve a chest radiograph, CT scan of chest, PET scan, CT-guided biopsy, mediastinoscopy, open lung biopsy, bronchoscopy with biopsy, endobronchial ultrasound, and endoscopic ultrasound with fine-needle aspiration of mediastinal lymph nodes (EBUS FNA). Tissue from biopsy of lymph nodes is subjected to both flow cytometry to rule out cancer and special stains (acid fast bacilli stain and Gömöri methenamine silver stain) to rule out microorganisms and fungi.


title: Sarcoidosis

text: Serum markers of sarcoidosis, include: serum amyloid A, soluble interleukin-2 receptor, lysozyme, angiotensin converting enzyme, and the glycoprotein KL-6. Angiotensin-converting enzyme blood levels are used in the monitoring of sarcoidosis. A bronchoalveolar lavage can show an elevated (of at least 3.5) CD4/CD8 T cell ratio, which is indicative (but not proof) of pulmonary sarcoidosis. In at least one study the induced sputum ratio of CD4/CD8 and level of TNF was correlated to those in the lavage fluid. A sarcoidosis-like lung disease called granulomatous–lymphocytic interstitial lung disease can be seen in patients with common variable immunodeficiency (CVID) and therefore serum antibody levels should be measured to exclude CVID.


title: Sarcoidosis

text: Differential diagnosis includes metastatic disease, lymphoma, septic emboli, rheumatoid nodules, granulomatosis with polyangiitis, varicella infection, tuberculosis, and atypical infections, such as "Mycobacterium avium" complex, cytomegalovirus, and cryptococcus. Sarcoidosis is confused most commonly with neoplastic diseases, such as lymphoma, or with disorders characterized also by a mononuclear cell granulomatous inflammatory process, such as the mycobacterial and fungal disorders.


title: Sarcoidosis

text: Although people with stage 1 radiographs tend to have the acute or subacute, reversible form of the disease, those with stages 2 and 3 often have the chronic, progressive disease; these patterns do not represent consecutive "stages" of sarcoidosis. Thus, except for epidemiologic purposes, this categorization is mostly of historic interest.


title: Sarcoidosis

text: In sarcoidosis presenting in the Caucasian population, hilar adenopathy and erythema nodosum are the most common initial symptoms. In this population, a biopsy of the gastrocnemius muscle is a useful tool in correctly diagnosing the person. The presence of a noncaseating epithelioid granuloma in a gastrocnemius specimen is definitive evidence of sarcoidosis, as other tuberculoid and fungal diseases extremely rarely present histologically in this muscle.


title: Sarcoidosis

text: Cardiac magnetic resonance imaging (CMR) is one modality for diagnosing cardiac sarcoidosis. It has 78% specificity in diagnosing cardiac sarcoidosis. Its T2-weighted imaging can detect acute inflammation. Meanwhile, late gadolinium contrast (LGE) can detect fibrosis or scar. Lesions at the subpericardium and midwall enhancement of basal septum or inferolateral wall is strongly suggestive of sarcoidosis. MRI can also follow up on the treatment efficacy of corticosteroids and prognosis of cardiac sarcoidosis.


title: Sarcoidosis

text: Treatments for sarcoidosis vary greatly depending on the patient. At least half of patients require no systemic therapy. Most people (>75%) only require symptomatic treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or aspirin. For those presenting with lung symptoms, unless the respiratory impairment is devastating, active pulmonary sarcoidosis is observed usually without therapy for two to three months; if the inflammation does not subside spontaneously, therapy is instituted.


title: Sarcoidosis

text: Major categories of drug interventions include glucocorticoids, antimetabolites, biologic agents especially monoclonal anti-tumor necrosis factor antibodies. Investigational treatments include specific antibiotic combinations and mesenchymal stem cells. If drug intervention is indicated, a step-wise approach is often used to explore alternatives in order of increasing side effects and to monitor potentially toxic effects.


title: Sarcoidosis

text: Corticosteroids, most commonly prednisone or prednisolone, have been the standard treatment for many years. In some people, this treatment can slow or reverse the course of the disease, but other people do not respond to steroid therapy. The use of corticosteroids in mild disease is controversial because in many cases the disease remits spontaneously.


