The Role of *Helicobacter pylori* Infection in the Development of Extradigestive Diseases

**Chapter 4**

## Extra Digestive Disease and *Helicobacter pylori* Infection

*Mihaela-Flavia Avram, Daniela Cornelia Lazăr and Sorin Olariu*

#### **Abstract**

*Helicobacter pylori* infection has been associated with gastric pathology and gastric oncogenesis for many years, but its extra-digestive implications are less known. This chapter aims to provide up-to-date information on its potential role in neurological disease (Alzheimer's disease, stroke, multiple sclerosis, Parkinson's disease), dermatological disease (urticaria, rosacea, psoriasis), ophthalmological disease (glaucoma, chorioretinitis, blepharitis), hematologic disease (anemia, thrombocytopenia, neutropenia), as well as cardio-vascular disease (myocardial infarction, coronary atherosclerosis, hypertension), COVID-19, and metabolic pathology (diabetes mellitus, metabolic syndrome). For each group of diseases, a short description will be presented as well as information from published research. It will provide the reader with a global insight into the role of *Helicobacter pylori* in different pathologies.

**Keywords:** *Helicobacter pylori*, extra-digestive disease, neurological pathology, dermatological disease, ophthalmological disease, hematologic disease, atherosclerosis, metabolic disease, COVID-19

#### **1. Introduction**

*Helicobacter pylori* (HP) is a gram-negative spiral bacillus discovered by Barry Marshall and Robin Warren in 1982. They isolated it in patients with chronic gastritis or gastro-duodenal ulcers, proving its importance as an etiologic factor for these conditions. The two pathologists received a Nobel Prize award for this discovery. In 1994, the World Health Organization recognized HP to be a group 1 gastric cancer carcinogen.

After discovering the multiple implications of HP in gastric pathology, the medical scientific community started to see associations between HP pylori and several extragastric diseases. As early as 1994 a relationship between HP infection and coronary heart disease was found in a pilot study on 111 male patients [1]. These results were the starting point of intense scientific efforts to elucidate the mechanisms through which HP contributes to atherosclerosis.

Many other diseases and syndromes and their possible association with HP started to be studied. Pathogenic mechanisms through which HP contributed to certain diseases were discovered. The next step was, naturally, to see if HP eradication

improved the outcome of certain diseases or if it lowered the risk of developing certain medical conditions.

The current chapter offers an overview of HP's association with several types of extra digestive diseases. It offers information on its pathogenic role and possible pathogenic mechanisms as well as the potential influence of eradication treatment upon the overall outcome. It covers various diseases (neurological, dermatological, ophthalmic, metabolic, cardiologic, and hematologic) and also discusses the influence of HP infection in COVID-19 patients.

There is a growing number of extra-digestive diseases that are studied in association with HP, and new mechanisms are discovered. This chapter includes only the seven most studied disease categories in relation to HP infection, with the intention of emphasizing the relationship between HP and different extra digestive disorders in this paper, which will enhance the comprehension of HP pathogenic mechanisms, improve clinical prognosis, and guide treatment.

#### **2. Neurological diseases**

As HP does not penetrate the central nervous system (CNS), it has been suggested that systemic immunological alterations caused by HP infection may play roles in neurological diseases.

Infection with HP has been demonstrated to induce regulatory T cells (Tregs), which can block adaptive immune responses, resulting in extra-gastric disease regulation [2, 3]. Multiple sclerosis, an inflammatory demyelinating disease of the CNS, has been linked to autoimmune T and B cell responses against CNS antigens; hence, the reduced prevalence of MS in HP-infected patients may be attributable to an increase in Tregs [3, 4].

By stimulating innate immunity, HP infection may contribute to the etiology of CNS disorders. Pro-inflammatory cytokines such as interleukin IL-1, IL-6, and tumor necrosis factor, as well as C-reactive protein, have been found to be elevated in patients with HP [5, 6]. Furthermore, individuals with Parkinson's and Alzheimer's disease had a greater incidence of HP infection compared to controls [7, 8]. Activation of brain resident innate cells, particularly microglia, is a common feature of CNS pathology in both Parkinson's disease and Alzheimer's disease [7].

*Alzheimer's disease* is one of the most frequent forms of dementia. It causes a progressive decline in cognitive functions. It has a great impact on patients, their families as well as the whole society, as these patients soon require continuous care for long periods of time. Its cause is not well established and no curative treatment is found up to date [9]. HP infection in these patients proved to increase inflammation and negatively impact the cognitive status, patients with HP scored lower mini-mental state examination score [10]. Another study showed a poorer outcome in verbal memory tests in patients HP positive, compared with HP-negative Alzheimer patients [11]. Eradicating HP in these patients has not been proven to be a treatment for Alzheimer's, but there is data indicating that HP treatment improved survival [12].

Ischemic *stroke* is the result of intracranial atherosclerosis. There are recognized risk factors for this condition: age, type 2 diabetes, arterial hypertension, and metabolic syndrome, but these cannot explain all the cases of stroke, so other causes have to be investigated [13]. As chronic inflammation is present in the process of plaque formation, chronic infections need to be investigated as potential risk factors. Several studies showed a correlation between HP and stroke. Positive anti-HP IgG, C-urea

breath test, and antiCag-A were significantly associated with a higher risk of stroke [14]. The association is even more evident in women less than 60 years old [15].

*Multiple sclerosis* is a chronic demyelinating disease of the central nervous system. Its cause is not discovered, but environmental factors are studied in the hope of finding its pathogenesis. Studies have surprisingly shown that HP is less common in patients with multiple sclerosis compared to patients with other neurological pathologies, as well as compared to controls [16, 17]. Experimental studies on mice showed that HP plays a beneficial role in reducing the severity of multiple sclerosis symptoms, possibly providing protection against demyelination [18]. These findings constitute a new direction in the study of the disease.

*Parkinson's disease* is a degenerative disease affecting the cells in the substantia nigra, which lead to the progressive loss of dopaminergic neurons. Early studies already showed a correlation between HP and this disease, patients with Parkinson's disease having a three times higher risk of testing positive for HP compared to controls [19].

HP infection seems to interfere with the treatment of Parkinson's disease, possibly due to the damage caused by the infection on the mucosa of the duodenum., This leads to an impaired absorption of L-dopa medicine in these patients with the need to increase treatment doses. HP treatment improves patients' response to L-dopa [20]. Eradicating HP proved to improve motor fluctuations and increase the daily 'on' time in advanced Parkinson patients, but no significant improvement in the quality of life was noted [21]. Based on numerous studies, in these patients, HP testing and evaluating the possibility of its eradication when present, seem to play a considerable role in improving treatment outcomes.

#### **3. Dermatological diseases**

*Urticaria* is a common skin disease characterized by edematous, erythematous, itching skin lesions that regress spontaneously within 24 hours. Chronic urticaria lasts more than 6 consecutive weeks and negatively influences the patient's quality of life. Its etiology is not well determined, drugs, foods, malignancies, and autoimmune disease are incriminated, but in many patients, no etiological factors are detected. A study on urticaria patients found HP antigens in 69% of the study group [22]. Other studies did not find any difference between the occurrence rate of HP in chronic urticaria but found a statistically significant clinical improvement in the urticaria symptoms in those patients treated for HP. A slow urticaria symptoms rebound phenomenon was observed after 6 weeks post HP eradication therapy, possibly due to reinfection [23].

*Rosacea* is an inflammatory skin disease affecting the central part of the face. It presents as a mixture of papules, pustules, erythema, and telangiectasias. Its etiology is unknown. Epidemiological studies found an association between HP infection and the development of rosacea. Two mechanisms through which HP produces the rosacea skin lesions were identified: the increase of nitrous oxide at the skin level (responsible for inflammation, vasodilatation, and immune stimulation) and specific cytotoxic reaction [24]. Associating HP eradication treatment with routine treatment in these patients showed a better effect than routine therapy alone [25].

*Psoriasis* is a chronic skin disease presenting as erythema, papules, and scales. The lesions appear usually on the elbows and knees but can involve other skin areas too. It greatly influences the patient's quality of life and up to date, no cure has been found.

Symptomatic treatment can help in controlling the clinical manifestations. HP infections are statistically associated with psoriasis while psoriasis patients with HP infection seem to have a higher Psoriasis Severity Score Index [26] showing a contribution of HP in the development of psoriasis, while no data is available concerning the possibility of psoriasis making patients more prone to HP infections. A recent nationwide populationbased cohort study on 41,500 patients with HP infection showed no association between HP and psoriasis, therefore further studies are needed to reach a conclusion [27].

