Acne & Scars Ramanjit Singh, Nidhi Rao
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Introduction, Epidemiology and Pathogenesis of Acne1

 
INTRODUCTION
Acne is an extremely common condition involving the sebaceous glands. The pilosebaceous unit of the skin gets affected in acne. The age group, which is affected, is of adolescents but the problem can continue to exist till middle age sometimes. Majority of adolescents experience some form of acne, with about 20% presenting with moderate-to-severe acne. Though a common condition but sequelae can be distressing for the patient in the form of acne scars and pigmentation. So, in spite of a self-limited course the treatment of acne becomes important.
Acne more often affects skin with greater number of oil glands. The lesions in acne comprise of comedones, which can be open and closed, papules, pustules, cysts and nodules. The common sites, which get involved, are face, chest, back and shoulders.
 
EPIDEMIOLOGY
Acne vulgaris is mostly a universal skin disease in western societies affecting 79–95% of the adolescent population. In 40–54% of men and women who are more than 25 years of age, acne is present or found in some degree. However, it is seen that persistence of acne can be there into middle age in 12% of women and 3% of men.
The individuals affected with acne are between 40 and 50 million in the United States. Acne, which mainly affects adolescent population, also affects children and adults. According to one study, people affected with acne were older than 25 years and 54% of women and 40% of men were affected. In this very group, facial acne accounted for 12% of women and 3% of men and it persisted into middle age. Similar results were reported by Cunliffe and Gould 20 years before.
The prevalence of acne increases by age, especially in pediatric age group. Clinically diagnosed acne is present in 28–61% of children between the ages of 10 and 12 years.
In adolescents, between the age group of 16 and 18 years, 79–95% of people are affected.2
Therefore, acne affects mainly adolescents but can also affect population above 25 years which is mainly in the Western world.
In non-Westernized societies, acne is less commonly seen as suggested by epidemiological evidences.
The US prevalence of severe acne was virtually nil in the first decade of life, but increased in a linear fashion from 11 years [1·7% (95% confidence interval (CI) 0·4–3·0%)] to 17 years of age [12·1% (95% CI 7·8–16·5%)] (Rao-Scott Chi-square, p < 0·0001). Severe acne was more common in Whites compared with other racial groups at age 14–15 years (p = 0·0004) and girls at age 11–13 (p = 0·02).
 
Racial and Socioeconomic Determinants of Severe Acne
According to a study, prevalence estimates were stratified by age because of significant interactions of age with race, sex and other demographic factors. There were no significant differences of the prevalence of severe acne across different racial groups at age 11–13 years and 16–17 years. However, the prevalence of severe acne was significantly higher in Whites compared with other racial groups at age 14–15 years. There was no significant association with Hispanic/Spanish origin. The prevalence of severe acne was higher in girls at age 11–13 years but not 14–15 or 16–17 years.
The prevalence of severe acne was lower in households with multiple children compared with only one child at age 11–13 years, but the association was inverted by age 16–17 years. There was a marginal association between the prevalence of acne at age 14–15 years and households with higher level of education.
However, there were no significant associations between severe acne and household income, birthplace outside the US or duration of residence in the US.1
 
PATHOGENESIS
There is no single cause or process which is involved in acne. The disease is multifactorial and is related with mainly the following factors:
  • Follicular hyperkeratinization
  • Colonization with Propionibacterium acne bacteria
  • Increased sebum production
  • Inflammatory mechanisms.
 
Follicular Hyperkeratinization
The initial change involved in the sebaceous gland is the alteration in the keratinization in the sebaceous follicle. The initiating factor in the generation of comedones is unknown but the processes which are involved can be stated as following.
Interleukin-1 alpha (IL-1α) androgens, increased DHT, relative deficiency of linoleic acid, and P. acne all contribute to abnormal hyperkeratinization. Among the above elucidated factors, IL-1α plays an important role in follicular hyperkeratinization.2
Recent studies have shown that vascular endothelial cell activation and inflammatory changes occur before increased IL-1α activity. All these above 3factors result in the triggering of keratinocyte leading to ‘keratinocyte activation cycle’. The changes, which take place, are keratinous material becomes more dense, decrease in lamellar granules and the proliferating keratinocytes are moved towards the center, causing an increase in the intraluminal pressure, and leads to hypoxia in the center of the duct which leads to the colony formation of P. acne and eventually all this leads to rupture of ducts and inflammation by the released antigens after the rupture of ducts.3,4
 
