Update in the Management of Rosacea

Panelists: James DelRosso, MD; Alan Shalita, MD; Guy Webster, MD, PhD

The diagnosis of rosacea is based upon clinical findings; there are no specific diagnostic tests. The National Rosacea Society Expert Committee on the classification and staging of rosacea has developed provisional diagnostic guidelines for rosacea.¹

The guidelines recommend the presence of one or more of the following primary features:

In addition, one or more of the following secondary features often appear with the primary features listed above, although can occur independently in some patients:

 

 

 

 

 

Case 1

The panel was presented with the case of a 41 year old white female with a 6-7 year history of waxing/waning facial redness that waxes and wanes and is associated with red bumps and pustules on the nose, cheeks and forehead.  She has “sensitive skin” which is often dry and flaky. Her skin improved on an oral antibiotic for a respiratory infection. She is seeing you to “get rid of the condition”.

It is important to identify the subtype of the disease as that will help dictate the response to treatment. Clinicians should recognize that these patients have increased transepidermal water loss (TEWL) from the central face. Dermatologists need to understand the importance of appropriate skin care in order to address the symptoms and, ultimately reduce the baseline symptoms. Studies have demonstrated that the skin characteristics of patients with rosacea show that about half of the patients scale and become itchy, about one third of the patients experience stinging and burning and these patients do not always have seborrheic dermatitis.

Etiology of Rosacea

The etiology of rosacea is unknown, although research suggests that symptoms are exacerbated by factors that trigger innate immune responses, such as the release of cathelicidin antimicrobial peptides. Studies have shown that patients with rosacea express abnormally high levels of cathelicidin in their facial skin and the proteolytically processed forms of cathelicidin peptides found in rosacea are different from those present in normal individuals. These cathelicidin peptides are a result of a post-translational processing abnormality associated with an increase in stratum corneum tryptic enzyme in the epidermis.²

Therapeutic Options: Topical Agents for the Treatment of Rosacea

 Metronidazole works through the inhibition of ROS generation from neutrophils. Azelaic Acid also works through the inhibition of ROS generation from neutrophils. Azelaic Acid also has decreased KLK-5 activity (serine protease activity); therefore,  decreasing the cathelicidin. It also downregulates the Toll-like receptor 2 (TLR2), similar to topical retinoids.

Retinoids also have a variety of ways in which they can modulate the disease, for instance they work through the inhibition of ROS generation from neutrophils and also have the downregulation of TLR2 and modulation of MMP activities, i.e., repair of dermal matrix degradation.

The tetracycline derivatives have a variety of down-regulating properties that appear to help with rosacea. They reduce inflammatory cytokines: IL-1b, IL-6, and TNF-1-a. They inhibit the serine protease activation of catheclicidin. They inhibit MMPs collagenase-8, -13, gelatinase -2, -9, elastase -12 and pro MMP activation and protect TIMP. Tetracyclines also inhibit nitric oxide activity and the arachidonic acid pathway.

Data on minocycline show the suppression of serene protease activity. Specifically, when patients were on minocylcine, the serene protease activity decreased, when they stopped it increased, and when they went back on the minocycline, it again decreased. (Yamasaki et al. Nature Medicine (2007) Aug 13 (8) 975-80)

As far as oral therapies for the treatment of rosacea, the tetracyclines are used; however, they are not FDA approved and there is reason to believe that dermatologists only need to use the subantimicrobial doses in order to garner the anti-inflammatory effect. These doses have widespread use and years of clinical experience. There are multiple pharmacokinetic and microbiologic studies. They are FDA-approved with large pivotal trials. Data exists with regards to the combination with topical therapy. Their efficacy is comparable to doxycycline 100 mg daily and there are potential safety advantages.

With the use of doxycycline (40mg Extended Release, QD) once can see demonstrated efficacy in papulopustular rosacea, there is a lack of antibiotic effect, efficacy is the same as that of doxycycline 100mg/QD, and there is a favorable safety profile. One 12-week study looking at doxycycline 40mg demonstrated that by week 4, close to half of the patients achieved clear or near-clear skin and by week 12, about 75% of the patients achieved clear or near-clear skin. The data were similar to that of patients utilizing add-on therapy in addition to doxycycline.

In conclusion, healthcare providers should be aware that there are a lot of data that show the efficacy of these agents for the management of papulopustular rosacea.

When comparing doxycycline 100mg to doxycycline 40mg, the effects were essentially the same based on one trial. Patients do not need to be exposed to changing their bacterial flora unnecessarily by starting with this treatment first, and; therefore, patients are not exposed at an antibiotic effect.

Case 2

The second case presented to the panel was a 42 year-old White female presents with a 7 year history of central facial (nose/malar eminences/chin) redness which waxed and waned in intensity over the years but is now persistently red There is central facial predominance.  She does not relate ever having any “red bumps” or “pus bumps” developing on her face, including during flares.  She has “sensitive skin”. She occasionally complains of itching and burning. She is interested in the correct diagnosis and treatment. Her health history is unremarkable otherwise.

Medical Treatments for the Redness of Rosacea

Erthematotalngiectatic rosacea (ETR) is more common than papulopustular rosacea. Available therapies include topical agents, such as metronidazole, azelaic acid, and oral agents such as the tetracyclines all of which improve primarily perilesional erythema. These products can occasionally help patients with their rosacea, but the background redness type does not always respond very well.  The critical issue is the presence of persistent telangiectatic mats in the affected areas.  The telangiectasias can be reduced when treated with laser/light devices.  Topical vasoconstrictors that can be used to reduce erythema (Oxymetazoline and Brimonidine) are in clinical trials and have shown excellent clincial responses during these clinical trials.

 

References:

1. Wilkin, J, Dahl, M, Detmar, M, et al. Standard classification of rosacea: Report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea. J Am Acad Dermatol 2002; 46:584.

2. Yamasaki K, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. 2007. Nat Med;13(8)975-980.