Table of Contents
What is Crohn's disease
Crohn's disease is a chronic inflammatory condition that can affect any part of the digestive tract.
It's a type of inflammatory bowel disease (IBD) that typically causes swelling and irritation in the lining of the digestive tract, which can lead to abdominal pain, diarrhea, fatigue, weight loss, malnutrition, and other symptoms.
Currently, there's no cure for Crohn's disease, but treatment can help manage the symptoms and prevent complications.
How common is Crohn's disease
A 2017 study found that the incidence of inflammatory bowel disease, including Crohn's disease, was stable or declining in North America and Europe, while the incidence was rising in newly industrialized countries in Africa, Asia, and South America.
Who's affected by Crohn's disease
Crohn's disease can affect anyone, but it is most commonly diagnosed in people between the ages of 15 and 35 and may be slightly more common in females than males.
Crohn's disease in children and young adults
While it is more common in adults, it's estimated that up to 25% of people with Crohn's disease are diagnosed before the age of 20.
The symptoms of Crohn's disease in children can be similar to those in adults, but they may also experience growth delays and problems with weight gain.
It is important for children with Crohn's disease to be under the care of a doctor who specializes in treating inflammatory bowel diseases in children.
Types of Crohn's disease
Crohn's disease can affect different parts of the digestive tract, and the location of the inflammation can determine the type of Crohn's disease you have.
There are several different types of Crohn's disease, including:
- Ileocolitis - About 50% of people with Crohn's disease have ileocolitis, making it the most common form of Crohn's disease. Ileocolitis is characterized by inflammation in the ileum (the lower part of the small intestine) and the colon (the large intestine).
- Crohn's Ileitis -This type of Crohn's disease affects only the ileum (the lower part of the small intestine).
- Gastroduodenal Crohn's disease - This type of Crohn's disease affects the stomach and the beginning of the small intestine (also called the duodenum).
- Jejunoileitis - This type of Crohn's disease affects the upper half of the small intestine (the jejunum). Jejunoileitis is more common in children (up to 20% of cases) than adults (up to 4% of cases) and is associated with malnutrition and growth delays in children.
- Crohn's colitis - This type of Crohn's disease only affects the large intestine (the colon).
It's important to note that your Crohn's disease might not fit neatly into one of these categories, and you may have a combination of types.
It is also possible for your type of Crohn's disease to change over time. A gastroenterologist can help determine your specific type of Crohn's disease.
Crohn's disease vs. ulcerative colitis
Crohn's disease and ulcerative colitis are both inflammatory bowel diseases (IBD). Crohn's disease can affect any part of the digestive tract and the entire thickness of the bowel wall, while ulcerative colitis only affects the innermost lining of the colon and rectum.
IBD vs. IBS
Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are two different conditions that affect the digestive tract.
IBD is a group of chronic disorders that cause inflammation in the digestive tract, while IBS is a functional disorder (a disturbance in bowel function) characterized by a collection of symptoms.
IBD and IBS patients may experience similar symptoms, such as bloating, gas, diarrhea, constipation, and abdominal pain. However, unlike IBD, IBS does not cause inflammation, rarely requires hospitalization or surgery, and has not been associated with an increased risk for colorectal cancer due to the lack of inflammation.
Signs and symptoms of Crohn's disease
The signs and symptoms of Crohn's disease can vary from person to person and may differ depending on the location and severity of inflammation in the digestive tract. Common symptoms may include
- Persistent diarrhea
- Bowel urgency
- Feelings of incomplete evacuation
- Fatigue (persistent low energy)
- Abdominal pain or cramping
- Blood in stool or rectal bleeding
- Reduced appetite and weight loss
- Pain or discharge around the anus
Extraintestinal manifestations of Crohn's disease
When symptoms of Crohn's disease occur outside of the gastrointestinal tract, they are called extraintestinal manifestations (EMs). EMs occur in 25-40% of people with inflammatory bowel disease and can significantly impact your quality of life.
Common EMs of Crohn's disease include
- Bones and muscles - Inflammation of the joints near the back and spine, also known as axial arthritis, may occur in up to 50% of people with Crohn's disease.
- Skin and mouth - Approximately 5-50% of individuals with Crohn's disease may develop oral canker sores. Additionally, erythema nodosum (red, painful bumps under the skin) may be present in 5-15% of cases. Pyoderma gangrenosum (large, painful sores) may occur in up to 2.6% of cases.
- Eyes - Inflammation of the middle layer of the eye (anterior uveitis) may occur in 5-12% of people with Crohn's disease
What is a Crohn's disease flare?
A Crohn's disease flare, or flare-up, is when you experience symptoms of the disease.
During a flare, you may experience abdominal pain, bowel urgency, diarrhea, or constipation. You may also notice increased fatigue, loss of appetite, or weight loss.
A Crohn's flare can last a few days to several months or years.
Does a flare mean you have inflammation?
Inflammation in the GI tract, also referred to as active disease, is poorly correlated with symptoms.
It's possible to have no symptoms with active inflammation. Likewise, it's possible to experience symptoms without having active disease. As a result, it's important to have your doctor continue to check your labs and scopes for inflammation, even if you're feeling symptom-free.
