|Year : 2018 | Volume
| Issue : 1 | Page : 49-57
Role of Helicobacter pylori eradication in the treatment of chronic idiopathic urticaria
Abdel Khalek H Younes1, Khaled M Tawfik1, Mohammed F Mohammed2, Refaat Ragheb1, Abeer A Abdel Tawaab3, Khaled A Eid2, Muhammad A Shawky2
1 Department of STDs and Andrology, Faculty of Medicine, Al Azhar University, Al-Minya, Egypt
2 Department of Gastroenterology & Hepatology (Tropical Medicine), Faculty of Medicine, Al Azhar University, Al-Minya, Egypt
3 General Mallawy Hospital, Al-Minya, Egypt
|Date of Submission||11-Nov-2015|
|Date of Acceptance||12-Jan-2016|
|Date of Web Publication||20-Nov-2018|
Khaled A Eid
Department of Gastroenterology & Hepatology (Tropical Medicine), Faculty of Medicine, Al Azhar University, Al-Minya, 71524
Source of Support: None, Conflict of Interest: None
Background Chronic urticaria is a common immunological disorder, with a prevalence of 15–25%. Several exogenous and endogenous causes have been proposed as causative agents; one of them is infection of the gastrointestinal tract. Despite thorough investigation, the etiology remains unresolved in more than 80% of the cases.
Objective The aim of the present study was to assess the prevalence of chronic idiopathic urticarial (CIU) patients presented with Helicobacter pylori infection and to study the effect of H. pylori eradication on the skin lesion in patients with CIU.
Methodology This prospective study was carried out at the outpatient clinic of Dermatology Department of Al Azhar Assuit University Hospital on 30 patients with chronic urticaria (20 women and 10 men); their ages ranged from 16 to 65 years. The duration of the disease ranged from 6 weeks to 18 years. A primary diagnosis of CIU was made when an etiological factor accounting for the majority of the lesions could not be elucidated during the history-taking and physical examination. All the patients were subjected to careful history-taking at initial visit; physical examination to assess the number of urticaria wheals, size, and distribution, and associated angioedema; gastroscopy to obtain gastric mucosal biopsy from the antrum; and histopathological assessment of the gastric mucosal biopsy using hematoxylin and eosin, and Giemsa stains. The patients were scored according to the severity of disease (number of wheals, area of distribution, and the duration of the disease; itching and style of life; history of angioedema). The patients were treated for 2 weeks with amoxicillin (1 g/twice daily), metronidazole (500 mg/three doses daily), and omeprazole (20 mg/twice daily). All patients were followed up during the study duration of 3 months. To assess eradication efficacy, a repeated H. pylori stool antigen test was carried out for each patient 6 weeks after the end of anti-H. pylori therapy. Statistical analysis of the data was performed by using the SPSS_16 software.
Results Fourteen patients (46.7%), aged less than 30 years, and 16 patients (53.3%), aged equal to or more than 30 years, were included in the present study. The mean of the ages of all patients was 34.9 years, and their age ranged from 16 to 65 years. There were 10 men (33.3%) and 20 women (66.7%). The mean of the duration of disease in all cases was 4 years, and ranged from 2 to 15 years. Nineteen patients presented with gastric symptoms. Seven patients (23.3%) had mild urticaria, 15 (50.0%) had moderate urticaria, and the remaining 8 (26.7%) had severe urticaria. Treatment results showed that 13 patients (43.3%) had complete remission, 12 patients (40.0%) had partial remission, and five patients (16.7%) showed no response. There was no statistically significant difference between age, sex, duration of illness, and gastric symptoms on the prognosis of urticaria after treatment. In addition, the results showed a highly statistically significant (P<0.01) difference between age categories and the gastric symptoms. The results also showed a statistically significant (P<0.05) difference between duration of disease and the gastric symptoms.
Conclusion H. pylori infection is considered as a main cause of CIU, specifically in patients with gastric symptoms, and the eradication of H. pylori may help in the treatment of CIU.
Keywords: chronic idiopathic urticaria, Helicobacter pylori eradication, treatment
|How to cite this article:|
Younes AH, Tawfik KM, Mohammed MF, Ragheb R, Abdel Tawaab AA, Eid KA, Shawky MA. Role of Helicobacter pylori eradication in the treatment of chronic idiopathic urticaria. Al-Azhar Assiut Med J 2018;16:49-57
|How to cite this URL:|
Younes AH, Tawfik KM, Mohammed MF, Ragheb R, Abdel Tawaab AA, Eid KA, Shawky MA. Role of Helicobacter pylori eradication in the treatment of chronic idiopathic urticaria. Al-Azhar Assiut Med J [serial online] 2018 [cited 2020 Apr 3];16:49-57. Available from: http://www.azmj.eg.net/text.asp?2018/16/1/49/244141
| Introduction|| |
Chronic spontaneous urticaria is defined as wheals arising spontaneously without any physical stimuli, and the disease lasts more than 6 weeks ,. Chronic urticaria (CU) is a common immunological disorder, with a prevalence of 15–25%. Several exogenous and endogenous causes have been proposed as causative agents (e.g. hyper-reactivity to foods; food additives or drugs; hidden and over infections in the ear, nose, and throat and in dental areas and the gastrointestinal tract, despite thorough investigations); the etiology remains unresolved in more than 80% of the patients .
