Helicobacter Pylori Treatment and Rosacea

Running title: Helicobacter Pylori Treatment and Rosacea

Parviz Saleh1, Mohammad Naghavi-Behzad2, Hamdieh Herizchi3, Fatemeh Mokhtari3, Mohammad Mirza-Aghazadeh-Attari2 , Reza Piri4*

1- Chronic Kidney Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

2- Students’ Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

3-Department of dermatology, Tabriz University of Medical Sciences, Tabriz, Iran

4- Medical Philosophy and History Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Effects of Helicobacter pylori Treatment on Rosacea: a Single Arm Clinical Trial Study

Abstract:

Rosacea is a chronic dermatologic disease. Helicobacter pylori has been discussed as one of its causative factors. In this clinical trial study, it was tried to evaluate the effect of H. pylori standard eradication protocol on the rosacea clinical course. In this single-arm clinical trial, patients with approved H. pylori infection based on serological studies were assessed to examine rosacea existence. Then, the patients with concurrent rosacea and H. pylori infection were included in the study and underwent a standard Helicobacter pylori eradication therapy. Rosacea was evaluated using Duluth rosacea grading score at beginning, 2 months later, and at the end of the trial (day 180). Of 872 patients with positive H. pylori, 167 patients (19.15%) manifested the clinical features of rosacea. The patients with concurrent rosacea were younger (p<0.001) and female gender predominance (p=0.03), when compared to rosacea free patients. Of 167 patients, 150 patients were received H. pylori eradication therapy, demonstrating 92% (138/150) cure rate. The Rosacea Duluth score grading on day 0, 60, and 180 among 138 patients significantly decreased in most of the criteria except for telangiectasias (P=0.712), phymatous changes (P=0.535), and the existence of peripheral involvement (P=0.431). The present study concluded that H. pylori eradication leads to improvement of rosacea.

Keywords: Rosacea, Helicobacter pylori, Prevalence, Eradication, Treatment

Effects of Helicobacter pylori Treatment on Rosacea

Introduction:

Rosacea 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 patterns, which allow identification of different subgroups of patients. In other words, rosacea includes a wide spectrum of dermatological manifestations with different severities (3-5). Pathogenesis of rosacea is thought be related to vascular changes, but the main process of pathogenesis for rosacea is still unknown. 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 have always tried to reveal the pathophysiology process by proposing possible pathogenic factors such as solar irradiation, sensitivity to noxious stimuli, change in redox status, and the presence of parasitic mites (Demodex folliculorum) (10-14).

The role of Helicobacter pylori related gastritis in the pathogenesis of rosacea has been also a subject of controversy. Diverse prevalence of H. pylori infection has been reported among rosacea patients (15-21), ranging from zero to 100%. Some studies have suggested that rosacea could be considered as an extra-gastric symptom of H. pylori infection or reported improved rosacea clinical course post H. pylori eradication (22) (23), while others concluded no significant relationship between H. pylori infection and rosacea (24, 25). Based on our literature review, no confident and precise conclusion has been made about any change in the clinical course of rosacea after 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 treatment protocol.

Subjects and Methods

Study design

In 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 study were screened for evaluation of concurrent rosacea disease. Then, the patients with concurrent rosacea clinical presentation and H. pylori infection were enrolled into the study. Considering sample 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 score (26) before and after H. pylori eradication protocol. Finally, the patients were examined 2 and 6 months after medication, to compare dermatological findings of rosacea with primary findings. All participants were provided an informed written consent, and the study protocol was in compliance with the Helsinki Declaration and was approved by the Ethics Committee of Tabriz University of Medical Sciences. In all stages of study patient’s information were anonymous and based on codes and patients could refuse to take part in the study at any stage. This study is registered at Iranian Registry of Clinical Trials (IRCT2015051418946N3).

Study population

All patients who were 20-65 years old, with confirmed H. pylori infection and active rosacea, attending clinical-educational centers of TUMS were included in the study. Prior H. pylori eradication treatment, the existence of any other dermatologic problem, allergy to clarithromycin or omeprazole, antibiotic therapy within past 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 stool 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 stool was transferred in a diluent vial, then it was vortexed for 20 seconds. 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 concluded based on the manufacturer’s recommendation.

Rosacea evaluation

Rosacea 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 secondary signs and symptoms of rosacea and graded them as absent, mild, moderate, or severe (0-3), based on the Duluth scoring system. Primary features of rosacea included: flushing (transient erythema), non-transient erythema, papules and pustules, telangiectasia. Secondary features included: burning or stinging, plaques, dry appearance, edema, ocular manifestations, peripheral location (present or absent), phymatous changes. Finally, rosacea condition was compared in day 0, day 60, and day 180 by the same team.

