Acne Treatment, Systemic Therapy, AntibioticsSYSTEMIC THERAPY Over the years, many different agents have been used systemically. The major systemic modalities that are currently being used include antibiotics and antibacterial agents, hormones, and an oral synthetic retinoid.
Antibiotics and antibacterial agents
Currently, the broad-spectrum antibiotics are widely used in the treatment of acne. Although the oral administration of tetracycline does not alter sebum production, it does decrease the concentration of free fatty acids while the esterified fatty acid content increases. This decrease in free fatty acids is seen with dosages ranging from 250 mg/day to 1 g/day. The free fatty acids are probably not the major irritants in sebum, but their level is an indication of the metabolic activity of the organism and its secretion of other proinflammatory products. The decrease in free fatty acids may take several weeks to become evident. This, in turn, is reflected in the clinical course of the disease during antibiotic therapy, as several weeks are often required for maximal clinical benefit. The effect, then, is one of prevention; the individual lesions require their usual time to undergo resolution. However, the fact that a decrease in free fatty acids does occur strengthens the rationale for the use of tetracycline. Tetracycline may act through direct suppression of the number of P. acnes, but part of its action may also be due to its anti-inflammatory activity. Decreases in free fatty acid formation also have been reported with erythromycin, demethylchlortetracycline, clindamycin, and minocycline. Most studies support the efficacy of tetracycline and its derivatives in the treatment of acne. In clinical practice, tetracycline is usually given initially in dosages of 500 mg/day to 1000 mg/day. While the dose is often decreased as improvement occurs and may be continued at a level of 250 mg/day or less, there is increasing concern that this may generate resistant strains. Tetracycline should be taken on an empty stomach to promote absorption. Erythromycin has been used in the past in patients who have difficulty in taking tetracycline on an empty stomach, but there is increasing evidence of the development of erythromycin-resistant strains of P. acnes from both the topical and systemic use of erythromycin. Therefore, it is wise to limit the use of oral erythromycin to those cases where tetracyclines are contraindicated, that is, in pregnant women and young children. Increasingly, doxycycline and minocycline are being used as alternatives for tetracycline or in tetracycline-unresponsive cases. These two drugs appear to be more effective than tetracycline, and drug resistance is less likely to occur, especially with minocycline. Doxycycline should be administered in dosages of 50 to 100 mg twice daily. The major disadvantage of the use of doxycycline is that it can produce photosensitivity reactions, and patients should be switched to another antibiotic, if possible, during the summer months. Minocycline is given in divided dosages at a level of 100 mg/day to 200 mg/day. Patients on minocycline should be monitored carefully as the drug can cause blue-black pigmentation, especially in the acne scars, as well as the hard palate, alveolar ridge, and anterior shins. Minocycline-induced autoimmune hepatitis and a systemic lupus erythematosus-like syndrome have been reported during minocycline therapy, but to date, these side effects are very rare. Oral clindamycin has been used in the past, but because of the potential of pseudomembranous colitis, it is now rarely used for acne. Although long-term, low-dosage antibiotic therapy is often continued for many months, very few side effects have been observed. Tetracyclines have an affinity for rapidly mineralizing tissues and are deposited in developing teeth, where they may cause irreversible yellow-brown staining; also, tetracyclines have been reported to inhibit skeletal growth in the fetus. Therefore, they should not be administered to pregnant women, especially after the fourth month of gestation, or to babies. The tetracyclines also should not be given to children younger than 8 years of age. The only safe antibiotic to administer to pregnant women or children is erythromycin. A rare complication, but one that can easily be missed, is the development of a gram-negative folliculitis. With prolonged antibiotic therapy, gram-negative organisms may proliferate in the anterior nares and spread out onto the surrounding skin. The physician should be alerted to this diagnosis if there is a sudden flare with pustules or nodules in a patient who is otherwise improving. Two types of lesions are seen. Most commonly there are multiple pustules with an intense inflammatory areola. This type of lesion is often caused by Enterobacter or Klebsiella. The patient may also have deep indolent nodules from which Proteus organisms are most often isolated. Culture confirmation is necessary, and antibiotic therapy should be governed by the results of sensitivity studies. Ampicillin is often the antibiotic of choice. Patients who do not show a response to antibiotics should be treated with a full course of isotretinoin . Tetracycline in dosages ranging from 1500 mg/day to 3500 mg/day has been used in patients with very severe acne. The results of this form of therapy are encouraging, particularly because the treated patients have otherwise been resistant to therapy. Patients under treatment with high-dose tetracycline should be carefully monitored with frequent laboratory evaluation. Trimethoprim-sulfamethoxazole combinations are also effective in acne. In general, because the potential for side effects is greater with their use, they should be used only in patients with severe acne who do not respond to other antibiotics. If trimethoprim-sulfamethoxazole is used, the patient must be monitored for potential hematologic suppression approximately monthly.
