Nghiên cứu tỷ lệ nhiễm helicobacter pylori ở bệnh nhân mày đay mạn và hiệu quả điều trị bằng phác đồ ba thuốc diệt vi khuẩn tt tiếng anh

MINISTRY OF EDUCATION AND TRAINING

MINISTRY OF DEFENCE

108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES

-------------------------------------------------

NGUYEN THI LIEN

RESEARCH ON THE PREVALENCE OF HELICOBACTER PYLORI
INFECTION IN PATENTS WITH CHRONIC URTICARIA AND THE
EFFECTIVENESS WITH BACTERIA ERADICATION
BY TRIPLE THERAPY

Speciality: Dermatology
Code: 62720152

ABSTRACT OF MEDICAL PHD THESIS

Hanoi – 2019


THE THESIS WAS DONE AT 108 INSTITUTE OF CLINICAL
MEDICAL AND PHARMACEUTICAL SCIENCES

Supervisors:
1. Ass. Prof. Pham Van Linh MD, PhD
2. Ass. Prof. Nguyen Tien Thinh MD, PhD

Reviewers:

1. Ass. Prof. Pham Thi Lan MD, PhD
2. Ass. Prof. Tran Ngoc Tu MD, PhD
3. Ass. Prof. Nguyen Ngoc Thuy MD, PhD

This thesis will be presented at Institute Council at: 108 Institute of
Clinical Medical and Pharmaceutical Sciences
Day
Month Year

The thesis can be found at:
1. National Library of Vietnam
2. Library of 108 Institute of Clinical Medical and
Pharmaceutical Sciences


LIST OF PUBLISHED ARTICLES RELATING TO THESIS

1. Nguyen Thi Lien, Pham Van Linh, Nguyen Tien Thinh
(2018), "Study of clinical characteristics in patients with
chronic urticaria infected Helicobacter pylori". Journal of
Clinical Medicine and Pharmacy 108, special issue, (13)
2018, 283-289

2. Nguyen Thi Lien, Pham Van Linh, Nguyen Tien Thinh
(2018), "Results of treatment of chronic urticaria infected
Helicobacter pylori with bactericidal treatment". Journal of
Clinical Medicine and Pharmacy 108, special issue, (13)
2018, 296- 301

3. Nguyen Thi Lien, Pham Van Linh, Nguyen Tien Thinh

(2018), "Recurrence study in patients with chronic urticaria
infected Helicobacter pylori

after bacteria eradication

treatment". Journal of Clinical Medicine and Pharmacy 108,
special issue, (13) 2018, 269- 276


1

INTRODUCTION
Chronic urticaria (CU) is a common skin disease
characterized by widespread, transient wheals occurring daily or
almost daily for at least 6 weeks. CU may result from several causes;
hidden or overt bacterial, viral, fungal, and protozoan agents have
been reported as possible initiating factors.
Helicobacter pylori (H. pylori) is defnitely suspected in the
etiopathogenesis of gastrointestinal disorders. Recent epidemiological
and experimental data have pointed to a strong relation of H. pylori
infection with the development of many extragastric diseases, such as
cardiovascular, immunologic, and some skin diseases. Many studies
have found an etiopathogenetic link between H. pylori infection and
CU and possible skin improvement after its eradication.
Vietnam localized in the region with high rates of H. pylori
infection. Based on the understanding of CU and H. pylori, we conducted
this thesis “Research on the prevalence of Helicobacter pylori infection
in patients with chronic urticaria and the effectiveness with bacteria
eradication by triple therapy” to further investigate the possible
association. The existence of a correlation between H. pylori and CU may

help the clinician to find more effective methods to treat people with CU.
The thesis has been conducted with two following purposes:
1. Determine the prevalence of Helicobacter pylori infection in
patients with chronic urticaria and clinical relevance of the disease.
2. Evaluate the effectiveness of chronic

urticaria treatment in

patients who infected H. pylori by antihistaminic H1 combined with
bacteria eradication by triple therapy.


