CHAPTER 135

Acne

Samantha Snider, MD

Acne vulgaris is a common chronic inflammatory skin disease that most frequently occurs in adolescents. The spectrum of disease can vary widely, but regardless of type and severity, acne can be severely distressing for patients. The psychological burden and negative effect on quality of life can be comparable to those with asthma, arthritis, or epilepsy. Primary care physicians should, therefore, acknowledge acne as a significant chronic medical problem and treat the condition early and aggressively to prevent permanent sequelae, such as scarring.

Epidemiology

Estimates indicate that more than 85% of people in the United States have been affected by acne and that more than $2 billion is spent annually on acne treatments. Acne most commonly occurs in individuals 9 to 24 years of age, with peak prevalence and severity during puberty. However, the condition can also affect neonates, young infants, and older adults (up to 26% of women and 12% of men). Preteens are more likely to experience comedonal lesions, with progression to more inflammatory lesions during the teenage years. The condition is usually more severe in males but typically lasts longer in females. Certain individuals may be genetically susceptible to acne. White teenagers are more likely to have acne than black, Hispanic, or Asian teenagers. However, patients with darker skin tones often have more issues with post-inflammatory discoloration and scarring.

Etiology

Acne has a complex, multifactorial etiology with many overlapping influences that are endogenous and exogenous (Box 135.1).

Internal (host) factors include hormones (eg, androgen excess, changes in estrogen or progesterone during menses, stress-induced cortisol release), skin microflora balance (especially with Cutibacterium [previously Propionibacterium] acnes), sebum overproduction, skin hyperkeratinization, and stimulation of internal inflammatory pathways.

External factors include medications and drugs (ie, progestin-only contraceptives, isoniazid, phenytoin, corticosteroids, anabolic steroids, and lithium-containing compounds), chemicals (ie, petroleum), oil- or wax-containing hair care products and cosmetics, overzealous facial cleansing, local skin occlusion from sports gear and excessive perspiration, and diet. While specific foods such as chocolate, caffeinated drinks, and fried or greasy foods have not been shown to directly cause or worsen acne, emerging research suggests that diets with high-glycemic indices or high dairy intake may contribute to inflammation and the development of acne lesions.

Pathophysiology

The pathogenesis of acne involves 4 major interrelated processes that naturally occur within the pilosebaceous unit: hyperkeratinization of follicular infundibulum, sebaceous gland overproduction and alteration of sebum composition, proliferation of C acnes, and immune response and inflammation (Box 135.2). Alteration or imbalance of any of these 4 normal processes can lead to formation of acne lesions.

Hyperkeratinization of Follicular

Infundibulum

Keratinocytes constitute 90% of the cells of the epidermis and function to produce a keratin barrier that protects against environmental damage. Activation of the innate immune system by internal or external factors will initiate pro-inflammatory biochemical cascades. One important pathway includes activation of toll-like receptors (TLR-2/4) and ensuing release of defensin and interleukin. Interleukin-1α specifically has been linked to increased keratinocyte proliferation, which, in turn, leads to overproduction of keratin and reduced desquamation and remodeling within the pilosebaceous unit. This results in the formation of a keratin plug within the follicular infundibulum. Keratin plugging leads to retention of sebum and cellular debris and subsequent development of the microcomedo, the earliest precursor lesion of acne.

Sebaceous Gland Overproduction and Alteration of Sebum Composition

Sebum is a complex mixture of oils that includes triglyceride and fatty acid breakdown products, wax esters, squalene, and cholesterol. Any alteration to the composition of these different lipids can contribute to acne lesion formation. A common cause of alteration is antioxidant and free radical imbalance. Exposure to pollution and UV radiation decrease skin antioxidants, such as vitamin E, and can lead to formation of reactive oxygen species. Increases in reactive oxygen species lead to subsequent oxidization of sebum lipids and inflammation that contribute to acne.

The amount of sebum produced is also important, because overproduction can contribute to inflammation and comedo formation. The sebaceous gland is highly sensitive to hormonal stimulation, especially the increase in androgens during puberty and corticotrophin-releasing hormone spikes during stress. Hormonal activation causes sebaceous glands to undergo hypertrophy, leading to an overall increase in sebum production. Diet can also lead to increase in sebum production via activation of insulinlike growth factor 1, leptin, and peroxisome proliferator-activated receptors (PPARα, β, and γ). Alternatively, activated retinoic acid and retinoid-X receptors have an antiproliferative effect on keratinocytes and inhibit lipid synthesis.

