Rosacea is an independent risk factor for Parkinson’s disease, according to data published online ahead of print March 21 in JAMA Neurology. Shared pathogenic mechanisms involving elevated matrix metalloproteinase activity could explain the association, but its clinical consequences require further study, according to the authors.
In a 2001 study of 70 patients with Parkinson’s disease, researchers observed that 18.6% of the population had rosacea and that 31.4% of participants had facial flushing associated with temperature changes. This study prompted Alexander Egeberg, MD, PhD, of the Department of Dermato-Allergology at the University of Copenhagen’s Herlev and Gentofte Hospital, and colleagues to evaluate a potential association between rosacea and Parkinson’s disease in a nationwide cohort of the Danish population.
The investigators included in the study all Danish citizens who were age 18 or older from January 1, 1997, to December 31, 2011. Patients with prevalent rosacea or Parkinson’s disease at baseline, as well as those with a history of antiparkinson dopaminergic drug use, were excluded. The investigators identified patients with rosacea by the first documentation of a hospital diagnosis of rosacea or the filling of a second prescription of topical metronidazole. The study’s primary end point was a hospital diagnosis of idiopathic Parkinson’s disease. The secondary end point was the initiation of treatment with antiparkinson dopaminergic agents.
The study’s final cohort included 5,472,745 people with a maximum follow-up of 15 years. In all, 68,053 people had rosacea, and the investigators designated the group of participants without rosacea as the reference population. In all, 22,387 people (43.8% women; mean age, 75.9) received a diagnosis of Parkinson’s disease during the study period. In addition, 93,411 people in the reference population and 1,169 people with rosacea initiated treatment with antiparkinson dopaminergic agents.
The incidence rates of Parkinson’s disease per 10,000 person-years were 3.54 in the reference population and 7.62 in patients with rosacea. The incidence rates of treatment with antiparkinson dopaminergic agents were 15.03 and 32.17, respectively. Parkinson’s disease occurred approximately 2.4 years earlier in patients with rosacea. The incidence rate ratio of Parkinson’s disease, adjusted for age, sex, socioeconomic status, smoking, alcohol abuse, comorbidity, and medication, was 1.71 in patients with rosacea, compared with the reference population. The adjusted incidence rate ratio of treatment with antiparkinson dopaminergic agents was 1.59 in patients with rosacea, compared with the reference population.
Dr. Egeberg and colleagues found a reduced risk of Parkinson’s disease among patients who had filled prescriptions for a tetracycline. This finding suggests a need for randomized trials of this drug class in patients with Parkinson’s disease, they said.
In mouse models of Parkinson’s disease, increased expression of MMP-3 and MMP-9 has been implicated in the loss of dopaminergic neurons and nigrostriatal pathway degeneration. “Patients with rosacea also have increased activity of MMP-1, MMP-3, and MMP-9 in affected skin regions,” said the authors. “The recognition of neurogenic rosacea … lends further support to a pathogenic link between the two diseases. However, we emphasize that these findings are hypothesis generating; the basis for the pathogenic link between rosacea and Parkinson’s disease is unknown.”