(1997; 132 pages) [French] [Spanish]
Acne is an inflammatory disease of the pilosebaceous units in the skin of the face, neck, chest and upper back. Typically, it first appears during early puberty when androgenic stimulation triggers excessive production of sebum and abnormal follicular keratinization, colonization by a Gram-positive bacterium (Propionibacterium acnes) and local inflammation. P. acnes produces inflammation through the production of extracellular products such as lipases, proteases, hyaluronidases and chemotactic factors.
Clinically, the disease varies in intensity from a minor condition, in which there are a few comedones (dilated pilosebaceous cysts containing sebum, cornified epithelium, bacteria and saprophytic yeasts) which heal without scarring, to a severe disfiguring disease in which nodules and sinuses form in areas of intense inflammatory reaction. Scarring is sometimes followed by keloid formation, particularly among Africans. There is no evidence that dietary manipulation can influence its course. Occasionally, systemic or topical exposure to specific chemicals is implicated. These include:
• orally administered drugs, notably corticosteroids, isoniazid, lithium carbonate, phenytoin, and halogen-containing sedatives and expectorants;
• topical exposure to an irritant oil or cosmetic;
• environmental exposure, even in minute amounts, to dioxin or halogenated phenolic compounds.
Since severe scarring of the skin resulting from severe nodular acne is a major social handicap, the disease should always be treated in its early stages.
Exposure to substances suspected of causing or aggravating the condition should be avoided. Drug therapy is directed to reducing secretion of sebum and follicular keratinization and to inhibiting inflammation. Mild cases usually respond satisfactorily to topical therapy alone. Oral antibiotics are commonly used in moderate to severe cases, while oral estrogens, antiandrogens or retinoids should be reserved for severe and unresponsive cases.
Systemic treatment must be sustained for several months before a response can be anticipated. During this time topical preparations should be applied to the affected areas to prevent the development of new lesions.
Benzoyl peroxide, which promotes desquamation and has a bactericidal action, is most widely used. Gel formulations are claimed to be more effective than creams or lotions, but they are also more irritant. Treatment is usually started with a 2.5% or 5% preparation applied once daily on alternate days. The frequency of application is then gradually increased as the initial irritant reaction subsides.
Tretinoin is claimed to be more effective than benzoyl peroxide in cases with a comedonal component, but it is also much more expensive. It reduces follicular hyperkeratosis by stimulating the turnover of epithelial cells. It is less effective in cases of inflammatory acne, which must be treated at the same time with a topical or systemic antibiotic or with topical benzoyl peroxide. It also induces a variable degree of irritation, which is aggravated by exposure to ultraviolet light.
Topical antibiotics such as erythromycin and clindamycin are widely used in the treatment of inflammatory acne. Treatment usually has to be maintained for 2-3 months before any benefit is obtained.
Preparations containing sulfur (which is also bactericidal and promotes desquamation) continue to be used, often in formulations additionally containing salicylic acid as a keratolytic agent. However, they are now considered obsolete in many countries because there is insufficient evidence of efficacy and more reliable products are available.
Systemic administration of estrogens, antiandrogens or retinoids should be considered only when topical treatment or the use of oral antibiotics fails or when severe nodular acne threatens to result in substantial scarring. These drugs should be administered by a dermatologist.
The clinical response to systemically administered antibiotics is probably not dependent upon the antimicrobial action alone. Penicillins, for instance, are likely to be effective only in cases of folliculitis due to Gram-negative bacteria, even though they are bactericidal to P. acnes. Tetracycline should be used at a dosage of 1 g daily (2 g daily for patients with severe involvement) for the first 2 months. Subsequently, the antibiotic dosage can be reduced in accordance with the clinical response and discontinued, if possible. The duration of therapy is dependent on the clinical response, and oral antibiotics may have to be continued for many months. It has been claimed that the emergence of resistance is less likely with the newer derivative, minocycline, which has a prolonged half-life and is used at a dosage of 50-100 mg daily. Tetracyclines may interfere with the metabolism of oral contraceptives. Barrier methods of contraception should consequently be used throughout treatment. Erythromycin is commonly substituted when tetracyclines are contraindicated. Sulfamethoxazole + trimethoprim may also be used, but it can cause side-effects, including drug eruptions and agranulocytosis.
Estrogens and antiandrogens, which produce clinical remission by reducing the secretion of sebum, can be used to supplement specific anti-acne therapy, but should be restricted to women because of their feminizing action. Combined oral contraceptives are often effective when administered at normal dosages. Products containing norethisterone are used in some countries because, by raising the serum concentrations of sex hormone-binding globulin, they reduce the plasma concentrations of free testosterone. Antiandrogens, such as cyproterone and chlormadinone, administered in combination with the estrogen ethinylestradiol (to assure a contraceptive action), have been claimed to be more effective.
The oral retinoic acid derivative isotretinoin, which is a more potent inhibitor of sebum production, is the most effective treatment available for severe cystic acne though very expensive. However, it often induces signs of chronic hypervitaminosis A, including cheilitis, dry eyes, generalized xerosis, pruritus and paronychia, and, most problematic of all, it is a proven and potent human teratogen. It is therefore imperative that pregnancy be excluded before this treatment is instituted. Effective contraception must be used during the 4 weeks preceding and following treatment, as well as during the treatment period. Should pregnancy occur despite these precautions, there is a high risk of severe malformation of the fetus.