Crohn's disease

Crohn’s disease

Crohn’s disease (lat. Crohn’s disease) is a systemic, chronic granulomatous ulceroconstrictive disease that affects all intestinal wall layers. The disease is of unknown cause, and together with ulcerative colitis, belongs to idiopathic inflammatory bowel diseases.

The disease was named after Dr. Burrill B. Crohn, who first described the medical literature disease in 1932. with colleagues Dr. Leon Ginzberg and Dr. Gordon D. Oppenheimer. The disease was originally called “terminal ileitis,” which was too frightening for patients because they mistakenly assumed they had a fatal (terminal) disease. The term “regional ileitis” was used for some time, but eventually, Crohn’s disease prevailed.

Although any part of the gastrointestinal tract can be affected – from the mouth to the anus, the area where the small intestine (terminal ileum) and colon (large intestine) meet is most commonly affected. This inflammation can affect all intestinal wall layers (transmurally) and can cause a range of symptoms, including abdominal pain, diarrhea, intestinal bleeding, and weight loss. These symptoms are not specific and can occur in many other disorders, including ulcerative colitis and gastrointestinal infections. The doctor diagnoses Crohn’s disease after a history and examination of the patient and after numerous diagnostic tests: blood tests, radiography, and often colonoscopy.

Treatment is most often based on anti-inflammatory and immunomodulatory drugs, intending to control symptoms. In many situations, surgical intervention is required.

There is no cure for Crohn’s disease – it is a chronic disease, so therapy goals are to control symptoms and make the patient feel better. By achieving these goals, patients can normally live without the limitations associated with this disease. Due to the disease’s chronic nature, patients must actively participate in treatment.

Epidemiology

Crohn’s disease incidence varies from country to country, but there are approximately 4-10 new cases per 100,000 inhabitants per year, with a prevalence of 27-106 per 100,000 inhabitants. Another idiopathic inflammatory bowel disease, ulcerative colitis, has an incidence of 6–15 new cases per 100,000 population per year, with a prevalence of 85–150 cases per 100,000 population.
Both conditions are widespread throughout the world but are more common in Western countries. The incidence is lower in non-white breeds.

Crohn’s disease is slightly more common in women than in men (M: F = 1: 1.2) and occurs at a younger age (average 26 years) than ulcerative colitis (M: F = 1.2: 1, average 34 years).

Etiology / pathogenesis

Although the etiology of idiopathic inflammatory bowel disease is unknown, it is increasingly known that they result from three essential interactive cofactors: genetic susceptibility, environmental factors, and the host immune response, where environmental factors represent both the local microenvironment (intestinal microflora) and nutritional environment.

The most widely accepted theory is that the immune system reacts abnormally to a substance in the gut, most likely a bacterium that normally resides in the gut. This excessive immune response initiates exposure to something from the environment. Some people develop this type of immune response. In contrast, others do not believe it to be linked to genetic factors and susceptibility – in other words, a person who develops Crohn’s disease is believed to inherit some defective gene genes that cause an over-immune response. Activation of the immune response naturally leads to intestinal infiltration by inflammatory cells. In patients with Crohn’s disease, once activated, the immune system does not “shut down,” resulting in the chronic inflammation characteristic of Crohn’s disease. Therefore, many current therapies focus on suppressing the immune response.

Genetic factors

There is considerable evidence that genetic factors contribute to Crohn’s disease’s development. It is more commonly seen in certain racial and ethnic groups; whites, especially of Jewish descent, whose relatives come from Eastern Europe (Ashkenazim), have a special risk. Additionally, there is a higher risk of Crohn’s disease if a person has a first-degree relative with Crohn’s disease. As mentioned earlier, about 20% of patients with this disease also have sick relatives in the first generation.

Environmental factors

Environmental factors appear to combine with genetic factors and lead to the development of Crohn’s disease. Certain environmental factors also affect the course of the disease. Unfortunately, environmental factors have not been well studied. However, the cause is either in the intestinal mucosa, which is becoming more permeable – a characteristic associated with smoking and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) – or changes in the bacterial flora of the gut, a situation that can occur with antibiotics or gastrointestinal infections.