2

Chapter 1
OVERVIEW
Urticaria is one of the most common skin diseases, and
patients may present with a wide spectrum of symptoms, including
sudden development of pruritic wheals or angiowheals. Chronic
urticaria (CU) is diagnosed when disease has been continuously or
intermittently present for at least 6 weeks. The chronic and acute
forms of urticarial differ in etiology, pathophysiology, and
underlying mechanism. Chronic urticaria has a significant impact on
quality-of-life due to the constant sensation of itching, regular
recurrence, and unknown etiology. An estimated 15% to 23% of
adults have experienced at least 1 episode of acute urticaria at some
time in their lives, and the prevalence of chronic urticaria in adults is
estimated at 0.5% to 5%. Previous studies have reported that chronic
idiopathic urticaria is associated with infection, pseudo-allergy to a
food, autoimmunity, and low serum level of vitamin D.

As of yet, the only reliable way to assess current disease
activity is the prospective determination of symptoms over several
consecutive days with the Urticaria Activity Score (UAS). The UAS
works as a daily diary quantifying wheals and itching. To assess the
quality of life of patients with CU, expert groups recommend using
the only existing specifc questionnaire, the CU-Q2oL.
Currently, in the process of finding out the cause of disease,
international guidelines for the treatment of chronic urticarial still
choose to treat symptoms with histamine H1 receptor antagonists, the
second generation is the treatment firstly. Effective treatment of
chronic urticaria is evaluated by the Urticaria Control Test (UCT).
Helicobacter pylori (H. pylori) is a frequent gastrointestinal
infectious agent having worldwide distribution. It is a Gram-


3

negative, microaerophilic, spiral bacterium that shows particular
tropism for the gastric mucosa, and induces a strong inflammatory
response with release of various bacterial and host dependent
cytotoxic substances. Part from its well-demonstrated role in
gastroduodenal diseases, some authors have suggested a potential
role of H. pylori infection in several extra-intestinal pathologies
including haematological, cardiovascular, autoimmune, and skin
diseases. In recent studies a possible association between H. pylori
infection and CU has been suggested. In fact, in some studies CU
patients showed regression of cutaneous signs and symptoms after H.
pylori eradication treatment.
Many studies on the role of H. pylori in chronic urticaria
have been conducted and proposed some theories to explain the

relationship between H. pylori infection and chronic urticaria:
Firstly, some protein components of H. pylori may play a
role in mast cell activation causing chronic urticaria.
Secondly, bacteria act as full and self-allergenic antigens,
causing an immune response. IgG and IgA antibodies associated with
19-kDa of H. pylori lipoproteins have been found to play a role in CU.
Thirdly, some inflammatory mediators have been released
during the immune response to H. pylori infection, which may play
an important role in the pathogenesis of urticaria, at least to create
out of nonspecific hypersensitivity of skin vessels with substances
that enhance vasodilation.
Finally, the process of bacterial infection reduces the barrier
function of the gastrointestinal mucosa, facilitating allergy food
particles into the blood. H. pylori may also increase the amount of
eosinophil cationic protein with a toxin secreted by eosinophilic
activation that contributes to chronic urticaria.


4

Chapter 2
SUBJECTS AND METHODS
2.1. SUBJECTS AND MATERIALS
2.1.1. SUBJECTS
* Purpose 1: 245 patients were treated chronic urticaria (CU)
in Haiphong Medical University hospital from 8/2016 to 02/2018.
- Diagnostic criteria for CU: The sudden appearance of wheals
and/or angiowheals. A wheal consists associated itching, a fleeting
nature, with the skin returning to its normal appearance, usually within
1–24 hours. The symtoms are continuous or recurrent at least 6 weeks.

- Diagnostic criterias for H. pylori infection:
+ The concentration of H.pylori antigen ≥ 0.05 ug/ml are
considered positive (CU/ H. pylori+)
+ The concentration of H.pylori antigen < 0.05 ug/ml are
considered negative (CU/ H. pylori-)
- Selection criteria for study patients: patients diagnosed with
chronic urticarial, agreed to participate in the study, agreed to be
tested for H.pylori infection
- Exclusive criterial: The patient used medications for gastrođuoenal and H.pylori eradication within 1 month before admission.
Patients with mental disorders, alcoholism, drug addiction HIV,
cancer, liver failure, kidney failure, heart failure. Women tho pregnant
or nursing. Patients who did not agree to participate in the research
* Purpose 2: 76 patients CU/H. pylori+ eradicated.
- Selection criteria for study patients: patients with chronic
urticarial infected H.pylori who bactericidal treatment. The patient


