Helicobacter Pylori Treatment and Rosacea

Helicobacter Pylori interposition and acne acne acne acne acne acne rosaceaRunning title Helicobacter Pylori Treatment and rosaceaParviz Saleh1, Mohammad Naghavi-Behzad2, Hamdieh Herizchi3, Fatemeh Mokhtari3, Mohammad Mirza-Aghazadeh-Attari2 , Reza Piri4*1- Chronic Kidney Diseases Research Center, Tabriz University of aesculapian Sciences, Tabriz, Iran2- Students Research delegacy, Tabriz University of Medical Sciences, Tabriz, Iran3-Department of dermatology, Tabriz University of Medical Sciences, Tabriz, Iran4- Medical Philosophy and History Research Center, Tabriz University of Medical Sciences, Tabriz, IranEffects of Helicobacter pylori Treatment on Rosacea a Single Arm Clinical Trial removeAbstractRosacea is a chronic dermatologic disease. Helicobacter pylori has been discussed as unrivaled of its causative circumstanceors. In this clinical visitation development, it was tried to appraise the rig of H. pylori standard annihilation protocol on the rosacea clinic al course. In this single-arm clinical foot race, patients with approved H. pylori transmitting based on serological studies were assessed to watch rosacea existence. Then, the patients with concurrent rosacea and H. pylori transmitting were included in the flying field and underwent a standard Helicobacter pylori annihilation therapy. Rosacea was evaluated using Duluth rosacea place soft touch at beginning, 2 months later, and at the end of the trial (day 180). Of 872 patients with positively charged degree H. pylori, 167 patients (19.15%) manifested the clinical features of rosacea. The patients with concurrent rosacea were younger (pKeywords Rosacea, Helicobacter pylori, Prevalence, Eradication, TreatmentEffects of Helicobacter pylori Treatment on RosaceaIntroductionRosacea is a chronic dermatological disorder mostly affects facial convexities, which is characterized by telangiectasia, flushing and papulopustular changes (1, 2). These findings tend to be in cluster patt erns, which exclusivelyow identification of varied subgroups of patients. In former(a) words, rosacea includes a wide spectrum of dermatological manifestations with different severities (3-5). Pathogenesis of rosacea is thought be related to vascular changes, only the main process of pathogenesis for rosacea is tranquilize undiscovered. A combination of dermal connective tissue damage and vascular dysfunction consisting endothelial damage, impaired reactivity, and autonomic dysfunction has been proposed (5-9). So researchers adjudge always tried to reveal the pathophysiology process by proposing possible morbific factors much(prenominal) as solar irradiation, sensitivity to noxious stimuli, change in redox status, and the presence of parasitic mites (Demodex folliculorum) (10-14).The division of Helicobacter pylori related gastritis in the pathogenesis of rosacea has been in addition a subject of controversy. Diverse preponderance of H. pylori transmission has been desc ribe among rosacea patients (15-21), ranging from zero to 100%. Some studies arrive at suggested that rosacea could be considered as an extra-gastric symptom of H. pylori infection or reported improved rosacea clinical course post H. pylori annihilation (22) (23), while others cogitate no strong relationship amidst H. pylori infection and rosacea (24, 25). ground on our literature review, no footsure and precise conclusion has been do closely any change in the clinical course of rosacea subsequently H. pylori eradication yet today. So the present clinical trial aimed to evaluate changes in the clinical course of rosacea after H. pylori eradication by standard discourse protocol.Subjects and MethodsStudy designIn this single-arm clinical trial which was conducted in clinical-educational centers of Tabriz University of Medical Sciences (Tabriz, Iran) from May 2013 to November 2015, patients with proved H. pylori infection based on serological matter were screened for evalu ation of concurrent rosacea disease. Then, the patients with concurrent rosacea clinical presentation and H. pylori infection were enrolled into the turn over. Considering savour number limitation, sampling was performed during a year to calculate sample size, then study power was calculated 0.85 according to that number of samples. Rosacea severity was graded using Duluth rosacea grading hold (26) before and after H. pylori eradication protocol. Fin everyy, the patients were figured 2 and 6 months after medication, to comp ar dermatological findings of rosacea with pristine findings. All participants were countenanced