CC BY
78
Clinical medicine
UDC 616.53-002.25-07:615.262 doi.org:10.31684/2541-8475.2019.1(13).36-42
MORPHOMETRIC ASSESSMENT OF THE THERAPY EFFICACY IN PATIENTS WITH MODERATE ACNE
Irkutsk State Medical University, Irkutsk Regional Dermatovenerologic Dispensary, Irkutsk
M.L. Abdukhalikova, I.O. Malova
In this study, we assessed the changes in facial skin morphometric indicators in the case of moderate acne against the background of systemic LIDOSE form isotretinoin therapy in 30 patients being administered isotretinoin in the LIDOSE form at the dose of 0.6-0.8 mg/kg a day until the achievement of the total course drug dose -100-120 mg/kg of body weight. The control group consisted of 30 practically healthy people. The study showed good efficiency and tolerability of the therapy, in the course of treatment, there was a reliable positive dynamics of objective changes in skin morphometric indicators. The morphometric study carried out in dynamics reflected the positive impact of isotretinoin in the LIDOSE form on pathogenetic mechanisms of moderate acne. Key words: isotretinoin in the LIDOSE form, acne, ultrasonic scanning, sebumetry, corneometry.
Among chronic inflammatory dermatoses of non-infectious genesis, acne vulgatis is one of the most frequent causes of resorting to a dermatologist. Common acne is diagnosed in 80% of the population aged 20-30 years (aged 17 years - in 86.1%). The frequency of occurrence of the disease does not depend on sex, but there is a heavier course in boys [1]. About 20% of patients have moderate and severe intensity of the disease [2].
The disease is characterized by the progredient course, formation of nosogenic psychoemotional disorders mainly of depressive series in about half of patients, sharply reduces the quality of life of patients, and the frequency of occurrence of severe forms leading to significant cosmetic defects in the form of hypo- and hypertrophic scars is from 5 to 15% of all cases of acne [3, 4, 5].
It should be recognized that the most effective method of treatment of moderate and severe forms of acne is conducting a course of therapy with systemic isotretinoin [6]. To date, a number of studies have been published demonstrating the high efficacy and safety of LIDOSE form isotretinoin therapy [7]. This drug allows to reduce a single dose of isotretinoin by 20%, to increase the safety of treatment, with that, it is cheaper than usual forms of isotretinoin, thus, it is available to more patients that determines the economic viability of its application [8].
Currently, a large number of papers have been published to assess the clinical efficacy of therapy in acne patients, which includes reduced comedone formation, regression of elements, dynamics of postinflammatory changes. However, in modern conditions, it is necessary to focus on objective data also when the assessment due to evidence-based medicine is required. To do this, it is rational to use non-invasive methods of assessing the skin condition, which include ultrasonic scanning of the skin, sebumetry, corneometry, allowing to
objectively analyze changes in morphometric parameters of the skin during treatment [9, 10, 11].
High-frequency ultrasound examination of the skin allows the study of morphological structures of the epidermis and dermis. This technique can be successfully applied to observe pathological processes in the skin, as well as to objectively assess the effectiveness of therapeutic impact, and, if necessary, to perform its additional correction in dermatological patients [11].
The principle of corneometry is based on the quantitative determination of moisture in the surface layer of the skin in the conditions of passing electric current. Electrical conductivity and current intensity between the sensor probes directly touching the skin surface are digitalized for measurements. The higher the moisture content in keratinocytes, the higher the electrical conductivity coefficient [9].
The principle of photometry is used to carry out sebumetry. A special synthetic tape sensitive to fats is applied to the skin surface and changes its optical density depending on the amount of fats. The pink surface of the paper becomes red after sebum absorption. Next, the sensor scans the color change, the microprocessor handles the data received and outputs them in numerical values [9].
The research objective is to assess changes in facial skin morphometric indicators in patients with moderate acne against the background of systemic LIDOSE form isotretinoin therapy.
Materials and methods
The study was conducted on the basis of the SBHI "Regional Dermatovenerologic Dispensary", 30 patients with moderate acne were under the supervision (the main group): 18 men (aged 17-33) and 12 women (aged 17-29) who received LIDOSE form isotretinoin (Acnecutan) at a dose of 0.6-0.8 mg/kg per day until the total course drug dose of 100-120 mg/kg of body weight. The moisturizing
cream was used to care for the facial skin. The duration of therapy of patients was 6-7 months.
The control group consisted of 30 practically healthy people aged from 18 to 35.
The duration of the disease in patients varied from 1 to 12 years (6.6±3.9 years). All patients noted the ineffectiveness of the previously conducted traditional therapy, the occurrence of frequent relapses of the disease. In all patients, rashes were widespread and localized on the skin of the face, back, upper chest, were presented by polymorphic rashes: comedones, papules, pustules, single indurative and phlegmonous rashes.
