CASE #2: Acne vulgaris

With about 10 million new cases diagnosed every year, acne vulgaris is the condition most commonly treated by dermatologists and affects almost everyone at some point in their lives.12 The clinical presentations of acne include open comedones (blackheads), closed comedones (whiteheads), red papules, pustules, cysts, milia, ice-pick scars, and atrophic scars. Acne most commonly occurs on the face but often affects the scalp, neck, chest, and back. In some cases, acne appears to be related to excess sebum production and oily skin. The lesions of acne are both inflammatory and noninflammatory, which has implications for treatment.

The differential diagnosis of acne includes eosinophilic pustular folliculitis (most closely associated with HIV infection), gram-negative folliculitis (GNF), perioral dermatitis, sebaceous hyperplasia, syringoma, tuberous sclerosis (adenoma sebaceum), trichoepithelioma, Demodex folliculitis, bacterial folliculitis, and papular sarcoidosis. The diseases that most closely resemble acne include GNF, rosacea (classically defined as a facial eruption lacking comedones), perioral dermatitis (thought to be a variation of rosacea), and acneiform drug eruptions (most commonly associated with epidermal growth factor blockers but related to lithium and phenytoin at a lower incidence).

Acne can manifest in tandem with other eruptions and result in scarring that lasts beyond its resolution.12 Acne vulgaris can overlap with acne rosacea or seborrheic dermatitis. Acne also can occur concurrently with GNF. Acne can leave behind hypertrophic scars, pitted scars, sinus tracts, keloids, and atrophic scars. In men of color, pseudofolliculitis is a common sequela of acne in the beard area. In old age, those who had acne earlier in life and suffered actinic damage can manifest with Favre-Racouchot syndrome, a condition whose relationship to acne is unclear.

The causes of acne are manifold and include infection with Propionibacterium acnes, which reside within the pilosebaceous unit in a biofilm. P. acnes can produce active enzymes and inflammatory mediators that may contribute to the condition’s progression, including smooth-muscle contracting substances, lipases, proteases, hyaluronate lyase, and phosphatase.

Acne is related to hormonal imbalances. Patients with acne have higher androgen levels, and those with androgen insensitivity syndrome do not develop acne. On the cellular level, acne has been related to defects in T-cell receptors. Some have linked intake of fatty foods to acne, but this ralationship remain controversial. Smoking is a clinically important contributory factor to acne prevalence and severity.

Acne can be caused by such oral medications as trazodone (Desyrel, Oleptro), haloperidol (Haldol), estrogens, phenytoin (Dilantin), isoniazid (Tubizid), lithium (Eskalith, Lithobid), and halogens. Epidermal growth factor blockers have been linked to an acneiform eruption (histologically a folliculitis) whose severity parallels clinical effect. Topical and oral corticosteroids can induce or worsen acne. Steroid acne is characterized by monomorphous dome-shaped papules on the chest and is often encountered in patients with collagen vascular diseases or with neurological pathology that requires protracted courses of such potent oral corticosteroids as dexamethasone (Decadron).

Acne treatments are varied and include proper cleaning regimens, topical agents, oral antibiotics, oral retinoids, and oral hormonal therapies.12 The skin can be easily irritated by topical agents that are used to treat acne. The use of mild, nondrying cleaning products and noncomedogenic moisturizers may help reduce this irritation.

Topical therapy is usually the best place to start treatment.12 If tolerated, benzoyl peroxide is the simplest and most cost-effective treatment. Bacterial resistance to benzoyl peroxide has not been noted. This agent varies in strength from 2.5% to 10% and can be used as a leave-on product or as a wash. It is available OTC and by prescription in various topical forms, including pads, soaps, washes, lotions, creams, and gels. Benzoyl peroxide is also available as part of combination products that also contain clindamycin or erythromycin. More so than other topical acne treatments, benzoyl peroxide can induce allergic contact dermatitis.

