The Influence of Helicobacter pylori Infection Treatment on Psoriasis Severity

Abstract

Helicobacter pylori infection is a condition caused by the gram-negative bacterium H. pylori affecting the mucous lining of the antrum portion of the stomach. At least 50% of the global population fall victim to this condition with Africans proven to have the highest prevalence rate of 70%, followed by South America and Western Asia with 69.4 and 66.6% respectively. In Africa, Nigeria is said to have the highest prevalence rate of H. pylori infection recording 87.7 to 89.7%. H. pylori infection is known to inflict a wide range of gastric complications including Peptic ulcer disease among others, and extra gastric complications such as Neurological diseases, as well as Dermatological diseases. Psoriasis, an autoimmune chronic inflammatory disease of the skin, affecting more than 100 million individuals globally, is one of the dermatological complications of H. pylori infection. It has been noted that H. pylori seem to play a major role in the development of psoriasis. Therefore, this chapter seeks to provide readers with the connection between H. pylori infection and Psoriasis as well as the influence the treatment of H. pylori infection has on Psoriasis severity.

1. Introduction

1.1 Helicobacter pylori

Helicobacter pylori (H. pylori) infection has over the years posed a global health burden significance, having a worldwide prevalence of 4.4 billion infected individuals approximately [1]. It has persisted for multiple decades among individuals at different part of the world, having a prevalence rate of 50% in the western world and an 80% prevalence rate among the population living in developing countries [2, 3]. A systematic review was carried out and it revealed that Africa, South America, and Western Asia had H. pylori infection prevalence rates of 70.1, 69.4, and 66.6%, respectively [4]. Epidemiological studies have projected Nigeria and South Africa to be the African nations experiencing high prevalence rates of 91 and 87% respectively when it comes to H. pylori infection, and 23% among Canadian adults in the Western world [5]. A systematic study conducted by Awuku et al. supported the fact that the adult population in developing countries has a higher prevalence rate of H. pylori infection as compared to children under 5 years with 90 and 50% respectively, whereas in developed countries like the USA has a higher prevalence rate of 10% among the adolescent individuals and 5% among children under 5 years of age [6]. A study conducted in Uganda by Aitala et al. shows that H. pylori infection among children varies with increasing ages ranging from 1 to 5 years, 6 to 10, and 11 to 15 with 16.2, 27.2, and 36.71% as their respective prevalence rate [7].

In 1982, two Australian researchers, Barry Marshall and Robin Warren conduct a study that included biopsies from 100 patients, and observed the presence of small, curved bacteria which will later be called Helicobacter pylori, in the lower stomachs in nearly all patients with gastric inflammation, duodenal ulcers, and stomach ulcers [8]. After this vital effort in the field of gastroenterology gained global recognition by the National Institutes of Health Consensus Development Conference in 1994, Food and Drug Administration (FDA) in 1996, and Centers for Disease Control and Prevention (CDC) in 1997, the Nobel Prize Foundation awarded Marshall and Warren a Nobel Prize in physiology and medicine later in the year 2005 [1, 8]. Recent studies have identified H. pylori to play a major role in the development of diseases such as gastritis and mucosa-associated lymphoid tissue (MALT)lymphoma, as well as peptic ulcer and gastric cancer [1].

Helicobacter pylori infection is caused by the gram-negative micro bacterium Helicobacter pylori (H. pylori), which is helicoidal, unipolar, and multiflagellate in nature having the tendency to cause gastritis, peptic ulcer disease (PUD) as well as gastric cancer by inhabiting the gastric mucosa of its victim [9]. It has an average length that ranges from 2.5 to 5.0 μm and width from 0.5 to 1.0 μm [10]. H. pylorus is a slow-growing microbe that can be cultured both on none selective agar media such as blood or chocolate agar and on selective agar media such as Skirrow’s media incubated at 35 to 37°C in a 5% oxygen atmosphere for 3 to 7 days [11]. This microorganism possesses 2 to 7 unipolar sheathed flagella rising from a smooth and rounded outer membrane which enhances its mobility through viscous solutions [12]. Under hostile conditions like stressed, old, or mal-nutritious and prolonged air exposure cultures, the microbe can become dormant enabling its long-term adaptation and survival in less favorable environment outside of the host organism [13]. Electron microscopic studies have identified that Helicobacter pylori can exist in spiral forms that are viable, can be cultured, virulent, and can infect experimental animals to cause inflammation [14]. The second form is the coccoid form, where the microbe is viable, but cannot be cultured and is less virulent to colonize or cause inflammation in experimental animals [14]. The final form is degenerative, and this form cannot be cultured and is considered as the death form of H. pylori [14].