Before the beginning of treatment with isotretinoin, 1 and 3 months after its beginning, blood biochemical parameters were studied: AST, ALT, alkaline phosphatase, triglycerids, cholesterol, creatinine (there were no deviations from the norm).
The Aramo SG unit (ARAM HUVIS Co., Ltd, South Korea) was used to assess the facial skin morphometric parameters. Facial skin diagnostics on this device allows to carry out corneometry (relative units - RU) and sebumetry (RU).
Ultrasound skin examination was carried out by the DUB SkinScanner (tpm GmbH, Taberna Pro Medicum, Germany) with a sensor of 22 MHz, scanning depth of 8 mm, and resolution of 72 ^m. The study was carried out on the skin of three localizations (forehead, chin, cheeks), these are the areas of the most pronounced inflammation and maximum amount of rashes. Epidermis and dermis thickness (^m), acoustic density (RU) were evaluated.
The study was approved by the local Ethics Committee of the Irkutsk State Medical University.
Statistical processing of the results was carried out in the STATISTICA 6.0 program. Parametric Student's t-test was used to calculate the statistical
significance. The critical level of significance when checking statistical hypotheses amounted to p<0.05.
Results and discussion
After completion of treatment, clinical recovery was observed in 27 (90.0%) patients; improvement in 3 (10.0%) patients; lack of effect was not registered. Against the background of treatment, 28 (93.3%) patients registered cheilitis, 17 (56.6%) patients - facial dermatitis, 14 (46.6%) patients -xerosis (skin dryness). Along with the above side effects, 3 (10%) patients had nasal hemorrhage, 2 (6.7%) patients - blepharoconjunctivitis.
Morphometric skin parameters were estimated after 1, 3 months from the beginning of therapy and after the completion of treatment.
Normally, in skin ultrasonic scanning, epidermis is represented by linear structures of high echoicity, it is clearly delimited from the dermis with a smooth contour. Two interconnected layers, the papillary one and the reticular one, form dermis. The papillary layer is formed by loose connective tissue, the reticular layer forms the most part of the dermal tissue. It consists mainly of collagen fibers of great diameter combining into large interweave fascicles with surrounding and branching elastic fibers. Also in the dermis structure, hypoechogenic structures of sebaceous, sweat glands, ducts, and blood vessels are visualized. In this regard, during ultrasonic scanning, dermis is visualized in the form of the different-sized acoustic reflection structure. Due to the fact that the reticular layer is more dense, there is a stronger acoustic reflection of the ultrasonic signal, accordingly, a brighter image of the lower dermis layers is formed. Subcutaneous tissue is represented by hypo- and anechogenic areas clearly delimited from the dermis (Figure 1).
Details of ultrasonic scanning of the skin in patients before and after treatment are given in Table 1.
Figure 1. Ultrasonic scanning of the healthy skin in the cheek area of the participant from the control group.
Note: *p according to t-test; pi - differences in the main and control groups before treatment; p2 - differences in the main and control groups after treatment; p3 - differences in the main group before and after treatment.
Table 1
Parameters of ultrasonic scanning of the skin in acne patients before and after treatment
Indicator Control group n=30 M±CT Main group before treatment * n=30 pi M±CT Main group after treatment n=30 M±CT P2* Pa*
Epidermis thickness, ^m
forehead chin cheeks 103.7±3.5 103.2±4.6 103.2±5.9 127.3±9.84 <0.01 128.7±13.4 <0.01 125.4±10.3 <0.01 81.1±6.78 81.1±7.4 80.7±6.09 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01
Epidermis acoustic density, RU
forehead chin cheeks 57.2±12.8 62.3±13.7 63.1±6.7 49.9±23.8 0.148 58.8±20.3 0.433 45.3±10.7 <0.01 70.4±12.6 70.6±14.6 67.6±11.7 <0.01 <0.05 0.072 <0.01 0.01 <0.01
Dermis thickness, ^m
forehead chin cheeks 1551.8±74.2 1008.9±62.8 1532.2±67.4 1925.5±136.3 <0.01 1063.2±89.6 <0.01 1924.6±148.0 <0.01 1800.8±137.0 1108.4±119.3 1745.5±96.4 <0.01 <0.01 <0.01 <0.01 0.102 <0.01
Dermis acoustic density, RU
forehead chin cheeks 5.1±1.1 4.03±0.7 6.4±1.07 3.1±0.98 <0.01 3.4±1.07 0.01 3.2±0.89 <0.01 6.4±1.3 6.1±1.1 6.3±1.3 <0.01 <0.01 0.623 <0.01 <0.01 <0.01
Figure 2. Ultrasonic scanning of the facial skin in the cheek area of the female patient from the main group before treatment.
