Wskaźniki fagocytozy u kobiet z trądzikiem w trakcie kompleksowego leczenia obejmującego stosowanie immunoterapii oraz probiotyków

Orysya О. Syzon, Marianna О. Dashko

Danylo Halytsky Lviv National Medical University, Lviv, Ukraine

ABSTRACT

Introduction: Acne is one of the most common dermatological diseases. It may have a chronic course, leaving permanent marks, and in last years has been tending to have more and more severe clinical course with widespread skin lesions. According to recent studies, the development of acne is due to the combined effect of endogenous and exogenous factors, among which endocrine diseases (quite a significant aspect), disorders of metabolic processes, reduced systemic immunity and phagocytic ability of mononuclear phagocytes and granulocytes at various stages of phagocytosis of pyogenic cocci, which contributes to more severe clinical course, and frequent relapse of this diseases. It was also proved that the intestinal microbiota plays an important role in the formation of homeostasis and immune response.

The aim of the study is to determine the evolution of phagocytosis indices in patients with acne under different comprehensive treatments, using oral antibiotics, immunotherapy, probiotics and low-dose birth control pills.

Materials and methods: We observed 93 women with acne aged from 18 to 25 years old. In 19 (20,43 %) patients mild acne was diagnosed, in 41 (44.09%) – moderate acne, in 33 (35.48 %) persons – severe acne, 54 (58,06%) persons suffered from acne up to 1 year, 39 (41,93%) – from 1 to 3 years. To assess the state of phagocytosis in patients with acne vulgaris, we determined phagocytic activity (PA) and phagocytic index (PI) of polymorphonuclear leukocytes, nitro blue tetrazolium recovery test (NBT test spontaneous) and NBT-test pyrogenal stimulated by the recognized methods.

Results: Analysis of the studied parameters of phagocytosis at the end of treatment showed a significant increase in patients of the core group who were administered a comprehensive treatment which included oral antibiotic, probiotic, low-dose birth control pills and autohemotherapy, as compared with the patients of other groups under study.

Conclusions: Using combined therapy for women with acne occurring against the backdrop of a sluggish process of phagocytosis and concomittant intestinal dysbiosis leads to normalization of the leading indices of phagocytosis (PI, PA, NBT tests both spontaneous and stimulated), and enchances their phagocytic activity both during capture and formation of bactericidal activity and in the final stages of phagocytosis justifying the feasibility of a combined use of antibiotics, probiotic, low-dose birth control pills and autohemotherapy in the treatment of acne.

Wiad Lek 2018, 71, 1 cz. II, -147

INTRODUCTION

Acne is one of the most common dermatological diseases. It may have a chronic course, leaving permanent marks (scars, blemishes, emotional disorders), and in recent years has been tending to have more and more severe clinical course with widespread skin lesions, formation of resistance to drugs of etiotropic treatment, leading to the chronic course, decrease or loss of patient’s capacity and social activity which signifies important medical and social aspects of the problem and justifies the topicality of improving treatment studies [1,2].

According to recent studies, the development of acne is due to the combined effect of endogenous and exogenous factors, among which endocrine diseases should be pointed out, as well as disorders of metabolic processes [3,4], reduced systemic immunity and phagocytic ability of mononuclear phagocytes and granulocytes at various stages of phagocytosis of pyogenic cocci, which contributes to more severe clinical course, and frequent relapse of this diseases [2]. It was also proved that the colon microbiota plays an important role in the formation of homeostasis and immune response. A relationship between the condition of the colon microbiota, indices of systemic immunity and phagocytosis and nature of clinical manifestations of acne justifying differentiated administration of probiotics and immunomodulation therapy in the comprehensive therapy were found [5].

According to modern standards [6,7,8,9], the treatment of acne is carried out in various ways: patients with mild acne are prescribed an external antibacterial and anti-inflammatory therapy (topical antibiotics, topical retinoid medicines, azelaic acid, benzoyl peroxide) only, but in case of moderate and severe forms, comprehensive treatment including systemic antibacterial, immunotropic, anti-inflammatory drugs, oral retinoid, low-dose birth control pills and other therapies are applied [6].

THE AIM

The objective of the study is to determine the evolution of phagocytosis indices in patients with acne under different comprehensive treatments, using oral antibiotics, immunotherapy (autohemotherapy), probiotics and low-dose birth control pills.

MATERIALS AND METHODS

We observed 93 women with acne aged from 18 to 25 years old. In 19 (20,43 %) patients mild acne was diagnosed, in 41 (44.09%) – moderate acne, in 33 (35.48 %) persons – severe acne, 54 (58,06%) persons suffered from acne up to 1 year, 39 (41,93%) – from 1 to 3 years. The control group consisted of 35 healthy individuals (donors) of the similar age. Patients were being observed during a year.

The considered criteria for the study were the following: patient’s age – 18 years old or more; clinical manifestations of acne, absence of chronic physical illness or exacerbation at the time of the examination.

To assess the state of phagocytosis in patients with acne vulgaris, we determined phagocytic activity (PA) and phagocytic index (PI) of polymorphonuclear leukocytes, nitro blue tetrazolium recovery test (NBT test spontaneous) and NBT-test pyrogenal stimulated by the recognized methods.

