Association of Helicobacter pylori infection and acne

Read metadata

A number of meta-analytical studies have identified associations of Helicobacter pylori (H. pylori) infection with several skin conditions including rosacea, chronic urticaria, and psoriasis. The clinical significance and mechanisms of development of such associations remain controversial. At the same time, there are no meta-analytic works devoted to the study of the prevalence of H. pylori infection in patients with acne.

OBJECTIVE

Systematization of data on the frequency of association between H. pylori infection and acne.

MATERIAL AND METHODS

Studies were searched in electronic databases MEDLINE/PubMed, EMBASE, Cochrane, Google Scholar, Russian Science Citation Index (RSCI) with a sample size from January 1, 1990 to November 2020. The final analysis selected publications containing detailed descriptive statistics (sample size patients with acne, the number of H. pylori-infected patients, people in the control group, H. pylori-infected in the control group) and allowing the results to be included in the meta-analysis. Papers devoted to studies in patients with rosacea were excluded from the analysis.

RESULTS

The final analysis included 5 studies with 629 acne patients. The generalized infection with H. pylori in acne was 77.844% (95 CI 54.769—94.232). In the analysis of infection, a random effect model was used since there was significant heterogeneity between the results (p<0.0001; I²=97.34%). In the control group, the generalized incidence of infection was 48.821% (95% CI 40.189—57.489). There was a statistically significant association between H. pylori infection and the presence of acne (OR 1.744, 95% CI 1.077—2.822; p=0.024).

CONCLUSION

A meta-analysis has shown that H. pylori infection is quite common in patients with acne and may be a risk factor for the development of this skin disease. However, additional large studies of a more homogeneous nature are needed to verify the results obtained and to study the potential causal relationships between H. pylori infection and acne.

Keywords:

Helicobacter pylori

acne vulgaris

acne

Authors:

D.N. Andreev

Burdenko Neurosurgical Center

I.V. Maev

A.I. Yevdokimov Moscow State University of Medicine and Dentistry

ORCID: 0000-0001-6114-564X

R.M. Umyarova

Moscow State University of Medicine and Dentistry named after A.I. Evdokimov

Received:

28.12.2020

Accepted:

02.06.2021

List of references:

