Nghiên cứu tỷ lệ nhiễm helicobacter pylori ở bệnh nhân mày đay mạn và hiệu quả điều trị bằng phác đồ ba thuốc diệt vi khuẩn tt tiếng anh

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENCE 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES - NGUYEN THI LIEN RESEARCH ON THE PREVALENCE OF HELICOBACTER PYLORI INFECTION IN PATENTS WITH CHRONIC URTICARIA AND THE EFFECTIVENESS WITH BACTERIA ERADICATION BY TRIPLE THERAPY Speciality: Dermatology Code: 62720152 ABSTRACT OF MEDICAL PHD THESIS Hanoi – 2019 THE THESIS WAS DONE AT 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES Supervisors: Ass Prof Pham Van Linh MD, PhD Ass Prof Nguyen Tien Thinh MD, PhD Reviewers: Ass Prof Pham Thi Lan MD, PhD Ass Prof Tran Ngoc Tu MD, PhD Ass Prof Nguyen Ngoc Thuy MD, PhD This thesis will be presented at Institute Council at: 108 Institute of Clinical Medical and Pharmaceutical Sciences Day Month Year The thesis can be found at: National Library of Vietnam Library of 108 Institute of Clinical Medical and Pharmaceutical Sciences LIST OF PUBLISHED ARTICLES RELATING TO THESIS Nguyen Thi Lien, Pham Van Linh, Nguyen Tien Thinh (2018), "Study of clinical characteristics in patients with chronic urticaria infected Helicobacter pylori" Journal of Clinical Medicine and Pharmacy 108, special issue, (13) 2018, 283-289 Nguyen Thi Lien, Pham Van Linh, Nguyen Tien Thinh (2018), "Results of treatment of chronic urticaria infected Helicobacter pylori with bactericidal treatment" Journal of Clinical Medicine and Pharmacy 108, special issue, (13) 2018, 296- 301 Nguyen Thi Lien, Pham Van Linh, Nguyen Tien Thinh (2018), "Recurrence study in patients with chronic urticaria infected Helicobacter pylori after bacteria eradication treatment" Journal of Clinical Medicine and Pharmacy 108, special issue, (13) 2018, 269- 276 INTRODUCTION Chronic urticaria (CU) is a common skin disease characterized by widespread, transient wheals occurring daily or almost daily for at least weeks CU may result from several causes; hidden or overt bacterial, viral, fungal, and protozoan agents have been reported as possible initiating factors Helicobacter pylori (H pylori) is defnitely suspected in the etiopathogenesis of gastrointestinal disorders Recent epidemiological and experimental data have pointed to a strong relation of H pylori infection with the development of many extragastric diseases, such as cardiovascular, immunologic, and some skin diseases Many studies have found an etiopathogenetic link between H pylori infection and CU and possible skin improvement after its eradication Vietnam localized in the region with high rates of H pylori infection Based on the understanding of CU and H pylori, we conducted this thesis “Research on the prevalence of Helicobacter pylori infection in patients with chronic urticaria and the effectiveness with bacteria eradication by triple therapy” to further investigate the possible association The existence of a correlation between H pylori and CU may help the clinician to find more effective methods to treat people with CU The thesis has been conducted with two following purposes: Determine the prevalence of Helicobacter pylori infection in patients with chronic urticaria and clinical relevance of the disease Evaluate the effectiveness of chronic urticaria treatment in patients who infected H pylori by antihistaminic H1 combined with bacteria eradication by triple therapy Chapter OVERVIEW Urticaria is one of the most common skin diseases, and patients may present with a wide spectrum of symptoms, including sudden development of pruritic wheals or angiowheals Chronic urticaria (CU) is diagnosed when disease has been continuously or intermittently present for at least weeks The chronic and acute forms of urticarial differ in etiology, pathophysiology, and underlying mechanism Chronic urticaria has a significant impact on quality-of-life due to the constant sensation of itching, regular recurrence, and unknown etiology An estimated 15% to 23% of adults have experienced at least episode of acute urticaria at some time in their lives, and the prevalence of chronic urticaria in adults is estimated at 0.5% to 5% Previous studies have reported that chronic idiopathic urticaria is associated with infection, pseudo-allergy to a food, autoimmunity, and low serum level of vitamin D As of yet, the only reliable way to assess current disease activity is the prospective determination of symptoms over several consecutive days with the Urticaria Activity Score (UAS) The UAS works as a daily diary quantifying wheals and itching To assess the quality of life of patients with CU, expert groups recommend using the only existing specifc questionnaire, the CU-Q2oL