Urticaria is also called hives or nettle rash: nettle rash is a herb with dark leaves and emits a stinging juice when broken . Urticaria is a heterogeneous disease that shares a distinct skin reaction pattern characterized by the sudden appearance of wheals, pruritus, and/or angioedema. It is estimated that anywhere from 12 to 22% of people will experience such symptoms at least once in their lives. Urticaria may become chronic in ∼25% of the affected patients . Untreated urticaria is associated with high direct and indirect healthcare costs and with impaired quality of life through diminished physical function, emotional problems, interference with sexual relationships, limitation of social interactions, and work-related factors. The considerable burden of urticaria highlights the need for timely diagnosis and effective treatment. Insights into the mechanisms underlying this family of diseases have paved the way for the incorporation of improved management strategies into treatment guidelines designed to help physicians optimize outcomes . Chronic spontaneous urticaria is defined by urticarial symptoms that last for 6 or more weeks. CU is usually observed following an inflammatory response mediated by mast cells. Its prevalence is reported to be around 0.6% in adults. In children, however, CU is less common and has been reported to affect 0.1–0.3% of all children. Although the etiology of CU is usually considered idiopathic, acute and chronic infections, as well as food and drug hypersensitivity reactions and autoimmunity, are recognized as potential etiologic factors .
Chronic idiopathic urticaria (CIU) is a disease characterized by itching and skin hives or wheals of unknown cause, which vary in size and last for at least 6 weeks . Angioedema occurs concurrently with CIU in about 50% of the cases and delayed pressure urticaria in about 40% . Gastrointestinal symptoms in the form of nausea, vomiting, and abdominal pain are present in around 40% of the patients of CIU .
Helicobacter pylori is gram negative, microaerophilic spiral rod-shaped bacteria that lives just beneath the antral gastric mucosa, on the surface of epithelial cells. Stomach infection caused by this organism results in the inflammation of the gastric mucosa, which can lead to gastritis, duodenal or gastric ulcer and even in rare cases to gastric carcinoma or mucosa associated lymphoid tissue lymphoma. Over 80% of the patients infected with this bacterium are asymptomatic .
A close relationship has been found between H. pylori infection and upper gastrointestinal disorders such as peptic ulcer diseases, gastric cancer, and gastric mucosa-associated lymphoid tissue lymphoma (Shinsaku Fukuda et al. 2004). Eradication of H. pylori is a part of the effective treatment and/or prevention of these disorders, and also reduces the occurrence of new gastric cancers after endoscopic resection . At present, the most common methods for the eradication of H. pylori infection consist of the administration of a proton pump inhibitor and antimicrobial agents such as amoxicillin, clarithromycin, metronidazole, fluoroquinolone, or tetracycline. Each of these agents has its own characteristics with respect to pharmacokinetics, pharmacodynamics, and pharmacogenomics, which theoretically affect treatment success attained with the different therapeutic regimens. This article describes the pharmacologic characteristics of the common agents used for eradication of H. pylori infection. This knowledge should be helpful for clinicians trying to achieve optimal eradication of H. pylori infection and investigators designing new treatment protocols .
| Patients and methods|| |
A total of 30 patients with CU were selected from the outpatient clinic of Dermatology Department of Al Azhar Assuit University Hospital. Patients were selected according to the definition put forward by Odom et al. , who defined CU as the recurrence of urticarial wheals daily or on most of days over a 6 or more weeks; the wheals usually last less than 24 h leaving normal skin behind. The patients included in the present study comprised 20 women and 10 men. Their ages ranged from 16 to 65 years. The duration of the disease ranged from 6 weeks to 18 years. A primary diagnosis of CIU was made when an etiological factor accounting for the majority of lesion could not be elucidated during the history-taking and physical examination.
The only inclusion criterion for the patients with CIU was their willingness to participate in the study. Following were the exclusion criteria: patients with allergy form chemicals, rheumatoid patients, patients aged less than 14 years and more than 65 years, patients with thyroid gland disturbance and parasitic infections, patients with liver and kidney diseases, pregnant women, those who took proton pump inhibitors 4 weeks before the study, patients with previous gastric surgery, and those with the coexistence of serious concomitant illness (e.g. decompensated liver cirrhosis or uremia).