In psoriasis patients with HP infection, eradicating the infection ameliorates psoriasis severity and the patients treated for both psoriasis and HP present rapid improvement compared to patients only treated for psoriasis [28, 29].

HP does not seem to be a causative factor in dermatological diseases, but HP eradication improves symptoms and positively impacts treatment results in these diseases, raising the theory of HP being a trigger for several chronic skin diseases.

#### **4. Ophthalmic diseases**

*Central serous chorioretinopathy* is usually unilateral and it is characterized by the presence of liquid accumulation under the macula. The visual acuity is reduced and the vision is blurred and distorted. In most cases, it is self-limited, but chronic, non-resolving, and recurrent forms are possible in 15% of patients [30]. The prevalence of HP infection in these patients was determined to be 2.5-fold higher compared to the control groups [31].

Treating the HP infection (if present) in patients with central serous chorioretinopathy proved to decrease both the duration of the disease and the rate of recurrence while improving distant prognosis [32].

*Open-angle glaucoma* is a disease of the optic nerve head associated with increased intraocular pressure. It is one of the most frequent causes of blindness worldwide. In 2000 a study confirmed the association of HP gastric infection with glaucoma in 88% of glaucoma patients. Later studies found the same association [33]. A meta-analysis including 2664 participants showed a positive association between HP and openangle glaucoma [34].

Giving treatment for HP infection has not yet been proven to improve or cure openangle glaucoma, but studies seem promising. Reduction in intraocular pressure was found after 2 months in glaucoma patients who received HP eradication therapy [35].

*Blepharitis* is a chronic inflammation of the eyelid margin that causes ocular irritation. It is one of the most common ophthalmic diseases [36]. Its connection with HP infection is not clearly determined. A study conducted on 186 patients with blepharitis showed an increased incidence of HP infection compared to the control group; the symptoms were more severe in HP-positive patients, and a clinical improvement in 50% of the patients treated for HP was observed. As both conditions are highly prevalent in the population, their relationship needs large studies in order to be exactly determined [37].

#### **5. Hematological diseases**

The association of HP infection with *iron deficiency anemia* is well documented. The guidelines for the treatment of HP state the necessity of eradicating HP infection in patients with iron deficiency anemia [38]. Hepcidin (a protein produced in the liver) has been studied as the key mechanism. This protein is responsible for the iron balance in the organism, regulating its intestinal absorption and its release from the

macrophages [39, 40]. HP infection upregulates the levels of hepcidin, in this case, treatment with iron is less efficient [41]. Also, the higher gastric acidity in HP infection decreases dietary iron absorption. HP gastric lesions bleeding can also be a cause of anemia [42, 43].

*Primary immune thrombocytopenia* (autoimmune thrombocytopenic purpura) is an autoimmune disease characterized by an isolated low blood platelet count whose cause cannot be determined. Many studies have reported the association of this type of thrombocytopenia with HP infection. The pathogenic mechanism is complex. Eradication of HP in these patients proved to increase platelet count by 26–100% [43–46].

Chronic vitamin B12 deficiency leading to *pernicious anemia*, peripheral neuropathy, and spinal cord lesions can be associated with HP infection [47]. The absorption of B12 at the gastric level is reduced in HP-related gastritis of the corpus. HP eradication treatment increases serum levels of B12 and decreases serum homocysteine (a component of the metabolic pathway of B12) [43].

*Chronic idiopathic neutropenia's* association with HP infection was confirmed in several studies. These findings suggest that testing for HP in these patients and eradicating the infection can be beneficial [48, 49].

#### **6. Cardio-vascular diseases**

*Coronary atherosclerosis* and *myocardial infarction* are the most frequent causes of mortality in many countries. There are well-known risk factors: hypertension, diabetes, obesity, dyslipidemia, smoking, and family history, but they are not present in all patients [50, 51]. Other causes need to be investigated in order to improve treatment and prevention.

Extensive metanalysis on 20,900 participants showed a correlation between HP and coronary atherosclerosis, even when various HP-detecting methods were used (anti-HP IgG, positive anti-CagA, positive HP stool antigen, positive HP histological staining) [52]. The correlation is even stronger in patients with myocardial infarction [53].

The mechanism by which HP can cause coronary heart disease is complex. HP in the atherosclerotic plaque stimulates inflammatory cells, which produce cytokines. They determine endothelial and vascular dysfunction. HP also increases the production of interleukin 1 and 6, C-reactive protein, and TNF-α. These substances cause instability in the atherosclerotic plaque. HP secretes vacuolating cytotoxin A, which reduces nitric oxide concentration and further damages the endothelial function. HP infection also increases platelet aggregation [54–58].

Eradication treatment in these patients seems to be beneficial. Early HP treatment introduction, especially in younger patients (<65 years) patients improved survival and decreased the appearance of coronary heart disease. The benefit was modest when HP treatment was given to older patients [59].

Chronic *arterial hypertension* is one of the most common diseases worldwide. It is considered a global public health problem, leading to a multitude of serious complications [60]. A positive association with HP has been found, although no correlation was evident between the grades of hypertension and HP infection status [61–63].

HP eradication treatment in infected hypertensive patients proved to reduce the blood pressure values, even to normal values in some cases [64, 65].

#### **7. Metabolic diseases**

*Diabetes* is the most frequent disease worldwide. Studies have found that HP infection increases an individual's risk of having type 1 or type 2 diabetes. There seems to be a correlation between HP infection and the levels of glycated hemoglobin in diabetic patients [66]. HP infection in patients with type 1 diabetes was associated with poorer glycemic control compared to patients without HP. Eradication of HP in these patients did not improve glycemic values in a short time follow-up [67].

Studies have shown an improvement in glucose homeostasis in patients with type 2 diabetes after HP eradication [68, 69].

*Metabolic syndrome* has five components: central obesity, high blood glucose (insulin resistance), high triglycerides, low HDL, and high blood pressure. In order to establish the diagnosis of metabolic syndrome, at least three of the components have to be present. The disorders are evaluated by measuring the following: fasting glucose levels, triglycerides levels, HDL levels, cholesterol levels, blood pressure, and waist circumference. The presence of this syndrome elevates the risk of an individual developing atherosclerotic cardiovascular disease, diabetes mellitus, and neurological and vascular complications [70, 71].

HP infection determines chronic inflammation and immune response. Inflammatory cytokines and adipokines are present. HP induces low leptin and high TNF-α in infected patients. This leads to insulin resistance, which is an important component of the metabolic syndrome [72–74].

Several studies have addressed this correlation. They showed that people with obesity had a 46% increase in the chance of being infected with HP compared to normal weight controls. The chance of diabetic patients to develop an HP infection is 27% higher than non-diabetic persons [75, 76]. Several studies have shown a correlation between HP infection and metabolic syndrome [77–80]. Nevertheless, there are a small number of studies that found no statistical association between them [81, 82].

The question of the benefit of HP eradication treatment on metabolic syndrome components has been investigated. A study showed beneficial change after treatment, with a reduction in total cholesterol, and LDL, an increase of HDL, and a reduction in waist circumference. No influence was seen on body weight, blood pressure, and triglyceride values [83].

In a South Korean study, 2267 subjects were followed for 5 years after HP eradication. The follow-up focused on metabolic parameters. The results showed that HP treatment significantly increased HDL in female patients, especially at the 1st year follow-up. Body mass index increased in males over time. No statistically significant influence was found for other factors [84]. A study conducted in Taiwan showed significant improvement in metabolic parameters after eradication treatment [85].

#### **8. COVID-19**

Although not a causative factor for COVID-19, recent studies have targeted a possible interaction between SARS-CoV-2 infection and concomitant HP presence in patients. The association of these two pathogens seems to make patients more prone to severe forms with digestive manifestations of COVID-19 [86].

In patients with both infections, there was no statistically significant difference in the severity of common symptoms (fever, dry cough, dyspnea, loss of taste, loss

of smell headache, nausea, vomiting) compared to COVID-19 patients without HP infection [86].

Patients with HP use a lot of anti-acid and acid-reducing medicine (proton pump inhibitors), which leads to a higher gastric pH. Gastric acidity is considered to offer digestive protection for COVID-19, so in these patients stopping the anti-acid and related medicine might be considered during the acute phase of COVID-19 [87].