Numerous epidemiological studies have demonstrated that eating contaminated foods, living in crowded areas, having a low socioeconomic status, and practicing poor personal and environmental hygiene are the main risk factors for contracting H. pylori infection, particularly in developing nations [15, 16]. Additionally, it has been established that swimming in rivers, streams, or pools increases one’s risk of H. pylori infection by three times as compared to non-swimmers [14]. The H. pylori bacteria can be found in close proximity to human environments in animals including cows, cats, dogs, and sheep, placing nearby people at risk of contracting the infection [17].

Few works of literature have been provided on the main route of infection, however, in both developing and developed nations, H. pylori infection occurs throughout infancy or adolescence and can spread through oral-oral or fecal-oral, person-to-person, as well as through zoonotic transmission [17, 18, 19]. H. pylori infection routes confined to the person–person transmission can be conceivable through direct contact with the saliva, vomit, or feces of the infected person, as well as from nursing mothers, family members, or caretakers even to babies at the early stages of life [7, 20]. Genetic susceptibility in the development of H. pylori infections is also possible in according to scientific studies [21]. Vertical and horizontal transmission are the two primary divisions of person-to-person transmission [22]. The spread of infection among members of the same family is the vertical mode of transmission, whereas the horizontal form of transmission includes contamination among individuals outside the family [22].

Gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma have been associated with Helicobacter pylori, a causative agent of gastritis and peptic ulcers [23]. H. pylori’s capacity to produce this range of illnesses is influenced by host, bacterial, and environmental variables [15, 24]. Urease, flagella, adhesins, δ-glutamyltranspeptidase, lipopolysaccharide, and vacuolating, cytotoxin are some of the bacterial components required for H. pylori to colonize the stomach mucosa, remain for decades, and cause a severe inflammatory response that damages host cells [15]. Non-steroidal anti-inflammatory medicines (NSAID), alcohol, and smoking are examples of environmental factors, and host factors like gene polymorphism and immune response can also play a role [24]. Despite the stomach’s unfavorable environment, H. pylori can use it as its principal site of colonization and survive there for years [1]. The four main steps necessary for H. pylori colonization and pathogenesis are as follows: (1) surviving in the acidic environment of the stomach; (2) moving toward epithelium cells through flagella-mediated motility; (3) attaching to host receptors by adhesins; and (4) inflicting tissue damage by releasing toxins [25]. At each crucial stage, H. pylori engages in a particular strategic activity to promote effective colonization, persistent infection, and disease pathogenesis [24]. In order to evade the stomach’s acidic environment and spread a chronic infection, the pathogen first enters the host stomach lumen and then localizes to the antrum and corpus for adaption before it neutralizes the stomach’s hostile acidic environment with its urease activity [26, 27]. Following effective colonization and sustained infection, H. pylori must first migrate toward the host gastric epithelial cells using flagella-mediated motility. Next, specific interactions between bacterial adhesins and host cell receptors ensue [27]. At last, cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA), among others, are released by H. pylori to cause damage to the host’s tissues [27]. Additionally, the gastric epithelial layer, which functions as the main point of contact between H. pylori and the host, secretes chemokines that stimulate neutrophils and start innate immunity, which in turn causes clinical illnesses like gastritis and peptic ulcer to develop [27].

Studies have shown that most Helicobacter pylori infections are asymptomatic, with about 30–35% of patients showing no symptoms, which is frequently seen in young people [28]. According to one school of thought, the host’s genetics, the properties of the bacteria, and the environment can all interact to cause a variety of clinical symptoms in the affected person [21]. Research among students found that nausea (25.5%), gastrointestinal discomfort (24.5%), and heartburn (20.2%) were the most common symptoms linked to H. pylori infections, followed by vomiting (12.8%), appetite loss (5.3%), and dyspepsia (3.2%) [29]. Some signs and symptoms commonly associated with H. pylori infection include fatigue, weakness, digestive bleeding, gastric reflux, weight loss, low appetite, bloating in the belly, dark stools, frequent burping, nausea, vomiting, gnawing or searing stomach pain [30, 31]. Although it can happen at other times, abdominal pain typically manifests itself in the early morning hours, between meals, and when the stomach is empty [32]. Late eradication of the H. pylori infection can be accompanied by both gastric and extra-gastric complications [33, 34]. Helicobacter pylori infection is the primary cause of gastric complications such as chronic gastritis, gastric ulcer, duodenal ulcer, gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma [35], and associated extra-gastric complications, including Allergic Diseases, Metabolic Diseases, Neurological Diseases, Inflammatory Bowel Diseases, Esophageal Diseases, Dermatologic Diseases, Ophthalmic Diseases, Hematological Diseases [36, 37].