All the patients were subjected to:
- Careful history-taking at the initial visit, and the following were assessed: the frequency of flare, associated itching, body regions affected, possible diurnal variation, the presence of any concomitant gastrointestinal disease or complaint, history of atopy, food allergy, and drug intake; in addition, patients were asked about the relation of urticaria to stress, cold, heat, pressure, and exercise to exclude the cases of physical urticaria and associated arthralgia, and to arthritis to exclude connective tissue disease.
- Physical examination to assess the following: number of urticaria wheals, size, and distribution; associated angioedema; any residual bruising after disappearance of the wheals to exclude urticarial vasculitis. Any systemic illness or focus of infection was also excluded.
- Gastroscope to obtain gastric mucosal biopsy from the antrum.
- Histopathological assessment of the gastric mucosal biopsy using haematoxylin and eosin and Giemsa stains.
The patients were scored according to the severity of the disease in terms of number of wheals, area of distribution, duration of the disease, itching and style of life, and history of angioedema.
The patients were treated for 2 weeks with the following:
- Amoxicillin (1 g/twice daily).
- Metronidazole (500 mg/three doses daily).
- Omeprazole (20 mg/twice daily).
All patients were followed up during the study duration of 3 months. To assess the eradication efficacy, a repeated H. pylori stool antigen test was performed for each patient 6 weeks after the end of the anti-H. pylori therapy. The effectiveness of eradication therapy on CU was assessed 3 months after treatment, using a three-point rating scale (complete remission, partial remission, or no response).
After obtaining verbal patient consent, patients were asked to fast and were prepared for endoscopy. They were prepared for gastroscopy by administering dormicum and buscopan ampules intravenously. They took the position for easy gastroscopy by laying on the left side and their left arm backward. The sterilized upper gastroscope was introduced then biopsy needle and gastric mucosal biopsy was taken from the antrum. The specimen were preserved in 10% aqueous solution of formalin and processed for routine staining. Haematoxylin and eosin and Giemsa stains for the detection of H. pylori and presence of inflammation.
The histopathological assessment
The gastritis was graded according to the number of inflammatory cells observed relative to the number of inflammatory cells present in histologically normal sections. The grades were as follows:
- Normal=normal number of mononuclear cells and polymorphnuclear leucocytes.
- Mildly increased number of mononuclear cells and very occasional polymorphnuclear leucocytes.
- Moderate=moderately increased mononuclear cells and polymorphnuclear leucocytes.
- Severe=moderately increased mononuclear cells and polymorphnuclear leucocytes, with intraepithelial polymorphnuclear leucocytes [Thomsen et al. (1990)] .
Statistical analysis of the data was performed by using SPSS_16 software (SPSS Inc., Chicago, IL, USA). Categorical data parameters were presented in the form of frequency and percent. Quantitative data were expressed in the form of mean±SD. The χ2-test was used for categorical data.
| Results|| |
[Table 1] presents the descriptive statistics of all the studied cases. Fourteen patients (46.7%) were less than 30 years of age and 16 (53.3%) were equal to or more than 30 years of age; the mean of ages of all patients was 34.9 years, and their ages ranged from 16 to 65 years. There were 10 men (33.3%) and 20 women (66.7%). In total, 20 patients had CU for less than 5 years and the remaining 10 patients had it for equal to or more than 5 years; the mean duration of the disease for all patients was 4 years, and the disease duration ranged from 2 to 15 years. A total of 19 patients had gastric symptoms, whereas 11 patients had no gastric symptoms. Seven patients (23.3%) had mild urticaria, 15 (50.0%) had moderate urticaria, and the remaining eight (26.7%) had severe urticaria. Results of stool antigen after the treatment of H. pylori were negative for the majority of the patients, 28 cases (93.3%), whereas for the remaining two (6.7%) they were positive. The results of the prognosis of urticaria after treatment were as follows: 13 patients (43.3%) had complete remission, 12 cases (40.0%) had partial remission, and five (16.7%) showed no response.
|Table 1 Age, sex, disease of duration, gastric symptoms, degree of urticaria, stool antigen after treatment and prognosis of urticaria of all studied cases|
Click here to view
[Table 2] shows the relation between age, sex, disease of duration, gastric symptoms, and the degree of urticaria and prognosis of urticaria after treatment. There was no statistically significant difference between age categories on the prognosis of urticaria after the treatment. There was no statistically significant difference between men and women on the prognosis of urticaria after treatment. The results indicated that there was no statistically significant difference between the duration of illness categories on the prognosis of urticaria after treatment. Results indicated that there was no statistically significant difference between gastric symptoms and the prognosis of urticaria after treatment. There was no statistically significant difference between degree of urticaria and the prognosis of urticaria after treatment.
