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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 37  |  Issue : 2  |  Page : 49-55

The role of Helicobater pylori as an aetiological factor for rosacea


1 Departement of Dermatology, STDs and Andrology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
2 Department of Surgery in Gastroenterology Surgery Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt
3 Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt

Date of Submission08-Oct-2016
Date of Acceptance30-Apr-2017
Date of Web Publication4-Aug-2017

Correspondence Address:
Bothaina M Ghanem
Department of Dermatology, STDs and Andrology, Faculty of Medicine, Mansoura University, Dakahlia, Mansoura
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejdv.ejdv_60_16

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  Abstract 


Background
Rosacea is a chronic cutaneous disorder characterized by persistent centrofacial erythema, telangiectases, papules, pustules, oedema, phymatous and ocular involvement. Despite being one of the most common skin disorders, its pathogenesis remains unclear and controversial. More recently, numerous studies have described an association with Helicobacter pylori.
Objective
This study was undertaken to investigate the prevalence of H. pylori in rosacea patients by performing gastroscopic biopsy, and if its eradication is a useful therapy for rosacea.
Patients and methods
This study was conducted on 54 patients with rosacea: 46 women and eight men, in addition to 26 healthy controls of similar age and socioeconomic status. Blood samples were taken from patients, and controls for the detection of H. pylori immunoglobulin G antibodies by enzyme-linked immunosorbent assay. Also, gastroduodenoscopy was done for 28 patients with rosacea, and two punch biopsies were taken for direct Gram stain, direct urease test and culture.
Results
Bacteriological tests were positive in 11 of these 28 (39.3%) patients. Seropositive prevalence was significantly higher in the rosacea group than in the control group (81.5 vs. 57.7%). On intake of H. pylori eradication therapy in the form of amoxicillin 500 mg/6 h and metronidazole 500 mg, thrice daily, for 10 days, the H. pylori positive group showed significant improvement in rosacea severity.
Conclusion
Our results suggest that H. pylori is a risk factor that may cause or aggravate rosacea condition. Its eradication leads to a favourable clinical outcome.

Keywords: gastroscopy, Helicobacter pylori, rosacea


How to cite this article:
Ghanem BM, El-Kholy AA, El-Ghawalby NA, El-Chennawy FA, Abdel Naby SM. The role of Helicobater pylori as an aetiological factor for rosacea. Egypt J Dermatol Venerol 2017;37:49-55

How to cite this URL:
Ghanem BM, El-Kholy AA, El-Ghawalby NA, El-Chennawy FA, Abdel Naby SM. The role of Helicobater pylori as an aetiological factor for rosacea. Egypt J Dermatol Venerol [serial online] 2017 [cited 2017 Aug 18];37:49-55. Available from: http://www.ejdv.eg.net/text.asp?2017/37/2/49/212104




  Introduction Top


Rosacea is an inflammatory disease affecting the central part of the face, characterized by erythema, papules, papulopustules and telangiectasia of unknown aetiology [1]

The cause of rosacea is not clearly known, but its genetic predisposition, gastrointestinal disturbances, Demodex folliculorum mites, topical steroids and psychogenic factors may contribute to this disorder [2],[3]. Various reports have linked rosacea with different gastrointestinal disturbances including peptic ulcer disease. More recently, numerous studies have described an association with Helicobacter pylori and the extragastric symptoms of cutaneous origin [4],[5].

An association of H. pylori with rosacea was originally issued by Rebora et al. [6]. H. pylori is a spiral shaped, motile, Gram negative bacterium that produces urease and resides on the gastric mucosa. Several techniques such as culture, serology by enzyme-linked immunosorbent assay (ELISA), urea breath test, histologic staining, immunohistochemistry and PCR represent the useful methods for identifying H. pylori which have variable sensitivity and specificity [7],[8].

Many authors have reported that H. pylori probably constitutes a risk factor in rosacea patients [6],[9],[10],[11]. On the other hand, some investigators contradict any association between rosacea and H. pylori infection [12],[13],[14].

On eradicating H. pylori in rosacea patients with chronic gastritis, the rosacea condition rapidly improved within 4 weeks, and did not recur within 2 years of follow-up [15],[16],[17]. On the other hand, other studies have reported no relation of the eradication of H. pylori with the clinical improvement of skin lesions [13],[14].

