Crohn’s Disease

Crohn’s Disease is a chronic inflammatory Autoimmune Disease which can affect any part of the digestive tract, from the mouth to the anal ring. It is also known as granulomatous colitis or partial enteritis, regional enteritis or Idiopathic Inflammatory Bowel Disease (IBD). It is not contagious nor is it a form of cancer, however there is a slightly increased risk of small bowel cancer, of the colon or anus, when the patient has been suffering from Crohn’s Disease for many years.

 

Diagnosis of Real Causes & Treatment of Crohn’s Disease

• Gradual restoration of cellular function
• Personalized therapeutic protocols, without chemical residues and excipients
• Treating the real causes
• Therapeutic formulas that work alone or in combination with any other medication
• Adopting a Molecular / Therapeutic Nutrition Plan

 

Clinical features of Crohn’s Disease

rohn’s Disease often causes abdominal pain and diarrhea. Diarrhea can accompanied by bleeding in the inflammation is in the colon or rectum. If the narrowing of the small intestine creates an obstruction, the waste (faeces) cannot pass easily.

This can cause constipation or, if the small intestine is filled from the point of obstruction and over with liquids and gases, nausea and vomiting. Patients with active Crohn’s Disease often experience fatigue and lethargy and may develop fever.

Anemia (reduced number of red blood cells) can occur due to blood loss, poor diet or poor absorption of vitamins and may contribute to fatigue. Sometimes anemia, like fever, simply indicates the presence of inflammation in the intestine, which will improve as soos as Crohn’s calms down.
In older women the disease has aa predominantly orthodontic location.

In children, a striking feature is the inhibition of sexual development to a significant extent. In particular delayed onset of period and delayed physical development.

The most common part of affection is the final ileum (the lower part of the small intestine), but Crohn’s can also affect the colon, or the small and large intestine. It is possible for more than one sections to be affected at the same time.

In this autoimmune disease the wall of one or more parts of the digestive system develop swelling and thickening due to chronic inflammation.

Thickening of the digestive tract wall can lead to an internal narrowing of the affected area.

The area of the anus can also be affected by:

• stretch marks on the rectum
• fistulas (small openings with pus) around the anus
• abscesses or dithynids (pus with pus) around the anus, or
• edema (swollen but often painless lumps) just outside the anus.

 

A small proportion of patients with Crohn’s disease exhibit extrinsic manifestations such as inflammation of the inner part of the eye, known as uveitis, chololithiasis and vertebral arthropathy (arthritis and enthesitis). Other manifestations of the disease may be observed on the skin (erythema nodosa and gangrene pyoderma), blood and endocrine system. Finally Crohn’s Disease may cause increased risk of blood clotting and pulmonary embolism, hemolytic anemia, osteoporosis or bone thinning,granulomatosa and other forms of oral granulomatosis.

 

Pathophysiology of Crohn’s disease

The exact cause of the onset of the disease remains unknown with the majority of studies documenting Crohn’s disease as a multifactorial condition which causes the immune system to malfunction.

Intestinal inflammation begins in the mucosa by the accumulation of inflammatory cells, the formation of ulcers and the development of reactive (granulomatous) tissue.

From the mucosa the inflammation spreads throughout the intestinal wall, resulting in wall thickening, fibrosis and tightening. 

Factors that contribute to the incidence of Crohn’s Disease

Heredity, that is, genetic predisposition, various environmental and microbial factors are associated with the onset of the disease. Studies have shown that Crohn’s disease appears to develop as a result of the immune system reaction to pathogenic microorganisms in genetically susceptible recipients.

