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6MEDICAL SCIENCES
УДК 616.34-002.157-07-08-092
Honcharuk L.M
PhD in Medical Sciences, Associate Professor Department of Internal Medicine Bukovinian State Medical University;
Piddubna A.A.
PhD in Medical Sciences, Associate Professor Department of Clinical Immunology, allergology and endocrinology Bukovinian State Medical University;
Piddubna A.A.
PhD in Medical Sciences, Associate Professor Department of Clinical Immunology, allergology and endocrinology Bukovinian State Medical University;
Andrushchak M. PhD in Medical Sciences, Associate Professor Bukovinian State Medical University;
Hulin I.
6th year student of 20 group Bukovinian State Medical University;
Hrentsner D. 6th year student of 20 group Bukovinian State Medical University; DOI: 10.24412/2520-6990-2023-9168-48-50 SOME ASPECTS OF PATHOGENESIS, CLINIC AND TREATMENT OF CROHN'S DISEASE
Abstract.
In modern conditions, the prevalence of diseases of the large intestine continues to grow, which is caused by constant stress, late referral due to fear and the inconvenience of discussing clinical symptoms and masking the clinic with extraintestinal manifestations. Crohn's disease is one of the most common chronic inflammatory bowel diseases. Given the severity of the course, the frequency of serious complications and disability, this pathology is an important social problem. The article provides a review of modern literature related to the pathomorphological changes of transmural lesions in Crohn's disease. Features of the classic course and extraintestinal manifestations of Crohn's disease are highlighted. Special attention is paid to pharmacotherapeutic methods of treatment from the standpoint of evidence-based medicine.
Key words: Crohn's disease, pathomorphology, clinic, treatment.
Crohn's disease (CD) is a chronic recurrent disease of the gastrointestinal tract of unknown etiology, manifested by transmural segmental granulomatous inflammation mainly of the small and upper parts of the large intestine, with the development of local and systemic complications [1]. This disease was first described by L. Ginzberg and G.D. Oppenheimer in 1932, later it was described by the American doctor V. Srohn (18841983), under whose name she entered the practice. In many countries of the world, there is a trend towards an increase in the incidence of CD. Data on the prevalence of CD in different countries of the world are ambiguous and indicate the frequency of the disease from 10 to 150 cases per 100,000 population, and such discrepancies are due to the difficulties of diagnosing the disease, especially before the appearance of complications, often the non-specificity of clinical manifestations, the lack of specific instrumental and laboratory methods research for the purpose of its diagnosis [2].
CD begins with inflammation of the crypts and the formation of abscesses, which then progress to the formation of small individual aphthoid ulcers. In the future, changes on the part of the mucous membrane can take the form of deep slit-like longitudinal and transverse ulcers, with areas of swelling of the mucous membrane, which gives it a characteristic "cobblestone" appearance.
Transmural spread of inflammatory changes is accompanied by lymphostasis, thickening of the intestinal wall and mesentery. Mesenteric fat spreads to the serous membrane of the intestine. Mesenteric lymph nodes may enlarge. Widespread inflammation can lead to thickening of the muscular plate of the mucous membrane, fibrosis and the development of strictures, which provokes intestinal obstruction. Abscesses and fistulas often develop, spreading to the surrounding organs - intestinal loops, bladder, lumbar muscle. Fistulas can open on the surface of the skin of the anterior abdominal wall and the lateral parts of the abdomen. Re-
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gardless of the degree of intraperitoneal disease activity, perianal fistulas and abscesses form in 25-33% of cases; these complications are often the most uncomfortable manifestations of Crohn's disease.
Non-caseous granulomas can be found in the lymph nodes, peritoneum, liver and all layers of the intestinal wall. Such granulomas are very pathognomonic, but in half of patients with Crohn's disease, they cannot be detected. Of course, the presence of granulomas is related to the patterns of the course of the disease. Areas of the affected intestine are intermittently and sharply demarcated from adjacent normal intestinal tissues (so-called unaffected segments), which is why it is called regional enteritis.
In approximately 35% of cases, Crohn's disease affects only the ileum (ileitis). In some cases, the entire small intestine is affected (jejunoileitis). Clinical signs of damage to the stomach, duodenum and esophagus are very rare, although microscopic signs of the disease are often detected in an antral biopsy, especially at a younger age. In the absence of surgical intervention, inflammation almost always spreads to areas of the small intestine. About 45% are lesions of the ileum and colon (or ileocolitis), with the predominant lesion of the right half of the colon. About 20% are lesions of only the colon (granulomatous colitis), most of which, unlike ulcerative colitis, do not affect the rectum [3].
