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The 2019 Rosacea Research Roundup

December 2019

Between phase 3 clinical trials testing the efficacy of new treatment modalities for the market, studies on the impacts on quality of life with the condition, and focuses on patient demographics, 2019 was an active year for research in rosacea. The Dermatologist compiled some of the industry’s top research from the past year that could help shape future upcoming studies and reviews on rosacea diagnosis, treatment, and management.

Examining Patient Quality of Life 
It is no secret that rosacea can have a significant negative effect on patient quality of life. In fact, 76% of patients reported feeling at least a small impact on quality of life in a multinational online survey.1 Rosacea can cause loss of confidence in one in three people, and 19% of people report making more than seven adaptions to their lifestyle to accommodate their condition.1 These changes include avoiding sun exposure, not consuming alcohol as well as spicy or hot foods, staying away from extreme temperature climates, and missing social activities.

For some patients, however, rosacea can have a very or extremely large impact as based on their Dermatology Life Quality Index score. Tan et al2 highlighted several factors that could help clinicians identify high-burden patients, defined as patients scoring positively in three of four categories:

  • Impact of rosacea on quality of life (score >5, where 0=no impact and 10=very high);
  • Level of behavior adaptation (score >6, where 0=not adapted and 10=extremely);
  • Willingness to pay for a cure (score >20% of monthly income); and
  • Time trade-off for a cure (score >6 months).

Compared with nonhigh-burden patients, the high-burden group tended to be younger (39.5±11.8 vs 45.9±14.0; P<.01), male (45.6% vs 31.0%; P<.01), employed (83.5% vs 69.4%; P<.01), urban dwelling (63.9% vs 42.9%; P<.01), and reporting a higher number of symptoms in the past 12 months (mean number, 5.0±3.5 vs 4.4±2.7; P<.05).2 In addition, high-burden patients were more likely to experience itching, burning, swelling, pain than their counterparts.

Similarly, a survey of 1044 people with rosacea conducted by the National Rosacea Society  found that successful treatment can have a significant impact on patient quality of life.3 In the survey results, 76% of participants reported at least some improvement in their skin after treatment; of this group, 40% reported improvements in their psychological well-being, 35% for social well-being, and 31% in occupational well-being.

Furthermore, improvements in quality of life were substantial when the symptoms of rosacea where nearly or completely eliminated by treatment. With almost clear or fully clear skin, 81%, 71%, and 62% of participants reported improvements in their psychological well-being, social lives, and workplace, respectively.3 These responses are in stark contrast to when only slight to moderate improvements in skin were noted, which saw only 24%, 21%, and 19% of respondents noting improvements in the same respective categories.

Results from a cross-sectional survey published in the Journal of Dermatology Research and Therapy detailed the psychosocial impact of rosacea on 19 female patients.4 The majority of participants commonly reported using makeup as cosmetic camouflage all of the time (42%) or often (26%), and zero reported to never or rarely using makeup to cover their rosacea. A small majority (53%) reported feeling frustration all of the time and an additional 32% reported feeling frustration often as a result of rosacea, and, similarly, 74% felt embarrassed by the condition all of the time or often. These results indicate that patients are constantly worried about their rosacea and how others perceive the condition.

Each of these three studies2-4 stresses the importance of a multifaceted treatment and management plan for patients with rosacea. Additional resources, such as adjunct therapies to address severity or mental health referrals, may benefit all patients with rosacea.

Identifying Rosacea in Skin of Color
In its June 2019 issue, the Journal of the American Academy of Dermatology published a comprehensive review on the global epidemiology and clinical spectrum of rosacea with particular interest to presentation in skin of color.5 Notably, the article states that rosacea is often underdiagnosed or misdiagnosed in patients with skin of color. The condition’s characteristic persistent facial erythema is reported less frequently than papules and pustules, likely due to the difficulty of recognizing erythema in darker Fitzpatrick skin types as well as the potential for hyperpigmentation to mask redness.6,7 

When diagnosing rosacea in patients with skin of color, the authors5 recommended several components to consider. First, a thorough examination of patient history should be conducted. This includes querying the patient for self-reported observations and history, asking questions such as:

  • Have you ever experienced a warm sensation or flushing over your face?;
  • Has your skin appeared more red than normal?;
  • Do your symptoms develop or get worse following certain triggers, eg, heat, spicy food, stress?; and
  • Do you have a family history of rosacea or, if no diagnosis was made, a history of signs and symptoms?