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H. pylori treatment

Standard two-week triple therapy was administered to eradicate H. pylori, including metronidazole 500 mg orally twice per day, clarithromycin 500 mg orally twice per day, and pantoprazole 40 mg orally per day.

Primary and secondary outcomes

The 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 measurement

All demographic information was collected at patients’ enrollment time. Patients’ rosacea stage was evaluated on day 0, 60, and 180, then they were compared. Same dermatology team reevaluated clinical course of rosacea to decrease inter-observer error.

Statistical methods

Statistical analysis was performed by SPSS software package, version 16.0, for windows (SPSS Inc.). Quantitative data 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 have been confounding factors were analyzed using multivariate analysis but they were not presented in results the section. P value less than 0.05 was considered statistically significant. Normal distribution of data was assessed using Kolmogorov-Smirnov test.

 

Results

In 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 patients is shown in Table 1; of all patients with a positive test for H. pylori, patients diagnosed with rosacea had lower ages (p>0.001) and the difference in gender 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 rejected 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 15.55±4.34, 14.11±3.96 and 12.57±3.62, respectively; the differences between all stages were statistically significant (p< 0.01) based on Friedman test, also the differences between all two stages were statistically significant based on Wilcoxon ranked-sum test (day 0 vs. day 60, p<0.01; day 60 vs. day 180, p<0.01; day 0 vs. day 180, p<0.01). Rosacea Duluth score parameters of patients at day 0, 60 and 180 of the trial are shown in Table 2; during the follow-up Duluth score grading demonstrated a statistically significant decrease in most of the criteria except telangiectasias, phymatous changes and the existence of peripheral involvement criteria.

Based on Wilcoxon signed-rank test, comparison of primary and secondary features of rosacea between stages of study is shown in table 3; Of secondary rosacea 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 not statistically significant.

Discussion

Rosacea 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 association 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 including race, culture and diet of these. In a study by Argenziano et al. potential association between rosacea and serological evidence 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 cure rate after routine triple therapy was 92%. During 6 months of follow-up, H. pylori eradication among those who had rosacea and H. pylori infection led to a significant improvement 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, telangiectasia, and peripheral involvement; this difference in phymatous changes, telangiectasia, and peripheral involvement might be due to the more time taking 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 decreased 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 effect of H. pylori eradication on rosacea is similar in both of the studies. In another study conducted by Rojo et al. on the role of H. pylori in rosacea and chronic urticarial, it was concluded that H. pylori eradication led to a significant improvement 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.

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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. pylori 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 while no statistically significant change was shown about telangiectasia.

According to the mentioned literature, different conclusions have been derived from studies about the efficacy 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 lack of control group, so it might have affected this study to prevent 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 treatment 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 scores 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 alterations in the dermatological pattern of rosacea might lead to a more confident conclusion.

 

Acknowledgments:

This Study was supported by Tabriz University of Medical Sciences.

Conflict of Interests:

No conflict of interests are declared

 

References:

1.Plewig G, Kligman A M. Acne and rosacea: Springer Science & Business Media: 2012.

2.Powell F C. Rosacea. New England Journal of Medicine 2005: 352: 793-803.

3.Tan J, Blume‐Peytavi U, Ortonne J, et al. An observational cross‐sectional survey of rosacea: clinical associations and progression between subtypes. British Journal of Dermatology 2013: 169: 555-562.

4.Tan J, Berg M. Rosacea: current state of epidemiology. Journal of the American Academy of Dermatology 2013: 69: S27-S35.

5.Steinhoff M, Buddenkotte J, Aubert J, et al. Clinical, cellular, and molecular aspects in the pathophysiology of rosacea. In: Journal of Investigative Dermatology Symposium Proceedings: Nature Publishing Group, 2011: 2-11.

6.Del Rosso J Q. Advances in Understanding and Managing Rosacea: Part 1 Connecting the Dots Between Pathophysiological Mechanisms and Common Clinical Features of Rosacea with Emphasis on Vascular Changes and Facial Erythema. Journal of Clinical & Aesthetic Dermatology 2012: 5.

7.Fimmel S, Abdel-Naser M B, Kutzner H, et al. New aspects of the pathogenesis of rosacea. Drug Discovery Today: Disease Mechanisms 2008: 5: e103-e111.

8.Pouralibaba F, Babaloo Z, Pakdel F, et al. Serum level of interleukin 17 in patients with erosive and non erosive oral lichen planus. J Dent Res Dent Clin Dent Prospects 2013: 7: 91.