Kubanov AA, Arabiyskaya EA, Samtsov AV, Kondrakhina IN, Makhakova YuB, Laceev DI. Acne vulgaris. Clinical guidelines of the Russian society of dermatovenerologists and cosmetologists. M. 2020. (In Russ.).
Williams HC, Dellavalle RP, Garner S. Acne vulgaris. Lancet. 2012;379 (9813):361-372. https://doi.org/10.1016/S0140-6736(11)60321-8
Tan JK, Bhate K. A global perspective on the epidemiology of acne. Br J Dermatol. 2015;172(1):3-12. https://doi.org/10.1111/bjd.13462
Heng AHS, Chew FT. Systematic review of the epidemiology of acne vulgaris. Sci Rep. 2020;10(1):5754. https://doi.org/10.1038/s41598-020-62715-3
Samuels DV, Rosenthal R, Lin R, Chaudhari S, Natsuaki MN. Acne vulgaris and risk of depression and anxiety: A meta-analytic review. J Am Acad Dermatol. 2020;83(2):532-541. https://doi.org/10.1016/j.jaad.2020.02.040
He L, Wu WJ, Yang JK, Cheng H, Zuo XB, Lai W, Gao TW, Ma CL, Luo N, Huang JQ, Lu FY, Liu YQ, Huang YJ, Lu QJ, Zhang HL, Wang L, Wang WZ, Wang MM, Xiao SX, Sun Q, Li CY, Bai YP, Li H, Zhou ZC, Zhou FS, Chen G, Liang B, Qi J, Yang XY, Yang T, Zheng X, Sun LD, Zhang XJ, Zhang YP. Two new susceptibility loci 1q24.2 and 11p11.2 confer risk to severe acne. Nat Commun. 2014;5:2870. https://doi.org/10.1038/ncomms3870
Navarini AA, Simpson MA, Weale M, Knight J, Carlavan I, Reiniche P, Burden DA, Layton A, Bataille V, Allen M, Pleass R, Pink A, Creamer D, English J, Munn S, Walton S; Acne Genetic Study Group, Willis C, Déret S, Voegel JJ, Spector T, Smith CH, Trembath RC, Barker JN. Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris. Nat Commun. 2014;5:4020. https://doi.org/10.1038/ncomms5020
Petridis C, Navarini AA, Dand N, Saklatvala J, Baudry D, Duckworth M, Allen MH, Curtis CJ, Lee SH, Burden AD, Layton A, Bataille V, Pink AE; Acne Genetic Study Group, Carlavan I, Voegel JJ, Spector TD, Trembath RC, McGrath JA, Smith CH, Barker JN, Simpson MA. Genome-wide meta-analysis implicates mediators of hair follicle development and morphogenesis in risk for severe acne. Nat Commun. 2018;9(1):5075. PMID: 30542056; PMCID: PMC6290788. https://doi.org/10.1038/s41467-018-07459-5
Maev IV, Andreev DN. Helicobacter pylori infection and associated diseases. M.: Remedium; 2018. (In Russ.).
Malfertheiner P, Venerito M, Schulz C. Helicobacter pylori Infection: New Facts in Clinical Management. Curr. Treat. Options Gastroenterol. 2018;16(4): 605-615. https://doi.org/10.1007/s11938-018-0209-8
Hooi JKY, Lai WY, Ng WK, Suen MMY, Underwood FE, Tanyingoh D, Malfertheiner P, Graham DY, Wong VWS, Wu JCY, Chan FKL, Sung JJY, Kaplan GG, Ng SC. Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology. 2017;153(2):420-429. https://doi.org/10.1053/j.gastro.2017.04.022
Zamani M, Ebrahimtabar F, Zamani V, Miller WH, Alizadeh-Navaei R, Shokri-Shirvani J, Derakhshan MH. Systematic review with meta-analysis: the worldwide prevalence of Helicobacter pylori infection. Aliment Pharmacol Ther. 2018;47(7):868-876. https://doi.org/10.1111/apt.14561
Maev IV, Andreev DN, Kucheryavyy YuA. Diagnostics and eradication therapy of Helicobacter pylori infection. M. 2021. (In Russ.).
Bordin D, Plavnik R, Tivanova E, Skibo I, Embutniex Yu, Maev I. Trends in the prevalence of Helicobacter pylori in Russia. Helicobacter. 2020;25(suppl 1):e12745:64-65.
Jørgensen AR, Egeberg A, Gideonsson R, Weinstock LB, Thyssen EP, Thyssen JP. Rosacea is associated with Helicobacter pylori: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2017;31(12):2010-2015. https://doi.org/10.1111/jdv.14352
Gu H, Li L, Gu M, Zhang G. Association between Helicobacter pylori Infection and Chronic Urticaria: A Meta-Analysis. Gastroenterol Res Pract. 2015;2015:486974. https://doi.org/10.1155/2015/486974
Yu M, Zhang R, Ni P, Chen S, Duan G. Helicobacter pylori Infection and Psoriasis: A Systematic Review and Meta-Analysis. Medicina (Kaunas). 2019;55(10):645. https://doi.org/10.3390/medicina55100645
Kutlubay Z, Zara T, Engin B, Serdaroğlu S, Tüzün Y, Yilmaz E, Eren B. Helicobacter pylori infection and skin disorders. Hong Kong Med J. 2014;20(4): 317-324. https://doi.org/10.12809/hkmj134174
Khodaeiani E, Halimi M, Hagigi A. Severe acne vulgaris is associated with helicobacter pylori infection: first report in the literature. Med Sci J. 2014; 14(2):92-96. https://doi.org/10.3923/jms.2014.92.96
Saleh R, Sedky Mahmoud A, Moustafa DA, Abu El-Hamd M. High levels of Helicobacter pylori antigens and antibodies in patients with severe acne vulgaris. J Cosmet Dermatol. 2020 Apr 25. https://doi.org/10.1111/jocd.13409
Khashaba SA, Diab NA, Abdallah EA, Said NM. Prevalence of Helicobacter pylori and impact of its eradication in acne vulgaris: a prospective cohort study. J Egypt Womens Dermatol Soc. 2020;17:45-49. https://doi.org/10.4103/jewd.jewd_50_19
Yutyaeva EV, Peretolchina TF, Glazkova LK. The role of diseases of the upper gastrointestinal tract in the pathogenesis of acne. Modern problems of dermatovenerology, immunology and medical cosmetology. 2012;1:23-29. (In Russ.).
Voloshina NA, Denisenko OI, Vasyuk VL. Features of the clinic and the course of acne vulgaris against the background of concomitant Helicobacter pylori infection of gastroduodenal localization. Ukrainian journal of dermatology, venereology, cosmetology. 2013;3:016-021. (In Russ.).
Novoselov AV, Novoselov VS, Sosnova EA, Kaptilny VA. Acne as an interdisciplinary problem. Archives of Obstetrics and Gynecology V.F. Snegireva. 2017;4(1):29-35. (In Russ.).
Santos MLC, de Brito BB, da Silva FAF, Sampaio MM, Marques HS, Oliveira E Silva N, de Magalhães Queiroz DM, de Melo FF. Helicobacter pylori infection: Beyond gastric manifestations. World J Gastroenterol. 2020; 26(28):4076-4093. https://doi.org/10.3748/wjg.v26.i28.4076
Hagymási K, Tulassay Z. Helicobacter pylori infection: new pathogenetic and clinical aspects. World J Gastroenterol. 2014;20(21):6386-6399. https://doi.org/10.3748/wjg.v20.i21.6386
Maev IV, Andreev DN, Kucheryavyi YA. Helicobacter pylori infection and extragastroduodenal diseases. Ter Arkh. 2015;87(8):103-110. (In Russ.). https://doi.org/10.17116/terarkh2015878103-110
Wroblewski LE, Shen L, Ogden S, Romero-Gallo J, Lapierre LA, Israel DA, Turner JR, Peek RM Jr. Helicobacter pylori dysregulation of gastric epithelial tight junctions by urease-mediated myosin II activation. Gastroenterology. 2009;136(1):236-246. https://doi.org/10.1053/j.gastro.2008.10.011
Saadat I, Higashi H, Obuse C, Umeda M, Murata-Kamiya N, Saito Y, Lu H, Ohnishi N, Azuma T, Suzuki A, Ohno S, Hatakeyama M. Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity. Nature. 2007;447(7142):330-333. https://doi.org/10.1038/nature05765