Colonization with Propionibacterium acne
Propionibacterium acne is an anaerobic bacterium, which is found mainly in adults as a normal commensal in the pilosebaceous unit. There has been no evidence to whether P. acne can initiate acne or comedogenesis but evidence is there to support that favorable microenvironment can increase comedone formation and inflammation. The mechanisms by which P. acne aggravate comedogenesis, are modulating differentiation of keratinocytes, increasing keratinocyte proliferation by stimulating insulin like growth factor (IGF)/insulin like growth factor-1 receptor (IGF-1R) system, inducing transglutaminase, K17, integrins, and filaggrin expression and decreasing K1 and K10 expression.
P. acne also induces innate immune responses by toll-like receptor (TLR) pathway, by activating complement, triggering adaptive immune responses by activating T-helper cells.57
 
Role of Sebaceous Gland and Increased Sebum Production
The sebaceous gland is a holocrine gland, which produces sebum. Sebum is a product of sebaceous gland, which consists of triglycerides (TG), fatty acid breakdown products, wax esters, squalene, cholesterol esters, and cholesterol. Excessive sebum production plays a very important role in pathogenesis of acne.
The triglyceride portion in the sebum appears to play a major role in pathogenesis of acne. The resident bacteria in the pilosebaceous unit hydrolyze TG and release fatty acids. Among these fatty acids, monounsaturated fatty acids (MUFAs) stimulate the morphological changes which causes comedogenesis. Other factors which are responsible in acne production related to sebum production are as follows:
  • Decrease in linoleic acid which favors comedogenesis already explained earlier.
  • Alteration of Δ6 and Δ9 unsaturated fatty acids which act as trigger for morphological changes and increased keratinization.
  • Sqalene peroxide which is a byproduct of lipid peroxidation also leads to the follicular hyperkeratinization, and upregulation and release of inflammatory mediators.
 
Androgens in the Pathogenesis of Acne
Hormones are also implicated in the pathogenesis of acne.
Androgen receptors are expressed in the pilosebaceous unit and when free testosterone enters the unit, its converted to DHT (dihydrotestosterone) 4by 5α reductase and stimulate proliferation of sebocytes. So testosterone, DHT, dehydroepiandrosterones sulfate (DHEAS) all have a role in the pathogenesis of acne which affects the sebaceous gland activity and also influence the keratinization of the follicular corneocytes.811
 
Dietary Factors
Earlier, there had been a consensus in the community of dermatology which did not support the role of diet in pathogenesis or aggravation of acne. But now the role of diet is also becoming clear. The diet which can majorly have an effect in acne is Western diet with a high glycemic index. High glycemic index means a diet with mainly carbohydrates, i.e. high carbohydrate diet which leads to hyperinsulinemia and therefore result in subsequent increase in androgens and IGF-1 activity which are involved in acne pathogenesis.
Various studies have been conducted in which diet had a role in acne. The diet which majorly affected acne in these studies were milk, ice creams, dairyfood and food with high fat content. The diet which showed protective effects were vegetable and fish intake. Studies show a protective role of a Mediterranean diet. A study shows increased iodine in diet can lead aggravation of acne.
So, there is a definite role of diet in acne and nowadays considering the usefulness of low glycemic index diet in other lifestyle diseases, it should be suggested in acne cases also.1215
 
Sunlight and Seasonal Influence
There have been no data which can support a particular season in the aggravation or resolution of acne. Studies have been conducted on this and there is no data which can support the influence of season on acne. Considering light treatment in acne whether sunlight can have a role cannot be very well stated.16,17
 
Stress
Stress increases the synthesis of glucocorticoids and adrenal androgens, which can further lead to the aggravation of acne.18,19
 