|Table 2 Relation between age, sex, disease of duration, gastric symptoms and degree of urticaria and prognosis of urticaria after treatment|
Click here to view
[Table 3] shows the relation between age, sex, disease of duration, gastric symptoms, and degree of urticaria and gastric symptoms. The results indicated that there was a highly statistically significant (P<0.01) difference between age categories on the gastric symptoms. No statistically significant difference was found between men and women. The results illustrated that there was a statistically significant (P<0.05) difference between duration of disease and gastric symptoms. Results illustrated that there was an obvious difference but not statistically significant.
|Table 3 Relation between age, sex, disease of duration, gastric symptoms and degree of urticaria and gastric symptoms|
Click here to view
| Discussion|| |
Urticaria is a mucocutaneous disease characterized by erythematous, edematous, and pruritic lesions of the dermis and/or hypodermis, resulting from the degranulation of mast cells and basophils and the release of inflammatory mediators, mainly histamine . Urticaria has historically been classified as either acute or chronic on the basis of its duration (acute: lasting fewer than 6 weeks; chronic: lasting 6 or more weeks) . In the recent years, many researchers evaluated the correlation between H. pylori infection with CU. H. pylori infection is the most important cause of peptic ulcer disease, and the possible relationship with the CU has been proposed. Much research has been conducted on the relationship between H. pylori infection and many other chronic diseases such as urticaria, delayed growth in children, lymphoma of stomach, etc. Some studies support that same kind of immunoallergic mechanisms are involved in peptic ulcer disease and CU .
The present study was conducted on 30 patients with CIU. Among them, 14 (46.7%) were aged less than 30 years and 16 (53.3%) equal to or more than 30 years; there were 10 men (33.3%) and 20 women (66.7%) ([Table 2]). The majority of CU patients were women ([Table 2]), an observation that also has been reported by Tebbe et al. , Ertam et al. , and Fraser and Robertson, (2013) . In their study, George and Adam  hypothesized that women in their third and fourth decades are at a high risk for urticaria due to the increased resistance to drugs, which develops as a result of the usual use of these drugs in pelvic inflammatory diseases, mainly antibiotics and metronidazole. Paul  reported that CU can affect anyone at any age (without a specific prevalence in specific age) ([Table 1]). In their study, Sabroe and Greaves  reported that this may be because of catching more pathogen-like H. pylori with age, and that more advanced lesions in stomach may occur leading to a more severe degree of CU. They also found that the degree of CU was significantly higher in men than in women (P<0.05); this may be due to the small number of men in this study (eight patients out of 30), and thus there was little chance to meet many patients with variable severties or that men are more prone to gastritis and peptic ulcer and thus are more liable to more enzymes, toxins, and mediators for inducing severe CU.
The present results also indicated that patients who had gastric symptoms and were aged more than 30 years were higher significantly (P<0.01) than the patients who were negative to gastric symptoms and were younger than 30 years whereas there was no significant difference between males and females in the incidence of gastric symptoms except it was higher (but insignificantly) in females than males and this may due to the higher number of females than males. The difference between the duration of illness and gastric symptoms was statistically significant (P<0.05). About half of the patients who had gastric symptoms had a duration of illness less than 5 years and the other half of the patients had a duration of urticaria more than 5 years. The difference between cases who had gastric symptoms and the patients who were negative in degree of urticaria was not significant.
The duration of CU in 20 patients (66.7%) was less than 5 years and for the remaining 10 patients (33.3%) it was equal to or more than 5 years. In our study, out of the 30 patients presenting with CIU, 11 presented with no gastric symptoms and the remaining 19 presented with gastric symptoms. These results agreed with those of Imran and Qazi , who found that there is an association between gastrointestinal symptoms and the presence of CU and its H. pylori etiology. In their study, Kalas et al.  found that 17 out of 40 patients with CU showed gastric symptoms, and that H. pylori was not higher than that of the age-matched healthy population. A study by Brodell and Beck  reported that the patients with CU associated with H. pylori infection may present only with hives/wheals without gastrointestinal symptoms or sometime with abdominal pain and CU. The skin manifestations, severity, and exacerbation might depend on the bacterial load and the intensity of inflammation. In their study, Campli et al. (1998)  found that the prevalence of gastrointestinal symptoms did not differ among their patients with CU, whether they were infected or uninfected with H. pylori, an observation that was also noticed by Teebbe et al. (1996)  and Bohmeyer et al. . These give a high importance to the investigation of H. pylori in CU patients irrespective of the existence of gastrointestinal symptoms. In addition, Kolibasova et al.  have found association between H. pylori and CU in their studies. Abdou et al.  studied the H. pylori infection in patients with CU against 40% of control subjects and they found that 57% of the patients were positive for H. pylori infection, but the difference did not reach statistically significant levels (P=0.47). The severity of urticarial symptoms was greater in the H. pylori-positive group than in the H. pylori-negative group (P=0.019). Heavy bacterial colonization (P=0.008) and intense gastric inflammation (P<0.0001) were associated significantly with severe clinical manifestations. Overall, 80% of the H. pylori-positive urticaria group experienced complete remission after receiving eradication therapy for H. pylori.
