Helicobacter pylori and inflammatory skin diseases

Abstract

Throughout the history of mankind, infections have been the major cause of diseases. Over the last decades, not only the incidence of emerging infectious diseases have increased, but also tremendous strides have been made in understanding the biology of several pathogenic microorganisms. Helicobacter pylori (H. pylori) is a spiral-shaped, gram-negative bacterium, which infects over the half of the world’s population. H. pylori has been implicated in the pathogenesis of a number of gastrointestinal disorders. However, new researches have demonstrated that H. pylori is also involved in the pathogenesis of various extragastric diseases. The difference in the clinical outcome of H. pylori infection may be explained, at least in part, by host response to the infection and H. pylori virulence factors. It is obvious that as developments in the research on H. pylori spring up, an understanding of the pathophysiology of H. pylori infection will continue to be identified. Here in this review, we summarize the current knowledge about H. pylori and its association with inflammatory skin diseases.

Key Words: Helicobacter pylori; Etiopathogenesis; Skin diseases; Inflammatory

Core tip:Helicobacter pylori (H. pylori) is a worldwide bacterium found almost entirely in humans. Although the majority of infected individuals remain asymptomatic, H. pylori has been implicated in the etiology of several gastric and extragastric disorders. H. pylori is generally acquired during childhood and persists lifelong due to the failure of the immune response to eradicate the bacterium. H. pylori has mechanisms to evade the immune response and to establish local and low-grade systemic inflammation. A number of studies have revealed that Helicobacter pylori-induced chronic low-grade inflammation may contribute to the pathogenesis of several disorders, including inflammatory skin diseases.

HELICOBACTER PYLORI

Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium, which is thought to infect about half of the world’s population. Barry Marshall and Robin Warren were the first researchers to isolate and culture this motile, S-shaped rod from human stomach, which was followed by demonstration of development of several upper gastrointestinal disorders, including chronic gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue (MALT) lymphoma and gastric cancer in the presence of Helicobacter pylori-induced gastric mucosal inflammation[1-4]. The prevalence of H. pylori varies significantly according to geographic region and country, those from developing countries are more prone to acquire H. pylori than subjects from highly developed industrialized countries[2]. One of the most successful human pathogen, H. pylori, exhibits a strict tropism for gastric epithelial lining, adhering specially to gastric epithelium, colonizing in the gastric mucosa, subsequently triggering the responsible inflammation for the resultant gastrointestinal diseases. Although there are a number of hypotheses to explain the precise underlying pathogenetic mechanism, one of the most appreciated one is that host immune response and H. pylori virulence factors interplay between each other in the development of these diseases[1,3-6].

Despite the worldwide high prevalence rate and the fact that H. pylori is most commonly acquired early in the childhood and if untreated, infection is lifelong, the majority of the individuals infected with H. pylori are asymptomatic[1,3-6]. Both the genetic characteristics of the host and genetic differences between strains of H. pylori determine the clinical outcome of the colonization[5,7]. H. pylori produces a number of virulence factors, including flagellins, which provide motility essential for evading from gastric peristalsis and immune challenge of the host, adhesins, conjugated proteins involved in the attachment of the organism to host cell surface. It has been long appreciated that key pathogenic pathways involved in H. pylori infection include chronic gastric inflammation and alternation of gastric physiology, including breakdown of protective gastric mucosal barrier. H. pylori produces different kinds of enzymes that are important in these pathogenetic effects[1,3-6]. The expressions of virulence-associated genes, cytotoxin-associated gene A (cagA) and vacuolating cytotoxin gene A (vacA), have been shown to be closely related with the diversity of clinical outcome of H. pylori infection. CagA protein, which is encoded by cagA gene, is associated with increased risk of developing atrophic gastritis, peptic ulcer and gastric cancer. The cytotoxin, vacA, causing severe vacuolation, has multiple effects on gastric epithelial cells: forms channels in membranes, alternates endosome/lysosome functions, increases transcellular permeability, induces apoptosis and promotes immune tolerance against H pylori[3,4,6,8].

