Crohn's disease: what is it, why does it occur and what are its symptoms?

Crohn's disease is one of the so-called non-specific intestinal inflammations. The exact cause of this disease is still unknown. It is thought to be a combination of several factors, mainly genetic and environmental.

The manifestations of the disease are very varied depending on the location and type of inflammatory foci. In addition to the intestinal manifestations, there are also a variety of extra-intestinal symptoms and complications that can drive the patient to the surgeon.

Crohn's disease is a chronic inflammatory disease affecting any part of the gastrointestinal tract. Inflammatory infiltrates are most often granulomatous in nature. Inflammation traverses the entire thickness of the organ wall and is confined to certain segments.

The most common location of inflammatory foci is the small intestine in its so-called ileocecal region and the terminal ileum (the terminal part of the small intestine with the transition to the large intestine).

However, any area can be affected, e.g. the oral cavity, oesophagus, stomach, colon and rectum.

Together with ulcerative colitis, it is grouped under the label IBD - inflammatory bowel disease.
They are referred to as non-specific intestinal inflammation, non-specific intestinal inflammation or chronic non-specific intestinal inflammation.
To date, the exact causes are not clear.

Crohn's disease is characterised by the formation of inflammatory deposits in the digestive tract and also by a series of symptoms manifesting outside the digestive tract. These manifestations are referred to as extraintestinal symptoms.

The eyes, skin, joints and liver are most commonly affected.

The disease is named after one of the authors of the first publication in which Crohn, Ginzberg and Oppenheimer characterised the nature of the disease. They knew that the inflammation had similar features to tuberculous bowel involvement but also had important differences.

In tuberculosis of the intestine, granulomatous inflammation also forms. Unlike tuberculosis, Crohn's disease does not involve necrosis (death) of the tissue within the granules.

The presence of granulomas is characteristic of Crohn's disease but is not a requirement for diagnosis. In histological examination of the intestine of Crohn's disease patients, granulomatous cells were found in only 60 % of tissue samples.

Crohn's disease occurs everywhere in the world, but some geographical differences can be noted.

The highest prevalence is in the developed and modern areas of the world, especially in North America, northern and western Europe. In contrast, lower prevalence is recorded in southern Africa, southern and eastern Europe and Australia.

In addition to geographical distribution, differences are also observed in different ethnic groups.

An example is North America. The prevalence of the disease is generally high in North America, but low in the Hispanic population living in North America. For example, members of the Jewish population are more often affected.

The higher prevalence in developed countries is attributed to the higher standard of hygiene of the population.

The cleaner the home and diet from birth, the less the immune system of the gut is stimulated by foreign pathogens. It is thus less mature. Immune cells are more likely to identify their own tissue as foreign and launch an attack against it.

This theory is now widely accepted and is referred to as the hygiene hypothesis.

At present, the direct cause of the disease is not yet fully clarified. We only know about the existence of certain factors that contribute to the development of this inflammatory disease.

Risk factors for Crohn's disease:

• Genetic influences
• dysregulation of the immune system
• dysfunction of the natural intestinal barrier
• insufficient microbial flora of the gut
• external factors

Genetic influences

The important role of genetics as a cause of Crohn's disease is illustrated by the high incidence of the disease in families. In first-degree relatives, the disease is up to 15 times more common.

Further evidence of genetic influences is the aforementioned high incidence in ethnic populations such as Jewish families.

In 1996, the IBD-1 gene, located on the long arm of chromosome 16, was described. The genetic mutation, known as CARD15, confers an increased risk of Crohn's disease. Three different variants of this mutation have been described so far.

Disorders of immune regulation

Crohn's disease is an inflammatory disease. The inflammation that most commonly affects the entire wall of the small intestine is immune-mediated inflammation.

This means that immune cells fail to recognize their own physiological tissues from foreign and pathological ones and start destroying them as pathogens. The result is chronic inflammation that destroys its own tissues.

The main immune cells mediating the inflammatory response are T-lymphocytes, specifically a subpopulation referred to as CD4+ lymphocytes or so-called helper T-lymphocytes.

Disruption of the intestinal barrier and microflora

A physiological intestinal microbiota goes hand in hand with proper immune processes. Probiotics protect the intestinal wall from inflammatory damage by building the intestinal mucosal barrier and restoring the immunological balance.

