Crohn's disease

Content

Introduction

Introduction

Crohn's disease is a chronic inflammatory bowel disease (Video). Inflammation can affect any part of the gastrointestinal system, from the mouth to the anus but, more commonly, it affects the last tract of the small intestine (ileitis) and / or the colon (ileocolitis or colitis). It affects the entire thickness of the intestinal wall and can cause wounds and adhesions with other parts of the intestine and / or with neighboring organs. If not treated properly it can irreversibly alter the affected areas (Video).

It is estimated that in Italy there are about 150,000 people suffering from chronic intestinal inflammatory diseases: of these, about 30-40% have Crohn's disease, which generally appears between 20 and 30 years of age or after 65 years old. It is not uncommon among children and adolescents either. The disease is more common in highly industrialized countries, such as Northern Europe and North America, while it is rare in developing countries.

The most common symptoms (symptoms) caused by the disease are:

  • diarrhea chronic, often nocturnal
  • abdominal pain
  • tiredness and weakness (exhaustion)
  • slimming
  • presence of blood and mucus in the stool (less common than in ulcerative colitis)

It is a disease that persists over time (chronic) and is characterized by periods in which more or less intense disorders (symptoms) occur (exacerbation phase) alternating with others in which the disorders are absent or very mild (remission phase). The frequency of exacerbations and the duration of periods of remission are influenced by the treatment of the disease which, in general, is prescribed by specialized centers for chronic inflammatory bowel diseases.

Sick people, undergoing regular visits and checks, maintain a good quality of working and social life (read the Hoax).

Symptoms

Symptoms

The most common disorders (symptoms) of Crohn's disease vary from person to person and based on which part of the intestine is affected. The most common are:

  • chronic diarrhea (lasting more than 6 weeks), even at night
  • cramps and abdominal pain, which typically get worse after eating
  • weakness, tiredness (exhaustion), general malaise
  • loss of appetite
  • unwanted weight loss, caused by the bad absorption by the intestine of the nutrients contained in food and / or by the reduction in the amount of food eaten due to the worsening of disorders (symptoms) after meals
  • presence of blood and mucus in the stool (not frequent)
  • low-grade fever
  • growth retardation in children, caused by malabsorption of nutrients
  • fistulas and / or abscesses in the area around the anus (perianal). They can be the first manifestation of Crohn's disease and are present, in the initial phase, in 10% of patients. Their appearance requires careful evaluation by the doctor and specific treatment

Some people have only some of these disorders (symptoms) and in a mild form; others suffer from more severe forms. The disease is characterized by more or less long periods in which there are no disturbances (remission) alternating with phases in which they become intense (exacerbation).

Less common symptoms that are usually caused by the appearance of local or general complications are:

  • fever above 38 degrees
  • nausea
  • He retched
  • joint swelling and pains (arthritis)
  • eye inflammation and irritation (uveitis)
  • skin manifestations with red nodules and swelling in the lower legs (erythema nodosum) or skin ulcers (pyoderma gangrenous) repeated over time (recurrent)
  • cuts in the mouth (mouth ulcers)

In case of diarrhea, abdominal pain that lasts over time, weight loss, blood in the stool it is advisable to contact your family doctor.

Causes

Causes

The causes of Crohn's disease are not known. It is believed that the disease is due to an abnormal response of the body's defense system (immune system) against the “good” germs that are normally present in the intestine (bacterial flora). The reaction is triggered by environmental factors in genetically predisposed people.

The reciprocal influence of the following factors would therefore contribute to the onset of the disease:

  • genetic predisposition
  • alterations in the reaction of the body's defense system in the intestine
  • environmental factors such as diet, intestinal infections had in the past and smoking habits, capable of directly influencing the immune response and / or intestinal bacterial flora

There is no scientific evidence that the disease can be caused by a particular type of diet, although it appears more frequently in industrialized countries characterized by a so-called "Western" diet (high in proteins, fats and refined sugars). Some dietary changes, as suggested by your doctor or nutritionist, can help improve or control disorders (symptoms).

Genetic predisposition

Genetic predisposition appears to play an important role in the onset of Crohn's disease. More than 200 genetic mutations have been identified that are more frequent in sick people than in the general population. Furthermore, the disease often occurs in several members of the same family (familiarity) or within certain ethnic groups. It is not hereditary, therefore it is not transmitted directly from parents to children, and it is not contagious.