The presence of inflammation can be confirmed by your doctor by looking at the lining of your GI tract during a colonoscopy or endoscopy, checking the levels of certain biomarkers in your blood and stool, or by examining a biopsy of your GI tract under a microscope.
When to see a doctor
Always call your doctor if you notice any changes in your bowel habits or symptoms, such as new or worsening abdominal pain, blood in your stool, nausea, vomiting, persistent diarrhea, unexplained weight loss, or a fever alongside any of these symptoms.
Your doctor can only help you if they're aware of your symptoms, so don't hesitate to let them know as soon as possible.
Questions to ask your doctor
- What type of Crohn's disease do I have?
- How will I know if I'm in a flare-up?
- How will I know if I'm in remission?
- How can I prevent flare-ups in the future?
- What's the best treatment option for me?
- When should I let you know about changes in my symptoms?
Causes of Crohn's disease
The exact cause of Crohn's disease is unknown, but it is thought to be caused by a combination of factors, including genetics, an abnormal immune system response, and environmental triggers.
Risk factors of Crohn's disease
- Family history - People with a family history of Crohn's disease are more likely to develop Crohn's disease than those without a family history. A 2015 study suggested that children of mothers with Crohn's disease had a 2.7% risk of developing Crohn's disease during their lifetime. According to two small studies, your risk of developing Crohn's disease may be as high as 30% if both of your parents have the IBD.
- Age - Crohn's disease can affect people of all ages, but it's most commonly diagnosed between the ages of 15 and 35.
- Cigarette smoking - People who smoke cigarettes are 1.76x more likely to develop Crohn's disease than those who do not smoke.18 Smoking may also increase the risk of worsening Crohn's disease, increase the risk of surgery, and decrease the effectiveness of certain medications.
- Ethnicity - Research studies suggest that the risk of developing IBD (including Crohn's disease) may be three times higher in non-Hispanic whites and 2-4 times higher in people of Ashkenazi Jewish heritage compared to non-Jewish ethnic groups.
- Certain medications - The use of NSAIDs such as aspirin or ibuprofen (Advil, Motrin), antibiotics, and birth control pills may slightly increase the risk of developing Crohn's disease.
Diagnosis & testing
- Blood tests - Your doctor may order blood tests to check for anemia (a lower-than-normal number of red blood cells) or signs of an active or inactive infection. Your doctor may also check for vitamin and nutrient deficiencies and signs of inflammation, such as your c-reactive protein levels (CRP) or erythrocyte sedimentation rate (ESR).
- Stool tests - In certain cases, your doctor may request a stool sample to measure inflammation or to check for a bacterial infection.
- Colonoscopy - A colonoscopy is a procedure in which your doctor, typically your gastroenterologist, uses a small, flexible camera to look inside your rectum and large intestine. During your colonoscopy, your doctor will examine the inner lining of your GI tract to look for signs of inflammation in the colon and ileum. Your doctor may also take small samples of your intestine - called biopsies - to check for microscopic inflammation and make a diagnosis.
- Capsule endoscopy - Your doctor may request a capsule endoscopy if she needs to examine your upper GI tract or your small intestine, which may not be accessible during a colonoscopy. During this procedure, you swallow a capsule containing a small camera that takes pictures as it passes through your system. After the camera is deposited in your stool, your doctor will examine the images for signs of Crohn's disease.
- Balloon enteroscopy - If your doctor needs to inspect your small intestine, she may request a balloon enteroscopy, also known as a deep endoscopy. This procedure uses a long, thin tube with a small camera and inflatable balloons to reach areas of your small intestine that are not accessible using other methods. This device, known as an enteroscope, may be inserted through your esophagus or anus, depending on the location your doctor is trying to inspect. Balloon enteroscopy may help diagnose and manage Crohn's disease involving the small intestine or a partial blockage of the small intestine, such as a stricture.
- CT scan - A CT (computed tomography) scan is a type of x-ray that doctors use to create detailed images of the inside of the body. Your doctor may order a CT scan to look at your intestines and surrounding organs. In some cases, your doctor may request a CT enterography which uses a special fluid (called contrast) to get a better picture of your bowel.
- MRI scan - An MRI (magnetic resonance imaging) scan uses a strong magnetic field and radio waves to take detailed images of the intestines and surrounding area. Your doctor may use an MRI scan to assess a fistula or examine a particular part of your bowel. During an MRI scan, you lay on a table inside a large, cylindrical machine. Since MRI scans do not use x-rays, they may be used instead of a CT scan to avoid radiation exposure.
- Biopsy - A biopsy is a small piece of your intestines your doctor may collect during a procedure. A pathologist will look at your biopsy under a microscope to confirm the presence or absence of inflammation.
- Ultrasound - An ultrasound is an imaging technique that uses sound waves to create images of the inside of your body. Your doctor may use an ultrasound to determine the presence and severity of inflammation in your intestines, monitor your bowels for therapy response and inform your treatment plan. Ultrasound may also be used to diagnose potential complications of Crohn’s disease such as a stricture.
Crohn's disease treatment options
There is no cure for Crohn's disease. However, there are many treatment options available.
