|Year : 2019 | Volume
| Issue : 1 | Page : 226-230
A study on chronic idiopathic urticaria and Helicobacter pylori infection
Magda M Hagag1, Azza G. A. Farag1, Nesreen G Elhelbawy2, Eman G. D. El-Gendy1
1 Department of Dermatology, Andrology and STDs, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Medical Biochemistry, Faculty of Medicine, Menoufia University, Menoufia, Egypt
|Date of Submission||03-Apr-2017|
|Date of Acceptance||23-Apr-2017|
|Date of Web Publication||17-Apr-2019|
Eman G. D. El-Gendy
Al-Menoufia, Shebien El-Kom
Source of Support: None, Conflict of Interest: None
The aim of this paper was to assess the effect of successful eradication of Helicobacter pylori (H. pylori) infection on the activity of chronic idiopathic urticaria (CIU) in patients with CIU infected with H. pylori.
Materials and methods
Medline databases including PubMed, Medscape, ScienceDirect, and EMF-Portal and all materials available in the Internet from 2005 to 2016 were searched. The initial search presented 28 articles, of which six met the inclusion criteria. The articles studied the relation between CIU and H. pylori infection and the effect of H. pylori eradication on the disease activity. If the studies did not fulfill the inclusion criteria, they were excluded. Study quality assessment included whether ethical approval was gained, eligibility criteria specified, appropriate controls, adequate information, and defined assessment measures. Comparisons were made by structured review, with the results tabulated.
In total, six potentially relevant publications were included, and they were all human studies. Several studies showed high prevalence of H. pylori infection in patients with CIU, with clinical improvement of the disease activity after H. pylori eradication, whereas other studies concluded that there is no evidence that eradication of H. pylori improves the outcome in patients with CIU. The high rate of spontaneous remission and the coexistence of multiple foci will always obscure the evaluation of any specific antimicrobial therapy.
We found that H. pylori may play a role in the pathogenesis of CIU, and H. pylori eradication therapy must be tried for positive cases with CIU.
Keywords: chronic idiopathic urticaria, chronic urticaria, H. pylori
|How to cite this article:|
Hagag MM, Farag AG, Elhelbawy NG, El-Gendy EG. A study on chronic idiopathic urticaria and Helicobacter pylori infection. Menoufia Med J 2019;32:226-30
|How to cite this URL:|
Hagag MM, Farag AG, Elhelbawy NG, El-Gendy EG. A study on chronic idiopathic urticaria and Helicobacter pylori infection. Menoufia Med J [serial online] 2019 [cited 2019 May 21];32:226-30. Available from: http://www.mmj.eg.net/text.asp?2019/32/1/226/256093
| Introduction|| |
Chronic urticaria (CU) is defined as the occurrence of daily or almost daily wheals and itching for at least 6 weeks. It is a common and potentially debilitating skin condition that affects up to 1% of the general population with variable duration, from typically several months to occasionally decades .
Chronic idiopathic urticaria (CIU) is defined as the occurrence of CU with no obvious cause, constituting up to 70% of cases .
CU develops in both children and adults, although it is more common in adults. Women are affected twice as men, and the condition typically begins in the third to fifth decade of life .
None of the theories of pathogenesis of CU have been fully established, and the best developed hypotheses include the autoimmune theory and theories involving histamine-releasing factors and the cellular defects theory .
CU is further classified into spontaneous, i.e., chronic spontaneous urticaria, and inducible, i.e., induced by physical stimuli, CU. In the new terminology, the term 'spontaneous' replaces the term 'idiopathic' and the term 'inducible' replaces the term 'physical' [Table 1] ,.
CU may be caused by foods, food additives, drugs, stress, diseases, physical causes (physical urticaria), and infections, including Helicobacter pylori (H. pylori) infection .
A new measurement has been developed to grade urticaria severity: the urticaria activity score recorded daily for a week (UAS7) [Table 2] . The UAS is based on the assessment of key urticaria symptoms (wheals and pruritus). It is suitable for the evaluation of disease activity by patients with urticaria and their treating physicians ,.
|Table 2: The urticaria activity score 7 for assessing disease activity in chronic spontaneous urticaria|
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H. pylori, previously was known as Campylobacter pylori, is a gram-negative, microaerophilic bacterium found in the stomach. H. pylori's helical shape (from which the genus name is derived) is thought to have evolved to penetrate the mucosal lining of the stomach. It may be present in other parts of the body, such as the eye .