At the moment, the etiology of CD is not completely known. According to the main theory, this is related to the development of a pathological reaction of the immune system to the intestinal flora and to food residues that enter the intestines. The autoimmune theory of the development of the pathology is considered
- antibodies are formed against intestinal tissues, which are defined as foreign, accordingly, a large number of leukocytes appear in this area. This leads to inflammation, the appearance of ulcers and erosions in the intestinal tract. Provocative factors are distinguished: predisposition at the genetic level; tendency to allergic manifestations; excessive smoking, alcohol consumption; frequent intake of medicines; adverse ecology.
CD has a chronic, multi-year course, periods of exacerbations and remissions usually alternate, but often the symptoms are observed constantly and cause significant disability and the need for surgical operations due to complications of the disease (60% of patients after 10 years); relapses after surgical treatment
— up to 70%.
Clinical picture of CD - general, intestinal and extraintestinal symptoms. General non-specific symptoms - weakness, rapid fatigue, lethargy, a slight increase in temperature, often of a wave-like nature.
Intestinal manifestations:
• frequent, constant abdominal pain, pain during defecation;
• nausea and vomiting;
• flatulence;
• diarrhea from 2-3 to 8-10 times a day. Feces may contain pus, blood, mucus;
• weight loss.
Extraintestinal manifestations. Skin manifestations. According to scientists, the prevalence of skin
manifestations in inflammatory bowel diseases among people aged 20-40 years is up to 40% [4,5]. The development of skin symptoms is associated with certain types of HLA antigens, namely HLADRB1*0103, HLA-B*27 and HLA-B*58, as well as with the TRAF3IP2 gene. The most frequent skin manifestations are erythema nodosum, gangrenous pyoderma [6].
Lesions of the locomotor system. They are characterized by minor joint damage or its absence. They are manifested by seronegative arthralgia or arthritis, which are noted in 10-20% of cases in people with CD. In patients with Crohn's disease and ankylosing spon-dylitis, the HLA-B27 antigen is determined in 25-75% of cases [7].
Ophthalmological manifestations. Damage to the organ of vision is in third place among extraintestinal manifestations. The most common visual manifestations are anterior uveitis and episcleritis, while scleritis, intermediate and posterior uveitis are extremely rare. Episcleritis is usually manifested by painless redness of the sclera and conjunctiva, as well as itching and a burning sensation. Uveitis is accompanied by more severe manifestations, such as headache and eye pain, photophobia, blurred vision [6,8].
Damage to the oral cavity. The oral cavity is often involved in the pathological inflammatory process. 10% of patients have periodontitis, aphthous stomatitis, and in more severe cases, vegetative pyostomatitis. Aphthous lesions are usually located on the mucous membrane of the lips and cheeks, but may also be present on the tongue and in the oropharyngeal region. Vegetative pyostomatitis is manifested by multiple pustular, sometimes hemorrhagic, rashes on any areas of the mucous membrane of the oral cavity, which have the appearance of "cobblestones" [6,9].
Treatment of CD. The first-line drugs are 5-ami-nosalicylates (5-ASA). Mesalazine is usually the drug of choice. With a severe refractory course, mesalazine is combined with its use in microenemas. Regular intake of 5-ASA drugs reduces the risk of developing colorectal cancer. Glucocorticoids (budenofalk) are used in combination with mesalazine in the absence of an effect from treatment with 5-ASA drugs and in severe forms of chronic inflammatory bowel diseases. When using budenofalk, the frequency of side effects characteristic of corticosteroids decreases, while the effectiveness of budenofalk in active forms of CD reaches 5370%, but depends on the localization of the process. Therapy with 5-ASA drugs and glucocorticosteroids in CD is insufficiently effective in 20-25% of cases. In such cases, immunosuppressants are prescribed. Antibacterial therapy - prescribed taking into account the microbiological examination of the intestinal contents, prevents the activation of opportunistic flora and the occurrence of sepsis [10].
Referenses.
1. Didnass A. For the European Crohn's Colitis Organisation - ECCO. The second European evidence based consensus on the diagnostic and management of Crohn's disease: current management / A. Didnass, G. Van Assche, J. Lindsay // JCC. - 2010. - Vol. 4. - P. 28-62.