An host-adapted pathogen, H. pylori has ability to mount an effective anti-immune response within the infected host, which results in a chronic lifelong infection. Although H. pylori employs elaborate strategies to evade the host’s immune system, complete avoidance from immune activation is not possible. When some of H. pylori proteins cross the gastric mucosal barrier, both innate and acquired defence mechanisms are activated[8,9]. There has been considerable evidence suggesting that systemic immune response evoked by H. pylori participates in the development of diseases other than gastrointestinal in origin. Although there are many more questions to be answered, H. pylori has been implicated as the causal agent of several extragastric diseases, including neurodegenerative, cardiovascular, pulmonary, endocrinological, ocular, autoimmune and dermatological ones[9-12]. In this review, we aimed to present a summary concerning association of H. pylori with inflammatory skin diseases. We briefly have reported on the present state of basic knowledge and a concise analysis of clinical studies conducted to evaluate the relation of H. pylori with inflammatory skin diseases.

PSORIASIS

Psoriasis is a common chronic inflammatory dermatosis characterized by erythematous, sharply demarcated papules and plaques covered by silvery white scales most commonly affecting scalp, lumbosacral region and extensor surfaces of elbows and knees in a symmetrical pattern. Psoriasis appears worldwide affecting both genders equally[13]. Psoriasis is an immune-mediated disorder. Although the immunopathogenesis of psoriasis has not been fully elucidated yet, it has been revealed that the main role in the immunological cascade of psoriasis is played by T cells. Interaction between inflammatory cytokines, dendritic cells, macrophages, and T-helper type 1 (Th1), Th17, regulatory T cell, Th22 cells contribute to the disease pathogenesis[14].

Genetic and environmental factors are involved in the etiology of psoriasis[15]. Environmental factors that have been claimed to contribute psoriasis include streptococcal tonsillitis[16], smoking[17], alcohol consumption[18], medications, stress, human immunodeficiency virus infection and trauma[15]. There is a growing body of evidence showing that superantigen-mediated T cell activation plays a critical role in the psoriasis pathogenesis. Superantigens are toxins produced by pathogenic bacteria and viruses. It has been suggested that H. pylori toxins, including the aforementioned ones can act as super-antigens, which mount inflammatory response dominated by activated T cells and monocytes. Indeed, superantigens have been presumed to directly trigger the inflammatory cascade, which is mediated by antigen-presenting cells, such as macrophages, dendritic cells and keratinocytes, thus contributing to development of psoriasis[19].

Several studies have been conducted to evaluate the role of H. pylori in the pathogenesis of psoriasis[20-26]. In one of the earlier studies about the possible relationship between H. pylori and psoriasis, Halasz[21] investigated serum immunoglobulin G (IgG) antibody titers against H. pylori in 33 psoriatic patients and established a causative link of this pathogen with psoriasis. In 2003, Qayoom et al[22] also investigated H. pylori seropositivity in a group of psoriasis patients and compared it to a group of healthy subjects. Although the seropositivity of H. pylori among the patients and controls were lower than the expected prevalence range, meaning that lower than the general population’s, since there was a statistically significant difference between the patient and control group and subjects with known upper gastrointestinal complaints were excluded from the study, they interpreted their study results as supporting a causal role of H. pylori in the pathogenesis of psoriasis[22].

Onsun et al[20] conducted a large-scale study to investigate the prevalence of H. pylori seropositivity in patients with psoriasis. Their study also aimed to figure out the relationship between disease severity and H. pylori infection, and to evaluate the impact of H. pylori infection on the response to psoriasis treatment. By means of assessing the H. pylori stool antigen in a total of 300 patients with psoriasis and 150 non-psoriatic healthy controls, it was found out that 184 psoriatic patients were infected with H. pylori. Fifty patients, which were selected from these H. pylori infected patients, randomized into two groups to receive acitretin with H. pylori eradication treatment or acitretin alone. In additon, they segregated 25 patients from the H. pylori infected patients, who received only H. pylori eradication treatment, not any systemic treatment for psoriasis. It was observed that disease severity index, Psoriasis Area Severity Index scores, were significantly higher in patients with H. pylori infection and H. pylori eradication treatment improved both the effectiveness of acitretin therapy and also the clinical outcome of the patients who did not receive acitretin[20].

