Acne and Acneiform Eruptions

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How common is acne?

Acne vulgaris is the most common dermatologic disorders, affecting between 40 million and 50 million individuals of all ages in the United States. Eighty-five percent of people between the ages of 12 and 24 years will have some acne. Moderate to severe acne affects around 20% of young people, and severity correlates with pubertal maturity. Acne persists into the 20s and 30s in around 64% and 43% of individuals, respectively. The heritability of acne is almost 80% in first-degree relatives. In the United States, the cost of acne is over $3 billion per year in terms of treatment and loss of productivity.

Bhate K, Williams HC. Epidemiology of acne vulgaris. Br J Dermatol. 2013;168:474–485.

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What is the pathophysiology of acne?

The pilosebaceous unit, made up of a follicle (pore), sebaceous gland, and a hair, is the target organ affected in acne. The face, chest, and back are areas with the greatest concentration of pilosebaceous follicles and correspond to the areas most commonly affected by acne lesions. The primary lesion of acne is the microcomedo. This is the result of obstruction of the sebaceous follicles by sebum, deficiency of linolenic acid, excessive secretion of androgens, excess of free fatty acid, and abnormally differentiated and desquamated keratinocytes that may produce large comedones ( Fig. 21.1 ). Proinflammatory cytokines including interleukin-1α (IL-1α) and tumor necrosis factor-α are, among others, considered to be responsible for furthering aberrant follicular hyperkeratinization.

The pathogenesis of acne vulgaris is multifactorial:

• Sebaceous gland hyperplasia with excess sebum production

• Excessive keratosis of excretory ducts and openings of sebaceous glands

• Inflammatory mediators in the skin

• Propionibacterium acnes colonization of the follicle

Bergler-Czop B. The aetiopathogenesis of acne vulgaris—what's new? Int J Cosmet Sci. 2014;36:187–194.

Contassot E, French LE. New insights into acne pathogenesis: Propionibacterium acnes activates the inflamasome. J Invest Dermatol. 2014;134:310–313.

Lee YB, Byun EJ, Kim HS. Potential role of the microbiome in acne: a comprehensive review. J Clin Med . 2019;8(7).

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What are the acne subtypes?

Acne presents in many forms and variations. The most common form is acne vulgaris, which is classified according to the predominant lesion type as comedonal, papular, pustular, nodular, or cystic. It can be graded as mild, moderate, or severe ( Fig. 21.2 ). Other clinical subtypes of acneiform skin lesions include:

• Acne conglobata

• Acne excoriée

• Acne fulminans

• Acne mechanica

• Acne rosacea

• Drug-induced acne

• Favre-Racouchot syndrome

• Infantile acne

• Neonatal acne

• Perioral dermatitis

• Pyoderma faciale

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How does the composition of sebum contribute to the formation of acne?

The major constituent of sebaceous lipid is triglyceride, which makes up over 50% of the lipid, wax esters account for 25%, squalene 15%, and there are small amounts of cholesterol esters and free cholesterol. Increased sebum production is characteristic of patients with acne, but the seborrhea itself is not sufficient to produce acne. Current evidence indicates that sebum composition (lipid quality) and not quantity plays a central role in the development of acne. Desaturation of the fatty acids in sebum may lead to the development of acne lesions. Lipoperoxidases characterize the sebum of acne patients, and this, along with other qualitative changes in the sebum lipids, induce alteration of keratinocyte differentiation and induce IL-1 secretion, leading to follicular hyperkeratinization.

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;28:527–532.

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Does stress exacerbate acne?