Close metadata

Introduction

Acne vulgaris is a chronic inflammatory skin disease manifested by open or closed comedones and inflammatory elements (papules, pustules and nodes) as well as post-inflammatory changes of varying severity (hyperpigmentation, scars) [1, 2]. According to approximate data, about 9.4% of the world population suffer from this disease [3]. Patients with acne showed a significant decrease in the life quality and social activity, as well as frequent comorbidity with psychological disorders [4]. Thus, in a recent meta-analysis summarizing the results of 42 studies, D.V. Samuels et al. [5] showed that acne was significantly associated with depression (r= 0.22, 95% CI 0.17—0.26; p<0.00001) and anxiety (r= 0.25, 95% CI 0.19—0.3; p<0.00001).

According to modern concepts, acne is considered as a multifactorial dermatosis where significant pathogenesis role is played by an increase in sebum production, follicular hyperkeratosis, colonization of Propionibacterium acnes (P. acnes) and inflammatory mediators released in the skin [1, 2]. Genome-wide associative studies have revealed more than 20 genetic specifics that determine an increased risk of acne, especially its complicated forms [6—8]. At the same time, other factors predisposing the disease are to be actively studied.

Helicobacter pylori (H. pylori) — microaerophilic spiral-shaped gram-negative bacteria colonizes the mucous membrane of the human stomach; it’s leading factor in gastroduodenal diseases development (chronic gastritis, gastric ulcer and duodenal ulcer, MALT lymphoma of the stomach and adenocarcinoma) [9, 10]. Recent reviews and meta-analyzes show that more than 40% of population in developing countries is infected with this microorganism [11, 12]. In general, this epidemiological trend is also typical for Russia with a tendency towards a gradual decrease in prevalence [13]. So, according to D. Bordin et al. [14] obtained in all Russian federal regions by using the ¹³C—urease breath test the prevalence of H. pylori infection was 42.5% in 2017 and 35.3% in 2019.

