Crohn's disease: Get informed

What is Crohn’s disease? 

Definition

Crohn's disease is a chronic inflammatory bowel disease (IBD). It is an autoimmune condition that can affect any part of the digestive tract, from the mouth to the anus. It mainly affects the final segment of the small intestine called the ileum (which connects the stomach to the colon), the colon (also called large intestine) and the anus. The damage is segmental (alternating with healthy areas) and asymmetrical (in relation to the median axis of the body).

The inflamed intestinal mucosa is weakened. It is prone to the development of ulcers, more or less deep, which can go as far as perforation. This can lead to the development of localized abscesses and peritonitis (infection of the abdominal cavity), or even the formation of fistulae (abnormal connection between the digestive tract and another organ) and narrowing of the digestive tract (stenosis).

This disease evolves through periods of flare-ups (painful attacks), interspersed with remissions (the symptoms of the disease reduce) of varying frequency (weeks, months, even years).

How common is Crohn’s disease?

The prevalence of Crohn’s disease varies considerably depending on the geographical position. Approximately 10 million people suffer with this condition throughout the world. The number of patients is higher in developed countries, with the highest rate in Europe (3 million people) and the United States.

It is estimated that there are currently about 780,000 people living with Crohn’s disease in the United States.

Crohn’s disease can develop at any age, but it is most often diagnosed in young adults (aged between 20 and 30). There has been an increase in cases among children, and 5% of the cases concern people aged over 60.

Crohn’s disease affects both men and women, women being slightly more affected (13 women for 10 men).

Finally, it is important to mention that 10 to 20% of patients are in durable remission following their first flare-up.

Symptoms and complications of Crohn’s disease

The symptoms of Crohn's disease occur only during flare-ups and are not very specific, which can delay the diagnosis.

Digestive symptoms

The main symptoms are:

• abdominal pain (spasms, burning): mainly after meals, can be intense, similar to pain caused by appendicitis;
• diarrhea: may last for several weeks, is abundant and liquid;
• anal pain and/or the presence of mucus or blood (sometimes in large quantities) in the stool
• loss of appetite (anorexia), nausea and vomiting.

Other common symptoms

Other common symptoms, associated with the digestive symptoms described above, may be observed:

• severe fatigue (asthenia)
• weight loss 
• fever
• pallor related to anemia due to iron or vitamin B12 deficiency;
• delayed growth and poor weight gain in children and teenagers.

Non-digestive symptoms

Other parts of the body can also be affected by inflammation, leading to:

• rheumatic joints: inflammation of the joints of the limbs (knees, ankles, wrists, etc.) or of the spine and pelvis (spondylarthritis);
• dermatological problems: such as mouth ulcers or erythema nodosum (hard, red and painful blisters on the legs and forearms, which have the size of a walnut);
• or eye problems such as uveitis (inflammation of the eye: iris, choroid).

Possible complications

Complications may require urgent treatment or even hospitalisation. They include:

• acute severe colitis which is characterized by bloody stools > 6 times a day, anemia (lack of red blood cells), weight loss and fever. It can lead to an enlarged colon, causing stomach pains and bloating. It increases the risk of perforation of the large intestine and peritonitis (infection of the abdominal cavity). It usually requires emergency care.
• intestinal stenosis: over time and without treatment, the walls of the inflamed intestine can thicken and their diameter can be reduced (this is called "stenosis"). This leads to partial or total obstruction of the intestinal transit (this is called "intestinal obstruction"). The main symptoms are bloating, intense intestinal cramps, constipation, even fecal vomiting and fever. This condition can be serious and may require hospitalisation.
• intestinal perforations: the weakened walls of the intestine can crack or rupture. This can lead to the formation of localized abscesses (accumulation of pus) in the abdominal cavity, or an infection of this cavity (peritonitis).
• formation of fistulae: the abnormal connection between the digestive tract and another organ. This can be between two parts of the intestine, between the intestine and the skin or between the intestine and the bladder. Fistulae between the anus and the perineum or vagina can also occur.
• malnutrition: deficiencies in vitamin B12 (necessary for proper renewal of the cells, particularly red blood cells, skin cells and neurons) and vitamin D (essential for calcium absorption and growth) are frequently observed in patients with Crohn's disease. Blood tests should therefore be carried out regularly.
• colon cancer: the risk of developing colon cancer is higher in people with Crohn's disease. Systematic screening for this cancer via colonoscopy should therefore be carried out when this part of the digestive tract is affected.
• biliary tract disorders: primary sclerosing cholangitis or PSC (inflammation and thickening of the ducts that carry bile from the liver to the small intestine) can develop in patients with Crohn's disease. In this case there is an increased risk of developing bile duct or colon cancer.

