Russian Journal of Skin and Venereal DiseasesRussian Journal of Skin and Venereal DiseasesРоссийский журнал кожных и венерических болезней1560-95882412-9097Eco-Vector6003910.17816/dv60039CLINICAL PICTURE, DIAGNOSIS, AND THERAPY OF DERMATOSESКЛИНИКА, ДИАГНОСТИКА И ЛЕЧЕНИЕ ДЕРМАТОЗОВResearch ArticleMicrobiome and acne vulgarisМикробиом и вульгарные угриMaZiyuanМаЦзыюань
Russian Federation

Post-graduate student of the Department of Skin and Venereal Diseases named after V.A. Rakhmanov, Institute of Clinical Medicine named after N.V. Sklifosovsky

аспирант кафедры кожных и венерических болезней им В.А.Рахманова Института клинической медицины им Н.В.Склифосовского

stephanie92@foxmail.comhttps://orcid.org/0000-0001-7136-40536602082412KocherginNikolay G.КочергинНиколай Георгиевич
Russian Federation

dr. medical sciences, prof. Department of Skin and Venereal Diseases named after V.A. Rakhmanov Institute of Clinical Medicine named after V.A. N.V. Sklifosovsky

д-р. мед наук, проф. кафедры кожных и венерических болезней им. В.А.Рахманова Института клинической медицины им. Н.В.Склифосовского

nkocha@yandex.ruI.M. Sechenov First Moscow State Medical University (Sechenov University)ФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет)151220202363883940402202122032021Copyright ©; 2020, Eco-VectorCopyright ©; 2020, ООО "Эко-Вектор"2020Eco-VectorООО "Эко-Вектор"https://rjsvd.com/1560-9588/article/view/60039

Acne vulgaris is a highly prevalent inflammatory skin disease involving sebaceous follicle. Although the pathogensis of acne remains uncertain, skin microbes are considered to plays an essential role in acne vulgaris. Cutibacterium acnes is the most important microbe in acne pathogenesis and its several processes: colonization, over-proliferation and inflammation have long been thought to contribute to the disease. Moreover, Staphylococcus epidermidis and Malassezia also synergistically collaborate with Cutibacterium acnes. Besides, given the growing number of patients who are treatment resistant, assessments are needed on phenotypic changes in the skin microbiome with retinoids and antibacterial therapy. Further research on the role of microbes in the pathogenesis of acne and the relationship between pathogenic microbes is expected to provide a new theoretical basis for clinical treatment of acne.

Вульгарные угри – широко распространённое воспалительное заболевание кожи с участием сальных фолликулов. Хотя патогенез акне до конца не изучен, считается, что кожные микробы Cutibacterium acnes играют важную роль в развитии вульгарных угрей. Колонизация C. acnes, их чрезмерное размножение с последующим воспалением, как давно признано, способствуют развитию болезни. Более того, Staphylococcus epidermidis и Malassezia также синергетически взаимодействуют с C. acnes. Таким образом, с учётом растущего числа пациентов, устойчивых к лечению, необходима оценка фенотипических изменений микробиома кожи под воздействием ретиноидов и антибактериальной терапии. Ожидается, что дальнейшее исследование роли микробов в патогенезе угрей и взаимосвязи между патогенными микробами обеспечит новую теоретическую основу для терапевтических подходов к акне.

