Acne Clinic: Morphogenesis

  • Gerd Plewig
  • Bodo Melnik
  • WenChieh Chen


The comedo is the initial, primary lesion of acne. It is an impaction of corneocytes within sebaceous follicles. Comedones develop through the following stages.


Dynamics of Comedones

  1. Bek-Thomsen M, Lomholt HB, Scavenius C, et al. Proteome analysis of human sebaceous follicle infundibula extracted from healthy and acne-affected skin. PLoS One. 2014;9:e107908.CrossRefGoogle Scholar
  2. Blair C, Lewis CA. Pigment in comedones. Br J Dermatol. 1970;82:572–83.CrossRefGoogle Scholar
  3. Brzuszkiewicz E, Weiner J, Wollherr A, et al. Comparative genomics and transcriptomics of Propionibacterium acnes. PLoS One. 2011;6:e21581.CrossRefGoogle Scholar
  4. Capitanio B, Lora V, Ludovici M, et al. Modulation of sebum oxidation and interleukin-1α levels associates with clinical improvement of mild comedonal acne. J Eur Acad Dermatol Venereol. 2014;28:1792–7.CrossRefGoogle Scholar
  5. Chapman SJ, Walsh A. Desmosomes, corneosomes and desquamation. An ultrastructure study of adult pig epidermis. Arch Dermatol Res. 1990;282:304–10.CrossRefGoogle Scholar
  6. Downie MM, Sanders DA, Kealey T. Modelling the remission of individual acne lesions in vitro. Br J Dermatol. 2002;147:869–78.CrossRefGoogle Scholar
  7. Eckhart L, Lippens S, Tschachler E, Declercq W. Cell death by cornification. Biochim Biophys Acta. 2013;1833:3471–80.CrossRefGoogle Scholar
  8. Germann H, Barran W, Plewig G. Morphology of corneocytes from human nail plates. J Invest Dermatol. 1980;74:115–8.CrossRefGoogle Scholar
  9. Hölzle E, Plewig G, Ledolter A. Corneocyte exfoliative cytology: a model to study normal and diseased stratum corneum. In: Marks R, Plewig G, editors. Skin models. Berlin: Springer; 1986. p. 183–93.CrossRefGoogle Scholar
  10. Hou SYE, Mitra AK, White SH, et al. Membrane structures in normal and essential fatty acid-deficient stratum corneum: characterization by ruthenium tetroxide staining and x-ray diffraction. J Invest Dermatol. 1991;96:215–23.CrossRefGoogle Scholar
  11. Jeremy AH, Holland DB, Roberts SG, et al. Inflammatory events are involved in acne lesion initiation. J Invest Dermatol. 2003;121:20–7.CrossRefGoogle Scholar
  12. Knutson DD. Ultrastructural observations in acne vulgaris: the normal sebaceous follicle and acne lesions. J Invest Dermatol. 1974;62:288–307.CrossRefGoogle Scholar
  13. Lavker RM, Leyden JJ, McGinley KJ. The relationship between bacteria and the abnormal follicular keratinization in acne vulgaris. J Invest Dermatol. 1981;77:325–30.CrossRefGoogle Scholar
  14. Leyden JJ, Kligman AM. Hairs in acne comedones. Arch Dermatol. 1972a;106:851–3.CrossRefGoogle Scholar
  15. Leyden JJ, Kligman AM. Hairs in acne comedones. Arch Dermatol. 1972b;106:851–3.CrossRefGoogle Scholar
  16. McGinley KJ, Marples RR, Plewig G. A method for visualizing and quantitating the desquamating portion of the human stratum corneum. J Invest Dermatol. 1969;53:107–11.CrossRefGoogle Scholar
  17. Ottaviani M, Alestas T, Flori E, et al. Peroxidated squalene induces the production of inflammatory mediators in HaCaT keratinocytes: a possible role in acne vulgaris. J Invest Dermatol. 2006;126:2430–7.CrossRefGoogle Scholar
  18. Plewig G. Regional differences of cell sizes in the human stratum corneum. II. Effects of sex and age. J Invest Dermatol. 1970;54:19–23.CrossRefGoogle Scholar
  19. Plewig G, Marples RR. Regional differences of cell sizes in the human stratum corneum. I. J Invest Dermatol. 1970;54:13–8.CrossRefGoogle Scholar
  20. Plewig G, Fulton JE, Kligman AM. Cellular dynamics of comedo formation in acne vulgaris. Arch Dermatol Forsch. 1971;242:12–29.CrossRefGoogle Scholar
  21. Plewig G, Nikolowski J, Wolff HH. Follicular keratinization. In: Marks R, Plewig G, editors. Stratum corneum. Berlin: Springer; 1983. p. 227–36.CrossRefGoogle Scholar
  22. Saurat JH. Strategic targets in acne: the comedone switch in question. Dermatology. 2015;231:105–11.CrossRefGoogle Scholar
  23. Selway JL, Kurczab T, Kealey T, Langlands K. Toll-like receptor 2 activation and comedogenesis: implications for the pathogenesis of acne. BMC Dermatol. 2013;13:10.CrossRefGoogle Scholar
  24. Shaheen B, Gonzalez M. Acne sans Propionibacterium acnes. J Eur Acad Dermatol Venereol. 2013;27:1–10.CrossRefGoogle Scholar