9.Naderi N J, Tirgari F, Esmaili F, et al. Vascular endothelial growth factor and Ki-67 antigen expression in relation to age and gender in oral squamous cell carcinoma. J Dent Res Dent Clin Dent Prospects 2012: 6: 103.

10.Tisma V S, Basta-Juzbasic A, Jaganjac M, et al. Oxidative stress and ferritin expression in the skin of patients with rosacea. Journal of the American Academy of Dermatology 2009: 60: 270-276.

11.Guzman-Sanchez D A, Ishiuji Y, Patel T, et al. Enhanced skin blood flow and sensitivity to noxious heat stimuli in papulopustular rosacea. Journal of the American Academy of Dermatology 2007: 57: 800-805.

12.Marks R. The enigma of rosacea. Journal of Dermatological Treatment 2007: 18: 326-328.

13.Lacey N, Delaney S, Kavanagh K, et al. Mite‐related bacterial antigens stimulate inflammatory cells in rosacea. British Journal of Dermatology 2007: 157: 474-481.

14.Golfroushan F, Azimi H, Ali E T H. Comparison of Efficacy of Topical Combination Solution of Salicylic Acid% 2 and Erythromycin% 4 with Topical Solution of Erythromycin 4% Alone in Mild to Moderate Acne Vulgaris Treatment: A Double-Blinded Randomized Clinical Trial. Medical Journal of Tabriz University of Medical Sciences & Health Services 2013: 34.

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15.Zandi S, Shamsadini S, Zahedi M, et al. Helicobacter pylori and rosacea. Eastern Mediterranean health journal= La revue de sante de la Mediterranee orientale= al-Majallah al-sihhiyah li-sharq al-mutawassit 2002: 9: 167-171.

16.Hernando-Harder A C, Booken N, Goerdt S, et al. Helicobacter pylori infection and dermatologic diseases. European Journal of Dermatology 2009: 19: 431-444.

17.El‐khalawany M, Mahmoud A, Mosbeh A S, et al. Role of Helicobacter pylori in common rosacea subtypes: a genotypic comparative study of Egyptian patients. The Journal of dermatology 2012: 39: 989-995.

18.Bhattarai S, Agrawal S, Rijal A, et al. The study of prevalence of Helicobacter pylori in patients with acne rosacea. Kathmandu University Medical Journal 2014: 10: 49-52.

19.Prelipcean C C, Mihai C, Gogălniceanu P, et al. Extragastric manifestations of Helicobacter pylori infection. Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi 2006: 111: 575-583.

20.Yousefi L, Ghotaslou R, Akhi M T, et al. Frequency of Helicobacter pylori blood-group antigen-binding adhesion 2 and sialic acid binding adhesion genes among dyspeptic patients in Tabriz, Iran: H. pylori babA2 and sabA genes. Journal of Analytical Research in Clinical Medicine 2015: 3.

21.Salehi M R, Aboei M S, Naghsh N, et al. A comparison in prevalence of Helicobacter pylori in the gingival crevicular fluid from subjects with periodontitis and healthy individuals using polymerase chain reaction. J Dent Res Dent Clin Dent Prospects 2013: 7: 238.

22.Szlachcic A. The link between Helicobacter pylori infection and rosacea. Journal of the European Academy of Dermatology and Venereology 2002: 16: 328-333.

23.Tüzün Y, Keskin S, Kote E. The role of Helicobacter pylori infection in skin diseases: facts and controversies. Clinics in dermatology 2010: 28: 478-482.

24.Daković Z, Vesić S, Vuković J, et al. Ocular rosacea and treatment of symptomatic Helicobacter pylori infection: a case series. Acta dermatovenerologica Alpina, Pannonica, et Adriatica 2007: 16: 83-86.

25.Mayr-Kanhäuser S, Kränke B, Kaddu S, et al. Resolution of granulomatous rosacea after eradication of Helicobacter pylori with clarithromycin, metronidazole and pantoprazole. European journal of gastroenterology & hepatology 2001: 13: 1379-1383.

26.Wilkin J, Dahl M, Detmar M, et al. Standard grading system for rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea. Journal of the American Academy of Dermatology 2004: 50: 907-912.

27.Chisholm S A, Watson C L, Teare E L, et al. Non-invasive diagnosis of Helicobacter pylori infection in adult dyspeptic patients by stool antigen detection: does the rapid immunochromatography test provide a reliable alternative to conventional ELISA kits? Journal of medical microbiology 2004: 53: 623-627.

28.Kyriakis K P, Palamaras I, Terzoudi S, et al. Epidemiologic aspects of rosacea. Journal of the American Academy of Dermatology: 53: 918-919.