Many gastroduodenal illnesses can be effectively treated and eradicated if H. pylori infection is early and correctly diagnosed [38]. There are both invasive and non-invasive diagnostic methods for the identification of H. pylori, and each test has benefits and drawbacks depending on the clinical situation [18, 38]. Although there is no single technique that can be used as the gold standard in clinical practice, numerous have been established and are necessary to get more accurate outcomes [38]. Endoscopic biopsy samples are used for invasive procedures, such as histology, culture, fast urease test, and molecular techniques [18, 39]. The real-time diagnosis of H. pylori during endoscopy is also made possible by advancements in endoscopic technology [38]. The most used non-invasive diagnostic methods are the urea breathing test and stool antigen test, whereas serology is beneficial for screening and epidemiological research [39]. Other than gastric mucosa, variable specimens have been studied using molecular approaches [38]. In addition to the H. pylori infection test, other tests are used to screen for precancerous lesions, gastric cancer, and H. pylori virulence factors and antibiotic sensitivity [38, 39]. In order to lower the prevalence of antibiotic resistance, the American College of Gastroenterology (ACG) advises testing in patients with symptoms of dyspepsia, active peptic ulcer disease, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma [40, 41].

Following endoscopic resection for an H. pylori-positive gastric adenoma [42], H. pylori eradication can be advised, and the chosen treatment plan should have an eradication rate of at least 90% [43, 44], to prevent local recurrence and to improve dyspeptic symptoms over the long term in patients with functional dyspepsia [45, 46]. There are other H. pylori treatment plans, including triple therapy, sequential therapy (the patient receives one treatment, then another), quadruple therapy, and triple therapy based on levofloxacin [45]. Studies have demonstrated that the eradication regimen is an effective management in reducing H. pylori infection linked with gastric cancer and extra-gastric complications [43]. Single and dual medication regimens have unacceptably poor cure rates and are not advised, but triple and quadruple therapies have shown eradication rates approaching 90% or higher [1, 43]. The goal of treating an H. pylori infection is to eradicate the H. pylori microbe, heal an ulcer that may be present in the duodenum or stomach, and avoid a recurrence of the infection, which may occur after 7 to 14 days of treatment [42]. In the treatment of the infection, antisecretory agents are used in combination with antimicrobial agents to achieve the bactericidal effect [1].

The bacterium can be eliminated with antibiotics such as Amoxicillin, Clarithromycin, Metronidazole, Tetracycline, or Tinidazole [47]. By preventing the stomach from producing gastric acid, Dexlansoprazole, Esomeprazole, Lansoprazole, or Omeprazole can reduce the amount of gastric acid secreted [47]. Common histamine H2-receptor antagonists (H2 blockers) like Cimetidine, Famotidine, Nizatidine, and Ranitidine are used to prevent histamine from mediating the production of gastric acid, which is necessary to erode the lining of the stomach [47]. Surgery is not a viable option for those with H. pylori infection and should only be suggested for those who are experiencing serious problems, such as malignancies [42]. Amoxicillin, Clarithromycin, and Proton-pump inhibitor (PPI) for a period of 14 days have been selected as the first-line eradication management for routine triple therapy [21, 42]. It has been shown that PPI, Metronidazole, Amoxicillin, and Clarithromycin have an eradication efficiency rate of 84.3% [15]. Even after treatment, patients must undergo another test to ensure that the Helicobacter pylori infection has been completely eliminated [21]. Sequential therapy has been shown to achieve positive outcomes with an efficiency rate greater than 90% in the eradication therapy technique [48]. The length of the eradication therapy is also crucial, and studies and recommendations from the European and American medical communities suggest that a consecutive 14-day course of treatment is the most effective among durations of 7, 10, or 14 days [48].

It is crucial that clinicians inform patients about the consequences of noncompliance because H. pylori antibiotic resistance, which is rising in most of the world, is a significant factor in treatment failure [44]. This resistance is brought on by decreased adherence to clinical regimens and nutrition therapies [43]. It has been demonstrated that a compliance rate of less than 80% reduces treatment effectiveness [44]. A medication susceptibility test should be performed before taking therapy in order to determine the appropriate regimen required for precise management [49]. Due to the rising abuse and overuse of antibiotics for the treatment of various infections in the majority of developing countries, H. pylori infection has a higher prevalence rate of antibiotic resistance than other bacteria [15]. Antibiotic resistance in young people is a result of some contributing variables, such as the failure to respond to therapy and inadequate gastric suppressants [42]. The World Health Organization (WHO) highlighted H. pylori resistance in 2017 as a significant factor in the treatment of H. pylori and as a prevalent source of community-acquired infection [15]. Since first-line therapy has been found to have a failure rate of roughly 20%, it has been suggested that second-line therapy be added to eliminate H. pylori [49].