Dynamics of Inflammation

  1. Akamatsu H, Horio T. The possible role of reactive oxygen species generated by neutrophils in mediating acne inflammation. Dermatology. 1998;196:82–5.CrossRefGoogle Scholar
  2. Ingham E, Gowland G, Ward RM, et al. Antibodies to P. acnes and P. acnes exocellular enzymes in the normal population at various ages and in patients with acne vulgaris. Br J Dermatol. 1987;116:805–12.CrossRefGoogle Scholar
  3. Ingham E, Eady A, Goodwin CE, et al. Pro-inflammatory levels of interleukin-1-like bioactivity are present in the majority of open comedones in acne vulgaris. J Invest Dermatol. 1992;98:895–901.CrossRefGoogle Scholar
  4. Kelhälä HL, Palatsi R, Fyhrquist N, et al. IL-17/Th17 pathway is activated in acne lesions. PLoS One. 2014;9:e105238.CrossRefGoogle Scholar
  5. Lee WL, Shalita AR, Suntharalingam K, Fikrig SM. Neutrophil chemotaxis by Propionibacterium acnes lipase and its inhibition. Infect Immun. 1982;35:71–8.PubMedPubMedCentralGoogle Scholar
  6. Leeming JP, Ingham E, Cunliffe WJ. The microbial content and complement C3 cleaving capacity of comedones in acne vulgaris. Acta Derm Venereol. 1988;68:468–73.PubMedGoogle Scholar
  7. Lheure C, Grange PA, Ollagnier G, et al. TLR-2 recognizes Propionibacterium acnes CAMP factor 1 from highly inflammatory strains. PLoS One. 2016;11:e0167237.CrossRefGoogle Scholar
  8. Norris JFB, Cunliffe WJ. A histological and immunocytochemical study of early acne lesions. Br J Dermatol. 1988;118:651–9.CrossRefGoogle Scholar
  9. Puhvel SM, Sakamoto M. A re-evaluation of fatty acids as inflammatory agents in acne. J Invest Dermatol. 1977a;68:93–9.CrossRefGoogle Scholar
  10. Puhvel SM, Sakamoto M. An in vivo evaluation of the inflammatory effect of purified comedonal components in human skin. J Invest Dermatol. 1977b;69:401–6.CrossRefGoogle Scholar
  11. Puhvel SM, Sakamoto M. The chemoattractant properties of comedonal components. J Invest Dermatol. 1978;71:324–9.CrossRefGoogle Scholar
  12. Puhvel SM, Sakamoto M. Cytotaxin production by comedonal bacteria (Propionibacterium acnes, Propionibacterium granulosum and Staphylococcus epidermidis). J Invest Dermatol. 1980;74:36–9.CrossRefGoogle Scholar
  13. Quanico J, Gimeno JP, Nadal-Wollbold F, et al. Proteomic and transcriptomic investigation of acne vulgaris microcystic and papular lesions: insights in the understanding of its pathophysiology. Biochim Biophys Acta. 2017;1861:652–63.CrossRefGoogle Scholar
  14. Sardana K, Verma G. Propionibacterium acnes and the Th1/Th17 axis, implications in acne pathogenesis and treatment. Indian J Dermatol. 2017;62:392–4.CrossRefGoogle Scholar
  15. Scott DG, Cunliffe WJ, Gowland G. Activation of complement—a mechanism for the inflammation in acne. Br J Dermatol. 1979;101:315–20.CrossRefGoogle Scholar
  16. Vowels B, Yang S, Leyden JJ. Induction of proinflammatory cytokines by a soluble factor of Propionibacterium acnes: implications for chronic inflammatory acne. Infect Immun. 1995;63:3158–65.PubMedPubMedCentralGoogle Scholar
  17. Webster GF. Inflammation in acne vulgaris. J Am Acad Dermatol. 1995;33:247–53.CrossRefGoogle Scholar
  18. Webster GF. Inflammatory acne represents hypersensitivity to Propionibacterium acnes. Dermatology. 1998;196:80–1.CrossRefGoogle Scholar
  19. Webster GF, Indrisano JP, Leyden JJ. Antibody titers to Propionibacterium acnes cell wall carbohydrate in nodulocystic acne patients. J Invest Dermatol. 1985;84:496–500.CrossRefGoogle Scholar