5

had not malignancy symptoms of gastrointestinal; no contraindication
to use of drug. Age ≥ 18. Patients agree to participate and follow the
treatment process properly
- Exclusive criterial: Patients do not qualify for selection.
Patients do not agree to participate in the study
2.1.2. MATERIALS
- Chemicals: HpAg kit of Dia.Pro Diagnostic, Italy
- Study devices: ELISA system, USA
- Drugs: Xyzal 5mg (Switzerland) Nexium MUPs 40mg (Sweden)
Ospamox 500mg (Sandoz-Imexpharm). Klacid 500mg (Abbott)
2.2. METHODS

2.2.1. Study Design: prospective, interventional, follow-up
2.2.2. Sample size of Study
- Purpose 1: Convenient sampling. From 8/2016 to 02/2018, 245
patients with chronic urticaria treated at Hai Phong Medical
University Hospital, responding selection and exclusion criteria.
- Purpose 2. Of 245 chronic urticarial patients, 76 patients were
CU/H. pylori+ eradicated.
2.3. Techniques and assessment standards
2.3.1. ELISA technique identified H. pylori antigen in stool (Stool
antigen assay - SAT).
* Prepare specimen
1. Thaw the specimen at room temperature (4 hours)
2. Prepare 2 sets of tubes each with the ID samples.
3. add 1 ml of diluent to each tube. Take about 0.2 g of each
sample into each tubes (weigh the tube before and after)
4. Votex for 1 minute, then centrifuge for 3000 cycles/3
minutes), transfer the solution to the second tube, centrifuge for 3000
cyclce/3 minutes then take 100µl suspension for testing.


6

* Assay procedure
1. Place the required number of strips in the plastic holder and
carefully identify the wells for calibrators and samples.
Leave A1+B1 wells empty for blanking purposes.
2. Pipette 100 µl Calibrators in duplicate into the calibration
wells (see the example of dispensation reported below).
3. Dispense then 100 µl Enzymatic Conjugate in all wells,
except for A1+B1, used for blanking operations

4. Following addition of the conjugate, incubate the microplate for
120 min at +37°C .
5. When the first incubation is over, wash the microwells as
previously described
6. Pipette 200 µl Chromogen/Substrate into all the wells,
A1+B1 included. Incubate the microplate protected from
light at room temperature (18-24°C) for 20 min.
7. Pipette 100 µl Sulphuric Acid into all the wells to stop the
enzymatic reaction
* Calculation of results
Calculate the mean OD450nm value of the calibrators. Then
draw a calibration curve possibly using a 4 parameters fitting
curve system. Then calculate on the curve the concentration of
H.pylori antigen in the sample. Samples showing a concentration of
H.pylori antigen ≥ 0.05 ug/ml are considered positive
2.3.2. Evaluation criteria
- Assess the level of disease activity with UAS (urticaria
activity score) score. For evaluation of symptoms of pruritus and
irritation, calculate the activity score of urticaria. The lowest total
score is 0, the highest is 6 points.


7

- Evaluate the effect of disease on the quality of patients' life
with Chronic Urticaria Quality of Life Questionnaire/CU-Q2oL. The
question set has 23 sentences with the rule of assessing the lowest
point of 1 (not at all), the highest score is 5 (a lot). The minimum CUQ2oL score is at least 23 and the maximum is 115. The higher the
average score corresponds to the lower the quality of life.
- Assess the level of disease control: with the Urticaria

Control Test - UCT. The UCT score of 12 or greater indicates
controlled disease. Values of 11 and lower reflect poor control.
- Evaluate H. pylori infection: The concentration of H.pylori
antigen ≥ 0.05 ug/ml are considered positive (CU/ H. pylori+). The
concentration of H.pylori antigen < 0.05 ug/ml are considered negative
(CU/ H. pylori-).
- Assessment response to H.pylori eradication treatment:
In group CU/ H.pylori+ qualifies for bactericidal treatment,
at 4 weeks after cessation of bacteriostatic treatment, re-test for H.
pylori antigen in the stool. Samples showing a concentration of
H.pylori antigen < 0.05 ug/ml are negatives: Diagnostic
CU/H.pylori+ eradicated. Samples showing a concentration of H.pylori
antigen ≥ 0.05 ug/ml are positives: Diagnostic CU/H.pylori+ noteradicated.
- Side effects: Record whether or not side effects and assess
the level.
2.4. Study procedure
2.4.1. Screening, selecting patients: Explain the objectives
and procedure to conduct research with the patients if the patient
agrees to sign the study agreement.