The result of the stool antigen, which was carried out after the end of treatment of H. pylori by 6 weeks, was negative for the majority of the patients, 28 cases (93.3%), whereas it was positive for the remaining two cases (6.7%). In our study, we used amoxicillin (1 g/twice daily), metronidazole (500 mg/three doses daily), and omeprazole (20 mg/twice daily) for the treatment of H. pylori, and this proved efficacious for the inhibition of the H. pylori. These results are in agreement those obtained in a study conducted by Gaig et al. , who studied the efficacy of the eradication of H. pylori infection in patients with CU by treating them with amoxicillin, metronidazole, and omeprazole. In addition, they observed a significant improvement in more than 70% of the CIU patients; baseline clinical score was seen in four out of the nine (44%) patients for whom H. pylori eradicated after active treatment, and in one patient out of seven (12.3%) for whom H. pylori could not be eradicated (P=0.19). In addition, they noticed no clinical differences in CIU characteristics between patients with and without improvement. No serious adverse effects were observed in the either treatment group. They concluded that the eradication of H. pylori may be useful for patients suffering from long-lasting CIU and H. pylori infection, although these results did not reach statistical significance, probably because of the strict conditions of the recruitment. Similar results were obtained in the study by Imran and Qazi  and Attumi and Graham . If H. pylori persisted after first-line therapy, patients were offered second-line therapy, comprising omeprazole 20 mg, amoxicillin 1000 mg, and metronidazole 500 mg twice a day for another 7 days. After completion of the therapy, all infected patients were prescribed antihistamines to be used as ‘rescue medicine’ (H. Vosoghineia et al., 2007) . They concluded that to improve the healing effectiveness and to decrease the risk of adverse effects, not only appropriate drug selection but also optimal dosage and duration of treatment are essential .
In this study, the results of the prognosis of urticaria after the treatment of H. pylori indicated that 13 patients (43.3%) had complete remission, 12 cases (40.0%) had partial remission, and five cases (16.7%) showed no response. These results are in agreement with those of a study conducted by Mogaddam et al. (2015) , a study designed to determine the prevalence of H. pylori infection using the stool antigen test in patients with idiopathic CU and to investigate the infected patients with CU following the eradication of H. pylori. The study was conducted on 200 people (100 patients with idiopathic CU and 100 healthy controls); they were tested for H. pylori antigen. To assess eradication efficacy, a repeated H. pylori stool antigen test was carried out for each patient 6 weeks after the end of anti-H. pylori therapy. The effectiveness of the eradication therapy on CU was assessed 3 months after treatment. They found that 36% patients with idiopathic CU were infected with H. pylori, whereas 23% of the controls were infected. Response to the eradication therapy was evident in 33 (91.7%) patients in whom H. pylori was eradicated, whereas three (8.33%) patients showed no response despite the eradication of H. pylori. Clinical follow-up of 33 successfully treated patients 3 months later revealed complete remission of urticaria in 54.5% of the patients, partial remission in 18.2%, and no improvement in 27.3%. They concluded that H. pylori infection should be included in diagnostic work-up of patients with no response to habitual treatment for CU or symptomatic gastrointestinal patients. In their study, Bonamigo et al. (1999)  found strong evidence that H. pylori is an etiological factor of urticaria; their study comprised 18 patients over 18 years with clinical and laboratory evidence of CU; H. pylori was evaluated by using serum IgG. In the patients positive with H. pylori, oral doses of amoxicillin, metronidazole, and omeprazole were given to eradicate the agent. In the cases treated to eradicate H. pylori, six patients had complete remission, four had partial remission, and two showed no improvement. Prevalence of H. pylori infection is significantly high in CU patients (20.6%), atopic dermatitis, and other skin conditions. Eradication of the H. pylori bacterium has a dramatic influence (37.0%) and good response in 60.8% − that is, most of the associated skin disorders. Therefore, prevalence of H. pylori infection is significantly high in patients with CU (20.6%), atopic dermatitis, and other skin conditions .
