Crohn’s Disease – Symptoms and Treatment

Definition of the Disease. Causes of the Condition

Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract, characterized by segmental involvement of the intestinal wall with the development of local and systemic complications. Synonyms for the disease include granulomatous enteritis, regional enteritis, transmural ileitis, and regional terminal ileitis.

Common Symptoms of Crohn’s Disease: abdominal pain, chronic diarrhea with mucus and blood streaks, or without them. The disease belongs to the group of inflammatory bowel diseases and, alongside nonspecific ulcerative colitis, can affect all segments of the gastrointestinal tract, from the oral cavity to the anus. The ileocecal region (the junction of the small intestine and large intestine) is the most favored localization of Crohn’s disease. When this area is affected, the symptoms of the disease resemble those of acute appendicitis, which complicates diagnosis in emergency cases.

Intestinal damage in Crohn’s disease

Prevalence of Crohn’s Disease

In most Western countries, the incidence of Crohn’s disease is 5-8 cases per 100,000 people per year. The main peak of incidence occurs between the ages of 20 and 40, with a smaller peak between 50 and 70 years old. Among patients with Crohn’s disease, 15-20% are younger than 20 years old. The overall prevalence of the disease is 120-200 cases per 100,000 people.

Causes of Crohn’s Disease

The exact causes of Crohn’s disease are still unknown. There are hypotheses that partially explain the triggering mechanisms of the disease:

  1. Genetic predisposition: Over 160 candidate genes have been described, and certain mutations in genes like NOD2 increase the risk of Crohn’s disease by 15-40 times.
  2. Environmental factors: In developed countries, the incidence rate is higher, and Crohn’s disease is more prevalent in northern regions.
  3. Immune and infectious factors: Patients with Crohn’s disease have compromised intestinal mucosal barriers, allowing bacteria to penetrate. Antimicrobial peptides secreted in Paneth cells (cells of the small intestine) protect the mucous membrane from bacterial invasion, but their expression is reduced in Crohn’s disease. Additionally, dysfunction of autophagy (the natural degradation of cell components) in Crohn’s disease increases bacterial survival. These mechanisms trigger an uncontrolled immune response, leading to chronic intestinal inflammation.

All these hypotheses indicate that the etiology of Crohn’s disease is multifactorial, but some aspects remain unclear.

Risk Factors

  • Age (15-35 years old)
  • Family history (20-25% of patients have a close relative with Crohn’s disease)
  • Race and ethnicity: The disease is more prevalent among white populations.
  • Smoking: Increases the risk of developing the disease and worsens prognosis.
  • Appendectomy (surgical removal of the appendix): Increases the risk of developing Crohn’s disease, with the reasons for this being unknown.

Symptoms of Crohn’s Disease

Crohn’s disease can affect any part of the gastrointestinal tract and other organs. The ileocecal area is the most commonly affected part of the intestine, occurring in 60-70% of all cases of Crohn’s disease. Segmental colitis, total colitis, and involvement of the anorectal area occur in 20-30% of patients, often in combination.

Distribution of gastrointestinal organ involvement in patients with Crohn’s disease, according to the Montreal classification:

Gastrointestinal Organ InvolvementFrequency of Occurrence
Terminal ileitis (involvement of the terminal ileum)40-50%
Ileocolitis (involvement of the ileum and colon)20%
Colitis (inflammation of the mucous membrane of the colon)50%
Involvement of upper gastrointestinal organs5%
Anorectal involvement20-30%

Clinical Presentation of the Disease
Symptoms of the disease vary depending on the segment of involvement. In most cases, patients experience the following symptoms:

  • Diarrhea: the most common symptom of Crohn’s disease.
  • Abdominal spasms, especially after eating.
  • Abdominal pain and bloating, potentially progressing to partial or complete intestinal obstruction.

These symptoms are sometimes accompanied by occult bleeding, leading to anemia. Additionally, patients often experience malnutrition and anorexia. Inflammation in adjacent tissues can lead to fistulas—unnatural communications between different body cavities. These, in turn, can lead to the formation of abscesses—pus-filled cavities that can manifest as pain (mostly dull), fever, or even sepsis.