8

2.4.2. Collecting clinical informations: Interview, examine,
clinical screening, we focus on obtaining thoroughly medical history:
history of allergies, urticaria, medical history of patients. The duration of
disease progression, factors tringer, Clinical characteristics…
2.4.3. Blood tests: Blood formulation, urea, creatinine, GOT,
GPT
2.4.4. Stool antigen test to determine H. pylori infection.

Instruct patients to take stool samples, transfer to the
Laboratory of Hai Phong Medical University Hospital. At the
Department, stool samples were stored in a negative cabinet of 40oC.
The specimens were collected and analyzed for analysis once a week.
2.4.5. Treatment
* Drug regimens are as follows:
Group 1: CU/ H.pylori- : Xyzal 5mg take 1 table/day x 4 weeks
Group 2: CU/H.pylori+ meeting inclusion criteria
Xyzal 5mg take 1 table/day x 4 weeks
H. pylori eradication treatment: use triple regimens during 10 days
Nexium 40mg x 2 tablets / day x 10 days. (2 times a day, 1
capsule each time, 30 minutes before breakfast and before dinner)
Ospamox 500mg x 4 tablets / day x 10 days. (2 times daily, 2
capsules, 1 hour after breakfast and 1 hour after dinner)
Klacid 500mg x 2 tablets / day x 10 days. (2 times a day, 1
capsule at a time, 1 hour after breakfast and 1 hour after dinner)
* Instruct patients to take medicine, monitoring side effects.
* Assessment response to H.pylori eradication treatment
2.4.6. Re-examination and evaluation
* Evaluate the effectiveness of treatment of chronic urticaria
After 2 weeks and 4 weeks of treatment, on each group, we


9

assesse the following criteria: Pruritus score, wheals score, UAS
score; Evaluate the effect of disease on the quality of patients' life ;
Side effects of drugs.
* Assess the level of control of chronic urticaria after treatment
- After cesscation treatment, in each group , at 2 weeks, 1

month, 2 months, 3 months we will assessing: The score UCT;
Evaluate whether the patient must re-use anti-allergy medication.
- At the time

after 2 weeks

treatment cesscation, the

patients poor control the disease, they must re-use antihistamines H1
will be used for histamine H1 resistance according to second-line
regimen (increase the dose twice).
Those patients controlled disease, who do not need to take
antihistamines H1 again, will continue to be monitored and reevaluated at the time after 1 month treatment cesscation
- The evaluation and monitoring are conducted similarly as
above at the time after stopping treatment for 1 month, 2 months, 3
months.
2.5. DATA PROCESSMENT
The data is processed by medical statictic method with Stata 14.0


10

Study design

245 Chonic Uticaria (CU)

159 CU/ H. pylori +

Hp-Ag/Stool

107 CU/ H. pylori +, Treatment
- XYZAL x 4 weeks
- H. pylori eradication treatment: use triple regimens x 10 days
After 4 weeks of H.pylori
eradication treatment

Hp-Ag/Stool

76 CU/H. pylori+ eradicated

31 CU/H. pylori+ not-eradicated

After 2 weeks, 4 weeks of treatment: Assesses
 Pruritus score, wheals score, UAS score
 Score CU-Q2oL
After cessation 2 weeks, 1 month, 2 month, 3 month: Assesses
 UCT score
 Rate of re-using antihistamin H1

86 CU/ H. pylori -

86 CU/ H. pylori Treatment
- XYZAL x 4 weeks


11

Chapter 3
RESULTS

3.1. Determine the rate of Helicobacter pylori infection in
patients with chronic urticaria and clinical relevance of the disease
From 8/2016 to 02/2018, there were 245 patients with
chronic urticaria meeting inclusion criteria. Testing for bacterial
antigens in the feces found the prevalence of H. pylori infection as
follows.
Table 3. 1: The rate of H. pylori infection in chronic urticaria
Patients

N

%

H. pylori infection

159

64,9

H. pylori Not-infection

86

35,1

Total

245

100

Conclusion: The rate chronic urticaria infected H. pylori (CU/H. pylori+ ) is
64,9%
Table 3. 2: Relationship between H. pylori infection and the
duration of symptoms
CU/H. pylori+
Patients
(n=159)
Time
n
%
< 1 hour
20
12,6