Immune system

Normally, the body's defense system (immune system) has the function of defending the body from bacterial and viral infections. In the digestive system there are numerous types of "good" bacteria (intestinal flora) involved in the digestion process of food. The immune system of healthy people recognizes them and, normally, does not attack them. In individuals affected by Crohn's disease, instead, the intestinal immune system does not recognize the "good" bacteria and triggers an inflammatory reaction to eliminate them. It is believed, in the current state of knowledge, that this is the mechanism underlying the inflammation present in the intestinal wall of people with the disease. Crohn: It is thought that an unidentified environmental trigger event is thought to determine the abnormal reaction of the immune system in genetically predisposed individuals.

Diagnosis

Diagnosis

Crohn's disease occurs with disorders (symptoms) common to other diseases. Its assessment (diagnosis) is complex and may require in addition to medical examinations also a series of clinical tests (Video).

Initial evaluation by the family doctor

The first step to ascertain the presence, or not, of the disease consists in the medical examination and in the initial evaluation of the disorders carried out by the attending physician. During the visit, the doctor in particular:

  • assess the disturbances (symptoms) and their possible presence during the night
  • inquires about any trips abroad in which you may have contracted traveler's diarrhea and asks if you are using any medications that could cause diarrhea
  • assess the presence of any risk factors, for example, family members already suffering from chronic inflammatory bowel diseases (Crohn's disease or ulcerative colitis), smoking habit, past surgical removal of the appendix (appendectomy), recent gastroenteritis
  • assess the general state of health, the state of nutrition and, through examination of the abdomen and inspection of the perianal area with rectal exploration, verifies the presence of suspicious signs of Crohn's disease.

Upon completion of the visit, the doctor may prescribe laboratory tests.

Blood analysis

Doctors prescribe blood tests to check for inflammation, ongoing infections, anemia due to malabsorption or intestinal blood loss. Blood tests include:

  • ESR, CBC with leukocyte formula, sideremia, tranferrinemia, ferritinemia, CRP, alpha-1-acid glycoprotein, total protein and electrophoresis, BUN, creatinine, ALT, AST, total and indirect bilirubin, alkaline phosphatase, gammaGT

Stool examination

The stool test is performed for:

  • search for bacteria, fungi and viruses capable of causing intestinal infection (fecal culture test)
  • search for parasites (parasitological examination of stool)
  • blood research not visible to the naked eye (search for occult blood)
  • evaluation of the presence and degree of intestinal inflammation (fecal calprotectin test)

Following the results of the blood and stool tests, the treating physician may refer the patient to the specialist in digestive system diseases (gastroenterologist) for further assessment of the disease (diagnosis) and / or prescribe further investigations such as colonoscopy, gastroduodenoscopy, enteroscopy with videocapsule, enteric magnetic resonance (entero-MRI) and computed entero-tomography (entero-CT), ultrasound of the intestinal loops, enema of the small or small intestine.

Colonoscopy

Colonoscopy is a "test used to examine the interior of the colon and the terminal part of the ileum (ileo-colonoscopy) by introducing a long, flexible tube, called an endoscope, through the anus and rectum. of an essential exam to ascertain (diagnose) Crohn's disease since it allows, through the removal of small tissue fragments (biopsies) to be analyzed under a microscope, to assess the state of the intestinal mucosa.

The endoscope is equipped, at one end, with a camera, which sends images to a screen showing the level and extent of inflammation in the colon walls and the terminal ileum. The endoscope is equipped with surgical instruments that are used to take tissue fragments from various parts of the intestine (biopsy).

The examination and biopsy can be bothersome but, in general, they are not painful; they often take place under sedation. The tissue samples taken are examined under a microscope to see if the intestinal tissue changes typical of Crohn's disease are present: presence ulcers and white blood cell infiltrations.

Esophagogastroduodenoscopy

It is prescribed in the suspicion of inflammatory lesions affecting the upper part of the digestive system. It allows to evaluate the involvement of the esophagus, stomach or duodenum.

