Acne treatment: review of consensus

The basic principles of acne treatment are well known and have been studied in sufficient detail. The purpose of this review is to show what approaches to acne treatment are accepted in different countries of the world, as well as to identify their similarities and differences

Acne occurs in 85–90% of adolescent patients, as well as in 64% of twenty-year-old men and women and 43% of thirty-year-old and older people. The prevalence of the disease among women is higher than among men.

Pathogenesis of acne

German researcher Gollnick HP and a group of co-authors and the Global Alliance to Improve Acne Treatment Outcomes agreed that acne should be considered a chronic disease rather than a “simple, limited disease of adolescents.” This statement is based on the known characteristics of a chronic disease: slow onset or sharp exacerbation of the process, negative impact on quality of life, extended course of treatment, possibility of relapse.

The pathogenesis of acne is characterized by the presence of several factors. Hereditarily caused hyperandrogenism is the initial link in the development of this nosology. Androgen-induced increased secretion of sebum leads to hypercolonization of the skin by the microorganisms Propionibacterium acnes. Due to a deficiency of linoleic acid, keratinization of the epidermis occurs, namely, excessive thickening of the stratum corneum of the skin in the funnel of the hair follicles, where the duct of the sebaceous gland opens, and increased permeability to water and products of bacterial metabolism. Activation of the process of lipid peroxidation as a result of microperforation of the follicular barrier causes the formation of an inflammatory reaction.

It is worth mentioning the immune disorders that manifest themselves in severe forms of acne (indurative, abscessing, phlegmonous acne), characterized by a decrease in immunity and an increase in the level of circulating immune complexes (CIC) and serum immunoglobulins M and G. We should also not forget about insulin resistance, which is often found in men and women with acne combined with metabolic syndrome.

Inflammatory elements persist in 50% of patients into adulthood. They also develop such negative phenomena as post-acne scars and persistent hyperpigmentation, which, in turn, can lead to anxiety and depressive disorders and dysmorphophobia. Therefore, specialists around the world in the field of dermatology and cosmetology regularly review existing recommendations regarding the treatment of patients with acne, conduct new research aimed at modernizing approaches to the treatment of acne and restoring skin in remission.

The importance of consensus

In many countries, clinical recommendations, or so-called consensuses, for the treatment of acne have been adopted and established as medical standards. What are they needed for?

Firstly, the prerequisite for the creation of unified recommendations for the treatment of acne was the need to systematize approaches to the choice of treatment, as well as the practicality of use by specialists due to the fact that the number of developed drugs and methods of treatment for this disease is huge. The modern stage of development of medicine requires a comprehensive approach to the treatment of acne, that is, the patient should be observed not only by a dermatologist, but also by doctors of other specialties.

Secondly, not all of the existing methods may have proven evidence in the scientific literature and may cause harm to the patient, be expensive and ineffective. It should be mentioned that acne treatment consensuses are based on three levels of evidence-based medicine, namely high-quality meta-analyses, systematic reviews of randomized controlled trials (RCTs) or RCTs with very low risk of bias, systematic reviews of case-control studies, or cohort studies, descriptions of clinical cases. Therefore, there is no doubt that the consensus only describes in detail treatment methods with a large scientific evidence base.

In order to identify similarities and differences in clinical recommendations from different countries, we analyzed the consensuses adopted by the American Academy of Dermatology, the European Academy of Dermatology and Venereology, the Russian Society of Dermatovenerology, and the countries of Southeast Asia. Special attention should be paid to the consensuses adopted in Germany and Spain, which have their own characteristics, as well as recommendations for the treatment of pediatric acne, developed in the USA, and post-pubertal acne, adopted by the European Academy of Dermatology and Venereology.

Consensus structure

First of all, it is worth considering the principle of structuring clinical recommendations for prescribing certain groups of drugs in the treatment of acne. Today there is no single universal acne classification system accepted in all countries. Treatment algorithms are based on two approaches to systematization: according to the severity of the disease or the form of clinical manifestations.

The basis of the American and Asian consensus recommendations is the severity of the disease: mild, moderate and severe. On the contrary, the recommendations of European countries and the Russian Federation are based on a classification according to the clinical forms of acne and are divided into four groups: comedonal, mild and moderate papulopustular, severe papulopustular and moderate nodular, severe nodular/conglobate acne. The German authors of the consensus took a more detailed approach to the algorithms for the treatment of acne and identified treatment recommendations separately for mild and moderate papulopustular forms, as well as for nodular and conglobate forms.