acne vulgarismicrobiomeantibactiral therapiesretinoidsвульгарные угримикробиомантибактериальная терапияретиноидыMonakhov SA, Ivanov OL. Acne: Handbook for Physicians. Moscow; 2010. (in Russian)Монахов С.А., Иванов О.Л. Акне. Методическое пособие для врачей. М.; 2010.Tan JK, Bhate K. A global perspective on the epidemiology of acne. Br J Dermatol. 2015;172(Suppl 1):3-12.Tan J.K., Bhate K. A global perspective on the epidemiology of acne. Br J Dermatol. 2015;172(Suppl 1):3-12.Nelyubova OI, Talnikova EE, Morrison AV. The skin microbiome and its role in health and disease. Russian Journal of Skin and Venereal Diseases. 2016;19(2):97. (in Russian)Нелюбова О.И., Тальникова Е.Е., Моррисон А.В. Микробиом кожи и его роль в норме и патологии // Российский журнал кожных и венерических болезней. 2016;19(2):97.Araviyskaya ER, Sokolovsky EV. The microbiome: a new era in the study of healthy and diseased skin // Vestnik Dermatologii i Venerologii. 2016;(3):102-9. (in Russian)Аравийская Е.Р., Соколовский Е.В. Микробиом: новая эра в изучении здоровой и патологически измененной кожи // Вестник дерматологии и венерологии 2016;(3):102-9.Gilchrist TC. A bacteriological and microscopical study of over 300 vesicular and pustular lesions of the skin, with a research upon the etiology of acne vulgaris. Johns Hopkins Hospital Report. 1900;(9):409-30.Gilchrist T.C. A bacteriological and microscopical study of over 300 vesicular and pustular lesions of the skin, with a research upon the etiology of acne vulgaris». Johns Hopkins Hospital Report. 1900;(9):409-30.Douglas HC, Gunter SE. The taxonomic position of Corynebacterium acnes. J Bacteriol. 1946;52(1):15-23.Douglas H.C., Gunter S.E. The taxonomic position of Corynebacterium acnes. J Bacteriol. 1946;52(1):15-23.Scholz CF, Kilian M. The natural history of cutaneous propionibacteria, and reclassification of selected species within the genus Propionibacterium to the proposed novel genera Acidipropionibacterium gen. nov., Cutibacterium gen. nov. and Pseudopropionibacterium gen. nov. Int J Syst Evol Microbiol. 2016;66(11):4422-32.Scholz C.F., Kilian M. The natural history of cutaneous propionibacteria, and reclassification of selected species within the genus Propionibacterium to the proposed novel genera Acidipropionibacterium gen. nov., Cutibacterium gen. nov. and Pseudopropionibacterium gen. nov. Int J Syst Evol Microbiol. 2016;66(11):4422-32.Fitz-Gibbon S, Tomida S, Chiu BH, Nguyen L, Du C, Liu M, et al. Propionibacterium acnes strain populations in the human skin microbiome associated with acne. J Invest Dermatol. 2013;133(9):2152-60.Fitz-Gibbon S., Tomida S., Chiu B.H., Nguyen L., Du C., Liu M., et al. Propionibacterium acnes strain populations in the human skin microbiome associated with acne. J Invest Dermatol. 2013;133(9):2152-60.Suskova VS, Pinson IYa, Olisova OYu. Immunopathological mechanisms of psoriasis. Russian Journal of Clinical Dermatology and Venereology. 2006;4(1):68-70. (in Russian)Сускова В.С., Пинсон И.Я., Олисова О.Ю. Иммунопатогенез псориаза // Клиническая дерматология и венерология. 2006;4(1):68-70.Graham GM, Farrar MD, Cruse-Sawyer JE, Holland KT, Ingham E. Proinflammatory cytokine production by human keratinocytes stimulated with Propionibacterium acnes and P. acnes GroEL. Br J Dermatol. 