In the literature, although there are also case reports describing the benefits of H. pylori eradication therapy in chronic psoriasis[27] and palmoplantar psoriasis[28,29], it is inevitable to detect studies showing that H. pylori infection is not associated with psoriasis[23,24,26]. In 2001, Fabrizi et al[23] performed [¹³C] urea breath test (¹³C-UBT) on 20 patients with psoriasis and a control group of 29 patients without any skin disorders, who were aged between 5 and 19 years, in order to investigate the presumed relationship between H. pylori and psoriasis. Results uncovered that the prevalence of H. pylori in children and teenagers with psoriasis was low and did not differ between the patient and control groups[23]. In a a case-control study including 61 patients with psoriasis and 61 healthy individuals, Azizzadeh et al[26] investigated seropositivity of H. pylori by measuring serum IgG antibody titers of H. pylori with enzyme-linked immunosorbent assay method. Accordingly, their study results revealed that there was no clear evidence to prove a causal relationship between psoriasis and H. pylori infection[26].

There have been several studies about the pathogenesis of psoriasis, which is regarded to be one of the most common and exceptional disease in dermatology practice. A lot of interest has been focused on the immune/inflammatory pathway in the pathogenesis of psoriasis.

Although the exact pathogenetic role of infectious agents remains to be determined and questions of paramount importance await to be answered, the superantigen theory has drawn growing interest in the immunopathogenesis of psoriasis[19]. It is obvious that there is a contradiction between the study results, which are about the causative role of H. pylori in the development of psoriasis[20-26] and further studies are needed to elucidate this possible role.

LICHEN PLANUS

Lichen planus is a chronic, inflammatory, papulosquamous dermatosis that affects skin, scalp, nails and mucous membranes. Lichen planus is a distinctive disease, which is designated by well-known six “Ps” mnemonic, that stands for: pruritic, polygonal, planar, purple, papules and plaques. Although the etiology of lichen planus is still under discussion, it is believed that lichen planus is a T-cell mediated autoimmune disease, of which pathogenesis is centralized on abnormal immune response[30,31]. Up to date, several studies have been conducted to evaluate the relationship of H. pylori with lichen planus[24,32-37]. In one of the earlier studies, it was revealed that the prevalence of peptic ulcer was three-fold higher in patients with chronic/repeating lichen planus when compared with controls[32].

In a hospital based cross-sectional descriptive study, H. pylori stool antigen was assessed in 105 lichen planus patients and it was found out that stool antigen was positive in 77% of the patients[33]. Likewise, Moravvej et al[34] demonstrated higher ¹³C-UBT rates in patients with lichen planus when compared with the control group. These studies suggest that H. pylori has a role in the etiology of lichen planus. A possible mechanism of pathogenesis relies on in the induction of autoimmunity by infectious agents. Lichen planus is a multifactorial disease, in which certain infectious diseases have been proposed to be associated with autoimmune processes in susceptible individuals[32].

On the other hand, in the literature there are studies which do not establish any clear evidence of causality relationship between H. pylori and lichen planus. In one of them, ¹³C-UBT performed in 30 patients with cutaneous lichen planus, in 30 patients with oral lichen planus, and in 30 healthy individuals. Accordingly, no significant association was found between lichen planus and H. pylori infection[35]. Daudén et al[24] also investigated the prevalence of H. pylori infection in patients with psoriasis and lichen planus by performing ¹³C-UBT and their study did not prove any pathogenetic role of H. pylori in the development of psoriasis and lichen planus[24]. Moreover, there are studies particularly focusing on the relationship of H. pylori with oral lichen planus, which also do not support the pathogenetic role[36,37]. As in psoriasis, the association of H. pylori with lichen planus seems to be mainly explained by induction of autoimmunity by infectious agents[32]. However, there are studies with conflicting results[24,32-37]. We suppose that further studies will demonstrate the presumed role of H. pylori in the pathogenesis of lichen planus.

PRURITUS AND PRURIGO NODULARIS

Pruritus, which is a common manifestation of several dermatologic diseases is defined as an unpleasant sensation that causes an intense desire to scratch. Pruritus is not only a symptom of a dermatosis, but also appears to be related with several systemic, neurologic and psychologic diseases[38]. Prurigo nodularis is a chronic dermatosis characterized by multiple lichenified papulonodular lesions located especially on extensor surfaces of the limbs. Prurigo nodularis is an intensely pruritic condition, which is almost entirely resistant to treatment. Although the etiology of prurigo nodularis has not been fully elucidated yet, a wide variety of systemic diseases have been implicated in the pathogenesis of prurigo nodularis[39,40].