This study was undertaken to investigate the prevalence of H. pylori in rosacea patients by performing gastroscopic biopsy, and if its eradication is a useful therapy for rosacea.


  Patients and methods Top


This study was conducted on 54 patients complaining of rosacea. The study proposal was approved by our Institutional Review Board (IRB), Mansoura Faculty of Medicine, Code number; R/16.08.14. The patients were selected from the Dermatology Outpatient Clinic of Mansoura University Hospital. The patients were 46 women and eight men, and their ages ranged from 25 to 65 years.

Criteria for selection of patients:
  1. Active lesions must be present.
  2. The patient was not on any antibiotics in the preceding 4 weeks.


In addition, 26 healthy controls of similar age and socioeconomic status were included in this study, who did not take oral antibiotics for 4 weeks.

All patients were subjected to thorough history taking. The patients were clinically examined, and rosacea severity was graded according to Walsgrave Hospital Rosacea scaling systems [18]. Blood samples were taken from all participants (patients and controls) for the detection of anti-H. pylori immunoglobulin G (IgG) antibodies.

Also, gastroduodenoscopy was performed on 28 patients who accepted this measure. Mucosae of stomach and duodenum were searched for gross pathology. Two punch biopsies were taken from the antrum and other two punch biopsies were taken from the duodenum. These biopsies were transported in sterile tubes containing sterile nutrient broth to be cultured with 1–2 h.

All patients were given H. pylori eradication therapy in the form of amoxicillin 500 mg/6 h and metronidazole 500 mg, thrice daily, for 10 days. The patients were followed up and the severity of rosacea was assessed at the end of treatment, 1 month and 6 months after the end of treatment. Only 26 out of 54 rosacea patients were regularly followed up.

Six months after the end of treatment, another blood sample was taken from these 26 patients who completed the follow up, for the detection of anti-H. pylori IgG antibodies to detect eradication of H. pylori.

Microbiological study

The biopsies taken from the antrum and duodenum were ground using sterile glass rod, and were subjected to the following tests:
  1. Direct Gram smear: H. pylori was seen as Gram negative curved or S-shaped bacilli [19].
  2. Direct urease test: A portion of the ground material was inoculated into Christensen urea agar and incubated microaerophillically for 24 h at 37°C. Change of colour of the media from yellow to pink within 24 h indicated positive urease test [19].
  3. Culture: The last portion of the ground material was inoculated on the Skirrow’s H. pylori selective medium, and incubated under moist microaerophilic environment (10% CO2 and 5% O2) in specific jar at 37°C for 5–7 days. The growth of small colonies (<2 mm in diameter) that are grey and translucent and positive for urease, and consisting of Gram negative spiral bacterial indicates the presence of H. pylori [20].


Serologic studies

Detection of anti-Helicobacter pylori immunoglobulin G antibodies

This was done by using ‘Capita H. pylori Kit’ (Trinity Biotech Plc, Bray, Ireland). It is a solid phase IgG ELISA.


  Results Top


This study was conducted on 54 rosacea patients and 26 age-matched and sex-matched controls ([Table 1] and [Table 2]). Of the 54 rosacea patients, only 28 patients accepted to do gastroduodenoscopy. Abnormal endoscopic findings in the stomach or duodenum or both were detected in only 13 (46.4%) patients ([Table 3]). From those 28 patients, H. pylori could be positively demonstrated in only 11 (39.3%) patients by one or more of the bacteriologic studies ([Table 4]).
Table 1 Age of both rosacea and control groups

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Table 2 Sex of both rosacea and control groups

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Table 3 Endoscopic findings of rosacea patients (n=28)

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Table 4 Results of bacteriologic studies (n=28)

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All patients with positive bacteriologic studies had also positive ELISA test for anti-H. pylori antibodies. However, 13 patients of the remaining 17 patients with negative bacteriologic studies showed positive ELISA, and only four patients showed negative ELISA test. The agreement between bacteriologic studies and ELISA test was not statistically significant ([Table 5]).
Table 5 Comparison between results of the bacteriological studies and enzyme-linked immunosorbent assay test for anti-Helicobacter pylori antibodies immunoglobulin G (n=28)