1.2 Psoriasis

Psoriasis is a chronic, immune-mediated inflammatory skin disease, characterize by red, scaly plaques occurring most commonly on the elbows, knees, scalp, and lower back, as well as any part of the skin surface [50]. The condition greatly affects people’s quality of life to the extent that it could be life-ruining and stigmatizing [50, 51]. Psoriasis is now considered a systemic disease and is associated with psychological, metabolic, arthritic, and cardiovascular comorbidities [50, 52], which have been proven by epidemiological studies to reduce the lifespan of affected individuals [50]. In addition to the psychological and social burden related to psoriasis, the cost to patients and healthcare systems is high [50, 53]. Psoriasis can occur at any age, although most patients present with the condition before 35 years old [50].

Psoriasis has probably been as old as modern man and has also been reported in non-human primates, but was recognized as a disease in the nineteenth century [51]. The root word of psoriasis was derived from the Greek word ‘Psora’, referred to as itch [51]. For centuries, patients with psoriasis suffered the same cruel fate as lepers because there was random grouping together of all inflammatory skin diseases which brought about the stigmatization of patients with psoriasis until it was separated from leprosy and its significant signs and types were also identified [51]. Essential signs were discovered by great physicians over the years such as the recognition of the Auspitz sign, Köbner’s phenomenon, Munro’s abscesses, generalized pustular psoriasis, and the Woronoff ring have provided important diagnostic tools which allowed physicians to be more confident in diagnosing psoriasis these days [51]. Today in the twenty first century, psoriasis is no longer regarded simply as a skin condition, but as a chronic autoimmune disease, characterized by systemic inflammation which affects not just the skin, but also joints and other bodily systems [51].

Psoriasis is a common chronic inflammatory disease with a prevalence rate of 0.33–0.6% in different races and affects approximately 125 million people worldwide [53]. Based on the 2020 US census data, there were an estimated 7.55 million US adults with psoriasis [54]. White individuals have been identified to have the prevalence rate of 3.6%, followed by other racial/ethnic groups (non-Hispanic, including multiracial) at 3.1%, Asian individuals at 2.5%, Hispanic individuals (including Mexican American and other Hispanic individuals) at 1.9%, and Black individuals at 1.5% [54]. Systematic reviews have revealed that psoriasis prevalence in children in Italy is approximately 2.1% and that the rates among adults vary from 0.4% in Asian countries to 8.5% in Norway [50, 54]. Higher prevalence rates have been reported at higher latitudes and in white people compared to other ethnic groups [50]. Adults were more likely than children to develop psoriasis [50]. From 0.02% (95% confidence interval 0.01 to 0.04%) in east Asia to 0.22% (0.06 to 0.81%) in Australasia and 0.21% (0.11 to 0.41%) in western Europe, psoriasis prevalence in children varies [50, 54]. From 0.14% (0.05 to 0.40%) in east Asia to 1.99% (0.64 to 6.60%) in Australasia, the disease affected adults in different ways [50]. Western Europe (1.92, 1.07 to 3.46%), central Europe (1.83, 0.62 to 5.32%), high-income North America (1.50, 0.63 to 3.60%), and high-income southern Latin America (1.10, 0.36 to 2.96%) were other locations with an occurrence rate of the disease above 1% [50, 53]. The scalp (43.0%; 1726/4016) was the area of the body most commonly afflicted by psoriasis that was difficult to cure, followed by the face (29.9%; 1200/4016), nails (24.5%; 982/4016), soles (15.6%; 628/4016), genitals (14.1%; 568/4016), and palms (13.7%; 551/4016), in that order [53]. Sixty-two percent (2602/4016), 42% (1702/4016), and 29% (878/4016) of all patients, respectively, had involvement in one or more, two or more, or three or more hard-to-treat areas [53].

There are several risk factors that can contribute to the development of psoriasis [55]. Today, it has been recognized that psoriasis results from a complex interaction between immunological, genetic, cellular, and environmental factors [51, 52, 55]. Since many people with psoriasis have a family history of the condition, researchers have identified a few genes that may be involved in its onset [52]. These genes all have an impact on how well the immune system works. The risk of having psoriasis may be increased by a number of extrinsic causes, like smoking, obesity, stress, cold temperatures, skin injuries, and certain races may also predispose a person to certain infections, including streptococcal and HIV infections, as well as some medications for treating heart disease, malaria, or mental health issues [55].