The guiding principle for prescribing treatment in the European Consensus and Russian Clinical Guidelines is to divide the strength of the recommendations into high, medium and low, depending on the quality of the evidence supporting the recommendations for each form of acne.

The American Academy of Dermatology, as well as a group of authors from Southeast Asia, reviews first-line treatment and alternative therapies for each acne severity level. However, the Asian Consensus still has a section on maintenance therapy, which distinguishes it from all the guidelines described above.

The German clinical guidelines are interesting in that the authors propose to systematize first-line treatment algorithms, alternative treatment, therapy for postpubertal women and in the case of pregnancy, as well as maintenance therapy for each of the five forms of acne.

Fifteen dermatologists participated in the Spanish consensus. By voting, the group of experts sought to reach consensus. Subsequently, the first-line treatment algorithms that received the most votes were adopted, and the second-line treatment algorithms that were accepted for consideration but did not receive unanimous support from the scientific group.

Acne treatment in Southeast Asia differs slightly from practices elsewhere in the world due to the characteristics of Asian skin. It is more susceptible to developing post-inflammatory hyperpigmentation and irritation when treated with topical retinoids, which is reflected in the consensus recommendations. A scientific group of thirteen leading dermatologists from Indonesia, Malaysia, the Philippines, Singapore, Thailand and Vietnam published a review of current acne treatment guidelines and developed regional guidelines for the treatment of acne.

Post-pubertal acne

Separately, it is worth considering the consensus on the treatment of postpubertal acne. Postpubertal acne can be late and persistent. Persistent acne is a condition that remains from adolescence, while late-onset acne first appears after the age of 18–25. This consensus is fundamentally different in that it is aimed at treating women of reproductive age. Consequently, the prescription of isotretinoin is quite difficult due to the desire of women to become pregnant, so alternative methods of treating acne are prescribed here. This is also the only consensus where special attention is paid to methods for correcting the post-acne symptom complex - scarring, post-inflammatory dyschromia, changes in the vascular pattern (stagnant spots, persistent erythema, telangiectasia).

Pediatric acne

Disease initiation, differential diagnosis, and acne-associated diseases vary by age. In this regard, in the United States, a group of pediatricians and dermatologists created a consensus on the treatment of pediatric acne based on evidence for the treatment of children with this nosology. The beginning of human life is divided into periods: newborn, infant, preschool and prepubertal. In each of them there are cases of acne. As a result of a thorough analysis of these data, experts came to the conclusion that treatment should be carried out only under the supervision of a pediatric endocrinologist, since the appearance of acne in childhood may indicate endocrinological pathology (for example, congenital adrenal hyperplasia) or the presence of androgen secretory tumors. Specific therapy, including local retinoids, antiseptics and the use of a topical antibiotic (erythromycin), is prescribed by a dermatologist in rare cases.

Principles of treatment

Around the world, when prescribing treatment for acne, it is prescribed to take into account three important factors: age, psychosocial disorder and comorbidities.

Isotretinoin is contraindicated in children under 12 years of age, but the doctor may prescribe it in severe cases. Tetracycline antibiotics are contraindicated in children under 8 years of age.

Significant psychosocial stress associated with acne increases the severity of the disease by one level, which, accordingly, should be reflected in the therapy prescribed to the patient.

Concomitant diseases associated with acne are primarily hormonal in nature. Thus, women with signs of virilization should, first of all, undergo a full examination and treatment by a gynecologist-endocrinologist. In this case, together with the dermatologist, a decision is made on the further prescription of isotretinoin.

Prescription of drug therapy

In all consensuses, the main groups of drugs recommended for topical use are topical retinoids, benzoyl peroxide, topical antibiotics, and azelaic acid. Systemic antibiotics and isotretinoin are used as systemic therapy. Additional treatment is a group of combined oral contraceptives with an antiandrogenic effect when absolute or relative hyperandrogenism is detected. This decision on the appointment is made by a gynecologist-endocrinologist based on the results of tests and examination.

Treatment algorithms for certain groups of drugs in different countries have their own characteristics.