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The association between abnormal endoscopic findings and positive bacteriologic studies was statistically significant, while their association with positive ELISA test was statistically insignificant ([Table 6]).
Table 6 Association between endoscopic findings and results of bacteriological studies (n=28) and results of enzyme-linked immunosorbent assay test for anti-Helicobacter pylori immunoglobulin G antibodies (n=28)

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ELISA test for anti-H. pylori IgG antibodies was done for all patients; positive ELISA test was significantly higher in the rosacea group than in the control group ([Table 7]).
Table 7 Results of enzyme-linked immunosorbent assay test for anti- Helicobacter pylori antibodies immunoglobulin G in both patients and control groups

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All rosacea patients, whether H. pylori positive, negative were treated with H. pylori eradication therapy with reassessment of rosacea severity at the end of treatment, that is after 10 days, 1 month and 6 months after the end of treatment. At the last follow-up visit another ELISA test for IgG anti-H. pylori antibodies was done. Only 26 rosacea patients completed the follow-up period; 20 patients were H. pylori positive and the others were H. pylori negative before treatment. Rosacea severity score of these two groups of patients were statistically indifferent ([Table 8]).
Table 8 Rosacea severity before treatment of both Helicobacter pylori positive and negative patients who complete the follow-up (n=26)

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At the end of treatment, H. pylori positive rosacea patients showed a statistically significant decrease in rosacea severity score, while H. pylori negative patients showed a statistically insignificant decrease in rosacea severity ([Table 9]).
Table 9 Response of both Helicobacter pylori positive and negative rosacea patients to Helicobacter pylori eradication therapy

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Six months after the end of treatment, ELISA test for IgG anti-H. pylori antibodies was done for the 20 H. pylori positive rosacea patients, 15 (75%) patients showed negative test, while five (25%) patients still showed positive test. A statistically significant improvement in rosacea severity was more marked and occurred more earlier in the 15 patients who became H. pylori negative after treatment than those who still were H. pylori positive ([Figure 1],[Figure 2],[Figure 3],[Figure 4]).
Figure 1 Response of both Helicobacter pylori positive and negative rosacea patients to Helicobacter pylori eradication therapy.

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Figure 2 Skirrow’s culture medium for Helicobacter pylori (small colourless colonies, few millimetres in diameter).

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Figure 3 Gram stain of the isolated Helicobacter pylori organisms.

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Figure 4 Christensen urea agar (left: negative test, right: positive test after 24 h).

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  Discussion Top


Rosacea, formerly known as acne rosacea is a distinct chronic inflammatory disease affecting particularly the central convexities (nose, central forehead, cheeks and chin) of the facial skin [21],[22].

Rosacea generally affects middle-aged, fair-skinned women, but it can affect those of any sex, age, or skin type [23]. Also, Berg and Liden [24] and Sharma et al. [12] found that rosacea is more common in women (76.5 and 89%, respectively). In the present study, about 85.2% of patients were women, while 14.8% were men ([Table 2]). Our results agree with the previous authors. The difference found between both sexes show that rosacea is in reality more common in women and this is not a consequence of tendency among women to consult physicians more frequently [24]. So, any factor supposed to be the cause of rosacea is expected to be associated also with female sex.

Rosacea has been linked with different gastrointestinal disturbances including peptic ulcer disease [4],[5]. At present, it is known that H. pylori plays the key in the development of gastritis, peptic ulcer, mucosa-associated lymphoid tissue lymphoma (MALT) lymphoma and even gastric cancer. H. pylori increases the synthesis of oxygen metabolites such as superoxide and proinflammatory cytokines. These cytokines have been shown to stimulate the synthesis of the inflammatory species nitric oxide contributing to the inflammation of the gastric mucosa and the skin changes [25],[26].

Many studies were done to clarify the relation between H. pylori and rosacea, through detecting the prevalence of H. pylori infection in rosacea patients, and the effect of its eradication on rosacea severity, but the obtained results were contradictory.

In this study, gross changes of stomach or duodenum were detected endoscopically in 13 (46.4%) patients ([Table 3]). In another Egyptian study, gastritis, gastric erosions and duodenal ulcers were found in 10 out of 14 (71.4%) rosacea patients [27]. Also, abnormal endoscopic findings were found in 61.5% of 13 patients with rosacea [28]. These findings suggest an association between rosacea and gastritis. On the other hand, Rebora [29] found that the frequency of gross abnormalities in stomach, duodenum or gall bladder in rosacea patients was similar to that in the general population, ∼13%. So, controlled studies are needed to confirm these results.

