Highlights of Rosacea Research 2022

This year, the National Rosacea Society (NRS) is celebrating its 30th year of fulfilling the mission of “improving the lives of people with rosacea through awareness, education, and support of medical research.”¹ Rosacea was considered a rare disease believed to affect fewer than 200 000 people in the United States when the NRS was formed in 1992. We now know that more than 16 million Americans have the condition. As rosacea continues to be investigated, this article summarizes 3 recent studies that shed light on the role of sex and age in the disease, its association with frontal fibrosing alopecia, and its link with increased skin cancer risk.

Clinical Aspects of Female Patients With Rosacea Vary Based on Age Groups

A study published in the Journal of Cosmetic Dermatology found that in female patients aged 45 years and older, rosacea’s clinical symptoms are more complex and challenging to treat.²

In this retrospective study, researchers aimed to analyze and compare the cutaneous features, aggravating factors, systemic diseases, and psychological states across age groups of 840 female patients with rosacea. Depending on the patients’ age at diagnosis, they were split into 3 groups: 30 years and younger, 31 to 44 years, and 45 years and older, with the mean age of 35.9±10.23 years.

Common cutaneous features included burning/stinging sensation, dry sensation, persistent erythema, pruritis, and telangiectasia. The common aggravating factors were hot temperature, emotional changes, spicy food, and sun exposure. Of the total group, 20.4% of the patients had comorbidities of systemic disorders, whereas 48.8% experienced anxiety and 35.2%, depression.

There were significant differences in the clinical characteristics of female patients with rosacea in different age groups. Middle-aged and older patients were more likely to develop telangiectasia and more severe and persistent erythema. They also had more diseases affecting the digestive, endocrine/metabolic, and cardiovascular systems and were relatively less affected by influencing factors.

Frontal Fibrosing Alopecia Associated With Rosacea

People with frontal fibrosing alopecia (FFA) may struggle with their appearance and experience quality of life issues. The cutaneous comorbidities of FFA have been studied in recent years, and several of these studies have reported rosacea. Up to this point, inflammation and immunologic responses are recognized to be involved in the pathogenesis of FFA and rosacea. However, the precise mechanism of FFA complicated with rosacea is yet unknown.

In a study published in Frontiers in Immunology, researchers aimed to clarify and quantify the correlation between FFA and rosacea by performing a comprehensive meta-analysis of observational studies and analyzing the gene expression profiles of FFA and rosacea to gain insight into their common pathogenesis.³

For the meta-analysis, 9 original observational studies that reported data on the association between FFA and rosacea (FFA prevalence in patients with rosacea, prevalence of rosacea in FFA, and odds ratio or hazard ratio) were included. The Gene Expression Omnibus database was used to explore the relationship between the hub genes and pathways to quantify their correlation.

Patients with FFA were more likely to develop rosacea than those without FFA. From the total of 1647 patients with FFA in the 9 studies, rosacea was seen in 23% of them; 65% of the patients were women older than age 50 years. According to the subgroup analyses of prevalence by sex, male patients had a pooled prevalence of 18% compared with female patients at 25%. The quality and stability of the results were confirmed by sensitivity analysis.

One hundred fifteen common differentially expressed genes and 13 hub genes were identified through the transcription datasets of FFA and rosacea. The inflammatory and immunologic responses were somewhat shared by the 2 diseases’ biologic mechanisms. There is a need for more research on the relationship between FFA and rosacea. The hub genes found in this study may serve as possible treatment targets in future research.

Skin Cancer and Actinic Keratosis in Patients With Rosacea

Inconclusive results and confl icting data still surround the relationship between rosacea and skin cancer. A study published in Acta Dermato-Venereologica revealed an increased risk of actinic keratosis and keratinocyte carcinoma in patients with rosacea.⁴

The researchers aimed to determine the risk of skin cancer among patients with rosacea in a nationwide population-based cohort study using data from the South Korean National Health Insurance Sharing Service.