The vascular endothelium is an important factor in vascular homeostasis, it regulates fibrinolysis, blood viscosity, monocyte/leucocyte adhesion, and angiogenesis. Endothelial vascular cells regulate inflammatory response at inflammation sites. Markers of vascular endothelial dysfunction (V-CAM, ICAM, TNF-α, IL-8, IL-1β) were present in severe forms of COVID-19 [88, 89]. Inflammatory activation is also caused by HP infection, so a strong inflammatory response can be seen in patients with both pathogens, leading to severe forms of COVID-19 [90].

In future studies, as more SARS-COV2 data will be available, more information concerning the results and consequences of the coexistence of these two infections will be discovered, leading to a better treatment choice.

#### **9. Conclusions**

*Helicobacter pylori*'s implication in human disease goes beyond gastric localization. Studies have shown its detrimental effect on various types of diseases, from neurological and hematological, to skin and metabolism.

The mechanisms through which HP contributes to the pathogenesis or influences the severity of extra gastric diseases are complex and partially understood, but they seem to have a common pathway-systemic inflammation. HP infection determines the release of proinflammatory factors (e.g., IL-1, IL-6, TNF, C-reactive protein) which lead to chronic inflammation. Chronic inflammation contributes to several chronic diseases affecting different organs and systems, such as dermatological, cardio-vascular hematological, metabolic, ophthalmic, and COVID-19. This mechanism seems to be similar in most chronic neurological diseases, except for multiple sclerosis, where the change of immune profile induced by HP infection, leading to an increase of Treg may have, according to some studies, a favorable effect on disease progression by reducing demyelination. Also, HP gastric infection can influence the response to treatment in certain diseases by decreasing drug absorption.

Future studies will give more information and will help in providing better treatment strategies for a lot of different diseases. Large-scale studies will provide even better information in this domain and molecular studies will give more information on etiopathogenic mechanisms.

Doctors of all specialties should take into consideration the possible presence of HP and consider its implications. They should evaluate the potential beneficial effect of eradication treatment upon the evolution of the disease they are treating or the health risk reduction it might provide.

#### **Conflict of interest**

The authors declare no conflict of interest.

### **Author details**

Mihaela-Flavia Avram1,2\*, Daniela Cornelia Lazăr3 and Sorin Olariu1,2

1 Department of Surgery X, 1st Surgery Discipline, "Victor Babeș" University of Medicine and Pharmacy Timișoara, Romania

2 Abdominal Surgery and Phlebology Research Center, "Victor Babes" University of Medicine and Pharmacy Timisoara, Timisoara, Romania

3 Department V of Internal Medicine I, Discipline of Internal Medicine IV, "Victor Babeș" University of Medicine and Pharmacy Timișoara, Romania

\*Address all correspondence to: avram.mihaela@umft.ro

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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### **Chapter 5**

## Changes in Vitamin B12, Iron, Thyroid Hormones, Thyroid Autoantibodies and Hematological Indices Levels in Patients Suffering from *Helicobacter pylori* Infection

*Saleh Nazmy Mwafy, Wesam Mohammad Afana and Asma'a Ali Hejaze*

#### **Abstract**

*Helicobacter pylori* infection has been recognized as a public health problem worldwide with raising prevalence in developing than the developed countries. More than 50% of the world's population infected, and 80% of infected have no symptoms. Megaloblastic anemia can occur due to impaired DNA synthesis resulting from deficiencies of vitamin B12 and folate. The development of autoantibodies to thyroid peroxidase (anti-TPO), thyroglobulin (anti-Tg), and thyroid-stimulating hormone receptor (TSH-R) is the main characteristic of autoimmune thyroid disease. *H. pylori* may decrease absorption of oral thyroxine by decreasing gastric acid secretion in the stomach. *H. pylori* has important role of in the development of autoimmune thyroid diseases, vitamin B12 deficiency and malfunctions of human. The primary goal of this chapter is to observe association between *H. pylori* infection in the gastric mucosa and of autoimmune thyroid diseases vitamin B12 deficiency because eradication of *H. pylori* can prevent the development of complications.

**Keywords:** vitamin B12, iron, thyroid hormones, thyroid autoantibodies, *Helicobacter pylori*

#### **1. Introduction**

*Helicobacter pylori* (*H. pylori*) is a spiral, flagellated, gram-negative bacteria, adapted to survive in the gastric lumen [1]. *H. pylori* is a bacterium that causes widespread infection, affecting over 50% of the world's population, but 80% of infected people are asymptomatic and more common in developing countries [2].

Megaloblastic anemia can result from impaired DNA synthesis resulting from vitamin B12 (cobalamin) and folic acid deficiency. Microorganisms synthesize vitamin B12, that is primarily found in low concentration levels in meals with an animal source, humans cannot synthesize vitamin B12. Early detection of vitamin B12 deficiency and rapid treatment of is important, since it is a reversible cause of demyelinated nervous system and bone marrow failure [3]. infection with *H. pylori* causes gastritis and it is associated with the progress of micronutrient deficiencies, peptic ulcer, gastric carcinoma [4].

Thyroid gland is one of the crucial organs in the human body that produces basic hormones: triiodothyronine (T3) and tetra-iodothyroxine (T4) which have an essential part in control of metabolic functions, development and growth. Thyroid dysfunction affecting various vital activities; those subsequent from hypo or hyper thyroid gland action leading to increase or decrease thyroid hormones T3 and T4 [5].

Hashimoto's thyroiditis (HT) is the most widely autoimmune thyroid disorders as one of most complications of thyroid dysfunctions. Autoimmune diseases occur when the immune system begins to attack its own self-antigens, so, that the characteristic feature of autoimmune thyroid disease is the presence of autoantibodies against thyroid antigens. Such diseases are triggered by factors including infectious agents, just like as infection with *H. pylori* [6, 7]. Luther et al. (2010) found that a high prevalence of people who have been diagnosed as thyroid patients were also infected with *H. pylori* which means that these bacteria play a critical part in the pathogenesis of such illnesses. *H. pylori* is one of the most well-known bacterial pathogens that infect human around the worldwide, which acquired in the early childhood and is carried throughout a lifetime if not treated with antimicrobial agents [8].

The present work sought to investigates the changes in vitamin B12, iron, thyroid hormones, thyroid autoantibodies and hematological indices levels in patients suffering from *H. pylori* infection.

#### **2.** *H. pylori*

#### **2.1 General characteristics**

*H. pylori* is considered to be as one of the furthermost common pathogenic bacteria that colonizes human stomach, varying from 70% in developing countries and less than 40% in the developed countries [9]. *H. pylori* is the main causative agent of gastritis and responsible for development of adenocarcinoma by stimulating cell proliferation and induces apoptosis [10]. *H. pylori* is a Gram- negative spiral bacteria measuring 2–4 μm in length, 0.5–1 μm in width and has 2–6 sheathed flagella 3 μm in length (Guo et al., 2011). *H. pylori* growth at optimal rang of: temperature 34-40C°, pH 5.5–8.0 but can survive at pH 4 and the key feature of *H. pylori* its microaeropholicity. Growth at optimal level of: 2–5% oxygen, 5–10% carbon dioxide and 85% nitrogen [11].

*H. pylori is* microaerophilic bacterium, requires lower oxygen concentrations than other bacteria to exist*.* It has a hydrogenase that may be utilized to generate energy by oxidizing the molecular hydrogen (H2) produced by intestinal bacteria, and it can generates urease, catalase, and oxidase [12]. These bacteria survive in the stomach for a long time without any indications in most of the infected people. In order to inhabit the stomach, *H. pylori* must survive in acidic pH, its persistence be influenced by the production of urease enzyme, in addition to this enzyme these pathogenic bacteria produce other enzymes which damage of host epithelial cells such as catalase, protease and phospholipase. *H. pylori* are vital for colonizing the stomach and make it possible for it to pass readily through the mucous layer [13].

*Changes in Vitamin B12, Iron, Thyroid Hormones, Thyroid Autoantibodies and Hematological… DOI: http://dx.doi.org/10.5772/intechopen.108036*

#### **2.2** *H. pylori* **classification**

*H. pylori* genus is a *Helicobacteraceae* family member and *Campylobacterales* order of proteobacteria. The digestive tracts of both humans and animals naturally contain the genus *Helicobacter*, which has more than 20 identified species and several more that are waiting proper classification [14].

#### **2.3 Prevalence of** *H. pylori* **infection**

*H. pylori* infection prevalence rates vary by age, place of origin, and socioeconomic position. Worldwide, *H. pylori* infection affects 50% of the population [15]. According to reports, up to 80% of people in undeveloped countries are infected with *H. pylori*. In Texas, the incidence of *H. pylori* among youngsters is 12.2%, whereas in India, it is 55.9% among people aged 11–16. [15, 16], and in northern Jordan is 82% [17] and in Gaza strip is (72.2%) [18].

