Egeberg A, et al. Association of rosacea with risk for glioma in a Danish nationwide cohort study. JAMA Dermatology 2016; 152: 541-545.
A nationwide cohort study of the Danish population of all citizens older than 18 over a 14-year period (1997-2011), encompassing 5,484,910 people was performed: 21,118 had glioma and 68,372 had rosacea. In the reference group of 5,416,538, 20,934 were diagnosed with glioma (incidence rate 3.34) and in the rosacea group 184 developed a glioma (incidence rate 4.99); the adjusted incidence rate ratio of glioma in patients with rosacea was 1.36. The authors hypothesize that matrix metalloproteinases that are involved in tissue remodeling may be the common denominator linking the two disorders. They suggest in their conclusion that an “increased focus on neurologic symptoms (e.g. headaches, memory loss, seizures, loss of muscle control, visual symptoms, dysarthria, cognitive decline, and personality changes) in patients with rosacea and timely referral to relevant specialists may be warranted.
I read this article with distinct personal interest. Last week I just paid a Shiva call to the brother of a close friend who died of glioblastoma multiforme; a few months ago, I visited my cousin who was diagnosed some months earlier; I lost a friend, and dermatology lost a giant, last year with Wally Burgdorf’s passing; and over the past few years I can add 3 other friends and acquaintances who have succumbed to glioblastoma multiforme. None had rosacea (to the best of my knowledge).
According to Bush et al (Current and future strategies for treatment of glioma. Neurosurg Rev 2016 April 16 Epub ahead of print):
“Currently, the only known risk factor for the development of malignant glioma is exposure to ionizing radiation, and no other environmental exposures including cell phone use, infection or trauma has been shown to have an effect. Thereare however, multiple studies ongoing that are evaluating the genetic risk factors for developing glioma. The use of genome-wide association studies (GWAS) has identified to date seven genomic variants that confer increased glioma risk.”
Egeberg et al state, correctly, that “The observational nature of our study does not allow establishment of causation and is open to the influence of unmeasured confounders.” Perhaps metalloproteinases play some pathogenic role in both conditions; does that link them? Like so many disorders, the pathogenesis comes likely down to genetics and environment. Indeed, Aldrich et al (Genetic vs. environmental factors that correlate with rosacea: A cohort-based survey of twins. JAMA Dermatol 2015; 151: 1213-9) concluded that:
“The study of twins allows us to separate genetic susceptibility and the influence of environmental factors affecting rosacea. We found that approximately half of the contribution to the NRS score could be accounted for by genetics and the other half by environment. We identified correlations between rosacea and UV radiation exposure, alcohol, smoking, skin cancer history, cardiac comorbidity, and age. These findings may help improve current management and expectations of individuals affected by rosacea.”
Both rosacea and the spectrum of gliomas are complex, multifactorial disorders. A relative risk of 1.36 does not seem particularly high – perhaps there is some link. Maybe those patients have similar genetic predisposition, such as HLA-DRA as the authors suggest, and in the context of an environmental exposure such as ionizing radiation, could have an elevated risk of an association. Obviously, if patients bring the aforementioned problems to my attention, they will be directed to a neurologist. Until more research is done, however, I will not be taking a thorough neurologic review of systems for my patients with rosacea.