Currently, a number of meta-analysis have established the associations of H. pylori with some skin diseases including rosacea (OR 3.12, 95% CI 1.92—5.07; p<0.0001), chronic urticaria (OR 1, 66, 95% CI 1.12—2.45; p= 0.01) and psoriasis (OR 1.19, 95% CI 1.15—2.52; p= 0.008) [15—17]. The clinical significance and mechanisms of such associations remain controversial [18]. However, the association of H. pylori and acne has not been investigated in meta-analytical studies. In the literature, there is evidence that patients with severe acne have both a higher frequency of H. pylori and significantly increased titer of antibodies to this microorganism compared with control individuals and patients with mild and moderate disease [19—21].

Objective. To systematize data on association between H. pylori and acne.

Material and methods

Data Search

Data search were carried out in the electronic databases MEDLINE/PubMed, EMBASE, Cochrane, Google Scholar, the Russian Science Citation Index (RSCI) from January 1, 1990 to November 2020. In these databases it was analyzed the titles and abstracts. To search the MEDLINE/PubMed database the following keyword combinations were used: acne (Title/Abstract) helicobacter (Title/Abstract), or acne (Title/Abstract) pylori (Title/Abstract), or acne vulgaris (Title/Abstract) helicobacter (Title/Abstract), as well as their analogs in Russian (for searching in the RSCI database).

Study selection criteria

Criteria for inclusion in meta-analysis: relevant publications in peer-reviewed periodicals in English or Russian as well as publications with detailed descriptive statistics allowing the data to be included in meta-analysis. The object of the study was acne patients; the frequency of H. pylori detection was analyzed. Studies devoted to patients with rosacea were excluded from the analysis. If duplicate results were found in two publications (from different or one electronic database) only one of them was selected for the final analysis.

Data Extraction

Two researchers (D.N.A. and R.M.U.) independently performed data extraction using standardized forms. The year of publication, country, methodology for H. pylori diagnosing, the total sample size of acne patients, the number of H. pylori-infected patients, the number of controls, and the number of H. pylori-infected among controls were analyzed. Any disagreement was resolved by negotiations.

Statistical analysis

Statistical data processing was carried out using special software MedCalc 19.5.3 (Belgium) in Microsoft Windows 10 (USA). Results are presented as pooled rates of H. pylori in acne patients (%) and 95% confidence intervals (95% CI). Heterogeneity between different studies was assessed using Cochrane's Q and I² criteria. At p<0.05 and I²>50 significant heterogeneities were observed. The probability of publication error was assessed by constructing a funnel—shaped scatter plot as well as calculating the Begg-Mazumdar correlation test and Egger's regression test.

Results

Data Search

A search in electronic databases identified 32 studies for further analysis. Out of these 32 studies, 18 papers were excluded since they were not original ones (15 — reviews, 1 — experimental study, 2 — other irrelevant works). The selected 14 studies were analyzed in details for compliance with inclusion criteria, and 9 studies were excluded afterwards (Fig. 1). As a result, the remaining 5 original studies met the criteria and were included in this meta-analysis (see Table) [19, 20, 22—24].

Fig. 1. CONSORT diagram detailing the study selection strategy.

Characteristics of the selected studies

Study, date	Country	Diagnostic method for H. pylori	Total number of acne patents	Total number of controls
E.V. Yutyaeva et al., 2012 [22]	Russia	Breath test with kinetic assessment of exhaled ammonia	258	No
N.A. Voloshina et al., 2013 [23]	Ukraine	ELISA of blood for IgG and / or histology chemistry of biopsy	96	No
E. Khodaeiani et al., 2014 [19]	Iran	¹³C-urease breath test	75	25
A.V. Novoselov et al., 2017 [24]	Russia	ELISA blood IgG	100	No
R. Saleh et al., 2020 [20]	Egypt	Feces antigen assay	100	100

Characteristics of included studies

The final analysis included 5 studies with 629 acne patients; the studies performed in Russia (n=2) [22, 24], Ukraine (n=1) [23], Iran (n=1) [19] and Egypt (n=1) [20]. In 2 studies the data were compared with control groups [19, 20]. All studies used heterogeneous methods for diagnosing H. pylori including blood ELISA for IgG [23, 24], breath test with kinetic assessment of exhaled ammonia [22], ¹³C-urease breath test [19] as well as analysis of microorganism antigen in feces [20].