H. pylori is one of the infections which has been reported to be associated with chronic pruritus and prurigo nodularis[19,41-44]. In 1999, Neri et al[42] screened 42 prurigo nodularis patients for H. pylori infection and found out that 40 patients were colonized with H. pylori and after H. pylori eradication treatment chronic itching was greatly reduced in 39 of these 40 patients[42]. Two Japanese studies have shown causal role for H. pylori in pruritic skin diseases[43,44]. Sakurane et al[44] examined serum levels of IgG antibody against H. pylori in 198 skin-diseased patients, 32 of which were diagnosed with pruritus cutaneous and 17 of which were diagnosed with prurigo chronica multiformis. One hundred and two of them were detected to be infected with H. pylori and after H. pylori eradication treatment, in 58% of patients with pruritus cutaneous and in 50% of patients with prurigo chronica multiformis intractable pruritus was subsided[44].

Likewise, Shiotani et al[43] investigated the prevalence of H. pylori infection and also the incidence of gastric cancer in patients with pruritic skin diseases. It was found out that 73.5% of patients with pruritus cutaneous and 76.2% of patients with prurigo chronica multiforme were H. pylori positive and early stage gastric cancer was detected in 5.6% of patients with cutaneous pruritus and 18.8% of patients with prurigo chronica multiforme. However, in the improvement of pruritus, H. pylori eradication treatment was effective only in one patient, who was diagnosed as prurigo chronica multiforme[43]. The association of H. pylori with refractory pruritus and the beneficial effect of eradication therapy in this indication have been also shown in other studies[41].

SWEET’S SYNDROME

Sweet’s syndrome, also designated as acute febrile neutrophilic dermatosis, is a neutrophilic dermatosis characterized by acute onset fever, neutrophilia, erythematous to violaceous tender plaques and nodules on face, neck, upper extremities and a typical histopathological finding of a dense upper dermal neutrophilic infiltrate[45-49]. Sweet’s syndrome is classified according to etiological and pathogenetic aspects of the disorder[46,47]. Classical Sweet’s syndrome, which generally occurs in women in their third to fifth decade of life is often associated with upper respiratory or gastrointestinal track infections, inflammatory bowel diseases and pregnancy. On the other hand, several other underlying diseases have been suggested as a predisposing factor for classical type of Sweet’s syndrome[46,47].

In 1997, Kürkçüoğlu et al[50] reported a 42-year-old woman who presented with a six-month history of recurrent episodes of fever, arthralgia, colicky abdominal pain and well-defined, infiltrated, erythematous plaques measuring up to 2 cm on face, neck and extremities. Her laboratory investigations showed elevated sedimentation rate and leukocytosis with neutrophilia. Gastrointestinal endoscopy revealed gastritis and H. pylori was identified in the gastric mucosal biopsy. Kürkçüoğlu et al[50] asserted that after H. pylori eradication treatment, patient’s skin lesions dramatically improved[50]. Although this is the only case of H. pylori associated-Sweet’s syndrome so far, since Sweet’s syndrome is considered as an abnormal immunological reaction to a variety of microbial insults[46], this case can prove the relation of H. pylori with Sweet’s syndrome.

ROSACEA

Rosacea is a common chronic inflammatory disorder, characterized by multiple clinical features including flushing, facial erythema, inflammatory papules, pustules and telangiectasias[51]. Several factors have been implicated in the pathogenesis of rosacea, which include genetic, enviromental, vascular, inflammatory factors and microorganisms^[52]. It is known that there is an association between rosacea and some gastrointestinal disorders. In addition, since a similar seasonal variation has been observed between peptic ulcer and rosacea, also both rosacea and peptic ulcer respond well to metronidazole, it has been proposed that H. pylori infection might play a triggering role in the pathogenesis of rosacea[52,53].