In ultrasonic scanning of the skin of acne patients before treatment (Figure 2), epidermis thickening and uneven structure (p<0.01), as well as reduction of its acoustic density draw attention, they are most likely due to follicular epidermal hyperprolifera-tion, whereby the epithelium of the upper part of the hair follicle, infundibulum, becomes hyperkeratotic, keratinocytes cohesion increases [12]. In the course of treatment (Figure 3), epidermis thickness significantly reduces in all studied areas (p<0.01). Before
treatment, epidermis acoustic density in acne patients was significantly lower than the control points only in the cheek area, which may be due to the fact that it is the area of the most pronounced inflammation and the maximum amount of rashes. Against the background of treatment, epidermis acoustic density increases in all studied areas (p<0.01). This confirms the impact of LIDOSE form isotretinoin on the strengthening and normalization of differentiation of keratinocytes.
Figure 3. Ultrasonic scanning of the facial skin in the cheek area of the female patient from the main group after treatment.
In addition, during ultrasonic scanning of the skin in acne patients before treatment, dermis thickening and reduce in its acoustic density (p<0.01) due to inflammation were noted: in the developed stage, inflammation in acne is a classic manifestation of type IV immunological reaction. As inflammation increases in the sebaceous hair follicle, granulomatous inflammation develops resulting in scar formation [2]. Because of this processes, uneven distribution of echo signal in dermis occurs (Figure 2).
After 1 month of treatment, an even greater increase in the dermis thickness was recorded. These changes can be explained by the recrudescence of the disease in patients in the 2-3 weeks of treatment. It is due to the fact that isotretinoin significantly reduces sebum production in the second week of treatment already, resulting in the rapid simultaneous release of P.acnes antigens into surrounding tissues and the following violent inflammatory reaction involving superantigens and/or Toll-like receptors. During the examination of patients after 3 months and after treatment, the dermis thickness stabilization can be noticed, its indicators remain above the ones of the control group (p<0.01).
When assessing the dynamics of changes in dermis acoustic density in the course of treatment, there is also a significant increase in indicators in all studied areas (p<0.01): there is an increase in indicators to the control values in the cheek area and higher values in the forehead and chin areas.
In ultrasonic scanning of the skin of patients after treatment (Figure 3), thin, dense, uniform epidermis draws attention, which corresponds to the normalization of the cycle of cell keratinization and desquamation. Along with this, homogeneous, dense, thickened dermis with a stronger acoustic
reflection of the ultrasonic signal is visualized. These changes indicate an improvement in the dermis structural organization and a decrease in the inflammation signs, an increase in the dermis main substance. One of the main reasons for the reliable dermis thickening can be the strengthening of its proliferative capabilities. Thickening and leveling the dermis borders can be associated with the improvement of its structural organization, primarily its fibrous structures and intercellular substance. This is probably one of the effects of systemic LIDOSE form isotretinoin on the acceleration of collagen synthesis due to the impact on the MMP expression system [13, 14, 15, 16, 17].
Analysis of dynamics of corneometry parameters revealed that initially, the skin of acne patients is overdried, most often due to the lack of rational moisturizing skin care (Figure 4). In our study, before the beginning of treatment with systemic LIDOSE form isotretinoin, we selected adequate moisturizing skin care for all patients, that is why even against the background of treatment with retinoid, our patients showed an improvement in the indicators of moisture in the forehead, chin skin areas (p<0.01), and in the cheek area (p<0.05).
The sebosuppressive effect of systemic LIDOSE form isotretinoin is rather pronounced, as shown in Figure 5, which demonstrates the dynamics of changes in the sebumetry indicators in patients in the forehead area, as this very area is the most appropriate for the assessing the characteristics of sebaceous glands secretion (here, the surface skin lipids are mainly secreted by sebaceous glands, and the share of lipids secreted by corneocytes amounts to 3-6%). A decrease in the sebumetry indicators is observed throughout the treatment process.
Figure 4. Dynamics of corneometry indicators in the forehead area against the background of LIDOSE form isotretinoin
therapy.
Figure 5. Dynamics of sebumetry indicators in the forehead area against the background of LIDOSE form isotretinoin
therapy.