H. pylori infection can be diagnosed by the following:
- A stool sample test to look for H. pylori:
Stool antigen assays seem to have a sensitivity and specificity near that of urea breath tests, particularly for initial diagnosis 
- Enzyme-linked immunosorbent assays:
It is the most commonly used serological method for the detection of anti-H. pylori immunoglobulin (Ig) G and IgM antibodies 
- C-urea breath test:
This method may be considered an excellent clinically useful and noninvasive tool for the diagnosis of H. pylori infection in older subjects 
- An upper gastrointestinal endoscopy:
Gastric biopsy is a highly sensitive and specific method for diagnose of H. pylori infection 
- Rapid urease test:
The basis of the test is the ability of H. pylori to secrete the urease enzyme, which catalyzes the conversion of urea to ammonia and bicarbonate. The test is performed at the time of gastroscopy. A biopsy of mucosa is taken from the antrum of the stomach and is placed into a medium containing urea and an indicator such as phenol red. The urease produced by H. pylori hydrolyzes urea to ammonia, which raises the pH of the medium, and changes the color of the specimen from yellow (negative) to red (positive) 
- Gastric juice PCR:
The use of gastric juice PCR is recommended to confirm H. pylori status in patients taking proton pump inhibitors 
Eradication of H. pylori infection has been shown to be effective in some patients with chronic autoimmune urticaria, psoriasis, alopecia areata, and Schoenlein–Henoch purpura .
| Materials and Methods|| |
The guidelines for conducting this review were according to those developed by the center for review and dissemination. It was used to assess the methodology and outcome of the studies.
We reviewed articles on the relation between H. pylori infection and CIU and the influence of H. pylori eradication on the disease activity in patients with CIU infected with H. pylori from Medline databases such as PubMed, Medscape, and ScienceDirect and also materials available in the Internet. We used CU/CIU/H. pylori as searching terms. In addition, we examined references from the specialist databases EMF-Portal (http://www.emf-portal.de), reference lists in relevant publications, and published reports about CIU and H. pylori infection. The search was performed in the electronic databases from 2005 to 2016.
All the studies were independently assessed for inclusion. They were included if they fulfilled the following criteria:
- Published in English language
- Published in peer-reviewed journals
- Focused on the relation between H. pylori infection and CIU
- Discussed the effect of H. pylori eradication on the CIU activity
- If a study had several publications on certain aspects, we used the latest publication giving the most relevant data.
If the studies did not fulfill the aforementioned criteria, they were excluded, such as studies on CIU owing to other causes, surveys about symptoms and health concerns of CIU without accurate disease activity assessment or accurate H. pylori infection detection, report without peer-review, not within national research program, letters/comments/editorials/news, and studies not focused on exposure to H. pylori infection.
The analyzed publications were evaluated according to evidence-based medicine (EBM) criteria using the classification of the US Preventive Services Task Force and UK National Health Service protocol for EBM in addition to the Evidence Pyramid [Figure 1].
US Preventive Services Task Force classification is as follows:
- Level I: evidence obtained from at least one properly designed randomized controlled trial
- Level II-1: evidence obtained from well-designed controlled trials without randomization
- Level II-2: evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research group
- Level II-3: evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled trials might also be regarded as this type of evidence
- Level III: opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
The quality of all the studies was assessed. Important factors included study design, attainment of ethical approval, evidence of a power calculation, specified eligibility criteria, appropriate controls, adequate information, and specified assessment measures. It was expected that confounding factors would be reported and controlled for and appropriate data analysis made in addition to an explanation of missing data.
A structured systematic review was performed with the results tabulated.
| Results|| |
Study selection and characteristics
In total, 28 potentially relevant publications were identified. A total of 22 articles were excluded as they did not meet our inclusion criteria. A total of six studies were included in the review as they were deemed eligible by fulfilling the inclusion criteria. The six articles included in this review were human case–control studies. These studies examined the prevalence of H. pylori infection in patients with CIU. Most studies also examined the effect of H. pylori eradication on the activity of CIU [Table 3]. The studies were analyzed with respect to the study design using the classification of the US Preventive Services Task Force and UK National Health Service protocol for EBM.
|Table 3: Association between chronic idiopathic urticaria and Helicobacter pylori infection in the literature|
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Prevalence of H. pylori infection in patients with chronic idiopathic urticaria
The studies examined the prevalence of H. pylori infection among patients with CIU in comparison with the healthy control.
One of the studies included in the review was done by Magen et al. . He studied 78 patients with CIU patient, and found that 45 (58%) patients were H. pylori infected.