CU/H. pylori(n= 86)
n
%

Total
n

%

2

2,3

22

9,0

P
< 0,01

1 hour-6 hours

38

23,9

39

45,4

77

31,4 < 0,01

> 6 hours

101

63,5

45

52,3

146

59,6 < 0,01

Conclusion: 59,6% of patients had a duration time of wheals
and pruritus lasting> 6 hours. Rate of CU/H.pylori+ has a long


12

duration of wheals and pruritus > 6 hours greater than the CU/H.
pylori- group (p <0.01).
Table 3. 3: The relationship between H. pylori infection and
the level of pruritus
Patients

CU/H. pylori+

CU/H. pylori-

(n=159)

(n= 86)

Total

p

Pruritus

n

%

n

%

n

%

Moderate

29

18,2

54

62,8

83

33,9

<0,01

Intense

130

81,8

32

37,2

162

66,1

<0,01

Conclusion:
100% of patients have moderate and intense itching. Rate
of CU / H. pylori + had severity of pruritus (81,8%) significantly
higher than the CU / H. pylori- group (p <0.01)
Table 3. 4: The relationship between H. pylori infection and
the level of wheals
Patients

CU/H. pylori+

CU/H. pylori-

(n=159)

(n= 86)

Wheals

Total

p

n

%

n

%

n

Moderate

71

44,7

81

94,2

152

62,0 <0,01

Intense

88

55,3

5

5,8

93

38,0 <0,01

%

Conclusion:
100%

patients have wheals on moderate and intense

level. The rate CU/H.pylori+ have wheals on intense level (55,3%)
significantly higher than the CU/H. pylori- group (p <0.01)


13

3.2. Treatment effect chronic urticaria with combination H. pylori
eradicated treatment by triple regimen
Table 3. 5: Pruritus score after treatment
Patients

Time

CU/ H. pylori+

CU/ H. pylori+

eradicated.

Not-eradicated

Group 1,

Group 2,

(n = 76)

(n = 31)

2,9 ± 0,2

2,9 ± 0,2

2,4 ± 0,5

1,6 ± 0,5

1,4 ± 0,5

1,4 ± 0,5

0,7 ± 0,5

1,2 ± 0,4

1,0 ± 0,2

CU/ H. pylori Group 3,

p

(n = 86)

Before
treatment

p13<0,05

(1)
After 2
weeks (2)
After 4
weeks (3)

p12>0,05
p13>0,05
p12<0,05
p13<0,05

p (1) (2) <
p (1) (2) < 0,05

p (1) (2) > 0,05

0,05

p (1) (3) < 0,05

p (1) (3) < 0,05

p (1) (3) <
0,05

Conclusion:
Before treatment, pruritus score of CU/H. pylori+ eradicated
significantly higher than the CU/H.pylori- group (p13<0,01).
After 4 weeks of treatment, the mean pruritus score of all 3
groups decreased compared to before treatment. CU/H.pylori+
eradicated group, the highest reduction, remains 1.0 ± 0.2. This point is
significantly lower than before treatment (p(1)(3) < 0,05) and the lowest
among 3 groups, the difference was significant with p12 <0.05; p13
<0.05


14

Table 3. 6: Wheals score after treatment
Patients

CU/ H. pylori+

CU/ H. pylori+

CU/ H. pylori -

Not-eradicated

Group 3,

Group 2, (n = 31)

(n = 86)

2,6 ± 0,5

2,6 ± 0,5

2,1 ± 0,2

1,8 ± 0,4

1,9 ± 0,3

1,9 ± 0,3

1,2 ± 0,5

1,5 ± 0,5

1,7 ± 0,5

p (1) (2) > 0,05

p (1) (2) < 0,05

p (1) (2) < 0,05

p (1) (3) < 0,05

p (1) (3) < 0,05

p (1) (3) < 0,05

eradicated.
Group 1,
Time

(n = 76)

p

Before
treatment

p13<0,05

(1)
After 2
weeks (2)
After 4
weeks (3)

p12>0,05
p13>0,05
p12<0,05
p13<0,05

Conclusion:
Before treatment, wheals score of CU/ H. pylori+ eradicated is
2,6 ± 0,5, significantly higher than the CU/H.pylori- group (p13<0,05)
After 4 weeks of treatment, the mean wheals score of all 3
groups decreased compared to before treatment. CU/H.pylori+
eradicated group, the highest reduction, remains 1.2 ± 0.5. This point
is significantly lower than before treatment (p(1)(3) < 0,05) and the
lowest among 3 groups, the difference was significant with p12
<0.05; p13 <0.05


15

Table 3. 7: UAS score after treatment
Patients

Time

CU/ H. pylori+

CU/ H. pylori+

CU/ H. pylori -

eradicated.

