Crohn’s Disease Causes and Treatment

Symptoms

Crohn’s disease manifests as inflammation that occurs primarily in the lower portion of the small intestine and in the colon. The typical course is chronically recurrent, meaning periods of quiescence are interrupted by episodes of disease. Common symptoms include:

  • Abdominal pain (more likely on the right side)
  • Nausea, vomiting
  • Diarrhea, constipation
  • Flatulence
  • Fever
  • Weight loss
  • Malabsorption
  • Fistulas
  • Partly life-threatening gastrointestinal bleeding.

In children, systemic and extraintestinal symptoms predominate. Stool consistency and frequency reflect the localization and extent of disease. Symptoms of Crohn’s disease can be quantitatively assessed using the Crohn’s Disease Activity Index (CDAI) to determine disease activity. Crohn’s disease can also be classified into different severity levels and categories.

Causes

Although the actual cause remains unclear, the disease is thought to be triggered by a wide variety of factors. Here, the focus is on a wide variety of environmental factors as possible triggers and a genetic predisposition.

Among genetic factors, complex multigenic predispositions consisting of single nucleotide and gene copy polymorphisms have been demonstrated. Normally, these genes are important for innate immunity and are responsible for the degradation of cellular structures and bacteria. Mutations disrupt the function of secretion-producing cells and thus damage the mucosal barrier of the intestine. This makes it easier for pathogenic microorganisms to invade and settle in the mucus and mucosa. Inflammation and visible tissue damage occur. There is an increased risk if relatives already have Crohn’s disease. The risk also increases with the number of single-nucleotide polymorphisms (SNP) in the intracellular NOD2 receptor.

Complications

Typical complications include the formation of a wide variety of fistulas, abscesses, and intestinal strictures. Extraintestinal manifestations of the disease with characteristic ocular, cutaneous, and joint involvement are also frequently observed. In addition, it is not uncommon to find laboratory abnormalities such as iron deficiency anemia or vitamin B12 deficiency. Complex courses of the disease are also characterized by lack of response to drugs and by repeated need for surgical intervention. Extensive bowel resections can lead to short bowel syndrome with malnutrition. If the colon is affected and the long-term course is characterized by persistent inflammatory activity, the risk of developing colorectal cancer increases.

Diagnosis

Diagnosis is made by medical treatment and is often established by a combination of biochemical, endoscopic, radiologic, and histologic findings. Colonoscopy plays an important role in this process. Depending on the intestinal involvement, the differential diagnosis to other diseases is broad and includes acute or chronic infections, ischemia and malignant tumors. In children, Crohn’s disease may be confused with eating disorders or endocrine disorders because of its systemic and extraintestinal symptoms.

Drug treatment

The main goal of therapy is to induce and maintain a symptom-free state, reverse nutritional deficiencies, and restore production of mature cells. Drug treatment is based on immunosuppression and modulation by suppressing granulocyte and macrophage activity, lymphocytic toxicity, and thus adaptive immune defense. There are two principles of therapy: 1. Step-up therapy:

  • Locally acting or systemic glucocorticoids are the agents of choice. Although they often do not induce healing of the intestinal mucosa, they are effective for clinical remission induction but not remission maintenance. If this therapy fails or dependence develops, immunosuppressants (usually azathioprine) are used first. TNF-alpha inhibitors are reserved for severe relapses as third-line therapy.

2. top-down principle:

  • Here, TNF-alpha inhibitors are used early with the idea that this may result in improved efficacy, lower dosing frequency, and lower cumulative dose of steroid therapy. The value of this approach is unclear today.

In the drug therapy of Crohn’s disease various drug groups used: Aminosalicylates are administered orally or rectally and are locally in the intestine anti-inflammatory and antimicrobial:

  • Mesalazine (e.g., Asacol, Mezavant, Pentasa, Salofalk).
  • Olsalazine (Dipentum, out of commerce).
  • Sulfasalazine (salazopyrin)

Antibiotics are administered orally and are antibacterial and anti-inflammatory:

Immunosuppressants are used orally or parenterally and suppress the immune system:

  • Azathioprine (Imurek, generic).
  • Mercaptopurine (Purinethol)
  • Methotrexate (various manufacturers)

Glucocorticoids immunosuppressive and anti-inflammatory. They are administered orally, locally or parenterally. They act systemically or as enemas locally:

  • Prednisolone (Spiricort, generics).
  • Budesonide (Budenofalk, Entocort)

TNF-alpha inhibitors (monoclonal antibodies) are approved as second- or third-choice agents for treatment when conventional therapies do not respond. They must be administered parenterally:

  • Infliximab (Remicade)
  • Adalimumab (Humira)
  • Certolizumab (Cimzia)

Integrin antagonists:

An enteral diet may alter inflammatory activity in Crohn’s disease. Possibly, fish oil with omega-3 fatty acids can support drug therapy in adults. However, convincing data on this are still lacking. The elementary diet for the therapy of an active relapse has nowadays a clinical value only in children. Vitamins and minerals are administered for deficiencies.