Prevalence of H. pylori in acne patients

The generalized H. pylori incidence in acne patients was 77.844% (95% CI 54.769–94.232) (Fig. 2). In the analysis a random effect model was used since there was significant heterogeneity between the results (p<0.0001, I²=97.34%). In the control group the generalized H. pylori incidence was 48.821% (95% CI 40.189—57.489). There was a statistically significant association between H. pylori infection and acne (OR 1.744, 95% CI 1.077—2.822; p=0.024).

Fig. 2. Forest diagram showing the generalized incidence of H. pylori in patients with acne.

The probability of publication bias was estimated by constructing a funnel-shaped scatter plot as well as calculating the Begg-Mazumdar test and Egger's regression test. Visual analysis of the funnel-shaped scattering diagram (Fig. 3) did not reveal significant asymmetry. In addition, the presence of statistically significant publication bias was excluded according to the results of the Begg-Mazumdar test (p=0.4386) and Egger's regression test (p=0.5638).

Fig. 3. Funnel scatter plot to assess the likelihood of publication bias.

Discussion

Acne is one of the most common skin diseases worldwide that occurs in many age groups, it significantly affects the patients’ life quality and often associated with anxiety and depression [4, 5]. The factors that contribute to the disease predisposition or modification of its course (more severe one) are not well understood. At the epidemiological level it has been shown that H. pylori is often associated with skin diseases such as rosacea, chronic urticaria, and psoriasis, although the clinical significance of these associations remains uncertain [15—17].

In the studies conducted up to the moment the detection rate of H. pylori in acne patients varies over a wide range from 47.9% to 100% [19, 20, 22—24]. The presented meta-analysis of 5 studies showed that the generalized H. pylori infection in acne patients was 77.844% (95 CI 54.769—94.232) while in control subjects it was 48.821% (95% CI 40.189—57.489). At the same time, a statistically significant association was found between H. pylori and acne (OR 1.744, 95% CI 1.077—2.822; p=0.024). In general, the data obtained may indicate a potential role of H. pylori in this skin disease predisposition or modification of its clinical course. A number of studies have noted that in patients with severe acne compared with control persons and patients with mild and moderate acne not only a higher incidence of H. pylori is detected but also a significantly increased titer of fecal antigen or antibodies to this microorganism were identified [19— 21]. Thus, in a recent study by R. Saleh et al. [20] with gradation of acne patients in accordance with the Global Acne Grading Scale it was shown that in the severe acne there were significantly higher levels of fecal antigen and titer of antibodies to H. pylori compared with patients suffering from mild and moderate forms, as well as control groups (p<0.001). Similar data were obtained in the work of S.A. Khashaba et al. [21] using ELISA.

The exact mechanisms of associations between H. pylori and cutaneous manifestations remain unknown [18]. It is assumed that chronic gastritis caused by H. pylori leads to increase in permeability of the stomach epithelial lining as well as the vessels walls of the mucous membrane, and a higher exposure of bacterial and alimentary antigens in the systemic circulation that can induce both the local release of inflammatory mediators in tissues and systemic immunological reactions (autoimmune and inflammatory processes; the formation of immune complexes induced by molecular mimicry and cross-reactive antibodies) [25–27]. It has been shown that cytotoxin CagA and H. pylori urease are capable to initiate the disorganization of cells’ tight junctions by increasing phosphorylation of myosin light chain as well as inactivation of the PAR1 family protein kinase that regulates the function of cell cytoskeleton [28, 29].

It should be noted, there are several leakages in our work. First, the studies included in the meta-analysis are represented by a small pool of investigations carried out in a limited number of countries (Russia, Ukraine, Iran, Egypt). Secondly, the analyzed studies are characterized by a significant heterogeneity of the methods used for H. pylori diagnosis. However, this is the first meta-analysis summarizing the results of various studies with H. pylori detection rate in acne patients.

Conclusion

A meta-analysis has shown that H. pylori is quite common in acne patients and may represents a risk factor for this skin disease. However, additional large homogeneous studies are needed to verify the results obtained and to investigate the potential causal association between H. pylori and acne.

Authors’ contributions:

The concept and design of the study: Andreev D.N., Maev I.V.

Collecting and interpreting the data: Andreev D.N., Umyarova R.M.

Statistical analysis: Andreev D.N.

Drafting the manuscript: Andreev D.N., Umyarova R.M.

Revising the manuscript: Maev I.V.

The authors declare no conflict of interest.