Another study done by Yadav et al.  68 CIU cases; 48 (70.58%) of them were H. pylori positive.
The study done by Kolacińska-Flont et al.  showed no difference between incidence of H. pylori among patients and control.
Moreover, Rostami et al.  carried out a study on 100 patients with CIU and 100 healthy control. They found that 36% of patients with CIU were infected with H. pylori, whereas only 23% of the healthy control were H. pylori infected.
The effect of H. pylori eradication therapy on chronic idiopathic urticaria activity
Of the studies included in this review, four have shown that there is a significant improvement of patients with CIU who were H. pylori infected after H. pylori eradication. For example, Rostami et al.  found that among the 33 patients who were successfully treated for H. pylori infection, 24 (72.7%) patients showed improvement of the CIU activity.
However, two of the studies included in the review showed no significant difference between patient treated with H. pylori eradication therapy and those who did not take the H. pylori eradication treatment. For example, the study done by Kolacińska-Flont et al.  showed that there is no effect of H. pylori eradication on urticaria in anti-H. pylori IgG-positive cases.
| Discussion|| |
CU still constitutes a problem in the daily work of dermatologists, as finding a cause is considered a challenge to both physicians and patients. The role of H. pylori in CIU is still a controversial subject, and the disappearance of CU after careful eradication of the pathogen is a matter of debate .
The aim of our study was to assess the effect of H. pylori eradication on patients with CIU infected with H. pylori.
An association between HP and CIU has been proposed. One of the suggested pathogenic mechanisms is an increase in gastric vascular permeability during infection resulting in increased exposure of the host to alimentary allergens. The other one is immunological stimulation by chronic infection, through mediator release leading to a nonspecific increase in sensitivity of the cutaneous vasculature to vasopermeability-enhancing agents .
In agreement with our study, Gonzalez Morales et al.  carried out a study on 20 patients with CIU with a positive urea breath test result for H. pylori infection. They were given H. pylori eradication therapy for 2 weeks. The urticaria disappeared in 11 (55%) patients, among which, urea breath test result became negative in nine (45%) patients and in two of them H. pylori persisted. However, urticaria persisted in nine (45%) patients; six of them showed negative urea breath test result and three showed positive urea breath test result .
Another study done by Magen et al.  enrolled 78 patients with CIU.13 C-urea breath test result was positive in 45 (58%) of them, of which 21 patient also had autologous serum skin test positive result (group A) and 24 patients autologous serum skin test negative result (group B). A total of 33 patients with CU served as control group. All patients with positive 13 C-urea breath test result received H. pylori eradication therapy. The effect of H. pylori eradication on CU was evaluated by UAS, measured at study entry and at 8 and 16 weeks later. At week 8, baseline UAS reduced from 4.7 ± 1.1 to 2.4 ± 1.4 (P = 0.027) in group A and from 4.3 ± 1.5 to 2.3 ± 1.2 (P = 0.008) in group B, without statistically significant difference between the two groups. In control group and in six patients with H. pylori eradication failure, no changes of UAS were noted .
Moreover, Yadav et al.  carried out a study on 68 patients of CIU. All patients underwent endoscopy with antral biopsy to identify HP infection. HP was present in 48 (70.58%) patients, and they were given H. pylori eradication treatment; 39 (81.25%) patients showed complete remission of CIU. However, 10 (50%) patients of those without HP infection showed improvement of CIU in response to symptomatic therapy, so they found a significant result between two groups .
Another study done by Rostami et al.  studied 100 patients with CIU and 100 healthy controls. They found that 36% of patients with CIU were infected with H. pylori. Response to eradication therapy was evident in 33 (91.67%) patients in whom H. pylori was eradicated whereas three (8.33%) patients showed no response. Clinical follow-up of 33 successfully treated patients 3 months later revealed complete remission of urticaria in 54.5% of patients with CIU, partial remission in 18.2% of patients, and no improvement in 27.3% of patients .
On the contrary, Hellmig et al.  studied 74 cases of CIU infected with H. pylori and 74 CIU cases without H. pylori infection as negative control. They followed up cases for 58 months. They concluded that there is no evidence that eradication of H. pylori improves the outcome in patients with CIU. They explained that they found at least one additional infectious focus in 81.1% of the cases, which obscures the evaluation of any specific antimicrobial therapy .