1. Genetic predisposition (related genes)
   There is serious evidence that Crohn’s disease is a result of genetic predisposition to multiple susceptibility genes. The gene currently responsible for about 20% of Crohn’s disease cases is NOD2 (located on chromosome 16).Mutations of this gene are associated with Crohn’s disease.
   The proteins produced by the NOD genes are thought to be cytosolic receptors for pathogenic bacterial signals. NOD proteins lead to activation of the NF-κB transcription factor, which in turn activates the production of inflammatory cytokines such as TNF-a, IL-1, IL-6, IL-12. IL-6 stimulates T-cell and B-cell proliferation and differentiation,while also mediating the hepatic expression of acute phase proteins.A new study linked the MDR1 gene to Crohn’s disease, MDR1, known as multidrug resistance protein 1, controls the process of eliminating toxins from the gut, thereby protecting the cells of the gastrointestinal tract.
   What Edinburgh researchers pointed out, led by Dr. Gwo-Tzer Ho, was that in people with idiopathic inflammatory bowel disease, MDR1 is dysfunctional.Other genes that may be responsible for regional enteritis are the IBD2 gene on chromosome 12, the IBD3 gene on chromosome 6, the IBD4 gene on chromosome 14, as well as various polymorphisms in cytokine genes.
2. Environmental factors
   Environmental factors contribute to the pathogenesis of Crohn’s disease by influencing its evolution, due to interaction with the intestinal microflora and the immune system.Studies have shown that smoking is the most important risk factor for developing Crohn’s disease, resulting in the most severe form of the disease and the most common cause of surgery in these patients.
   Medications associated with Crohn’s disease include non-steroidal anti-inflammatory (NSAIDs), oral contraceptives, antibiotics and more.Stress plays an important role in the pathogenesis of Crohn’s disease.
   It has been suggested that stress can activate or reactivate intestinal inflammation, leading to worsening of clinical symptoms.Stress triggers pathways from the hypothalamus to the sympathetic and parasympathetic nervous system affecting the intestinal nervous system,which in turn determines endocrine and gastrointestinal motility.Nutrition is directly linked to both the appearance and progression of Crohn’s disease.Western lifestyle with increased fat and sugar consumption and reduced fiber intake appears to be influencing disease prevalence.
   Increased consumption of total fat, but also of saturated and monounsaturated fatty acids seems to increase the risk of developing Crohn’s Disease.

   Reduced consumption of omega-3 fatty acids and increased consumption of omega-6 fatty acids also appears to be associated with an increased risk of developing the disease.

   Saturated and unsaturated fats play an important role in shaping the intestinal microbiome as well as Toll-like macrophage receptors. Consumption of fiber, especially soluble fiber, seems to have a protective role against Crohn’s Disease, in fact, some studies reduce the risk by up to 40%.

   Finally, recent data suggest that vitamin D may also be involved in the pathogenesis of the disease.

   Vitamin D deficiency is very common among patients with Crohn’s Disease.

3. Microbial factorsIt has been suggested that reduced exposure to intestinal bacteria and improved hygiene in early childhood can lead to an increase in abnormal immune responses in later life.Coexistence with more siblings also results in greater exposure to intestinal bacteria in early childhood. Patients with Crohn’s disease appeared to be more likely to live with fewer siblings and in smaller families.Furthermore, studies have shown that the lower the birth rate, the greater the risk of developing Crohn’s Disease.
   Differences in environmental conditions between rural and urban areas may explain the increased incidence of IRD in urban areas.Finally, studies have shown that patients with Crohn’s disease diagnosed in adulthood were less likely to live with domestic cats before the age of 5 years.In contrast, exposure to cats at an early age is associated with childhood Crohn’s disease.Several microorganisms appear to be involved in the pathogenesis of Crohn’s disease.

   In recent years, research has focused on the study of an adherent type E. coli, Adherent-invasive escherichia coli (AIEC).
   Recently, AIEC infection has been shown to affect microRNAs by reducing protein expression required for the autophagic response to intestinal epithelial cells.

   Other pathogenic bacteria, such as Campylobacter and Salmonella, have also been blamed for the pathogenicity of the disease.

 

Quality of life of patients with Crohn’s disease

Disease adversely affects social activity to varying degrees in more than half of patients, with one in five describing the problem as severe. Six out of ten patients feel sad or frustrated by their illness, with the problems being more severe in patients who have been diagnosed relatively recently.