A first-line treatment for acne involves the use of such topical retinoids as tretinoin (Retin-A), adapalene (Differin), and tazarotene (Tazorac). Retinoids increase epidermal differentiation and help normalize and abate follicular hyperproliferation and hyperkeratinization. They are the only topical medications that open and abate closed comedones (i.e., noninflammatory acne). Topical retinoids decrease the quantity of micro-comedones, comedones, and inflammatory papules and pustules. Retinoids are effective as monotherapy or can be combined with topical regimens that include antibiotics and benzoyl peroxide. Topical retinoids can also be used in conjunction with oral antibiotics.

Topical retinoids should be applied to clean, dry skin once daily. If irritation occurs with daily use, they can be applied every other day or every third day. Skin irritation, flaking, peeling, and redness have been linked to the use of topical retinoids. Mild, non-drying skin cleaners and noncomedogenic moisturizers may help reduce this irritation. Alternate-day dosing may be used if irritation persists. Topical retinoids thin the stratum corneum and can be associated with sun sensitivity.

Such topical antibiotics as erythromycin and clindamycin are a mainstay of acne treatment. These agents, like their oral counterparts, are particularly effective against inflammatory acne; acne related to P. acnes responds to topical or oral antibiotics. Antibiotics do not abate comedones and carry the risk of bacterial resistance. The development of resistance is lessened if topical antibiotics are used in combination with benzoyl peroxide.

Oral antibiotics are effective in the treatment of acne, particularly when related to inflammation or P. acnes infection. Tetracyclines are commonly used to treat acne. Doxycycline and minocycline each 50-100 mg b.i.d. are effective treatments for acne. Sustained-release forms of doxycycline and minocycline might have a better side-effect profile than generics but are much more expensive. Some think that more lipophilic antibiotics and antibiotics with less P. acnes resistance, such as minocycline, are more effective than tetracycline.

While oral erythromycin has long been used in the treatment of acne, P. acnes resistance has greatly reduced its utility in therapy. Azithromycin has been suggested as an effective acne treatment and may be more useful than erythromycin because of its longer half-life, greater anti-inflammatory activity, greater coverage of gram-negative organisms, and fewer GI adverse effects. TMP/SMX b.i.d. in a double-strength tablet is an effective therapy for acne that often works when other antibiotics fail.

Among women, oral contraceptives (OCs) are effective for acne that waxes and wanes with the menstrual period and is related to excess androgen. Several OCs are approved for the treatment of acne vulgaris. OCs increase sex hormone-binding globulin; this decreases circulating free testosterone, thereby abating acne. Combination birth-control pills have shown efficacy in the treatment of acne vulgaris.

Isotretinoin (Accutane), a systemic retinoid, is the single most effective agent for the treatment of acne of all types. A cumulative dose of 120 to 150 mg/kg is optimal; it is preferred that isotretinoin 1.0 mg/kg be given in a divided dose b.i.d. for five months or that therapy be initiated at a dose of 0.5 mg/kg/day for four weeks and increased as tolerated until a dose of 1.0 mg/kg daily is achieved. Some experts advocate a six-month regimen of treatment with low-dose isotretinoin (20 mg/day) and note that such dosing is cheaper and has a lower incidence of severe side effects than higher-dose regimens.

Fertile women must be informed that isotretinoin is a teratogen. In the United States, isotretinoin can only be distributed if patients, clinicians, and pharmacists participate in the iPLEDGE (www.ipledgeprogram.com) program. This program requires patient enrollment and confirmation of a negative pregnancy test in fertile women before a pharmacist will distribute the isotretinoin.

Pharmacologic doses of nicotinamide 1.5 g/day, given in two or three divided doses, have been used for acne, often in combination with zinc, copper, and folic acid.13 Oral and topical zinc have been advocated as treatments for acne, but strong evidence of its effect has yet to be established.

After multiple negative pregnancy tests, the patient was enrolled in the iPLEDGE system and given isotretinoin 30 mg b.i.d. with norgestimate/ethinyl estradiol. Five months later, her acne had abated almost completely.

Ms. Woody is a family nurse practitioner at the Colgate Palmolive Health and Wellness Center in New York City. Dr. Scheinfeld is assistant clinical professor of dermatology at Columbia University in New York City, where he has a private practice. Neither author has any relationship to disclose relating to the content of this article.



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