A common goal of treatment is to reduce inflammation, symptoms, and complications of Crohn's disease. In the best-case scenario, treatment may lead to periods of deep remission and few, if any, symptoms.
No single treatment works for everyone, so it's important to work with your doctor to find the best option for you.
These medications are used to reduce inflammation within your gastrointestinal tract. There are two types of anti-inflammatory drugs commonly used in Crohn's disease.
- Steroids: Steroids such as prednisone and budesonide are typically used for a short period of time to reduce inflammation. They may be used with other medications, and the dosage is typically tapered down over time.
- 5-Aminosalicylates (5-ASAs): These medications, including mesalamine (Lialda) and sulfasalazine, are generally not recommended for use in Crohn's disease patients. Despite being widely used in the past, doctors today generally do not consider these medications to be effective in reducing inflammation in people with Crohn's disease.
Immune system suppressors (immunomodulators)
These types of drugs help to reduce inflammation by decreasing the activity of your immune system. Common immune system suppressors include azathioprine (Azasan, Imuran), mercaptopurine (Purinethol, Purixan), and methotrexate (Trexal).
Biologics prevent and reduce inflammation in the digestive system by targeting and blocking certain parts of your immune system that cause inflammation. Biologics are effective at treating moderate to severe cases of Crohn's disease as they can induce and maintain remission.
Common biologics used to treat Crohn's disease include:
- Vedolizumab (Entyvio): This gut-specific medicine prevents certain immune cells from binding to other cells in your intestines.
- Infliximab (Remicade), Adalimumab (Humira), Certolizumab pegol (Cimzia): These medications (also known as TNF inhibitors) suppress the immune system by blocking the activity of TNF, a substance in the body that can cause inflammation.
- Ustekinumab (Stelara), Risankizumab (Skyrizi): These medications interfere with how your body's immune cells communicate with each other, reducing inflammation.
Crohn's disease may cause infections leading to abscesses (pockets of puss) and fistulas (tunnels that form in the intestinal wall or skin). Antibiotics may be used to help treat these complications. Two common types of antibiotics used include ciprofloxacin (Cipro) and metronidazole (Flagyl).
Antidiarrheal medications and supplements
Your doctor may recommend a fiber supplement to bulk up your stools and reduce mild to moderate diarrhea. For severe cases of diarrhea, loperamide (Imodium) is sometimes recommended.
It's important to note that antidiarrheal medications and supplements may not be appropriate and could be harmful for patients with stricturing Crohn's disease or certain infections. You should always talk to your doctor before starting any supplement.
Surgery is often used to treat Crohn's disease if medications are ineffective. It's estimated that up to 60% of people with Crohn's disease may require surgery at some point in the first 20 years after diagnosis.
While surgery can't cure Crohn's disease, it is often used to treat complications, such as fistulas, bleeding, and bowel obstructions, and to reduce symptoms.
Common types of surgery for Crohn's disease include
- Small bowel resection: Removing the damaged portions of the small intestine
- Partial or subtotal colectomy: Removing the damaged portions of the large intestine
- Total proctocolectomy and ileostomy: Removing all of the large intestine and rectum and placing an ostomy where a bag is attached externally to collect stool
It's important to work with a registered dietitian with experience working with people with Crohn's disease to develop a personalized nutrition plan.
Your dietitian will help you prevent or correct malnutrition and avoid restrictive eating habits which may negatively impact your relationship with food. Your dietitian will also be able to help you come up with recipes, meals, and snack ideas that fit with your lifestyle and preferences.
Certain lifestyle factors, such as stress and poor sleep quality, may lead to more severe symptoms of Crohn's disease.
- Stress: Research suggests that people who experience higher levels of stress, new sources of stress, or a recent life event are more likely to experience a Crohn's disease flare.
- Sleep quality: 51-80% of people with Crohn's disease suffer from poor sleep quality, which is associated with a greater risk for worse disease outcomes. In a recent study, poor sleep quality was also associated with increased risk for surgery and hospitalizations in people with Crohn's disease.
Mental health care
People with Crohn’s disease are more likely to experience anxiety and depression than healthy individuals. Anxiety and depression are also more common when you have active disease compared to remission.
It may be helpful to consult with a GI-specific psychologist to process a new diagnosis or cope with the symptoms and worries that people with Crohn’s disease often experience.
Is Crohn's curable?
There is no cure for Crohn's disease. However, with proper treatment and management, people with Crohn's disease can often lead normal, active lives.
Crohn's disease diet
Diet guidelines for Crohn's disease
A recent study from the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) suggested general diet guidelines for people with Crohn's disease.
For people with Crohn's disease, the guidelines recommend increasing the following foods in your diet:
If you have stricturing Crohn’s, you should consult your doctor and dietitian before making any changes to your diet, as increasing certain fruits and vegetables could lead to complications.
The guidelines recommend decreasing the following foods in your diet:
- Saturated and trans fats
- Artificial sweeteners
- Titanium dioxide
- Unpasteurized dairy products
Crohn's disease diets
- Exclusive enteral nutrition (EEN): EEN is a formula-based diet (no solid foods) and is recommended as the first-line treatment to help children with mild to moderate Crohn's disease get into remission.