2004;150(3):421-8.Graham G.M., Farrar M.D., Cruse-Sawyer J.E., Holland K.T., Ingham E. Proinflammatory cytokine production by human keratinocytes stimulated with Propionibacterium acnes and P. acnes GroEL. Br J Dermatol. 2004;150(3):421-8.Jugeau S, Tenaud I, Knol AC, Jarrousse V, Quereux G, Khammari A, Dreno B. Induction of Toll-like receptors by Propionibacterium acnes. Br J Dermatol. 2005;153(6):1105-13.Jugeau S., Tenaud I., Knol A.C., Jarrousse V., Quereux G., Khammari A., Dreno B. Induction of Toll-like receptors by Propionibacterium acnes. Br J Dermatol. 2005;153(6):1105-13.Mouser PE, Baker BS, Seaton ED, Chu AC. Propionibacterium acnes-reactive Th1 cells in the skin of patients with acne vulgaris. J Invest Dermatol. 2003;121(5):1226-8.Mouser P.E., Baker B.S., Seaton E.D., Chu A.C. Propionibacterium acnes-reactive Th1 cells in the skin of patients with acne vulgaris. J Invest Dermatol. 2003;121(5):1226-8.Kistowska M, Meier B, Proust T, Feldmeyer L, Cozzio A, Kuendig T, et al. Propionibacterium acnes promotes Th17 and Th17/Th1 responses in acne patients. J Invest Dermatol. 2015;135(1):110-8.Kistowska M., Meier B., Proust T., Feldmeyer L., Cozzio A., Kuendig T., et al. Propionibacterium acnes promotes Th17 and Th17/Th1 responses in acne patients. J Invest Dermatol. 2015;135(1):110-8.Isard O, Knol AC, Aries MF, Nguyen JM, Khammari A, CastexRizzi N, Dreno B. Propionibacterium acnes activates the IGF-1/IGF-1R system in the epidermis and induces keratinocyte proliferation. J Invest Dermatol. 2011;131(1):59-66.Isard O., Knol A.C., Aries M.F., Nguyen J.M., Khammari A., Castex-Rizzi N., Dreno B. Propionibacterium acnes activates the IGF-1/IGF-1R system in the epidermis and induces keratinocyte proliferation. J Invest Dermatol. 2011;131(1):59-66.Huang YC, Yang CH, Li TT, Zouboulis CC, Hsu HC. Cell-free extracts of Propionibacterium acnes stimulate cytokine production through activation of p38 MAPK and Toll-like receptor in SZ95 sebocytes. Life Sci. 2015;139:123-31.Huang Y.C., Yang C.H., Li T.T., Zouboulis C.C., Hsu H.C. Cell-free extracts of Propionibacterium acnes stimulate cytokine production through activation of p38 MAPK and Toll-like receptor in SZ95 sebocytes. Life Sci. 2015;139:123-31.Zouboulis CC, Jourdan E, Picardo M. Acne is an inflammatory disease and alterations of sebum composition initiate acne lesions. J Eur Acad Dermatol Venereol. 2014;28(5):527-32.Zouboulis C.C., Jourdan E., Picardo M. Acne is an inflammatory disease and alterations of sebum composition initiate acne lesions. J Eur Acad Dermatol Venereol. 2014;28(5):527-32.Beylot C, Auffret N, Poli F, Claudel JP, Leccia MT, Del Giudice P, Dreno B. Propionibacterium acnes: an update on its role in the pathogenesis of acne. J Eur Acad Dermatol Venereol. 2014;28(3):271-8.Beylot C., Auffret N., Poli F., Claudel J.P., Leccia M.T., Del Giudice P., Dreno B. Propionibacterium acnes: an update on its role in the pathogenesis of acne. J Eur Acad Dermatol Venereol. 2014;28(3):271-8.McDowell A, Barnard E, Liu J, Li H, Patrick S. Corrigendum: Proposal to reclassify Propionibacterium acnes type I as Propionibacterium acnes subsp. acnes subsp. nov. and Propionibacterium acnes type II as Propionibacterium acnes subsp. defendens subsp. nov. Int J Syst Evol Microbiol. 