Although a great deal of uncertainty persists regarding the pathogenesis of rosacea, recent research has expanded understanding of the pathophysiology of the condition, identifying no fewer than six potential contributing factors: 1.) exposure to UV radiation; 2.) reactive oxygen species; 3.) vascular hyper-reactivity; 4.) neuropeptides; 5.) exacerbation of innate immune response; 6.) microbes.1 Some of these proposed contributors are controversial, and the extent to which any or all of them influences the disease in any particular patient may vary tremendously. There is consensus, however, that the symptoms of rosacea indicate chronic cutaneous inflammation and that an altered innate immune response contributes to this inflammation.2

Recently, increased attention has been paid to the role of barrier dysfunction in rosacea. The epidermal barrier, which modulates immune response, is responsible for blocking the entry of microbes and allergens. The stratum corneum contains precursors of the primary cytokines, interleukin-1α and interleukin- 1β, as well as TNF-α, IFN-γ, IL-1, and GMCSF. These cytokines mediate keratinocyte differentiation and growth—aimed at repairing the barrier— and mount both local and systemic inflammatory and immune responses targeting pathogens.3

The role of serine proteases in modulating epidermal barrier function or dysfunction has been elucidated4 and is of consequence in the pathogenesis of rosacea. Inflammation and associated redness, scaling, and itching have been shown to be directly influenced by changes in the proteolytic balance of the skin;1 elevated protease levels have been identified in rosacea and other dermatoses.6,7 At the same time, transepidermal water loss (TEWL), a marker of barrier dysfunction, is shown to increase protease levels.12

These findings regarding barrier dysfunction may explain why use of moisturizers and gentle skin care can improve rosacea. One trial found use of a moisturizing skin cleanser (Cetaphil, Galderma) neither increased TEWL in rosacea patients nor contributed to worsening of symptoms.8 Also, concomitant use of a moisturizer has been shown to improve symptom scores in rosacea patients treated with topical azelaic acid compared to those on medication alone.9

Diagnosis and Patient Assessment
A National Rosacea Society (NRS) Expert Committee has identified four major subtypes of rosacea: erythematotelangiectatic (ETR), papulopustular (inflammatory), phymatous, and ocular.10 The majority of treatments indicated for use in rosacea target the inflammation that produces papules and pustules and can diminish localized erythema associated with these lesions. Currently no available therapies are shown to manage background or generalized erythema. Lasers can address telangiectases and dilated capillaries. Ocular rosacea may appear independent of and with greater frequency than cutaneous rosacea and warrants careful consideration by the dermatologist.5 Phymatous rosacea may require surgical intervention (including ablative lasers) and/or isotretinoin.

Treatment Strategies for ETR
Treatments primarily used in the management of ETR include topical metronidazole (Metrogel 1%, Galderma) and topical azelaic acid (Finacea gel 15%, Intendis), oral doxycycline, and anti-inflammatory dose doxycycline 40mg (Oracea, Galderma). These agents are shown to produce a reduction in papules and pustules and to possibly improve the appearance of facial erythema.12 In conjunction with proper skin care, treatment may be associated with improvements in skin texture.

Relatively recently, there has been interest in the use of pimecroliums (Elidel, Novartis) to manage rosacea, with data showing similar efficacy to metronidazole in reduction of inflammatory lesions and improvement in physician global assessment (PGA) scores.13 Based on evidence that topical tretinoin confers mild anti-inflammatory effects, it has been used successfully for rosacea,14 though it may be best used as maintenance therapy to reduce overall signs of photodamage in the rosacea patient.

Finally, antimicrobial therapy is another treatment option that is gaining greater attention in the literature and in clinical practice. While the role of Demodex in rosacea is controversial, accumulating evidence suggests that a distinct diagnosis called Demodex dermatitis that mimics roscaea may exist.15

Regardless of the therapeutic entity selected, all patients must use gentle skincare and appropriate moisturizers, which are shown to be integral to the management of inflammatory dermatoses. While the incorporation of moisturizing ingredients in topical formulations may provide therapeutic benefits, these moisturizing effects may not be sufficient to replace use of a stand-alone moisturizer.16 Given the importance importance of moisturizers in supporting therapy and the emerging evidence that rosacea is indeed a disease of barrier dysfunction, use of a barrier repair cream may be appropriate for rosacea patients. Clinical experience supports the potential benefits of these agents in the therapeutic regimen: A 45-year-old patient with ETR recalcitrant to standard topical therapies (metronidazole and azelaic acid) deferred systemic therapy. Because of known barrier dysfunction in roscaea, she was prescribed EpiCeram Emulsion (Promius Pharma) for use twice daily on her face, with notable improvement evident at four weeks. At 14 weeks she had significant improvement in erythema and in flaking, scaling, and dryness. (Figs. 1-3)

Dr. Bikowski has served on the speaker's bureau, advisory board or is a shareholder or consultant to Galderma, Intendis, and Promius.