The two best-studied environmental factors are smoking and nonsteroidal antirheumatic drugs. Smoking has been shown not only to increase the risk of Crohn’s disease but also to worsen the disease’s course. Smokers may have a weakened response to certain medications and are more prone to develop relapses after surgery.

Nonsteroidal antirheumatic drugs (e.g., ibuprofen, naproxen) may trigger the development of Crohn’s disease, although there is no extensive medical literature on this case. The use of cox-2 inhibitors in patients with inflammatory bowel disease appears to be safer.

Diet

Little is known about dietary risks, but diet probably carries a certain risk factor. Of course, there is no single dietary factor associated with the onset of Crohn’s disease. A diet rich in refined sugars is most often mentioned in this context. When Crohn’s disease is diagnosed, there is no specific food that the patient should eat or avoid, and often only a more balanced diet is advised.

No diet is effective in relieving symptoms. Many patients mistakenly restrict themselves to dairy products and fruits, which more often leads to various nutritional deficiencies than reducing symptoms. Only patients with severe strictures or small bowel obstructions should follow a diet and avoid foods that cannot be easily digested, such as the skin of fruits, nuts, seeds, pineapples, mushrooms, and fresh vegetables. Of course, patients with established lactose intolerance should avoid dairy products.

Pathology

The serosa is granular and dark gray, and often the fatty tissue of the mesentery wraps around the intestine’s surface. The mesentery of the intestine’s affected part is also thickened, edematous, and sometimes fibrotic. The intestinal wall is thickened due to edema, inflammation, fibrosis, and hypertrophy of the muscular appropriate. The result is almost always a narrowing of the lumen, which can sometimes be seen on X-rays with barium contrast as a thin strip. Strictures can also occur in the colon but are usually less severe. Crohn’s disease’s classic feature is the sharp demarcation of the intestine’s affected and healthy parts. When multiple segments are affected, the affected part segments are normal (“skip lesions”).

ccs
Crohn’s disease (colon). You can see a deep fissure that spreads into the muscle wall, then another, shallow ulcer (top right), and the relative preservation of the mucosa between the affected segments. Abundant lymphocyte aggregates are present, which are seen as dense blue clusters of cells between the mucosa and submucosa.

Characteristic signs of early disease are focal mucosal ulcers (aphthous ulcers), edema, and loss of normal mucosal texture. As the disease progresses, mucosal ulcers turn into long, linear ulcers, which are usually oriented along the intestine axis. Narrow fissures from between the mucosa folds, often penetrating deep into the intestinal wall, and lead to adhesions and serositis. Further expansion of the fissure leads to the formation of fistulas or adhesions, often to adjacent organs, outside the skin, or into a blind cavity. Perforations, or localized abscesses, may also develop.

Histological characteristics of Crohn’s disease are:

  • Inflammation of the mucous membranes;
  • Chronic mucosal damage;
  • Ulcerations
  • Transmural inflammation affecting all layers of the wall.
  • Noncaseating granulomas.
  • Other mural changes.

Types of Crohn’s disease

According to location

  • Gastroduodenal Crohn’s disease:
    • Uncommon – symptoms in approximately 5% of patients
    • It affects the stomach and the first part of the small intestine (duodenum);
    • Symptoms include nausea, loss of appetite, weight loss, vomiting, and upper abdominal pain;
  • Jejunoileitis – inflammation of the second part of the small intestine (jejunum)
    • Not common
    • Symptoms include diarrhea, abdominal pain (usually after meals), malnutrition due to nutrient malabsorption, and weight loss.
  • Ileitis – inflammation of the back of the small intestine (ileum)
    • It occurs in approximately 30% of patients;
    • Symptoms include diarrhea, abdominal pain (usually in the lower right quadrant), and weight loss.
  • Ileocolitis – inflammation of the ileum and colon (usually right-sided):
    • The most common type of disease affects approximately 50% of patients.
    • Symptoms similar to Crohn’s ileitis: diarrhea, abdominal pain (often in the lower right quadrant), and weight loss
  • Crohn’s colitis – inflammation of the colon only:
    • Not uncommon, it affects approximately 20% of patients with Crohn’s disease;
    • Symptoms include diarrhea, rectal bleeding, and abdominal pain.
    • Perianal disease and extraintestinal manifestations of Crohn’s disease are more common when the colon is affected. Unlike ulcerative colitis, where the inflammation is continuous and almost always starts from the rectum, progressing to the colon, Crohn’s disease usually spares the rectum. Also, Crohn’s disease is often not continuous – there may be healthy intestine segments between the affected segments.
  • Perianal disease
    • It affects approximately one-third of patients with Crohn’s disease.
    • The patient may have fistulas, fissures, skin growths, or abscesses
      • Perianal fistulas result from smaller centers of infection and inflammation that penetrate from the anal muscle (sphincter) to the skin around the anus. This leads to drainage of mucus, stool, or pus from the opening around the perianal area. If the opening is closed, abscesses may develop, which will characteristically present with swelling and pain around the perianal area, with accompanying fever. Typically, this requires antibiotic treatment and often surgical drainage.
      • Fissures are ulcerations on the skin that cover the anal canal, often painful.
      • Cutaneous growths: Patients with Crohn’s disease often develop around the anus. Sometimes they can be replaced with hemorrhoids. They are often not painful or clinically relevant.