A number of studies in several countries showed the high prevalence of H. pylori infection in CU patients, followed by clinical remission of CU after the H. pylori eradication therapy. In the first one of these studies, back in 1994, Kolibasova et al.  assessed 21 patients with CU and H. pylori infection. Eradication therapy against the bacterium led to the remission of urticaria in 95% of the cases. Later on, Bohmeyer et al.  carried out an endoscopic assessment in 10 patients with CU, finding H. pylori in the gastric mucosa in eight of them; they reported that the skin lesions disappeared within a few days of treatment with amoxicillin and omeprazole. Another study showed that the eradication of H. pylori infection by triple therapy significantly and equally reduces urticarial activity score in CU patients with positive and negative autologous serum test . A growing body of evidence suggests that 30–50% of CU results from an autoimmune process involving functional histamine-releasing anti-Fc RI a autoantibodies or, less commonly, anti IgE autoantibodies. A study by Appelmelk et al. (2009)  first demonstrated the molecular mimicry between H. pylori and lipopolysaccharide and anti-Lewis antibodies in autoimmune type-B gastritis. Further evidence was provided by the highly positive autologous serum skin test results in CU patients with H. pylori IgG antibodies (Morgan and Khan) . Treatment and eradication of H. pylori was reported to be associated with the remission of CU [Ozkaya-Bayazit et al. (1998) , Yadav et al. (2008) , and Di Campli et al. (1998)] . However, the association remains controversial and the pathogenic mechanisms have never been confirmed (Shiotani et al. 2009).
Our results indicated that women were sluggish to respond to the treatment than were men, but the difference was not statistically significant; four men (30.8%) had complete remission, whereas nine women (69.2%) had complete remission; half of the patients (six cases) who had partial remission were men and the rest were women. However, all patients (100.0%) who had no response were women. These results are in agreement with those of a study by Hellmig et al.  and Mogaddam et al. (2015), who found that there was no significant difference between men and women as regards the response to the treatment of H. pylori. In addition, in our study, the effect of the duration of illness on the results of the prognosis of urticaria after the treatment of H. pylori indicated that it was obvious that the number of cases who had short duration of illness responded much more than did patients who had long duration (more than 5 years), but the difference was not significant. The results are in agreement with those of a study by Chiu et al.  and Persechino et al. , who studied the prevalence of H. pylori infection and the effects of its eradication on CU and found that there was no significant relation between the degree and duration of illness and the remission of urticaria.On the inner surface of the gastrointestinal tract, our H. pylori comes in an intimate contact with bacteria, parasites, enzymes, toxins, and various dietary substance and their breakdown products. All those substances and agents including H. pylori itself and its toxin may affect GALT homeostasis and may activate an immune response. On the other hand, we must remember that H. pylori toxin release and subsequent possible complement activation could also occur. During the complement activation process, anaphylotoxins C3a and C5a are generated. The interaction of these complements’ regiments with specific receptors on mast cell and basophil cause the release of histamine . However, there is increasing evidence that H. pylori may also be involved in other dermatologic diseases. Clinical association between H. pylori and Rosacea and Sjogren’s syndrome have been reported . In addition, association is present between H. pylori and pruritus cutaneous, atopic dermatitis, nummular dermatitis, and prurigo chronica multiformis (Sakurane et al. 2002) .
Wedi et al.  suspected that an autoimmune pathogenesis or considerable vascular impairment can be found in the cases of CU related to H. pylori. The systemic effect of H. pylori may involve increased mucosal permeability to alimentary antigen, immunomodulation, autoimmune mechanism, or the impairment of vascular integrity. One possibility is the development, in genetically predisposed person, of autoantibodies by molecular mimicry, perhaps against lipopolysaccharide of H. pylori . In addition, the study by Hidvegi et al. (2001)  supported the hypothesis that there is an increased lymphocyte reactivity in CU, perhaps further enhanced by the presence of H. pylori, which may be involved as a trigger in the pathogenesis of CU. Asero  found that out of 29 patients with CU only one had a total disappearance of symptoms after the successful eradication of H. pylori infection, for whom the results of upper gastrointestinal endoscopy were positive. Therefore, their study indicated no association between H. pylori and CU.
In developing countries like Egypt the H. pylori infection is more common and occurs at a younger age than in developed countries, which may put the H. pylori as a cause of CU. The prevalence of H. pylori in large portion of our population does not rule out the role of H. pylori infection in CU, as individual susceptibility may exist. Finally, a further study would be helpful in establishing the relation between CU and H. pylori infection in our population, especially with evaluation after treatment.
| Conclusion|| |
H. pylori infection is considered as the main cause of CIU, specific in patients with gastric symptoms, and the eradication of H. pylori may help in the treatment of CIU. The prevalence of H. pylori was high in CU patients included in this study, and that is why we recommend further investigation for the H. pylori infection in patients with CIU to identify the subset of patients who are infected and who could benefit from the eradication therapy. H. pylori should be included in the diagnostic work-up of all patients with CIU, especially if they complain of gastric troubles, as the treatment of H. pylori by complete cause of optimal dose and duration of triple therapy may help in the recovery of CU in these patients.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Brunetti L, Francavilla R, Miniello VL, Platzer MH, Rizzi D, Lospalluti ML. High prevalence of autoimmune urticaria in children with chronic urticaria. J Allergy ClinImmunol 2004; 114:922–927.
