Acne and its clinical variants are among the most common causes of patient visits to the physician for cutaneous disorders. Severe forms of these disorders can be disfiguring and debilitating; and because the face is the primary site of involvement, patients will often seek therapy for even mild forms. Therapeutic approaches will therefore be stressed in this topic.
Epidemiology and Etiology
Acne vulgaris is the most common dermatologic problem of adolescent years; it usually begins in puberty. Age of onset and severity of disease are affected by sex, genetics, and external factors such as cosmetics and medications. Acne is usually more severe in males than in females and often begins earlier (i.e., in early adolescence) in males. Acne often subsides after the teenage years, but the disease can remain a problem for adults in the third and fourth decades and beyond. A significant portion of women experience premenstrual flares of acne; this phenomenon may be more common in older women.1
Genetic factors clearly play a role in severe acne. A family history of severe acne can often be elicited during the workup of affected patients. Various external factors, such as occlusive cosmetics, can contribute to acne, and certain medications (e.g., cor-ticosteroids, adrenocorticotropic hormone [ACTH], phenytoin sodium, isoniazid, lithium, progestins, potassium iodide, bromides, and actinomycin D) can cause acnelike lesions [see 2:VI Cutaneous Adverse Drug Reactions].
Pathogenesis
Multiple factors contribute to the development of acne in susceptible persons. Among the most significant are alterations in keratinization, accumulation of sebum, and inflammation. An-drogenic influences may contribute to some of these factors.
Modified keratinization of the follicular infundibulum leads to proliferation and increased cohesiveness of keratinocytes, which causes plugs to form. These plugs block follicular outlets, allowing cellular debris in sebum to form comedones (the noninflammatory lesions of acne that are the precursor lesions of inflammatory acne).
The composition of sebum does not appear to be altered in patients with acne; however, sebaceous glands are often larger and sebum production is often greater in persons affected with acne than in unaffected persons.2 Sebum is comedogenic and inflammatory, which may account for its role in acne.3 Inflammation in acne has also been attributed to the anaerobic diphtheroid Propionibacterium acnes. The presence of P. acnes correlates with the occurrence of acne in adolescents.4 The microbe’s role in inflammation has been attributed to lipases, proteases, and hyalu-ronidases, as well as to chemotactic factors. For example, P. acnes may activate Toll-like receptor 2 and thereby trigger inflammatory cytokine responses.5
Androgens play a role in the development of acne, as evidenced by increased levels of dehydroepiandrosterone sulfate (DHEAS) in girls with acne6 and an association of acne with en-docrinopathies characterized by increased levels of circulating androgens. For example, the occurrence of acne is increased in patients with congenital adrenal hyperplasia, polycystic ovaries, and some ovarian and adrenal tumors. Androgens act to increase sebum production and enlarge sebaceous glands; they may also contribute to the follicular hyperkeratinization that leads to acne. However, serum androgen levels are usually within the normal range in patients with acne. Some researchers have postulated that local production of androgens in the skin can lead to acne. Skin biopsies from patients with acne show increases in 5a-reductase activity.7 This increased androgenic activity may result in the conversion of testosterone to dihydrotestos-terone in the skin, leading to the development of acne.
Diagnosis
Clinical features
The characteristic skin lesions of acne include open and closed comedones, erythematous papules, pustules, nodules, cysts, and scars. The most commonly affected site is the face, but in more severely affected individuals, the back and chest can be involved as well.
Comedonal Acne
Comedones consist of keratinized cells and sebum. Come-donal acne consists of a predominance of open and closed comedones. Open comedones (blackheads) are black papules measuring 0.1 to 2 mm that are easily extruded with gentle pressure. The material that is removed is greasy and has a gray-white color. Contrary to popular belief, the dark color of open comedones is caused by melanin, not by dirt or oxidized fatty acids. Closed comedones (whiteheads) consist of white papules measuring 0.1 to 2 mm; unless extracted, they persist somewhat longer than open comedones, often for weeks to months.