- Crohn's disease exclusion diet with partial enteral nutrition (CDED-PEN): CDED-PEN is a diet in which a portion of your calories come from a specific nutrition formula, and the rest comes from a specific list of mandatory and allowed foods. Research suggests that the CDED-PEN diet can help children with mild-to-moderate Crohn's disease get into and stay in remission. This diet may also significantly reduce fecal calprotectin levels in adults with mild-to-moderate Crohn's disease.
- Crohn's disease exclusion diet (CDED): A recent study showed that the CDED diet without PEN may be just as effective as the CDED-PEN diet at helping adults with mild-to-moderate Crohn's disease get into and stay in remission.
- Mediterranean diet: This diet includes regular consumption of fruits, vegetables, whole grains, fish, legumes, nuts, and olive oil, while eggs, chicken, and dairy are consumed in moderation. Red meat and sweets are consumed infrequently with the Mediterranean diet. In a randomized controlled trial, the Specific carbohydrate diet (SCD) didn’t outperform the Mediterranean diet in adults with mild-to-moderate Crohn's disease therefore would be preferable over the SCD, given it’s less restrictive nature.
- Specific carbohydrate diet (SCD): This diet includes a list of “legal” foods such as fruits, vegetables, fish, meat, homemade yogurt, and aged cheeses and “illegal” foods such as grains, processed foods, soy, and certain vegetables. The SCD diet has been suggested in research to reduce symptoms in adults with mild-to-moderate Crohn's disease but was not more effective than the Mediterranean diet.
- Low-FODMAP diet: The low-FODMAP diet is a short-term diet in which certain foods are initially eliminated from your diet and then reintroduced to test your tolerance. This diet may help reduce certain symptoms in people with inflammatory bowel disease and overlapping irritable bowel syndrome. However, the diet has not been shown to reduce inflammation.
Diets without enough research supporting their use in Crohn's disease
- Anti-inflammatory diet (AID)
- Autoimmune protocol diet (AIP)
- Gluten-free diet
- Low-fiber diet
- Low-residue diet
Restriction and disordered eating in Crohn's disease
It's estimated that up to 96% of people with inflammatory bowel disease have disordered eating behaviors with food and beverage avoidance being the most common. Factors that increase your risk of disordered eating include:
- Having a diagnosis of Crohn's disease
- Believing that you have active disease or inflammation
- Being female
- Dietary misinformation
- Having a fear of triggering symptoms
How to maintain a healthy relationship with food
While restriction is a normal response to symptoms, it's important not to normalize restriction as it can lead to nutrient deficiencies, weight loss, malnutrition, worsened anxiety and depression, and a decreased quality of life .
To maintain a healthy relationship with food and take a more relaxed approach to your diet:
- Focus on increasing the variety of foods in your diet rather than restricting foods.
- Resist self-imposed diets and work with your doctor and registered dietitian to create a diet that's individualized to your unique needs.
- Make small diet changes over time rather than large changes all at once.
People with Crohn's disease may experience complications associated with the disease, including:
- Anemia: Anemia is a complication of Crohn's disease in which your body does not produce enough healthy red blood cells which carry oxygen. Anemia due to an iron deficiency is common in people with IBD and is caused by blood loss and poor iron absorption due to inflammation. A common symptom of iron deficiency anemia is chronic fatigue.
- Anal fissures: An anal fissure is a tear in the lining of the anus or the skin around the anus. Anal fissures are prone to infection and may result in painful bowel movements.
- Arthritis: Arthritis is one of the most common complications of Crohn's disease, occurring in 10-35% of people with inflammatory bowel disease. People with arthritis may experience joint pain and stiffness, most commonly in the low back region.
- Blood clots: People with Crohn's disease are at a 1.5-3.5x greater risk of blood clots in their veins compared to the general population.
- Bowel obstruction: A bowel obstruction occurs when something, such as a stricture, blocks the small or large intestine, slowing or preventing food and liquid from passing through the bowels. A bowel obstruction is a serious complication and requires immediate medical attention.
- Cancer: Research suggests that people with Crohn's disease of the large intestine (the colon) are 4.5x more likely to develop colorectal cancer than the general population. Those with Crohn’s disease of the small intestine are 18-27x more likely to develop small-bowel cancer than the general population.
- Fistulas: A fistula is an abnormal connection, or tunnel, that develops between the intestine and another organ, such as the bladder or vagina, or between the intestine and the skin. Fistulas may lead to abscesses (pockets of puss), infection, malnutrition, and holes in the bowel wall. Perianal fistulas, or tunnels between the anus and the skin, are among the most common complications of Crohn's disease and occur in 23-38% of cases.
- Liver disease: Crohn's disease is associated with several liver complications, the most common of which is fatty liver disease, which affects 2-40% of people with the condition. Gallstones, which occur in 11-34% of cases, are also common. In rare cases (1-3%), people with Crohn's disease may also develop primary sclerosing cholangitis.