#### **2.4 Mode of transmission**

#### *2.4.1 Person-person route*

Humans have been identified as a major *H. pylori* reservoir [19]. Person to-person contact is believed to be the primary route of transmission in developed and developing countries. Close personal relationships, especially those inside the family, between parents and children, siblings and siblings, and spouses and spouses, has been consistently verified as a major factor of transmission [20].

#### *2.4.2 Oral-oral route*

Using a polymerase chain reaction*, H. pylori* DNA has been found in the saliva of people who tested positive [21]. Additionally, *H. pylori* bacteria have been effectively found in infected dental plaque. However, isolation has not always been effective, possibly due to *H. pylori's* transitory existence in the buccal cavity or low detection capabilities brought on by the co-existence of several other microorganisms.

#### *2.4.3 Fecal-oral route*

Fecal-oral is the main route of *H. pylori* transmission, *H. pylori* has been identified in human feces by culture and by PCR of its DNA. [22] Nevertheless, this has not been replicated by other researchers [23]. These findings provided evidence of the potential contribution of *H. pylori* fecal shedding into the environment.

#### *2.4.4 Iatrogenic transmission*

Endoscopes frequently utilized for upper gastrointestinal procedures, because they aren't properly disinfected in between procedures, could be the cause of an iatrogenic infection [24].

#### *2.4.5 Mechanisms of infection*

Most *H. pylori* are located in the gastric mucosa of the stomach; however, a few are also observed adherent to the gastric mucosal epithelium. The bacteria are well suited to survive in the harsh conditions of the stomach, where very few others organisms can. Despite the fact that *H. pylori* is thought of as an extracellular bacteria, there is evidence that the bacteria have a method of intracellular invasion [25]. The human stomach is colonized by *H. pylori*, and about 50% of the worldwide people is colonized by it. Its gastric mucosa infection has been related to a variety of upper gastrointestinal tract illnesses, including chronic gastritis, peptic ulcer, stomach cancer and mucosa-associated lymphoid tissue lymphoma [26]. *H. pylori* typically results in an asymptomatic stomach infection, and documented side effects of this infection include chronic gastritis, peptic ulcer disease, and atrophic gastritis. Most infected individuals remain asymptomatic despite the fact that the infection almost always results in stomach inflammation, whereas a small percentage of people develop atrophic gastritis [27]. During its progression, the disease can have several manifestations including acute gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia, growth failure, malnutrition and finally cancer [28]. *H pylori* is the major cause of histologic gastritis and also plays an important role in the development of peptic ulcers, gastric carcinoma, and primary gastric B-cell lymphoma [29].

The etiology of atrophic gastritis and gastric cancer has been rewritten since the detection of *H. pylori* during the 1980s. *H. pylori* infection, which typically develops in early childhood and lasts a lifetime if untreated, is now recognized as the primary cause of atrophic gastritis [27]. One severe consequence of atrophic gastritis is the malabsorption of cobalamin (vitamin B12), which is frequent in the elderly due to hypo- or achlorhydria with subsequent bacterial overgrowth, and reduced production and secretion of intrinsic factor. Carmel et al., hypothesized that *H. pylori* infection may be crucial in the decline in acid production, the reduction in intrinsic factor secretion, and the subsequent emergence of vitamin B12 insufficiency [30]*. H. pylori* inhabiting the whole gastric epithelial and has a significant urease activity that results in the creation of ammonia to protect itself against the acidity of the stomach. It also produces other enzymes, including glycosulfatase and phospholipase A2 and C, which are associated with the development of stomach mucosal injury [31]. *H. pylori* induces an inflammatory response through the gastric epithelium, with production of pro-inflammatory cytokines, such as interleukin 1β and interleukin 8. Some *H. pylori* genotypes, especially those vacuolating toxin A (Vac-A) and cytotoxin-associated gene A (Cag-A) positive, are associated with greater pathogenicity and more severe sickness. Cag-A positive strains cause the stomach mucosa to react more violently to inflammation and produce more pro-inflammatory cytokines. Even while it only phenotypically manifests in 60% of *H. pylori* strains, the VacA gene, which causes the vacuolization and death of gastric epithelial cells, is genetically expressed in all of them [32]. Gastritis, including atrophic and non-atrophic gastritis, and peptic ulcers, are etiologically linked to *H. pylori* (especially duodenal ulcer)*.* The primary gastric B-cell lymphoma (also known as mucosa-associatedlymphatic-tissue or MALT-lymphoma) and stomach adenocarcinoma have a strong correlation with *H. pylori*. *H. pylori* has been therefore classified by IARC/WHO as "group 1 carcinogen" [33].

#### **2.5 Diagnosis of** *H. pylori* **infection**

Infections are typically diagnosed by looking for dyspeptic symptoms and performing tests that may reveal *H. pylori* infection [34]. The diagnostic tools for *H. pylori* are serology, rapid urease test (RUT), urea breath test (UBT), endoscopy and biopsy/

*Changes in Vitamin B12, Iron, Thyroid Hormones, Thyroid Autoantibodies and Hematological… DOI: http://dx.doi.org/10.5772/intechopen.108036*

histopathology, PCR, for DNA of *H. pylori* and *H. pylori* stool antigen (HpSA). The simplest test of *H. pylori* is serologic, including the assessment of specific IgG level in serum [27, 35].

#### **3. Anemia**

#### **3.1 Definition of anemia**

Anemia is the most common blood disorder is characterized by a decrease in the number of red blood cells or a less-than-normal quantity of hemoglobin in the blood. The most widely used standards of anemia are those set by the World Health Organization, which identify hemoglobin levels of less below 12 g/dL for women and bellow 13 g/dL for males [36]. Globally, the most prevalent type of anemia was iron deficiency. It is a major public health issue that affects both advanced and developing societies, having a significant negative impact on people's health as well as social and economic development.

#### **3.2 Common causes of anemia**

*Anemia from active bleeding;* Heavy menstrual bleeding or, wounds and gastrointestinal ulcers or cancers [37, 38]. *Iron deficiency anemia;* Inadequate food intake, poor health and improper care [39]. *Anemia of chronic disease;* Long-term medical condition such as a chronic infection or a cancer [40]. A*nemia related to kidney disease*; Diminish production of renal erythropoietin which in turn diminishes the production of RBC [41]. *Anemia related to pregnancy*; Water weight gain during pregnancy dilutes the blood, which may be reflected as anemia [42]. *Anemia related to poor nutrition*; Deficiency of vitamins and minerals required to make RBC [42]. *Pernicious anemia*; A problem in the stomach or the intestines leading to poor absorption of vitamin B12 [43]. *Sickle cell anemia*; Is due to a point mutation in the β globin gene, resulting in the creation of abnormal hemoglobin molecules with a hydrophobic motif that is exposed in its deoxygenated state [44]. *Hemolytic anemia*; hemolysis-related anemia, which is caused by the abnormal breakdown of RBC, blood vessels, and extravascular locations throughout the body [45]. *Thalassemia*; This is another group of hereditary anemia of hemoglobin related causes. It varies in severity from mild thalassemia minor to severe thalassemia major [46]. *A plastic anemia*; Occasionally some viral infections may severely affect the bone marrow and significantly diminish production of all blood cells chemotherapy (cancer medications) and some other medications may pose the same problems and radiation [47].

#### **3.3 Iron deficiency anemia**

#### *3.3.1 Definition*

Iron deficiency anemia (IDA) is A decrease in overall hemoglobin concentration caused on by a deficiency of iron required for maintaining normal physiologic processes. Iron deficiency anemia results from inadequate iron absorption to a accommodate an increase in requirements attributable to growth or arising from a prolonged negative iron balance, one of these conditions causes a reduction in iron storage as indicated by blood ferritin levels or bone marrow iron content [48].

#### *3.3.2 Causes*

Iron-deficiency anemia may develop from a variety of conditions, including stomach ulcers, ulcerative colitis, piles, and colon cancer, which can all induce gut bleeding and result in anemia. Anemia can be brought on by bleeding brought on by kidney or bladder illness. Anemia caused by iron deficiency can be brought on by a number of illnesses, including cancer and rheumatoid arthritis. Iron deficiency anemia is correlated with long-term aspirin use [49].

#### *3.3.3 Diagnosis of iron deficiency anemia*

Iron deficiency anemia were diagnosed by the first result on a regular complete blood count is typically low hemoglobin in the context of a lowered MCV, and the ferritin level was below 1010 ng/dl [50].