Inflammatory Acne
Erythematous papules, pustules, nodules, and cysts are the predominant lesions in inflammatory acne [see Figure 1]. Erythematous papules range in size from 3 to 10 mm and can develop into pustules or resolve into an erythematous macule that fades. Postinflammatory hyperpigmentation can occur. Pustules are superficial and usually dry in a few days. Nodules, which are 1 cm or larger, are erythematous and tender. They can be firm at onset but often become fluctuant. In severely affected individuals, these lesions form fluctuant sinuses that open to the surface through multiple tracts. Postinflammatory pigmentary changes and scarring commonly occur.
Clinical Variants of Acne
Acne conglobata Acne conglobata is a severe, scarring form of acne in which large cysts and abscesses become confluent to form draining sinus tracts. Scarring is often severe. Topical acne therapy and oral antibiotics are frequently ineffective; patients may require treatment with oral isotretinoin [see Treatment, below]. Intralesional injection of corticosteroids and drainage of abscesses are temporarily helpful.
Figure 1 Inflammatory acne is characterized by erythematous papules and pustules.
Acne cosmetica A persistent, low-grade form of acne can result from the use of greasy, occlusive cosmetics, moisturizers, and sunscreens. Women are most commonly affected.
Acne excoriee Picking of minor acne lesions can cause large ulcers and erosions that heal with scarring. Young women are most typically affected.
Acne mechanica An acneiform eruption can result from repeated trauma associated with the wearing of sports helmets, shoulder pads, and bras and from the chin rests of violins and violas (so-called fiddler’s neck).
Pomade acne A form of acne results from the use of thick oils in the hair. Comedones, papules, and pustules are usually found close to the hairline. Black men and women are most commonly affected.
Acne in neonates and children Neonatal acne has been attributed to maternal androgens, as well as androgens secreted by the neonatal adrenal gland. Erythematous papules and pustules may last for 2 to 3 months after birth but usually resolve spontaneously.
Infantile acne develops between 3 and 6 months after birth. This condition is characterized by inflamed papules and pustules; it signals early secretion of androgens by the gonads, particularly in boys. This condition may last until age 5. It has been suggested that affected infants may be predisposed to severe acne later in life.
Laboratory tests
The clinical features of acne are so commonly recognized that laboratory investigation is usually not necessary. Laboratory tests should be considered, however, for female patients who have other signs of hyperandrogenism, such as hirsutism or irregular menses. Serum for determining DHEAS and free testosterone levels and for determining the ratio of luteinizing hormone to follicle-stimulating hormone (LH:FSH) should be obtained 2 weeks before the onset of menses [see Table 1]. Tests should also be undertaken in patients whose conditions do not respond to adequate doses of isotretinoin, the most potent treatment available for acne [see Treatment, below].
Differential Diagnosis
Clinical features of acne are sufficiently distinctive that diagnosis is usually obvious. Nevertheless, a number of disorders can be mistaken for acne.
Folliculitis The perifollicular pustules of folliculitis can be distinguished from the lesions of acne by their distribution. Folli-culitis can affect the trunk and extremities and is not limited to the usual sites of acne (i.e., the face, back, and chest). Malassezia folliculitis is characterized by erythematous acneiform papules that do not respond to typical acne therapies. Gram stain of pus from the lesions reveals gram-positive budding yeast [see 2:VII Fungal, Bacterial, and Viral Infections of the Skin].
Gram-negative folliculitis In patients on long-term antibiotics, superficial pustules or nodules can develop at the anterior nares and spread outward on the face. This condition responds promptly to oral ampicillin; however, isotretinoin has become the treatment of choice.
Milia Milia are white pinpoint cysts that resemble closed comedones. They frequently occur around the eyes but can develop anywhere on the face. If untreated, they last for months or years. Milia can be opened with a small surgical blade and their contents easily drained.
Perioral dermatitis Long-term use of topical corticosteroids on the face can result in acneiform, erythematous, inflamed papules on the chin and cheeks. Despite the name, the area immediately around the mouth is typically spared in perioral dermatitis. A similar eruption can occur in patients who have not used corticosteroids.
Chloracne Cysts and closed comedones that resemble acne lesions can be caused by exposure to halogenated hydrocarbons.
Hidradenitis suppurativa Hidradenitis suppurativa is a chronic condition in which inflamed cysts in the axillae and groin form fluctuant sinuses with draining tracts.
