which is upregulated and hyper-responsive in facial skin of
patients with rosacea as compared to normal skin. Studies in
rosacea have demonstrated enhanced receptor recognition
through increased expression of TLR-2, and increases in both
the AMP cathelicidin and SC serine protease activity (KLK-5),
which leads to greater production of pro-inflammatory and
vasoactive peptides (ie, LL-37). Clinical manifestations of rosacea
correlate with the augmented immune response including
erythema associated with diffuse dermal infiltration with lymphocytes
(Th1) and macrophages, vascular inflammation with
vasodilation and perivascular edema, and in some cases inflammatory
lesions related to the chemoattraction of neutrophils
with perifollicular inflammation. Other mechanisms associated
with rosacea interface with the innate immune response such as
MMPs, ROS, and SC permeability barrier function. Ultimately,
the major presentations of rosacea appear to be inflammatory
dermatoses with a variety of mechanisms contributing to the
underlying pathophysiology. Current evidence supports that
the presence of a microbial organism is not a primary or mandatory
component of the pathogenesis of rosacea. Currently,
available therapies for rosacea exhibit modes of action that appear
to correlate with the inhibition of inflammatory cascades
involved in the pathophysiology of at least some presentations
of rosacea. Additional studies are needed to further clarify the
pathogenesis of rosacea and modes of action of therapeutic
agents used in treatment, including new therapies.
This article is based on an academic rountable discussion completed
in New York City in August 2011 chaired by the lead author
with participation by all the authors listed on this article. Much
of the discussion was based on research presented by Dr. Richard
Gallo as well as information from literature review. The paper
was mostly written by the lead author with input from the other
authors, with administrative support from Educational Awareness
Solutions (Norwalk, Connecticut) and without input from any
other sources. The participants at the roundtable did receive an
honorarium for their attendance and involvement at the roundtable,
and in the case of the chairperson, for assisting in review and
preparation of a large body of references provided to the participants.
None of the authors received honoraria related to writing
of the article. The project was supported by an educational grant
from Galderma Laboratories provided to Educational Awareness
Solutions (Norwalk, Connecticut).
Dr. Del Rosso has served as a consultant, speaker, and/or researcher
for Allergan, Bayer (Intendis), Galderma, LeoPharma, Medicis, Nitro-
Bio, Obagi Medical Products, Onset Dermatologics, Pharmaderm,
Primus, Promius, Ranbaxy, TriaBeauty, Triax, Unilever, Valeant, and
Dr. Gallo completed research that was funded by the National Institutes
of Health and US Veterans Affairs and in the past by the
National Rosacea Foundation. He has served as a consultant, and/or
researcher for Allergan, Bayer (Intendis), Galderma, Novartis, Johnson
and Johnson, Colgate-Palmolive, Sente, and Skin Epibiotics.
Dr. Kircik has served as a speaker, consultant, and/or researcher for
Abbott, Acambis, Allergan, Amgen, Assos Pharma, Astellas Pharma,
Asubio, Bayer (Intendis), Biogen-Idec, Biolife, Biopelle, Breckinridge
Pharma, Colbar, Centocor, Combinatrix, Dusa, Embil, EOS, Ferndale,
Galderma, Genentech, GlaxoSmithKline, Innovail, Johnson &
Johnson, Laboratory Skin Care, LeoPharma, Medical International
Technologies, Medicis, Merz, NanoBio, Novartis, Nucryst Pharmaceutical,
Obagi Medical Products, Onset Dermatologics, Promius,
PharmaDerm, Quatrix, Serono, SkinMedica, ToleRx, Triax, UCB, Valeant,
Warner-Chilcott, and ZAGE.
Dr. Thiboutot has served as a consultant for Galderma and Bayer
(Intendis) and as a researcher for Galderma.
Dr. Baldwin has served as a speaker, consultant and/or researcher
for Allergan, Galderma, GlaxoSmithKline, Medicis, Onset Dermatologics,
Ranbaxy, and Valeant.
Dr. Cohen has served as consultant, for Brickell Biotech, Dermira,
Dr. Tattoff, Ferndale, Galderma, Johnson and Johnson, LeoPharma,
Onset Dermatologics, Topica, and Vyteris. He serves on the
Board of Directors of Brickell Biotech, Topica, and Vyteris. He owns
stock or stock options with Brickell Biotech, and Dermira.
- Crawford GH, Pelle MT, James WD. Rosacea I: etiology, pathogenesis, and
subtype classification.J Am Acad Dermatol. 2004;51:327-341.
- Wilkin J, Dahl M, Detmar M, et al. Standardized classification system of
rosacea: Report of the National Rosacea Society Expert Committee on the
classification and staging of rosacea. J Am Acad Dermatol. 2002;46:584-587
- Odom R, Dahl M, Dover J, et al. Standard management options for rosacea,
part 1: overview and broad spectrum of care. Cutis. 2009;84:43-47.
- Del Rosso JQ, Baldwin H, Webster G. American Acne & Rosacea Society rosacea
medical management guidelines. J Drugs Dermatol. 2008;7:531-533.
- McAleer MA, Fitzpatrick P, Powell FC. Papulopustular rosacea: prevalence
and relationship to photodamage. J Am Acad Dermatol. 2010;63:33-39.
- Abram K, Silm H, Oona M. Prevalence of rosacea in an Estonian working
population using a standard classification. Acta Derm Venereol.2010;90:269-73.
- Woolery-Lloyd H, Good E. Acne and rosacea in skin of color. Cosmet Dermatol. 2011;24:159-162.
- Steinhoff M, Buddenkotte J, Aubert J, et al. Clinical, cellular, and molecular
aspects in the pathophysiology of rosacea. J Invest Dermatol. 2011;15:2-11.
- Schwab VD, Sulk M, Seeliger S, et al. Neurovascular and neuroimmune aspects
in the pathophysiology of rosacea. J Invest Dermatol. 2011;15:53-62.
- Bamford JTM. Rosacea: current thoughts on origin. Semin Cutan Med
- Steinhoff M, Stander S, Seelinger S, et al. Modern aspects of cutaneous
neurogenic inflammation. Arch Dermatol. 2003;139:479-488.
- Thibotout D, Thieroff-Ekerdt R, Graupe K. Efficacy and safety of azelaic acid
(15%) gel as a new treatment for papulopustular rosacea: results from two
vehicle-controlled randomized phase III studies. J Am Acad Dermatol. 2003;48:836-845.
- Elewski B, Fleischer AB, Pariser DM et al. A comparison of 15% azelaic
acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular
rosacea. Arch Dermatol. 2003;139:1444-1450.
- Del Rosso JQ, Baum EW. Comprehensive medical management of rosacea:
an interim study report and literature review. J Clin Aesthetic Dermatol. 2008;1:20-25.