Enteroscopy with videocapsule

This is a new type of examination that is carried out by ingesting a capsule as large as an antibiotic tablet. The capsule passes inside the intestine and allows the visualization of the small intestine by transmitting images to a portable device. The capsule is subsequently eliminated in the faeces. The examination does not allow to take tissue samples from the intestinal walls (biopsies) and is preceded by a radiological investigation to exclude the presence of narrowings in the small intestine.

Enteric magnetic resonance imaging (entero-MRI) and entero-computed tomography (entero-CT)

They allow to evaluate the state of the small intestine in people suspected of Crohn's disease. They are sensitive tests, useful for determining the stage of the disease and the intestinal tracts involved, as well as any complications such as fistulas and abscesses.

To carry out them it is necessary to ingest a contrast liquid (enterography); alternatively, the contrast agent can be administered through a flexible tube that goes from the nose to the small intestine (enteroclysis). The contrast agent allows you to see the inside of the intestine more clearly during MRI or entero-CT.

Whenever possible, entero-MRI is preferred because compared to CT it does not expose the person to ionizing radiation.

Ultrasound of the intestinal loops

The ultrasound of the intestinal loops allows to evaluate the intestinal wall in a non-invasive and radiation-free way. It is useful for checking for intestinal lesions characteristic of Crohn's disease and for complications such as the presence of narrowings, fistulas and / or abscesses. This type of ultrasound must be performed in specialized centers.

Enema of the small or tenuous seriatum

It is an exam, now almost out of use thanks to the development of new diagnostic imaging techniques, used to examine the loops of the small intestine that cannot be seen with colonoscopy (it can only reach the last 20 centimeters).

The investigation consists in introducing a liquid containing a contrast medium, called barium, into the small intestine through a flexible tube that passes through the nose and throat. The barium lines the walls of the small intestine making them clearly visible on X-rays. Through a series of radiographs taken in succession, the areas of narrowing (stenosis) and inflammation caused by Crohn's disease are highlighted.

After the examination it is advisable to drink a lot to eliminate the barium through the faeces which, for a few days, may be white in color.

Therapy

Therapy

Currently, there are no treatments that can definitively cure Crohn's disease; treatment (therapy) is aimed at maintaining disturbance-free periods (remission) for as long as possible and relieving them when they are present, improving the quality of life and preventing (preventing) complications from occurring.

In children it also has the objective of promoting normal growth and development of the organism.

Care must be adapted to each individual since the disease manifests itself in a variable way from person to person and changes over time, based on the extent, location and type of lesions, on the one hand, and on the activity and to the severity of the disease, on the other.

The sick person is usually followed by a team (team) of specialists in multiple disciplines (gastroenterologists, internists, nutritionists, ophthalmologists, rheumatologists, dermatologists, surgeons and specialized nurses) to manage all aspects of the disease and its possible complications .

Control of disorders (symptoms)

When the disease is active it can cause moderate to severe symptoms (symptoms). In the absence of local complications, drug therapy can be prescribed. Surgery is generally not the first choice treatment.

Initial care

The purpose of the treatment is to reduce inflammation and promote the appearance of long periods without disturbances. Stopping smoking is always recommended before any drug prescription. Medicines that your doctor may prescribe include:

  • anti-inflammatory drugs, such as mesalazine (5-ASA) or sulfosalazopyrine which act directly on the intestinal mucosa during passage into the intestine. There is no convincing evidence for mesalamine for its efficacy in Crohn's disease, however some doctors prescribe it as maintenance therapy in stages of disease remission Sulfosalazine is used in the presence of mild joint manifestations
  • corticosteroids, (such as prednisone or prednisolone) to be taken by mouth (orally) or given intravenously. Corticosteroids have a powerful anti-inflammatory action throughout the organism, suppressing and modulating the immune response, but they have numerous side effects such as weight gain, swelling of the face, increased vulnerability to infections, 'weakening of the bones (osteopenia and osteoporosis). For this reason the dosage of the drug is progressively reduced as the disorders begin to improve
  • liquid diet, in children, in some cases the initial cure consists of a liquid diet, known as the elementary diet, to reduce inflammation by putting the intestines to rest

Immunosuppressive and biological drugs

There are other types of drugs available, called immunosuppressants, which can be used when the disease returns (flare-up) after a period of well-being or when symptoms (symptoms) reappear after decreasing doses of corticosteroid drugs.