Not-eradicated

Group 3,

Group 1, (n = 76)

Group 2, (n = 31)

(n = 86)

5,5 ± 0,6

5,5 ± 0,6

4,4 ± 0,6

3,3 ± 0,8

3,2 ± 0,7

3,3 ± 0,7

1,9 ± 0,7

2,7 ± 0,8

2,7 ± 0,6

p (1) (2) > 0,05

p (1) (2) < 0,05

p (1) (2) < 0,05

p (1) (3) < 0,05

p (1) (3) < 0,05

p (1) (3) < 0,05

p

Before
treatment

p13<0,01

(1)
After 2
weeks (2)
After 4
weeks (3)

p12>0,05
p13>0,05
p12<0,05
p13<0,05

6
5.5
5
4

CU/H.pylori+
eradicated

4.4
3.3

2.7
3

CU/H.pylori+ Noteradicated

3.3
2

1.9
CU/ H. pylori-

1
0
BEFORE
TREATMENT

AFTER 2 WEEKS

AFTER 4 WEEKS

Figure 3. 1: UAS score after treatment


16

Conclusion table 3.23, figure 3.1:
- Before treatment, wheals score of CU/ H. pylori+ eradicated is
5,5 ± 0,6, significantly higher than the CU/H.pylori- group (p13<0,05)
- After 4 weeks of treatment, the mean UAS score of all 3
groups decreased compared to before treatment. CU/H.pylori+
eradicated group, the highest reduction, remains 1,9 ± 0,7. This point
is significantly lower than before treatment (p(1)(3) < 0,05) and the
lowest among 3 groups, the difference was significant with p12
<0.05; p13 <0.05

Table 3. 8: The influence on the quality of life before and
after treatment
Patients

Time

CU/ H. pylori+
eradicated.
Group 1, (n = 76)

CU/ H. pylori+
Not-eradicated
Group 2, (n = 31)

CU/ H. pylori Group 3,
(n = 86)

p

67,8 ± 9,5

66,6 ± 11,2

61,0 ± 10,8

p12>0,05
p13<0,05

42,4 ± 5,4

43,5 ± 6,0

44,8 ± 6,0

p12>0,05
p13>0,05

33,2 ± 5,9

35,2 ± 5,5

40,5 ± 6,5

p12>0,05

p13<0,05

p (1) (2) > 0,05
p (1) (3) < 0,05

p (1) (2) > 0,05
p (1) (3) < 0,05

p (1) (2) > 0,05
p (1) (3) < 0,05

Before
treatment
(1)
After 2
weeks (2)
After 4
weeks (3)


17

67.8

70
65
60
55
50
45

40
35
30

61
44.8
40.5

42.4

33.2
BEFORE
TREATMENT

AFTER 2 WEEKS

CU/H.pylori-

AFTER 4 WEEKS

CU/H.pylori+ eradicated

CU/H.pylori+ Not-eradicated

Figure 3. 2: The influence chronic urticaria on the quality
of life before and after treatment
Conclusion table 3.30, figure 3.2:
- Before treatment, the CU/ H. pylori + eradicated group has a
score that affects the overall aspects of QoL is 67.8 ± 9.5 higher than that
of the CU / H. pylori- group (p13<0,05).

- After 4 weeks, score of QoL decrease (quality of life
increased) in all 3 group. Score the group CU/ H. pylori + eradicated
reduced score to 33.2 ± 5.9, significantly lower than before treatment
and lower than the other 2 groups (p12 <0.05; p13 <0.05)
Table 3. 9: Side effects
CU/H. pylori –
Patients CU/H. pylori+
(n=107)
(n=86)
p
Symtopm
n
%
n
%
Drowsiness
0
0
1
1,2
> 0,05
Tiredness

1

0,9

0

0

> 0,05

Dry mouth

2

1,9

0

0

> 0,05

Conclusion: After 4 weeks of treatment, the proportion
of patients with side effects was very low and there was no
difference between the two groups.