Acne Conglobata

  1. Balakirski G, Neis MM, Megahed M. Acne conglobata induced by adalimumab. Eur J Dermatol. 2017;27:320–1.PubMedGoogle Scholar
  2. Grech I, Giatrakos S, Damoraki G, Kaldrimidis P, et al. Impact of TNF haplotypes in the physical course of acne vulgaris. Dermatology. 2014;228:152–7.CrossRefGoogle Scholar
  3. Hennes R, Mack A, Schell H, Vogt HJ. 13-cis-retinoic acid in conglobate acne: a follow-up study of 14 trial centers. Arch Dermatol Res. 1984;276:209–15.CrossRefGoogle Scholar
  4. Marcusson JA, Tyden G. Acne conglobata in transplant patients treated with isotretinoin. Br J Dermatol. 1988;118:310–2.CrossRefGoogle Scholar
  5. Rebora A, Dallegri F, Patrone F. Neutrophil functions in acne conglobata. Dermatologica. 1979;159:217–20.CrossRefGoogle Scholar
  6. Rosner IA, Richter DE, Huettner TL, Kuffner GH, et al. Spondyloarthropathy associated with hidradenitis suppurativa and acne conglobata. Ann Intern Med. 1982;97:520–5.CrossRefGoogle Scholar
  7. Sosis AC, Panet-Raymond G, Goldenberg DM. XYY chromosome complement in a patient with nodulocystic acne. Dermatologica. 1973;146:222–8.CrossRefGoogle Scholar
  8. Wilkins JW Jr, Voorhees JJ. Prevalence of nodulocystic acne in white and negro males. Arch Dermatol. 1970;102:631–4.CrossRefGoogle Scholar
  9. Wollenberg A, Wolff H, Jansen T, Schmid MH, et al. Acne conglobata and Klinefelter’s syndrome. Br J Dermatol. 1997;136:421–3.CrossRefGoogle Scholar