The dermatologic manifestations of psoriasis can be classified into different groups depending on their characteristics [56]. Nail psoriasis is the type that affects the fingernails and toenails, causing pitting, abnormal nail growth, and discoloration [56]. Young people and children are most commonly affected by Guttate psoriasis, which is characterized by small, drop-shaped patches of scaling on the trunk, arms, or legs and is typically brought on by a bacterial infection like strep throat [52]. Smooth patches of inflammatory skin that get worse with friction and perspiration are the main symptoms of inverse psoriasis, which primarily affects the skin folds of the groin, buttocks, and breasts [55]. This kind of psoriasis may be brought on by fungi [52]. A rare form of psoriasis called Pustular psoriasis can affect tiny portions of the palms or soles or form large patches with distinct pus-filled blisters [56]. The least frequent type of psoriasis, Erythrodermic psoriasis can cover the entire body with a peeling rash that can itch or burn violently and is typically short-term (acute) or long-term (chronic) [55]. The most prevalent form of psoriasis is Plaque psoriasis [56], which results in scale-covered, dry, elevated skin patches (plaques) [52]. They might be few or numerous and typically show up on the scalp, lower back, elbows, and knees [56]. The color of the patches varies depending on the skin tone, and on dark or Black skin, in particular, the afflicted skin may recover with transitory color changes (post-inflammatory hyperpigmentation) [56]. Joints are impacted by Psoriatic arthritis, which is typically a severe case of psoriasis [55]. The final one is Sebo-psoriasis, a kind of psoriasis that crosses with seborrheic dermatitis and often manifests on the face and scalp as red bumps and plaques with a greasy yellow scale [52].

The hallmark of psoriasis is sustained inflammation that leads to uncontrolled keratinocyte proliferation and dysfunctional differentiation [52]. The histology of the psoriatic plaque shows epidermal hyperplasia of about 10 times the usual [51], and the inflammatory infiltrates are composed of dermal dendritic cells, macrophages, T cells, and neutrophils [52]. This epidermal hyperplasia process results in the thickening, crusting and scaling of the skin [51]. Neovascularization is also a prominent feature [52]. The inflammatory pathways active in plaque psoriasis and the rest of the clinical variants overlap but also display discrete differences that account for the different phenotypes and treatment outcomes [52]. The process in psoriatic patients can occur in only 2 days [52]. It soon became clear that the high turnover of epidermal cells was caused by a series of autoimmune reactions, in which a portion of the body’s immune system overreacts and targets healthy tissues [51, 52]. Following the production of certain inflammatory chemicals called cytokines, the resultant inflammation causes reddish, thickened, dry, and scaly skin as characteristics of psoriasis [51, 52, 56]. It has also been identified that psoriatic disease blocks the action of a specific type of immune cell called a T-cell, or they block inflammatory proteins (cytokines) such as tumor necrosis factor-alpha (TNF-alpha), and interleukins (17A, 12, and 23) which play an essential role in the development of the skin and joint manifestations of psoriasis [51].

The signs and symptoms of psoriasis can vary depending on the type of psoriasis present in the individual [55]. The following are the top five psoriasis signs and symptoms: Rashes or red, inflammatory skin patches that are frequently covered in loose, silver-colored scales [55]. In more severe cases, the plaques will spread and converge, covering substantial amounts [52, 55]. Scratching itchy, irritated skin can cause small patches of the skin to split or bleed [55]. Psoriasis can also be associated with psoriatic arthritis, which causes achy, swollen joints, usually common in approximately 10–30% of people with psoriasis [53, 54, 55].

People with psoriasis may also be more likely to get certain complications such as cancers, Crohn’s disease, diabetes, metabolic syndrome, obesity, osteoporosis, uveitis (inflammation of the middle of the eye), liver disease, metabolic diseases, cardiovascular diseases, such as heart attacks, strokes, chronic kidney disease (CKD), gastrointestinal diseases, malignancy, mood disorders, infections and psoriatic arthritis (PsA), and mental health problems, such as low self-esteem, anxiety, depression as well as psoriatic arthritis, a chronic form of arthritis that causes pain, swelling, and stiffness of the joints and places where tendons and ligaments attach to bones (entheses) [55].

Psoriasis is primarily diagnosed through clinical means [56]. The most prevalent clinical form of psoriasis, which affects 80–90% of psoriasis sufferers, is chronic plaque psoriasis [56]. Erythematous plaques that are clearly defined, symmetrical, and covered in a silvery scale are the distinguishing features of classic plaque psoriasis [56]. In a physical examination, the skin is examined to identify lesions and note their distribution, size, form, and appearance [57]. During a physical exam, the psoriatic patient may be asked about his or her symptoms, medical and family history [57]. Also, a Skin Biopsy may be required to accurately diagnose the type of psoriasis [58].