Stress is a part of the modern routine; it affects individuals across their lifetime and may be correlated with acne. Studies demonstrate that a marked percentage of adults (50% to 71%) reported that the lesions worsened during stress periods. Sleep is one of the main regulators of the homeostasis of the body and is directly connected with well-being. Insufficient sleep represents an inherent stress condition in humans, increasing secretion of stress hormones, which may influence acne development. In one survey of 4576 consecutive patients with various dermatologic problems, 55% of those with acne reported that episodes of emotional stress were closely related to exacerbation of their acne. A prospective cohort study, published in 2003, of 22 university students with acne during exams showed increased acne severity that was significantly associated with increased stress levels. Another study in high school students also found that increased stress correlated with increased acne severity. There did not seem to be an increase in sebum production during times of stress in this study. The mechanisms underlying the triggering or aggravation of acne by stress remain unclear. Stress induces secretion of different neurotransmitters, cytokines, and hormones (corticotropin-releasing hormone, cortisol, glucocorticoids), which have skin receptors and can aggravate several skin diseases including acne. A recent study showed that skin diseases influence emotional status, through chemical mediators released by epidermal keratinocytes.

Albuquerque RG, Rocha MA, Bagatin E, et al. Could adult female acne be associated with modern life? Arch Dermatol Res. 2014;306:683–688.

Yosipovitch G, Tang M, Dawn AG, et al. Study of psychological stress, sebum production and acne vulgaris in adolescents. Acta Derm Venereol. 2007;87:35–39.

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Does diet affect acne?

Historically, there was strong interest in the role of food (e.g., chocolate, sugar, iodine) in the exacerbation of acne; however, when several studies done in the late 1960s failed to demonstrate a link, this concept fell out of vogue with dermatologists. However, there has been renewed interest in a link between diet and acne as epidemiologic studies demonstrated that acne prevalence is low in rural, nonindustrialized societies and increases with the adoption of a Western diet. Milk and other dairy products have been implicated in three separate studies. There is some evidence to support the concept that milk products with low-fat content (e.g., skim milk) may be more important than other products with a low-fat content. It has been hypothesized that the hormonal content, not the fat in milk, may be responsible for the exacerbation of acne.

The role of glycemic load on exacerbation of acne has also received scrutiny, and several prospective trials have now been completed. One prospective randomized 12-week study done on teenage boys and young men demonstrated that subjects on a low–glycemic index diet lost significantly more weight and had significantly improved acne when compared to the subjects that had been on a high–glycemic index diet. The relative contribution of the high–glycemic load diet on acne pathogenesis versus the improvement in insulin and hormone levels with weight loss is unknown.

Adebamowo CA, Spiegelman D, Danby FW, et al. High school dietary intake and teenage acne. J Am Acad Dermatol. 2005;52:207–214.

Kumari R, Thappa DM. Role of insulin resistance and diet in acne. Indian J Dermatol Venereol Leprol. 2013;79:291–299.

Smith RN, Man NJ, Braue A, et al. The effect of a high-protein, low glycemic-load diet versus a conventional, high glycemic-load diet on biochemical parameters associated with acne vulgaris: a randomized, investigator-masked controlled trial. J Am Acad Dermatol. 2007;57:247–256.

Spencer EH, Ferdowsian HR, Barnard ND. Diet and acne: a review of the evidence. Int J Dermatol. 2009;48:339–347.

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When can teenagers with acne expect their acne to resolve?

Acne persists into the 20s and 30s in around 64% and 43% of individuals, respectively. Most teenage boys can anticipate clearing of their acne between 20 and 25 years of age. For women, the news is not so good. The majority of patients with adult acne, including adult-onset acne, are women. A study of 2000 adults found that 3% of men and 5% of women still had a degree of acne between the ages of 40 to 49 years.

Bhate K, Williams HC. Epidemiology of acne vulgaris. Br J Dermatol. 2013;168:474–485.

Mwanthi M, Zaenglein AL. Update in the management of acne in adolescence. Curr Opin Pediatr . 2018;30(4):492–498.

