Faculty Member - University of Health Sciences, Hamidiye Faculty of Medicine, Department of Physiology

"Crohn's disease is a common disease around the world and its incidence is increasing."

Title:

What is Crohn's disease?

Crohn's disease is a chronic inflammatory bowel disease. It can involve any part of the digestive system from the mouth to the anus. It is common in the ileum, which is the last part of the small intestine, and in the colon. Inflammation can be seen in all layers of the intestine. Its appearance is "intermittent" as there are healthy tissues between the inflamed areas. The intestinal surface has a "cobblestone" appearance caused by clefts and cracks surrounded by areas of submucosal edema. Marked inflammatory and fibrotic changes occur in the submucosal layer. After a while, the intestinal wall thickens and often loses its elasticity.

Who is at risk?

Although the factors that cause Crohn's disease are not fully known, the immune system, genetic predisposition, previous infections, dietary habits, allergic, and environmental factors play a role in the development and progression of the disease. Despite it is mostly known as a disease of Western societies, its incidence has increased at an alarming rate in recent years as dietary habits, environmental and social factors have changed in newly industrialized countries.

It has been reported that the risk of disease is 8-10 times higher in first-degree relatives of people with Crohn's disease, and this risk is even higher among twins. Occurrence of the disease, its severity and complications, areas of involvement and differences in treatment response can be explained by the genetic dissimilarities between individuals.

International studies have shown that Crohn's disease is more common in women than in men and the risk of the disease increases in women over the age of 35.

Smoking is a major risk factor for Crohn's disease, doubling the risk of disease development, especially at an early age, and is thought to cause resistance to treatment.

Diets rich in sugar, omega-6 fatty acids, polyunsaturated fatty acids, fat, and meat (except fish) have been shown to increase the risk of Crohn's disease, while plant-based diets rich in fiber have been shown to reduce the risk. Patients have been found to have antibodies against milk proteins and baker's yeast. It has also been suggested that low intakes of zinc and vitamin D and high iron intakes may play a role in the development of Crohn's disease.

Patients have dysbiosis of the gut microbiota and are characterized by a marked reduction in microbial diversity compared to healthy individuals. Disruption of the microbiota in early childhood (especially due to antibiotic use) can affect the gut immune response and alter susceptibility to disease. Stress, air pollution, hygiene, and diet are other factors that influence the composition and functional activity of the gut microbiota.

How is it diagnosed?

The first step in the diagnosis is a detailed history (familial, social, and medical) and physical examination. Laboratory findings such as erythrocyte sedimentation rate, C-reactive protein, leukocyte, and platelet counts are examined. In addition, fecal calprotectin protein measurement is valuable in excluding different diseases in adults and children.

Medical imaging can be used to confirm the diagnosis and monitor disease activity. The endoscopy procedure is useful for directly visualizing the affected areas, determining the extent of disease involvement and for biopsy. A bowel biopsy is confirmatory rather than diagnostic. Endoscopic biopsy is important to differentiate Crohn's disease from other inflammatory bowel diseases such as ulcerative colitis and to exclude acute colitis, dysplasia (precursor changes in cells before cancer develops), or cancer.

What are the symptoms?

Crohn's disease is an aggressive and slowly progressing disease with high morbidity. Diarrhea, abdominal pain, rectal bleeding, fever, weight loss, and fatigue are the most common symptoms. The course of the disease can vary from mild symptoms to the need for hospitalization and surgery. In children and adolescents, the initial symptoms may be insidious, such as growth retardation, inadequate sex hormone secretion, joint inflammation, weight loss or fever of unknown origin. In Crohn's patients, abdominal pain is common due to involvement of all intestinal layers. Obstruction due to thickening of the intestinal wall and narrowing of the lumen, nausea and vomiting may occur. Bloody and mucousy diarrhea may be observed. Ulceration around the anus due to diarrhea is common.

What are the complications?

Although the course of the disease is different in most patients, perforation, fistula (abnormal connection), abscess and small bowel obstruction are the most common complications of Crohn's disease. There is also an increased incidence of cancer in Crohn's patients. In addition to the digestive system, patients may have inflammatory disorders such as inflammation of the joints, erythema nodosum (inflammation of the subcutaneous fatty tissue), inflammation of the eyes, mucosal aphthous ulcers, sclerosing cholangitis (autoimmune disease of the bile ducts) and liver cirrhosis. Kidney disorders such as nephrolithiasis (kidney stones) due to increased oxalate absorption associated with steatorrhea (fatty stools) have been detected in 1/3 of patients. Amyloidosis (accumulation of a protein called amyloid in tissues) and thromboembolic disease (severe reduction in blood flow due to clots), which are indicators of systemic inflammation, are serious complications of Crohn's disease. In addition, malnutrition is common in patients.