Statistical analysis of the results of research was carried out by the methods of statistical analysis using software (Excel, Statistica 6.0), the difference of averages was considered probable at p <0.05.

RESULTS AND DISCUSSION

Before treatment, patients with acne had probable decrease in PI (by 31.7%, p <0.001) with the downward trend of PA (by 8.82%, p>0.05), characterizing the initial stages of phagocytic process, as well as probable reduction of spontaneous NBT-test (by 24.8%, p <0.01) and stimulated NBT test (by 22.2%, p <0.001), which represent the final stage of the process of phagocytosis. At the same time, women with acne had concomitant dysbiosis of the large intestine cavity of I- IV degree and interdependence between changes of parameters of systemic immunity and phagocytosis, the degree of intestinal dysbiosis and severity of clinical course of acne was established (Figure 1), justifying the administration of probiotics and immunotropic therapy for these patients.

In order to optimize the treatment of acne, taking into consideration the found changes in systemic immunity indices of these patients, phagocytosis and colon microbiota, we developed a complex therapeutic method which suggests the administration of immunotherapy (autohemotherapy) [10,11], probiotic containing Escherichia coli Nissle 1917, low-dose birth control pills that have antiandrogenic effect and oral antibiotics (including doxycycline).

To determine the effectiveness of the developed method of combined therapy of acne, the patients under study were divided into 3 groups, using random method, and women in the groups were of similar age and clinical forms of acne. The first comparative group included 29 women who received systemic therapy, including oral antibiotics (including doxycycline) 0.1g twice a day during 14 days, probiotic containing Escherichia coli Nissle 1917 (1 capsule once a day duringr 1 month two times a year) and autohemotherapy according to the admitted scheme (2.0-4.0-6.0-8.0-10.0-8.0-6.0-4.0-2.0); the second comparative group consisted of 33 patients who were administered probiotic containing Escherichia coli Nissle 1917, low-dose birth control pills (for 12 month) and autohemotherapy; and the third (basic) group numbered 31 patients who were administered a comprehensive systemic therapy treatment which included oral antibiotics (including doxycycline) 0.1g twice a day 14 days, probiotic containing Escherichia coli Nissle 1917 (1 capsule once a day during 1 month two times a year), low-dose birth control pills (during 12 months) and autohemotherapy. All patiets also received external antibacterial and anti-inflammatory therapy: the women with mild acne azelaic acid, benzoyl peroxide, with moderate and severe acne additionally topical retinoid medicines.

The evaluation of the results of different treatments for acne was conducted basically on the analysis of the evolution of clinical and laboratory indices of blood including those of phagocytosis, that are shown in the table.

According to the results of the conducted studies (Table 1),patients of the 1st comparative group, who received systemic therapy, including oral antibiotics, probiotic and autohemotherapy. were likely to increase their PI by 26.18% (p <0.05), NBT-test of spontaneous and stimulated (by 15.38%, p<0.01 and 13.08% respectively, p <0.05), but preserving significant difference of PA and stimulated NBT-test with those of the control group (a decrease by 26.45%, p <0.001 and 17.41%, p <0.001 respectively).

Women with acne in the second comparative group, due to the use of probiotic, low-dose birth control pills, autohemotherapy at the end of treatment, showed probable growth of PI rates by 36.27% (p <0.001), NBT-test of spontaneous and stimulated (by 17.82%, p <0.05 and 14.22%, p <0.01 respectively), but without probable difference to the patients of the first comparative group with preserving significant difference of PI and stimulated NBT-test with the same parameters in control group (a decrease by 19.19%, p <0.05 and 15.02%, p <0.001 respectively).

However, patients with acne in the core group who received combined therapy which included oral antibiotic, probiotic, low-dose birth control pills (for 12 month) and autohemotherapy, experienced probable increase in PI and PA (by 43.66%, p <0.001 and 11.98%, p <0.05 respectively), spontaneous NBT-test (by 20.6%, p <0.01) as well as stimulated NBT test (by 30.77%, p <0.001) with the approximation of most of them, except NBT-test stimulated, to the values of those in the control group.

Analysis of the studied parameters of phagocytosis at the end of treatment also showed a significant increase in patients of the core group compared to those of patients in other comparative groups. Thus, the rate of PI at the end of end of the treatment in patients of the main group was significantly higher both comparing to the indices of the patients in the 1st comparison group (by 20.95%, p <0.01), while stimulated NBT test relative to the 1st comparative group (by 12.39%, p <0.01) and to the 2st comparative group (by 9.24%, p <0.01). The obtained better results on the evolution of the phagocytosis indices in patients of the main group could be related to the following: direct stimulating effect of immunotherapy, low-dose birth control pills have regulatory influence on the homeostasis of woman’s organism and by a decrease of microbial intestinal load on macrophages and granulocytes as a result of normalizing probiotic action on concomitant dysbiotic disturbances of the large intestine in such patients.

