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The tetracycline family of antibiotics are extremely useful in acne because they have multiple modes of action, functioning as antibiotics that reduce bacterial populations, and as anti-inflammatory drugs that attack acne from a second front.

Tetracyclines, especially doxycycline and minocycline are highly anti-inflammatory in many cell systems (Table 1). Neutrophil and monocyte chemotaxis is inhibited through calcium chelation, blunting the migration of cells to the follicle (13). Granuloma formation in vitro (14) and in vivo (15) is inhibited; with minocycline and doxycycline roughly 10-fold more active than tetracycline. In this model, macrolides and cephalosporines were inactive. Protein kinase C is inhibited (15), perhaps interfering with signal transduction. Generation of reactive oxygen species and the oxidative burst in neutrophils is decreased (16). Nitric oxide production is modulated (17). Matrix metalloprotease and collagenase activity is inhibited (18-20). In vivo, tetracyclines have been demonstrated to be highly active in treating purely inflammatory diseases including rheumatoid arthritis, bullous pem-phigoid, and sarcoidosis (21). Nonantibiotic derivatives of doxycycline have been recently developed that are highly anti-inflammatory and even antineoplastic through inhibition of angiogenesis and may be of use in acne and other inflammatory diseases (22-24).

Concentrations of tetracyclines that are below the antibiotic threshold still have anti-inflammatory activity. Low doses of doxycycline and minocycine that do not affect bacterial growth decrease the production of neutrophil chemo-attractants by P. acnes (25,26). Subminimal inhibitory doses also retain the ability to inhibit inflammation in vivo and improve diseases such as acne, rosacea, and periodontitis (27-29).

TABLE 1 Anti-inflammatory Activity of Antibiotic Classes

Inhibition of

Neutrophil chemotaxis

Granuloma formation

Protein kinase C

Nitric oxide

Sub-MIC chemotactic factor

Macrolides Tetracyclines Ciprofloxacin Cephalosporines


+++ +

+++ +


++ ++

Abbreviation: MIC, minimal inhibition concentration.

Abbreviation: MIC, minimal inhibition concentration.

TABLE 2 Significant Adverse Effects of Doxycycline and Minocycline

Doxycycline Cutaneous: phototoxicity Gastrointestinal: GI upset, nausea Minocycline

Cutaneous: hyperpigmentation, especially in areas of chronic inflammation Neurologic: light-headedness/vertigo

Allergic: urticaria, serum-sickness-like reactions, systemic hypersensitivity reactions Abbreviation: GI, gastrointestinal.

Antibiotic resistance is less a problem with the tetracyclines than the macrolides, but resistance in P. acnes has been documented. In general, tetracycline resistant strains are cross-resistant to doxycycline but sensitive to minocycline (30).

Choice of oral antibiotic by dermatologists for treating acne has shifted over the past few decades. Currently, the once frequently prescribed tetracycline is used relatively infrequently, with the majority of patients treated with doxycycline or minocycline. Tetracycline has multiple disadvantages, including greatest effect of diet on absorption, lower anti-inflammatory and antibacterial activity, and lower effect on acne lesions (30-32). There are few studies that address the relative potency of these two drugs in treating acne, and the few that do are fairly small and do not involve the more severe patients and manage to show only equivalence (33). However, there is good reason to believe that minocycline is the stronger drug. In my experience, there have been many patients with significant acne who fail to respond to doxycycline yet have an excellent response when switched to minocy-cline. The reason for this may lie in the greater lipophilicity of minocycline and the greater activity in a lipid milieu. This is reflected in a 10-fold greater reduction of P. acnes by minocycline when compared with doxycycline (32).

The side effect profile (Table 2) of doxycycline and minocycline also differs, most notably in the incidence of photosensitivity with doxycycline and the occurrence of hypersensitivity reactions with minocycline. Photosensitivity is very common at higher doses of doxycycline. The minocycline hypersensitivity reactions are uncommon and include urticaria, serum sickness-like reactions, and what has been termed a lupus-like reaction that in reality is probably not an activation of systemic lupus erythematosus but a generalized drug-induced reaction that resembles lupus (34).

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