Conclusion
Our study showed high efficacy (90% of clinical recovery) and good tolerability of treatment of moderate acne with LIDOSE form isotretinoin. In the course of treatment, there was a reliable positive dynamics of objective changes in the skin morphometric indicators covering all links of the disease pathogenesis: strengthening and normalization of differentiation of keratinocytes, strengthening of dermis proliferative capabilities
resulting in a curative effect on already existing scar deformations in acne patients, also prevention of new scars occurs. During acne treatment with systemic LIDOSE form isotretinoin, anti-inflammatory and powerful sebosuppressive effects are observed. Besides, with properly selected and regular use of moisturizing skin care in patients during treatment, it is possible to reduce the most common side effect of therapy, retinoid dermatitis, to minimal manifestations. Thus, the LIDOSE drug
form allows reducing the dose of isotretinoin while maintaining high efficacy and minimal risk of side effects. The morphometric study carried out in dynamics objectively reflected the positive impact of isotretinoin in the LIDOSE form on pathogenetic mechanisms of moderate acne.
Conflict of interest. The authors declare that there is no conflict of interest.
References:
1. Kungurov N.V., Kokhan M.M., O.V. Shabardina O.V. Experience of therapy of patients with moderate and severe acne with isotretinoin
drug. Vestnik Dermatologii i Venerologii. 2013; 1:5662.
2. Akhtyamov S.N. Practical dermatocosmetology. Acne, scars, pitted acne scars and acneiform dermatoses. M., 2010: 280.
3. Adaskevich V.P. Acne vulgaris and rosacea. M., 2003.
4. Samgin M.A., Monakhov S.A. Acne. Etiopathogenesis, clinic, therapy. Guidance manual for doctors. M., 2012.
5. Masukova S.A., Sanakoeva E.G., Ilyina I.V. Isotretinoin in acne therapy.Russian Journal of Clinical Dermatology and Venereology. 2012; 2: 79-85.
6. Eady EA, Gloor M, Leyden JJ. Propionibacterium acnes resistanse: a worldvite problem. Dermatology. 2003; 20(6): 54 -56.
7. Lehucher-Ceyrac D, Weber-Buisset MJ. Isotretinoin and acne in practice: a prospective analysis of 188 cases over 9 years. Dermatology. 1993; 186: 123-128.
8. Volkova E.N., Osipova N.K., Grigorjeva A.A. et al. Progressive technologies in managements of patients with acne. Russian Journal of Clinical Dermatology and Venereology. 2010; 1: 74-78.
9. Panova O.S., Gubanova E.I., Lapatina N.G. et al. Modern methods of assessing aquation and biomechanical skin features. Vestnik Dermatologii i Venerologii. 2009; 2: 80-87.
10. Sergeeva I.G., Krinitsyna V.V., Onipchen-ko V.V. et al. Clinical and morphological characteristics of the skin condition in acne patients in dynamics of LIDOSE form isotretinoin therapy. Vestnik Dermatologii i Venerologii. 2012; 5: 120-126.
11. Goryachkina M.V., Belousova T.A. Differentiated approach to selection of dermatocosmet-ic agents in complex treatment of acne in women. Vestnik Dermatologii i Venerologii. 2012; 6: 96-103.
12. Kang S, Cho S, Chung JH, et al. Inflammation and extracellular matrix degradation mediated by activated transcription factors nuclear factor-kappa B and activator protein-1 in inflammatory acne lesions in vivo. Am J Patol. 2005; 166: 1691.
13. Baumann L. Cosmetic dermatology. Principles and practice. Ed. N.N. Potekaeva. M., 2012: 688.
14. Trivedi NR, Gilliland KL, Zhao W, et al. Gene array expression profiling in acne lesions reveals marked upregulation of genes involved in inflammation and matrix remodeling. J Invest Dermatol. 2006; 126: 1071.
15. Layton AM. Optimal management of acne to prevent scarring and psychological sequelae. Am J Clin Dermatol. 2001; 2: 135.
16. Janssen de Limpens AM. The local treatment of hypertrophic scars and keloids with topical retinoic acid. Br J Dermatol. 1980; 103: 319.
17. Mizutani H, Yoshida T, Nouchi N, et al. Topical tocoretinate improved hypertrophic scar, skin sclerosis in systemic sclerosis and morphea. J Dermatol. 1999; 26: 11.
Contacts
Corresponding author: Abdukhalikova Maria Leonidovna, cosmetologist of the Cosmetology Department, Regional Dermatovenerologic Dispensary, Irkutsk. 664011, Irkutsk, ul. Gusarova, 2. Tel.: 8 (950) 0691917. E-mail: [email protected]
Author information
Malova Irina Olegovna, Doctor of Medical Sciences, Professor of the Department of Dermatovene-reology and Cosmetology, Irkutsk State Medical University, Irkutsk.
664003, Irkutsk, ul. Krasnogo Vosstaniya, 1.
Tel.: (3952) 242313.
E-mail: [email protected]