an informed written consent, and the study protocol was in compliance with the Helsinki resolve and was approved by the Ethics Committee of Tabriz University of Medical Sciences. In either stages of study patients information were anonymous and based on codes and patients could refuse to defer part in the study at any stage. This study is registered at Iran ian Registry of Clinical Trials (IRCT20cl51418946N3).Study populationAll patients who were 20-65 historic period old, with realizeed H. pylori infection and active rosacea, attending clinical-educational centers of TUMS were included in the study. previous H. pylori eradication treatment, the existence of any other dermatologic problem, all(a)ergy to clarithromycin or omeprazole, antibiotic therapy inwardly gone 2 months, topical treatment of rosacea in past 3 weeks, history of hospitalization in past 6 months, pregnancy and breastfeeding, patients were considered as exclusion criteria of the study.H. pylori infection evaluation H. pylori smoke antigen test was implicated to confirm H. pylori infection before enrolling the patients into this study (day 0) and to confirm H. pylori eradication (day 60). Stool samples were collected in a standard container. In the laboratory, using an applicator stick 4-5 mm of feces was transferred in a diluent vial, then it was vortexed for 20 s econds. Then, 4 drops of vial were dispensed in ImmunoCard STAT HpSA kit (Meridian Diagnostics, Inc., OH, USA) positive predictive value of this test was 89.3% based on literature (27). The positive and negative results were reason out based on the manufacturers recommendation.Rosacea evaluationRosacea severity was evaluated using Duluth rosacea grading score (26) at beginning (day 0), 2 months later (day 60), and at end of the trial (day 180). Dermatology team examined rosacea based on detecting primary and junior-grade signs and symptoms of rosacea and graded them as absent, mild, mode respect, or severe (0-3), based on the Duluth scoring frame. Primary features of rosacea included flushing (transient erythema), non-transient erythema, papules and pustules, telangiectasia. Secondary features included glowing or stinging, plaques, dry appearance, edema, visual manifestations, computer peripheral location (present or absent), phymatous changes. Finally, rosacea condition was analysed in day 0, day 60, and day 180 by the same team.H. pylori treatmentStandard two-week triple therapy was administered to eradicate H. pylori, including metronidazole cholecalciferol mg orally doubly per day, clarithromycin 500 mg orally twice per day, and pantoprazole 40 mg orally per day.Primary and substitute solventsThe primary outcome was the severity of rosacea before and after H. Pylori eradication. Secondary outcomes were H. Pylori eradication rate and prevalence of rosacea among patients with H. Pylori and demographic differences between H. Pylori positive patients with rosacea and without rosacea.demographic and outcome measurementAll demographic information was collected at patients enrollment time. Patients rosacea stage was evaluated on day 0, 60, and 180, then they were comp bed. resembling dermatology team reevaluated clinical course of rosacea to decrease inter-observer error.statistical methodsStatistical analysis was performed by SPSS software package, v ersion 16.0, for windows (SPSS Inc.). Quantitative selective information are presented as mean standard deviation (SD), while qualitative data are demonstrated as frequency and percent (%). Paired sample t-test, chi-square, and Friedman test were used for analysis of data. Mann-Whitney U test was used to compare between groups and Wilcoxon ranked sum test was used to compare within groups. Probable confounding factors were considered as inclusion and exclusion criteria. However, some factors which could commence been confounding factors were analyzed using multivariate analysis but they were non presented in results the section. P value less than 0.05 was considered statistically probatory. Normal dissemination of data was assessed using Kolmogorov-Smirnov test.ResultsIn the present study 872 patients with positive H. pylori stool antigen were assessed by dermatologists team. Of 872 patients, 167 patients had clinical features of rosacea. Some demographic information about pati ents is shown in Table 1 of all patients with a positive test for H. pylori, patients diagnosed with rosacea had lower ages (p0.001) and the difference in sex composition was also statistically significant (p=0.034) in this conclusion, multivariate analysis was used. Based on