Immunosuppressive medicines (azathioprine or mercaptopurine) reduce the reaction of the body's defense system (immune response) causing the death of most of the white blood cells responsible for inflammation. They can be combined with the initial drug therapy. The treatment with immunosuppressants, however, has limitations which consist in the long time required (a few months) before they are effective and in the need to continue the treatment for long periods. The most common side effects are nausea and vomiting, malaise, pancreatitis and liver problems. They are not suitable for everyone and require frequent laboratory checks. Another immunosuppressive medicine available is methotrexate which causes the death of white blood cells by a different mechanism.

Unlike azathioprine and mercaptopurine, methotrexate should not be taken within six months before conception (in both men and women) because it can cause fetal malformations and should be avoided during pregnancy and breastfeeding.

If you are planning to have children, pregnant and then breastfeeding, it is important to consult your doctor to agree on the most suitable treatment.There are no contraindications to pregnancy in women with Crohn's disease, but it is preferable that it occurs at a time when the disease does not cause disturbances (phase of remission).

For patients who have not benefited from treatment with cortisone and / or immunosuppressants, new anti-inflammatory drugs called biologics are available, such as infliximab (currently in "band H", therefore only available at the hospital level) or adalimumab. These are monoclonal antibodies that work by blocking the so-called tumor necrosis factor-alpha (TNF-α), a molecule involved in the mechanisms that trigger the inflammatory process of Crohn's disease. Recently, new monoclonal antibodies directed towards other molecules that contribute to the inflammatory process (currently in "range H", therefore available only at the hospital level), such as ustekinumab (against interleukin 12/23), vedolizumab (directed against some molecules that cause inflammatory cells to migrate from the blood to the inflamed area). The doctor who specializes in the treatment of chronic inflammatory bowel diseases will choose the type of biologic to be administered based on the characteristics of the patient. Biological drugs have been shown to be highly effective in helping many sufferers to have periods when the disease does not manifest itself (remission). Not in all people, however, the treatment is effective and in some it tends to lose its effectiveness over time. Side effects include:

  • allergic reactions, such as itching, swelling of the lips and hands, trouble swallowing, high fever and joint pain. Allergic reactions can occur at the time of drug administration or even after 10-12 days (fever and joint pain). They are more common when resuming treatment after a long break. In case of an allergic reaction it is necessary to consult a doctor immediately
  • viral and / or bacterial infections of the airways and urinary tract
  • skin manifestations such as psoriasis and eczema (for monoclonal antibodies that work by blocking tumor necrosis factor-alpha - TNF-α)

Medicines to reduce ailments (for example, anti-diarrhea or pain relievers) or supplements to restore the correct levels of nutrients and vitamins decreased due to malabsorption and / or vitamins may also be used during drug treatment of the disease. or by reducing the power supply.

Surgery

Surgical therapy is indicated if drug treatment proves ineffective and if local complications occur. It does not cure Crohn's disease which, therefore, can recur. When this occurs, it is usually the tissues surrounding the surgically removed area that are involved. For this reason, surgery is not usually the first treatment to be performed. However, surgical removal of the inflamed intestinal tract is suggested as first choice in young people if the disease is not very extensive and there is no active inflammation.

The surgery consists in removing the inflamed intestinal tract and re-establishing intestinal continuity by joining the healthy parts (anastomosis) that are above and below the eliminated one. In relation to the tract affected by the inflammation (small intestine or colon) and the " extension of the disease, the surgeon identifies and illustrates to the patient the type of surgery most suitable for his case.

Maintaining the disturbance-free period (remission)

Remission is a stage of the disease in which there are no complaints (symptoms) or they are very mild. During periods of remission, doctors consider whether to continue prescribing maintenance treatment or not. It is important to have regular check-ups and to see your doctor if any complaints (symptoms), such as diarrhea, recur.

Lifestyle changes (diet and smoking)

There is no diet recommended for people with Crohn's disease. However, many individuals notice an aggravation of disorders (symptoms) when they eat certain foods. It may be useful to write a diary noting the foods consumed and any disorders that have appeared. Many sufferers find it beneficial to limit the consumption of milk and dairy products, foods high in fat and fiber, spicy foods, alcohol and caffeine.

