ANALIZA POZIOMU ODPORNOŚCI U PACJENTÓW Z TRĄDZIKIEM O RÓŻNYM PRZEBIEGU KLINICZNYM

Marianna O. Dashko, Orysya O. Syzon, Ulyana V. Fedorova

Danylo Halytsky Lviv National Medical University, Lviv, Ukraine

ABSTRACT

Introduction: Acne is chronic recurrent dermatosis, one of the essential skin inflammation in the structure of dermatological pathology, especially in young people of working age, often caused by persistent cicatricial changes in the skin, and affecting negatively the psychoemotional state of patients, their quality of life and working capacity. It has been established by today that the pathogenesis acne is complex and multifactorial, and the changes of immune reactivity of the organism play an important role in its clinical course development.

The aim of the article is to determine and analyze the values of the systemic immunity in patients suffering from acne with different clinical course.

Materials and methods: 128 patients with acne aged from 18 to 35, among which 74 women (57,8 %) and 54 men (42,2 %) were observed. According to the clinical criteria, 26 patients (20,31%) were diagnosed with comedonal form of acne, 40 patients (31.25%) had papules, 10 people (7.81%) –papular-pustular acne, 29 of the observed (22.65%) had pustules, 9 patients (7.03%) suffered from acne conglobata, and 14 patients (10.94%) were diagnosed with post-acne. The control group consisted of 34 practically healthy people (donors) of the same age.

Results: Consequently, most of the patients with acne had varying degrees of changes in rates of systemic immunity – the likely reduction in relative and absolute number of total lymphocytes, T-lymphocytes and their subpopulations against the growing number of B lymphocytes and the level of IgM and IgG, which generally indicates the formation in these patients secondary immunodeficiency state of T-link intensified by activation of humoral immunity in response to the development of skin inflammation. The most significant changes in rates of systemic immunity with the depletion of T-cell immunity were found in patients with papular-pustular and pustular acne, and still more significant – in patients with acne conglobate, which justifies differentiated treatment by immunomotropic drugs for these patients.

Conclusion: In patients with acne, changes in systemic immunity indexes that indicate the formation of secondary immunodeficiency state T-cell link, amid an adequate humoral immunity have been found. Relationship between the causes of changes of systemic immunity has been established.

 

Wiad Lek 2018, 71, 2 cz. I, -300

 

INTRODUCTION

Acne is chronic recurrent dermatosis, one of the essential skin inflammation in the structure of dermatological pathology, especially in young people of working age, often caused by persistent cicatricial changes in the skin, and affecting negatively the psychoemotional state of patients, their quality of life and working capacity[1,2]. It has been established by today that the pathogenesis acne is complex and multifactorial, and the changes of immune reactivity of the organism play an important role in its clinical course development [3,4,5] The high level of acne incidence, the tendency to a chronic course of formation of resistance to treatment, frequent cases of development of deep forms determine the important medical and social significance of the problem. [2,6,7,8] However, the information about the immune system in these patients is often ambiguous and contradictory – it is often recorded as manifestation of increased immune activity and the formation of secondary immunodeficiency state, which may contribute to chronic dermatoses and their resistance to standard therapy tools [9,10,11,12]. In this regard, the urgent task of modern dermatology is to establish the nature of changes of systemic immunity in patients with acne with different clinical course in order to clarify the pathogenetic factors and develop differentiated methods of treatment.

THE AIM

The Objective of the article is to determine and analyze the values of the systemic immunity in patients suffering from acne with different clinical course.

MATERIALS AND METHODS

128 patients with acne aged from 18 to 35, among which 74 women (57,8 %) and 54 men (42,2 %) were observed. They had been selected for the study according to the following criteria: clinical signs of acne, age 18+, absence of chronic somatic diseases or their exacerbations at the moment of the study.