H. pylori produces cytokines that contribute to inflammation in gastric mucosa and host response emerges which leads to infiltration of inflammatory cells[54]. H. pylori is proposed to induce rosacea by cytotoxin mediated chronic inflammation and gastrin induced flushing[55]. Increased activity of reactive oxygen species have been reported in patients infected with H. pylori and rosacea is associated with generation of reactive oxygen species that are released by inflammatory cells[56,57]. Since the first report of an association between rosacea and H. pylori by Rebora et al[58] in 1994, there have been numerous studies investigating the prevalence of H. pylori infection in rosacea patients[58-61]. The results of those studies are conflicting, as some suggest that the prevalence of H. pylori infection is significantly increased in rosacea patients[59-61] and others suggest no association between H. pylori infection and rosacea[51,61-64]. This discrepancy might be due to different methods of evaluation of H. pylori infection between these studies. The effect of H. pylori eradication treatment in rosacea patients have been also studied. Several authors reported significant decrease in the severity of rosacea with H. pylori eradication therapy, especially in cases with papulopustular type[52,62,64,65]. But it was also suggested that the improvement of rosacea symptoms after the treatment of H. pylori might be due to the antioxidant effects of the drugs used rather than H. pylori eradication[66].

El-Khalawany et al[52] studied 68 patients with rosacea concomitant with dyspeptic symptoms and 54 controls only with dyspeptic symptoms to assess the role of H. pylori in rosacea patients who had dyspeptic symptoms. Screening for H. pylori was performed with H. pylori serum IgG and stool antigen test and gastric endoscopy was performed in H. pylori positive cases. H. pylori vacA alleles, cagA and epithelium factor antigen (iceA) genotypes were assessed by polymerase chain reaction. Significantly higher number of patients than controls were infected with H. pylori and 63.3% of the infected patients had papulopustular rosacea (PPR). Gastric ulceration and inflammation was also higher in PPR cases than erythematotelangiectatic (ETR) cases and controls. Analysis of H. pylori genotypes revealed that vacA s1m1 was more detected in PPR cases and there was a significant elevation of cagA/vacA s1m1 positivity in ETR cases. After the eradication regimen of H. pylori, a significant improvement was observed in PPR cases compared with ETR patients. The authors concluded that H. pylori had a significant etiological role in rosacea patients who had dyspeptic symptoms and the PPR type was more influenced by H. pylori infection. The authors suggested that the role of H. pylori in PPR is different from that in ETR and this is regarded to be caused by certain virulent strains that increases the inflammatory response in gastric mucosa and cutaneous lesions[52]. In addition, Boixeda de Miquel et al[65] observed higher improvement rates in PPR lesions compared with ETR after eradication of H. pylori suggesting an association between inflammatory rosacea and H. pylori infection[65].

Szlachcic et al[61] examined the prevalence of H. pylori by 13C-UBT, Campylobacter-like organism test (CLO-test), H. pylori culture and serology in rosacea patients and controls with dyspeptic symptoms. They also investigated the presence of H. pylori in oral cavity by CLO-test, H. pylori culture and saliva anti-H. pylori antibodies. They performed gastroduedonoscopy and fundic biopsy samples were taken for histological evaluation. H. pylori infection was significantly higher in the rosacea group and a noticeable number of rosacea patients showed chronic active gastritis predominantly in the anthrum and corpus while those in the control group showed mild gastritis confined to anthrum only. Among rosacea patients, 67% were CagA positive, while in the control group only 32% were CagA positive. With anti-H. pylori therapy the symptoms of rosacea disseapeared or decreased in most of the subjects. As the eradication rate of H. pylori was lower in the oral cavity than gastric mucosa the authors suggested that the lack of improvement of cutaneous symptoms in rosacea after eradication of H. pylori from the gastric mucosa may depend on the bacteria in the oral cavity[61]. As a conclusion, especially papulopustular rosacea can be considered as one of the extragastric symptoms of H. pylori infection and the eradication of H. pylori may lead to improvement of rosacea and associated gastrointestinal symptoms.

BEHÇET’S DISEASE

Behçet’s disease (BD) is a systemic vasculitic syndrome, characterized by recurrent aphthous stomatitis, genital ulcers, skin lesions and relapsing uveitis. Also articular, vascular, gastrointestinal, cardiopulmonary and neurological involvements may be observed in these patients[67,68]. Though the exact etiology of the disease has not been fully elucidated yet, enviromental factors including viral and bacterial agents and genetic factors are implicated in the pathogenesis of BD[67]. As H. pylori infection is more prevalent in areas where BD is common and both BD and H. pylori may cause ulcers in the gastrointestinal tract, it has been suggested that H. pylori may play a role in the pathogenesis BD. The possible mechanism of action of H. pylori and other bacterial infections in the pathogenesis of BD might be related with molecular homology of bacterial antigens and human heat shock protein, which is proposed as a possible antigen in BD[69].