Currently, in the process of finding out the cause of disease, international guidelines for the treatment of chronic urticarial still choose to treat symptoms with histamine H1 receptor antagonists, the second generation is the treatment firstly Effective treatment of chronic urticaria is evaluated by the Urticaria Control Test (UCT) Helicobacter pylori (H pylori) is a frequent gastrointestinal infectious agent having worldwide distribution It is a Gram- negative, microaerophilic, spiral bacterium that shows particular tropism for the gastric mucosa, and induces a strong inflammatory response with release of various bacterial and host dependent cytotoxic substances Part from its well-demonstrated role in gastroduodenal diseases, some authors have suggested a potential role of H pylori infection in several extra-intestinal pathologies including haematological, cardiovascular, autoimmune, and skin diseases In recent studies a possible association between H pylori infection and CU has been suggested In fact, in some studies CU patients showed regression of cutaneous signs and symptoms after H pylori eradication treatment Many studies on the role of H pylori in chronic urticaria have been conducted and proposed some theories to explain the relationship between H pylori infection and chronic urticaria: Firstly, some protein components of H pylori may play a role in mast cell activation causing chronic urticaria Secondly, bacteria act as full and self-allergenic antigens, causing an immune response IgG and IgA antibodies associated with 19-kDa of H pylori lipoproteins have been found to play a role in CU Thirdly, some inflammatory mediators have been released during the immune response to H pylori infection, which may play an important role in the pathogenesis of urticaria, at least to create out of nonspecific hypersensitivity of skin vessels with substances that enhance vasodilation Finally, the process of bacterial infection reduces the barrier function of the gastrointestinal mucosa, facilitating allergy food particles into the blood H pylori may also increase the amount of eosinophil cationic protein with a toxin secreted by eosinophilic activation that contributes to chronic urticaria Chapter SUBJECTS AND METHODS 2.1 SUBJECTS AND MATERIALS 2.1.1 SUBJECTS * Purpose 1: 245 patients were treated chronic urticaria (CU) in Haiphong Medical University hospital from 8/2016 to 02/2018 - Diagnostic criteria for CU: The sudden appearance of wheals and/or angiowheals A wheal consists associated itching, a fleeting nature, with the skin returning to its normal appearance, usually within 1–24 hours The symtoms are continuous or recurrent at least weeks - Diagnostic criterias for H pylori infection: + The concentration of H.pylori antigen ≥ 0.05 ug/ml are considered positive (CU/ H pylori+) + The concentration of H.pylori antigen < 0.05 ug/ml are considered negative (CU/ H pylori-) - Selection criteria for study patients: patients diagnosed with chronic urticarial, agreed to participate in the study, agreed to be tested for H.pylori infection - Exclusive criterial: The patient used medications for gastrođuoenal and H.pylori eradication within month before admission Patients with mental disorders, alcoholism, drug addiction HIV, cancer, liver failure, kidney failure, heart failure Women tho pregnant or nursing Patients who did not agree to participate in the research * Purpose 2: 76 patients CU/H pylori+ eradicated - Selection criteria for study patients: patients with chronic urticarial infected H.pylori who bactericidal treatment The patient had not malignancy symptoms of gastrointestinal; no contraindication to use of drug Age ≥ 18 Patients agree to participate and follow the treatment process properly - Exclusive criterial: Patients not qualify for selection Patients not agree to participate in the study 2.1.2 MATERIALS - Chemicals: HpAg kit of Dia.Pro Diagnostic, Italy - Study devices: ELISA system, USA - Drugs: Xyzal 5mg (Switzerland) Nexium MUPs 40mg (Sweden) Ospamox 500mg (Sandoz-Imexpharm) Klacid 500mg (Abbott) 2.2 METHODS 2.2.1 Study Design: prospective, interventional, follow-up 2.2.2 Sample size of Study - Purpose 1: Convenient sampling From 8/2016 to 02/2018, 245 patients with chronic urticaria treated at Hai Phong Medical University Hospital, responding selection and exclusion criteria - Purpose Of 245 chronic urticarial patients, 76 patients were CU/H pylori+ eradicated 2.3 Techniques and assessment standards 2.3.1 ELISA technique identified H pylori antigen in stool (Stool antigen assay - SAT) * Prepare specimen Thaw the specimen at room temperature (4 hours) Prepare sets of tubes each with the ID samples add ml of diluent to each