According to the clinical criteria (figure 1), 26 patients (20,31%) were diagnosed with comedonal form of acne, 40 patients (31.25%) had papules, 10 people (7.81%) –papular-pustular acne, 29 of the observed (22.65%) had pustules, 9 patients (7.03%) suffered from acne conglobata, and 14 patients (10.94%) were diagnosed with post-acne. The control group consisted of 34 practically healthy people (donors) of the same age.

To provide proper assessment of systemic immunity in patients with acne, we determined the following: total and relative number of T-lymphocytes (CD3+), T-helpers (CD3+CD4 +) and T-suppressor lymphocytes (CD3+CD8+), the number of B lymphocytes (CD19+), applying monoclonal antibodies by indirect immunofluorescence to cell surface antigens and serum of (Ig) immunoglobulins of class M, G, A according to the known method. Statistical analysis of the results of research was carried out by the methods of statistical analysis using the computer program Statistica 7.0, the probable average difference was considered at p<0,05.

RESULTS AND DISCUSSION

In determining the indices of systemic immunity in patients with acne, there were established their probable changes which indicate the development of secondary immune deficiency in these patients, byT-cell population mainly, as well as a disturbance of absolute number of total lymphocytes, T-helper ones (with CD3 + CD4 +) and T suppressor (with CD3 + CD8 +) lymphocytes, while the most significant changes in these parameters were established in patients with moderate and severe acne with chronic and deep forms [13,14].

While determining the indicators of the systemic immunity in 128 patients with acne, we established their probable (р<0,001) changes, as compared with the indicators for patients in the control group (Table І):
decrease in relative and absolute number of total lymphocytes pool – by 20,4
 % (28,9±0,69 %, in the control group – 36,3±0,91 %) and by 21,2 % (1,90±0,051 G/l (this index marks giga-/ liter) in the control group – 2,41±0,10 G/l), T-lymphocytes (СD3+) – by 19,2 % (47,1±1,33 %, in the control group – 58,3±1,09 %) and 33,7 % (0,955±0,033 G/l in the control group – 1,44±0,082 G/l), T-helpers (CD3+CD4+) lymphocyte subpopulations – accordingly by 11,7 % (33,1±0,34 %, in the control group – 37,5±0,91 %) and by 22,9 % (0,613±0,022 G/l in the control group – 0,796±0,054 G/l), and the relative number of T-suppressors (CD3+CD8+) lymphocytes – by 13,9 % (18,5±0,15 %, in the control group – 21,5±0,93 %) against the backdrop of increasing relative and absolute number of B lymphocytes (CD19+) – by 14,3 % (25,6±0,30 %, in the control group – 22,4±0,81 %) and 35,2 % (0,488±0,014 G/l in the control group – 0,360±0,020 G/l) and IgM levels – by 25,7 % (1,81±0,047 G/l in the control group – 1,44±0,06 G/l) and IgG – by 40,4 % (13,3±0,25 G/l in the control group – 9,49±0,34 G/l).

The analysis of systemic immune system indexes in patients with acne, taking into account its different the clinical form and depth of skin lesions presented in the table, has showed that in patients with comedonal form of acne there is a decrease in the relative amount of the total pool of lymphocytes by 10,5 %, p<0,05, with papular form of acne – by 13,7 %, p<0,01, a decrease in the relative and absolute amount of T-lymphocytes (with comedonal form – by 8,5 % and by 21,5 %, p<0,01, with papular form – by 7,5%, p<0,001 and by 20,1 %, p<0,01, with post-acne – by 12,0 %, p<0,001 and by 18,7 %, p<0,05), the relative amount of T-helpers (СD3+CD4+) with comedonal form of acne – by 9,9 %, p<0,001, with papular form – by 6,24% and with post-acne – by 8,1%, p<0,05 and absolute amount of B lymphocytes (with comedonal form – by 29,4 %, with papular form – by 35,7 %, and with post-acne – by 47,4 %, p<0,001.