The underlying mechanism is to promote protective immune regulation and reduce pro-inflammatory activity.

External factors

External factors that contribute to an increased risk of Crohn's disease include the following:

1. Smoking
2. high levels of refined sugar in the diet
3. stress
4. infection with certain pathogens that trigger an inflammatory response
5. excessive use of non-steroidal anti-inflammatory drugs (painkillers)

The symptoms of Crohn's disease depend mainly on the site of inflammation, from the oral cavity to the rectum.

Affection of the oral cavity

Affection of the oral cavity is referred to as Crohn's disease of the mouth. Inflammation can damage the mucous membranes of the lips, cheeks and gums.

Typical manifestations include:

• Pain
• burning
• bleeding
• swelling
• difficulty chewing food in the mouth, lack of appetite, weight loss, malnutrition
• aphthae and deep ulcers in the mouth

oesophageal involvement

This is a relatively rare form of the disease. It is almost always accompanied by involvement of the small intestine. Most often it is inflammation of the last third of the oesophagus.

The disease has three stages:

1. Initial stage - characterized by active inflammation with swelling, numerous erosions and linear ulcers.
2. Second stage - narrowing of the esophagus
3. Third stage - the last stage of the disease is accompanied by inability to swallow, painful swallowing, vomiting, weight loss and malnutrition

Gastroduodenal form

The gastroduodenal form is characterised by involvement of the stomach and duodenum. Within the upper part of the alimentary canal, this is the most commonly affected area.

Common symptoms include pain and discomfort after eating. Nausea, vomiting and diarrhoea are rather rare in this form.

Rarely, pancreatitis, biliary colic or gastric bleeding with vomiting of blood may be associated.

Affection of the small intestine

Crohn's disease most commonly occurs in the area of the small intestine called the terminal ileum.

Affection of this area is manifested by symptoms such as

• increased fatigue
• increased body temperature, subfebrile
• weight loss
• loose stools
• abdominal pain
• formation of internal or external fistulas (a fistula is the formation of a connection or outlet between an organ or organ and the skin)

Affection of the colon and rectum

Ongoing chronic inflammation affecting the last part of the digestive tract has the following symptoms:

• frequent and loose stools
• blood in the stool
• tenesmus - painful pressure on the stool when passing a small amount
• a palpable "lump" in the lower abdomen, especially on the right
• uncomfortable stools and digestive problems
• formation of fistulas (adhesions) between adjacent organs such as the bladder or uterus and penetration of stool into these organs with secondary severe infection
• formation of fistulas that protrude from the intestine onto the surface of the skin, e.g. in the rectal area
• formation of painful abscesses around the rectum
• formation of adhesions and intestinal obstruction
• perforation of the bowel
• anaemia
• malnutrition

Extraintestinal symptoms

Crohn's disease also includes symptoms that manifest themselves in organs outside the digestive tract. These are referred to as extraintestinal or extraintestinal symptoms. They are most commonly seen in inflammatory bowel disease.

Extraintestinal symptoms include:

• cutaneous manifestations, e.g. erythema nodosum (inflammation of the subcutaneous fatty tissue) or pyoderma gangrenosum (a skin disease with tissue death that may follow injury and non-healing of the skin)
• mucosal manifestations, e.g. aphthae on the mucous membranes of the cheeks and lips
• ocular manifestations, e.g. conjunctivitis, iritis, iritis and uveitis, scleritis, glaucoma
• joint manifestations, especially arthritis, e.g. sacroiliitis or spondylitis
• thinning of the bones (osteopenia)
• formation of kidney stones (nephrolithiasis)
• gallbladder involvement known as sclerosing cholangitis
• calcification of the liver, autoimmune hepatitis, cirrhosis, liver abscess
• haematological manifestations such as anaemia, increased leukocyte count, deficiency or increased platelet count, clotting disorders, thrombosis
• inflammation of the heart compartments, e.g. endocarditis or myocarditis
• amyloidosis

Diagnosis of Crohn's disease is very difficult. It is a non-specific intestinal inflammation that can have a variety of symptoms. Currently, the most important factors in diagnosis are to distinguish Crohn's disease from ulcerative colitis (also a non-specific inflammation of the gut) and the infectious cause of the inflammation.