title: Sarcoidosis

text: Antimetabolites, also categorized as steroid-sparing agents, such as azathioprine, methotrexate, mycophenolic acid, and leflunomide are often used as alternatives to corticosteroids. Of these, methotrexate is most widely used and studied. Methotrexate is considered a first-line treatment in neurosarcoidosis, often in conjunction with corticosteroids. Long-term treatment with methotrexate is associated with liver damage in about 10% of people and hence may be a significant concern in people with liver involvement and requires regular liver function test monitoring. Methotrexate can also lead to pulmonary toxicity (lung damage), although this is fairly uncommon and more commonly it can confound the leukopenia caused by sarcoidosis. Due to these safety concerns it is often recommended that methotrexate is combined with folic acid in order to prevent toxicity. Azathioprine treatment can also lead to liver damage. However, the risk of infection appears to be about 40% lower in those treated with methotrexate instead of azathioprine. Leflunomide is being used as a replacement for methotrexate, possibly due to its purportedly lower rate of pulmonary toxicity. Mycophenolic acid has been used successfully in uveal sarcoidosis, neurosarcoidosis (especially CNS sarcoidosis; minimally effective in sarcoidosis myopathy), and pulmonary sarcoidosis.


title: Sarcoidosis

text: As the granulomas are caused by collections of immune system cells, particularly T cells, there has been some success using immunosuppressants (like cyclophosphamide, cladribine, chlorambucil, and cyclosporine), immunomodulatory (pentoxifylline and thalidomide), and anti-tumor necrosis factor treatment (such as infliximab, etanercept, golimumab, and adalimumab).


title: Sarcoidosis

text: In a clinical trial cyclosporine added to prednisone treatment failed to demonstrate any significant benefit over prednisone alone in people with pulmonary sarcoidosis, although there was evidence of increased toxicity from the addition of cyclosporine to the steroid treatment including infections, malignancies (cancers), hypertension, and kidney dysfunction. Likewise chlorambucil and cyclophosphamide are seldom used in the treatment of sarcoidosis due to their high degree of toxicity, especially their potential for causing malignancies. Infliximab has been used successfully to treat pulmonary sarcoidosis in clinical trials in a number of cases. Etanercept, on the other hand, has failed to demonstrate any significant efficacy in people with uveal sarcoidosis in a couple of clinical trials. Likewise golimumab has failed to show any benefit in those with pulmonary sarcoidosis. One clinical trial of adalimumab found treatment response in about half of subjects, which is similar to that seen with infliximab, but as adalimumab has better tolerability profile it may be preferred over infliximab.


title: Sarcoidosis

text: Ursodeoxycholic acid has been used successfully as a treatment for cases with liver involvement. Thalidomide has also been tried successfully as a treatment for treatment-resistant lupus pernio in a clinical trial, which may stem from its anti-TNF activity, although it failed to exhibit any efficacy in a pulmonary sarcoidosis clinical trial. Cutaneous disease may be successfully managed with antimalarials (such as chloroquine and hydroxychloroquine) and the tetracycline antibiotic, minocycline. Antimalarials have also demonstrated efficacy in treating sarcoidosis-induced hypercalcemia and neurosarcoidosis. Long-term use of antimalarials is limited, however, by their potential to cause irreversible blindness and hence the need for regular ophthalmologic screening. This toxicity is usually less of a problem with hydroxychloroquine than with chloroquine, although hydroxychloroquine can disturb the glucose homeostasis.