Skin Hygiene
Skin hygiene related to washing face can have an effect on acne. Studies conducted are less in these subjects, but few studies which were conducted show improvements in skin lesions in group who washed their face twice daily compared to people who did it once daily. Excessive face washing, i.e. washing face 4 times or more than that did not have any positive or negative effect on acne.
So, despite this little evidence, washing face twice daily should be recommended to patients. In another study, washing face with alkaline soap as compared to syndet soap caused aggravation and worsening of acne.20,21
REFERENCES
  1. Silverberg JI, Silverberg NB. Epidemiology and extracutaneous comorbidities of severe acne in adolescence: A US population-based study. Br J Dermatol. 2014; 170(5):1136–42.5
  1. Knutson DD. Ultrastructural observations in acne vulgaris: the normal sebaceous follicle and acne lesions. J Invest Dermatol. 1974;62:288–307.
  1. Jarrousse V, Castex-Rizzi N, Khammari A, Charveron M, Dreno B. Modulation of integrins and filaggrin expression by Propionibacterium acnes extracts on keratinocytes. Arch Dermatol Res. 2007;299(1):441–7.
  1. Hughes BR, Morris C, Cunliffe WJ, Leigh IM. Keratin expression in pilosebaceous epithelia in truncal skin of acne patients. Br J Dermatol. 1996;134:247–56.
  1. Bruggemann H, Henne A, Hester F, Liesegang H, Wieser A, Strittmatter A, et al. The complete genome sequence of Propionibacterium acnes, a commensal of human skin. Science. 2004;305:671–3.
  1. Lee SE, Kim JM, Jeong SK, Jeon JE, Yoon HJ, Jeong MK, et al. Protease activated receptor-mediates the expression of inflammatory cytokines, antimicrobial peptides, and matrix metalloproteinases in keratinocytes in response to Propionibacterium acnes. Arch Dermatol Res. 2010;302:745–56.
  1. Medzhitov R, Preston-Hurlburt P, Kopp E, Stadlen A, Chen C, Ghosh S, et al. My D 88 is an adaptor protein in the h Toll/IL-1 receptor family signalling pathways. Mol Cell. 1998;2:253–8.
  1. Downing DT, Stewart ME, Wertz PW, Strauss JS. Essential fatty acids and acne. J Am Acad Dermatol. 1986;14:221–5.
  1. Pappas A, Johnson S, Liu JC, Eisinger M. Sebum analysis of individuals with and without acne. Dermatoendocrinol. 2009;1:157–61.
  1. Knutson DD. Ultrastructural observations in acne vulgaris: the normal sebaceous follicle and acne lesions. J Invest Dermatol. 1974;62:288–307.
  1. Melnik BC. Fox O1- The key for the pathogenesis and therapy of acne? J Dtsch Dermatol Ges. 2010;8:105–14.
  1. Horton R, Pasupuletti V, Antonipillai I. Androgen induction of steroid 5α reductase may be mediated via insulin like growth factor-1. Endocrinology. 1993;133:447–51.
  1. Fan W, Yanase T, Morinaga H, Okabe T, Nomura M, Daitoku M, et al. Insulin like growth factor 1/insulin signalling activates androgen signalling through direct interactions of Fox O1 with androgen receptor. J Biol Chem. 2007;282:7329–38.
  1. Rudman SM, Philpott MP, Thomas GA, Kealey T. The role of IGF-1 in human skin and its appendages: morphogen as well as mitogen? J Invest Dermatol. 1997;109:770–7.
  1. Jung JY, Yoon MY, Min SU, Hong JS, Choi YS, Suh DH. The influence of dietary patterns on acne vulgaris in Koreans. Eur J Dermatol. 2010;20(6):768–72.
  1. Kawada A, Aragane Y, Kamayama H, Sangen Y, Tezuka T. Acne phototherapy with a high intensity, enhanced, narrow-band, blue light source: J Dermatol Sci. 2002;30: 129–35.
  1. Mills OH, Kligman AM. Ultraviolet photherapy and photochemotherapy of acne vulgaris: Arch Dermatol. 1978;114:221–3.
  1. Chiu A, Chon SY, Kimball AB. The response of skin disease to stress: changes in the severity of acne vulgaris as affected by examination stress. Arch Dermatol 2003;139:897–900.
  1. O Sullivan RL, Lipper G, Lerner EA. The neuroimmunocutaneous endocrine network:relationship of mind and skin. Arch Dermatol. 1998;134:1431–5.
  1. Choi JM, Lew VK, Kimbell AB. A single blinded, randomised, controlled clinical trial evaluating the effect of face washing on acne vulgaris. Pediatr Dermatol. 2006;23: 421–7.
  1. Korting HC, Ponce-Posche E, Klovekorn W, Schmotzer G, Arenz-Corell M, Braun Falco O. The influence of the regular use of a soap or an acidic syndet bar on pre acne. Infection. 1995;23:89–93.