Favre-Racouchot disease Numerous open and closed comedones can appear around the eyes of elderly patients, especially men who have worked outdoors for much of their lives. This condition has been attributed to a lifetime of sun exposure.
Table 1 Laboratory Evaluation for Women with Acne and Signs of Hyperandrogenism
|
Finding |
Suspected Condition |
|
DHEAS 4,000-8,000 ng/ml > 8,000 ng/ml |
Congenital adrenal hyperplasia Adrenal tumor |
|
LH: FSH ratio >2.0 |
Polycystic ovary disease |
|
Testosterone (unbound) 20-40 yr, > 107.5 pmol/L 41-60 yr, > 86.7 pmol/L 61-80 yr, > 69.3 pmol/L |
Polycystic ovary disease; ovarian tumor Polycystic ovary disease; ovarian tumor Polycystic ovary disease; ovarian tumor |
DHEAS—dehydroepiandrosterone sulfate
FSH—follicle-stimulating hormone
LH—luteinizing hormone
Rosacea Rosacea is a common condition that usually begins after 30 years of age. It is so similar to acne in some individuals that it has been called acne rosacea. Skin lesions consist of ery-thematous papules, pustules, and telangiectasia [see Figure 2]. Facial flushing is a common feature. In patients with a predominance of inflamed papules and pustules, differentiation from acne can be difficult. Presence of telangiectasia and the occurrence of flushing help distinguish rosacea from acne, as does the absence of comedones.
Common triggers of rosacea include alcohol, exercise, extremes of temperature, and hot or spicy foods. With long-standing disease, hypertrophy of sebaceous glands, swelling, erythema, and scarring of the nose lead to rhinophyma. Ocular involvement is common in rosacea and can include blepharitis and conjunctival hyperemia or, less commonly, iritis, episcleritis, superficial punctuate keratopathy, and corneal neovascularization.9
Helicobacter pylori may play a role in the pathogenesis of rosacea.10 Further work must be done, however, to confirm the contribution of H. pylori to this antibiotic-responsive condition. An immunologic reaction to the mite Demodex folliculorum has been suggested, but not proved, as a contributing factor.
Treatment
Treatment of acne depends on the type and severity of lesions and on the patient’s response to treatment. Comedonal acne is usually best managed with topical retinoids and acne surgery; inflammatory acne is treated with a range of topical therapies and may require oral therapy in moderate to severe cases. Because nodules and cysts are more likely than comedones to cause scarring, they are treated more quickly with oral antibiotics and, if necessary, isotretinoin (see below). Intralesional cor-ticosteroids administered by dermatologists can prevent scarring from cysts. Incision and drainage of infected cysts may be necessary but can contribute to scarring. Unroofing of sinus tracts and other surgical procedures are best performed by physicians with expertise in dermatologic surgery [see Table 2]. Scars can be treated with dermabrasion or laser abrasion. The appearance of depressed scars can be improved by chemical peels and other resurfacing procedures, as well as by the injection of filler substances such as injectable collagen.11
Numerous over-the-counter cleansing agents are available to help patients remove seborrhea and oily debris from the skin, re-sulting in subjective improvements. Overmanipulation of lesions by picking, squeezing, or excessive washing can lead to exacerbation of lesions and even scarring.
Figure 2 Erythematous papules, pustules, telangiectasia, and flushing are features of rosacea.
Table 2 Surgical Treatments for Acne Lesions and Acne Scars
|
Lesions |
Extraction of comedones |
|
Drainage of pustules and cysts |
|
|
Intralesional injection of corticosteroids in cysts |
|
|
Excision and unroofing of sinus tracts and cysts |
|
|
Scars |
Dermabrasion |
|
Laser abrasion |
|
|
Acid peels |
|
|
Injection of filling materials (e.g., collagen) |
|
|
Excision |
|
|
Punch autografts |
Topical preparations, including sunscreens, soaps, and cosmetics, should be oil-free and noncomedogenic. Many over-the-counter oil-free, noncomedogenic moisturizers are available for persons who have dry skin and acne.
There is no role for dietary change in the management of acne. Previous beliefs that chocolate or oily foods cause acne have been disproved.