title: Sarcoidosis

text: Recently selective phosphodiesterase 4 (PDE4) inhibitors like apremilast (a thalidomide derivative), roflumilast, and the less subtype-selective PDE4 inhibitor, pentoxifylline, have been tried as a treatment for sarcoidosis, with successful results being obtained with apremilast in cutaneous sarcoidosis in a small open-label study. Pentoxifylline has been used successfully to treat acute disease although its use is greatly limited by its gastrointestinal toxicity (mostly nausea, vomiting, and diarrhea). Case reports have supported the efficacy of rituximab, an anti-CD20 monoclonal antibody and a clinical trial investigating atorvastatin as a treatment for sarcoidosis is under-way. ACE inhibitors have been reported to cause remission in cutaneous sarcoidosis and improvement in pulmonary sarcoidosis, including improvement in pulmonary function, remodeling of lung parenchyma and prevention of pulmonary fibrosis in separate case series'. Nicotine patches have been found to possess anti-inflammatory effects in sarcoidosis patients, although whether they had disease-modifying effects requires further investigation. Antimycobacterial treatment (drugs that kill off mycobacteria, the causative agents behind tuberculosis and leprosy) has also proven itself effective in treating chronic cutaneous (that is, it affects the skin) sarcoidosis in one clinical trial. Quercetin has also been tried as a treatment for pulmonary sarcoidosis with some early success in one small trial.


title: Sarcoidosis

text: Because of its uncommon nature, the treatment of male reproductive tract sarcoidosis is controversial. Since the differential diagnosis includes testicular cancer, some recommend orchiectomy, even if evidence of sarcoidosis in other organs is present. In the newer approach, testicular, epididymal biopsy and resection of the largest lesion has been proposed.


title: Sarcoidosis

text: People with sarcoidosis may have a range of symptoms that do not correspond with objective physical evidence of disease but that still decrease quality of life.


title: Sarcoidosis

text: Physical therapy, rehabilitation, and counseling can help avoid deconditioning, and improve social participation, psychological well-being, and activity levels. Key aspects are avoiding exercise intolerance and muscle weakness.


title: Sarcoidosis

text: Low or moderate-intensity physical training has been shown to improve fatigue, psychological health, and physical functioning in people sarcoidosis without adverse effects. Inspiratory muscle training has also decreased severe fatigue perception in subjects with early stages of sarcoidosis, as well as improving functional and maximal exercise capacity and respiratory muscle strength. The duration, frequency, and physical intensity of exercise needs to accommodate impairments such as joint pain, muscle pain, and fatigue.


title: Sarcoidosis

text: Neurostimulants such as methylphenidate and modafinil have shown some effectiveness as an adjunct for treatment of sarcoidosis fatigue.


title: Sarcoidosis

text: Treatments for symptomatic neuropathic pain in sarcoidosis patients is similar to that for other causes, and include antidepressants, anticonvulsants and prolonged-release opioids, however, only 30 to 60% of patients experience limited pain relief.


title: Sarcoidosis

text: The disease can remit spontaneously or become chronic, with exacerbations and remissions. In some cases, it can progress to pulmonary fibrosis and death. In benign cases, remission can occur in 24 to 36 months without treatment but regular follow ups are required. Some cases, however, may persist several decades. Two-thirds of people with the condition achieve a remission within 10 years of the diagnosis. When the heart is involved, the prognosis is generally less favourable, though corticosteroids appear effective in improving AV conduction. The prognosis tends to be less favourable in African Americans than in white Americans. In a Swedish population-based analysis, the majority of cases who did not have severe disease at diagnosis had comparable mortality to the general population. The risk for premature death was markedly (2.3-fold) increased compared to the general population for a smaller group of cases with severe disease at diagnosis. Serious infections, sometimes multiple during the course of disease, and heart failure might contribute to the higher risk of early death in some patients with sarcoidosis.


title: Sarcoidosis

text: Some 1990s studies indicated that people with sarcoidosis appear to be at significantly increased risk for cancer, in particular lung cancer, lymphomas, and cancer in other organs known to be affected in sarcoidosis. In sarcoidosis-lymphoma syndrome, sarcoidosis is followed by the development of a lymphoproliferative disorder such as non-Hodgkin lymphoma. This may be attributed to the underlying immunological abnormalities that occur during the sarcoidosis disease process. Sarcoidosis can also follow cancer or occur concurrently with cancer. There have been reports of hairy cell leukemia, acute myeloid leukemia, and acute myeloblastic leukemia associated with sarcoidosis. Sometimes, sarcoidosis, even untreated, can be complicated by opportunistic infections although these are rare.


title: Sarcoidosis

text: Sarcoidosis most commonly affects young adults of both sexes, although studies have reported more cases in females. Incidence is highest for individuals younger than 40 and peaks in the age-group from 20 to 29 years; a second peak is observed for women over 50.