According to the sample

The symptoms and signs of Crohn’s disease are a reflection of the location and the disease pattern.

  • Inflammatory form – a form of the disease caused by inflammation of the intestines. Symptoms include diarrhea, abdominal pain, weight loss, fever, bleeding, fatigue, loss of appetite, and stunted growth (in children). Patients may also develop small bowel obstruction or mass in the right lower quadrant. Such patients respond best to therapy. This pattern is typical early in Crohn’s disease.
  • Fibrostenotic form – usually seen in patients with ileitis. Over time, continuous inflammation can lead to scarring of the intestinal wall. The accumulation of scar tissue on the intestinal wall causes the bowel to narrow. Eventually, the bowel becomes so narrow that even a small inflammation causes the lumen to close, resulting in small bowel obstruction. It is characterized by severe abdominal pain, nausea, vomiting, and constipation. Most obstructions resolve quickly with conservative therapy (no food, IV fluids). Patients with strictures often need surgery to remove part of the bowel with scars, to prevent obstruction in the future.
  • Perforating / fistulizing form – because Crohn’s disease affects all layers of the intestinal wall, patients may develop perforations, leading to squeezing of intestinal contents into the abdominal cavity; or they may develop fistulas, which is an abnormal connection or tunnel from one part of the intestine to another, or even to another organ.
    • Perforation – may present acutely with severe abdominal pain, rigid abdomen, fever, and shivering. The symptoms may be similar to those of appendicitis. Alternatively, it may present with an abdominal mass, fever, chills, and mild pain. Perforation usually results in an intra-abdominal abscess (accumulation of bacteria and inflammatory cells) that requires antibiotic treatment and drainage, most often surgery.
    • Fistula – the symptoms of a fistula depend on the organ to which the fistula leads: examples of different types of fistula include the bladder (entero-vesical fistula), vagina (entero-vaginal fistula), skin (entero-cutaneous fistula), and small intestine (entero-enteric fistula). The most common fistula is actually a perianal fistula.
      • An entero-vesical fistula usually leads to recurrent urinary tract infections. Patients may also complain of gas, blood, or stool in the urine.
      • An entero-vaginal fistula may be present, with gas or stool passing through the vagina.
      • Entero-cutaneous fistulas cause drainage of intestinal contents through the skin surface.
      • Entero-enteric fistulas may be asymptomatic or present through diarrhea or abdominal mass.

Clinical picture

Common symptoms of Crohn’s disease:

  • Diarrhea
  • Abdominal pains
  • Loss of appetite and weight
  • Fever
  • Fatigue
  • Rectal bleeding
  • Perianal lesions
  • Slowed growth in children
  • Complications: Fistulas, perforations, abscesses
  • UGI symptoms
  • Extraintestinal manifestations

The symptoms of Crohn’s disease can range from mild to severe. Abdominal pain, diarrhea, and weight loss are the most common symptoms of Crohn’s disease. Constitutional symptoms of malnutrition, lethargy, anorexia, nausea, vomiting, and minor fever may be present, and in up to 15% of patients, there are no gastrointestinal symptoms. Crohn’s disease can also affect other parts of the body, including the joints, skin, liver, and eyes. Together, all of them are called extragastrointestinal manifestations and are rarely among the first symptoms manifested by a patient with Crohn’s disease. In children, it can manifest through delayed development and growth. Approximately one-third of patients with Crohn’s disease will develop symptoms personally, including fibroepithelial polyps, fissures (rupture of the anal skin), fistulas, or abscesses. Enteric fistulas (for example, on the bladder or vagina) will occur in 20-40% of cases, equally distributed between external and internal fistulas; the latter usually occur after surgery.