2017;67(11):4880.McDowell A., Barnard E., Liu J., Li H., Patrick S. Corrigendum: Proposal to reclassify Propionibacterium acnes type I as Propionibacterium acnes subsp. acnes subsp. nov. and Propionibacterium acnes type II as Propionibacterium acnes subsp. defendens subsp. nov. Int J Syst Evol Microbiol. 2017;67(11):4880.Dekio I, McDowell A, Sakamoto M, Tomida S, Ohkuma M. Proposal of new combination, Cutibacterium acnes subsp. elongatum comb. nov., and emended descriptions of the genus Cutibacterium, Cutibacterium acnes subsp. acnes and Cutibacterium acnes subsp. defendens. Int J Syst Evol Microbiol. 2019;69(4):1087-92.Dekio I., McDowell A., Sakamoto M., Tomida S., Ohkuma M. Proposal of new combination, Cutibacterium acnes subsp. elongatum comb. nov., and emended descriptions of the genus Cutibacterium, Cutibacterium acnes subsp. acnes and Cutibacterium acnes subsp. defendens. Int J Syst Evol Microbiol. 2019;69(4):1087-92.Dekio I, Culak R, Misra R, Gaulton T, Fang M, Sakamoto M, et al. Dissecting the taxonomic heterogeneity within Propionibacterium acnes: Proposal for Propionibacterium acnes subsp. acnes subsp. nov. and Propionibacterium acnes subsp. elongatum subsp. nov. Int J Syst Evol Microbiol. 2015;65(12):4776-87.Dekio I., Culak R., Misra R., Gaulton T., Fang M., Sakamoto M., et al. Dissecting the taxonomic heterogeneity within Propionibacterium acnes: Proposal for Propionibacterium acnes subsp. acnes subsp. nov. and Propionibacterium acnes subsp. elongatum subsp. nov. Int J Syst Evol Microbiol. 2015;65(12):4776-87.McDowell A, Barnard E, Nagy I, Gao A, Tomida S, Li H, et al. An expanded multilocus sequence typing scheme for propionibacterium acnes: investigation of ‘pathogenic’, ‘commensal’ and antibiotic resistant strains. PLoS One. 2012;7(7):e41480.McDowell A., Barnard E., Nagy I., Gao A., Tomida S., Li H., et al. An expanded multilocus sequence typing scheme for propionibacterium acnes: investigation of ‘pathogenic’, ‘commensal’ and antibiotic resistant strains. PLoS One. 2012;7(7):e41480.Kwon HH, Yoon JY, Park SY, Suh DH. Analysis of distribution patterns of Propionibacterium acnes phylotypes and Peptostreptococcus species from acne lesions. Br J Dermatol. 2013;169(5):1152-5.Kwon H.H., Yoon J.Y., Park S.Y., Suh D.H. Analysis of distribution patterns of Propionibacterium acnes phylotypes and Peptostreptococcus species from acne lesions. Br J Dermatol. 2013;169(5):1152-5.Holland KT, Cunliffe WJ, Eady EA. Intergeneric and intrageneric inhibition between strains of Propionibacterium acnes and micrococcaceae, particularly Staphylococcus epidermidis, isolated from normal skin and acne lesions. J Med Microbiol. 1979;12(1):71-82.Holland K.T., Cunliffe W.J., Eady E.A. Intergeneric and intrageneric inhibition between strains of Propionibacterium acnes and micrococcaceae, particularly Staphylococcus epidermidis, isolated from normal skin and acne lesions. J Med Microbiol. 1979;12(1):71-82.Mertz D, Frei R, Periat N, Zimmerli M, Battegay M, Fluckiger U, Widmer AF. Exclusive Staphylococcus aureus throat carriage: At-risk populations. Arch Intern Med. 2009;169(2):172-8.Mertz D., Frei R., Periat N., Zimmerli M., Battegay M., Fluckiger U., Widmer A.F. Exclusive Staphylococcus aureus throat carriage: At-risk populations. Arch Intern Med. 2009;169(2):172-8.Fanelli M, Kupperman E, Lautenbach E, Edelstein PH, Margolis DJ. Antibiotics, acne, and Staphylococcus aureus colonization. Arch Dermatol. 