- Malnutrition: When your body isn't receiving or absorbing the nutrients it needs, you may experience malnutrition. Common symptoms of Crohn's disease, such as diarrhea, cramping, and abdominal pain, may make it harder to eat enough to nourish your body and harder for your body to absorb the nutrients you consume. You should work with a registered dietitian to address malnutrition.
- Medication risks & interactions: You may experience side effects from the medications your doctor prescribes to treat your Crohn's disease. Your gastroenterologist will be able to tell you about the risks and benefits of all of your medications to find a solution that works for you.
- Osteoporosis: Studies have suggested that people with IBD may have lower bone mineral density and a higher risk of fractures than the general population. It's estimated that 14-42% of people with IBD may have osteoporosis.
- Skin disorders: Skin disorders are one of the most common complications of IBD. You may experience red bumps or blisters on your skin, fistulas or fissures around your rectum, or canker sores in and around your mouth.
- Strictures: A stricture refers to a narrowing or constriction of the digestive tract caused by inflammation and/or scar tissue build-up associated with Crohn's disease. Strictures may lead to partial or complete blockages of your intestines and may require surgery to treat.
- Ulcers: These open sores can occur anywhere in the digestive tract in people with Crohn's disease and can be painful and uncomfortable.
- Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol EI, Panaccione R, Ghosh S, Barkema HW, Kaplan GG. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012 Jan;142(1):46-54.e42; quiz e30. doi: 10.1053/j.gastro.2011.10.001. Epub 2011 Oct 14. PMID: 22001864.
- Shivashankar R, Tremaine WJ, Harmsen WS, Loftus EV Jr. Incidence and Prevalence of Crohn's Disease and Ulcerative Colitis in Olmsted County, Minnesota From 1970 Through 2010. Clin Gastroenterol Hepatol. 2017 Jun;15(6):857-863. doi: 10.1016/j.cgh.2016.10.039. Epub 2016 Nov 14. PMID: 27856364; PMCID: PMC5429988.
- Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol EI, Panaccione R, Ghosh S, Wu JCY, Chan FKL, Sung JJY, Kaplan GG. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017 Dec 23;390(10114):2769-2778. doi: 10.1016/S0140-6736(17)32448-0. Epub 2017 Oct 16. Erratum in: Lancet. 2020 Oct 3;396(10256):e56. PMID: 29050646.
- Hovde Ø, Moum BA. Epidemiology and clinical course of Crohn's disease: results from observational studies. World J Gastroenterol. 2012 Apr 21;18(15):1723-31. doi: 10.3748/wjg.v18.i15.1723. PMID: 22553396; PMCID: PMC3332285.
- Santos MPC, Gomes C, Torres J. Familial and ethnic risk in inflammatory bowel disease. Ann Gastroenterol. 2018 Jan-Feb;31(1):14-23. doi: 10.20524/aog.2017.0208. Epub 2017 Oct 26. PMID: 29333063; PMCID: PMC5759609.
- Yang H, McElree C, Roth MP, Shanahan F, Targan SR, Rotter JI. Familial empirical risks for inflammatory bowel disease: differences between Jews and non-Jews. Gut. 1993 Apr;34(4):517-24. doi: 10.1136/gut.34.4.517. PMID: 8491401; PMCID: PMC1374314.
- Rosen MJ, Dhawan A, Saeed SA. Inflammatory Bowel Disease in Children and Adolescents. JAMA Pediatr. 2015 Nov;169(11):1053-60. doi: 10.1001/jamapediatrics.2015.1982. PMID: 26414706; PMCID: PMC4702263.
- Gajendran M, Loganathan P, Catinella AP, Hashash JG. A comprehensive review and update on Crohn's disease. Dis Mon. 2018 Feb;64(2):20-57. doi: 10.1016/j.disamonth.2017.07.001. Epub 2017 Aug 18. PMID: 28826742.
- Baldassano RN, Piccoli DA. Inflammatory bowel disease in pediatric and adolescent patients. Gastroenterol Clin North Am. 1999 Jun;28(2):445-58. doi: 10.1016/s0889-8553(05)70064-9. PMID: 10372276.
- Belli DC, Seidman E, Bouthillier L, Weber AM, Roy CC, Pletincx M, Beaulieu M, Morin CL. Chronic intermittent elemental diet improves growth failure in children with Crohn's disease. Gastroenterology. 1988 Mar;94(3):603-10. doi: 10.1016/0016-5085(88)90230-2. PMID: 3123302.
- Levine JS, Burakoff R. Extraintestinal manifestations of inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2011 Apr;7(4):235-41. PMID: 21857821; PMCID: PMC3127025.
- Rogler G, Singh A, Kavanaugh A, Rubin DT. Extraintestinal Manifestations of Inflammatory Bowel Disease: Current Concepts, Treatment, and Implications for Disease Management. Gastroenterology. 2021 Oct;161(4):1118-1132. doi: 10.1053/j.gastro.2021.07.042. Epub 2021 Aug 3. PMID: 34358489; PMCID: PMC8564770.
- Sun Y, Li L, Xie R, Wang B, Jiang K, Cao H. Stress Triggers Flare of Inflammatory Bowel Disease in Children and Adults. Front Pediatr. 2019 Oct 24;7:432. doi: 10.3389/fped.2019.00432. PMID: 31709203; PMCID: PMC6821654.
