Rosacea affects an estimated 16 million US adults,1 but its underlying cause remains unclear. Studies presented at the 2014 American Academy of Dermatology (AAD) annual meeting offered some insights about the mechanism of inflammation, suggesting that doxycycline 40 mg modified release (MR) may improve the symptoms of papulopustular rosacea by modulating factors that augment inflammation. Other investigators reported treatment success for rosacea with novel agents.
Inflammation Markers Abated with Doxycycline 40 mg Modified Release
The presence of an inflammatory component to rosacea is well established, but the seminal pathogenic processes responsible for its development remain an active area of investigation. The factors that are thought to be associated with rosacea include an augmented innate immune response; increased antimicrobial peptides in the skin (including cathelicidins); increased activity of the cutaneous members of the kallikrein family of serine proteases; and upregulation of certain matrix metalloproteinases (MMPs), which activate kallikrein.
“While these biomarkers were identified in advanced disease states, it was unclear whether effective therapy known to improve PPR [papulopustular rosacea] would result in modification of these biomarkers,” Anna Di Nardo, MD, PhD, Divison of Dermatology, University of California, San Diego, stated in her poster.
Mouse models have shown that MMP levels of more than 0.01 relative fluorescence units (RFUs) at baseline indicate a state of inflammation. In their multicenter, randomized, double-blind, placebo-controlled study of 170 patients with papulopustular rosacea, Dr Di Nardo and colleagues confirmed this finding, showing that patients with this type of rosacea who had MMP levels of more than 0.01 RFUs at baseline responded to doxycycline 40 mg MR treatment with a reduction in this inflammatory marker to levels less than 0.01. Treatment with doxycycline MR also maintained or reduced MMP levels in patients who improved clinically, as was demonstrated by a reduction in lesion count and improvements in the Investigator’s Global Assessment score. Doxycycline MR was well tolerated in both arms.
In addition, patients without elevated MMP levels also benefited from doxycycline 40 mg MR, with clearing or near clearing of lesions, essentially to the same degree as the patients with elevated inflammatory biomarkers.
The investigators concluded, “MMP levels do not always reflect the clinical status of the disease, but the baseline MMP levels may predict clinical treatment success depending on where in the rosacea inflammatory cycle the MMP levels are when treatment with doxycycline MR is administered.”
In another study led by Eugene Y. Huang, MD, PhD, of Therapeutics Clinical Research, San Diego, CA, patients with papulopustular rosacea who showed clinical success with doxycycline 40 mg MR also had increased cathelicidin levels at baseline compared with patients who did not show clinical success at weeks 8 and 12. In addition, patients treated with doxycycline 40 mg MR had significantly lower levels of total protease activity at week 4 than patients receiving placebo.
Treatment with clinical success was correlated with significantly lower total MMP levels at week 12.
In addition to reducing lesions, “doxycycline 40 mg MR also affected rosacea-associated biochemical markers, providing an avenue to further explore the inflammatory component of rosacea,” Dr Huang and colleagues stated.
Microfocused Ultrasound for Erythematotelangiectatic Rosacea
A pilot study showed that for the treatment of erythematotelangiectatic rosacea, with the hallmark symptom of skin erythema, microfocused ultrasound with visualization (MFU-V) was safe and effective. The results of the study were presented by Mark Lupin, MD, FRCPC, of the University of British Columbia, Vancouver, Canada.
A total of 12 patients with erythematotelangiectatic rosacea were randomized to 2 groups for this phase 1 study, with an optional phase 2 study. Group A received 1 MFU-V treatment with 15 lines on each cheek; Group B received 2 treatments 14 days apart, with 15 treatment lines on each cheek. Photographs were taken before and immediately after treatment and at 14 days, 30 days, and 90 days posttreatment.
For each time point, at least 50% of the patients had improved, according to physician assessment; the percentage varied depending on the transducer (10-1.5 mm, 7-3 mm, 4-4.5 mm) and on whether they received 1 or 2 treatments.
For the most part, Dr Lupin rated 50% to 75% of patients improved in Group A, and 50% to 100% improved in Group B. In Group A, 33% of patients noticed an improvement and 17% were satisfied with their treatment at 90 days. In Group B, 67% of patients reported an improvement and 50% were satisfied at 90 days. The modality was safe, with no serious adverse events reported.
- Del Rosso JQ. Introduction. Cutis. 2010;86(5 suppl):4-6.