Rosacea Research Roundup

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Any views and opinions expressed are those of the author(s) and/or participants and do not necessarily reflect the views, policy, or position of The Dermatologist or HMP Global, their employees, and affiliates. 

The following studies show potential links between systemic inflammatory conditions both on the skin and in the body, which can inform the way clinicians ask questions and identify the best course of treatment for their patients with rosacea.

IBD May Lead to Rosacea

For the first time, a new study has shown that the presence of inflammatory bowel disease (IBD), a well-known comorbidity of rosacea, as well as its subtypes, ulcerative colitis (UC) and Crohn disease (CD), may lead to rosacea, according to a report published in the scientific journal Nature Scientific Reports.¹

“Our findings provided evidence for a causal impact of IBD, UC, and CD on rosacea, but not vice versa,” the investigators wrote. “The elevated incidence of rosacea in patients with IBD should be recognized by doctors to make an early diagnosis and initiate specialized therapy.”

Comorbidity alone does not necessarily mean that one causes the other, although these associations are notable because they provide potential helpful indicators, such as the patterns and causes of each, or of risk factors that may make them likely to appear together. Rosacea has been linked to a wide range of comorbidities, including a growing number of potentially life-threatening systemic illnesses, and IBD and its subtypes in particular have recently been shown to often appear alongside rosacea, although sometimes with conflicting interpretations.^2-4

The study used data from the FinnGen Consortium project, which collected biologic samples from 500000 participants in Finland with the aim of improving health through genetic research. The investigators in the new study were able to isolate genetic characteristics from rosacea and IBD only but avoided complicating variables for both disorders, such as cardiometabolic disease, Helicobacter pylori infection, Demodex mite infection, migraine, depression, anxiety, and obesity.

Using Mendelian randomization, they found evidence that a genetic predisposition to IBD, UC, and CD was linked to an elevated risk of rosacea. The reverse was not true, however; there was no evidence that genetic predisposition to rosacea raised a patient’s risk of IBD, UC, or CD.

Although the results may clarify the causal relationship between rosacea and IBD, the underlying mechanisms of that link have not yet been fully elucidated, the investigators noted. The 2 disorders share many factors: both are chronic inflammatory conditions involving the interplay between genetic and immunologic elements; both have abnormalities in innate and adaptive immunity; and both have common risk factors, such as smoking, obesity, and small intestinal bacterial overgrowth. Moreover, the investigators observed that certain medications used to treat IBD, such as topical or systemic corticosteroids, have been reported in the literature to be associated with rosacea’s onset. They also noted that medication-induced symptoms of rosacea often resolve after discontinuation of the triggering medication.

More research is required to further understand the patho-physiologic processes behind this association, the investigators concluded.

Inflammation Pathway Involving Demodex Mites Revealed
Demodex mites have long been a conundrum for patients with rosacea. Unlike other environmental triggers, they are unavoidable because they are normal inhabitants of facial skin,⁵  but they do exist in greater numbers on the skin of individuals with rosacea.^6,7 Researchers in South Korea found a link between the presence of elevated numbers of Demodex mites and several molecules that have been identified as playing a role in the inflammation of rosacea, according to a recent study in the Journal of the European Academy of Dermatology and Venereology.⁸

“The findings of this study are instrumental for understanding the underlying causes of rosacea and could potentially lead to the development of new treatments,” the investigators wrote. “The identification of this pathway as a therapeutic target could represent a major breakthrough for rosacea research.”

In an in vitro study, researchers applied mineral oil to the skin of 38 patients with rosacea and squeezed, collecting the oil and skin microbiome contents on glass slides. They then grouped the samples into 3 categories: those containing no mites (12 samples), those with 1 to 9 mites (16 samples), and those with more than 10 mites (10 samples). An mRNA expression lab test of the samples showed that expression levels of genes related to rosacea were significantly increased in the groups with higher Demodex counts, including toll-like receptor 2, kallikrein-5, and cathelicidin LL37. The higher Demodex samples also showed increased levels of transient receptor potential vanilloid 1, a neuroinflammatory molecule, as well as tropomyosin receptor kinase A and nerve growth factor, which play a role in pain sensation.

“This research offers an explanation for the skin sensitization and cutaneous neurogenic inflammation symptoms associated with rosacea, which are caused by increased LL37 in the presence of larger Demodex population counts in the skin of patients with rosacea,” the investigators indicated. They suggested that the results may provide further insight into the disease process in rosacea.