Zuberbier T, Asero R, Bindslev-Jensen C, Walter Canonica G, Church MK, Giménez-Arnau A et al.
EAACI/GA2LEN/EDF/WAO guideline: definition, classification, and diagnosis of urticaria. Allergy 2009; 64:1417–1426.
Jonathan A, Bernstein MD. Chronic urticaria: an evolving story immunology and allergies. Isr Med Assoc J 2005; 7:774–777.
Kaplan AP. Chronic urticaria: pathogenesis and treatment. J Allergy ClinImmunol 2004; 114:465–474.
Akelmaa AZ, Metea E, Cizmeci MN, Kanburoglub MK, Malli DD, Bozkaya D. The role of mean platelet volume as an inflammatory marker in children with chronic spontaneous urticaria. Allergol Immunopathol (Madr) 2013; 43(1):10–13.
Greaves MW. Chronic idiopathic urticaria. Curr Opin Allergy Clin Immunol 2003; 3:363–368.
Federman DG, Kirsner RS, Moriarty JP, Concato J. The effect of antibiotic therapy for patients infected with Helicobacter pylori
who have chronic urticaria. J Am Acad Dermatol 2003; 49:861–864.
Juhlin L. Recurrent urticaria: clinical investigation of 330 patients. Br J Dermatol 1981; 104:369–379.
Morgan M, Khan DA. Therapeutic alternatives for chronic urticaria: an evidence-based review, part 1. Ann Allergy Asthma Immunol 2008; 100:403–412.
Kaloorazi NA, Mohammadi M. Helicobacter pylori
infection and extragastric diseases. J Biol Today’s World 2013; 2:121–132.
Ibrahim MS, Adam AA, Abdelhalim KA. Helicobacter pylori
immunoglobulin-M antibodies among urticaria and non-urticaria patients attending khartoum Dermatology Hospital, Sudan. Am J Res Commun 2014; 2:XX–XX.
Odom RB, James WD, Berger TG. Erythma & urticaria In: XXX XXX Andrew’s diseases of the skin clinical dermatology. 9th ed. XXX : Saunders Company 2000;161–171.
Thomsen L, Gavin J, Tasman-Jones C. Relation of Helicobacter pylori to the human gastric mucosa in chronic gastritis of the antrum. Gut 1990; 31:1230–1236.
Magen E, Delgado J-S. Helicobacter pylori
and skin autoimmune diseases. World J Gastroenterol 2014; 20:1510–1516.
Magen E, Mishal J. Possible benefit from treatment of Helicobacter pylori
in antihistamineresistant chronicurticaria. Clin Exp Dermatol 2013; 38:7–12.
Tebbe B, Christoph C, Geilen J. Helicobacter pylori
and chronic urticaria. J Am Acad Dermatol 1996; 39:685–686.
Ertam I, Biyikli SE, Yazkan FA, Aytimur D, Alper S. The frequency of nasal carriage in chronic urticaria patients. J Eur Acad Dermatol Venereol 2007; 21:777–780.
Fraser K, Robertson L. Chronic urticaria and autoimmunity. Skin Therapy Lett 2013; 18:5–9.
George JJ, Adam H. Helicobacter pylori
. In: XXX XXX Clinician’s manual on Helicobacter pylori
. XXXX: XXXX 1995. 93–98
Paul S. Urticaria: evaluation and treatment. Am Fam Physician 2011; 83:1078–1084.
Sabroe RA, Greaves MW. The pathogenesis of chronic idiopathicurticaria. Arch Dermatol 1997; 133:1003–1008.
Imran M, Qazi M. Chronic idiopathic urticaria, gastrointestinal symptoms and Helicobacter pylori
infection. J Pak Assoc Dermatol 2008; 18:207–211.
Kalas D, Pronai L, Ferenczi K, Palos G, Daróczy J Connection between Helicobacter pylori
infection and chronic gastrointestinal urticaria. Orv Hetil 1996; 137:1969–1972.
Brodell LA, Beck LA Differential diagnosis of chronic urticaria. Ann Allergy Asthma Immunol 2008; 100:181–188.
Di Campli C, Gasbarrini A, Nucera E, Franceschi F, Ojetti V, Torre ES et al.
Beneficial effects of Helicobacter pylori eradication on idiopathic chronic urticaria. Dig Dis Sci 1998; 43:1226–1229.
Bohmeyer J, Heller A, Hartig C et al.
Association of chronic urticaria with Helicobacter pylori
-induced antrum gastritis. Hautarzt 1996; 47:106–108.
Kolibasova K, Cervenkova D, Hegyi E et al. Helicobacter pylori
: ein möglicher ätiologischer Faktor del chronischen Urticaria. Dermatosen 1994; 42:235–236.