#### *3.3.4 Pathophysiology of iron deficiency by H. pylori*

Common symptoms of IDA include: breathlessness, tiredness, dizziness, tachycardia, headache and paleness [51]. The pathophysiologic mechanisms by which *H. pylori* is associated with the development of ID and ID anemia are not fully understood. It is still not known why some patients manifest this association and why in other patients it is not present, or there are other associations; or why some of the infections are asymptomatic [15]. Over the past decade, it has been linked *H. pylori* and ID development with a recently discovered hormone called hepcidin [52]. This hormone is produced in the liver and regulates iron metabolism in enterocytes and releases stored iron from macrophages of the reticuloendothelial system [53]. Hepcidin increases following *H. pylori* infection and acts as an acute phase reactant in reaction to the inflammation created in the gastric mucosa, culminating in a condition characterized as chronic illness or inflammatory anemia [54]. According to preliminary research, serum levels of hepcidin were raised in *H. pylori*-infected patients but returned to normal after the infection was eradicated, allowing the iron to be absorbed by enterocytes and freed from reticuloendothelial system macrophages, where it had been trapped [55]. Other possible causes of iron imbalance in patients infected with *H. pylori* are chronic gastritis, which occurs in all individuals infected with *H. pylori* [15]. This can cause bleeding when it becomes erosive gastritis, especially in patients with active bleeding peptic ulcers [56] and in patients who chronically ingest non-steroidal anti-inflammatory drug including aspirin [43].

#### **3.4 Vitamin B12**

#### *3.4.1 Definition and structure*

Vitamin B12 or cyanocobalamin is relatively large and complex water-soluble vitamin. The molecular weight of vitamin B12 is equal to 1355.4 [57]. All cobalamins that may be physiologically active are represented by vitamin B12. The name "cobalamin" is used to describe a class of cobalt-containing substances known as corrinoids, each of which has a lower axial ligand that contains a cobalt-coordinated nucleotide (5,6-dimethylbenzimidazole as a base. Cyanocobalamin, which is used in most supplements, is readily converted to the coenzyme forms of cobalamin (methylcobalamin and 5- deoxyadenosylcobalamin) in the human body [58]. The partial structures *Changes in Vitamin B12, Iron, Thyroid Hormones, Thyroid Autoantibodies and Hematological… DOI: http://dx.doi.org/10.5772/intechopen.108036*

of vitamin B12 compounds show only those portions of the molecule that differ from vitamin B12 1: 5-deoxyadenosylcobalamin; 2,'methylcobalamin; 3, hydroxocobalamin; 4, sulfitocobalamin; 5, cyanocobalamin or vitamin B12 [57].

#### *3.4.2 Sources of vitamin B12*

Vitamin B12 is synthesized only in certain bacteria [59]. In the natural food chain system, more predatory organisms have larger concentrations of vitamin B12 that bacteria produce. The main dietary sources of vitamin B12 are thought to be animal foods (meat, milk, eggs, fish, and shellfish) rather than plant foods [58]. Some plant foods, such as edible algae or blue-green algae (cyanobacteria), however, contain large amounts of vitamin B12. Vitamin B12 compounds in algae appear to be inactive in mammals [60]. Foods contain various vitamin B12 compounds with different upper ligands; methylcobalamin and 5-deoxyadenosylcobalamin function, respectively, as coenzymes of methionine synthase (EC 2.1.1.13), which is involved in methionine biosynthesis and of methylmolonyl- CoA mutase (EC 5.4.99.2), which is involved in amino acid and odd-chain fatty acid metabolism in mammalian cells [61]. Humans have a complex process for gastrointestinal absorption of dietary vitamin B12 [62]. The recommended dietary allowance of vitamin B12 for adults is set at 2.4 μg/day in the United States and Japan; however, daily body loss of the vitamin is estimated to be between 2 and 5 μg/day [63]. According to a study by Bor et al., in 2006, a daily consumption of 6 μg of vitamin B12 is sufficient to maintain a stable level of serum vitamin B12 and vitamin B12-related metabolic indicators [64].

#### *3.4.3 Vitamin B12 functions*

Cobalamin, or vitamin B12, comes in a variety of forms, such as cyano-, methyl-, deoxyadenosyl-, and hydroxy-cobalamin. Food contains small amounts of the cyano form, which would be utilized in supplements. The other forms of cobalamin can be changed into the methyl- or 5-deoxyadenosyl forms that seem to be necessary as cofactors for L-methyl-malonyl-CoA mutase and methionine synthase. For the formation of purines and pyrimidines, methionine synthase is necessary. The reaction, in which the methyl group of methyltetrahydrofolate is transferred to homocysteine to generate methionine and tetrahydrofolate, requires folate as a co-factor and also depends on methylcobalamin. Megaloblastic anemia develops as a result of a vitamin B12 shortage and the disruption of the process that causes RBCs to mature. Megaloblastic anemia is also brought on by a folate deficit, which is unrelated to vitamin B12 [65]. Methylmalonyl CoA mutase changes methylmalonyl CoA into succinyl CoA, and it needs the cofactor 5-deoxyadenosylcobalamin to do so. The neurological consequences of vitamin B12 deficiency are assumed to be caused by a flaw in this process and the accompanying buildup of methylmalonyl CoA [65].

#### *3.4.4 Deficiency of vitamin B12*

Vitamin B12 deficiency is usually caused by the malabsorption of vitamin B12 although dietary inadequacy is common in the elderly, vegans or ovo-lacto vegetarians with poor diets. Other contributing factors include insufficient intrinsic factor synthesis, atrophic gastritis, disease-related disruption of vitamin B12 absorption in the ileum, bacterial overgrowth, resection, drug-nutrient interactions, and other less prevalent genetic abnormalities [66]. Pernicious anemia is the end stage of an

auto-immune gastritis and results in the loss of synthesis of IF. It is this loss of IF that causes vitamin B12 deficiency and if untreated, megaloblastic anemia and neurological complications develop [66].

#### *3.4.5 Mechanism of vitamin B12 deficiency*

A mechanism that has been proposed to explain this association is that the action of *H. pylori* decreases gastric acid secretions which leads to hypochlorhydria [67]. On the one hand, protein-bound vitamin B12 must be released by the action of gastric acid in the stomach, yet hypochlorhydria itself increases the bacteria of the stomach and intestines. These bacteria may in turn make use of the vitamin B12 themselves [68]. This mechanism is supported decreased vitamin B12 levels secondary to chronic use of PPIs [69]. In addition, it has been proposed that vitamin B12 deficiency is secondary to decreased production of intrinsic factor due to atrophic gastritis (pernicious anemia) which results from chronic *H. pylori* infections [70]. However, one study has concluded that the association between *H. pylori* and vitamin B12 deficiency is independent of atrophic gastritis [71].

#### **3.5 Thyroid hormones and autoantibodies**

#### *3.5.1 Thyroid hormones*

The thyroid gland, which is shaped like a butterfly and is located at the base of the neck right behind the larynx, generates the essential hormones T4 and T3 [72]. Thyroid hormones are essential for numerous functions including: brain development, growth, fuel metabolism, reproduction, regulate body temperature and blood pressure [73]. TSH, which is made by the pituitary gland and regulates the production of T3 and T4, was responsible for controlling T3 and T4 levels. TSH production controlled by thyroid releasing hormone (TRH) produced by the hypothalamus [74]. This means that thyroid gland regulates its hormonal secretion with the aid of hypothalamus and the pituitary gland in a way that TRH is triggered pituitary to secrete TSH which in turn tells thyroid gland to capture iodine from the blood to synthesized and produced T4 and T3. Hypothalamus and pituitary gland decrease TRH and TSH when T4 is reach to a satisfactory level in circulation [75].

#### *3.5.2 Thyroid autoantibodies*

Auto-antibodies cause cellular damage and modify thyroid gland function. Sensitized T-lymphocytes and/or autoantibodies that attach to thyroid cell membranes result in cell lysis and inflammatory responses, causing cellular damage. Alterations in thyroid gland function result from the action of stimulating or blocking auto-antibodies on cell membrane receptors. TPO, Tg, and the TSH receptor are the three main thyroid auto-antigens involved in autoimmune thyroid disease (ATD). [75]. Thyroid peroxidase is the key enzyme catalyzing both the iodination and coupling reaction for the synthesis of thyroid hormone. It is membrane-bound and found in the cytoplasm of thyrocyte. It was earlier known as thyroid microsomal antigen. Anti-TPO autoantibodies are found in patients with autoimmune hypothyroidism and Graves' disease (GD). Together with Tg antibodies, these are the predominant antibodies in Hashimoto's thyroiditis. Anti-TPO antibodies are mainly of the IgG class with IgG1and IgG4 subclasses in excess [76].