18

3.2.2. Control chronic urticaria
Table 3. 107: Summary of disease control level after 3 months of
cessation treatment
CU/ H. pylori+
CU/ H. pylori+
CU/ H. pylori Patients
Not-eradicated
Group 3,

eradicated.
p
(n = 86)
Group 1, (n = 76) Group 2, (n = 31)
urticaria
control
n
%
n
%
n
%
Controlled
28
36,8
2
6,5
3
3,5
p12<0,01
poor
p13<0,01
48
63,2
29
93,5
83
96,5
control
100.0%

96.1%
78.9%

80.0%
61.3%
60.0%
40.0%

55.3%
41.9%

36.8%

29.0%
16.2%

20.0%

6.5%

12.8%

0.0%

5.8%

3.5%

After 2 weeks After 1 month After 2 month After 3 month

cessation Xyzal cessation Xyzal cessation Xyzal cessation Xyzal
CU/H.pylori -

CU/H.pylori+ eradicated

CU/H.pylori+ Not-eradicated

Figure 3. 3: Well-controlled disease after treatment cessation
Conclusion table3.37, figure 3.3:
After 2 weeks of xyzal cessation, the rate patients well-controlled
disease of the CU/H.pylori+ eradicated group is highest (96.1%) (p12
<0.01; p13 <0.01).
After 3 months treatment cessation, the rate patients wellcontrolled disease of the CU/H. pylori+ eradicated group is (36,8%),
significantly higher than the CU/H. pylori+ Not-eradicated group (6,5%)
and CU/H.pylori- group (3,5%) (p12<0,01; p13<0,01)


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Chapter 4
DISCUSSION
4.1. Determine the rate of Helicobacter pylori infection in
patients with chronic urticaria and clinical relevance of the disease.
In this study, we tested H. pylori antigen in stool, determined
64.9% of chronic urticaria patients were infected with H. pylori (CU/
H. pylori+). In the world, H. pylori infection was found with high
rate in patients with chronic urticaria. In 2015, Huiyuan Gu analyzed
16 studies found that the rate of H. pylori infection in chronic
urticaria is 49,74% higher in the control group. The difference
indicates that H. pylori infection may be a risk factor for developing

chronic urticaria, increasing the risk of chronic urticarial.
Regarding the duration time of symptom, 59.6% of patients
had the duration time lasting> 6 hours, in which, the rate of CU/H .
pylori+ group was significantly higher than the CU/H. pylori - group
(table 3.14). Regarding symptoms (table 3.18, table 3.19), 100% of
patients had moderate and intense itching and wheals. The incidence
of severe itchy in CU/H.pylori+ group (81.8%) was statistically
significantly higher than the CU/H.pylori- group (37.2%). Percentage
of patients with severe wheals in CU/H. pylori+ group (55.3%) was
significantly higher than the CU/H. pylori- group
4.2. Treatment effect of chronic urticaria with
combination bacterial eradication treatment by triple regimen
4.2.1. Treatment effect
Progression of itching and wheals
Before treatment, pruritus score and wheals scores of CU/H.
pylori+ eradicated group significantly higher than the CU/H.pylorigroup (p13<0,01). After 4 weeks of treatment, the mean pruritus
score of CU/H.pylori+ eradicated group was 1.0 ± 0.2 highest
reduction. This point is significantly lower than before treatment and


20

the lowest among 3 groups, the difference was significantly. After 4
weeks of treatment, the mean wheals score of all 3 groups were
decreased compared to before treatment. CU/H.pylori+ eradicated
group, the highest reduction, remains 1.2 ± 0.5. This point is
significantly lower than before treatment (p(1)(3) < 0,05) and the lowest
among 3 groups, the difference was significant with p12 <0.05; p13
<0.05. Before treatment, UAS score of CU/ H. pylori+ eradicated was
5,5 ± 0,6, significantly higher than the CU/H.pylori- group (p13<0,05).