2011;147(8):917-21.Fanelli M., Kupperman E., Lautenbach E., Edelstein P.H., Margolis D.J. Antibiotics, acne, and Staphylococcus aureus colonization. Arch Dermatol. 2011;147(8):917-21.Khorvash F, Abdi F, Kashani HH, Naeini FF, Narimani T. Staphylococcus aureus in Acne Pathogenesis: A Case-Control Study. N Am J Med Sci. 2012;4(11):573-6.Khorvash F., Abdi F., Kashani H.H., Naeini F.F., Narimani T. Staphylococcus aureus in Acne Pathogenesis: A Case-Control Study. N Am J Med Sci. 2012;4(11):573-6.Fey PD, Olson ME. Current concepts in biofilm formation of Staphylococcus epidermidis.Future Microbiol. 2010;5(6):917-33.Fey P.D., Olson M.E. Current concepts in biofilm formation of. Future Microbiol. 2010;5(6):917-33.Pathak R, Kasama N, Kumar R, Gautam H. Staphylococcus epidermidis in human skin microbiome associated with acne: A cause of disease or defence? Res J Biotechnol. 2013;8(12):78-82.Pathak R., Kasama N., Kumar R., Gautam H. Staphylococcus epidermidis in human skin microbiome associated with acne: A cause of disease or defence? Res J Biotechnol. 2013;8(12):78-82.Otto M. Staphylococcus epidermidis – the ‘accidental’ pathogen. Nat Rev Microbiol. 2009;7(8):555-67.Stevens NT, Sadovskaya I, Jabbouri S, Sattar T, O’Gara JP, Humphreys H, Greene CM. Staphylococcus epidermidis polysaccharide intercellular adhesin induces IL-8 expression in human astrocytes via a mechanism involving TLR2. Cell Microbiol. 2009;11(3):421-32.Stevens N.T., Sadovskaya I., Jabbouri S., Sattar T., O’Gara J.P., Humphreys H., Greene C.M. Staphylococcus epidermidis polysaccharide intercellular adhesin induces IL-8 expression in human astrocytes via a mechanism involving TLR2. Cell Microbiol. 2009;11(3):421-32.Christensen GJ, Scholz CF, Enghild J, Rohde H, Kilian M, Thurmer A, et al. Antagonism between Staphylococcus epidermidis and Propionibacterium acnes and its genomic basis. BMC Genomics. 2016;17:152.Christensen G.J., Scholz C.F., Enghild J., Rohde H., Kilian M., Thurmer A., et al. Antagonism between Staphylococcus epidermidis and Propionibacterium acnes and its genomic basis. BMC Genomics. 2016;17:152.Lai Y, Cogen AL, Radek KA, Park HJ, Macleod DT, Leichtle A, et al. Activation of TLR2 by a small molecule produced by Staphylococcus epidermidis increases antimicrobial defense against bacterial skin infections. J Invest Dermatol. 2010;130(9):2211-21.Lai Y., Cogen A.L., Radek K.A., Park H.J., Macleod D.T., Leichtle A., et al. Activation of TLR2 by a small molecule produced by Staphylococcus epidermidis increases antimicrobial defense against bacterial skin infections. J Invest Dermatol. 2010;130(9):2211-21.Xia X, Li Z, Liu K, Wu Y, Jiang D, Lai Y. Staphylococcal LTA-induced miR-143 inhibits Propionibacterium acnes – mediated inflammatory response in skin. J Invest Dermatol. 2016;136(3):621-30.Xia X., Li Z., Liu K., Wu Y., Jiang D., Lai Y. Staphylococcal LTA-induced miR-143 inhibits Propionibacterium acnes – mediated inflammatory response in skin. J Invest Dermatol. 