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Discuss the role of topical retinoid therapy in acne vulgaris

The single most important topical medications used to treat acne are retinoids. There are numerous topical preparations to choose from that are less irritating and decrease the most common complaint associated with this class of acne therapy. These include adapalene (Differin), tazarotene (Tazorac), and tretinoin (Avita, Retin-A, Retin-A Micro). Twelve weeks of use is required for maximum benefit. Retinoids are the only drugs that normalize keratinization within the follicular infundibulum and prevent comedo formation. Propionibacterium acnes, the anaerobic bacterium associated with acne pathogenesis, stimulates the innate immune response via Toll-like receptors (TLRs). This sets off an inflammatory cascade of cytokines. Retinoids are known to downregulate TLRs and inhibit downstream inflammatory transcription factors. Recent recommendations from a global alliance to improve outcomes in acne recommended that retinoid-based combination therapy (retinoid plus antimicrobial or benzoyl peroxide [BPO]) be the first-line treatment for most forms of acne vulgaris. Retinoids have been shown to maintain improvement achieved with this initial combination therapy.

Sevimli Dikicier B. Topical treatments of acne vulgaris: efficiency, side effects, and adherence rates. J Int Med Res. 2019;47:2987–2992.

Kolli SS, Pecone D, Pona A, Cline A, Feldman SR. Topical retinoids in acne vulgaris: a systematic review. Am J Clin Dermatol . 2019;20:345–365.

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What is the role of topical antibiotics in the treatment of acne vulgaris?

It is important to understand that acne vulgaris is not an infection. In general, topical antibiotic monotherapy should be avoided, particularly for long periods of time because of the development of bacterial resistance. More than half of patients undergoing therapy with a single topical antibiotic will develop resistance. Topical antibiotics are useful, as they do reduce Propionibacterium acnes colonization on the skin and reduce the bacteria's proinflammatory effects.

In general, it is best to utilize topical antibiotics (erythromycin, clindamycin, and sodium sulfacetamide) in combination with BPO either as fixed-dose combination products or two separate medications. BPO has the added benefit of being modestly comedolytic and can minimize the risk for bacterial antibiotic resistance. Other topical treatments are α-hydroxy acids, salicylic acid, azelaic acid, dapsone, and taurine bromamine. Minocycline topical foam is currently being studied for the treatment of moderate to severe acne.

Bonati LM, Dover JS. Treating acne with topical antibiotics: current obstacles and the introduction of topical minocycline as a new treatment option. J Drugs Dermatol . 2019;18:240–244.

Dessinioti C, Katsambas A. Propionibacterium acnes and antimicrobial resistance in acne. Clin Dermatol . 2017;35:163–167.

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Discuss oral antibiotic use in acne vulgaris

Oral antibiotics are indicated in patients with inflammatory lesions (red papules, pustules, or nodules) of moderate to severe grade. There is a low evidence level that oral antibiotics are more effective than topical preparations for mild to moderate facial acne. Tetracyclines are the first-line oral antibiotic therapy in acne. Minocycline and doxycycline are most frequently used. Sarecycline, a novel tetracycline, has recently been FDA approved for the treatment of acne in patients 9 years of age and older. Overall, there is insufficient evidence to support one tetracycline over another in terms of efficacy. Antibiotics reduce the numbers of P. acnes in the follicles and also have numerous anti-inflammatory effects.

Oral antibiotics should never be used as monotherapy in acne because of a significant problem with antibiotic resistance, and only two of the four main pathophysiologic mechanisms of disease are being addressed. Oral antibiotics should be combined with a keratolytic such as a topical retinoid and topical BPO. Oral therapy will take 4 to 8 weeks to show significant improvement. After adequate clinical response in 3 to 6 months, the dose should be tapered in an attempt to provide maintenance with topical medications. Erythromycin is an alternative in patients who are intolerant or allergic to tetracyclines and may be used in pregnancy; however, because of worldwide resistance, the use of this antibiotic has waned. Alternative oral antibiotics such as clindamycin, azithromycin, cotrimoxazole, and quinolones should be used cautiously because of increased potential for severe adverse reactions.

Chien AL, Tsai J, Leung S, et al. Association of systemic antibiotic treatment of acne with skin microbiota characteristics. JAMA Dermatol . 2019;155:425–434.

Adler BL, Kornmehl H, Armstrong AW. Antibiotic resistance in acne treatment. JAMA Dermatol . 2017;153:810–811.Kircik, L. What’s new in the management of acne vulgaris. Cutis 2019;104(1).

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