Another study against the results of our study was done by Kolacińska-Flont et al. , in 2012 who had compared the anti-H. pylori IgG titer in 62 patients with CIU and 55 control subjects and evaluated the effect of H. pylori eradication on urticaria. They concluded that the anti-H. pylori IgG titer was similar in patients with CIU and controls, so H. pylori eradication had no effect on urticaria in anti-H. pylori IgG-positive cases with gastric complaints. However, the diagnostic value of anti-H. pylori IgM antibodies is highly specific than anti-H. pylori IgG antibodies .
| Conclusion|| |
Our study concluded that H. pylori may play a role in the pathogenesis of CIU. Therefore, anti-H. pylori eradication therapy should be tried for positive cases with CIU especially for those who do not respond to habitual treatment of CU.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Mogaddam MR, Yazdanbod A, Ardabili NS, Maleki N, Isazadeh S. Relationship between Helicobacter pylori and idiopathic chronic urticaria: effectiveness of Helicobacter pylori eradication. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii. 2015; 32
Buss YA, Garrelfs UC, Sticherling M. Chronic urticaria-which clinical parameters are pathogenetically relevant? A retrospective investigation of 339 patients. J Dtsch Dermatol Ges 2007; 5
Confino-Cohen R, Chodick G, Shalev V, Leshno M, Kimhi O, Goldberg A. Chronic urticaria and autoimmunity: associations found in a large population study. Journal of allergy and clinical immunology 2012; 129
Vonakis BM, Saini SS. New concepts in chronic urticaria. Curr Opin Immunol 2008; 20
Maurer M, Rosén K, Hsieh HJ, Saini S, Grattan C, Gimenéz-Arnau A, et al.
Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. New England Journal of Medicine. 2013; 368
Zuberbier T, Aberer W, Asero R, Bindslev-Jensen C, Brzoza Z, Canonica GW, et al.
The EAACI/GA 2 LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy 2014; 69
Yadav MK, Rishi JP, Nijawan S. Chronic urticaria and Helicobacter pylori
. Indian J Med Sci 2008; 62
Młynek A, Zalewska-Janowska A, Martus P, Staubach P, Zuberbier T, Maurer M. How to assess disease activity in patients with chronic urticaria?. Allergy 2008; 63
Metz M, Bergmann P, Zuberbier T, Maurer M. Successful treatment of cholinergic urticaria with anti-immunoglobulin E therapy. Allergy 2008; 63
Magerl M, Borzova E, Giménez-Arnau A, Grattan CE, Lawlor F, Mathelier-Fusade P, et al.
The definition and diagnostic testing of physical and cholinergic urticarias–EAACI/GA2LEN/EDF/UNEV consensus panel recommendations. Allergy 2009; 64
Cotticelli L, Borrelli M, D'alessio AC, Menzione M, Villani A, Piccolo G, et al.
Central serous chorioretinopathy and Helicobacter pylori. European journal of ophthalmology 2006; 16
Yakoob J, Rasool S, Abbas Z. Gastric juice for the diagnosis of Helicobacter pylori
infection in patient on proton pump inhibitors. World J Gastroenterol 2008; 114
Veijola L, Myllyluoma E, Korpela R, Rautelin H. Stool antigen tests in the diagnosis of Helicobacter pylori infection before and after eradication therapy. World journal of gastroenterology 2005; 11
Wilkins T, Khan N, Nabh A, Schade RR. Diagnosis and management of upper gastrointestinal bleeding. Am Fam Physician 2012; 85
Blaser MJ. An endangered species in the stomach. Sci Am 2005; 292
Gonzalez Morales JE, Leal Vilareal L, Castillo Satazr Nde J, Gonzalez Martinez E. Correlation between chronic idiopathic urticaria and infection due to H. pylori
. Rev Alerg Mex 2005; 52
Magen E, Mishal J, Schlesinger M. Eradication of Helicobacter pylori
infection equally improves chronic urticaria with positive and negative autologous serum skin test. Helicobacter 2007; 12
Hellmig S, Troch K, Ott SJ, Schwarz T, Fölsch UR. Role of Helicobacter pylori infection in the treatment and outcome of chronic urticaria. Helicobacter 2008; 13
Kolacińska-Flont M, Antczak-Marczak M, Pawłowski M, et al.
IgG titre in patients with chronic idiopathic urticaria and the effect of Helicobacter pylori
eradication on urticarial. Postep Derm Alergol 2012; 29
Bartels LE, Jepsen P, Christensen LA, Gerdes LU, Vilstrup H, Dahlerup JF. Diagnosis of Helicobacter pylori infection is associated with lower prevalence and subsequent incidence of Crohn's disease. Journal of Crohn's and Colitis. 2015; 10
[Table 1], [Table 2], [Table 3]