H. pylori a causative factor of gastritis can be detected by obtaining an antral and duodenal mucosal biopsies for direct smear stained by Gram stain, direct urease test and culture [30],[31],[32]. These methods need endoscopy which is invasive to obtain the biopsies. So, for epidemiological studies, serological tests for detecting anti-H. pylori antibodies are done [33].

In this study, bacteriological tests were done for 28 patients, and were positive in only 11 (39.3%) patients, while serological test for anti-H. pylori IgG antibodies was positive in 24 out of these 28 (85.7%) patients. The association between the bacteriological and serologic tests was statistically insignificant ([Table 5]). The association between abnormal endoscopic findings and positive bacteriological tests was statistically significant, while their association with positive serologic test was statistically insignificant ([Table 6]). This difference between the results of the bacteriologic tests, and the serologic test may be due to many factors. First, H. pylori has a patchy distribution in the gastric mucosa, which can lead to sampling errors and false negative results [34]; second, H. pylori is present not only in the gastric and duodenal mucosa, but can be retrieved from the oral cavity, and was detected by the PCR technique in the saliva, dental plaque [35], tongue, cheek and palate [36]. H. pylori in the oral cavity, which is near the classic site of rosacea, can lead to positive serologic test and at the same time negative bacteriologic tests on biopsies taken from the antrum and duodenum.

Since serological test (ELISA) is noninvasive, rapid and useful for epidemiological studies [33], it was done for all 54 rosacea patients, and 26 control. In this study, seropositive prevalence was significantly higher in the rosacea group than in the control group (81.5 vs. 57.7%) ([Table 7]). Our results go hand in hand with the authors who believe that H. pylori probably constitutes a risk factor [6],[9],[10],[11], and contradict others who deny any association between rosacea and H. pylori infection [12],[13],[14].

On intake of H. pylori eradication therapy that contains metronidazole, for both H. pylori positive, negative rosacea patients, the H. pylori positive group showed significant improvement in rosacea severity. This started at the end of treatment, and continued for 1 month, then persisted up to 6 months, while H. pylori negative group showed no significant improvement in rosacea severity ([Table 8] and [Table 9]). Our results go hand in hand with many authors, who found a more favourable clinical response to anti-H. pylori treatment in H. pylori positive than in H. pylori negative patients [17],[28],[39],[40],[41],[42]. On the other hand, other studies reported no relation of the eradication of H. pylori with the clinical improvement of skin lesions [13],[14].

To confirm eradication of H. pylori in positive rosacea patients, ELISA test for anti-H. pylori antibodies was done 6 months after treatment. Patients who became negative (75%) showed earlier and more marked improvement in rosacea than patients who still are H. pylori positive ([Table 9]). This finding suggests that eradication of H. pylori has a more favourable clinical outcome.

The improvement in the cases remained; H. pylori positive is strange and was not expected. However many factors can explain it. The bacterial load of H. pylori may be decreased, but not completely disappeared; hence improvement in rosacea occurred while anti-H. pylori antibody ELISA test still remained positive. Our ELISA kit for anti-H. pylori was qualitative and not quantitative, so it cannot detect the mild decrease in the level of anti-H. pylori antibodies that may occur in some cases after H. pylori eradication. Al Mokadem et al. [27] reported a quantitative decrease in the level and not complete disappearance of anti-H. pylori IgG antibodies (by using quantitative kits), despite proved eradication of H. pylori by culture and PCR.

So, our results suggest that H. pylori is a risk factor that may cause or aggravate rosacea condition. Its eradication leads to a favourable clinical outcome.

However, H. pylori cannot be found in every case of rosacea. Also, H. pylori infection is common, while rosacea has a very low prevalence. There is no age-related increased frequency of H. pylori infection as that of rosacea, and there is no association with female sex as that of rosacea. So, H. pylori infection cannot be supposed to be the direct cause of rosacea, but an exacerbating factor, which on its eradication causes improvement of rosacea.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]



 

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