Treatment of psoriasis is still based on controlling the symptoms [55]. Topical and systemic therapies as well as phototherapy are available in the treatment of psoriasis [51]. In practice, a combination of these methods is often used, and treatment is usually lifelong which is aimed at remission [52, 53]. Scientific research has proved that care for patients with psoriasis requires not only treating skin lesions, stopping skin cells from growing so quickly, removing scales and joint involvement, but it is also very important to identify and manage common comorbidity that already exists or may have developed, including cardiovascular and metabolic diseases as well as psychological conditions [51, 55]. Treatments may depend on how severe the psoriasis is and how responsive it has been to previous treatment and self-care measures [54]. Topical therapy may involve the use of Corticosteroids, Vitamin D analogs, Retinoids, Tazarotene, Calcineurin inhibitors, Salicylic acid, Coal tar, and Anthralin [50, 55]. Light therapy is a first-line treatment for moderate to severe psoriasis, either alone or in combination with medications [52]. It involves exposing the skin to controlled amounts of natural or artificial light [52]. The use of light therapy includes Sunlight, Goeckerman therapy, Ultraviolet B (UVB) broadband, Ultraviolet B (UVB) narrowband, Psoralen plus ultraviolet A (PUVA), and Excimer laser [52]. Oral or injected medications may include Steroids, Biologics, Methotrexate, and Cyclosporine [52].

2. Helicobacter pylori and psoriasis

2.1 Positive correlation

Onsun et al. studied the prevalence of H. pylori seropositivity in psoriasis patients, the link between PASI (Psoriasis Area and Severity Index) scores and H. pylori infection, and the effect of H. pylori infection on treatment response. To ascertain the prevalence of H. pylori seropositivity in psoriasis, the association between PASI scores and H. pylori infection, and the effect of H. pylori infection on the response to treatment, 300 patients with plaque-type psoriasis and 150 non-psoriatic healthy controls were studied. Both patients and controls had a stool antigen test for H. pylori. PASI scores were used to evaluate each patient’s illness severity. From 184 H. pyloric-infected psoriatic patients, 50 were chosen at random. These 50 were divided into two groups, with the first group (n = 25) receiving acitretin monotherapy and the second group (n = 25) receiving H. pyloric treatment. Twenty-five (25) patients who only underwent H. pyloric treatment without receiving any systemic therapy were also contrasted with the two groups. The PASI scores of the patients were assessed and contrasted 8 weeks later. Psoriatic patients (n = 184) had a 61.3% prevalence of H. pylori infection, compared to 59.3% in controls (n = 89/150; P > 0.05). Patients who received both acitretin and treatment for H. pylori infection improved more quickly than those who received only acitretin (mean PASI score drop, 3.38 ± 1.99; P < 0.001 vs. 1.22 ± 0.77; P < 0.05). Patients who solely underwent H. pylori therapy showed significant improvement compared to controls (mean PASI score decreased from 2.85 to 1.25; P < 0.001). According to this research, H. pylori infections may contribute to the severity of psoriasis, and eliminating them will improve the effectiveness of psoriasis treatment [59].

A case–control study was conducted on 40 patients with psoriasis Vulgaris and 40 age-matched and sex-matched healthy individuals. The aim of the study was to clarify the role of Helicobacter pylori infection in psoriatic patients with palm and sole affection. This case–control study was conducted at the Dermatology, Andrology, and Sexually transmitted diseases and Medical Biochemistry Departments of the Faculty of Medicine, Menoufia University. Every patient underwent a thorough medical examination and history taking. Using an enzyme-linked immunosorbent test, the anti-H. pylori immunoglobulin G levels in the blood were determined. Statistics were used to compare anti-H. pylori immunoglobulin G serum levels to psoriasis area and severity index score. Patients with Psoriasis Vulgaris of either sex who had not previously received either systemic (3 months) or topical (2 weeks) treatment for their psoriasis met the inclusion criteria. Exclusion criteria included patients with other dermatological diseases except for psoriasis Vulgaris, patients with autoimmune diseases such as systemic lupus erythematosus, patients with inflammatory bowel diseases, patients with chronic diseases such as chronic renal failure, and patients having infectious conditions at the time of blood sampling such as bacterial infections [60].

In the PASI score, the body is divided into four sections: head (H), arms (A), trunk (T), and legs (L). Each of these areas is scored by itself, and then the four scores are combined into the final PASI score. In each of these areas, the percentage of the total surface area that was impacted was graded on a scale from 0 to 6, where grade 0 corresponds to 0% of the involved area, grade 1 to less than 10%, grade 2 to 10–29%, grade 3 to 30–49%, grade 4 to 50–69%, grade 5 to 70–89%, and grade 6 to 90–100% of the involved area. According to the findings, patients who did not exhibit palm and sole affection had a higher prevalence of H. pylori infection. However, 50% of palm-affected and sole-affected patients were positive for H. pylori infection (P = 0.02). Therefore, it was concluded that H. pylori may play a significant role in the development of palmoplantar psoriasis and may provide important clues to assist in the development of new therapeutic strategies for palmoplantar psoriatic patients through its eradication [60].