Crohn’s disease causes and risk factors

The causes of Crohn's disease are still poorly understood, but various factors (genetic, immunological and environmental) have been identified in the development and worsening of the symptoms of the disease:

• genetic predisposition: many genes predisposing to Crohn's disease have been identified. For example, the NOD2/CARD15 gene codes for proteins involved in the functioning of the immune system and increases the risk of the disease by a factor of 5.
• dysbiosis or changes in the intestinal microbiota (also known as the gut flora, consisting of the bacteria naturally present in the gut): the immune system abnormally attacks the "good" bacteria and leads to inflammation of the intestinal wall, as observed in patients with Crohn's disease.
• tobacco: this is the main factor causing Crohn's disease. It increases the risk and severity of flare-ups and reduces treatment effectiveness.
• diet may be involved in Crohn's disease, but its direct influence has not yet been proven.
• finally, stress is not, to date, recognized as an independent risk factor.

Diagnosing Crohn’s disease

The diagnosis of Crohn's disease is made by a multidisciplinary team (GP, gastroenterologist, radiologist, rheumatologist, ophthalmologist, surgeon, pediatrician if the patient is a child). 

Clinical examination and tracking of the disease activity

The doctor starts by questioning the patient and performing a clinical examination: prolonged diarrhea, unexplained abdominal pain, presence of ulcerations, fissures or an abscess in the anal region, etc.

The Crohn's disease activity is then measured using a special scoring tool: the CDAI (Crohn's Disease Activity Index) which takes into account the following (over a period of one week):

• the number of liquid stools;
• stomach ache;
• the patient's general condition;
• the patient's weight;
• level of hemoglobin (the substance that carries oxygen into the blood and the level of which is reduced in the presence of anemia);
• extra-intestinal manifestations.

When the CDAI is < 150, the disease is in remission. Between 150 and 220, the disease activity is said to be mild, then moderate between 220 and 450, and it becomes severe if CDAI is > 450.

Complementary examinations to confirm the diagnosis

Several additional examinations are performed to confirm the diagnosis of Crohn's disease:

• ileocoloscopy is used to assess the extent of intestinal lesions in Crohn's disease (discontinuous damage to the intestinal wall, with alternating deep lesions and healthy areas). It consists of introducing a flexible tube with a small camera into the intestine (through the anus) to examine the rectum, the colon and the terminal part of the small intestine. It is performed under general anesthesia or sedation and requires the colon to be emptied of its contents beforehand (the patient can fast, take intestinal lavage preparation before the examination, or even follow a residue-free diet and take laxative medication a few days before the examination).
• Biopsy (taking samples of small fragments of the intestinal wall) may be performed and samples analyzed to help with the diagnosis.
• In the long term, colonoscopy is also useful for monitoring the progression of Crohn's disease.
• Oeso-gastro-duodenal endoscopy (EOGD or upper GI endoscopy) is performed to look for an upper location (in the oesophagus, stomach or the proximal part of the small intestine called the duodenum) of Crohn's disease. Biopsy can also be performed occasionally.
• Blood tests allow to look for anemia (decreased red blood cell count), inflammatory syndrome (increased blood levels of C-reactive protein or CRP and ESR), vitamin deficiencies (decreased blood levels of vitamins B12 and D), and assessment of renal (creatinine clearance calculations) and hepatic (elevated blood levels of ASAT and ALAT transaminases, and gamma-GT) damage that may be caused by Crohn's disease.
• Bacteriological and parasitological analysis of the stool (coproculture) is used to rule out an infection that may explain the digestive symptoms.

Specific tests to complete the diagnosis

In some cases, specific examinations are necessary to complete the diagnosis:

• A capsule endoscopy: carried out when the cause of the digestive bleeding has not been identified by gastroscopy or colonoscopy. The patient swallows a tablet-sized capsule containing a small camera that transmits the images to a computer system. This recording is painless and is performed without anesthesia, in an outpatient setting.
• An entero-MRI (or MRI of the intestines) is used to assess the extent of Crohn's disease lesions and the presence of fistulae or abscesses in the abdominal cavity.
• An enteroscan (or CT scan of the intestines, using X-rays) helps to locate abscesses or a possible intestinal obstruction (partial or total obstruction of bowel movement) related to Crohn's disease.
• An abdominal ultrasound (a painless examination carried out using a device that emits ultrasound) can reveal fistulae or a narrowing of the inner diameter of the intestine.

Treatments for Crohn’s disease

Treatments for Crohn’s disease allow to reduce the symptoms, avoid relapses and improve patients’ quality of life.