Smoking is a known risk factor for the onset of Crohn's disease. Furthermore, it negatively influences the evolution of the disease. Quitting smoking is therefore the first cure to follow.

Complications

Complications

People with Crohn's disease can experience various intestinal and extra intestinal complications. The most common are:

Intestinal narrowing (stricture)

Chronic and long-lasting inflammation can cause scar tissue to form inside the intestine and narrow it in some places. When the intestine becomes too narrow to allow its contents to pass through, obstruction or intestinal blockage. The signals consist of the absence of stool evacuation associated or not with the non-emission of intestinal gas, pain, cramps and abdominal pain, repeated vomiting. If these complaints (symptoms) are neglected there is a risk of bowel perforation. If bowel obstruction is suspected, call 911 or go to the emergency room immediately.

Intestinal strictures are treated through a surgical procedure, called stricturoplastic, which consists in the execution of a plastic aimed at widening the intestinal wall, or by the surgical removal of the narrow tract. In some cases the stenosis is dilated by means of a balloon inserted during colonoscopy.

Fistulas

In the inflamed tract of the intestine, abnormal communications may develop, called fistulas, due to the deepening of wounds (ulcers) that pierce the intestinal wall creating a communication with the adjacent intestinal loops, with the abdominal wall or with the wall of nearby organs (enteroenteric, enterocutaneous, enterovesical, enterovaginal fistulas). Ulcers can also lead to abscesses in the abdomen (intra-abdominal).

The presence of enterocutaneous, enterovaginal and enterovesical fistulas and intra-abdominal abscesses represent an indication for surgical intervention.

In the case of perianal disease, a combination of medical and surgical treatment is often required.

Extra-intestinal complications

They can be represented by:

  • osteoporosis, weakening of the bones caused by intestinal malabsorption or treatment with corticosteroids
  • iron deficiency anemia (from iron deficiency), caused by malabsorption or bleeding from the digestive tract. It can manifest itself with disorders (symptoms) such as tiredness, shortness of breath, pale complexion
  • vitamin B12 or folate deficiency anemia, determined by the malabsorption of these substances in the digestive system
  • uveitis (eye inflammation)
  • swelling and pain in the joints (arthritis)
  • kidney stones, as a consequence of intestinal malabsorption
  • gallbladder stones, linked to a defect in the absorption of bile acids
  • erythema nodosum, appearance of skin lumps with redness and swelling on the lower legs
  • gangrenous pyoderma, rare complication that causes the appearance of skin ulcers covered with bleeding material and purulent mucus. It occurs more frequently in the skin of the lower limbs
  • growth retardation, can occur in children as a result of malabsorption of nutrients in food caused by inflammation of the intestine

Tumors of the colon and rectum

If the inflammation is localized in the colorectal, there may be a slightly higher risk of developing colon and rectal cancer than the general population. If your doctor thinks you fall into the risk categories, you need to have a colonoscopy and intestinal biopsy on a regular basis.

Bibliography

Bibliography

Boirivant M, Cossu A. Inflammatory bowel disease. Oral Diseases. 2012; 18 : 1-15

Di Domenicantonio R, Cappai G, Arcà M, Agabiti N, Kohn A, Vernia P, Biancone L, Armuzzi A, Papi C, Davoli M. Occurrence of inflammatory bowel disease incentral Italy: a study based on health information systems [Summary]. Digestive and Liver Disease. 2014; 46 : 777-82

Pallone F, Calabrese E. IBD: Crohn's disease. Recent Advances in Medicine. 2016; 107 : 292-6

Scardapane A, Stabile Ianora AA, Cuccurullo V, Pizza NL, Capasso R, Gatta G. Role of nuclear medicine techniques in therapeutic planning and in the follow-up of inflammatory bowel disease. Recent Advances in Medicine. 2012;103 : 431-4 

In-depth link

In-depth link

Italian Unitary Colonproctology Society (SIUCP). Crohn's disease

FRIENDS Onlus. Crohn's disease

Humanitas Research Hospital. Crohn's disease

European Crohn's and Colitis Organization (ECCO), European Federation of Crohn's and ulcerative Colitis Associations (EFCCA). Patients Guidelines on Crohn's Disease (CD)

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