ACNE - NEJM REVIEW

Clues:
In mild Acne: benzoyl peroxide (2.5-5%) plus (clindamicine or adapalene) in topical use twice daily
In moderate acne: benzoyl peroxide plus oral Doxicicline 100mg twice daily
In severe Acne: Isotretinoine 40 mg once dailyplus oral doxicicline 100mg twice daily (if it's women, add hormonal therapy)


Acne is a follicular disease, the principal abnormality of which is impaction and distention
of the pilosebaceous unit. The cause of the hyperproliferation of keratinocytes
and the abnormalities of differentiation and desquamation are unknown. It is likely that
hyperresponsiveness to the stimulation of sebocytes and follicular keratinocytes by
androgens leads to the hyperplasia of the sebaceous glands and the seborrhea that
characterize acne.
7-9
Propionibacterium acnes colonizes the follicular duct and proliferates in teenagers with
acne.10

This organism probably contributes to the development of inflammation. With
this combination of factors present, the follicular epithelium is invaded by lymphocytes;
it ruptures, and sebum, microorganisms, and keratin are released into the dermis.
Neutrophils, lymphocytes, and foreign-body giant cells accumulate and produce the
erythematous papules, pustules, and nodular swellings characteristic of inflammatory
acne

The diagnosis of acne is usually readily made. Acne is characterized by open and closed
comedones (blackheads and whiteheads), which are present either alone or, more
commonly, with pustules and erythematous papules concentrated on the face and
upper trunk. Many systems for grading the severity of disease have been used. The severity
of acne is generally assessed by the number, type, and distribution of lesions.

For the mild, primarily comedonal, types of acne (Fig. 1), topical retinoids may be used alone, where as for patients with more severe acne, the use of these products in combination with topical or oral antimicrobial agents is appropriate. Randomized, double-blind, multicenter comparative studies have shown a reduction of 38 to 71 percent in noninflammatory and inflammatory lesion counts. Direct comparisons of topical retinoids have indicated that tazarotene in a 0.1 percent gel is more efficacious than 0.1 percent tretinoin or 0.1 percent adapalene, 14,15 although tazarotene also tends to be the most irritating. The maximum therapeutic response to topical retinoids occurs over approximately 12 weeks.




Antimicrobials
Topical antimicrobial agents are effective in the treatment of inflammatory disease.
24 Benzoyl peroxide is a bactericide and is an excellent first-line
medication. The response to this agent is rapid, with improvement noted as early as five days after treatment has begun, but irritation is common. Water-based products, as compared with alcoholbased products, when used at low peroxide concentrations (2.5 to 5 percent) will help to limit this problem and have an efficacy similar to that of other products in this class. Topical clindamycin or erythromycin also may be useful, but, as documented in many randomized,
clinical trials, these agents are most effective when used in combination with benzoyl peroxide or
topical retinoids

Oral Antibiotics
Oral antibiotics are indicated for moderate-tosevere disease, for the treatment of acne on the
chest, back, or shoulders, and in patients with inflammatory disease in whom topical combinations have failed or are not tolerated.
When oral therapy is warranted, tetracycline is inexpensive and often effective in previously untreated cases. Clinical experience and limited data have suggested that doxycycline, minocycline, and trimethoprim– sulfamethoxazole are more effective than tetracycline.
Doxycyline and minocycline are both preferred over trimethoprim–sulfamethoxazole
because of the side-effect profile.
Starting the therapy at higher doses is recommended, since the response cannot be judged for at
least six weeks and full efficacy is not apparent for three months.
Oral antibiotic therapy generally is taken over a three-to-six-month course. Eventual discontinuance is the goal, followed by long-term topical therapy. Resistance is an increasing problem, since 60 percent of P. acnes isolates are resistant to at least one antibiotic; resistance is most common with the use of erythyromycin (50 percent of cases), clindamycin (35 percent), and tetracycline (25 percent). Tetracyclineresistant strains of P. acnes are usually also resistant
to doxycycline, so a switch to minocycline is recommended if resistance to tetracycline is suspected.

Therapy with oral contraceptives containing estrogen or with spironolactone, an androgen antagonist, is often useful in women with hyperandrogenism and in women with normal serum androgen levels. The effects on acne of injectable progestins and patch systems have not been evaluated, and progesterone-only contraceptives may make acne worse.

deep-seated nodules of the lower face and neck (Fig. 6) are part of a subset of patients in whom
hormonal treatment may be especially useful.

Patients with severe acne that does not clear with combined oral and topical therapy are candidates for treatment with oral isotretinoin Approximately 40 percent of patients remain free
of acne after one course of treatment, 40 percent have a recurrence of low severity that responds to medications to which the acne had previously been resistant, and 20 percent will need repeated treatment with isotretinoin at a future time.

Patients younger than 16 years, those with severe acne on the trunk, and adult women are more likely than others to have a relapse. The chance of a prolonged remission is greater when a total dose of 120 to 150 mg per kilogram of body weight is achieved.

Most patients can be started on 20 to 40 mg per day, with an increase
to 40 to 80 mg over several months. Isotretinoin is teratogenic, so it must be used with hormonal therapy. Isotretinoin may cause hypertriglyceridemia and, to a lesser extent, can affect cholesterol levels. Alterations in dosing or dietary interventions usually allow for the continuation of treatment. Drying of the nasal mucosa may occur, which can lead to colonization
of S. aureus , the potential complications of which include abscesses, conjunctivitis, impetigo,
cellulitis, and folliculitis. These complications may be prevented with the use of intranasal bacitracin