What are the therapeutic approaches?

Despite advances in treatment modalities over the last decade, there is no definitive cure as the cause of the disease is unknown. Therapeutic approaches are aimed at alleviating inflammation and symptoms. Treatment protocols vary according to the degree of intestinal involvement and the site of inflammation, which determines the severity of the disease. Smoking cessation is a component of treatment.

The first step in the treatment of the disease is medication. Medicines are usually used gradually. First, drugs with fewer side effects are prescribed; if these do not provide the desired relief, other drugs are used. Medical treatment includes corticosteroids, 5-aminosalicylates, and immunomodulatory agents such as thiopurines and TNF-alpha blockers. New biological agents are also being developed.

Recently, fecal microbiota transplantation to increase microbial diversity has become a potential therapeutic strategy to eliminate dysbiosis of the gut microbiota.

In Crohn's disease, the area and length of involvement, frequency, and duration of the active period of the disease significantly affect malabsorption and nutrient deficiency. This causes abdominal pain, nausea, vomiting, diarrhea, and loss of fluid-electrolytes, vitamins and trace elements during periods of exacerbation of the disease, and accelerates weight loss by reducing food intake and appetite. Therefore, the primary goal of medical nutrition therapy is to improve and maintain nutritional status and to maintain remission. Individual differences and the condition of the patients should be taken into account when organizing medical nutrition therapy, and the patient should be tried to be fed orally as much as possible. In children with Crohn's disease, nutritional therapy is recommended as a first-line treatment.

Approximately 50-70% of Crohn's patients require surgical treatment. Surgery is usually performed when medical treatment has failed and to manage complications such as stenosis, fistula, abscess, and perforation of the digestive tract or to relieve obstruction. Surgical removal (resection) of the small intestinal sections can result in complications associated with short bowel syndrome, including malabsorption, diarrhea, and nutrient deficiencies. Symptoms are related to the size and location of the resection. The disease may recur within 1-3 years following surgical intervention.

Conclusion

Crohn's disease is a common disease with an increasing prevalence worldwide. Numerous genetic and environmental factors are associated with the development of the disease. Furthermore, dysbiosis plays an important role in the development of the disease and the effectiveness of treatment. Smoking, antibiotic intake in early childhood and western-style eating habits are important environmental factors in the etiology of the disease. In recent years, significant progress has been made in understanding the role of intestinal inflammation in the pathogenesis of the disease. These developments have contributed to the investigation of new therapeutic approaches, such as fecal microbiota transplantation, which may be preferred over or supplement existing medical and surgical treatment strategies. Medical nutrition therapy is prominent in preventing symptoms such as diarrhea and abdominal pain, which are common in patients, and in maintaining remission. Consumption of quality fiber or omega-3 fatty acid intake has been shown to prevent intestinal inflammation in humans. The use of probiotics and/or prebiotics in medical nutrition therapy has led to conflicting results and more scientific research is needed.

Basoglu, I. A. and Karakoyun, B. Crohn’s disease: etiology, pathogenesis and treatment strategies. (2023).

Begümhan Ömeroğlu Yel (2018). Sıçanlarda deneysel kolit modelinde Gilaburu’nun (Viburnum opulus L.) olası tedavi edici ve koruyucu etkilerinin araştırılması. Marmara Üniversitesi, Sağlık Bilimleri Enstitüsü, Beslenme ve Diyetetik Anabilim Dalı, Yüksek Lisans Tezi. (Danışman: Doç. Dr. Berna Karakoyun Laçin)

Dolinger M, Torres J, Vermeire S. Crohn's disease. (2024).

Hülya Buzcu (2024). Sıçanlarda asetik asit ile oluşturulan deneysel kolit modelinde phoenixin-14'ün olası tedavi edici etkilerinin araştırılması. Sağlık Bilimleri Üniversitesi, Sağlık Bilimleri Enstitüsü, Tıbbi Fizyoloji Anabilim Dalı, Doktora Tezi. (Danışman: Prof. Dr. Berna Karakoyun Laçin)

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