Proliferation of Cutibacterium Acnes

Cutibacterium acnes is a gram-positive anaerobic diphtheroid bacterium that plays a major role in acne pathogenesis. Cutibacterium acnes normally exists in balance alongside Staphylococcus epidermidis as the predominant cutaneous microflora of the sebaceous follicle. In the setting of normal microflora balance, C acnes limits proliferation of Staphylococcus aureus and Streptococcus species, whereas S epidermidis helps limit proliferation of C acnes. When left unchecked, C acnes releases hyaluronate lyase and CAMP (Christie Atkins Munch Petersen, the researchers who discovered the factor) factors that cause extracellular matrix degradation and porphyrins that oxidize sebum, and can form a strong antibiotic resistant biofilm—all of which lead to inflammation that can cause acne.

Immune Response and Inflammation

The innate immune system also plays a key role in acne lesion formation and subsequent scarring. Innate immune responses release inflammatory mediators that activate the hyperkeratinization that causes keratin plugging, which, in turn, leads to the rupture of the pilosebaceous follicle and expulsion of follicular contents into the dermal layer of skin. This spillage of sebum, keratin, and bacteria leads to further inflammation and the development of inflammatory acne lesions. In addition, specific cytokines such as interleukin-8/10 also attract circulating inflammatory cells into the tissue and promote pustular acne lesions. Many inflammatory cytokines can also induce matrix metalloproteinases (eg, MMP-9) that cause dermal matrix destruction and subsequent scar formation.

Clinical Presentation

The lesions of acne primarily affect the face, especially central facial areas, or the T-zone, which includes the forehead, nose, and chin. Lesions can also be found on other areas of the body that are dense in sebaceous glands, including the neck, chest, shoulders, and back.

There are a number of different types of acne lesions (Box 135.3). Lesions are typically described as comedonal (non-inflamed) or inflammatory. Comedones can be open or closed to the environment. Closed comedones, or whiteheads, are small, flesh-colored bumps with no surrounding erythema that are caused by plugging of the sebaceous follicle and resultant dilation that is closed to the surface of the skin. Open comedones, or blackheads, are small, dome-shaped papules with an open orifice that contains central dark material. These also occur as a result of dilatation of the follicular orifice but are open to the outside environment. The dark-colored material at the surface of the skin within open comedones is not dirt; therefore, patients should not attempt to scrub off or pick out the lesion. The dark color is actually caused by a number of processes, including melanin deposition in the horny cells, interference with the transmission of light through compacted epithelial cells, and oxidation of keratin and sebum.

Pustules and papules are inflammatory lesions. Pustules lie in the superficial epidermal layer of the skin, and papules form in the lower dermal layer. Because of their deeper location, papules are often accompanied by a more severe inflammatory reaction, and scarring may result. Nodules or cysts are suppurative inflammatory lesions located deep within the dermis. Associated with the most severe form of acne, nodules are the result of deep papules that suppurate and rupture, and then subsequently become lined with epithelium to form cysts.

Evaluation

History

A detailed history investigating the medical and psychosocial aspects of acne is key (Box 135.4). It is often helpful to start with the psychological effects first. How do patients feel about their acne and how does it affect their life? Do they desire treatment at this time, and if so, what are their expectations about treatment and recovery? From a medical standpoint, the health professional should determine how long the acne has been present, the types of lesions that are present, if and how the condition has ever been treated, and what has or has not worked in the past. A general review of systems is important to exclude symptoms associated with androgen excess or other metabolic disorders that may be contributing to acne breakouts.

Physical Examination

The physical examination should focus on the primary sites of acne— face, chest, back, and shoulders—although the entire skin should be inspected closely at the first visit. Currently no universally accepted grading scale for acne severity exists. However, American Academy of Dermatology guidelines currently use the number of lesions and extent of inflammation as the main factors to determine severity (Table 135.1). The presence of nodular lesions is of particular importance, because this indicates more severe acne even in the absence of other lesions and typically requires systemic treatment. The presence and extent of scarring should also be assessed as a possible predictor of outcome.

A complete physical examination at the initial visit is important to assess for signs of hormonal imbalance that may be contributing to symptoms. Androgen excess can present with hirsutism, male pattern baldness, obesity, and acanthosis nigricans. Indications of virilization, such as congenital adrenal hyperplasia or androgen-producing tumors, have more severe effects, such as clitoromegaly, loss of female body contour, and deepening of the voice. Signs of steroid use or cortisol excess include central obesity, moon facies, stretch marks, buffalo hump, and decreased testicular volume in males. Acne in prepubescent children older than 1 year is never normal and is cause for concern for precocious puberty and hormone-secreting tumors. Signs include axillary and pubic hair, breast development in females, and testicular enlargement in males.

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