Fathy et al. conducted a study with the aim to evaluate the occurrence of H. pylori infection in chronic plaque-type psoriasis patients in order to determine a possible contribution to the pathogenesis of psoriasis. They compared 20 patients with chronic plaque-type psoriasis with 20 healthy, age- and sex-matched controls for H. pylori infection by using H. pylori IgG quantitative enzyme immunoassay (ELISA test). Patients under the age of 18, women who were expecting or nursing babies, and anyone who had taken antibiotics 40 days or histamine H2-receptor antagonists (H2 blockers) 14 days before sample withdrawal were all excluded from the study. Patients with peptic ulcer disease, gastrointestinal tract complaints, autoimmune or skin conditions, or those who had received therapy for psoriasis in the past were also disqualified. Every candidate conducted a background check, paying particular attention to their psoriasis history (onset, precipitating factors, course, and duration of the disease). Clinical examination revealed that the patients had persistent plaque-type psoriasis. The severity and breadth of psoriasis were assessed using the Psoriasis Area and Severity Index (PASI score). Greater values were associated with more severe psoriasis. In psoriatic patients, the mean (SD) prevalence of H. pylori IgG seropositivity was considerably higher than in controls (67.7 ± 32.5 vs. 33.9 ± 15.1; P < 0.05). These findings can support the hypothesis that H. pylori and psoriasis are related. For a definitive confirmation, large-scale investigations and additional research are needed for psoriatic patients who are H. pylori seropositive [61].

2.2 Negative correlation

A study conducted by Cinar et al. at Ankara Numune Education and Research Hospital Dermatology Department among 120 histopathologically diagnosed psoriasis patients and seropositive for Helicobacter pylori. The aim of the study was to evaluate the possible effect of Helicobacter pylori eradication on the psoriasis course. The Helicobacter pylori positivity was established using the carbon-14 urea breath test. The study also excluded patients under the age of 18 and those who had used any systemic medication within the previous 6 months or any topical medication other than emollients within the previous month. The psoriasis area severity index was used to assess the severity of the disease (PASI). At the commencement, at the conclusion of the eradication therapy (15th day), and at the 30th day, the patient’s psoriasis area severity index (PASI) scores were computed. The difference in the mean PASI score between the two groups was compared. The study did not include anyone with a PASI score higher than 10. After the confirmation of H. pylori positivity, eighty (80) of the patients were given eradication therapy for H. pylori for fourteen (14) days which were clarithromycin (500 mg/twice daily), lansoprazole (30 mg/twice daily), and amoxicillin (1000 mg/twice daily). Forty psoriasis patients were chosen to be in the control group. The patients in the control group were not given any medication for H. pylori eradication. The mean age and sex distribution between the patient and control groups were similar. Prior to therapy, the body mass indices (BMI) of the patients were also determined to identify whether there would be a correlation between the BMI and H. pylori eradication response. The study’s findings revealed a statistically significant decline in the treatment group’s mean PASI score in percentage terms on both the 15th and 30th days. However, there was no discernible difference in the groups’ PASI-50 or PASI-75 responses. The patients’ responses to eradication therapy did not correlate with their body mass indices. So it was concluded that although there was a decrease in the mean PASI scores after eradication therapy, the number of patients who had a PASI-50 response was not significant, hence H. pylori eradication is not effective in healing psoriasis [62].

A case–control study was done on 61 patients with Psoriasis Vulgaris (cases) and 61 healthy individuals (controls) in Fatemiye Hospital (referral center for the treatment of skin diseases), Semnan, Iran. The aim of this study was to determine the relationship between H. pylori seropositivity and psoriasis. The Semnan University of Medical Sciences ethical commission in Iran gave its approval before the study could begin. The inclusion criteria were met by otherwise healthy people who had seen a dermatologist for cosmetic issues (control group) and patients with known Psoriasis Vulgaris (case group). Excluded from the study were patients having a history of gastrointestinal issues, those who had taken oral corticosteroids or b-blockers, or who had used topical or systemic treatment for 2 or 6 months, respectively. Prior to starting treatment, psoriatic patients had a clinical evaluation based on the PASI score and percentage of body surface area affected. To assess the severity of skin illness, the PASI was utilized. The effect of IgG against H. pylori was examined in all patients using an enzyme-linked immunosorbent assay (ELISA) kit (DRG Instruments, GmbH, Marburg, Germany) according to the manufacturer’s protocol. Ten (16.4%) of the psoriatic patients and 8 (13%) of the control groups had an H. pylori seropositive test result; the average IgG serum level was 17.3 IU/ML in psoriatic patients and 16.1 IU/ML in the control group. The difference in serum levels between the two groups was not meaningful (P = 0.302). It was shown that neither the severity of psoriasis nor the serum level of IgG Anti-H. pylori were found to be significantly correlated with either the presence or absence of psoriasis. It was also suggested that more research be done to determine whether H. pylori infection is one of the factors causing or exacerbating psoriasis [63].