tube Take about 0.2 g of each sample into each tubes (weigh the tube before and after) Votex for minute, then centrifuge for 3000 cycles/3 minutes), transfer the solution to the second tube, centrifuge for 3000 cyclce/3 minutes then take 100µl suspension for testing * Assay procedure Place the required number of strips in the plastic holder and carefully identify the wells for calibrators and samples Leave A1+B1 wells empty for blanking purposes Pipette 100 µl Calibrators in duplicate into the calibration wells (see the example of dispensation reported below) Dispense then 100 µl Enzymatic Conjugate in all wells, except for A1+B1, used for blanking operations Following addition of the conjugate, incubate the microplate for 120 at +37°C When the first incubation is over, wash the microwells as previously described Pipette 200 µl Chromogen/Substrate into all the wells, A1+B1 included Incubate the microplate protected from light at room temperature (18-24°C) for 20 Pipette 100 µl Sulphuric Acid into all the wells to stop the enzymatic reaction * Calculation of results Calculate the mean OD450nm value of the calibrators Then draw a calibration curve possibly using a parameters fitting curve system Then calculate on the curve the concentration of H.pylori antigen in the sample Samples showing a concentration of H.pylori antigen ≥ 0.05 ug/ml are considered positive 2.3.2 Evaluation criteria - Assess the level of disease activity with UAS (urticaria activity score) score For evaluation of symptoms of pruritus and irritation, calculate the activity score of urticaria The lowest total score is 0, the highest is points - Evaluate the effect of disease on the quality of patients' life with Chronic Urticaria Quality of Life Questionnaire/CU-Q2oL The question set has 23 sentences with the rule of assessing the lowest point of (not at all), the highest score is (a lot) The minimum CUQ2oL score is at least 23 and the maximum is 115 The higher the average score corresponds to the lower the quality of life - Assess the level of disease control: with the Urticaria Control Test - UCT The UCT score of 12 or greater indicates controlled disease Values of 11 and lower reflect poor control - Evaluate H pylori infection: The concentration of H.pylori antigen ≥ 0.05 ug/ml are considered positive (CU/ H pylori+) The concentration of H.pylori antigen < 0.05 ug/ml are considered negative (CU/ H pylori-) - Assessment response to H.pylori eradication treatment: In group CU/ H.pylori+ qualifies for bactericidal treatment, at weeks after cessation of bacteriostatic treatment, re-test for H pylori antigen in the stool Samples showing a concentration of H.pylori antigen < 0.05 ug/ml are negatives: Diagnostic CU/H.pylori+ eradicated Samples showing a concentration of H.pylori antigen ≥ 0.05 ug/ml are positives: Diagnostic CU/H.pylori+ noteradicated - Side effects: Record whether or not side effects and assess the level 2.4 Study procedure 2.4.1 Screening, selecting patients: Explain the objectives and procedure to conduct research with the patients if the patient agrees to sign the study agreement 10 Study design 245 Chonic Uticaria (CU) 159 CU/ H pylori + Hp-Ag/Stool 107 CU/ H pylori +, Treatment - XYZAL x weeks - H pylori eradication treatment: use triple regimens x 10 days After weeks of H.pylori eradication treatment Hp-Ag/Stool 76 CU/H pylori+ eradicated 31 CU/H pylori+ not-eradicated After weeks, weeks of treatment: Assesses  Pruritus score, wheals score, UAS score  Score CU-Q2oL After cessation weeks, month, month, month: Assesses  UCT score  Rate of re-using antihistamin H1 86 CU/ H pylori - 86 CU/ H pylori Treatment - XYZAL x weeks 11 Chapter RESULTS 3.1 Determine the rate of Helicobacter pylori infection in patients with chronic urticaria and clinical relevance of the disease From 8/2016 to 02/2018, there were 245 patients with chronic urticaria meeting inclusion criteria Testing for bacterial antigens in the feces found the prevalence of H pylori infection as follows Table 1: The rate of H pylori infection in chronic urticaria Patients N % H pylori infection 159 64,9 H pylori Not-infection 86 35,1 Total 245 100 Conclusion: The rate chronic urticaria infected H pylori (CU/H pylori+ ) is 64,9% Table 2: Relationship between H pylori infection and the duration of symptoms CU/H pylori+ Patients (n=159) Time n % < hour 20 12,6 CU/H pylori(n= 86) n % Total n % 2,3 22 9,0 P < 0,01 hour-6 hours 38 23,9 39 45,4 77 31,4 < 0,01 > hours 101 63,5 45 52,3 146 59,6 < 0,01 Conclusion: 59,6% of patients had a duration time of wheals and pruritus lasting> hours Rate of CU/H.pylori+ has a long 12 duration of wheals and pruritus > hours greater than the CU/H pylori- group (p