The clinical picture is variable and depends in part on the region of the intestine affected. The disease can occur gradually or acutely. Abdominal pain may be quantitative, indicating obstruction, but usually has no special characteristics, and sometimes only a minimal amount of discomfort is present. Diarrhea is present in 80% of all cases, and in intestinal diseases, it usually contains blood, making it difficult to distinguish from ulcerative colitis. Steatorrhea may be present in small bowel disease. Acute pain in the right iliac fossa, which mimics appendicitis, can occur with Crohn’s disease. If a laparotomy is performed, an edematous reddish terminal ileum is found. There are other causes of acute ileitis. Up to 30% of patients with acute ileitis turn out to have Crohn’s disease. Crohn’s disease can be complicated by anal and perianal diseases, which occur in about 25% of cases, and often appear years before the symptoms associated with the small and large intestine.

Diagnosis

There is no single test for Crohn’s disease. The diagnosis uses a combination of:

  • Medical history,
  • physical examination,
  • laboratory tests
  • endoscopy (gastroscopy / colonoscopy)
  • X-rays (CT, magnetic resonance imaging),
  • tissue biopsy (pathological findings).

Medical history and physical examination

There is no substitute for a good medical history and physical examination; the doctor will ask several questions regarding the symptoms to narrow down possible diagnoses. Details of medical history help doctors decide if tests are necessary. The doctor will ask about the chronicity, acuteness, and severity of the symptoms. They will ask questions about palliative (things that relieve symptoms) and provocative (things that make symptoms worse) factors, especially whether bowel movements or food worsen or improve symptoms. Data on medications taken, contact with sick people, travel, smoking, family history of gastrointestinal disorders are important.

A physical seizure is also important in a definitive diagnosis. The doctor will examine the oral cavity for ulcers, pressing the abdomen will look for places of discomfort, masses in the abdomen, rashes, swelling of the joints, and perianal disease. Often, a doctor in primary care will seek a gastroenterologist’s advice if the conclusions of the examination indicate inflammatory bowel disease.

Blood tests

Several blood tests can help diagnose Crohn’s disease. Complete blood count (CBC, from eng. complete blood count ) may show anemia or an elevated white blood cell or platelet count – where both leukocytes and platelets are markers of inflammation or infection. Sedimentation rate (ESR, from eng. erythrocyte sedimentation rate ) and C-reactive protein (CRP) are other nonspecific markers of inflammation that are often measured for suspected Crohn’s disease. Low albumin can also be seen in patients with long-lasting or severe symptoms. These results may confirm inflammation but do not prove what exactly causes the inflammation. The stool can also be tested for bacteria and parasites, both of which can cause infections that mimic the symptoms of Crohn’s disease. There are newer stool tests that test for the presence of intestinal inflammation, but like serological tests, they are not specific for Crohn’s disease. They must be looked at as part of other intestinal diseases and infections.

Complete blood count, sedimentation rate, and CRP are blood tests performed serially in patients diagnosed with Crohn’s disease to assess inflammation, especially when the patient complains of symptoms that indicate worsening of their disease. If a patient with symptoms has a history of recent international travel, consumption of undercooked or fresh food, recent administration of antibiotics due to unrelated disease, stool samples may be taken to assess bacteria or parasites’ presence to determine if there is no concomitant gastrointestinal infection.

There are several newer serological markers (ASCA, ANCA, amps, anti-CBir1) that can help make the diagnosis. So far, these markers are not yet accurate enough to make a diagnosis based on them alone. Nevertheless, they can be useful in combination with a medical history, physical examination, radiological and endoscopic findings.

Endoscopy

endoscopy
Small bowel endoscopy – the first picture shows a normal small bowel, and the second picture shows a small bowel affected by Crohn’s disease.