title: Sarcoidosis

text: Sarcoidosis occurs throughout the world in all races with an average incidence of 16.5 per 100,000 in men and 19 per 100,000 in women. The disease is most common in Northern European countries and the highest annual incidence of 60 per 100,000 is found in Sweden and Iceland. In the United Kingdom the prevalence is 16 in 100,000. In the United States, sarcoidosis is more common in people of African descent than Caucasians, with annual incidence reported as 35.5 and 10.9 per 100,000, respectively. Sarcoidosis is less commonly reported in South America, Spain, India, Canada, and the Philippines. There may be a higher susceptibility to sarcoidosis in those with celiac disease. An association between the two disorders has been suggested.


title: Sarcoidosis

text: There also has been a seasonal clustering observed in sarcoidosis-affected individuals. In Greece about 70% of diagnoses occur between March and May every year, in Spain about 50% of diagnoses occur between April and June, and in Japan it is mostly diagnosed during June and July.


title: Sarcoidosis

text: The differing incidence across the world may be at least partially attributable to the lack of screening programs in certain regions of the world, and the overshadowing presence of other granulomatous diseases, such as tuberculosis, that may interfere with the diagnosis of sarcoidosis where they are prevalent. There may also be differences in the severity of the disease between people of different ethnicities. Several studies suggest the presentation in people of African origin may be more severe and disseminated than for Caucasians, who are more likely to have asymptomatic disease. Manifestation appears to be slightly different according to race and sex. Erythema nodosum is far more common in men than in women and in Caucasians than in other races. In Japanese people, ophthalmologic and cardiac involvement are more common than in other races.


title: Sarcoidosis

text: It is more common in certain occupations, namely firefighters, educators, military personnel, those who work in industries where pesticides are used, law enforcement, and healthcare personnel. In the year after the September 11 attacks, the rate of sarcoidosis incidence went up four-fold (to 86 cases per 100,000).


title: Sarcoidosis

text: It was first described in 1877 by Dr. Jonathan Hutchinson, a dermatologist as a condition causing red, raised rashes on the face, arms, and hands. In 1889 the term lupus pernio was coined by Dr. Ernest Besnier, another dermatologist. Later in 1892 lupus pernio's histology was defined. In 1902 bone involvement was first described by a group of three doctors. Between 1909 and 1910 uveitis in sarcoidosis was first described, and later in 1915 it was emphasised, by Dr. Jörgen Nielsen Schaumann, that it was a systemic condition. This same year lung involvement was also described. In 1937 uveoparotid fever was first described and likewise in 1941 Löfgren syndrome was first described. In 1958 the first international conference on sarcoidosis was called in London, likewise the first USA sarcoidosis conference occurred in Washington, D.C., in the year 1961. It has also been called Besnier–Boeck disease or Besnier–Boeck–Schaumann disease.


title: Sarcoidosis

text: The word "sarcoidosis" comes from Greek [σάρκο-] "sarco-" meaning "flesh", the suffix "-(e)ido" (from the Greek εἶδος -eidos [usually omitting the initial e in English as the diphthong epsilon-iota in Classic Greek stands for a long "i" = English ee]) meaning "type", " resembles" or "like", and "-sis", a common suffix in Greek meaning "condition". Thus the whole word means "a condition that resembles crude flesh". The first cases of sarcoïdosis, which were recognised as a new pathological entity, in Scandinavia, at the end of the 19th century exhibited skin nodules resembling cutaneous sarcomas, hence the name initially given.


title: Sarcoidosis

text: The World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) is an organisation of physicians involved in the diagnosis and treatment of sarcoidosis and related conditions. WASOG publishes the journal "Sarcoidosis, Vasculitis and Diffuse Lung Diseases". Additionally, the Foundation for Sarcoidosis Research (FSR) is devoted to supporting research into sarcoidosis and its possible treatments.


title: Sarcoidosis

text: There have been concerns that World Trade Center rescue workers are at a heightened risk for sarcoidosis.