Extra-intestinal manifestations of terminal ileitis occur in approximately 20-40% of patients, and their occurrence depends on the activity of the disease.

Extra-intestinal manifestations of Crohn’s disease include:

Blood– Anemia (weakness, dizziness, “flashes” before the eyes, pale skin).
– Thrombophilia (pathological increase in blood clotting with the formation of thrombi).
Joints– Sacroiliitis (pain below the lower back, radiating to the abdomen, buttock, thigh, or knee).
– Peripheral arthritis (pain, swelling, redness of the knees, ankles, elbows, wrists, and other joints).
– Ankylosing spondylitis (pain and stiffness in the sacrum and lower back, which occur at rest, especially in the second half of the night and closer to the morning, and decrease with movement and exercise).
Eyes– Uveitis (redness, irritation, and pain in the eyes, increased sensitivity to light, blurred vision, tearing).
– Episcleritis (redness of the sclera, tearing, photophobia, appearance of transparent discharge from the conjunctiva, but without impaired visual function).
BonesOsteoporosis and osteopenia (pathological bone fragility).
Skin– Erythema nodosum (dense nodules located in the dermis or subcutaneous tissue, with redness of the skin above them).
– Pyoderma gangrenosum (furuncle-like elements on the skin with transparent or hemorrhagic contents against the background of redness).
Chest– Pleuritis (shortness of breath, feeling of lack of air, chest pain).
– Myocarditis (shortness of breath, pain behind the sternum, weakness).
Kidneys– Amyloidosis (deposition of amyloid protein in kidney tissues with the development of renal failure).
– Nephrolithiasis (formation of stones in the kidneys – pain in the lower back, blood in the urine).
PancreasPancreatitis (pain in the upper abdomen radiating to the back, loose stool).
Hepatobiliary tract– Cholelithiasis (stones in the gallbladder – colicky pain in the right hypochondrium).
– Primary sclerosing cholangitis (damage to the liver ducts, manifested by pain in the abdomen, itching, jaundice of the mucous membranes, skin, fever, weakness).
– Cholangiocarcinoma (cancer of the bile ducts – weakness, weight loss, pain in the right hypochondrium, jaundice).
– Autoimmune hepatitis (pain in the right hypochondrium, jaundice, weakness).

Anemia is the most common accompanying condition of Crohn’s disease, mainly caused by iron deficiency due to chronic inflammation, less commonly due to intestinal bleeding or vitamin B12 deficiency. The second most commonly affected tissues in Crohn’s disease are the joints. Eye involvement is noted in 2-13%, and skin involvement in 2-15% of cases. Sclerosing cholangitis usually occurs only in patients with Crohn’s colitis. Pancreatitis affects up to 4% of patients but is often a side effect of medication and cholelithiasis (gallstones).

Pathogenesis of Crohn’s disease:

The pathogenesis of Crohn’s disease remains poorly understood due to its unknown causes and diverse manifestations (possible involvement of all parts of the gastrointestinal tract and other organs).

The lesions in Crohn’s disease are systemic in nature. Causal factors lead to an abnormal defensive reaction of the body, with genetic predisposition to immune system dysfunctions playing an important role. The pathogenesis of Crohn’s disease is explained by the development of autoaggression, which is the immune system’s damage to its own cells, classifying Crohn’s disease as an autoimmune disorder.

Antibodies (protective proteins produced by the body in response to external stimuli), or more precisely, autoantibodies, attack the body’s own tissues and organs, leading to inflammation. The intestinal wall bears the brunt of the damage in Crohn’s disease. Accumulation of plasma cells occurs within the thickness of the intestinal wall, which produce antibodies that damage the intestinal wall. Subsequently, a chain of events occurs, leading to the formation of microabscesses spreading throughout the thickness of the intestinal wall, distinguishing Crohn’s disease from another inflammatory bowel disease—nonspecific ulcerative colitis. The specific characteristic of Crohn’s disease, distinguishing it from other similar diseases in its manifestations, is the appearance of a “cobblestone” pattern when the intestinal wall is affected.

These described pathophysiological processes lead to tissue and organ damage of varying severity: from minor, not affecting the overall condition, to severe manifestations—”lightning-like occurrences” that threaten life, even despite comprehensive therapy.