CONCLUSIONS

Using combined therapy with the inclusion of oral antibiotic, probiotic, low-dose birth control pills and autohemotherapy for women with acne occurring against the backdrop of a sluggish process of phagocytosis and concomittant intestinal dysbiosis leads to normalization of the leading indices of phagocytosis (PI, PA, NBT tests both spontaneous and stimulated), and enchances their phagocytic activity both during capture and formation of bactericidal activity and in the final stages of phagocytosis, justifying the feasibility of a combined use of antibiotics, probiotic, low-dose birth control pills and autohemotherapy in the treatment of acne.

In the future we are planning to determine and analyze the evolution of other homeostasis indices in a combined treatment of patients, suffering from acne by using oral antibiotics, probiotic, low-dose birth control pills and autohemotherapy as a complex.

REFERENCES

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2. Zouboulis C, Schagen S, Alestas T. The sebocyte culture: a model to study the pathophysiology of the sebaceous gland in sebostasis, seborrhoea and acne. Archives of Dermatological Research. 2008; 300 (8): 397-413

3. Foti, C; Romita, P; Borghi, et al. Contact dermatitis to topical acne drugs: a review of the literature. Dermatologic Therapy. 2015; 28(5): 323–329.

4. Penera G., Hay R. A guide to antibiotic resistance in bacterial skin infections. Inl. of Eur. Acad. Dermatol. Venereol. 2005; 19(5): 531-545.

5. Karvatska Yu. P, Denysenko O.I The state of systemic immunity in patients with acnevulgaris with different degrees of changes in biocenosis of the large intestine. Ukr. J. of Dermatol. Venereol. Cosmetol. 2014; 1(52): 35-40

6. Zaenglein A.L; Pathy A.L; Schlosser B.J et al. Guidelines of care for the management of acne vulgaris. Journal of the American Academy of Dermatology. 2016; 74(5):945–973

7. Leccia MT, Auffret N; Poli F et al. Topical acne treatments in Europe and the issue of antimicrobial resistance. Journal of the European Academy of Dermatology and Venereology. 2015; 29 (8): 1485–1492.

8. Gamble, R; Dunn, J; Dawson, A; et al.: Topical antimicrobial treatment of acne vulgaris: an evidence-based review. American Journal of Clinical Dermatology. 2012; (13)3: 141–152.

9. Sagransky M., Yentzer B.A.; Feldman S.R.: Benzoyl peroxide: A review of its current use in the treatment of acne vulgaris. Expert Opinion on Pharmacotherapy. 2009; (10)15: 2555–2562.

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A reappraisal. J Int Med Res. 1994; 22(3):131-44.

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ADDRESS FOR CORRESPONDENCE

Marianna Dashko

Department of Dermatology, Venereology

Danylo Halytsky Lviv National Medical University

Konovalets str., 1

79014, Lviv, Ukraine

e-mail: mariannadashko@gmail.com

Received: 14.09.2017

Accepted: 22.12.2017

Figure 1. Distribution of patients with different severity of acne according to the degree of dysbiosis.

Table І. Evolution of phagocytosis indices in patients with pyoderma after different therapies(M±m)

Indices, measurement units

Patients with acne (n=93)

Control group

(n=35)

1st group

(n1=29)

2nd group
(n
2=33)

3rd group

(n3=31)

Phagocytic activity, %

Before treatment

54.9±

1.65

54.1±2.08

p1-2>0.05

55.9±2.54

p1-3>0.05; p2-3>0.05

62.9±

4.28

After treatment

58.5±

1.34

57.9±1.64

p1-2>0.05

62.6±1.92

p1-3>0.05; p2-3>0.05

Р (before/after treatment)

Р>0.05

Р>0.05

Р<0.05

Phagocytic index

Before treatment

4.01±

0.406**

4.08±0.264***

p1-2>0.05

4.26±0.298***

p1-3>0.05;p2-3>0.05

6.88±

0.540

After treatment

5.06±

0.302**

5.56±0.242*

p1-2>0.05

6.12±0.242

p1-3<0.01;p2-3>0.05

Р (before/after treatment)

Р<0.05

Р<0.001

Р<0.001

spontaneous NBT-test

Before treatment

9.88±

0.224**

10.1±0.598*

p1-2>0.05

10.0±0.709*

p1-3>0.05; p2-3>0.05

12.5±

0.850

After treatment

11.4±

0.244

11.9±0.672

p1-2>0.05

12.6±0.624

p1-3>0.05; p2-3>0.05

Р (before/after treatment)

Р<0.01

Р<0.05

Р<0.01

stimulated NBT test

Before treatment

21.4±

0.972***

21.8±0.859***

p1-2>0,05

20.8±0.698***

p1-3>0.05; p2-3>0.05

29.3±

0.723

After treatment

24.2±

0.634***

24.9±0.436***

p1-2>0,05

27.2±0.648*

p1-3<0,01; p2-3<0.01

Р (before/after treatment)

Р<0.05

Р<0.01

Р<0.001

Notes:

1. * – The degree of probability of the indices deference relative to control group of patients:

* – р<0.05; ** – p<0.01; *** – p<0.001.

2. p1-2, p1-3, p2-4 – probability of the indices deference in patients of different groups.

3. Р – probability of the indices deference in the groups of patients before and after the treatment.