The study cohort was comprised of patients aged 30 to 89 years with records of 3 or more primary rosacea diagnoses with pertinent ICD-10 codes from 2010 to 2019. Patients without any history of rosacea during the observation period comprised the control group. Patients with lupus erythematosus, seborrheic dermatitis, or acne diagnostic codes between 2009 and 2019 were not included in the control group.

From 2009 to 2019, new instances of actinic keratosis; skin cancer, including nonmelanoma skin cancer; cutaneous melanoma; gastric cancer; colorectal cancer; and liver cancer were characterized based on possessing 1 or more pertinent ICD-10 codes. Gastric, colorectal, and liver cancers were selected as common cancers in South Korea to compare with skin cancer. For categorical variables, the Pearson _x2 test or Fisher exact test was applied, whereas the Student t-test was used for continuous variables. Each skin condition's incidence rate (IR) was estimated per 1,000 person-years; the IR ratio (IRR) was computed by comparing the IRs with the matched control group. Results of a multivariable stratified Cox proportional hazards model analysis were displayed as an adjusted hazard ratio, with 95% CIs. Hazard ratios were modified for hypertension, diabetes, and dyslipidemia. The supreme test for proportional hazards assumption was used to validate the proportional hazard assumption.

For actinic keratosis analysis, a total of 10953 patients with rosacea were matched with a control group of 21906 patients. Female patients comprised 64.7% of the patients with rosacea, and 61.2% of them were aged 40 to 59 years. In the rosacea group, the prevalence of hypertension, diabetes, and dyslipidemia was noticeably higher than those in the control group, with 30.4%, 15.4%, and 16.4%, respectively. When compared with the control group, the IRR of actinic keratosis in patients with rosacea was statistically significant at 4.48. After accounting for comorbidities, the study group’s risk of actinic keratosis was higher than that of the control group.

For skin cancer analysis, a total of 10 973 rosacea patients were matched with a control group of 21946 patients. When compared with the control group, the IRR of skin cancer in patients with rosacea was statistically significant at 2.61. Analysis of subgroups showed a higher risk of nonmelanoma skin cancer. Each analysis met the proportional hazard assumption.

For gastric, colorectal, and liver cancer analysis, a total of 10825 patients with rosacea were matched with a control group of 21650 patients. When compared with the control group, the IRR of gastric, colorectal, or liver cancer in patients with rosacea was not statistically significant. Each analysis met the proportional hazard assumption.

Comparing patients with rosacea with the control group revealed an increased risk of actinic keratosis and nonmelanoma cancer, but no statistically significant increase in the risk of melanoma or gastric, colorectal, or liver cancer.

In conclusion, this South Korean study discovered that people with rosacea are more likely to develop actinic keratosis and nonmelanoma skin cancer, possibly because these conditions share similar pathogenic factors such as UV radiation. The study findings might strengthen the case for sun protection in patients with rosacea. To clarify the shared pathogenic mechanisms and genetic factors between rosacea and skin cancer, additional studies in various populations with thorough clinical data, genetic analysis, and a longer follow-up period are required.

References

1. National Rosacea Society celebrates 30 years. News release. National Rosacea Society. November 1, 2022. Accessed November 8, 2022. https://www.rosacea.org/press/2022/november/national-rosacea-society-celebrates-30-years

2. Yang F, Wang L, Shucheng H, Jiang X. Diff erences in clinical characteristics of rosacea across age groups: a retrospective study of 840 female patients. J Cosmet Dermatol. Published online October 13, 2022. doi:10.1111/jocd.15470

3. Liu L, Chen Y, Chen J, et al. Association between frontal fibrosing alopecia and rosacea: results from clinical observational studies and gene expression profiles. Front Immunol. 2022;13:985081. doi:10.3389/fimmu.2022.985081

4. Cho SI, Lee H, Cho S. Risk of skin cancer and actinic keratosis in patients with rosacea: a nationwide population-based cohort study. Acta Derm Venereol. 2022;102:adv00803. doi:10.2340/actadv.v102.2563