*Changes in Vitamin B12, Iron, Thyroid Hormones, Thyroid Autoantibodies and Hematological… DOI: http://dx.doi.org/10.5772/intechopen.108036*

Thyroglobulin made out of two identical subunits. It is discharged by the thyroid follicular cells into the follicular lumen and stored as the colloid. Each Tg molecule has around 100 tyrosine residues. These deposits were coupled to form the thyroid hormones T3 and T4. The sequence of human Tg has been determined [77]. Thyroglobulin autoantibodies are found in patients with lymphocytic thyroiditis and Graves' disease patients. They are polyclonal and mainly of IgG class with all four subclasses represented. TSH controls the cell surface expression of TPO and Tg altering the mRNA transcription of these two proteins. Both blocking and stimulating Autoantibodies are found in the sera of GD patients replicate these effects [78].

Our previous experimental results [79] indicated statistically significant positive correlation between TSH levels and anti TPO and anti Tg at baseline. Also, there were statistically significant negative correlations between fT3, fT4 levels and anti-TPO and anti-Tg. This result agrees with a previous study in which statistically significant positive correlations between TSH levels and anti TPO and anti-Tg were reported. Also these findings are in agreement with that obtained by [80]. Lin et al. (2014) who found elevated levels of both anti-Tg and anti-TPO in patients with radiation-induced hypothyroidism, in addition to positive correlation between TSH and anti-Tg and a negative correlation between fT4 and anti-TPO [80].

Hou et al. (2017) who observed reduction of thyroid autoantibodies in patients with GD and HT after pharmaceutical eradication of *H. pylori* infection [81]. *H. pylori* plays role in ATD pathogenesis. Genetic factors include thyroid specific genes and immune regulatory genes while none genetic factors include: smoking, stress, iodine intake, medication, pregnancy and bacterial and virus infection that have been implicated with etiology of ATD [82]. Strong correlation between IgG anti–*H. pylori* antibodies and thyroid auto-antibodies as well as the observation that eradication of *H. pylori* infection is followed by gradual decrease in the levels of thyroid autoantibodies, supposed that *H. pylori* antigens might be involved in the development of autoimmuno atrophic thyroiditis or that autoimmuno function in this disease may increase the likelihood of *H. pylori* infection [83]. El-Eshmawy et al., (2011) who found that a correlation between *H. pylori* infection and the presence of autoantibodies against thyroid antigens, and highly significant prevalence of *H. pylori* infection in the ATD patients when compared with healthy individuals [84].

#### **4. Conclusions**

*H. pylori* appears to play a role in the onset of IDA and vitamin B12. *H. pylori* patients had significant decreases in vitamin B12, serum iron and hemoglobin levels. An insufficient response to the medication may be caused by *H. pylori* gastritis. A raise in *H. pylori* IgG, anti-TPO, anti-TG, and TSH levels and a decrease in fT4, fT3, and other hematological markers appear to before *H. pylori* treatment in hypothyroidism Palestinian females. Patients receiving triple therapy for *H. pylori* infection OAC may help patients feel better overall by restoring their vitamin B12, serum iron, and hemoglobin levels. In people with gastritis, vitamin B12 levels are highly associated with Hb and RBCs. As a result, it could be thought of as a helpful indicator for patients with anemia with gastritis. *H. pylori* is responsible for hypothyroid patients getting large doses of L-T4 poor response. However, these parameters were nearly improved by 14-day conventional triple treatment with omeprazole, amoxicillin, and clarithromycin. Routine testing of vitamin B12, iron, ferritin and total iron binding

capacity level and immunological thyroid alterations were recommended for *H. pylori* patients and gastroscopy confirmation of *H. pylori* infection.

### **Conflict of interest**

The authors declare no conflict of interest.

### **Author details**

Saleh Nazmy Mwafy\*, Wesam Mohammad Afana and Asma'a Ali Hejaze Faculty of Science, Department of Biology, Al Azhar University – Gaza, Gaza Strip, Palestine

\*Address all correspondence to: smwafy@hotmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Changes in Vitamin B12, Iron, Thyroid Hormones, Thyroid Autoantibodies and Hematological… DOI: http://dx.doi.org/10.5772/intechopen.108036*

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#### **Chapter 6**

## *Helicobacter Pylori* Infection Correlates with Lower Prevalence and Subsequent Incidence of Crohn's Disease

*Chenxiao Hu, Ting Lei, Natalie Tai, Yan Li, Xiujing Feng, Zhi Huang and Yun Lu*

#### **Abstract**

According to some researchs, Crohn's disease (CD) and Ulcerative colitis (UC), two chronic inflammatory bowel illnesses, may be protected against *Helicobacter pylori* infection. Many case–control studies have revealed that individuals with CD and UC had lower *H. pylori* prevalence than healthy controls. However, whether or not *H. pylori* plays a protective role in the development of Crohn's disease is debatable. CD was more common in *H. pylori*-negative individuals than in *H. pylori*-positive patients. After eradication of *H. pylori*, the CD was more common in the *H. pylori*-negative group than in the *H. pylori*positive group over the previous research follow-up period. Although it has been strongly indicated in previous studies that *H. pylori* infection plays a significant role and triggers autoimmune reactions and may be implicated in the pathogenesis of autoimmune diseases, the role of *H. pylori* in inflammatory bowel disease, including Crohn's disease, is unclear.

**Keywords:** *Helicobacter pylori*, Crohn's disease, immune cells, cytokines, Cronh's Disease and *H. pylori* correlation

#### **1. Introduction**

Crohn's disease (CD) is an inflammatory disease that could cause chronic inflammation throughout the gastrointestinal tract without a definite etiology [1]. Even though the incidence of CD has been increasing for several decades worldwide, it is more common in northern Europe and the United States compared to other areas, including southern Europe [2]. In addition to the primary contributor to the disease, which is the genetic predisposition, there is a growing body of evidence to support the concept that environmental variables, in particular the gut flora and antigens, are also involved in the development of Crohn's disease (CD). Several different infections have been proposed as potential causes of CD without solid evidence supporting these hypotheses. There is an unmet need to investigate the role of bacteria during CD development. Helicobacter pylori (*H. pylori*) is a type of bacteria that could cause ulcers in the stomach. Although it has been strongly indicated in previous studies that *H. pylori* infection plays a significant role and triggers autoimmune reactions and may be implicated in the pathogenesis of autoimmune diseases, the role of *H. pylori* in inflammatory bowel disease (IBD), including Crohn's disease, is unclear [3].

*H. pylori* is a stain of Gram-negative bacteria that is very infectious and found in the mucosa of the human stomach. Chronic *H. pylori* infection is quite common. It is estimated that roughly 20 percent of Danish patients diagnosed with dyspepsia are infected with *H. pylori* [4]. Most cases of *H. pylori* infection occur in children and young adults [5]. Inadequate sanitation and poor socioeconomic standards have been reported as factors that correlate the increased risk of *H. pylori* infection, which is prevalent in certain countries such as India, China, and Brazil, where the incidence of *H. pylori* infection is considered over 50 percent [6]. Living quality and sanity go hand in hand with the development of the economy, which may explain why the prevalence of *H. pylori* infection has significantly decreased as the western style civilization grown grow. A persistent *H. pylori* infection is a significant factor for the development of chronic gastritis, peptic ulcer disease, and stomach cancer. Oddly, while the incidence of *H. pylori* infection has been going down, the number of people developing chronic inflammatory conditions including Crohn's disease is going up for no apparent reason [7]. This observation has given rise to the hypothesis that *H. pylori* infection may have host-protective role.

#### **2. Epidemiological correlation between CD and** *H. pylori*

*H. pylori* caused active infection is responsible for the prolonged inflammation of the colon and cecum that are seen in immunocompromised rodents [8–11]. However, the findings from patients were difficult to interpret. The intestinal mucosa of the majority of patients did not contain Helicobacter, or the presence of *H. pylori* was only discovered in a minority of those individuals [12–16]. In addition, results from meta-analysis revealed that *H. pylori* infection plays a protective role CD from an etiology point of view [10, 17–19]; however, the heterogeneity among the studies that were included in the meta-analysis and the possibility of publication bias limit the confidence that could be placed in these findings. Furthermore, it is still controversial whether *H. pylori* serves a protective role in the development of CD, a persistent inflammatory condition of gastrointestinal tract [18, 20]. As shown by the results, having *H. pylori* infection was associated with a lower risk of Crohn's disease (CD), and this correlation remains even after potential confounding factors such as socioeconomic status were taken into account (**Table 1**) [6, 10, 19, 21–30]. On the other hand, it was revealed in other studies that the presence of an *H. pylori* infection was associated with an increased frequency of CD [18, 31, 32].