the results, rosacea prevalence among patients with positive H. pylori stool antigen was 19.15% (167/875).Of 167 patients with positive H. pylori stool antigen and rosacea, 17 patients jilted to take part in the study while 150 patients agreed. Of 150 patients who underwent H.pylori eradication therapy, 138 (92%) had negative H. pylori stool antigen (successful treatment) at the end of the trial. Rosacea Duluth score at day 0, 60 and 180 was 15.554.34, 14.113.96 and 12.573.62, respectively the differences between all stages were statistically significant (pBased on Wilcoxon signed-rank test, comparison of primary and supplementary features of rosacea between stages of study is shown in table 3 Of secondary r osacea features, burning or stinging, plaques, dry appearance edema and ocular manifestations the difference between two stages of study were mostly significant but the differences for peripheral involvement and phymatous change were mostly non statistically significant. give-and-takeRosacea as a chronic dermatological disease, with an almost unknown pathogenesis process so far, has been the subject of many studies. One of the proposed pathogenic processes attributed to rosacea is gastric infection with H. pylori, so many researchers have tried to examine this sleeper by trying to investigate the correlation between H. pylori infection and rosacea or by observing changes of rosacea after H. pylori eradication. Based in the present study, Prevalence of rosacea among H. Pylori positive patients was 19.15% in this study, which seems as twice as the highest reported rate in other populations, ranging from 1-10% (2, 28-31). This different has been correlated to various variables includ ing race, culture and diet of these. In a study by Argenziano et al. potential association between rosacea and serological tell of H. pylori infection was investigated and they concluded that there is a significant association between rosacea and H. pylori infection (32), while Abram et al. evaluated several suspected risk factors for rosacea and concluded that there was no statistically significant differences between rosacea patients and those of control group (33).Patients with rosacea and H. pylori infection had female gender predominance and lower age in comparison to those suffering only H. pylori infection. H. pylori curative rate after routine triple therapy was 92%. During 6 months of implement, H. pylori eradication among those who had rosacea and H. pylori infection led to a significant progress in rosacea condition based on Duluth score grading. There was a significant decrease in intensity of almost all primary and secondary criteria except phymatous changes, telang iectasia, and peripheral involvement this difference in phymatous changes, telangiectasia, and peripheral involvement index be due to the more time winning nature of these criteria to be resolved. Based on the literature, diverse conclusions have been made regarding rosacea resolution after H. pylori eradication. In a study by Szlachcic et al. investigating the link between Helicobacter pylori infection and rosacea, it was concluded that after H. pylori eradication therapy among patients with rosacea and H. pylori infection, H. pylori cure rate was 97%, and in 85% of patients the symptoms of rosacea rock-bottom markedly or disappeared within 2-4 weeks (22) although H. pylori cure rate in the present study is less than that reported in this study, the violence of H. pylori eradication on rosacea is similar in both of the studies. In some other study conducted by Rojo et al. on the role of H. pylori in rosacea and chronic urticarial, it was concluded that H. pylori eradication le d to a significant benefit both in rosacea (75.6%) and urticarial (85.7%) when compared with control group (22%) in 4 weeks (34) results of that study is similar to what was concluded in the present study, although no precise description of clinical features of rosacea was presented after treatment.On the hand, Bamford et al. in a study investigating effect of treatment of H. pylori infection on rosacea concluded that rosacea was significantly improved after H. pylori eradication, although this improvement was also significant in control group, the difference between the improvement of rosacea was not statistically significant between intervention and control group (35) this fact that both groups had significant improvement in rosacea totally undermined the association of H. pylori infection and rosacea which was concluded in the present study, also in this article the improvement was attributed