At the same time, probable decrease (p<0,001) in the absolute and relative amount of the total pool of lymphocytes was identified in patients with papular-pustular acne, as compared with the control group: by 32,8 % and by 48,5 %, with pustular acne – by 34,4 % and by 46,5 %, with acne conglobata – by 47,4 % and by 34,4 % correspondingly. These patents were also defined with probable decrease in the relative and absolute amount of T-lymphocytes (CD3+), as compared with the control group: in patients with papular-pustular acne – by 24,4 % and by 62,1 %, in patients with pustular acne – by 15,8 % and by 34,7 %, and in patients with acne conglobata – by 28,9 % and by 54,6 %, p<0,001) accordingly. Alongside, a decrease in the relative and absolute amount of T-helping (СD3+CD4+) lymphocytes has been identified, as compared with the control group: in patients with papular-pustular acne – by 27,2 % and by 57,4 %, p<0,001, in patients with pustular acne – by 17,3 %, p<0,001 and by 21,9 %, p<0,01; in patients with acne conglobata – by 33,3 % and by 49,9 %, p<0,001).

The analysis of indicators of systemic humoral immunity in patients with different clinical forms of acne revealed a significant increase in the relative and absolute amount of B-lymphocytes (CD19+), as compared with the control group: in patients with papular-pustular acne (correspondingly, by 14,3 %, p<0,05 and by 32,4 %, p<0,001), in patients with pustular (by 22,7 % and by 52,4 %, p<0,001), and in patients with acne conglobate (by 37,1 % та 34,3 %, p<0,001). Moreover, in patients with certain clinical forms of acne, a probable increase in levels IgM and IgG has been observed, as compared with the relative indexes of control (correspondingly, in patients with papular-pustular acne – by 45,8 % and by 63,3 %, with papular form of acne – by 54,2 % and by 68,6 %, with acne conglobate – by 96,5 % and by 90,72 % p<0,001).

Consequently, most of the patients with acne had varying degrees of changes in rates of systemic immunity – the likely reduction in relative and absolute number of total lymphocytes, T-lymphocytes and their subpopulations against the growing number of B lymphocytes and the level of IgM and IgG, which generally indicates the formation in these patients secondary immunodeficiency state of T-link intensified by activation of humoral immunity in response to the development of skin inflammation. The most significant changes in rates of systemic immunity with the depletion of T-cell immunity were found in patients with papular-pustular and pustular acne, and still more significantin patients with acne conglobate, which justifies differentiated treatment by immunomotropic drugs for these patients.

CONCLUSION

In patients with acne, changes in systemic immunity indexes that indicate the formation of secondary immunodeficiency state T-cell link, amid an adequate humoral immunity have been found. Relationship between the causes of changes of systemic immunity has been established.

REFERENCES

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3. 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; 5: 945–973

4. Leccia, MT; Auffret, N; Poli, F; Claudel, JP; Corvec, S; Dreno, B.: Topical acne treatments in Europe and the issue of antimicrobial resistance. Journal of the European Academy of Dermatology and Venereology. 2015; 8:1485–1492.

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

6. 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; 15: 2555–2562.

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8. Jih M.H., Friedman P.M., Goldberg L.H., Robles M., Glaich A.S., Kimyai-Asadi A.: The 1450 nm diode laser for facial inflammatory acne vulgaris: dose response and 12 month follow-up study. J Am Acad Dermatol. 2006; 55: 80–87.

9. Haedersdal M., Togsverd-Bo K., Weigell S.R., Wulf H.C.: Long pulsed dye laser versus long pulsed dye laser-assisted photodynamic therapy for acne vulgaris. J Am Acad Dermatol. 2008; 58: 387–394.

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14. Wilcox H.E., Farrar M.D., Cunliffe W.J. et al Resolution of inflammatory acne vulgaris may involve regulation of CD+4 T-cells responcesto Propionbacterium acnes. Brit. J.Dermatol. 2007; 156: 460-465.