Drug treatments

A variety of drugs can be used depending on the different manifestations of Crohn's disease, but they all work to lower the activity of the immune system. These include:

Anti-inflammatory drugs: 

• Amino-salicylates, administered orally, have an anti-inflammatory action on the intestinal mucosa. There are two main ones: mesalazine or 5-ASA (Pentasa®), which is better tolerated, and sulfasalazine. Their efficacy for Crohn's disease is moderate. They are mainly used to prevent recurrence after intestinal surgery.
• Corticosteroids are used during Crohn's disease flare-ups. They can be administered orally, such as prednisolone, dexamethasone, methylprednisolone, betamethasone or budesonide (Entocort®) that has a more local action, but also rectally, as an enema when Crohn's disease affects the rectum and the left colon, such as hydrocortisone, or in the form of the injection during severe attacks. They are prescribed for short periods of time (maximum 3 months, with a gradual decrease in doses before they are stopped), in order to limit the side effects (high blood pressure, muscle atrophy, weight gain, osteoporosis, etc.). This is why it is also important to have a diet rich in proteins (meat, fish, eggs), low in salt, sugars and fats, as well as supplementing in calcium and vitamin D.

It is also important to mention that people with Crohn's disease should avoid taking aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, diclofenac  (Voltarol®), or niflumic acid. These substances are frequently prescribed to control fever or pain, and can make the symptoms of the disease worse. Thus, for the relief of common pains, the use of paracetamol should be preferred.

Immunosuppressants: 

• azathioprine (Imuran®) is prescribed for severe forms of Crohn's disease in patients who are intolerant to or dependent on corticosteroids (symptoms reappear as soon as corticosteroid doses are reduced and patients relapse rapidly after treatment is stopped). It can achieve a prolonged steroid-free remission of Crohn's disease after a few weeks to a few months. Common side effects of azathioprine include nausea, blood abnormalities (requiring regular blood tests) and an increased risk of infection (the presence of fever requires prompt medical attention).
• methotrexate, which is slow-acting, is used in severe forms of Crohn's disease as maintenance treatment. It is generally prescribed as an injection, once a week, via intramuscular or subcutaneous route (Metoject®, Imeth®), at a dose of 25 mg. It requires regular liver, kidney and blood monitoring.

The most common side effects are malaise, digestive problems, a drop in white blood cells count and inflammation of the mouth. Folic acid supplementation, at a distance from methotrexate intake, can reduce the frequency of some of these side effects. Finally, methotrexate has a teratogenic risk (malformation of the foetus during pregnancy). Effective contraception is therefore necessary for women of childbearing age taking this treatment, and if they wish to become pregnant, they should make an appointment with their doctor to adapt their treatment, and some time should be allowed to elapse between stopping the treatment and conception.

Biological therapy: 

Biological treatments are derived from living organisms or substances from these organisms that weaken the body's immune responses and reduce inflammation in the long term. They are prescribed as a second-line treatment for moderate to severe forms of Crohn's disease in people for whom standard treatment is not effective (corticosteroid resistance). Because of the increased risk of infection to which they expose the patients, they require a thorough medical check-up (search for latent tuberculosis, dental abscess, ongoing viral infection, etc.) prior to the initiation of treatment and their initial prescription is reserved for hospital specialists.

Among biological treatments, anti-TNFα are used when corticosteroids or other immunosuppressants have not been effective, or are contraindicated or poorly tolerated. By binding to TNF (Tumor Necrosis Factor), a protein involved in inflammation, these drugs block its action and reduce inflammatory reactions. They are administered in injectable form: via infusion for infliximab (Remicade® and biosimilars) or subcutaneously for adalimumab (Humira® and biosimilars).

Infliximab is also prescribed when Crohn's disease has caused fistulae, and in children over 6 years of age.

Other biological treatments are also used in people with Crohn's disease for whom previous treatments are not effective or contraindicated:

• Vedolizumab (Entyvio®) is an immunomodulator (which acts on the immune system) that blocks a protein on the surface of certain immune cells in the gut and thus reduces inflammation in the gut. It is available as a powder for injection, reserved for hospital use only, and is administered as a 30-minute infusion.
• If this drug fails or is contraindicated, ustekinumab (Stelara®) can be used. This is an inhibitor of human interleukins (molecules involved in inflammation). It is an injectable solution, administered subcutaneously.
  These biologicals also require regular medical supervision because of their side effects, in particular the risk of infection.

It is important to mention that before starting an immunosuppressive or immunomodulatory treatment, vaccinations must be up to date: anti-pneumococcal every 5 years and anti-influenza every year.

Surgery:

Sometimes medication is not enough to control Crohn's disease. In this case, surgery becomes necessary, especially if the patient has complications: stenosis (narrowing of part of the intestine), perforation of the intestine, abscesses in the abdominal cavity or fistulae (abnormal connection between the digestive tract and another organ).