- Bernstein, Charles N MD1,2; Singh, Sunny BSc1; Graff, Lesley A PhD1,3; Walker, John R PhD1,3; Miller, Norine RN1; Cheang, Mary MS1. A Prospective Population-Based Study of Triggers of Symptomatic Flares in IBD. American Journal of Gastroenterology 105(9):p 1994-2002, September 2010. | DOI: 10.1038/ajg.2010.140
- Feagins LA, Iqbal R, Spechler SJ. Case-control study of factors that trigger inflammatory bowel disease flares. World J Gastroenterol. 2014 Apr 21;20(15):4329-34. doi: 10.3748/wjg.v20.i15.4329. PMID: 24764669; PMCID: PMC3989967.
- Moller FT, Andersen V, Wohlfahrt J, Jess T. Familial risk of inflammatory bowel disease: a population-based cohort study 1977-2011. Am J Gastroenterol. 2015 Apr;110(4):564-71. doi: 10.1038/ajg.2015.50. Epub 2015 Mar 24. PMID: 25803400.
- Laharie D, Debeugny S, Peeters M, Van Gossum A, Gower-Rousseau C, Bélaïche J, Fiasse R, Dupas JL, Lerebours E, Piotte S, Cortot A, Vermeire S, Grandbastien B, Colombel JF. Inflammatory bowel disease in spouses and their offspring. Gastroenterology. 2001 Mar;120(4):816-9. doi: 10.1053/gast.2001.22574. PMID: 11231934.
- Mahid SS, Minor KS, Soto RE, Hornung CA, Galandiuk S. Smoking and inflammatory bowel disease: a meta-analysis. Mayo Clin Proc. 2006 Nov;81(11):1462-71. doi: 10.4065/81.11.1462. Erratum in: Mayo Clin Proc. 2007 Jul;82(7):890. PMID: 17120402.
- Parkes GC, Whelan K, Lindsay JO. Smoking in inflammatory bowel disease: impact on disease course and insights into the aetiology of its effect. J Crohns Colitis. 2014 Aug;8(8):717-25. doi: 10.1016/j.crohns.2014.02.002. Epub 2014 Mar 11. PMID: 24636140.
- Nguyen GC, Chong CA, Chong RY. National estimates of the burden of inflammatory bowel disease among racial and ethnic groups in the United States. J Crohns Colitis. 2014 Apr;8(4):288-95. doi: 10.1016/j.crohns.2013.09.001. Epub 2013 Sep 24. PMID: 24074875.
- Yan B, Panaccione R, Sutherland L. I am Jewish: what is my risk of developing Crohn's disease? Inflamm Bowel Dis. 2008 Oct;14 Suppl 2:S26-7. doi: 10.1002/ibd.20691. Erratum in: Inflamm Bowel Dis. 2009 Sep;15(9):1438-47. PMID: 18816782.
- Ananthakrishnan AN, Higuchi LM, Huang ES, Khalili H, Richter JM, Fuchs CS, Chan AT. Aspirin, nonsteroidal anti-inflammatory drug use, and risk for Crohn disease and ulcerative colitis: a cohort study. Ann Intern Med. 2012 Mar 6;156(5):350-9. doi: 10.7326/0003-4819-156-5-201203060-00007. PMID: 22393130; PMCID: PMC3369539.
- Ko Y, Butcher R, Leong RW. Epidemiological studies of migration and environmental risk factors in the inflammatory bowel diseases. World J Gastroenterol. 2014 Feb 7;20(5):1238-47. doi: 10.3748/wjg.v20.i5.1238. PMID: 24574798; PMCID: PMC3921506.
- Lichtenstein, Gary R MD, FACG1; Loftus, Edward V MD, FACG2; Isaacs, Kim L MD, PhD, FACG3; Regueiro, Miguel D MD, FACG4; Gerson, Lauren B MD, MSc, MACG (GRADE Methodologist)5,†; Sands, Bruce E MD, MS, FACG6. ACG Clinical Guideline: Management of Crohn's Disease in Adults. American Journal of Gastroenterology 113(4):p 481-517, April 2018. | DOI: 10.1038/ajg.2018.27
- Peyrin-Biroulet L, Harmsen WS, Tremaine WJ, Zinsmeister AR, Sandborn WJ, Loftus EV Jr. Surgery in a population-based cohort of Crohn's disease from Olmsted County, Minnesota (1970-2004). Am J Gastroenterol. 2012 Nov;107(11):1693-701. doi: 10.1038/ajg.2012.298. Epub 2012 Sep 4. PMID: 22945286; PMCID: PMC3572861.
- Xia SL, Min QJ, Shao XX, Lin DP, Ma GL, Wu H, Cao SG, Jiang Y. Influence of Vitamin D3 Supplementation on Infliximab Effectiveness in Chinese Patients With Crohn's Disease: A Retrospective Cohort Study. Front Nutr. 2021 Oct 22;8:739285. doi: 10.3389/fnut.2021.739285. PMID: 34746207; PMCID: PMC8568764.
