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Properly Treating Acne
Summarized By: Robert W. Griffith, MD
Acne is a rite of passage that, according to some estimates, affects 85-100% of people aged 12 to 24 years of age. Its management was largely revolutionized by the introduction of isotretinoin in the early 1980s. Dr Bershad of Mount Sinai Hospital, New York, has recently reviewed the current treatment choices for acne.
Acne -- the condition
Acne is caused by chronic inflammation behind a follicular duct that is blocked by a comedo (a plug of sebum and keratin). Comedones appear as 'blackheads' and 'whiteheads'. If a comedo causes the follicular wall to rupture, subsequent infection leads to papules, pustules, nodules, and cysts.
Lesions are usually seen on the face and upper trunk. Frequency and severity (including scarring) are greater in male adolescents, whereas persistence into adulthood is commoner in females.
Contrary to popular wisdom, hygiene and diet play almost no role in the etiology of acne. An adolescent surge of androgenic hormones against a genetic predisposition is a more likely mechanism. The inflammation that occurs is usually caused by the recruitment of neutrophils by a diphtheroid bacteria -- Propionobacterium acnes.
Approaches to treatment
In the early ('comedonal') stages, where open and closed comedones are the main feature, the treating physician should manually extract the impacted comedones with the appropriate instrument, every 3 to 6 weeks. Patients should not try to express comedones themselves, because of the risk of infection or scarring from excessive trauma. Topical medications used in this stage are the keratolytic agents -- the retinoids, azelaic acid, and alpha-hydroxy acids.
These keratolytic compounds are analogs of vitamin A that can be given topically or orally. The first to be developed was tretinoin, which has been used topically since 1971. It works by increasing the turnover of follicular cells, normalizing keratinization and extrusion of comedones. Subsequent derivatives and formulations have led to better-tolerated topical retinoids, including some with prolonged duration of action by employing slow-release agents.
Nevertheless, retinoids applied topically can produce local skin irritation, and increase sun sensitivity. The most recently developed ones, adapalene and tazarotene, have demonstrated improved reduction in comedones with less local irritation; they also have some intrinsic anti-inflammatory activity. In one form of therapy developed by Dr Bershad, tazarotene is applied once or twice daily for only 2-5 minutes per application; this short-contact regimen can produce a 50% reduction in comedonal acne lesions within a 12-week period.
When infection is present, so that the predominant lesions are papules or pustules, topical or systemic antibiotics can supplement keratolytic agents. Often a topical antibiotic is applied in the morning, and a keratolytic compound at bedtime. If it's necessary to avoid the risk of antibiotic resistance developing, the antibiotic can be applied twice during the day and the keratolytic at bedtime.
The topical antibiotics used today are usually clindamycin or erythromycin as hydrophilic gels or lotions. 1% clindamycin solution has been shown to be as effective in treating inflammatory acne as 250 mg oral tetracycline twice daily. Topical antibiotics are sometimes used as fixed combinations with benzoyl peroxide or zinc, both of which have anti-inflammatory activity. Sulfur compounds are also used.
Benzoyl peroxide is a potent bactericidal agent supplied in gels, lotions, and cleansers. It reduces comedones as well as improving inflammatory acne. However, it produces dry skin and sometimes bleaching of the skin and clothing. Occasionally, allergic contact dermatitis can develop.
Systemic antibiotic treatment includes: tetracyclines (including minocycline and doxocycline), erythromycin, azithromycin, and triomethaprim with or without sulfamethoxazole. The increasing occurrence of antibiotic-resistant bacteria has led to the use of full-dose antibiotics given for 2-3 weeks, repeated if there are flare-ups. Phototoxicity (tetracyclines), dizziness (minocycline), gastrointestinal distress (erythromycin), and drug eruptions (triomethaprim) are the commonest side effects of systemic antibiotic administration.
Hormonal therapy maybe considered in some cases -- there is a direct correlation between serum androgen levels and acne. Possibly the sebaceous glands of acne-prone subjects are hypersensitive to androgens. A triphasic combination oral contraceptive, containing norgestimate and ethinyl estradiol, has been approved specifically for acne treatment in females; it has few intrinsic androgenic effects and minimal anti-estrogenic effects. An alternative anti-androgen drug for use in women is spironolactone, which can be combined with an oral contraceptive.
Severe nodulocystic acne will respond to all the treatments described so far to a limited extent, but today oral isotretinoin (13-cis-retinoic acid) is the treatment of choice. It suppresses sebum production to pre-adolescent levels, and promotes keratinocyte shedding. One full course produces significant improvement in about 80% of patients, lasting for 3 years or more. An international consensus on dosage was reached in 1997: a cumulative dose of 120 mg per kilogram body weight over a 20-week period, using the original oral formulation1. One or more new dosage forms possessing improved absorption characteristics are in development, and prescribers must bear this in mind when determining dosage schedules.
Rare but serious side effects of isotretinoin include severe headache, nausea and vomiting, which may possibly be the signs of pseudotumor cerebri. Acute pancreatitis has also been reported. More commonly, the following may occur: dry, cracked skin or lips, nosebleeds, conjunctivitis, patchy eczema, myalgia, arthralgia, hyperlipidemia, and hypersensitivity to sunlight. In rare instances there are symptoms of depression, and suicide has been reported in patients taking the drug, but a large controlled study failed to find a clear association between isotretinoin and depression. Tetracyclines should not be given with isotretinoin, as they may increase the risk of pseudotumor cerebri.
The major problem encountered with isotretinoin treatment is the risk of a teratogenic effect. In addition to careful patient selection and contraceptive counseling, monthly pregnancy testing is mandatory for sexually active women during treatment.
Relapses can occur in up to 60% after isotretinoin treatment, but only a third of these are severe enough to require a repeat course of the drug. An 8-week drug-free interval is necessary before starting a second course of treatment.
Dr Bershad explains that acne patients are often inadequately treated, because: they don't seek medical treatment, the therapy is not individually optimized, or compliance is poor. Good physician-patient communication is necessary to ensure that the patient follows the chosen therapeutic regimen carefully. All acne medication is essentially prophylactic, so that treatment must be applied to nonlesional skin, and continued when the condition is at its best.
Topical therapy should be used, when possible, to avoid possible systemic side effects. Combination of a keratolytic agent with an antibiotic is a logical approach. Isotretinoin is an extremely effective drug for difficult cystic acne, but its side-effect profile requires appropriate precautions and patient monitoring. The perfect drug for acne has not yet been found.
The Modern Age of Acne Therapy: A review of current treatment options. SV. Bershad, Mt Sinai J Med, 2001, vol. 68, pp. 279--286
1. Roaccutane treatment guidelines: Results of an international survey. WJ. Cunliffe, PC. Van der Kerkhof, R. Caputo, et al., Dermatology , 1997, vol. 194, pp. 351--357