title: Sarcoidosis

text: Comedian and actor Bernie Mac had sarcoidosis. In 2005, he mentioned that the disease was in remission. His death on 9 August 2008 was caused by complications from pneumonia, though Mac's agent states the sarcoidosis was not related to his fatal pneumonia.


title: Sarcoidosis

text: American football player Reggie White died in 2004, with pulmonary and cardiac sarcoidosis being contributing factors to his fatal heart arrhythmia.


title: Sarcoidosis

text: Joseph Rago, Pulitzer Prize-winning writer known for his work at "The Wall Street Journal", died of sarcoidosis complications in 2017.


title: Sarcoidosis

text: Several historical figures are suspected of having sarcoidosis. In a 2014 letter to the British medical journal "The Lancet", it was suggested that the French Revolution leader Maximilien Robespierre may have had sarcoidosis, causing him impairment during his time as head of the Reign of Terror. The symptoms associated with Ludwig van Beethoven's 1827 death have been described as possibly consistent with sarcoidosis. Author Robert Louis Stevenson (1850–1894) had a history of chronic coughs and chest complaints, and sarcoidosis has been suggested as a diagnosis.


title: Sarcoidosis

text: Sarcoidosis generally does not prevent successful pregnancy and delivery; the increase in estrogen levels during pregnancy may even have a slightly beneficial immunomodulatory effect. In most cases, the course of the disease is unaffected by pregnancy, with improvement in a few cases and worsening of symptoms in very few cases, although it is worth noting that a number of the immunosuppressants (such as methotrexate, cyclophosphamide) used in corticosteroid-refractory sarcoidosis are known teratogens. Increased risks associated with sarcoidosis ranging from 30 to 70% have been reported for preeclampsia/eclampsia, cesarian or preterm delivery as well as (non-cardiac) birth defects in first singleton pregnancies. In absolute numbers, birth defects and other complications such as maternal death, cardiac arrest, placental abruption or venous thromboembolism are extremely rare in sarcoidosis pregnancies.


title: Tyrus (wrestler)

text: George Murdoch (born February 21, 1973) is an American professional wrestler and cable news personality known by his ring/stage name Tyrus. As a wrestler, he is signed to the National Wrestling Alliance (NWA), where he is the reigning NWA Worlds Heavyweight Champion in his first reign. As a cable news personality, he appears on Fox News, and its sister streaming service Fox Nation, primarily as a co-host/panelist on the late-night talk show "Gutfeld!", as well as a contributor/fill-in host on other programs.


title: Tyrus (wrestler)

text: After training in WWE's developmental territories, such as Deep South Wrestling (DSW) and Florida Championship Wrestling (FCW), Murdoch under the ring name Brodus Clay debuted during the fourth season of "NXT", a WWE television show where rookies were paired with established WWE wrestlers as mentors. He debuted on the main roster as Alberto Del Rio's bodyguard. During 2012, WWE changed his gimmick to The Funkusaurus, a funk dancer accompanied by his backup dancers the Funkydactyls. He wrestled in WWE until his departure in 2014. From 2014 to 2017, Murdoch wrestled in Total Nonstop Action Wrestling (TNA, now Impact Wrestling) under the ring name of Tyrus. In 2021, he joined the NWA, where he won the NWA World Television Championship, and later the promotion's primary title — the Worlds Heavyweight Championship.


title: Tyrus (wrestler)

text: Tyrus published his autobiography "Just Tyrus: A Memoir" in 2022, which has become a "New York Times" bestseller.


title: Tyrus (wrestler)

text: Murdoch is biracial; his father is black, and his mother is white. He has stated that when he was born, his father was 19 years old and his mother was 15. In 2018, Murdoch disclosed a childhood incident in which his abusive father damaged his eye by hitting him; this incident led his mother to leave his father. While Murdoch's mother moved back to her parents' home, Murdoch has stated that he and his brother were not welcome there because their father was black. According to Murdoch, he and his brother lived with a foster family for many years; during this time, Murdoch was "obsessed" with changing his skin color, thinking that this would allow him to be reunited with his family. Murdoch and his brother eventually lived with their mother again, but Murdoch left home at age 15.