Topical therapy
Comedonal Acne
Topical retinoids are among the most effective therapies for comedonal acne; these preparations unplug follicles and allow penetration of topical antibiotics and benzoyl peroxide. Retinoids can be used in combination with antibacterial agents and are also effective in the management of inflammatory acne.12 They are often irritating when first applied; patients can reduce the irritation by reducing the frequency of application. Significant improvement is evident within 6 weeks and can continue for 3 to 4 months, at which time the frequency of application can be reduced, depending on the patient’s response.
Newer formulations of retinoids that are purportedly less irritating include a tretinoin microsponge vehicle and adapalene, but few comparative studies examining irritation have been per-formed.13,14 Tazarotene, a topical retinoid used for acne and psoriasis, can be used effectively in a short-contact method, in which it is applied for seconds to minutes.15
Inflammatory Acne
Topical antibiotics are not as effective as retinoids or benzoyl peroxide for inflammatory acne, but they are less irritating and better tolerated. The resistance of P. acnes to antibiotics has been well documented; such resistance threatens the efficacy of this form of acne therapy in the future.16,17 It is therefore useful to prescribe antibiotics in combination with benzoyl peroxide, which does not induce resistance. A combined formulation of clin-damycin 1% and benzoyl peroxide 5% has been found to produce faster and greater reductions in P. acnes than formulations containing clindamycin alone.18 Moreover, the combination of benzoyl peroxide and clindamycin resulted in greater improvement in acne than either of its individual components alone.19
A commonly used regimen includes the combined antibiot-ic-benzoyl peroxide gel in the morning and topical retinoid in the evening. Azelaic acid, an anticomedonal and antibacterial agent, offers yet another choice for the topical treatment of acne. It, too, can be used in combination with topical retinoids, ben-zoyl peroxide, or topical antibiotics.20 Salicylic acid, an over-the-counter comedolytic agent, plays a minor role in the treatment of acne. Skin-colored sulfur-resorcinol lotions are available; these very effective drying and peeling agents can be useful for treating individual lesions [see Table 3].
Table 3 Topical Therapies for Acne
|
Medication |
Formulation |
Frequency of Application |
Primary Mechanism of Action |
Adverse Effects |
|
Azelaic acid |
20% cream |
b.i.d. |
Anticomedonal, antibacterial |
Stinging, irritation |
|
Benzoyl peroxide |
2.5%, 5%, 10% creams, gels, lotions, washes |
b.i.d. |
Antibacterial |
Dryness, irritation, allergic contact dermatitis |
|
Antibiotics |
||||
|
Clindamycin |
1% solutions, lotions, gels |
b.i.d. |
Antibacterial |
Antibiotic resistance |
|
Erythromycin |
2% solutions, creams, gels, pledgets, wipes |
b.i.d. |
Antibacterial |
Antibiotic resistance |
|
Erythromycin-benzoyl peroxide |
3% erythromycin-5% benzoyl peroxide gel |
b.i.d. |
Antibacterial |
Dryness, irritation, allergic contact dermatitis; deteriorates if not refrigerated |
|
Sodium sulfacetamide-sulfur |
10% sodium sulfacetamide, 5% sulfur lotions |
b.i.d. |
Antibacterial |
Dryness, irritation, allergic contact dermatitis |
|
Retinoids |
||||
|
Adapalene |
0.1% gels |
q.d. |
Comedolytic |
Dryness, irritation, photosensitivity |
|
Tazarotene |
0.05%, 0.1% gels |
q.d. |
Comedolytic |
Dryness, irritation, photosensitivity |
|
Tretinoin |
0.025%, 0.05%, 0.1% creams; 0.01%, 0.025% gels; 0.05% solutions |
q.d. |
Comedolytic |
Dryness, irritation, photosensitivity |
|
Sulfur and resorcinol |
2% resorcinol, 8% sulfur lotions, creams |
q.d., b.i.d. |
Comedolytic |
Dryness, peeling, allergic contact dermatitis |
|
Salicylic acid |
0.5%-2% gels, pads, soaps |
q.d., b.i.d. |
Comedolytic |
Dryness, irritation |