Lankarani et al[69] investigated H. pylori infection in 48 patients with BD using serology and ¹³C-UBT. They demonstrated higher ¹³C-UBT positivity rates in patients with BD but the results of serology was not significantly different between two groups. They suggested that the reason for these conflicting findings may be related with the fact that serology can not differentiate between ongoing infection and previous exposure[69]. Cakmak et al[68] investigated 40 patients with BD with fiberoptic esophagogastroduedonoscopy and ¹³C-UBT and no significant difference was found in H. pylori positivity rates between the patient and control groups[68]. Ersoy et al[70] reported that there was no difference between BD patients and the control group in respect to H. pylori prevalence rates when biopsy specimens taken during upper gastrointestinal endoscopy were compared[70].

Apan et al[67] investigated H. pylori seropositivity and cagA status in patients with BD. While the seropositivity of H. pylori was not significantly different between the patient and control groups, the prevalence of cagA positivity was significantly higher in BD compared to controls and H. pylori eradication therapy had significantly decreased the clinical symptoms of the BD patients[67]. Avci et al[71] reported that although H. pylori seroprevalence between BD patients and controls did not show significant difference, in patients with BD who had H. pylori infection various clinical manifestations regressed after the eradication of H. pylori[71]. These findings suggest that although the prevalence of H. pylori is not increased in BD patients, eradication therapy of H. pylori may improve the clinical outcome of BD in H. pylori infected patients.

HENOCH-SCHONLEIN PURPURA

Henoch-Schonlein purpura (HSP) is a type of leukocytoklastic vasculitis of small vessels, characterized by IgA containing deposits in the skin, joints, gastrointestinal mucosa and glomeruli[72,73]. It is commonly observed in children and characterized with palpable purpura, abdominal pain, gastrointestinal hemorrhage, arthralgia and renal involvement[72,74]. Though the pathogenesis of HSP is not clear, it is thought that an antigenic particle, which may be related with exogenous sources like bacterial and viral infections, vaccinations and drugs, elicits an antigenic stimulus, causes elevation of circulating IgA and complement activation, eventually leading to vasculitis[72,75].

Few case reports have described an association between H. pylori infection and HSP in children and adults[76,77]. In addition, resolution of gastrointestinal symptoms and purpuric rashes have been described in HSP patients with H. pylori eradication treatment[72,75,78]. These reports suggest a causative role of H. pylori in the pathogenesis of HSP. Xiong et al[79] performed a meta-analysis about the association of H. pylori infection with HSP development in Chinese children. They reported that 49.27% (369/749) of children with HSP had the evidence of H. pylori infection compared with 23.39% (131/560) of children in the control group and H. pylori eradication therapy was capable of reducing the recurrences of HSP. They suggested it is advisable to screen H. pylori infection in children with HSP, particularly in those with gastrointestinal manifestations[79].

Cai et al[80] investigated the effect of H. pylori eradication therapy on prognosis in children with HSP. 153 children with HSP were divided into three groups: group 1 included patients with H. pylori infection who received H. pylori eradication therapy in addition to conventional therapy, group 2 included control group, in which patients were H. pylori positive but only received conventional therapy for HSP, group 3 included H. pylori infection-negative group, who also received conventional therapy for HSP. The response and recurrence rates of HSP were not significantly different between three groups but the incidence of HSP nephritis was significantly lower in the H. pylori infection treatment group. The authors concluded that H. pylori eradication therapy may be useful in reducing the incidence of HSP in children infected with H. pylori[80].

Novák et al[73] investigated H. pylori antibodies in 11 adult patients with HSP and the serological investigations revealed H. pylori infection in 10 patients. Patients in the acute phase had significantly higher levels of anti H. pylori IgG levels compared to patients in remission phase. In addition, anti H. pylori IgA levels were elevated with significant difference in patients in the remission phase[73]. We suggest that it would be useful to investigate H. pylori infection in patients with HSP, especially if they have gastrointestinal manifestations of HSP. Summary of some of the studies concerned with the association of H. pylori in the pathogenesis of inflammatory skin diseases is shown in Table 1.