*H. pylori* infection and the prevalence of Crohn's disease, ulcerative colitis, and celiac disease also been investigated in a cohort of more than 50,000 Danish citizens who successively underwent a first-time urea breath test [33]. Although the previous research has shown that there is a correlation between *H. pylori* infection and IBD, the results have been inconsistent [33, 34]. The occurrences of CD, UC were used as part of a follow-up checklist in order to determine whether or not the possible protective benefits of *H. pylori* lingered after the bacteria has probably been eradicated.

A number of hypotheses have been proposed to explain this discovery. For instance, if patients with Crohn's disease received antibiotics prior to an *H. pylori* eradicating *H. pylori*, the rate of *H. pylori* infections in Crohn's disease patients would be smaller [33, 35–37]. This would lead to a reduction in the prevalence of *H. pylori*

Helicobacter Pylori *Infection Correlates with Lower Prevalence and Subsequent Incidence… DOI: http://dx.doi.org/10.5772/intechopen.107943*


#### **Table 1.**

*Helicobacter pylori infection rates in patients with CD.*

infections in patients with CD. It is possible that *H. pylori* is just a proxy marker for exposure to an environment that protects against Crohn's disease. Alternatively, it may be a case of selection biases where patients seeing doctor regularly get tested for *H. pylori* more often than those patients seeing doctors for a cause [38]. There are various potential sources of bias and confounding variables, including the fact that individuals with Crohn's disease may have received other medical treatments that have an effect on *H. pylori*, or the fact that publishing biases may have distorted the findings [35, 39].

Various researches included the ecological epidemiology studies in order to tackle the issue of overcoming biases and confounding in their researches. Information regarding the prevalence and incidence of CD was combined with geographically and temporally matched studies of the prevalence of *H. pylori* [2, 3, 16, 17, 30, 39]. Shah et al. also expanded that epidemiology study strategy and conduct an in-depth analysis of the published researches on the epidemiology of Crohn's disease from 1990 to 2016, comparing the findings of this research with findings on the incidence of *H. pylori* infection. A combined data set included 22 incidence and 19 prevalence data pairs for Crohn's disease and *H. pylori* derived from 13 different countries was included [35, 40]. However, there are still a number of possible risks associated with the research. There is a possibility that the presence of *H. pylori* is not the sole factor that differentiates the non-exposed group from the group that has been exposed to *H. pylori*. Nevertheless, antibiotics may have been administered in an inconsistent manner, which may had an impact on the outcomes [41, 42]. During the time period between 1990 and 2016, these nations may have seen the most significant shifts in both the incidence and prevalence of CD, as well as the prevalence of *H. pylori*. The incidence of Crohn's disease is reduced in proportion to the percentage of the population that is infected with *H. pylori* [7, 15, 32, 33, 35].

#### **3. Molecular mechanisms**

A few different immunological mechanisms that are responsible for the possible negative correlation between *H. pylori* infection and IBD have been proposed. First, it was demonstrated that immune cell activation was suppressed by *H. pylori* DNA, including dendritic cells, macrophages, and other types of immune cells, which in

turn reduced the severity of the colitis [43–45]. Other possible mechanisms by which gastric mucosa is protected by *H. pylori* infection from *S. typhimurium*-induced inflammation include the suppression of the inflammatory T helper 1/17 (Th1/17) response in the lower GI Tract. This has been found in mice, so was the increased production of the anti-inflammatory interleukin-10 (IL-10) in mesenteric lymph nodes [46, 47]. Infection with *H. pylori* may be associated with the presentation of microbiota in the gut. The presence of mutations in genes that are known to be associated with CD provided evidence that microbiota play a part in the pathogenesis of the illness. This might be accomplished by a change in the immune response, mucosal permeability, or the metabolic products of microbes [48–52]. Antibiotics and probiotics are two examples treatments targeting bacteria, and there has been a recent increase of the use of both approaches. Stomach mucosal infection caused by *H. pylori* has been shown to have an effect on the intestinal microbiota, resulting in a considerable decrease in gut inflammation. Treg cell activation is of the highest significance in this respect because Treg cells inhibit inflammatory and immunological responses to gut bacteria, perhaps by secreting anti-inflammatory and immunosuppressive cytokines [53–56]. This hypothesis helps to explain why the immune system tolerates a wide variety of "non-self" gut bacteria, despite their location on the mucosal surface of the digestive tract. It has been shown that infection with *H. pylori* increases the number of regulatory T cells in the mucosa of the stomach and in the peripheral circulation [54]. This infection also alters the actions of these cells, perhaps by affecting the expression of certain receptors. *H. pylori* modifies the host immune response to change the inflammatory Th1/17 pattern. This is accomplished by upregulating Foxp3, a marker of regulatory T cells, in the gastric mucosa. By inhibiting protective immunological response, regulatory T cells (also known as Treg cells) maintain a constant level of *H. pylori* colonization [57, 58]. Additionally, mucosal modifications that impede stomach colonization by *H. pylori* and/or its spontaneous elimination in response to CD therapy, particularly 5-aminosalicylic acid treatment, may account for the decreased incidence of *H. pylori* infection in CD patients [9, 59, 60].

Probiotics may be useful to reduce intestinal inflammation if they are administered to reestablish a healthy balance in the microbiota of the gut and/or to reset the immunological systems that have been dysregulated [19]. The anti-inflammatory and immune-modulatory effects of probiotics help decrease inflammation by inhibiting the production of pro-inflammatory cytokines and enhancing the production of anti-inflammatory cytokines. This is how probiotics work to reduce inflammation. There have been conflicting reports on using probiotics in terms of efficacy as part of a therapeutic strategy to eradicate *H. pylori*. In a number of clinical studies, the standard triple therapy for *H. pylori* was supplemented with adjuvant medications (such as lactoferrin and probiotics), trying to lower the risks of adverse side effects and raising the change of complete eradication [9, 35, 39, 50, 54]. The addition of lactoferrin or probiotics to the triple therapy did not result in an increase in the rate of *H. pylori* eradication; however, it did result in a reduction in epigastric pain, vomiting, and diarrhea, indicating a less degree of inflammation [53, 57]. This paradox may be caused antibiotic resistance, as well as the difference in treatment regimens used by different organizations.

The toxic strains of *H. pylori* are the most common cause of infection in people with CD. On the basis of the results of other studies demonstrating a higher incidence of Helicobacteraceae in patients with CD, it has been hypothesized that Helicobacteraceae may play a role in the etiology of CD, and that various strains of *H. pylori* may be able to adapt to colonize extra-gastric regions [61–64]. These hypotheses are based

Helicobacter Pylori *Infection Correlates with Lower Prevalence and Subsequent Incidence… DOI: http://dx.doi.org/10.5772/intechopen.107943*

on the observation that CD patients have a higher prevalence of Helicobacteraceae. Additionally, it was shown that CD patients who exhibited a UC-like phenotype had higher prevalence rates of *H. pylori* in their stomachs [61, 64]. Because of the *H. pylori*-induced immune activation, there is a good chance that interleukin-12 (IL-12) and the Th1 immune response will be elevated [65, 66]. CD is an example of a Th1-related sickness, and TNF and IL-2 are two examples of Th1 cytokines that contribute to the development of the disease [66]. Infection with *H. pylori* promotes inflammation of the gut epithelium, which then secretes IL-8, attracting neutrophils that are involved in the pathogenesis of IBD [67, 68].