2016;136(3):621-30.Polesko IV, Osipov GA, Kabaeva TI. Microecology of the human body with seborrhea, atopic dermatitis and acne. Children’s Infections. Russian Journal. 2006;5(3):26-33. (in Russian)Полеско И.В., Осипов Г.А., Кабаева Т.И. Микроэкология организма человека при себорее, атопическом дерматите и акне. Детские инфекции. 2006;5(3):26-33.Kang SH, Kim HU. The isolation of Malassezia yeasts in the comedones of acne vulgaris. Korean J Med Mycol. 1999;4:33-9. doi: 10.5021/ad.2009.21.1.18.Kang S.H., Kim H.U. The isolation of Malassezia yeasts in the comedones of acne vulgaris. Korean J Med Mycol. 1999;4:33-9. doi: 10.5021/ad.2009.21.1.18.Numata S, Akamatsu H, Akaza N, Yagami A, Nakata S, Matsunaga K. Analysis of facial skin-resident microbiota in Japanese acne patients. Dermatology. 2014;228(1):86-92.Numata S., Akamatsu H., Akaza N., Yagami A., Nakata S., Matsunaga K. Analysis of facial skin-resident microbiota in Japanese acne patients. Dermatology. 2014;228(1):86-92.Coelho MA, Sampaio JP, Gonсalves P. Living and thriving on the skin: Malassezia genomes tell the story. mBio. 2013;4(2):e00117-13.Coelho M.A., Sampaio J.P., Gon?alves P. Living and thriving on the skin: Malassezia genomes tell the story. mBio. 2013;4(2):e00117-13.Akaza N, Akamatsu H, Takeoka S, Mizutani H, Nakata S, Matsunaga K. Increased hydrophobicity in Malassezia species correlates with increased proinflammatory cytokine expression in human keratinocytes. Med Mycol. 2012;50(8):802-10.Akaza N., Akamatsu H., Takeoka S., Mizutani H., Nakata S., Matsunaga K. Increased hydrophobicity in Malassezia species correlates with increased proinflammatory cytokine expression in human keratinocytes. Med Mycol. 2012;50(8):802-10.Song YC, Hahn HJ, Kim JY, Ko JH, Lee YW, Choe YB, Ahn KJ. Epidemiologic study of Malassezia yeasts in acne patients by analysis of 26S rDNA PCR-RFLP. Ann Dermatol. 2011;23(3):321-8. doi:10.5021/ad.2011.23.3.321.Song Y.C., Hahn H.J., Kim J.Y., Ko J.H., Lee Y.W., Choe Y.B., Ahn K.J. Epidemiologic study of Malassezia yeasts in acne patients by analysis of 26S rDNA PCR-RFLP. Ann Dermatol. 2011;23(3):321-8. doi: 10.5021/ad.2011.23.3.321Bek-Thomsen M, Lomholt HB, Kilian M. Acne is not associated with yet-uncultured bacteria. J Clin Microbiol. 2008;46(10):3355-60.Bek-Thomsen M., Lomholt H.B., Kilian M. Acne is not associated with yet-uncultured bacteria. J Clin Microbiol. 2008;46(10):3355-60.Brook I, Frazier EH, Cox ME, Yeager JK. The aerobic and anaerobic microbiology of pustular acne lesions. Anaerobe. 1995;1(6):305-7.Brook I., Frazier E.H., Cox M.E., Yeager J.K. The aerobic and anaerobic microbiology of pustular acne lesions. Anaerobe. 1995;1(6):305-7.Samtsov AV, Araviyskaya ER. Federal clinical guidelines for the management of patients with acne. Moscow: Russian Society of Dermatovenereologists and Cosmetologists; 2013. (in Russian)Самцов А.В., Аравийская Е.Р. Федеральные клинические рекомендации по ведению больных акне. М.: Российское общество дерматовенерологов и косметологов; 2013.Hayashi N, Kurokawa I, Siakpere O, Endo A, Hatanaka T, Yamada M, Kawashima M. Clindamycin phosphate 1.2%/benzoyl peroxide 3% fixed-dose combination gel versus topical combination therapy of adapalene 0.1% gel and clindamycin phosphate 1.2% gel in the treatment of acne vulgaris in Japanese patients: A multicenter, randomized, investigator-blind, parallel-group study. J Dermatol. 