- Wintjens DSJ, de Jong MJ, van der Meulen-de Jong AE, Romberg-Camps MJ, Becx MC, Maljaars JP, van Bodegraven AA, Mahmmod N, Markus T, Haans J, Masclee AAM, Winkens B, Jonkers DMAE, Pierik MJ. Novel Perceived Stress and Life Events Precede Flares of Inflammatory Bowel Disease: A Prospective 12-Month Follow-Up Study. J Crohns Colitis. 2019 Mar 30;13(4):410-416. doi: 10.1093/ecco-jcc/jjy177. PMID: 30371776.
- Graff LA, Vincent N, Walker JR, Clara I, Carr R, Ediger J, Miller N, Rogala L, Rawsthorne P, Lix L, Bernstein CN. A population-based study of fatigue and sleep difficulties in inflammatory bowel disease. Inflamm Bowel Dis. 2011 Sep;17(9):1882-9. doi: 10.1002/ibd.21580. Epub 2010 Dec 22. PMID: 21830266.
- Sofia MA, Lipowska AM, Zmeter N, Perez E, Kavitt R, Rubin DT. Poor Sleep Quality in Crohn's Disease Is Associated With Disease Activity and Risk for Hospitalization or Surgery. Inflamm Bowel Dis. 2020 Jul 17;26(8):1251-1259. doi: 10.1093/ibd/izz258. PMID: 31820780; PMCID: PMC7365809.
- Levine A, Rhodes JM, Lindsay JO, Abreu MT, Kamm MA, Gibson PR, Gasche C, Silverberg MS, Mahadevan U, Boneh RS, Wine E, Damas OM, Syme G, Trakman GL, Yao CK, Stockhamer S, Hammami MB, Garces LC, Rogler G, Koutroubakis IE, Ananthakrishnan AN, McKeever L, Lewis JD. Dietary Guidance From the International Organization for the Study of Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol. 2020 May;18(6):1381-1392. doi: 10.1016/j.cgh.2020.01.046. Epub 2020 Feb 15. PMID: 32068150.
- van Rheenen PF, Aloi M, Assa A, Bronsky J, Escher JC, Fagerberg UL, Gasparetto M, Gerasimidis K, Griffiths A, Henderson P, Koletzko S, Kolho KL, Levine A, van Limbergen J, Martin de Carpi FJ, Navas-López VM, Oliva S, de Ridder L, Russell RK, Shouval D, Spinelli A, Turner D, Wilson D, Wine E, Ruemmele FM. The Medical Management of Paediatric Crohn's Disease: an ECCO-ESPGHAN Guideline Update. J Crohns Colitis. 2020 Oct 7:jjaa161. doi: 10.1093/ecco-jcc/jjaa161. Epub ahead of print. PMID: 33026087.
- Levine A, Wine E, Assa A, Sigall Boneh R, Shaoul R, Kori M, Cohen S, Peleg S, Shamaly H, On A, Millman P, Abramas L, Ziv-Baran T, Grant S, Abitbol G, Dunn KA, Bielawski JP, Van Limbergen J. Crohn's Disease Exclusion Diet Plus Partial Enteral Nutrition Induces Sustained Remission in a Randomized Controlled Trial. Gastroenterology. 2019 Aug;157(2):440-450.e8. doi: 10.1053/j.gastro.2019.04.021. Epub 2019 Jun 4. PMID: 31170412.
- Szczubełek M, Pomorska K, Korólczyk-Kowalczyk M, Lewandowski K, Kaniewska M, Rydzewska G. Effectiveness of Crohn's Disease Exclusion Diet for Induction of Remission in Crohn's Disease Adult Patients. Nutrients. 2021 Nov 17;13(11):4112. doi: 10.3390/nu13114112. PMID: 34836367; PMCID: PMC8618677.
- Yanai H, Levine A, Hirsch A, Boneh RS, Kopylov U, Eran HB, Cohen NA, Ron Y, Goren I, Leibovitzh H, Wardi J, Zittan E, Ziv-Baran T, Abramas L, Fliss-Isakov N, Raykhel B, Gik TP, Dotan I, Maharshak N. The Crohn's disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn's disease (CDED-AD): an open-label, pilot, randomised trial. Lancet Gastroenterol Hepatol. 2022 Jan;7(1):49-59. doi: 10.1016/S2468-1253(21)00299-5. Epub 2021 Nov 2. PMID: 34739863.
- Davis C, Bryan J, Hodgson J, Murphy K. Definition of the Mediterranean Diet; a Literature Review. Nutrients. 2015 Nov 5;7(11):9139-53. doi: 10.3390/nu7115459. PMID: 26556369; PMCID: PMC4663587.
- Lewis JD, Sandler RS, Brotherton C, Brensinger C, Li H, Kappelman MD, Daniel SG, Bittinger K, Albenberg L, Valentine JF, Hanson JS, Suskind DL, Meyer A, Compher CW, Bewtra M, Saxena A, Dobes A, Cohen BL, Flynn AD, Fischer M, Saha S, Swaminath A, Yacyshyn B, Scherl E, Horst S, Curtis JR, Braly K, Nessel L, McCauley M, McKeever L, Herfarth H; DINE-CD Study Group. A Randomized Trial Comparing the Specific Carbohydrate Diet to a Mediterranean Diet in Adults With Crohn's Disease. Gastroenterology. 2021 Sep;161(3):837-852.e9. doi: 10.1053/j.gastro.2021.05.047. Epub 2021 May 27. Erratum in: Gastroenterology. 2022 Nov;163(5):1473. PMID: 34052278; PMCID: PMC8396394.