Very often, bowel interior inspection by colonoscopy, sigmoidoscopy, or endoscopy using a fiberoptic endoscope is required to diagnose Crohn’s disease. A long, flexible tube with a light source and a camera attached is inserted into the anus (“sigmoidoscopy” – if only the lower third of the colon is examined, “colonoscopy” – if the colon is fully examined). Colonoscopy is often preferred when considering Crohn’s disease because it is often possible to reach the end of the small intestine, the terminal ileum, which is often affected by Crohn’s disease. In Crohn’s disease, the inside of the colon and terminal ileum appears swollen, inflamed, and often with ulcerations. Inflammation is often limited and discontinuous, unlike ulcerative colitis.

colon endoscopy
Colon endoscopy – The first picture shows a normal colon, the second picture shows a colon affected by Crohn’s disease.

Small samples – biopsies – are taken during endoscopy to be examined under a microscope, and possible inflammation traces are found. A specific type of inflammation known as noncaseating granulomas can be seen in approximately 20% of patients with Crohn’s disease and can help confirm the diagnosis. A combination of endoscopy and pathological specimens is almost always necessary to diagnose. This procedure can be delayed in patients with signs of severe colitis because the bowel inside is very vulnerable and can be damaged by the endoscope. Sometimes, if patients have many symptoms related to the upper gastrointestinal tract, such as upper abdominal pain, reflux, nausea – gastroscopy or upper endoscopy may be done to examine the esophagus, stomach, and the first part of the small intestine (duodenum).

Radiography

Endoscopy and colonoscopy can only see the beginning and end of the small intestine so that other radiological tests can visualize the small intestine. The test most commonly used to visualize the small intestine is double-contrast irigography (en. small-bowel series, upper GI series, or small bowel follow-through ). During this test, the patient drinks a contrast containing barium. A series of radiographs are then taken that may show inflammation, fistulas, or strictures of the small intestine, if present.

Double contrast irigography
Double-contrast irigography – barium study – arrows show narrowing of the small intestine due to Crohn’s disease.

Other radiological tests, such as CT or MRI, are often needed to perform a complete bowel evaluation and rule out complications of Crohn’s disease, such as perforations, abscesses, and fistulas. CT and MRI are mainly used to “look outside” at the intestines, i. to look for complications on the intestinal wall, but newer oral contrast dyes and specialized techniques allow these tests to give a closer look at the small intestinal wall as well.

Endoscopic capsule

The endoscopic capsule is a new imaging method that allows inspection of the small intestine. Patients swallow a pill containing a camera and a light source. The camera then transmits the images to a recording device and allows inspection of the small intestinal mucosa in a relatively non-invasive manner. This method is mainly used in patients with gastrointestinal bleeding when no bleeding source can be found on upper endoscopy or colonoscopy.

Precautions must be taken in patients with established Crohn’s disease because of the risk of capsule retention, as in this case, the capsule will need to be surgically removed. Also, these studies should be evaluated with caution to avoid misdiagnosis – for example, nonsteroidal antirheumatic drugs can cause small bowel ulcers, which can be misinterpreted as similar lesions in Crohn’s disease, and asymptomatic ulcers can actually be seen in up to 15% of a generally healthy population. Currently, this method is not used to examine the esophagus, stomach, or colon. It cannot be used to take a biopsy, so it is not a substitute for endoscopic procedures but can be used in specific circumstances.

Differential diagnosis

All other diarrhea causes should be ruled out, and stool cultures should always be done. Crohn’s disease should be suspected in all patients with evidence of malabsorption, for example, in megaloblastic anemia or malnutrition and children with short stature. Ileocolic tuberculosis is common in developing countries, making it difficult to diagnose Crohn’s disease. Microscopy and cultures for tuberculosis in any available tissue are essential in developing countries. Sometimes trial therapy with antitubercular drugs is also needed. Lymphomas can sometimes affect the ileum and caecum.

Complications

Pyodera gangrenosum
Pyoderma gangrenosum – a skin complication in patients with Crohn’s disease

Several complications can occur with Crohn’s disease.

Small bowel obstruction is the most common complication of bowel blockage, usually of the small intestine. Obstruction occurs due to inflammation of the intestinal wall, which eventually leads to scarring and narrowing the intestine’s lumen. Over time, the intestinal lumen becomes so narrow that even minor inflammation can lead to lumen closure and small bowel obstruction. The patient will usually have cramping abdominal pain, abdominal distension, nausea, and, if it is a more severe case, vomiting, lack of bowel movement, or inability to pass gas. In this situation, patients are usually advised not to eat, which usually leads to improvement. IV fluids may be required. If the obstruction does not resolve and returns despite therapy, surgery is usually required.