Mild acne ⎼ in particular, with mild comedonal and moderate papulopustular forms ⎼ implies the prescription of both single-drug topical therapy and a combination of drugs. When treating pubertal acne, the use of topical retinoids and benzoyl peroxide, and in some cases azelaic acid, is recommended. There is no evidence of significant systemic absorption of topical retinoids, but given their known oral teratogenicity, postpubertal women are not advised to become pregnant during topical retinoid treatment. As for azelaic acid, it is the drug of choice for post-pubertal acne as monotherapy for both non-inflammatory and inflammatory acne, as well as for post-inflammatory hyperpigmentation. Azelaic acid demonstrates similar efficacy to other topical treatments for mild to moderate acne and provides a favorable tolerability profile, including during pregnancy and breastfeeding, and high patient satisfaction rates.

In European and Russian recommendations, the drug of choice is adapalene in combination with benzoyl peroxide or a topical antibiotic (clindamycin). Dermatologists in Southeast Asia adhere to similar treatment tactics, but as an alternative therapy they prescribe topical preparations containing salicylic acid and sulfur. According to American experts, topical use of Dapsone gel 5% is recommended for mild acne, especially in adult women, when previous local treatment has not produced results.

For moderate acne, experts in the USA, Europe and Southeast Asia unanimously decided to prescribe a systemic antibiotic, while maintaining recommendations for the use of topical therapy with benzoyl peroxide and retinoids; a topical antibiotic is prescribed in extreme cases. In a consensus on postpubertal acne, Dreno B. et al. prescribe treatment algorithms using groups of tetracyclines (lymecycline, doxycycline, minocycline) and macrolides (erythromycin).

The European and Russian consensus directive prescribes the use of isotretinoin in patients with severe papulopustular, nodular and conglobate forms of acne. In contrast, the first-line treatment of the German, Spanish and Southeast Asian consensus, as well as the European consensus on postpubertal acne, is systemic antibiotics in combination with topical retinoids and benzoyl peroxide. Following the recommendations of the American Academy of Dermatology, isotretinoin is used only in cases of failure to respond to treatment with a course of systemic antibiotics and a combination of local therapy.

For severe acne with a nodular/conglobate form and a high risk of scarring, all world experts unanimously recommend the use of oral isotretinoin.

Maintenance therapy for acne

According to the consensus of Germany, Spain and Southeast Asian countries, topical retinoids alone or in combination with benzoyl peroxide should be used as maintenance therapy for acne. A feature of the Spanish consensus is the recommendation for the use of alpha hydroxy acid. For postpubertal women, it is recommended to combine azelaic acid 15⎼20% with topical retinoids (for example, adapalene 0.1% or tazarotene 0.1%). Local or systemic antibiotics are not recommended for use. When adjusting the duration of maintenance therapy, it is necessary to take into account the effectiveness of the drug, its tolerability and the patient’s adherence to treatment.

When prescribing therapy for women with postpubertal acne, an integrated approach should be used, combining standard treatment algorithms and auxiliary cosmetological techniques, and taking into account the specific characteristics of aging skin. Other factors that must be taken into account include the extent, severity and duration of the disease, response to previous treatment, and susceptibility to scar formation and inflammatory hyperpigmentation. Cosmetic treatments include light therapy (lasers, blue, blue-red, enhanced pulsed light, pulsed dye lasers and photodynamic therapy), chemical peels based on glycolic acid (30, 35, 50 or 70%), salicylic acid (20– 30%) and Jessner's solution, mechanical procedures including comedonal extraction and dermabrasion.

Thus, we see how similar and at the same time different approaches to treating such a common problem as acne are. It is necessary to take into account all factors of pathogenesis together. In addition to similar manifestations of the disease, there are national and climatic features that should be remembered.

An interdisciplinary approach is also required in treatment. Cooperation of dermatologists and dermatocosmetologists with gynecologists-endocrinologists, andrologists and therapists, as well as an individually selected set of drugs will give the best result.

Literature:

Alena Kislitsyna, resident physician, Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology, Department of Health (DZM) (Russia)

Anna Sergeeva, dermatovenerologist, cosmetologist at Professor Yutskovskaya Clinic LLC, teacher at Professor Yutskovskaya School LLC (Russia)

Les Nouvelles Esthetiques Ukraine 5 (105)/2017