Abdou AG, Elshayeb EI, Farag AG, Elnaidany NF. Helicobacter pylori infection in patients with chronic urticaria: correlation with pathologic findings in gastric biopsies. Int J Dermatol 2009; 48:464–469.
Gaig P, García-Ortega P, Enrique E, Papo M, Quer JC, Richard C. Efficacy of the eradication of Helicobacter pylori
infection in patients with chronic urticaria. A placebo-controlled double blind study. Allergol Immunopathol (Madr) 2002; 30:255–258.
Attumi TA, Graham DY. Increasing the duration of dual amoxicillin plus omeprazole Helicobacter pylori
eradication to 6 weeks: a pilot study. J Gastroenterol Hepatol 2012; 27:59–61.
Vosoghineia H, Farid R, Azad FJ, Zakavi R, Talaei-Khoei M, Hossini A et al.
Effects of Helicobacter pylori eradication on chronic idiopathic urticaria. Iranian J Med Sci 2007; 33:18–21.
Ksiądzyna D, Szandruk M, Szeląg A. Treatment prospects of Helicobacter pylori
infection. Prz Gastroenterol 2012; 7:70–77.
Mogaddam MR, Yazdanbod A, Ardabili NS, Maleki N, Isazadeh S. Relationship between Helicobacter pylori and idiopathic chronic urticaria: effectiveness of Helicobacter pylori eradication. Adv Dermatol Alergol/Postȩpy Dermatologii i Alergologii 2015; 32:15.
Bonamigo R, Leite C, Bakos L. Study about the association of Helicobacter pylori and idiopathic chronic urticaria. Rev Assoc Med Bras 1999; 45:09–14.
Couturier MR. The evolving challenges of Helicobacter pylori
disease, diagnostics, and treatment, part I. Clin Microbio Newsl 2013; 35:3.
Appelmelk BJ, Simoons-Smit I, Negrini R, Moran AP, Aspinall GO, Forte JG et al.
Potential role of molecular mimicry between Helicobacter pylori lipopolysaccharide and host Lewis blood group antigens in autoimmunity. Infect Immunity 1996; 64: 2031–2040.
Özkaya-Bayazit E, Demir K, Özgüroğlu E, Kaymakoğlu S, Özarmağan G. Helicobacter pylori eradication in patients with chronic urticaria. Arch Dermatol 1998; 134:1165–1167.
Yadav M, Rishi J, Nijawan S. Chronic urticaria and Helicobacter pylori. Indian J Med Sci 2008; 62:157–162.
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Di Campli C, Gasbarrini A, Nucera E, Franceschi F, Ojetti V, Torre ES et al.
Beneficial effects of Helicobacter pylori eradication on idiopathic chronic urticaria. Dig Dis Sci 1998; 43:1226–1229.
Hellmig S, Troch K, Ott SJ et al.
Role of Helicobacter pylori
infection in the treatment and outcome of chronic urticaria. Helicobacter 2008; 13:341–345.
Chiu YC, Tai WC, Chuah SK, Hsu PI, Wu DC, Wu KL et al.
The clinical correlations of Helicobacter pylori
virulence factors and chronic spontaneous urticaria. Gastroenterol Res Pract 2013; 2013:6.
Persechino S, Annibale B, Caperchi C, Persechino F, Narcisi A, Tammaro A et al.
Chronic idiophatic urticaria and Helicobacter pylori
: a specific pattern of gastritis and urticaria remission after Helicobacter pylori
eradication. Int J Immunopathol Pharmacol 2012; 25:765–770.
Valsecchi R, Pigatto P. Chronic urticaria and Helicobacter pylori
. Acta Dermatol Venereol 1998; 78:440–442.
Rebora A, Drago F, Parodi A. May Helicobacter
be important for the dermatologist? Dermatology 1995; 191:6–8.
Sakurane M, Shiotani A, Furukawa F. Therapeutic effects of antibacterial treatment for intractable skin diseases in Helicobacter pylori‐positive Japanese patients. J Dermatol 2002; 29:23–27.
Wedi B, Raap U, Kapp A. Chronic urticaria and infections. Curr Opin Allergy Clin Immunol 2004; 4:387–396.
Greaves MW. Chronic urticaria. J Allergy Clin Immunol 2000; 105:664–672.
Hidvégi B, González-Cabello R, Temesvári E, Szentmihályi A, Nagy E, Fekete B et al.
The effect of heat-inactivated Helicobacter pylori on the blastogenic response of peripheral blood mononuclear cells of patients with chronic urticaria. Int Arch Allergy Immunol 2001; 126:167–172.
Asero R. Leukotriene receptor antagonists may prevent NSAID induced exacerbations in patients with chronic urticaria. Ann Allergy Asthma immunol 2000; 85:150–157.
[Table 1], [Table 2], [Table 3]