Classification and stages of Crohn’s disease:

  1. Levitan’s Classification, 1974:
  • Based on the localization of the pathological process:
    • Enteritis (ileitis) – inflammation of the ileum.
    • Enterocolitis (ileocolitis) – inflammation of the small and large intestine.
    • Colitis – inflammation of the mucous membrane of the large intestine.
    • Inflammation of the upper gastrointestinal organs (duodenum, stomach, esophagus).
  • Based on the severity of clinical manifestations:
    • Mild form – with no significant disruption of the general condition; abdominal pain, frequent loose stool with blood and mucus.
    • Moderate form – worsening of the general condition, weakness, pallor of the skin, moderate abdominal distention, intensification of abdominal pain, frequent urge for defecation, loose stool with more mucus and blood.
    • Severe form – significant deterioration of the general condition, severe weakness, decreased or complete cessation of motor activity, pronounced pallor, dizziness in the horizontal position, severe abdominal pain, constant urge for defecation, stool with mucus and blood, often complications develop.
  • Based on the course of the disease:
    • Acute – manifestation of the disease with the appearance of symptoms and subsequent transition to a chronic continuous course or remission.
    • Chronic, or recurrent, i.e., with periods of exacerbation and remission or continuous.
  1. Vienna Classification of Crohn’s Disease:
  • Based on age at diagnosis:
    • A1 – 40 years and younger.
    • A2 – older than 40 years.
  • Based on the localization of the process:
    • L1 – terminal ileum.
    • L2 – colon (colitis).
    • L3 – ileocolitis.
    • L4 – upper gastrointestinal tract.
  • Based on the nature of the course:
    • B1 – non-stricturing (without narrowing of the lumen), non-penetrating (without penetration into neighboring organs).
    • B2 – stricturing.
    • B3 – penetrating.
  1. Montreal Classification of Crohn’s Disease:
  • Based on age at diagnosis:
    • A1 – 16 years and younger.
    • A2 – 17-40 years.
    • A3 – older than 40 years.
  • Based on the localization of the process:
    • L1 – terminal ileum.
    • L2 – colon.
    • L3 – ileocolon.
    • L4 – upper gastrointestinal tract.
    • L1+ L4 – terminal ileum + upper gastrointestinal tract.
    • L2+ L4 – colon + upper gastrointestinal tract.
    • L3+ L4 – ileocolon + upper gastrointestinal tract.
  • Based on the nature of the course:
    • B1 – non-stricturing, non-penetrating.
    • B2 – stricturing.
    • B3 – penetrating.
    • B1p – non-stricturing, non-penetrating + perianal disease.
    • B2p – stricturing + perianal disease.
    • B3p – penetrating + perianal disease.

Stages of the disease are not typically distinguished. In Crohn’s disease, intestinal involvement begins with the ileocecal region and then spreads to other parts of the gastrointestinal tract, causing inflammation of the intestinal wall with the formation of abscesses, deep ulcers, strictures, and penetrations into neighboring organs. The severity of the disease varies from mild, without disruption of the general condition, to very severe, life-threatening conditions.

the complications of Crohn’s disease:

Complications Requiring Urgent Surgical Treatment:

  • Acute Intestinal Obstruction: In this condition, there is a blockage preventing the movement of intestinal contents towards the rectum. In Crohn’s disease, obstruction is caused by severe inflammatory processes with the formation of thick scars and edema.
  • Perforation: This is a defect in the intestinal wall with the exit of contents into the free abdominal cavity and/or into adjacent organs, possibly leading to the formation of a fistula. The cause of perforation in Crohn’s disease is transmural (involving all layers of the intestinal wall) inflammation.
  • Bleeding: Bleeding of varying severity occurs in Crohn’s disease, from capillary bleeding, which does not require surgical treatment, to severe arterial or venous bleeding due to damage to larger blood vessels.
  • Toxic Megacolon: This serious condition is characterized by a sudden excessive dilation of the colon lumen, with absorption of contents into the blood and the development of a systemic inflammatory reaction.