29.Tan J, Berg M. Rosacea: Current state of epidemiology. Journal of the American Academy of Dermatology: 69: S27-S35.

30.McAleer M A, Fitzpatrick P, Powell F C. Papulopustular rosacea: Prevalence and relationship to photodamage. Journal of the American Academy of Dermatology 2010: 63: 33-39.

31.Abram K, Silm H, Oona M. Prevalence of Rosacea in an Estonian Working Population Using a Standard Classification. Acta Dermato-Venereologica 2010: 90: 269-273.

32.Argenziano G, Donnarumma G, Arnese P, et al. Incidence of anti‐Helicobacter pylori and anti‐CagA antibodies in rosacea patients. International journal of dermatology 2003: 42: 601-604.

33.Abram K, Silm H, Maaroos H I, et al. Risk factors associated with rosacea. Journal of the European Academy of Dermatology and Venereology 2010: 24: 565-571.

34.Rojo-Garcia J M, Munoz-Perez M A, Escudero J, et al. Helicobacter pylori in rosacea and chronic urticaria. Acta dermato-venereologica 2000: 80: 156-157.

35.Bamford J T, Tilden R L, Blankush J L, et al. Effect of treatment of Helicobacter pylori infection on rosacea. Archives of dermatology 1999: 135: 659-663.

36.Herr C, Hee You C. Relationship between Helicobacter pylori and Rosacea. J Korean Med Sci 2000: 15: 551-554.

37.El-khalawany M, Mahmoud A, Mosbeh A-S, et al. Role of Helicobacter pylori in common rosacea subtypes: A genotypic comparative study of Egyptian patients. The Journal of Dermatology 2012: 39: 989-995.

 

Tables:

Table 1. Demographic information about patients with positive H. pylori stool antigen (%)

Variables

Patients with*

P value

+ HPA without rosacea (N=705)

+HPA with rosacea (N=167)

Age (years old)

54.38±10.71

43.21±9.84

<0.001

Gender

337 (47.81%) female,

368 (52.19%) male

95 (56.89%) female,

72 (43.11%) male

0.03

Marital status

Single, Divorced or widowed (643(91.2%)),

Married (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 Mean ± Standard Deviation and number (%)

 

Table 2. Rosacea Duluth grading of patients at day 0, 60 and 180 of trial (N=138)*.

Variables

Day 0 **

Day 60**

Day 180**

P value

Primary Features

Flushing

2.28 ± 0.71

2.02 ± 0.51

1.82 ± 0.52

<0.001

Non-transient erythema

2.34 ± 0.54

1.9 ± 0.64

1.42 ± 0.72

<0.001

Papules and pustules

1.8 ± 0.59

1.71 ±0.51

1.58 ± 0.52

<0.001

Telangiectasia

1.78 ± 0.93

1.72 ±0.67

1.74 ± 0.84

0.194

Secondary Features

Burning or stinging

1.17 ± 0.82

1.02 ±0.81

0.94 ± 0.78

<0.001

Plaques

1.51 ± 1.12

1.32 ±0.74

1.05 ± 0.82

<0.001

Dry appearance

1.72 ± 1.18

1.64 ±1.22

1.46 ± 0.95

<0.001

Edema

1.12 ± 0.74

1.08 ±0.81

0.92 ± 0.58

<0.001

Ocular manifestations

0.84 ± 0.36

0.78 ±0.41

0.71 ± 0.45

<0.001

Presence in peripheral location

18 (13.4%)

18 (13.4%)

16 (11.59%)

0.368

Phymatous changes

0.94 ± 0.71

0.86 ±0.68

0.90 ± 0.74

0.139

*Friedman’s test was performed.

**Data are shown as Mean ± Standard Deviation

 

Table 3. Comparison of severity of primary and secondary features of rosacea between stages of study*

Variables

P value

Day 0 vs. day 60

Day 60 vs. day 180

Day 0 vs. day 180

Primary Features

Flushing

<0.001

<0.001

<0.001

Non-transient erythema

<0.001

<0.001

<0.001

Papules and pustules

<0.001

<0.001

<0.001

Telangiectasia

0.181

0.614

0.401

Secondary Features

Burning or stinging

0.003

0.129

0.001

Plaques

0.011

<0.001

<0.001

Dry appearance

0.228

0.001

0.001

Edema

0.351

0.004

<0.001

Ocular manifestations

0.010

0.002

<0.001

Presence in peripheral location

1

0.157

0.317

Phymatous changes

0.001

0.472

0.477

*Wilcoxon signed-rank test was used.

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