From being the rumored girlfriend of George Clooney to writing a book about her illness, Karen has captured the hearts of many.
Born on May 23, 1962, in New York City, Karen is the daughter of Carol, a housewife, and Phil Duffy, a developer.
She was Catholic, but attended a public school in New Jersey.
Before entering showbiz, Karen attended the University of Colorado Boulder, where she earned a degree in recreational medicine.
Little did she know that her life was about to change dramatically.
Enter showbiz
After a few years of college, Karen started modeling and acting in TV commercials.
But her life and fame changed when she became a video jockey (VJ) for MTV under the name Duff in the early 1990s.
During that time, VJs had minor roles in several movies including Dumb and Dumber, Blank Check, Malcolm X, and more.
The actress has over 20 credits to her name, but hasn't starred in anything since 2009.
By 1995, she was working for documentary filmmaker, Michael Moore as a correspondent for his shows, TV Nation and The Avail Truth.
Karen ventured into other aspects of her career in the '90s.
She became the "Charlie Girl" for the face of Revlon and Almay Cosmetics.
In 1994, Karen co-hosted the pay-per-view TV program, Elvis: The Tribute, with singer Kris Kristofferson.
Don't look around
At the height of her fame, Karen was rumored to be dating George Clooney.
However, the two have been lifelong friends and have supported each other over the years.
The two were so close that they attended the 1995 Emmy Awards together.
It was the last day of her life when she was not in pain.
"I was with George last night when I was healthy and literally, this disease just kind of hit me," she told People in 2017.
"It was the next day that I became symptomatic with sarcoidosis. That picture marks the end of my healthy life with one of the most charming and hilarious gentlemen. Talk about going out with a bang!" She recently told the outlet in an interview.
The day after Amy, she woke up with an excruciating head and neck pain.
Flying from Los Angeles to New York City, her doctor found a dormant "mostasioli-sized lesion" against her brain stem and spinal cord.
It crushed his nerves, causing unimaginable pain.
Nine months later, doctors diagnosed her with sarcoidosis of the central nervous system.
Neurosarcoidosis is a chronic chronic disease that affects the brain, spinal cord and optic nerves.
This causes a lot of swelling in those areas, resulting in pain.
Karen, a lively, 34-year-old, while traveling the world runs into a terminally ill man.
According to PEOPLE, "Sometimes her health was so precarious that she spent weeks in the hospital and once her funeral took place when her doctors feared her respiratory system was in danger of shutting down."
There is no cure for the disease, but she is receiving a combination of treatments, steroids, morphine, a pain patch, and chemotherapy to ease the pain.
George has been there for her through it all- from her book releases to attending events together to just being a good friend to her.
Chronicling her pain
Despite living with chronic pain, Karen continued to work.
In 2000, she became an author when she released her first book, Model Patient: My Life as an Incurable Wise-A**.
The book brought his life into the limelight and how it all came to an abrupt end when he got the diagnosis.
But Karen did not learn to hide from life, but chose to run towards it.
In the 2000s, he continued to star in minor roles such as Fantastic Mr Fox, Crafty and Pepper Ann.
Karen hosted Tiny House of Horrors on TLC and appeared as a co-host on Live Earth.
Duffy told People that being with her family and friends has been "an important form of therapy for her" for the past 20 years.
Life outside the spotlight
After the 2000s, Karen stopped acting and focused on her family and writing.
In 1997, she married John Lambrose.
They had one child together, Jack, who was born via surrogate.
George was the one who encouraged her and her husband to have a child.
It was difficult to conceive with all the procedures she had done, but she helped them find a doctor to help them.
He published his second book, Backbone: Living with Chronic Pain Without Turning Into One in 2017.
It was a way she could describe her daily life with chronic pain and suffering, while using humor and acceptance to cope.
George couldn't attend the release of his book because he was on "paternity leave," but he did send a tequila fountain.
He was featured in the book and also wrote a blurb for it.
“My friend Karen Duffy, who lives with unimaginable pain, has taught me a lot; That my complaints are the most ridiculous in the world,” it read.
In her book, she told readers that she usually only gets up three days a week and that the slightest touch, including wind, would "sting her neck."
He is still a big part of her and her son's life.
He even gave him his first dog a few years back.
Book 3 and life now
Karen made a surprise appearance on The Real Housewives of New York City in 2018.
She was last seen on TV.
In the same year, he spoke at the US Pain Foundation and Gala.
Now, Karen focuses on being a wife and mother and writer.
Her third book, Wise Up: Irreverent Enlightenment from a Mother Who's Been Through It, was released on April 12.
The book is written in the form of letters to her 18-year-old son, Jack, with a mix of life lessons and funny stories.
Jack is a high school hockey player.
Karen recently celebrated her 60th birthday with friends last year and is currently co-producing two films - New World and The World's Greatest Bear Run Ever.
Karen has used writing as a form of therapy.
He hopes that his words and books will inspire others and help others who are struggling with chronic pain.