Fistula

Crohn’s disease can also cause inflammation and ulcers that pass through the affected part of the intestine to surrounding organs, such as the skin (entero-cutaneous fistulas), bladder (entero-vesical fistulas), vagina (rectovaginal fistulas), or other parts of the intestine (entero -enteric fistulas). The most common type of fistula is perianal. Depending on the affected organ, fistulas are defined as internal (bladder, intestine) or external (skin). Some fistulas that occur between two parts of the intestine do not require therapy. Fistulas of other organs may respond to therapy (immunomodulators), but surgery may be required. Abscesses require surgical drainage. Acute perforation is an indication of surgery. Such patients have acute presentations with severe abdominal pain, rigid abdomen, fever, and shivering. The symptoms may be similar to those of appendicitis.
Perianal fistulas – the most common type of fistula. Sometimes they can be treated therapeutically, but surgical intervention is also required in some cases.

Osteopenia/osteoporosis

mild bone thinning (osteopenia) occurs in while 50% of patients with Crohn’s disease, and more severe bone thinning (osteoporosis) may occur in about 15% of patients. This complication is more common in patients who need steroid therapy and in smokers, patients with more active disease, and in those with low calcium and vitamin D intake. As a result, a special radiograph called bone mineral density testing is recommended for patients taking steroids, postmenopausal patients, patients who had fractures with mild trauma, and patients with moderate to severe Crohn’s disease. Patients with osteopenia/osteoporosis need blood tests that rule out other causes of bone loss, including an overactive thyroid gland and low blood levels of vitamin D. All patients with Crohn’s disease should be instructed to take calcium supplements and vitamin D daily. Some patients require additional medications, such as bisphosphonates, to prevent further bone loss.

Colon cancer

There is an increased risk of colon cancer in patients with Crohn’s disease. Risk factors include more serious illness, longer duration of illness, a family history of colon cancer, or the concomitant presence of primary sclerosing cholangitis (PSC). Monitoring with colonoscopies and biopsies is recommended every two years after diagnosis, for eight to ten years. The exception is patients with primary sclerosing cholangitis, who should go for follow-up colonoscopies immediately after diagnosis.

Small bowel cancer

there is a clear increased risk of small bowel adenocarcinoma in patients with Crohn’s disease, but this remains an infrequent complication. This type of cancer usually occurs in long-term active disease or stricture areas. There is currently no recommended follow-up test due to the rare occurrence of complications.

Excessive bacterial growth

It is typically presented by diarrhea and abdominal cramps. Bacteria grow excessively in the small intestine, usually around strictures, fistulas, or loss of the valve between the small and large intestine (ileocecal valve). It is treated with antibiotics.

Nutritional deficiencies

Nutritional complications can also be seen, including protein, calorie, or vitamin deficiencies. These deficiencies are caused by inadequate intake, intestinal protein loss, or poor nutrient absorption due to existing inflammation. Vitamin B12 deficiency is often seen in patients who have had a resection of part of the terminal ileum, the part of the intestine where vitamin B12 is absorbed. The same patients may develop diarrhea due to malabsorption of bile salts. Patients who have had a larger ileal resection have a risk of fat malabsorption, leading to a deficiency of fat-soluble vitamins (vitamins A, D, E, and K). Vitamin D deficiency is not uncommon and is usually associated with a dairy restriction imposed by the patient on suspicion of lactose intolerance. Malabsorption is another cause of vitamin D deficiency.

Kidney stones

Diarrhea and malabsorption of fat can lead to kidney stones, which present with severe pain in the lower lateral back and blood in the urine.

Gallstones – Malabsorption of gallstones may be a predisposition to gallstones. Stones usually remain asymptomatic but may present with intermittent pain in the right upper abdomen. Patients with gallstones may also develop inflammation of the gallbladder (cholecystitis), infection of the liver ducts (ascending cholangitis), or inflammation of the pancreas (pancreatitis). If symptoms occur, the gallbladder is usually surgically removed (cholecystectomy).
Extraintestinal manifestations of Crohn’s disease (EIM) – Crohn’s disease can affect organs outside the gastrointestinal tract in about 25% of patients. They are usually categorized according to the organ affected and associated with disease activity. EIMs are more common in patients in whom the disease affects the colon. Places that can be affected are:

Joints

Crohn’s disease can affect the lower spine or peripheral joints (knees, ankles, etc.)