title: Tyrus (wrestler)

text: In 1990, Murdoch attended Quartz Hill High School in Los Angeles County, California, and then in 1992, Antelope Valley College. By 1995, he was attending the University of Nebraska at Kearney, where he studied to become a teacher. He played college football during his school days. However, Murdoch has stated that his football career ended when surgery to remove a ruptured appendix severed nerves ending in his leg, leaving him with a permanent limp.


title: Tyrus (wrestler)

text: After signing a contract with World Wrestling Entertainment (WWE), Murdoch was assigned to Deep South Wrestling (DSW), a WWE developmental territory. He debuted in September 2006 and began using the ring name G-Rilla along with adopting the gimmick of a street thug. In his first match for the promotion, he defeated Big Bully Douglas in a dark match on September 7. The following month, G-Rilla became the enforcer for Urban Assault, a tag team composed of Eric Pérez and Sonny Siaki. However, he got in a feud with The Bag Lady, which cost Urban Assault a match for the DSW Tag Team Championship against The Major Brothers (Brian and Brett) on October 26. The group eventually won the championships from them on November 30, but the situation repeated on December 21, when G-Rilla started fighting with Bag Lady's ally Freakin' Deacon at ringside and it caused Urban Assault to lose to the Major Brothers. The same night, Deacon defeated G-Rilla in a singles match, after which Perez, Siaki, and new member Afa Jr. attacked G-Rilla, throwing him out of the group.


title: Tyrus (wrestler)

text: In early January 2007, G-Rilla feuded with Urban Assault, attacking the members during matches. He then formed a tag team with former enemy Freakin' Deacon, with the pair defeating Urban Assault in their first match together. They went on to defeat teams including Frankie Coverdale and Bob Hoskins, the Samoan Fight Club of Siaki and Afa Jr., Shawn Osborne and Jon Bolen, and Robert Anthony and Johnny Curtis. In March, they faced and defeated the DSW Tag Team Champions, Team Elite (Mike Knox and Derrick Neikirk) in two successive non-title matches. However, in March 2007 Deacon was beaten up with steel chairs by Neikirk and Knox, the events of the night sent Deacon into a mental breakdown. The team dissolved shortly after.


title: Tyrus (wrestler)

text: In June 2007, Murdoch made his debut at FCW's inaugural show on June 26, using the name G-Rilla and defeating Shawn Osborne. Three months later, on September 15, G-Rilla won a battle royal to become the number one contender to the FCW Southern Heavyweight Championship by last eliminating Teddy Hart. He challenged Harry Smith for the championship on September 25, but lost via disqualification which meant that Smith retained the championship. The following month, G-Rilla continued to feud with Smith and Hart, who had formed The Hart Dynasty with TJ Wilson and Ted DiBiase, Jr., allying himself with Osborne, Jake Hager and Afa, Jr. G-Rilla briefly formed a tag team with Robert Anthony in December 2007, but on February 4, 2008, Murdoch was released from his contract with WWE. He would not wrestle for the next two years.


title: Tyrus (wrestler)

text: After a two year hiatus, in January 2010, Murdoch re-signed with WWE and was assigned to FCW. In March, Murdoch, once again using the name G-Rilla, formed an alliance with The Uso Brothers, Tamina, and Donny Marlow. He went on to defeat both Jacob Novak and Rudy Parker, before changing his ring name to Brodus Clay, a play on Snoop Dogg's real name (Calvin Cordozar Broadus), in May 2010. On June 16, Clay and Marlow challenged Los Aviadores (Hunico and Epico) for the FCW Florida Tag Team Championship, but were unsuccessful. That same month, Clay and Marlow began referring to themselves as the Colossal Connection. The Colossal Connection would unsuccessfully challenge Los Aviadores and Derrick Bateman and Johnny Curtis for the FCW Florida Tag Team Championship over the following months. In October, Clay appeared at a WWE house show, where he lost to JTG.


title: Tyrus (wrestler)

text: During the finale of season three of "NXT", Clay was named part of the fourth season, with Ted DiBiase and Maryse as his Pros. He made his in-ring debut on "NXT" on the December 14, 2010 episode, teaming with DiBiase to defeat Byron Saxton and his mentor Chris Masters. Clay won a four-way elimination match on the January 25 episode of "NXT", earning the right to choose a new Pro. He picked Alberto Del Rio as his new Pro, and then attacked DiBiase. The following week, Clay defeated DiBiase in a singles match; Del Rio "temporarily" passed Pro responsibilities of Clay to his manager Ricardo Rodriguez, but never returned for the rest of the season. In the season finale on March 1, Clay ended the competition in second place, losing to Curtis.