Solid Persistent Facial Edema of Acne

  1. Camacho-Martinez F, Winkelmann RK. Solid facial edema as a manifestation of acne. J Am Acad Dermatol. 1990;22:129–30.CrossRefGoogle Scholar
  2. Carney JW. Solid edema of face (??). Arch Dermatol. 1966;94:664–6.CrossRefGoogle Scholar
  3. Choi WT, Stetsenko GY, Zhang J, et al. Cutaneous angiosarcoma clinically presenting as progressive solid facial edema in a 43-year-old male. Dermatol Online J. 2013;19:20409.PubMedGoogle Scholar
  4. Connelly MG, Winkelmann RK. Solid facial edema as a complication of acne vulgaris. Arch Dermatol. 1985;121:87–90.CrossRefGoogle Scholar
  5. Dragan LR, Baron JM, Stern S, Shaw JC. Solid facial edema preceding a diagnosis of retro-orbital B-cell lymphoma. J Am Acad Dermatol. 2000;42(5 Pt 2):872–4.CrossRefGoogle Scholar
  6. Friedman SJ, Fox BJ, Albert HL. Solid facial edema as a complication of acne vulgaris: treatment with isotretinoin. J Am Acad Dermatol. 1986;15:286–9.CrossRefGoogle Scholar
  7. Helander I, Aho HJ. Solid facial edema as s complication of acne vulgaris: treatment with isotretinoin and clofazimine. Acta Derm Venereol (Stockh). 1987;67:535–7.Google Scholar
  8. Jungfer B, Jansen T, Przybilla B, Plewig G. Solid persistent facial edema of acne: successful treatment with isotretinoin and ketotifen. Dermatology. 1993;187:34–7.CrossRefGoogle Scholar
  9. Okubo A, Takahashi K, Akasaka T, Amano H. Four cases of Morbihan disease successfully treated with doxycycline. J Dermatol. 2017;44:713–6.CrossRefGoogle Scholar
  10. Tosti A, Guerra L, Bettoli V, Bonelli U. Solid facial edema as a complication of acne vulgaris in twins. J Am Acad Dermatol. 1987;17:843–4.CrossRefGoogle Scholar
  11. Yell JA, Mbuagbaw J, Burge SM. Cutaneous manifestations of systemic lupus erythematosus. Br J Dermatol. 1996;135:355–62.CrossRefGoogle Scholar

Dynamics of Scars

  1. Ali FR, Kirk M, Madan V. Papular acne scars of the nose and chin: an under-recognised variant of acne scarring. J Cutan Aesthet Surg. 2016;9:241–3.CrossRefGoogle Scholar
  2. Clark AK, Saric S, Sivamani RK. Acne scars: how do we grade them? Am J Clin Dermatol. 2018;19:139–44.CrossRefGoogle Scholar
  3. Kang S, Lozada VT, Bettoli V, Tan J. New atrophic acne scar classification: reliability of assessments based on size, shape, and number. J Drugs Dermatol. 2016;15:693–702.PubMedGoogle Scholar
  4. O’Brien L, Pandit A. Silicon gel sheeting for preventing and treating hypertrophic and keloid scars. Cochrane Database Syst Rev. 2006;1:CD003826.Google Scholar
  5. Tan J, Thiboutot D, Gollnick H, Kang S. Development of an atrophic acne scar risk assessment tool. J Eur Acad Dermatol Venereol. 2017;31:1547–54.CrossRefGoogle Scholar
  6. Thomé EP, Steglich RB, Meotti CD, et al. Case for diagnosis. Papular elastorrhexis. An Bras Dermatol. 2012;87:651–3.CrossRefGoogle Scholar
  7. Varadi DP, Saqueton AC. Perifollicular elastolysis. Br J Dermatol. 1970;83:143–50.CrossRefGoogle Scholar
  8. Watson JB. Monoporous and polyporous acne. Arch Dermatol. 1959;80:167–70.CrossRefGoogle Scholar
  9. Wilson BB, Dent CH, Cooper PH. Papular acne scars. A common cutaneous finding. Arch Dermatol. 1990;126:797–800.CrossRefGoogle Scholar
  10. Wortsman X, Claveria P, Valenzuela F, et al. Sonography of acne vulgaris. J Ultrasound Med. 2014;33:93–102.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Gerd Plewig
    • 1
  • Bodo Melnik
    • 2
  • WenChieh Chen
    • 3
  1. 1.Department of Dermatology and AllergyLudwig-Maximilian-University MunichMunichGermany
  2. 2.Department of Dermatology, Environmental Medicine and Health TheoryUniversity of OsnabrückOsnabrückGermany
  3. 3.Department of Dermatology and AllergyTechnical University of MunichMunichGermany

Personalised recommendations