Abstract and Introduction
Abstract
The etiology of papulopustular rosacea (PPR) is not well understood yet appears to involve both the innate and adaptive immune response in addition to possible infestation with Demodex mites. Current treatments for PPR consist mainly of antibiotics. Ivermectin cream 1%, a new topical treatment for PPR, possesses both anti-inflammatory and anti-parasitic properties. After 12 weeks of treatment, subjects treated with ivermectin cream 1% had significantly greater reductions in PPR symptoms and enhanced diseaserelated quality of life improvements compared to subjects who received vehicle. Furthermore, PPR symptoms continued to improve with prolonged treatment (40 weeks). Ivermectin cream 1% offers a multi-pronged approach to combat the complex pathophysiology of rosacea.
Introduction
Rosacea is a chronic inflammatory condition affecting the central facial skin of the cheeks, nose, chin and forehead. Rosacea typically affects females approximately 30 years of age and increases in severity throughout the lifespan. The exact cause of rosacea is unknown and its pathogenesis is not well understood. Innate and adaptive immune responses, vascular abnormalities, dermal microorganism imbalances, and environmental factors may interact to produce chronic inflammation and the development of fibrosis. Four subtypes of rosacea have been identified: 1) erythematotelangiectatic rosacea, 2) papulopustular rosacea (PPR), 3) phymatous rosacea, and 4) ocular rosacea; yet, whether these represent a distinct variation or a continuum of disease severity remains a matter of debate. PPR, previously known as acne rosacea, is characterized by erythema, telangiectasia, papules, pustules, edema, and sometimes pain, stinging or burning. Patients report that symptoms are a cause of low self-esteem, as they are a source of shame, embarrassment, and physical discomfort. Treatment is strongly encouraged to moderate the detrimental effect on patient quality of life (QoL) and to prevent the condition from worsening. Few therapeutic alternatives exist for the treatment of PPR. There is some evidence supporting the efficacy of azelaic acid, topical metronidazole and sub-antimicrobial dose doxycycline in the treatment of moderate to severe rosacea, although it remains unclear which agent is most effective.
Ivermectin is derived from avermectin, a class of broadspectrum anti-parasitic agents isolated from the fermentation of Streptomyces avermitilis. Ivermectin possesses both antiparasitic and anti-inflammatory properties and has been shown to reduce the number of Demodex mites in demodicidosis and blepharitis and to inhibit the production of lipopolysaccharide inflammatory cytokines, such as tumor necrosis factor-alpha and interlukin (IL)-1b, while upregulating the production of the anti-inflammatory cytokine IL-10. Because PPR is recognized as an inflammatory condition whose pathogenesis may involve parasitic infestation with Demodex mites, vehicle-controlled and active comparator trials were undertaken to evaluate the efficacy and safety of topical ivermectin 1% cream in the treatment of PPR.