ADDRESS FOR CORRESPONDENCE

Marianna Dashko

Department of Dermatology, Venereology

Danylo Halytsky Lviv National Medical University

Konovalets str., 1, Lviv, 79014, Ukraine,

e-mail: mariannadashko@gmail.com

Received: 20.02.2018

Accepted: 10.04.2018

Fig. 1. Distribution of patients according to the clinical criteria.

Table І. Values of the systemic immunity in patients suffering from acne with different clinical course

Values, units

Control group n=34

Comedonal form of acne n1=26

Papular acne n2=40

Papular-pustular acne

n3=10

Pustular acne

n4=29

Acne conglobata n5=9

Post-acne

n6=14

Lymphocytes , %

36,3±

0,912

32,5±

1,12*

31,6±1,22**

p1-2->0,05

24,4±1,13***

p1-3<0,001

p2-3<0,01

23,8±1,29***

p1-4<0,001

p2-4<0,001

p2-4>0,05

19,1±0,707***

p1-5<0,001

p2-5<0,001

p3-5<0,01

p45>0,05

31,4±0,845***

p1-6>0,05

p3-6<0,001

p2-6>0,05

p46<0,01

p56<0,001

Lymphocytes, G/l

2,41±

0,10

2,04±

0,042*

2,18±0,060*

p1-2>0,05

1,24±0,062***

p1-3<0,001

p2-3<0,001

1,29±0,041***

p1-4<0,001

p2-4<0,001

p3-4>0,05

1,58±0,049***

p1-5<0,001

p2-5<0,001

p3-5<0,001

p45<0,001

2,22±0,042***

p1-6>0,05

p2-6>0,05

p3-6<0,001

p46<0,01

p56<0,001

CD 3+

(T-lymphocytes) %

58,3±

1,09

53,3±

0,492***

53,9±0,373***

p1-2>0,05

44,1±0,676***

p1-3<0,001

p2-3<0,001

49,1±0,608***

p1-4<0,001

p2-4<0,001

p3-4<0,001

41,4±0,719**

p1-5<0,001

p2-5<0,001

p3-5<0,05

p45<0,001

51,4±0,527***

p1-6<0,05

p3-6<0,001

p2-6<0,001

p46<0,05

p56<0,001

CD 3+

(T-lymphocytes)

G/l

1,44±

0,082

1,13±

0,025**

1,15±0,049**

p1-2>0,05

0,546±0,031***

p1-3<0,001

p2-3<0,001

0,948±0,046***

p1-4<0,01

p2-4<0,01

p3-4<0,001

0,654±0,025***

p1-5<0,001

p3-5<0,05

p2-5<0,001

p45<0,01

1,17±0,027*

p1-6>0,05

p3-6<0,001

p2-6>0,05

p46<0,001

p56<0,001

CD3+CD 4+

(T-helpers) %

37,5±

0,912

33,8±

0,202***

35,2±0,289*

p1-2<0,001

27,3±0,577***

p1-3<0,001

p2-3<0,001

31,0±0,438***

p1-4<0,001

p2-4<0,001

p3-4<0,001

25,0±0,535***

p1-5<0,001

p3-5<0,01

p2-5<0,001

p45<0,001

34,2±0,352*

p15>0,05

p2-6>0,05

p3-6<0,001

p46<0,001

p56<0,001

CD3+CD4+

(T-helpers ),

G/l

0,796±

0,054

0,73±

0,015

0,768±0,024

p1-2>0,05

0,339±0,014*

p1-3<0,001

p2-3<0,001

0,622±0,015**

p1-4<0,001

p2-4<0,001

p3-4<0,001

0,399±0,019***

p1-5<0,001

p3-5<0,05

p2-5<0,001

p45<0,001

0,760±0,018

p15>0,05

p2-6>0,05

p3-6<0,001

p46<0,001

p56<0,001

CD3+CD 8+

(Tsuppressors ) %

21,5±0,934

19,5±

0,356

18,7±0,160**

p1-2<0,05

16,8±0,222*

p1-2<0,001

p2-3<0,001

18,0±0,314**

p1-4<0,01

p2-4<0,05

p3-4<0,001

16,4±0,429**

p1-5<0,001

p2-5<0,001

p3-5>0,05

p45<0,05

18,2±0,023*

p1-6<0,05

p2-6>0,05

p3-6<0,001

p46>0,05

p56<0,001

CD3+CD 8+

(Tsuppressors)