Blood tests

A routine blood test with biochemical examination and blood count is essential in the diagnosis of Crohn's disease.

Abnormalities such as increased sedimentation rate, anaemia, thrombocytopenia, lymphocytosis, pathological liver markers, elevated CRP and others may already be detected during this examination.

Another blood test is the detection of antibodies. The most commonly used tests are perinuclear antibodies to neutrophil cytoplasm (pANCA) and antibodies to Saccharomyces cerevisae (ASCA).

These antibodies may also be present in other diseases such as celiac disease. The combination of both is highly specific for Crohn's disease, especially when trying to distinguish Crohn's disease from ulcerative colitis.

Antibody positivity tends to be associated with higher disease aggressiveness, but their monitoring is not relevant in monitoring the effect of treatment.

Endoscopic examination and tissue biopsy

Endoscopic examination (examination with the insertion of a probe into the organ) used in the differentiation of Crohn's disease includes colonoscopy.

In colonoscopy, a camera system is introduced into the colon and examined by looking into part of the small intestine. In addition to being able to view the entire surface of the lining of the intestine, a tissue sample - a biopsy - can be taken.

The tissue taken during the biopsy is then subjected to further examinations which provide much valuable information about the nature of the inflammation taking place.

Crohn's disease is characterised by segmental inflammatory involvement of the mucosal surface. Ulcerative colitis is characterised by continuous involvement of the entire surface. Longitudinal ulcerations, squamous reliefs and redness can also be observed on the mucosa.

A modern method of endoscopy, called capsule endoscopy, is used to examine the small intestine. In this type of examination, the patient swallows a capsule which scans the mucosa as it passes through the digestive tract.

This method is convenient for examining hard-to-reach areas of the digestive tract. It is comfortable and painless, but more expensive. It is not used for examining pregnant women.

The disadvantage compared to conventional endoscopy is the impossibility of mucosal sampling or therapeutic intervention, e.g. removal of an intestinal polyp.

A common side effect is that the capsule gets stuck in the digestive tract. This can be avoided by using a retention capsule which gradually disintegrates after insertion.

The 2 mm core of the capsule is easily mixed with the diet and eliminated from the body.

In addition to colonoscopy, gastroscopy, which is an endoscopic examination of the stomach, is also performed. A sample of the mucosa can also be taken during this examination. This examination is particularly necessary if the patient has symptoms characteristic of the gastroduodenal form of the disease.

Histological examination

After a successful colonoscopic or gastroscopic examination and biopsy, the removed tissue is subjected to histological examination.

At least 2 biopsies from 5 parts of the colon, including the rectum and the last section of the small intestine, the terminal ileum, are needed to establish a diagnosis of Crohn's disease.

Imaging examination

Several types of imaging examinations are useful for the diagnosis of non-specific intestinal inflammation, e.g. enteroclysis, ultrasonography, computed tomography (CT) or magnetic resonance imaging (MRI).

Enteroclysis is an examination of the small intestine using a contrast agent that is injected into the intestine with a probe. After the intestine is filled, the patient is imaged on X-ray or CT.

This examination is the gold standard in diagnosing the extent of involvement or in detecting complications of the disease, such as fistulas or abscesses.

MRI enterography offers even greater sensitivity as it does not burden the body with radiation. It is particularly suitable for the examination of paediatric patients.

The course of Crohn's disease is characterized by four phases:

• initial flare-up
• remission, i.e. the resting phase
• relapse of the disease, i.e. acute relapse of the disease
• relapse, i.e. return of the disease

Based on the course of the disease, two types of patients can be defined:

• The aggressive type, which tends to have a severe course of the disease with the formation of complications such as fistulas and abscesses. This type is at risk of requiring surgical management.
• The indolent type has less frequent and milder attacks of the disease, with adhesions and stenoses of the intestine forming more frequently than fistulas.

The activity of the disease is divided into three stages:

1. Mild to moderate stage - It is characterized by a course without the occurrence of malnutrition, without fevers and large inflammatory foci in the intestine.
2. Moderate to severe stage - The disease does not respond as well to treatment as the first stage, with frequent fevers, abdominal pain, anemia, and significant weight loss.
3. Severe to fulminant stage - Severe condition persists with glucocorticoid treatment with fevers, severe abdominal pain, malnutrition, anaemia and obstructive bowel syndrome.