Second, the authors5 recommended dermatologists familiarize themselves with the other clinical signs and symptoms of rosacea. These include noting the signs concentrated in the central face as well as dry appearance, edema, and hyperpigmentation. In particular, clinicians should observe the presence of acneiform papules and pustules, which will lack comedones (thus differentiating rosacea from acne). Additionally, ocular symptoms (itching, irritation) and thickening of the nasal and medial cheek skin can also be present.

Third, erythema and telangiectasia can be identified with a number of other methods outside of seeing with the naked eye. One example discussed was using a magnifying glass or microscope slide; when the glass/slide is pressed against the skin and the skin pales, erythema is present. Another example reviewed was photographing patients against a dark blue background with adequate lighting to help distinguish erythema and telangiectasia more readily. 

As for treatment, patients with skin of color should follow similar approaches to that of lighter Fitzpatrick skin types. However, dermatologists should be careful to address postinflammatory hyperpigmentation as well as avoid further pigmentary complications. Also, dermatologists should stress the importance of appropriate skin care with patients. This includes use of a gentle, nonalkaline, fragrance-free emollient cleanser; a silicone-based moisturizer; light, water-based cosmetics; and, most importantly, use of sunscreen/physical sunblock. Patients should also be counseled on rosacea triggers.

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Associations With Comorbidities
The past year has seen multiple studies link rosacea with additional comorbidities. Most recently, researchers in Turkey found a connection between patients with rosacea and increased risk of anxiety disorders.8 In this study, 194 patients with rosacea and 194 age- and sex-matched controls were evaluated by the Generalized Anxiety Disorder 7-item scale and the Generalized Anxiety Disorder Severity Scale to determine relation between rosacea and anxiety. Overall, the study found various risk factors for anxiety in patients with rosacea, including:

  • Phymatous rosacea (P<.05);
  • Female gender (P<.05);
  • Prior history of psychiatric morbidity (P<.05);
  • Self-reported rosacea flare-up with stress (P<.001); 
  • Low educational level (P<.05); and
  • Condition left untreated (P=.04).

Previous research has linked rosacea with an increased risk of certain cancers.9-11 A study conducted in China that compared 7548 patients with confirmed malignancy and 8340 cancer-free controls explored other possible associations between rosacea and cancer.12 This study did find that 98.95% of the 190 female patients with breast cancer also had erythematotelangiectatic rosacea.

Withal, these results are based solely on relative association.13 As Tjahjono et al13 discuss, physicians should be careful and transparent in their discussions of risks with patients regarding rosacea. For example, relative risk for thyroid cancer is 1.60 and the attributable risk is 1.41; yet, the number of patients that need to be seen in 1 year to attribute one case of thyroid cancer to rosacea is 7080. Therefore, using absolute terms instead of relative ones are critical to understanding rosacea’s overall impact.13

The Product Pipeline
Upcoming products offer new possibilities to mitigating the symptoms of rosacea. Among those new treatments is FMX103, a 1.5% minocycline foam for the treatment of moderate to severe papulopustular rosacea. Two phase 3, randomized, multicenter, double-blind, vehicle-controlled studies sought to determine if FMX103 is an effective and safe option for patients.14 Between the studies, 1522 patients were randomized 2:1 to either the FMX103 group or the vehicle group and used either FMX103 or vehicle once daily to the face for 12 weeks.

At baseline, patients had mean inflammatory lesion counts of 28.5 and 30.0 in the FMX103 treatment group vs 29.0 and 30.2 for the vehicle. After 12 weeks of treatment, the FMX103 group demonstrated significant reductions in the mean inflammatory lesion count from baseline vs vehicle (FX2016-11, −17.57 vs −15.65, P=.003; FX2016-12, −18.54 vs −14.88, P<.0001).

Since the clinical studies, a New Drug Application for FMX103 has been approved by the FDA, with June 2, 2020, set as the Prescription Drug User Fee Act action date.15

Moisturization and sun protection are essential steps to skin care with rosacea, and one upcoming product hopes to fulfill both these needs. A tinted daily SPF-30 facial moisturizer (DFM30) was tested on patients with mild to moderate rosacea and nontransient erytema to assess its efficacy, tolerability, and ability to improve dry skin barrier function on rosacea-prone skin.16 After the initial application of DFM30 on day 1, 33.3% of patients showed improved covering of skin redness improved. After 22 days of use, image analysis suggested redness was significantly lower than at baseline, and chromameter readings on the cheeks showed significantly lower erythema. 