2018;45(8):951-62. doi: 10.1111/1346-8138.14497Hayashi N., Kurokawa I., Siakpere O., Endo A., Hatanaka T., Yamada M., Kawashima M. Clindamycin phosphate 1.2%/benzoyl peroxide 3% fixed-dose combination gel versus topical combination therapy of adapalene 0.1% gel and clindamycin phosphate 1.2% gel in the treatment of acne vulgaris in Japanese patients: A multicenter, randomized, investigator-blind, parallel-group study. J Dermatol. 2018;45(8):951-62. doi: 10.1111/1346-8138.14497Snarskaya ES. Antibacterial therapy of acne vulgaris. Vestnik Dermatologii i Venerologii. 2019;95(5):58-67. (in Russian)Снарская Е.С. Антибактериальная терапия вульгарных акне // Вестник дерматологии и венерологии. 2019;95(5):58-67.Eady EA, Cove JH, Holland KT, Cunliffe WJ. Superior antibacterial action and reduced incidence of bacterial resistance in minocycline compared to tetracycline-treated acne patients. Br J Dermatol. 1990;122(2):233-44.Eady E.A., Cove J.H., Holland K.T., Cunliffe W.J. Superior antibacterial action and reduced incidence of bacterial resistance in minocycline compared to tetracycline-treated acne patients. Br J Dermatol. 1990;122(2):233-44.Arzumanyan VG, Masyukova SA, Sergeev AYu, Grebenyuk DV, Ilina IV, Alieva ZA, et al. Sertaconazole and new possibilities of therapy in dermatology. Immunopathology, allergology, infektology. 2016;(4):80-4. (in Russian)Арзуманян В.Г., Масюкова С.А., Сергеев А.Ю., Гребенюк Д.В., Ильина И.В., Алиева З.А. и др. Сертаконазол и новые возможности терапии в дерматологии // Иммунопатология, аллергология, инфектология. 2016;(4):80-4.Borovaya A, Olisova O, Ruzicka T, Sardy M. Does isotretinoin therapy of acne cure or cause depression? Int J Dermatol. 2013;52(9):1040-52. doi: 10.1111/ijd.12169Borovaya A., Olisova O., Ruzicka T., Sardy M. Does isotretinoin therapy of acne cure or cause depression? Int J Dermatol. 2013;52(9):1040-52. doi: 10.1111/ijd.12169Olisova OYu. Effectiveness of systemic retinoids for acne. Russian Medical Journal. 2016;(1):602-6. (in Russian)Олисова О.Ю. Эффективность системных ретиноидов при акне // Русский медицинский журнал. 2016;(10):602-6.Olisova OYu, Ma Ziyuan. Effectivness vs ineffectiveness of systemic retinoids in acne. Effective pharmacotherapy. 2020;16(9):18-22. (in Russian)Олисова О.Ю., Ма Цзыюань. Эффективность vs неэффективность системных ретиноидов при акне // Эффективная фармакотерапия. 2020;16(9):18-22.Lvov AN, Khaldin AA. Experience with the combined gel Isotrexin used in topical therapy for different forms of acne. Russian Journal of Skin and Venereal Diseases. 2008;10(5):83-5. (in Russian)Львов А.Н., Халдин А.А. Опыт применения комбинированного геля Изотрексин в наружной терапии различных форм угревой болезни // Российский журнал кожных и венерических болезней. 2008;10(5):83-5.McCoy WH, Otchere E, Rosa BA, Martin J, Mann CM, Mitreva M. Skin ecology during sebaceous drought-how skin microbes respond to isotretinoin. J Investig Dermatol. 2019;139(3):732-5.McCoy W.H., Otchere E., Rosa B.A., Martin J., Mann C.M., Mitreva M. Skin ecology during sebaceous drought-how skin microbes respond to isotretinoin. J Investig Dermatol. 2019;139(3):732-5.