Acne Vulgaris and Related Disorders Part 2

Systemic therapy

Systemic agents are warranted for patients with nodulocystic acne or inflammatory acne that is not responsive to topical therapy. Oral antibiotics are usually the first line of systemic treatment. Isotretinoin has generally been reserved for patients whose acne is refractory to antibiotics. Isotretinoin may be used as initial therapy in patients with particularly severe acne to prevent scarring and in patients with a history of antibiotic intolerance.

Antibiotics

Antibiotics have both antibacterial and anti-inflammatory effects that are beneficial in treating acne. The antibiotics most commonly used for acne are doxycycline, erythromycin, mino-cycline, tetracycline, and trimethoprim-sulfamethoxazole [see Table 4]. Because antibiotic resistance is a major problem with many of the older antibiotics, minocycline has been prescribed for many acne patients even though it is considerably more expensive. Strains of P. acnes that are resistant to minocycline have begun to emerge, however, and this may limit the usefulness of this drug in the future.21 The duration of treatment with oral antibiotics depends on patient response. Azithromycin given at a dosage of 500 mg/day for 4 days, repeated at 10-day intervals for four cycles, is as effective as minocycline given at a dosage of 100 mg/day for 6 weeks.22 Further refinements of regimens with these newer antibiotics will undoubtedly be performed before they achieve more widespread usage.

A lupuslike syndrome has been reported in patients taking oral minocycline. Synovitis, the presence of antinuclear antibodies, and elevations in hepatic transaminase levels were reported, but renal disease and central nervous system disease do not oc-cur.23 Upon discontinuance of minocycline, symptoms resolve, but upon retreatment, the syndrome recurs.

Controversy about the long-term use of antibiotics for the treatment of acne was raised by a 2004 study that suggested a correlation between antibiotic use and breast cancer risk. The study found that an increase in the cumulative number of days of antibiotic use—including use of tetracyclines and macrolides, which are prescribed for acne—was associated with greater breast cancer risk.24 Although the results of this study have been questioned because of the way the study was performed and other shortcomings of the study, the possibility of increased risk remains a concern.

Isotretinoin

Oral isotretinoin is the most effective agent available for the treatment of acne. It results in long-lasting remissions or cures in the majority of patients treated. Because of its serious potential adverse effects, however, isotretinoin is not generally used as first-line therapy except for unusual cases.

Most of the side effects of isotretinoin are dose related and affect a majority of patients treated. For example, cheilitis uniformly occurs in patients treated with significant doses. Myalgias, dryness of mucous membranes, dry eczematous skin changes, and hyperlipidemia frequently occur. Total serum cholesterol levels can rise in patients taking isotretinoin, and triglyceride levels can rise sufficiently to cause pancreatitis.

Teratogenicity occurs with the administration of even a single dose of isotretinoin to pregnant women. Birth control counseling is an essential part of the management of women for whom isotre-tinoin is prescribed. The use of two forms of contraception is advised. Despite major educational efforts, pregnancies in women receiving isotretinoin continue to occur, resulting in severe birth defects.25 With the introduction of generic isotretinoin, concern over teratogenicity increased. In response, the manufacturers of isotre-tinoin started a program in which physicians and pharmacists who prescribe and administer isotretinoin must register and agree to require that patients receiving isotretinoin undergo pregnancy testing on a regular basis.26 Unfortunately, this program failed to eliminate pregnancies in women treated with isotretinoin. Attempts to enforce guidelines on the safe use of isotretinoin27 have been deemed inadequate, and as a result, more stringent barriers to the prescription of isotretinoin are being instituted.28

Table 4 Commonly Prescribed Systemic Therapies for Acne

There have been several instances of suicide and depression occurring in patients receiving oral isotretinoin.29,30 Teenagers with severe acne may be at increased risk for suicide, regardless of the treatment they are using. A study compared the risk of depression, psychotic symptoms, suicide, and attempted suicide in acne patients receiving isotretinoin with the risk in acne patients being treated with oral antibiotics. The relative risk of depression or psychosis for isotretinoin-treated patients was 1.0, and the relative risk of suicide and attempted suicide was 0.9, suggesting that isotretinoin does not cause depression.31 A study of pharmacy prescriptions yielded similar results. Prescriptions for antidepressants were quantified in 2,821 patients who filled isotretinoin prescriptions for the first time, and they were again quantified for patients filling isotretinoin prescriptions for a second time. The ratio of antide-pressant use with the first prescription of isotretinoin to antide-pressant use with the second prescription was not significantly different from 1.0—a finding that does not support an association between the use of isotretinoin and the onset of depression.32

Pseudotumor cerebri is a rare side effect of isotretinoin. It occurs more commonly in patients who are concomitantly given oral antibiotics.

Extensive counseling and monitoring—including complete blood counts, chemistry screens, and pregnancy tests when appropriate—should be done before treatment with isotretinoin; such counseling and monitoring should continue at 2-week intervals during the first month of treatment and monthly thereafter. Depending on patient response, treatment with 0.5 to 1.0 mg/kg/day in two divided doses should be continued to a cumulative dose of 120 to 150 mg/kg. Some clinicians have continued low-dose isotretinoin therapy for more than 6 months. Rarely, a second course of therapy is indicated when acne recurs.

Hormone Therapy

Estrogens in the form of oral contraceptives can be beneficial for patients with acne; progestins, however, can exacerbate the condition. The newer progestins—desogestrel, norgestimate, and gestodene—have less androgenic activity and therefore are less likely to exacerbate acne. A combination of ethinyl estradiol and norgestimate has been shown to be beneficial in the treatment of acne.33 An oral contraceptive containing ethinyl estradiol in graduated doses, along with stable doses of norethindrone acetate, has been shown to have minimal androgenic activity and is also used for the treatment of acne.34 A combined oral contraceptive containing ethinyl estradiol and drospirenone has also been found to effectively treat acne.35 These agents are ideal for women who are seeking birth control methods and for women who are not candidates for, or who have not responded to, oral antibiotics or isotretinoin. Oral contraceptives can be particularly helpful to women with polycystic ovary syndrome. It is noteworthy that the beneficial effects of combined oral contraceptives are diminished in patients who are obese.36

Some concerns have been raised about the concomitant use of antibiotics and oral contraceptives because some antibiotics may interfere with contraceptive activity. Reviews of large numbers of patients treated concomitantly with oral contraceptives and antibiotics have not revealed significant increases in pregnan-cies.37 Nevertheless, caution is advisable when a patient uses an antibiotic and an oral contraceptive together, especially one of the newer contraceptives that contain low doses of estrogen.

Phototherapy

A number of light sources have been tested for the treatment of acne. Photodynamic therapy using topical 6-aminolevuIinic acid has demonstrated efficacy for acne. Photodynamic therapy did not reduce P. acnes numbers or sebum excretion, so the mechanism by which it works is not entirely known.38 A blue light administered twice weekly for 4 consecutive weeks has demonstrated efficacy for acne but not for nodulocystic lesions.39 The 1,064 nm Q-switched neodymium:yttrium-aluminum-garnet (Nd:YAG) laser has proved useful for the treatment of acne scarring.40

Treatment of rosacea

Avoidance of triggers such as alcohol, hot or spicy foods, and heat are an important part of the therapeutic regimen offered to patients with rosacea. Sunscreens are likewise important. Telan-giectasia can be treated with laser therapy. Papules and pustules respond to the same topical and oral antibiotics used for acne, although benzoyl peroxide is less commonly used for rosacea. Flushing is difficult to treat. Azelaic acid may offer some benefit for the erythema associated with rosacea.