G/l

0,336±

0,042

0,397±

0,011

0,409±0,014

p1-2>0,05

0,207±0,011

p1-3<0,001

p2-3<0,001

0,364±0,014

p1-4>0,05

p2-4>0,05

p3-4<0,001

0,260±0,010

p1-5<0,001

p3-5<0,01

p2-5<0,001

p45<0,001

0,405±0,010

p1-6>0,05

p2-6<0,001

p3-6>0,05

p46>0,05

p56<0,001

CD 19+

(Blymphocytes)

%

22,4±

0,812

23,0±

0,459

22,3±0,366

p1-2>0,05

25,6±0,747*

p1-3<0,01

p2-3<0,001

27,5±0,347***

p1-4<0,001

p2-4<0,05

p3-4<0,001

30,7±0,521***

p1-5<0,001

P2-5<0,001

p3-5<0,001

p45<0,001

23,9±0,595

p1-6>0,05

p2-6<0,05

p3-6>0,05

p46<0,001

p56<0,001

CD 19+

(Blymphocytes) G/l

0,36±

0,02

0,467±

0,012***

0,490±0,016***

p1-2>0,05

0,478±0,012***

p1-3>0,05

p2-3>0,05

0,550±0,012***

p1-4<0,001

p2-4<0,01

p3-4<0,01

0,485±0,018***

p1-5>0,05

p2-5>0,05

p3-5>0,05

p45<0,05

0,532±0,016**

p1-6<0,001

p2-6>0,05

p3-6<0,05

p46>0,05

p56>0,05

Immunoglobulin A, G/l

1,98±

0,06

1,78±

0,077***

1,83±0,071

p1-2>0,05

1,60±0,027**

p1-3>0,05

p2-3>0,05

1,93±0,076

p1-4>0,05

p2-4>0,05

p3-4>0,05

1,48±0,166***

p1-5>0,05

p3-5>0,05

p2-5<0,05

p45<0,05

1,87±0,080

p1-6>0,05

p2-6>0,05

p3-6>0,05

p46>0,05

p56<0,05

Immunoglobulin M, G/l

1,44±

0,06

1,33±

0,056

1,56±0,042

p1-2>0,05

2,10±0,093***

p1-3<0,001

p2-3<0,001

2,22±0,082***

p1-4<0,001

p2-4<0,001

p3-4>0,05

2,83±0,101***

p1-5<0,001

p2-5<0,001

p3-5<0,001

p45<0,001

1,90±0,037***

p1-6<0,001

p3-6<0,05

p2-6<0,001

p46<0,001

p56<0,001

Immunoglobulin G, G/l

9,49±

0,34

10,63±

0,394

12,1±0,217***

p1-2<0,001

15,5±0,404***

p1-3<0,001

p2-3<0,001

16,0±0,181***

p1-4<0,001

p2-4<0,001

p3-4>0,05

18,1±0,195***

p1-5<0,001

p2-5<0,001

p3-5<0,001

p45<0,001

11,9±0,270***

p1-6<0,05

p2-6>0,05

p3-6<0,001

p46<0,001

p56<0,001

Notes:

1. Differences in the degree of probability compared to the control group:

* – р<0,05; ** – p<0,01; *** – p<0,001.

2. p1-2, p1-3, p1-4, p2-5 – Differences in the probability of different groups of patients