Current Treatment

Role of Inflammation

Rosacea is a Chronic Inflammatory Disease

While research has not completely ruled out a microbial component in the pathogenesis of rosacea (e.g., Demodex mite overgrowth), there is strong evidence that rosacea is primarily—if not solely—an inflammatory disease.

This view is supported by histopathologic findings that include follicular and perivascular leukocytic infiltrates1,2 and an absence of pathologic microflora.3 It is further reinforced by research demonstrating that the antibiotics effective against rosacea work by suppressing a variety of proinflammatory mediators thought to play a primary role in rosacea pathophysiology (Figure 1).4 These include tumor necrosis factor alpha (TNF-α), the interleukins IL-1 and IL-6, and the neutrophil-derived compounds nitric oxide (NO), matrix metalloproteinases (MMPs), and various reactive oxygen species (ROS).

inflammatory mediators involved in Rosacea

Sequence of Events

While the evolution of the inflammatory response in rosacea has not been precisely elucidated, investigators suspect a sequence of events similar to the following:

  • Vasodilation of dermal capillaries, possibly mediated by histamine, prostacyclin, prostaglandin E2, nitric oxide, or other vasoactive compounds, causes initial erythema
  • Prolonged dilation weakens capillary walls, allowing neutrophils and proinflammatory cytokines such as TNF-α, IL-1, and IL-6 to leak into the surrounding dermis
  • Extravascular fluid builds up, overwhelming lymphatic vessels, and results in edema
  • Additional neutrophils are recruited by chemotactic factors released from inflamed dermal tissues
  • Activated neutrophils release degradative compounds, including matrix metalloproteinases (collagenases and gelatinases), reactive oxygen species, and nitric oxide—that exacerbate the inflammatory response and lead to tissue damage5,6,7

Why Antimicrobial Agents are Used to Treat Rosacea

Antimicrobials in the tetracycline class possess potent anti-inflammatory properties that are independent of their ability to suppress or kill pathogens. In the case of the antibiotics used to treat rosacea, it is their ability to modulate inflammation that is most likely responsible for their therapeutic effect. By contrast, the antimicrobial activity for which these agents are better known contributes largely to unwanted adverse effects and raises the risk of antimicrobial resistance.

For more information on the role of inflammation in rosacea, see our Emerging Concepts Series, a set of articles from key opinion leaders highlighting emerging concepts in rosacea management for you to read and share with your staff.

Treatment Challenges
  1. Jansen T, Plewig G. Rosacea: classification and treatment. J R Soc Med. 1997;90:144-150.
  2. Buechner SA.Rosacea: an update. Dermatology. 2005;210:100-108.
  3. Millikan L. The proposed inflammatory pathophysiology of rosacea: implications for treatment. Skinmed. 2003;2:43-47.
  4. Attur MG, Dave MN, Mohandas N, et al. Regulation of inflammatory mediators by tetracyclines. In: Nelson M, Hillen W, Greenwald RA, eds. Tetracyclines in Biology, Chemistry and Medicine. Basel, Switzerland: Birkhauser Verlag; 2001.
  5. Bikowski JB.Subantimicrobial dose doxycycline for acne and rosacea. Skinmed. 2003;2(4):234-245.
  6. Miyachi Y. Potential antioxidant mechanism of action for metronidazole: implications for rosacea management. Adv Ther. 2001;18(6):237-243.
  7. Jones D. Reactive oxygen species and rosacea. Cutis. 2004; 74(suppl 3):17-20,32-34.