Table 1 Summary of some of the studies concerned with the association of Helicobacter pylori in the pathogenesis of inflammatory skin diseases, shown in order of publication date.

Ref.	Study design	Result
Halasz[21]	Investigation of serum H. pylori IgG antibody titers in 33 psoriatic patients	Suggesting a potential link of H. pylori with psoriasis
Daudén et al[24]	Performing 13C-UBT on 84 patients with psoriasis and 61 patients with lichen planus	Suggesting no evidence of a link between H. pylori and psoriasis and H. pylori and lichen planus
Fabrizi et al[23]	Performing 13C-UBT on 20 psoriatic patients and 29 healthy controls	Suggesting no evidence of a link between H. pylori and psoriasis
Szlachcic[61]	Performing 13C-UBT, CLO-test, oral cavity CLO-test, bacterial culture and fundic biopsy, investigation of serum and saliva H. pylori IgG and IgA antibody titers	Suggesting a potential link of H. pylori with rosacea and improvement of symptoms of rosacea with H. pylori eradication treatment
Qayoom et al[22]	Investigation of serum H. pylori seropositivity in 50 psoriatic patients and healthy controls	Suggesting a potential link of H. pylori with psoriasis
Novák et al[73]	Investigation of serum H. pylori seropositivity in 11 adult HSP and 20 healthy adult patients	Suggesting a potential link of H. pylori with HSP
Shiotani et al[43]	Investigation of serum H. pylori IgG antibody titers in 134 patients with pruritic skin diseases	Suggesting a potential link of H. pylori with pruritic skin diseases and H. pylori positivity in pruritic skin diseased patients with gastric cancer
Moravvej et al[34]	Performing 13C-UBT on 80 patients with lichen planus and 80 patients with other skin diseases	Suggesting a potential link of H. pylori with lichen planus
Ersoy et al[70]	Performing endoscopy, histopathological examination and RUT in 45 patients with BD and 40 healthy controls	Suggesting no evidence of a link between H. pylori and BD
Cakmak et al[68]	Performing 13C-UBT in 40 patients with BD and 40 healthy controls	Suggesting no evidence of a link between H. pylori and BD
El-Khalawany et al[52]	Investigation of serum H. pylori IgG antibody titers and H. pylori stool antigen in 68 patients with rosacea and 54 healthy controls and performing H. pylori genotyping	Suggesting a potential link of H. pylori with rosacea and certain virulent strains with rosacea subtypes
Onsun et al[20]	Investigation of H. pylori stool antigen in 300 psoriatic patients and 150 healthy controls; investigation of H. pylori stool antigen in 25 patients before and after acitretin treatment	Suggesting a potential link of H. pylori with the etiology and the severity of psoriasis
Lankarani et al[69]	Performing 13C-UBT and investigation of H. pylori seropositivity in 48 patients with BD and 48 healthy controls	Suggesting a potential link of H. pylori with BD

H. pylori: Helicobacter pylori; Ig: Immunoglobulin;

¹³C-UBT: ¹³C urea breath test; CLO-test: Campylobacter-like organism test; HSP: Henoch-Schonlein purpura; RUT: Rapid urease test; BD: Behçet’s disease.

CONCLUSION

H. pylori is a world-wide spread bacterium, which is estimated to infect more than half of the world’s population. H. pylori has been implicated in the pathogenesis of a number of gastrointestinal system disorders, also classified as a gastric carcinogen since it has been proven that H. pylori-induced chronic gastric inflammation triggers the events that can promote gastric carcinogenesis. Recent studies have suggested that H. pylori induces not only local inflammation, but also systemic inflammation. There is a growing body of evidence concerning the causative role of Helicobacter pylori-induced systemic inflammation in the pathogenesis of several extragastric diseases, including endocrinological, autoimmune and dermatological ones. However, conflicting results were noted among the individual studies, which evaluate the pathogenetic role of H. pylori in the development of these diseases. In this review, we have concentrated on the pathogenetic role of H. pylori in the pathogenesis of inflammatory skin diseases. On the other hand, we think that there is a need for further studies to better define the role of H. pylori in inflammatory skin diseases.