Skin

The two most common rashes associated with Crohn’s disease are erythema nodosum, which presents as painful raised red bumps, and pyoderma gangrenosum, in which the skin develops ulcerations.

Eyes

uveitis presents as pain and/or vision changes. Episcleritis is a painless redness of the conjunctiva and sclera.

Liver

Fatty liver is the most common liver disease in patients with Crohn’s disease, but primary sclerosing cholangitis (PSC) is a more severe form of associated liver disease. PSC is an inflammation of the liver ducts that can cause liver failure. Patients with PSC have a higher risk of developing liver duct cancer.

Treatment and goals of therapy

Crohn’s disease treatment options:

  • Induction of remission
    • Oral or intravenous glucocorticosteroids
    • Enteral nutrition
    • Oral glucocorticosteroids + azathioprine or 6-mercaptopurine (6MP)
  • Maintaining remission
    • Aminosalicylates
    • Azathioprine, 6MP, mycophenolate mofetil
  • Treatment of glucocorticosteroid resistant diseases / immunosuppressive therapy
    • Methotrexate
    • Intravenous cyclosporine
    • Infliximab (TNF-α antibody)
  • Perianal disease
    • Ciprofloxacin and metronidazole

The main goals of Crohn’s disease treatment are:

  • Initiate remission
  • Maintain remission
  • Improve the patient’s quality of life
  • Minimize toxicity.

There is no cure for Crohn’s disease; it is a chronic disease that patients will deal with for a lifetime. Therefore, the main goal of therapy is to control inflammation and symptoms and restore normal feeling to the patient (initiate remission), maintain normal feeling (maintain remission), and achieve all this with as few drugs as possible (less toxicity and fewer side effects). By achieving this, the patient’s quality of life improves. It works to achieve the goal of living without the limitations imposed by the disease.

Patients with mild symptoms probably only need symptomatic treatment. It would help if you quit smoking. Diarrhea can be controlled with loperamide or codeine phosphate. Diarrhea in long-term inactive disease may be due to bile salts’ malabsorption and should be treated with cholestyramine. If caused by vitamin B12, folic acid, or iron deficiency, anemia should be treated with appropriate haematinics. Anemia in a more active disease is usually normochromic and normocytic and will usually improve as the patient’s condition improves. Patients with active (moderate/severe) seizures are likely to be hospitalized. Patients with moderate to severe Crohn’s colitis are treated identically to ulcerative colitis.

Glucocorticosteroids are often used to induce remission in moderate to severe Crohn’s disease attacks (oral prednisolone 30-60 mg/day). In Crohn’s disease, which affects the ileum and caecum, but not the colon, budesonide’s slow administration is as effective as prednisolone orally. Budesonide has high topical potency and, due to extensive hepatic inactivation, has low systemic availability, which induces less suppression of endogenous cortisol and reduces steroidal side frequency and intensity effects. The overall remission/response rate varies from 60% to 90%, depending on the type, location, and extent of the disease.

Enteral nutrition is rarely used, but it is a good way to encourage remission in moderate to severe attacks of Crohn’s disease, and its effectiveness is independent of nutritional status. If enteral diets with low fat (1.3% of total calories) and low linoleic acid content are used as the main diet for 28 days, remission induction rates are similar to those achieved with steroids. Relapse rates, however, are high, especially in patients with colon disease.

Relapses often occur after steroid dose adjustment and/or after cessation of enteral nutrition. Alternative treatment strategies must be applied, e.g., a temporary increase in steroid dose to re-induce and maintain remission. Aminosalicylates are particularly useful in Crohn’s colitis. The immunosuppressive agent azathioprine (AZA) and its metabolite 6-mercaptopurine (6MP) are effective in inducing and maintaining remission and having the property of saving steroids. Mycophenolate mofetil, which suppresses T and B lymphocytes’ proliferation, is also effective in maintaining remission.

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