After 4 weeks of treatment, the mean UAS score of all 3 groups
decreased compared to before treatment. CU/H.pylori+ eradicated
group, the highest reduction, remains 1,9 ± 0,7. This point is
significantly lower than before treatment (p(1)(3) < 0,05) and the lowest
among 3 groups, the difference was significant with p12 <0.05; p13
<0.05. Fukuda’s study found that among patients with H. pylori positive,
microbial eradicated, 35% of patients had complete remission and 65%
had partial remission of urticaria symptoms. In the group of patients
without treatment for H. pylori, 22% of patients were partially
reduced and 78% of patients did not improve. Federman DG,
analyzing 10 studies the removal of H. pylori was found to be
significantly associated with reduced symptoms.
The influence of chronic urticaria on the quality of life
Before treatment, the CU/ H. pylori + eradicated group
has CU-QoL score was 67.8 ± 9.5, higher than that of the CU/H.
pylori- group (p13<0,05). Score of the CU/H.pylori+ eradicated
group was reduced to 33.2 ± 5.9, significantly lower than before
treatment and lower than the other 2 groups. (Table 3.30).
Persechino S. reported in patients with CU/H.pylori+
after bacteriostatic treatment, 50.66% showed a complete reduction
of urticaria symptoms, 22.66% showed a partial decrease symptoms.
In the study of Tareen Attiya (2015), 75% of patients treated for


21

bactericidal treatment, an improvement in urticaria symptoms were
improved, and the quality of life in patients treated with bactericidal
treatment improved significantly compared to untreated patients.
Side effects in treatment, table 3.32, we found nausea and

bitterness are common side effects. Most of these side effects are
mild, transient, self-limiting that do not significantly affect treatment.
4.2.2. Disease control
After 3 months treatment cessation, the rate patients wellcontrolled disease of the CU/H. pylori+ eradicated group was (36,8%),
significantly higher than the CU/H. pylori + Not-eradicated group (6,5%)
and CU/H.pylori- group (3,5%). Yi-Chun Chiu, monitoring the
CU/H.pylori+ eradicated group, after 3 months, 58.3% of patients
were completely reduced symptoms of urticaria. In 2018, Robert
Pawłowicz reported a double-blind, placebo-controlled trial
assessing the effectiveness of H.pylori eradication treatment in
patients with CU which was significantly effective but only
temporary. Through analyzing reports in the literature, it might be the
following reasons:
Firstly, is that bacteria can act as an irritant of
pathophysiological processes leading to the CU? Antibody production
may continue even after the H. pylori eradication, contributing to the
interpretation of cases with urticaria infected H. pylori, eradication of
bacteria, but still urticaria expression. Secondly is that the deteriorating
clinical condition has been identified as possibly due to bacterial
infection. Finally, in addition to the re-infection factor in the stomach,
the role of H.pylori residing in extra-gastric sites was also discussed by
many reports, perhaps with its virulence factors, H. pylori in the extragastric sites continues to have a long-lasting effect on chronic
urticaria?


22

CONCLUSION
Through a study of 245 patients of chronic urticaria who
were treated at Hai Phong University Medical Hospital from 8/2016 02/2018, the thesis has some main conclusions:

1. The prevalence of Helicobacter pylori infection in
patients with chronic urticaria and clinical relevance of the disease.
The rate of H. pylori infection in patients with chronic
urticaria was 64.9%. The proportion of patients with duration of
wheals and pruritus persists > 6 hours was 59.6%. In CU/H.pylori+
group this rate was 69.2% significantly greater than the CU/H.pylorigroup. All

patients (100%) have moderate/severe itching and

wheals. In CU/H.pylori+ group, the incidence of severe pruritus was
81.8%; the incidence of severe wheal was 55.3%, significantly
greater than the CU/H.pylori- group.
2. The efficacy chronic urticaria treatment in combination
symptomatic treatment with bacteria eradication by triple-regimen
- Effectiveness treatment of chronic urticaria
Before treatment, UAS score of the CU/H.pylori+
eradicated group (5.5 ± 0.6) was significantly higher than that in
CU/H. pylori-. After 4 weeks of treatment, this score was decreased to
1.9 ± 0.7. This score was significantly lower than before treatment and
compared with the other two groups.
Before treatment, CU-QoL score of the CU/H. pylori+
eradicated group (67.8 ± 9.5) was higher than in CU/ H. pylori- group.
After 4 weeks of treatment, the QoL score of CU/H. pylori+
eradicated group was reduced to 33.2 ± 5.9, which was significantly