title: Tyrus (wrestler)

text: Following his stint in NXT, on the March 7 episode of "Raw", Clay debuted as Del Rio's new bodyguard and replaced him in his match against Christian in a losing effort. As Del Rio was feuding with Edge and Christian, Clay faced off with single matches against them and also teamed with Del Rio to face Edge and Christian. Clay accompanied Del Rio to the ring at WrestleMania XXVII for his match with Edge. On the April 25 episode of "Raw", Del Rio was drafted to Raw, while Clay remained on SmackDown. Clay's final appearance with Del Rio occurred on May 1 at Extreme Rules, when he interfered on Del Rio's behalf as Del Rio faced Christian in a ladder match for the vacant World Heavyweight Championship. Despite this, Del Rio was unsuccessful in winning the match. After a three-month absence due to the filming of the movie "No One Lives", Clay reappeared on the August 4, 2011 episode of "Superstars", where he defeated Pat Silva. Over the next few weeks, Clay continued to squash various jobbers on "Superstars".


title: Tyrus (wrestler)

text: WWE ran vignettes promoting his return to television on the November 7, 2011 episode of "Raw". However, Clay's television return was continuously delayed by authority figure John Laurinaitis to be "next week", with this trend continuing all the way into January 2012. Clay made his television return on the January 9, 2012 episode of "Raw" as a face (heroic character) with a fun-loving, funk dancing gimmick, with the nickname "The Funkasaurus" and began using Ernest "The Cat" Miller's theme song "Somebody Call My Momma". Now accompanied by The Funkadactyls (Naomi and Cameron) and announced as hailing from "Planet Funk", Clay incorporated gyrations and dance moves into his various squash wins on both "Raw" and "SmackDown".


title: Tyrus (wrestler)

text: At WrestleMania XXVIII, Clay made an on-stage appearance, calling and dancing with Momma Clay. The following night on "Raw", Clay started a feud with Dolph Ziggler and Jack Swagger when he saved Santino Marella from them. Clay and Marella beat Ziggler and Swagger on the April 9 episode of "Raw". On the April 20 episode of "SmackDown", Clay began a brief association with Hornswoggle. At Extreme Rules, Clay defeated Ziggler. By May, Clay was on a 21-match winning streak since adopting the Funkasaurus gimmick.


title: Tyrus (wrestler)

text: On the May 28 episode of "Raw", Big Show justified his recent heel turn by blaming Clay. Hearing this, Clay then challenged Big Show to a match that night. Before the match could start, Big Show attacked Clay at ringside and brutally assaulted him. On the June 8 episode of "SmackDown", Clay was banned by General Manager John Laurinaitis from appearing on "Raw" "to protect him from Big Show" so he was transferred to SmackDown. Big Show's attack also led Clay to vow to be more aggressive in the ring. At No Way Out, Clay defeated David Otunga in the pre-show match. Later during the pay-per-view, Clay interfered in the main event steel cage match, costing Big Show the match to John Cena and as per the match stipulation, causing the firing of John Laurinaitis. Big Show then made an appearance on the June 22 episode of "SmackDown", leading to Clay physically confronting him. With Laurinaitis fired, Clay was allowed to return to Raw from June 25, where he faced Big Show; Big Show defeated Clay to end Clay's 24-match winning streak. Clay then began a feud with Damien Sandow on the July 30 episode of "Raw"; Sandow attacked Clay when he laughed at a video of Sandow's beatdown at the hands of DX. Clay and Sandow finally faced off on the August 20 episode of "Raw", where Sandow won, but he was attacked by Clay after the match. At the Survivor Series pay-per-view, Clay took part in 10 man elimination tag team match alongside Tyson Kidd, Justin Gabriel, Rey Mysterio and Sin Cara, but he was the first man out after being eliminated by Tensai.