- Cox SR, Lindsay JO, Fromentin S, Stagg AJ, McCarthy NE, Galleron N, Ibraim SB, Roume H, Levenez F, Pons N, Maziers N, Lomer MC, Ehrlich SD, Irving PM, Whelan K. Effects of Low FODMAP Diet on Symptoms, Fecal Microbiome, and Markers of Inflammation in Patients With Quiescent Inflammatory Bowel Disease in a Randomized Trial. Gastroenterology. 2020 Jan;158(1):176-188.e7. doi: 10.1053/j.gastro.2019.09.024. Epub 2019 Oct 2. PMID: 31586453.
- Day AS, Yao CK, Costello SP, Andrews JM, Bryant RV. Food avoidance, restrictive eating behaviour and association with quality of life in adults with inflammatory bowel disease: A systematic scoping review. Appetite. 2021 Dec 1;167:105650. doi: 10.1016/j.appet.2021.105650. Epub 2021 Aug 12. PMID: 34391842.
- Kaitha S, Bashir M, Ali T. Iron deficiency anemia in inflammatory bowel disease. World J Gastrointest Pathophysiol. 2015 Aug 15;6(3):62-72. doi: 10.4291/wjgp.v6.i3.62. PMID: 26301120; PMCID: PMC4540708.
- Larsen S, Bendtzen K, Nielsen OH. Extraintestinal manifestations of inflammatory bowel disease: epidemiology, diagnosis, and management. Ann Med. 2010 Mar;42(2):97-114. doi: 10.3109/07853890903559724. PMID: 20166813.
- Scoville EA, Konijeti GG, Nguyen DD, Sauk J, Yajnik V, Ananthakrishnan AN. Venous thromboembolism in patients with inflammatory bowel diseases: a case-control study of risk factors. Inflamm Bowel Dis. 2014 Apr;20(4):631-6. doi: 10.1097/MIB.0000000000000007. PMID: 24552828; PMCID: PMC4116613.
- Jess T, Gamborg M, Matzen P, Munkholm P, Sørensen TI. Increased risk of intestinal cancer in Crohn's disease: a meta-analysis of population-based cohort studies. Am J Gastroenterol. 2005 Dec;100(12):2724-9. doi: 10.1111/j.1572-0241.2005.00287.x. PMID: 16393226.
- Stidham RW, Higgins PDR. Colorectal Cancer in Inflammatory Bowel Disease. Clin Colon Rectal Surg. 2018 May;31(3):168-178. doi: 10.1055/s-0037-1602237. Epub 2018 Apr 1. PMID: 29720903; PMCID: PMC5929884.
- Hellers G, Bergstrand O, Ewerth S, Holmström B. Occurrence and outcome after primary treatment of anal fistulae in Crohn's disease. Gut. 1980 Jun;21(6):525-7. doi: 10.1136/gut.21.6.525. PMID: 7429313; PMCID: PMC1419665.
- Schwartz DA, Loftus EV Jr, Tremaine WJ, Panaccione R, Harmsen WS, Zinsmeister AR, Sandborn WJ. The natural history of fistulizing Crohn's disease in Olmsted County, Minnesota. Gastroenterology. 2002 Apr;122(4):875-80. doi: 10.1053/gast.2002.32362. PMID: 11910338.
- Restellini S, Chazouillères O, Frossard JL. Hepatic manifestations of inflammatory bowel diseases. Liver Int. 2017 Apr;37(4):475-489. doi: 10.1111/liv.13265. Epub 2016 Nov 6. PMID: 27712010.
- Farraye FA, Melmed GY, Lichtenstein GR, Kane SV. ACG Clinical Guideline: Preventive Care in Inflammatory Bowel Disease. Am J Gastroenterol. 2017 Feb;112(2):241-258. doi: 10.1038/ajg.2016.537. Epub 2017 Jan 10. Erratum in: Am J Gastroenterol. 2017 Jul;112(7):1208. PMID: 28071656. FA, Melmed GY, Lichtenstein GR, Kane SV. ACG Clinical Guideline: Preventive Care in Inflammatory Bowel Disease. Am J Gastroenterol. 2017 Feb;112(2):241-258. doi: 10.1038/ajg.2016.537. Epub 2017 Jan 10. Erratum in: Am J Gastroenterol. 2017 Jul;112(7):1208. PMID: 28071656.
- Mikocka-Walus A, Knowles SR, Keefer L, Graff L. Controversies Revisited: A Systematic Review of the Comorbidity of Depression and Anxiety with Inflammatory Bowel Diseases. Inflamm Bowel Dis. 2016 Mar;22(3):752-62. doi: 10.1097/MIB.0000000000000620. PMID: 26841224.