Topical therapy may be useful 1) in the management of mild acne; 2) in combination with oral therapy in moderate to severe forms,with more inflammation and a tendency to scar; and 3) as maintenance treatment
Choice of topical agents depends upon acne variety. For comedonal acne, anticomedogenic agents are indicated, whereas antibacterial agents are required in inflammatory acne.Retinoids, azelaic acid, salicylic acid, and benzoyl peroxide are effective for comedones. Benzoyl peroxide, azelaic acid and topical antibiotics such as erythromycin and clindamycin are most effective in reducing inflammatory lesions.
Antibiotics act both as bacteriostatic/bactericidal on P. acnes and as direct antiinflammatory agents. Inhibition of P. acnes growth indirectly reduces inflammation. Antibiotics currently used are tetracyclines, macrolides
(erythromycin) and clindamycin. Topical antibiotics are indicated in the treatment of inflammatory acne, particularly milder forms and are available in a variety of vehicles such as creams, lotions, ointments, gels and solutions.
Antibiotics have been formulated in combination with other anti-acne agents such as benzoyl peroxide and topical retinoids. The principal
side-effect of topical antibiotics is the induction of bacterial resistance. Combination with benzoyl peroxide increases the bactericidal effect of the antibiotics, while reducing the risk of bacterial resistance development.
Topical retinoids acting on gene transcription regulate cell proliferation and differentiation and to a lesser extent inflammation, they also prevent microcomedonal formation and resolve mature comedones leading to:
a) reducedproduction of keratohyalin granules by
follicular keratinocytes, and b) inhibition of corneocytes accumulation and cohesion, increasing in this way infundibular keratinocytes
turnover. Retinoids, particularly adapalene,possess some anti-inflammatory activities,though they do not have a direct antibacterial effect. Tretinoin, the first topical retinoid used in acne, is available as a cream,gel or solution in a variety of concentrations. It has recently become available in new formulations such as microsponges or propylpolymers in order to minimize irritation. Adapalene is a naphtoic acid derivative with retinoid-like activity.Adapalene has been demonstrated to be equally effective as tretinoin, but better tolerated than the latter
It is available as gel, cream and solution. Isotretinoin is an alternative preparation with similar properties to tretinoin. It is available as cream or gel, either alone or in combination with topical antibiotic (erythromycin,
clindamycin). Tazarotene is a synthetic acetylenic retinoid authorized in psoriasis and acne. Formulated into a topical gel, it is active on cell proliferation, cell differentiation and inflammation. Although epidemiological studies haven’t demonstrated an increased risk of birth defects in infants whose mothers used topical retinoids during pregnancy, their use during
pregnancy is not recommended due to their teratogenic potential.
Benzoyl peroxide exercises a potent antimicrobial activity through the release of free oxygen radicals. It suppresses P. acnes in sebaceous follicles much faster than antibiotics, leading to a rapid reduction of the inflammatory lesions
number. P. acnes does not develop resistance to benzoyl peroxide, which maintains its efficacy after years of use. Benzoyl peroxide seems to have a mild comedolytic effect while it is not sebosuppressive. It often induces skin irritation, but a true allergic contact dermatitis is very rare. Benzoyl peroxide is available in different formulations such as gels, creams, lotions, and soaps as well as in some combination products.
Azelaic acid is effective on P. acnes suppression, even if less than benzoyl peroxide. The anti-inflammatory effect of azelaic acid seems to be related to a decreased production of reactive oxygen species by neutrophils.Azelaic acid
may also regulate the ductal cell keratinization,reducing the number of comedones. It is not sebosuppressive.
Chemical peels are usually considered as an adjunct to the basic treatment of acne vulgaris.
Unfortunately thereare no conclusive clinical trials comparing chemical peels with standard acne therapy in terms of efficacy and tolerability.
In case of acne scarring, chemical peels are useful to treat superficial scars and to improve medium-depth scars. In our experience the best option is the combined peel with 25% salicylic acid lotion and 25–30% TCA gel because the
sequential use of two agents allows the application of low concentrations of TCA with maximum benefits and minimal side effects
For medium and deep scars other treatments are available Systemic therapy for acne includes antibiotics, isotretinoin and hormones Oral treatment is indicated in cases of:
1) moderate and severe acne; 2) acne with tendency to scars development; and 3) psychological distress related to acne. Systemic antibiotics are indicated for moderate-severe inflammatory acne not responding to topical treatments. Systemic antibiotics acton: 1) suppression of P. acnes growth; 2) inhibition of bacterial lipases; 3) reduction of free fatty
acids; and 4) reduction of inflammation.