2. Mishchuk V. V. Efektyvnist mikrohranuliarnoi formy 5-aminosalitsylovoi kysloty v pisliaoperatsiinomu periodi uskladnenoi khvoroby Krona / V.V. Mishchuk // Shpytalna khirurhiia. Zhurnal imeni L. Ya. Kovalchuka. - 2016. - № 4. - S.68-71.
3. Lichtenstein GR. ACG Clinical Guideline: Management of Crohn's Disease in Adults / EV Loftus, KL Isaacs, MD Regueiro, LB Gerson, BE. Sands // Am J Gastroenterol. - 2018. -Apr;113(4). - P. 481-517.
4. Chavez-Álvarez S. Cutaneous manifestations in inflammatory bowel disease / Chavez-Álvarez S., Gómez-Flores M., OcampoCandiani J. //Gac Med Mex. - 2016. - 152(5). - P.622-630.
5. Vavricka S. R. Frequency and risk factors for extraintestinal manifestations in the Swiss inflammatory bowel disease cohort / S. R. Vavricka, L.Brun, P. Ballabeni, V. Pittet, et.al. //American Journal of Gastroenterology. - 2011. - 106(1). -P.110-119.
6. Uvarova K. H. Pozakyshkovi proiavy zapalnykh zakhvoriuvan kyshechnyka / K.H. Uvarova
// Aktualni problemy suchasnoi medytsyny. - 2020. -Vypusk 5. - S.63-73.
7. Vavricka S. R. Extraintestinal manifestations of inflammatory bowel disease / S. R. Vavricka, A.Schoepfer, M. Scharl, P.L.Lakatos, et al.// Inflammatory bowel diseases. - 2015. - 21(8). - P.1982-1992.
8. Annese V. A Review of extraintestinal manifestations and complications of inflammatory bowel disease / V. A. Annese //Saudi journal of medicine & medical sciences. - 2019. - 7 (2). - P.66-73.
9. Lankarani K. B. Oral manifestation in inflammatory bowel disease: a review / K. B. Lankarani, G. R. Sivandzadeh, S. Hassanpour //World journal of gastroenterology: WJG. - 2013. - 19 (46). -Pro8571.
10. National Institute for Health and Care Excellence (2019) Crohn's disease: management. NICE guideline [NG129].
УДК 616.342-002-036.1-085.262.1-092
Honcharuk L.M
PhD in Medical Sciences, Associate Professor Department of Internal Medicine Bukovinian State Medical University;
Piddubna A.A.
PhD in Medical Sciences, Associate Professor Department of Clinical Immunology, allergology and endocrinology Bukovinian State Medical University;
Andrushchak M. PhD in Medical Sciences, Associate Professor Bukovinian State Medical University;
Kulchytska V.
6th year student of 20 group Bukovinian State Medical University;
Vilkhovetska V. 6th year student of 20 group Bukovinian State Medical University; DOI: 10.24412/2520-6990-2023-9168-50-52 SOME ASPECTS OF THE PATHOGENESIS OF GASTRODUODENOPATHY ASSOCIATED WITH NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
Abstract.
Nonsteroidal anti-inflammatory drugs have a wide spectrum of therapeutic action, uniquely combining antiinflammatory, analgesic, antipyretic and antithrombotic effects, influencing the processes of neogenesis, cell adhesion and apoptosis. That is why NSAIDs are the most widely used drugs in medicine. Every year, 500 million prescriptions for these drugs are written in the world, about 30 million people take them every day, 2/3 ofpatients - without a prescription and medical supervision. NSAID-induced gastroduodenopathy develops when NSAIDs are taken at a dose that inhibits prostaglandin production and increases gastric motility, causing increased mucosal permeability, neutrophil infiltration, and free radical formation, which ultimately leads to gastric damage.
Key words: gastropathies, nonsteroidal anti-inflammatory drugs, pathogenesis
The therapeutic and side effects of non-steroidal anti-inflammatory drugs (NSAIDs) are provided by the pathogenetic mechanism of inhibiting the activity of the enzyme cyclooxygenase (COX) in the metabolism of arachidonic acid, as a result of which the synthesis of prostaglandins (PG) decreases. To date, two
isoforms of cyclooxygenase have been identified -COX-1 and COX-2. The COX-1 enzyme is constantly present in the alimentary canal (AC), kidneys, platelets and ensures the synthesis of thromboxane A2, PG E2 and prostacyclin, which have a cytoprotective effect. Under physiological conditions, COX-2 is localized in