Study Delves Deeper Into Rosacea and Headaches
A recent study in Turkey examined the relationship between rosacea and headaches, finding that different types of headaches were significantly associated with certain presentations of rosacea, and patients with moderate or severe rosacea were more likely to experience headaches.⁹

The study enrolled 300 patients diagnosed with rosacea (214 women, 86 men) and 320 control subjects with neither rosacea nor any mast cell activation illnesses (208 women, 112 men). Patients experiencing headaches were assessed using the International Headache Classification, and headaches were categorized as migraine, tension-type headaches, secondary-type headaches (due to an underlying medical condition), or cluster-type headaches.

Among the rosacea group, headaches were more common among women than men, and the median age of those with head-aches was lower. Migraine was the most common type of headache observed, comprising 59.3% of the total, followed by tension-type (28.6%), secondary-type (11.0%) and cluster-type (1.1%). Twice as many patients with rosacea experienced migraines than in the control group (18.0% vs 9.0%, P =.11). In 81.3% of patients with rosacea who had headaches, onset occurred after the diagnosis of rosacea. The investigators found there was a positive correlation between rosacea severity and migraine severity.

Although the percentage of patients with rosacea experiencing headaches was similar to that of the control group (30.3% vs 25.0%, P=.138), the rate of headaches among patients with pre-dominantly erythematotelangiectatic rosacea (ETR) was significantly higher than in patients with predominantly papulopustular rosacea or rhinophyma (35.2% vs 16.2% vs 23.1%, respectively; P =.007). In terms of comorbidities, patients with rosacea who also had a peptic ulcer were more likely to experience headaches. Among common rosacea triggers, only sunlight was significantly associated with headache.

The rates of migraine and stress-type headaches were comparatively more common among patients with ETR than in other subtypes, whereas tension headaches were more common among those with rhinophyma. The prevalence of burning, stinging, and itching (common but nondiagnostic phenotypes of rosacea) was higher in patients who experienced headaches than in those who did not and was also higher in patients who had migraines than those experiencing other headache types.

The researchers noted that the results highlighted the connection between migraine and ETR. “The predominant ETR subtype, categorized as a subtype of rosacea with diverse clinical features and insufficient treatment outcomes, may denote a distinctive patient cohort, which demonstrates classic rosacea symptoms, but stems from different pathogenic mechanisms,” they wrote.

References​​​​​​​

1. Li M, He SX, He YX, Hu XH, Zhou Z. Detecting potential causal relationship between inflammatory bowel disease and rosacea using bi-directional Mendelian randomization. Nature Sci Rep. 2023;13(1):14910. doi:10.1038/s41598-023-42073-6
2. Spoendlin J, Karatas G, Furlano RI, et al. Rosacea in patients with ulcerative coli-tis and Crohn’s disease: a population-based case-control study. Inflamm Bowel Dis. 2016;22(3):680-687. doi:10.1097/MIB.0000000000000644
3. Kim M, Choi KH, Hwang SW, et al. Inflammatory bowel disease is associ-ated with an increased risk of inflammatory skin diseases: a population-based cross-sectional study. J Am Acad Dermatol. 2017;76(1):40-48. doi:10.1016/j. jaad.2016.08.022
4. Egeberg A, Weinstock LB, Thyssen EP, et al. Rosacea and gastrointestinal disorders: a population-based cohort study. Br J Dermatol. 2017;176(1):100-106. doi:10.1111/bjd.14930.
5. Thoemmes MS, Fergus DJ, Urban J, Trautwein M, Dunn RR. Ubiquity and diversity of human-associated Demodex mites. PLoS One. 2014;9(8):e106265. doi:10.1371/journal.pone.0106265.
6. Jarmuda S, O’Reilly N, Zaba R, et al. Potential role of Demodex mites and bacteria in the induction of rosacea. J Med Microbiol. 2012;61(Pt 11):1504-1510. doi:10.1099/jmm.0.048090-0
7. Forton FMN. Papulopustular rosacea, skin immunity and Demodex: pityriasis folliculorum as a missing link. J Eur Acad Dermatol Venereol. 2012;26(1):19-28. doi:10.1111/j.1468-3083.2011.04310.x
8. Lee SG, Kim J, Lee YI, Kim J, Choi YS, Ham S, Lee JH. Cutaneous neurogenic inflammation mediated by TRPV1-NGF-TRKA pathway activation in rosacea is exacerbated by the presence of Demodex mites. J Eur Acad Dermatol Venereol. 2023;37(12):2589-2600. doi:10.1111/jdv.19449
9. Alizada M, Sahin T, Sener O, et al. Evaluation of dermatological and neurological aspects of the relationship between rosacea and headaches. Diagostics (Basel). 2023;14(1):23. doi:10.3390/diagnostics14010023