INTRODUCTION
Rosacea can be classified into four different subtypes,
of which papulopustular rosacea (PPR) has
been the most extensively studied with regard to
pathophysiology and treatment.1-3 Papulopustular rosacea is
characterized by both fluctuating and persistent central facial
erythema, along with the intermittent emergence of inflammatory
papules and pustules, or both.2,4 Similar to the diffuse
macular erythema of erythemato-telangiectatic rosacea, the
papules and pustules of PPR tend to concentrate primarily
on the central face, including the inner cheeks, nose, central
forehead, and chin. Some patients with PPR also experience
symptoms that reflect facial skin sensitivity, such as burning
and/or stinging, especially during flares.1
Histopathologic study demonstrates that rosacea has a significant
inflammatory component; however, the etiologic agent is
still debated.5 Current basic science and clinical data support
the contention that bacteria are not definitively involved in the
pathogenesis of rosacea, which is primarily driven by inflammatory
mechanisms.6-9 Because it is anti-inflammatory effects
and not antibiotic activity that is required to modify the process
caused by the inflammation of rosacea, subantimicrobial
dosing of oral doxycycline has emerged as a commonly used
approach by many clinicians. Anti-inflammatory dose doxycycline,
specifically defined as once daily administration of doxycycline 40 mg formulated as a modified-release capsule
(30 mg immediate-release and 10 mg delayed-release beads),
has been shown to be subantimicrobial, has demonstrated efficacy
and safety for treatment of PPR in multiple studies, and
is approved by the Food and Drug Administration for PPR.10-15
As a result, some clinicians avoid prescribing oral antibiotics
(such as tetracyclines) in dosages that produce antibiotic selection
pressure, which would include doxycycline given in doses
of 50 mg or more daily.10
Anti-inflammatory therapy devoid of antibiotic activity is recommended
for initial treatment of PPR in accordance with
guidelines for management of rosacea published by the
American Acne and Rosacea Society.16 The combination of
topical therapy with either metronidazole or azelaic acid and
oral anti-inflammatory dose doxycycline with topical therapy
(eg, metronidazole, azelaic acid) is often used for faster
control of a moderate or severe flare of PPR, as reported by
several investigators.13-15
In this review, we discuss the latest data on the pathogenesis of
PPR, how current therapies address the underlying pathophysiology
of PPR, and why combination therapy may represent the
optimal approach for the treatment of flares of PPR that are
moderate to severe in magnitude.15