Similarly, more than six in ten patients (65%) report feeling stressful (stress) as a result of the disease.

Almost out of four patients may even feel angry over the problems of the disease, with women and young people expressing it more strongly.

Four out of ten patients face significant difficulties fulfilling their professional obligations due to the disease.

Young people aged 18-39 and adults 40-49 seem to be more strongly affected.

More than one in two patients is forced to be absent from one to more than 20 days per year from work, either because of problems with the disease or because of the time needed to monitor and treat it.

One out of three patients has not disclosed the disease to anyone in their work environment (employers and coworkers), as he considers it personal or fears it will affect his professional life.

Three out of ten patients reported not having the desired support from their work environment (employers and colleagues) when their health problem is known.

Also, three out of ten patients report that they do not have the appropriate facilities from their employers to cope with the problems that result from their illness.

 

History and epidemiology of Crohn’s Disease

Crohn’s Disease was first described in 1913 by the Scottish surgeon, Dalziel.

However, it was named so in honor of New York doctor Burrill Crohn, who in 1932 presented with his colleagues a series of patients with this condition.

More than five million people worldwide live with Crohn’s Disease.Crohn’s Disease is more common in Europeans with incidence rates ranging from 5 to 12 per 100,000.

It is more common in white people than in other populations. Specifically, Crohn’s Disease affects about 50 people per 100,000 populationand the annual number of new incidents varies from 1 to 8 per 100,000 population in different regions.

It is a more common condition in northern European countries as well as in the United States of America compared to Central and Southern Europe and the Middle East (with the exception of Israel), while it is rare in Asian and African countries.

The disease affects a larger proportion of residents of large urban centers than residents of rural areas and this has been found to be largely the case in Greece.

Most studies show that Crohn’s Disease has a higher incidence rate in women than men( ratio of men to women 1: 1.16) however, data on Greece show a lower male dominance.

Recent international research has shown that there are more and more cases of Crohn’s, especially among adolescents and children.
It usually affects young adults 10-40 years of age and 60% are under 35 years of age it occurs more frequently in smokers than in non-smokers.

 

Traditional systemic treatments and modern treatments with biological agents in Crohn’s disease.

Most people start treatment with medicines containing masalamine. Sulfasalazine is the most common of these drugs.Some patients take corticosteroids to control inflammation. These drugs are the most effective for active Crohn’s Disease.

Other drugs used for Crohn’s Disease are those that suppress the immune system (azathioprine, 6-mercaptopurine). However, these drugs can cause side effects, such as nausea, vomiting and diarrhea and may reduce the body’s resistance to infection.

Antibiotics are used to treat bacterial overgrowth in the small intestine caused by narrowing, syringes or previous surgery.

The treatments that are used to fight Crohn’s Disease are mainly focused on reducing the symptoms of the disease and at the same time causing stressful cellular conditions manifested by a number of undesirable side effects such as nausea, increase in liver enzymes, myelosuppression (reduction of white blood cells, pancytopenia), greater susceptibility to infection, dryness of the skin and mucous membranes, hair loss, elevated serum triglycerides, renal damage,hypertension, gingival hyperplasia while these drugs are also known to cause teratogenicity if taken by pregnant women.

Infliximab, a modern biological therapy is a chimeric human-mouse antibody that binds selectively to the soluble and transmebrane types of tumor neurosis factor alpha (TNFa).

TNFa is a protein produced by the immune system that can cause inflammation associated with Crohn’s Disease. The use of biological agents also aims to reduce the symptoms of the disease but there are reports that link them to the emergence of new bacterial infections, the resuscitation of chronic infections (tuberculosis, HBV infection, HCV infection), and neoplastic diseases (skin cancer, lymphomas).

 

Functional Medicine and Crohn’s Disease Management

The unsuccessful treatment of Crohn’s disease as well as the side effects of the chemical pharmaceuticals used by conventional medicine has led many researchers and scientists to develop alternative therapies, which have positive effects in the treatment of the disease.