In addition, patients who reported feeling DFM30 relieved and neutralized visible redness also stated they would purchase the product. Overall, DFM30 was well-tolerated and could improve cutaneous barrier function and the appearance of rosacea.


References
1. Tan J, Steinhoff M, Bewley A, Gieler U. Rosacea: Beyond the visible report. British Medical Journal. https://hosted.bmj.com/media/images/burden-of-rosacea-beyond-the-visible.pdf. June 2018. Accessed November 26, 2019.

2. Tan J, Steinhoff M, Bewley A, Gieler U, Rivers V. Identifying high-burden patients with rosacea by demographic and disease-related factors. Presented at: American Academy of Dermatology Annual Meeting; March 1-5, 2019; Washington, DC.

3. Terhaar E. New rosacea survey shows positive impact of clear skin. National Rosacea Society. https://www.rosacea.org/blog/2019/june/new-rosacea-survey-shows-positive-impact-clear-skin. June 3, 2019. Accessed November 26, 2019.

4. Al Abadie M, Asharaff F, Al Abadie D. Psychosocial impact of rosacea on women. J Dermatol Res Ther. 2019;5(2). doi:10.23937/2469-5750/1510074

5. Alexis AF, Callender VD, Baldwin HE, Deai SR, Rendon MI, Taylor SC. Global epidemiology and clinical spectrum of rosacea, highlighting skin of color: review and clinical practice experience. J Am Acad Dermatol. 2019;80(6):1722-1729.e7. doi:10.1016/j.jaad.2018.08.049

6. Tan J, Blume-Peytavi U, Ortonne JP, et al. An observational cross-sectional survey of rosacea: clinical associations and progression between subtypes. Br J Dermatol. 2013;163(3):555-562. doi:10.1111/bjd.12385

7. Kundu RV, Patterson S. Dermatologic conditions in skin of color: part I. Special consideration for common skin disorders. Am Fam Physician. 2013;87(12):850-856. 

8. Uysal PI, Akdogan N, Hayran Y, Oktem A, Yalcin B. Rosacea associated with increased risk of generalized anxiety disorder: a case-control study of prevalence and risk of anxiety in patients with rosacea [published online October 30, 2019]. Ann Bras Dermatol. doi:10.1016/j.abd.2019.03.002

9. Li WQ, Zhang M, Danby FW, Han J, Quershi AA. Personal history of rosacea and risk of incident cancer among women in the US. Br J Cancer. 2015;113(3):520-523. doi:10.1038/bjc.2015.217

10. Egeberg A, Hansen PR, Gislason GH, Thyssen JP. Association of rosacea with risk for glioma in a Danish nationwide cohort study. JAMA Dermatol. 2016;152(5):541-545. doi:10.1001/jamadermatol.2015.5549

11. Egeberg A, Fowler JF Jr, Gislason GH, Thyssen JP. Rosacea and risk of cancer in Denmark. Cancer Epidemiol. 2017;47:76-80. doi:10.1016/j.canep.2017.01.006

12. Long J, Li J, Yuan X, et al. Potential association between rosacea and cancer: a study in a medical center in southern China. J Dermatol. 2019;46(7):570-576. doi:10.1111/1346-8138.14918

13. Tjahjono LA, Cline A, Huang WW, Fleischer AB Jr, Feldman SR. Rosacea: relative risk versus absolute risk of malignant comorbidities. J Am Acad Dermatol. 2019;81(2):623-624. doi:10.1016/j.jaad.2019.01.013

14. Gold LS, Del Rosso JQ, Bhatia ND, Hooper D, Nahm W, Stuart I. Efficacy and safety of FMX103 (1.5% minocycline foam) in the treatment of moderate-to-severe papulopustular rosacea: results from two phase 3 randomized, multicenter, double-blind, vehicle-controlled studies. Poster presented at: SDPA Annual Fall Dermatology Conference; November 21-24, 2019; Scottsdale, AZ.

15. Foamix announces FDA acceptance of its new drug application for FMX103 minocycline foam for the treatment of moderate-to-severe papulopustular rosacea [press release]. Bridgewater, NJ; October 17, 2019. https://www.foamix.com/news-releases/news-release-details/foamix-announces-fda-acceptance-its-new-drug-application-fmx103. Accessed November 27, 2019.

16. Baldwin H, Santoro F, Lachmann N, Teissedre S. A novel moisturizer with high sun protection factor improves cutaneous barrier function and the visible appearance of rosacea-prone skin [published online February 25, 2019]. J Cosmetic Dermatol. doi:10.1111/jocd.12889