Complications Not Requiring Urgent Surgical Treatment:

  • Stricture: Develops as a result of inflammatory reactions in the intestinal wall followed by proliferation (growth) of connective tissue and narrowing of the lumen. The degree of lumen narrowing varies from clinically insignificant to complete lumen narrowing with the development of acute intestinal obstruction.
  • Fistula: Formation of an abnormal connection between the intestinal lumen and nearby cavities, organs, or the external environment.
  • Abscess: Formation of a pus-filled cavity due to incomplete fistula or perforation of the intestinal wall.
  • Dysplasia: Cellular changes that develop during prolonged inflammatory processes and may eventually give rise to neoplasia with the formation of malignant cells.
  • Cancer of the Small or Large Intestine: Result of neoplasia development.

The diagnostics of Crohn’s disease:

Diagnostic Process:

  • Clinical Assessment: Diagnosis is based on the clinical presentation, disease progression, and diagnostic methods including laboratory tests, endoscopy, histology, and radiology.
  • Laboratory Investigations: Initial laboratory tests, in addition to standard blood and urine analyses, include assessing inflammatory markers such as C-reactive protein (CRP) to evaluate tissue damage during inflammation. Fecal calprotectin and lactoferrin are examined to differentiate inflammation from functional complaints, as these proteins are markers of intestinal inflammation. However, these tests are not specific to Crohn’s disease and are mainly used for patient monitoring during and after treatment. Albumin levels are important, especially in the preoperative period, as low concentrations are associated with a higher risk of complications.
  • Endoscopy: For diagnosis, ileocolonoscopy and multifocal biopsy from the terminal ileum and each segment of the colon are performed. Endoscopy is also used to exclude involvement of the upper gastrointestinal tract and in the postoperative period.
  • Radiological Investigations: Ultrasound is recommended for acute conditions and to detect fistulas, strictures, abscesses, and to monitor bowel inflammation during treatment. Plain X-rays are used in emergency situations, such as bowel obstruction and perforation. Magnetic resonance imaging (MRI) and CT enterography (computed tomography) accurately identify intestinal lesions and complications such as fistulas and abscesses. MRI and CT are performed during the initial evaluation when there is a high suspicion of Crohn’s disease. MRI is preferred over CT as it does not involve exposure to radiation. CT is used when surgical intervention is planned, for example, abscess drainage. Capsule endoscopy is used when standard imaging methods are inconclusive. Double-balloon enteroscopy is indicated when biopsy is required (e.g., to exclude malignancies) or for therapeutic procedures such as stricture dilation. MRI is the primary method for perianal lesions. Endosonography is an alternative but is used less frequently due to anal stenosis and pain, especially in severe perianal lesions.

Differential Diagnosis:

  • Crohn’s disease should be differentiated from irritable bowel syndrome, ulcerative colitis, and infectious colitis. In cases of acute lower abdominal pain, the main differential diagnoses are acute appendicitis and Yersinia enterocolitis. Granulomatous chronic inflammatory bowel diseases may be caused by systemic inflammatory diseases such as sarcoidosis or tuberculosis. Malignant lymphomas and small bowel cancers sometimes lead to small bowel strictures and conglomerates of bowel loops, which should also be differentiated from Crohn’s disease.
  • Treatment for Crohn’s disease is primarily conservative, but sometimes surgical intervention may be necessary, especially in isolated short segments of ileocecal inflammation or in emergency situations.
  • The choice of medications depends on the activity of the disease, its localization, and the presence of complications such as strictures and abscesses. It is also important to advise patients on the harmful effects of smoking, which can lead to postoperative recurrences.
  • First-line therapy includes local and systemic steroids, mesalazine, antibiotics, and immunosuppressants, depending on the severity and localization of the disease.
  • Patients with perianal involvement typically receive antibiotics and immunomodulators.
Prognosis and Prevention:
  • The prognosis for Crohn’s disease is often unfavorable, with a high risk of complications and recurrences.
  • Surgical treatment is required in approximately half of patients, and recurrences after surgery occur in nearly half of patients within ten years.
  • There are currently no specific preventive measures, but regular doctor visits and adherence to their recommendations can help prevent recurrences.
  • Studies suggest that early intervention in childhood, as well as consumption of natural, minimally processed foods in the diet, may reduce the risk of developing Crohn’s disease, likely by maintaining a healthy gut microbiome.