An integrated way of treating Crohn’s disease is applied in Functional Medicine, where, with the help of specialized examinations, the imbalances in the body which synergistically lead to the disruption of the immune system and eventually to the onset of the disease are understood.

In this way it is possible to apply a therapeutic regimen based on phytochemicals (essentially chemicals-dyes and other-naturally occurring in plants) without causing stressful cellular states and in combination with the appropriate nutritional plan restore disturbed homeostasis at the cellular and hormonal level thereby aiming not only at reducing symptoms but also at eliminating the etiology of the disease.

 

 

 

 

References

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• Sartor RB. Mechanisms of disease: pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol. 2006;3(7): 390–407.
• Itta M. Minderhoud, Bas Oldenburg, Marguerite E.I. Schipper, Jose – J.M. ter Linde, Melvin Samson. Serotonin Synthesis and Uptake in Symptomatic Patients with Crohn’s Disease in Remission. Clinical Gastroenterology and Hepatology. June 2007
• R. Spiller. Recent advances in understanding the role of serotonin in gastrointestinal motility in functional bowel disorders: alterations in 5-HT signaling and metabolism in human disease. Neurogastroenterology and Motility. Jul. 2007
• Jean-Eric Ghia, Nan Li, Huaqing Wang et al. Serotonin has a key role in pathogenesis of experimental colitis. Gastroenterology. Nov 2009
• Stein, A., Hinz, M., & Uncini, T. (2010). Amino acid-responsive Crohn’s disease: a case study. Clinical and experimental gastroenterology, 3, 171.
• Hinz, M., Stein, A., & Uncini, T. (2012). Relative nutritional deficiencies associated with centrally acting monoamines. Int J Gen Med, 5, 413-430.Loddo I, Romano C. Inflammatory bowel disease: genetics, epigenetics, and pathogenesis. Frontiers in immunology. 2015 Nov 2;6:551. Ni J, Wu GD, Albenberg L, Tomov VT. Gut microbiota and IBD: causation or correlation?. Nature reviews Gastroenterology & hepatology. 2017 Oct;14(10):573.
• Liu TC, Stappenbeck TS. Genetics and pathogenesis of inflammatory bowel disease. Annual Review of Pathology: Mechanisms of Disease. 2016 May 23;11:127-48.
• De Souza HS, Fiocchi C. Immunopathogenesis of IBD: current state of the art. Nature reviews Gastroenterology & hepatology. 2016 Jan;13(1):13.
• Davies JM, Abreu MT. The innate immune system and inflammatory bowel disease. Scandinavian Journal of Gastroenterology. 2015 Jan 2;50(1):24-33.
• Zhao M, Burisch J. Impact of genes and the environment on the pathogenesis and disease course of inflammatory bowel disease. Digestive diseases and sciences. 2019 Jul 15;64(7):1759-69.
• Knight-Sepulveda K, Kais S, Santaolalla R, Abreu MT. Diet and inflammatory bowel disease. Gastroenterology & hepatology. 2015 Aug;11(8):511.
• Lewis JD, Abreu MT. Diet as a trigger or therapy for inflammatory bowel diseases. Gastroenterology. 2017 Jan 1;152(2):398-414.
• Bernstein CN. Psychological stress and depression: risk factors for IBD?. Digestive Diseases. 2016;34(1-2):58-63.
• Bernstein CN. The brain-gut axis and stress in inflammatory bowel disease. Gastroenterology Clinics. 2017 Dec 1;46(4):839-46.
• Tontini GE, Vecchi M, Pastorelli L, Neurath MF, Neumann H. Differential diagnosis in inflammatory bowel disease colitis: state of the art and future perspectives. World journal of gastroenterology: WJG. 2015 Jan 7;21(1):21.  Ananthakrishnan AN. Epidemiology and risk factors for IBD. Nature reviews Gastroenterology & hepatology. 2015 Apr;12(4):205-17.
• Pituch-Zdanowska A, Banaszkiewicz A, Albrecht P. The role of dietary fibre in inflammatory bowel disease. Przeglad gastroenterologiczny. 2015;10(3):135.