A nationwide population-based longitudinal cohort study was conducted with the aim to investigate the association between H. pylori infection and psoriasis. Between 2000 and 2013, the Longitudinal Health Insurance Research Database of the National Health Insurance Research Database in Taiwan yielded 41,539 patients with H. pylori infection and 83,078 matched controls for the study. To match the age, sex, comorbidities, and medical visits at a 1:2 ratio, propensity score analysis was employed. The adjusted hazard ratio of psoriasis was estimated using multiple Cox regression analysis. Additionally, stratified analysis and sensitivity testing were performed. Patients were excluded if they had ever been diagnosed with psoriasis before the index date, were diagnosed before 2000, or had undergone anti-H. pylori therapy before the index date or an appropriate propensity score-matched control could not be identified. Only patients who had been diagnosed with psoriasis at least three times at outpatient clinics, or were admitted at least once, were eligible for inclusion in the final analysis. Patients were disqualified if they had ever received a psoriasis diagnosis prior to the index date, had their condition diagnosed before the year 2000, or had had anti-H. pylori medication prior to the index date, or if a suitable propensity score-matched control could not be found. For inclusion in the final analysis, only patients who had received a psoriasis diagnosis at least three times at outpatient clinics or who had been hospitalized at least once were qualified [64].

In addition, it identified comorbidities related to H. pylori infection and psoriasis, namely systemic lupus erythematosus, ankylosing spondylitis, rheumatoid arthritis, Sjogren syndrome, hypertension, diabetes mellitus, hyperlipidemia, coronary artery disease, osteoporosis, cerebral vascular accident, asthma, chronic obstructive pulmonary disease and, chronic kidney disease, chronic liver diseases, chronic urticarial, tuberculosis, pneumonia, sepsis, and herpes zoster. Comorbidities were defined, using the relevant diagnostic codes, as at least one hospital admission or two outpatient visits of a given disease within 2 years before the index date. These comorbidities were considered covariates in the multivariate analysis [64].

Between the H. pylori and control cohorts, there were no appreciable differences in the incidence rates of psoriasis (4.58 vs. 4.20 per 100,000 person-months, crude relative risk: 1.092, 95% confidence interval: 0.917–1.302). In patients with H. pylori infection, there was no discernible difference in psoriasis risk after multivariate adjustment (adjusted hazard ratio: 1.081, 95% confidence interval: 0.907–1.288). Men, the elderly, people with diabetes, hyperlipidemia, chronic obstructive pulmonary disease, or tuberculosis all had a significantly greater risk of developing psoriasis. The stratified analysis also confirmed that H. pylori infection was not correlated with an increased risk of psoriasis based on follow-up duration, sex, and age. This retrospective population-based longitudinal cohort study, conducted in Taiwan, found no association between H. pylori infection and risk of psoriasis. Based on follow-up duration, sex, and age, the stratified analysis further indicated that H. pylori infection was not associated with a higher risk of psoriasis. No correlation between H. pylori infection and risk of psoriasis was discovered in this retrospective population-based longitudinal cohort investigation carried out in Taiwan [64].

3. Conclusion

Helicobacter pylori infection is a global health burden affecting not less than half the world’s population for the past years. The gram-negative bacterium, Helicobacter pylori being its causative agent, also causes a broad spectrum of both gastric and extra gastric disorders among its victim. Dermatological diseases such as Psoriasis are known among the extra gastric disorders to be identified with Helicobacter pylori’s negative impact. Psoriasis is a chronic, immune-mediated inflammatory skin disease known to affect approximately 125 million individuals worldwide. Although some studies have presented the negative correlations between H. pylori and psoriasis, many more current studies have overridden the formal facts and have gone further to prove that H. pylori eradication has a positive influence on psoriasis severity.

Acknowledgments

Extending sincere gratitude to all authors and publishers of the books and articles used as references in this research work. Good wishes to all who will find this research work useful in their various field of study. Many appreciations and gratitude to the sponsors and funders of this research work. Thank you.