Surgical treatment of Crohn's disease usually involves removing the parts of the digestive tract that are affected by inflammatory or stenotic lesions: this is called bowel resection. In some cases, the surgeon cannot suture the healthy parts of the intestine together and so attaches it to an opening in the abdomen (a stoma). Through this temporary opening, the contents of the intestine are evacuated into a pouch that must be changed regularly. It remains in place until the operated areas have healed and the continuity of the intestine is restored.

However, recurrences after surgery are common and require appropriate preventive drug treatment.

Living with Crohn’s disease

Crohn's disease can have significant consequences on patients' daily lives, including physical, psychological, social and professional impact.

Follow-up care

The attending physician tracks the disease progression and establishes the frequency of medical appointments. Seeing a hepato-gastroenterologist is recommended once or twice a year when the disease is in remission, and more frequently if it has not stabilized or if it has worsened.

Follow-up care is based on regular clinical examinations, biological analyses (blood tests) and regular colonoscopies. The severity of the disease can then be assessed by the CDAI score (mentioned above).

In order to help the doctor assess the severity of the disease, keeping a diary can be useful. The following should be noted every day: the number of stools and their appearance, the frequency and intensity of stomach pains, appetite and weight, the times of day when symptoms are most intense, etc.

Follow-up visits also provide an opportunity to assess the effectiveness and tolerance of the treatment, as well as the patient's nutritional status.

It should be noted that patients undergoing corticosteroid treatment for more than 6 months must be subject to special monitoring: blood pressure, bone density, measurement of blood glucose (sugar) levels, eye examination, etc.

Adopting a healthy lifestyle

Stopping smoking is essential when Crohn's disease is diagnosed. Smoking increases the severity and frequency of flare-ups and the need for surgery.

It is important that children with Crohn's disease live in a smoke-free environment.

Food does not trigger the inflammation of the intestine, but can temporarily increase the symptoms. A balanced and varied diet is preferable in order to avoid any deficiency. Mineral (calcium, iron, etc.) and vitamin (vitamin D, vitamin C, etc.) supplements may also be necessary.

During flare-ups, a low-fiber diet (limited in fruit and vegetables) may be recommended to avoid accentuating digestive symptoms (diarrhea, pain, bloating). It may also be worth keeping a food diary to identify the foods that aggravate the symptoms (red meat, certain types of cereal and dairy products are often mentioned). Spicy foods and caffeinated drinks can also make the symptoms of Crohn's disease flare-ups worse.

Pregnancy

Crohn's disease does not affect fertility. However, flare-ups can lead to miscarriages. It is therefore advisable to plan a pregnancy when Crohn's disease is in remission, as the risk of relapse is lower.

Most drugs prescribed as maintenance treatment for Crohn's disease are compatible with pregnancy, with the exception of methotrexate, which requires effective contraception because of its teratogenic risk (malformation of the foetus during pregnancy).

However, it should be noted that Crohn’s disease is related to family history (particularly in people of Ashkenazi Jewish origin). The risk of developing Crohn's disease in children and teenagers is 4 to 6 times greater if one of the parents has the disease.

Social life

Crohn's disease does not interfere with normal schooling, sports and professional life.

In addition, patient education programs are becoming more and more common in hospitals. These are individual or group sessions that provide patients with personalized information in order to understand and master their care pathway (understanding the disease, treatments, sharing difficulties and improving daily life, etc.).

Finally, patients can benefit from psychological support, and contact patient organisations to learn more about their disease, meet other patients, etc.

There is, for example Crohn's and Colitis Foundation, non-profit organization which has been funding research studies and clinical trials in IBD since 1967. It also helps patients and caregivers find information about their disease and receive all the support they need. Moreover, the organization educates healthcare professionals and publishes 2 scientific journals.

To conclude, Crohn's disease is the most common chronic inflammatory bowel disease and is becoming more and more common, particularly due to the lifestyle of people living in the developed countries. There is no cure for the disease, but medications usually allow long-lasting control of the disease and a satisfactory quality of life outside flare-ups.

Sources

Maladie de Crohn, SNFGE

La maladie de Crohn, Digest Science

Maladie de Crohn, HAS

Maladie de Crohn : définition et facteurs favorisants, Ameli

https://www.afa.asso.fr/comprendre-maladie-inflammatoire-intestin/comprendre-la-maladie/maladie-de-crohn/ 

LA MALADIE DE CROHN, AFA

Maladies inflammatoires chroniques de l’intestin (MICI), INSERM

Maladie de Crohn, Vidal

Published Sep 28, 2017 • Updated Jan 30, 2022