Oxytetracycline and its derivatives are the most commonly used oral antibiotics. Second-generation tetracyclines such as minocycline, doxycycline
and lymecycline present longer halflives, enhanced bacterial activity and lower
toxicity compared with the first generation ones. Minocycline (100–200 mg daily), doxycycline (100–200 mg daily) and lymecycline (150–300 mg daily) are equally effective, while lymecyclines seems to have a lower side-effect
profile. Antibiotics have to be given for prolonged periods of time; however, if a good response is not obtained after 3 months of treatment, an alternative therapy has to be kept in consideration. Side effects of tetracyclines include
gastrointestinal symptoms, vaginal candidiasis,dizziness, phototoxicity (doxycycline)and pseudotumor cerebri, autoimmune disorders
and pigmentation (minocycline). In patients allergic to tetracyclines or in females contemplating pregnancy, erythromycin represents
an acceptable alternative. The third-line treatment is oral trimethoprim. The increasing
P. acnes resistance to antibiotics, mostly macro-lides (erythromycin) and lincosamides (clindamycin) represents an important problem, to be suspected in cases of clinical response failure.Combining systemic antibiotics with topical
retinoids provides more rapid efficacy,while the concurrent use of benzoyl peroxide reduces the risk of resistant P. acnes strains development.
Oral Isotretinoin (13-cis-retinoic acid) efficacy is based on its specific actions against all four factors implicated in acne pathogenesis. Isotretinoin targets are 1) sebum suppression;2) comedolysis (normalization of follicular epithelial
desquamation); 3) anti-inflammatory effect; and 4) P. acnes reduction ensuing to sebum suppression. Indications for systemic isotretinoin
treatment are a) severe nodulo-cystic acne; b) acne unresponsive to conventional systemic antibiotic therapy; c) acne relapsing during or after conventional therapy; d) scarring acne; and e) severe psychological disability
related to acne. The drug is usually administered at a daily dosage of 0.5 mg/Kg, until a total cumulative dose of 100–150 mg/Kg has been
attained. A starting dosage lower than 0.5 mg/Kg/day with a gradual increase until the highest tolerable dosage reduces the risk of a severe flare of acne. Higher doses are associated with faster responses,but also with troublesome side effects. Isotretinoin treatment achieves a complete acne clearing in a large proportion of patients, while a further course is rarely required
Side effects of isotretinoin include first of all teratogenicity,mucocutaneous
problems, ocular dryness,muscoloskeletalm symptoms, hyperostosis and DISH, headache, elevation in sebum tryglicerides and liver enzymes. Monitoring of liver function tests and lipid profile is suggested before starting and during isotretinoin treatment.
Hormonal therapy can be an effective treatment in females affected by inflammatory acne. Different varieties of hormonal therapies are available. Oral estrogens are used due to their anti-acne effect by decreasing the level of circulating androgens and increasing sex-hormonebinding protein. In contraceptive pills estrogens are administered as a combination with progestins. The most used estrogenic component is largely ethinyl estradiol. Second-generation progestins (ethynodiol diacetate,norethindrone, levonorgestrel) and third-generation progestins (desogestrel, norgestimate, gestodene) have a lower androgenic activity than first-generation progestins. Inflammatory lesions, scarring and severe seborrhea can suggest the administration of the combination oral
estrogen/progestin in women. The improvement is usually slow.
Cyproterone acetate (CPA) is a progestational antiandrogen that blocks the androgen receptors. It is combined with ethinyl estradiol in an oral contraceptive formulation, which is indicated in female acne patients with a high level of seborrhea, therapy resistant papulo-pustular acne or acne conglobata not responding to other treatments. Spironolactone is an antiandrogen which blocks androgen-receptors, alters steroidogenesis by adrenals and gonads and inhibits 5-α reductase.
In doses of 100–200 mg daily it reduces sebum production and improves inflammatory acne in women. During treatment, birth control measures are required due to the risk of male fetus feminization.(C)Vincenzo Bettoli et al.
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