COMMENTARY

Rosacea: 5 Things to Know

Graeme M. Lipper, MD

Disclosures

September 19, 2018

2. Antibiotics Work, but Not for the Reason You Might Think

Low-dose doxycycline (40 mg once daily) is the only US Food and Drug Administration (FDA)-approved oral treatment for rosacea,[14] although off-label systemic therapies include other antibiotics (minocycline, azithromycin), oral ivermectin, and isotretinoin.[15]

Historically, tetracyclines for rosacea were assumed to target proinflammatory bacteria, such as Propionibacterium acnes and Staphylococcus epidermidis. Similar assumptions were made for topical antimicrobials (metronidazole, azelaic acid, sodium sulfacetamide) and the antiparasitic drug ivermectin, which was thought to work by suppressing overgrowth of the cutaneous mite Demodex folliculorum.

But is rosacea really an infectious process? A growing body of evidence points to a different etiology: hyperactivity of the cutaneous innate immune system.[5,16,17]

Simply put, innate immunity is a primitive, nonspecific immune system that protects epithelial barriers, such as the skin and gut, from microbial, chemical, and physical injury. Critical components of this pathway include the Toll-like receptor and nucleotide-binding domain and leucine-rich repeat-containing families; when activated, these increase expression of proinflammatory cytokines, proteases, and antimicrobial peptides (eg, cathelicidin) in the skin.[16,17]

In rosacea, inflamed skin expresses increased levels of cathelicidin and proteases. In a 12-week study, doxycycline (40 mg/day) reduced inflammatory lesions and improved global assessment scores compared with placebo. Clinical improvement correlated with a drop in cathelicidin and protease activity, supporting the idea that doxycycline improves rosacea via anti-inflammatory rather than antimicrobial mechanisms.[18] Similar anti-inflammatory effects have been demonstrated for topical metronidazole, azelaic acid, and ivermectin.[19,20]

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