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Original Investigation |

Exploring the Association Between Rosacea and Parkinson Disease A Danish Nationwide Cohort Study

Alexander Egeberg, MD, PhD1,2; Peter Riis Hansen, MD, PhD, DMSci2; Gunnar H. Gislason, MD, PhD2,3,4; Jacob P. Thyssen, MD, PhD, DMSci1
[+] Author Affiliations
1Department of Dermato-Allergology, Herlev and Gentofte University Hospital, University of Copenhagen, Hellerup, Denmark
2Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
3The Danish Heart Foundation, Copenhagen
4The National Institute of Public Health, University of Southern Denmark, Copenhagen
JAMA Neurol. 2016;73(5):529-534. doi:10.1001/jamaneurol.2016.0022.
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Importance  The pathogenesis of rosacea is unclear, but increased matrix metalloproteinase target tissue activity appears to play an important role. Parkinson disease and other neurodegenerative disorders also display increased matrix metalloproteinase activity that contribute to neuronal loss.

Objective  To investigate the risk of incident (new-onset) Parkinson disease in patients with rosacea.

Design, Setting, and Participants  A nationwide cohort study of the Danish population was conducted using individual-level linkage of administrative registers. All Danish citizens 18 years or older from January 1, 1997, to December 31, 2011 (N = 5 472 745), were included. Data analysis was conducted from June 26 to July 27, 2015.

Main Outcomes and Measures  The main outcome was a diagnosis of Parkinson disease. Incidence rates (IRs) per 10 000 person-years were calculated, and incidence rate ratios (IRRs) adjusted for age, sex, socioeconomic status, smoking, alcohol abuse, medication, and comorbidity were estimated by Poisson regression models.

Results  A total of 5 404 692 individuals were included in the reference population; of these, 22 387 individuals (9812 [43.8%] women; mean [SD] age at diagnosis, 75.9 [10.2] years) received a diagnosis of Parkinson disease during the study period and 68 053 individuals (45 712 [67.2%] women; mean age, 42.2 [16.5] years) were registered as having rosacea. The IRs of Parkinson disease per 10 000 person-years were 3.54 (95% CI, 3.49-3.59) in the reference population and 7.62 (95% CI, 6.78-8.57) in patients with rosacea. The adjusted IRR of Parkinson disease was 1.71 (95%, CI 1.52-1.92) in patients with rosacea compared with the reference population. There was a 2-fold increased risk of Parkinson disease in patients classified as having ocular rosacea (adjusted IRR, 2.03 [95% CI, 1.67-2.48]), and tetracycline therapy appeared to reduce the risk of Parkinson disease (adjusted IRR, 0.98 [95% CI, 0.97-0.99]).

Conclusions and Relevance  Rosacea constitutes an independent risk factor for Parkinson disease. This association could be due to shared pathogenic mechanisms involving elevated matrix metalloproteinase activity. The clinical consequences of this association require further study.

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Rosacea and central nervous system disorders
Posted on May 11, 2016
LiQin Sheng1, HaiRong Ma1, HaiCun Shi2, PingLei Pan2
1 Department of Neurology, Kunshan Hospital of Traditional Chinese Medicine, Kunshan, P.R. China 2 Department of Neurology, Affiliated Yancheng Hospital, School of Medicine, Southeast University, Yanc
Conflict of Interest: No Conflicts of Interest Declared

Rosacea is a common skin disorder. However, rosacea is underestimated and receives less attention in neurological disorders. Recent epidemiologic data from Denmark’s national health care system show increased risks of Parkinson’s disease (PD)1, dementias such as Alzheimer disease (AD)2, multiple sclerosis (MS)3, Glioma4, and depression and anxiety disorders (DAD)5 in patients with rosacea. These results further advance the field of concomitant occurrence of central nervous system (CNS) disorders and rosacea. But the relationships between these disorders remain uncertain. Were these CNS disorders associated with risks of rosacea? Are they influenced by each other? Do these patients with co-occurring neurologic symptoms represent a distinct clinical subtype: neurogenic rosacea? Does rosacea also increase risks of other CNS disorders, such as stroke, meningitis, amyotrophic lateral sclerosis, and Huntington’s disease in the nationwide Danish population? These questions are particularly intriguing as they could affect our clinical strategies. More epidemiologic data are warranted to clarify their associations.

What is the common neurobiological basis between rosacea and these CNS disorders? Egeberg et al speculate that the matrix metalloproteinases (MMPs) involving in neuroinflammation may be the common basis for the pathogenic link between rosacea and these CNS disorders.1, 2, 4, 5 Importantly, they found that tetracycline-class antibiotics, these drugs with MMPs inhibitor function and with potentially neuroprotective effect, reduced the risk of PD1 in patients with rosacea, which lends support for their hypothesis. If the neuroprotective effect was true, however, Egeberg et al did not report whether tetracycline-class antibiotics could affect the risks of AD, MS, Glioma, and DAD in patients with rosacea. Although the exact pathophysiology in patients with rosacea and CNS disorders remains to be further addressed, a series of studies in patients with rosacea by Egeberg et al call our attention to a timely recognition of the neuropsychiatric symptoms and to an appropriate management. In addition, more research is needed to understand the diverse roles of MMPs and specific MMP inhibitors should be further explored.6, 7

Author Contributions: L.Q.S. and P.L.P. contributed to the concept. L.Q.S., H.R.M., H.C.S., and P.L.P. contributed to drafting the manuscript.

Potential Conflicts of Interest: Nothing to report.

References
1. Egeberg A, Hansen PR, Gislason GH, Thyssen JP. Exploring the Association Between Rosacea and Parkinson Disease: A Danish Nationwide Cohort Study. JAMA neurology. 2016 Mar 21.
2. Egeberg A, Hansen PR, Gislason GH, Thyssen JP. Patients with rosacea have increased risk of dementia. Annals of Neurology. 2016.
3. Egeberg A, Hansen PR, Gislason GH, Thyssen JP. Clustering of autoimmune diseases in patients with rosacea. Journal of the American Academy of Dermatology. 2016 Apr;74(4):667-72.e1.
4. Egeberg A, Hansen PR, Gislason GH, Thyssen JP. Association of Rosacea With Risk for Glioma in a Danish Nationwide Cohort Study. JAMA dermatology. 2016 Jan 27.
5. Egeberg A, Hansen PR, Gislason GH, Thyssen JP. Patients with Rosacea Have Increased Risk of Depression and Anxiety Disorders: A Danish Nationwide Cohort Study. Dermatology (Basel, Switzerland). 2016;232(2):208-13.
6. Mukherjee A, Swarnakar S. Implication of matrix metalloproteinases in regulating neuronal disorder. Molecular biology reports. 2015 Jan;42(1):1-11.
7. Rosenberg GA. Matrix metalloproteinases and their multiple roles in neurodegenerative diseases. The Lancet Neurology. 2009 Feb;8(2):205-16.
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