There are many proposed non-antimicrobial actions of
tetracyclines. Pathways affected by these medications are often overexpressed in various dermatologic conditions.
Matrix metalloproteinases (
MMPs) are
enzymes best known for breaking down connective tissue
proteins and are upregulated in conditions involving dermal destruction. Inhibition of
MMPs by
tetracyclines has been emphasized as one major non-antimicrobial action. Other effects of
tetracyclines that are important in dermatology include inflammatory
cytokine regulation, inhibition of leukocyte chemotaxis and activation, and anti-oxidation. Dermatologists have utilized the non-antimicrobial benefits of using
tetracycline, through their success in treating disorders that do not have a primary infectious etiology such as
rosacea. Even in
acne, there is believed to be overactive
inflammation to a normally commensal organism which is inhibited by
tetracyclines. These medications have also been reported as successful in cases of less common skin conditions, such as
pyoderma gangrenosum and
bullous pemphigoid, both of which involve
inflammation and dermal destruction which are inhibited by
tetracyclines. The pathologic mechanisms of several dermatologic conditions are reviewed, followed by evidence of how
tetracyclines and chemically modified
tetracyclines (CMTs; structurally altered
tetracyclines to remove antimicrobial properties while retaining non-antimicrobial properties) affect these pathways. Clinical testing of sub-antimicrobial
doxycycline, in both 20mg twice daily and 40 mg once daily (controlled release; 30 mg immediate release, 10mg delayed release) forms, in
rosacea and
acne is reviewed as evidence that non-antimicrobial actions are valuable for treatment. Chemically modified tetracycline-3 (CMT-3) for
Kaposi's sarcoma is highlighted as the only clinical evidence available for CMTs in dermatology. Certain evidence of success using antimicrobial
tetracyclines in inflammatory conditions of the skin is reviewed as well, because they are likely working through non-antimicrobial properties. Finally, dermatologic side effects of non-antimicrobial
tetracyclines are assessed.