Oral therapy for rosacea

Journal of Drugs in Dermatology, Jan, 2006 by Hilary E. Baldwin

Oral Therapeutic Options

Antibiotics

Oral antibiotics have been used off-label since the 1950s because it was assumed that an infection was the underlying cause of rosacea. The problem arises in that there is little to no evidence supporting the premise that rosacea is a primarily bacterial infection. Not surprisingly, no antibiotic is FDA approved for the treatment of rosacea. As of February 6, 2003, the FDA required labeling on all systemic antibacterial drugs that state that these agents should be used only to treat or prevent bacterial infections. Although the intention of this labeling was to reduce the unnecessary use of antibiotics in viral respiratory infections, it remains pertinent to rosacea.

Tetracyclines

Tetracycline was brought to the market in 1952 and the derivatives doxycycline (1966) and minocycline (1972) soon followed. At the time of their introduction, they were known to be bacteriostatic and broad-spectrum. In the past 25 years, research into the immunomodulatory effects of the tetracyclines took precedence. (9)

Tetracyclines are known to down regulate production of proinflammatory cytokines such as IL-1 and TNF alpha. (10) They also inhibit matrix metalloproteinases (MMP). (11,12) MMPs are calcium or zinc containing proteolytic enzymes produced by inflammatory cells that degrade collagen. As such, tetracyclines decrease inflammation during an inflammatory response such as that seen in rosacea. (10)

Tetracyclines are highly effective for papulopustular acne, requiring only 3 to 4 weeks of treatment for substantial improvement. (13,14) Sneddon was the first to demonstrate the effectiveness of tetracycline in treating papulopustular rosacea in 1966. (15) Erythema and telangiectatic forms did not improve as readily. Relapses, however, often occur upon discontinuation. (15) Two separate studies demonstrated relapse rates of 25% at 1 month, 50% to 60% at 6 months, and 70% within 1 to 4 years. (16,17)

Tetracycline 250 to 1000 mg QD, doxycycline 100 to 200 mg QD, and minocycline 100 to 200 mg QD are most commonly used. There are no controlled trials for doxycycline and minocycline. Use of oral tetracyclines until clinical improvement followed by a taper to topical antibiotics offers an alternative. There are patients for whom low-dose, long-term antibiotics are necessary for control.

Doxycycline hyclate 20 mg BID (Periostat) has recently been reported to be effective in the treatment of rosacea with a low incidence of adverse effects. Bikowski treated 50 patients with all types of rosacea and noted at 4 weeks, an 80% to 100% improvement in inflammatory lesions and a 50% reduction in erythema. (18) There was also a decrease in size of telangiectasias noted.

Periostat has been FDA approved since 1998 for the treatment of adult periodontitis. The labeling permits continuous use for up to 12 months, and as such it is the only tetracycline approved for long-term use. Its major contribution to rosacea therapy is that the 20 mg dose results in sub-antimicrobial blood levels. As such, it is less likely to cause bacterial resistance and is immune to the FDA labeling mandate. Several studies have shown no effect on antibiotic susceptibility patterns in up to 18 months of continuous therapy and 9 months post-treatment. (14,19,20)