The elimination of *H. pylori* with the use of clarithromycin and/or proton pump inhibitors (PPIs) has been related to a decrease in Th1 factors, which may provide some degree of protection against CD [69, 70]. Nevertheless, no epidemiological data is available so far to support this idea. It has been shown that the common antibiotic clarithromycin has anti-inflammatory and immunomodulatory effects. These effects include a large decrease in the release and gene expression of Th1 factors and a smaller reduction in the synthesis of Th2 factors [71]. However, in other studies, it was shown that clarithromycin, but not amoxicillin, is able to reduce the levels of immunological components indicative of Th1, Th2, and Th17 [72–74]. Patients with steroid-sensitive asthma showed a decrease in Th2 factors after taking clarithromycin, whereas those with "infection-induced" steroid-resistant asthma showed a decrease in Th1/Th17 factors [72, 75]. In a randomized clinical trial that was controlled with a placebo, researchers found that the antibiotic clarithromycin was effective in treating persons with active CD for 1 month [76], possibly due to bacterial resistance. Because of the potential of PPIs to lower the amount of acid produced by the stomach, microbial growth in the upper GI tract may considerably increase. PPIs, on the other hand, inhibit the membrane H<sup>+</sup> /-ATPase of some gut microorganisms, which results in bacteriostatic and even bactericidal effects. Omeprazole has been shown to provide complete relief from UC symptoms in as little as 5 days. Lansoprazole may be beneficial in the treatment of IBD, including CD, by inhibiting the synthesis of specific proinflammatory cytokines in macrophages. *In vitro* research result revealed that the addition of lansoprazole to the culture media led to a decrease in the production of inflammatory cytokines (TNF- and IL-1) [77], which were produced by monocytes from peripheral blood. Because of their anti-inflammatory and immunomodulatory nature, clarithromycin and PPIs have been proposed as potential preventative approaches for CD; however, the epidemiological data to support this hypothesis is inadequate.

Putting aside any and all objections, the current research is a significant evidence that lends credence to the idea that the occurrences of *H. pylori* and CD have an negative association. More and more research results with consistent finding on the relationship between *H. pylori* infection and the CD development have been published. It has been suggested that *H. pylori* induce the development of regulatory T cells and impairs dendritic cell maturation, consequently resulting in a tolerogenic phenotype, which is a part of the mechanisms that *H. pylori* utilize to avoid host immune reactions.

Recent research results suggest that the processes that are responsible for the association may be more convoluted than previously thought. This is due to the fact that variables other than *H. pylori* infection influences the progression of CD. The findings of Shah et al. suggest that *H. pylori* may "serve as a signal for other gastrointestinal illnesses," which would provide some protection against CD [40]. It is noted in this study that the microbiota in the upper gastrointestinal tract differ among individuals

who are positive for *H. pylori* from individuals who are negative for the infection. Following the elimination of *H. pylori*, the changes of microbiota was found. Because it is considered that the gastrointestinal microbiota has a significant contribution to the development of CD, it is possible that a change in the components of the microbiota might change a person's vulnerability to CD. Since the relationship is clear, future research needs to focus more on the mechanisms that contribute to *H. pylori* infection, particularly in children. Another hotspot in the field would be the investigations focused on concomitant factors to *H. pylori* infection, such as alterations in the gut microbiota, which may potentially impact the etiology of Crohn's disease. A decision of the eradication of *H. pylori* in asymptomatic persons, in particular in patients with established Crohn's disease, should eventually be made based on the data collected from this type of researches.

#### **4. Conclusion**

Researchers have concluded that *H. pylori* should be classified as a suppress factor since patients with infections may have a reduced prevalence and subsequent incidence of CD. The Kyoto global agreement recommends eradicating *H. pylori* of each afflicted unless there are compelling reasons not to. This is because *H. pylori* may be associated with gastritis, which has been linked to an increased risk of developing stomach cancer. Despite the high infection incidence and the enormous amounts of antibiotics used, eradication of H. pylori has not been proven by various country recommendations. Unfortunately, epidemiologists specializing in *H. pylori control* paid little attention to the total impacts except for increased CD. *H. pylori* has an immunological tolerance mechanism, which allows it to stay in the mucosa while also the induced tolerogenic Th cells, immunosuppressive Tregs and cytokines are maintaining the critical systemic immune homeostasis. Consequently, the eradication of *H. pylori* with antibiotics is known to have greatly altered the microenvironment of gut bacteria. From the current review, this strategy has an indirect dramatic effect on immunological homeostasis, which may provide the potential risk of CD. The risk of gastric cancer in H. pylori-infected may not be calculated precisely, also the precise assessment of the risk of CD after *H. pylori* eradication is hard to be predicted and evaluated either. Therefore, the decreased prevalence and subsequent incidence of CD demonstrated the critical need for improved and individualized treatments for *H. pylori* infection.

Helicobacter Pylori *Infection Correlates with Lower Prevalence and Subsequent Incidence… DOI: http://dx.doi.org/10.5772/intechopen.107943*

#### **Author details**

Chenxiao Hu1† , Ting Lei2† , Natalie Tai3 , Yan Li4 , Xiujing Feng4 , Zhi Huang<sup>5</sup> \* † and Yun Lu6 \* †

1 The Information Center, The 1st Hospital of Lanzhou University, China

2 Department of Obstetrics and Gynecology, Key Laboratory for Gynecologic Oncology Gansu Province, The First Hospital of Lanzhou University, China

3 University of Maryland, USA

4 Independent Scholar

5 Cleveland Clinic, Lerner Research Institute, USA

6 Kent State University, USA

\*Address all correspondence to: huangz@ccf.org and ylu13@kent.edu

† These authors contributed equally to this work.

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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#### **Chapter 7**

## The Influence of *Helicobacter pylori* Infection Treatment on Psoriasis Severity

*Sampson Weytey*

#### **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.

**Keywords:** *Helicobacter pylori*, infection, antrum, psoriasis, dermatological, autoimmune, chronic, inflammatory, disease

#### **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-toperson, as well as through zoonotic transmission [17–19]. *H. pylori* infection routes

#### *The Influence of* Helicobacter pylori *Infection Treatment on Psoriasis Severity DOI: http://dx.doi.org/10.5772/intechopen.108870*

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

#### *The Influence of* Helicobacter pylori *Infection Treatment on Psoriasis Severity DOI: http://dx.doi.org/10.5772/intechopen.108870*

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

#### *The Influence of* Helicobacter pylori *Infection Treatment on Psoriasis Severity DOI: http://dx.doi.org/10.5772/intechopen.108870*

(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 [53–55].

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].

#### *The Influence of* Helicobacter pylori *Infection Treatment on Psoriasis Severity DOI: http://dx.doi.org/10.5772/intechopen.108870*

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

#### *The Influence of* Helicobacter pylori *Infection Treatment on Psoriasis Severity DOI: http://dx.doi.org/10.5772/intechopen.108870*

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.

### **Acknowledgements**

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.

#### **Author details**

Sampson Weytey School of Nursing, Valley View University, Accra, Ghana

\*Address all correspondence to: sampsonweytey@gmail.com

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*The Influence of* Helicobacter pylori *Infection Treatment on Psoriasis Severity DOI: http://dx.doi.org/10.5772/intechopen.108870*

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### *Edited by Daniela Cornelia Lazăr*

This book represents a comprehensive effort to investigate the complexity of *Helicobacter pylori* infection. As editors and contributors, we aim to provide a thorough exploration of the pathogenesis, diagnostic approaches, and contemporary clinical strategies in managing *H. pylori-*associated diseases. This book takes us through the multifaceted world of *H. pylori* infection. The first section provides thorough insights into the most recent knowledge of the pathogenesis, virulence factors, and complex adaptive modalities of *H. pylori* that allow it to colonize the stomach, evade our immune defenses, and trigger inflammation. This book's forefront lies in the evolution of diagnosis and clinical management. The book presents modern indications and treatment regimens for *H. pylori* infection, taking on the emerging challenges posed by antibiotic resistance and exploring the promise of future therapeutic strategies. An increasing number of investigations suggest that *H. pylori* infection might be involved in many extra gastric disorders such as cardiovascular, metabolic, neurological, dermatological, hematologic, ophthalmic, hepatobiliary, or even allergic diseases. The second section of our book provides the latest information on the potential role of this bacterium in different extra gastric conditions. Doctors of all specialties should take into consideration the possible presence and implications of *H. pylori* infection. This book is more than just a scientific treatise, it is a testimony to the enduring quest for knowledge and the impact it has on human health. It is addressed to a diverse audience, including healthcare professionals, researchers, students, and individuals intrigued by the fascinating world of microbes and their influence on our well-being. As you turn the pages, prepare to unravel the mysteries of *H. pylori* infection. This book will equip you with the latest knowledge, ignite your curiosity, and inspire you to contribute to the ongoing battle against this enigmatic foe. Join us on this journey and let us unlock the secrets of *H. pylori* together.

Published in London, UK © 2024 IntechOpen © SciePro / iStock

*Helicobacter pylori*

Infection - An Up to Date on the Pathogenic Mechanisms, Diagnosis and Clinical Management

*Helicobacter pylori* Infection

An Up to Date on the Pathogenic Mechanisms,

Diagnosis and Clinical Management

*Edited by Daniela Cornelia Lazăr*