to probable placebo effect. In another study by Herr et al. relationship between H. py lori and rosacea was examined by evaluating the response of patients with rosacea to H. pylori eradication, and they concluded that there was no statistically significant change in rosacea condition both in intervention and control group, although papulopustules had significantly decreased in intervention group comparing baseline and follow-up (36), which is the only improvement detected after H. pylori eradication in this study, but in the present study besides improvement of papulopustules, almost all the other clinical manifestations of rosacea had improved.In a study by El-khalawany evaluating the effect of H. pylori eradication in rosacea subtypes it was concluded that H. pylori eradication led to a significant improvement in rosacea, where papulopustular subtype improved significantly more than erythematotelangiectatic subtype (37) these results are similar to the results of present study, since in the present study almost all clinical manifestations of rosacea had decreased w hile no statistically significant change was shown about telangiectasia.According to the mentioned literature, different conclusions have been derived from studies about the energy of H. pylori eradication in rosacea treatment ranging from significant improvement in rosacea (22) or significant improvement between baseline and follow-up but not when compared to control group (35) to no significant improvement in rosacea. One of the reasons which might be responsible for these diverse conclusions is multifactorial nature of rosacea where ethnic group, bacterial subtypes or genetics might be other confounding factors.One of the main limitations of this study was leave out of control group, so it might have affected this study to stay fresh coming to a precise and confident conclusion, also this might have led to undermining probable placebo effect of administered treatment. The main thought behind not including a control group was not willing to deprive patients of H. pylori treatme nt where their H. pylori infection had already been proved. Another factor which could have resulted in a more precise and reliable conclusion was including possible confounding factors such as gender, ethnic groups, and occupational environment status and analyzing rosacea improvement while taking confounding factors into account.In conclusion, the present study indicated that prevalence of rosacea among patients with H. pylori infections is slightly more than what literature attribute to different populations, it also showed a statistically significant improvement in rosacea when Duluth pull ahead were compared between baseline and follow-up. Considering the present controversy about the association of H. pylori infection and rosacea, it is suggested that further clinical trials considering multifactorial nature of rosacea take all possible confounding factors into account, also as far as rosacea is a dermatological condition with different manifestations, recognition of alterati ons in the dermatological pattern of rosacea might lead to a more confident conclusion.AcknowledgmentsThis Study was supported by Tabriz University of Medical Sciences.Conflict of InterestsNo betrothal of interests are declaredReferences1.Plewig G, Kligman A M. Acne and rosacea Springer Science transaction Media 2012.2.Powell F C. Rosacea. novel England daybook of Medicine 2005 352 793-803.3.Tan J, BlumePeytavi U, Ortonne J, et al. An observational cross sectional survey of rosacea clinical associations and progression between subtypes. British ledger of Dermatology 2013 169 555-562.4.Tan J, Berg M. 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Demographic information about patients with positive H. pylori stool antigen (%)VariablesPatients with*P value+ HPA without rosacea (N=705)+HPA with rosacea (N=167)Age (years old)54.3810.7143.219.84 gender337 (47.81%) female,368 (52.19%) male95 (56.89%) female,72 (43.11%) male0.03Marital statusSingle, split or widowed (643(91.2%)), matrimonial (62(8.8%))Single, Divorced or widowed (145 (86.82%)),Married (22 (13.18%))0.1+HPA Positive H. pylori antigen* U Mann-Whitney test was used.**Data are shown as immoral Standard Deviation and number (%)Table 2. Rosacea Duluth grading of patients at day 0, 60 and 180 of trial (N=138)*.Variables twenty-four hours 0 **Day 60**Day 180**P valuePrimary FeaturesFlushing2.28 0.712.02 0.511.82 0.52Non-transient erythema2.34 0.541.9 0.641.42 0.72Papules and pustules1.8 0.591.71 0.511.58 0.52Telangiectasia1.78 0.931.72 0.671.74 0.84