Oxidative stress and ferritin expression in the skin of patients with rosacea Vesna Sredoja Tisma, MD, MSc, a Aleksandra Basta-Juzbasic, MD, PhD, b Morana Jaganjac, BSc, c Luka Brcic, MD, PhD, d Ivan Dobric, MD, PhD, b Jasna Lipozencic, MD, PhD, b Franz Tatzber, MD, PhD, e Neven Zarkovic, MD, PhD, c and Marija Poljak-Blazi, BSc, PhD c Zagreb, Croatia, and Vienna, Austria Background: Rosacea is a common chronic light-sensitive inflammatory skin disease of unknown origin. The purpose of this work was to determine the parameters of oxidative stress, antioxidative capacity, and the pathophysiologic role of ferritin expression in skin cells of patients with rosacea. Objectives: The investigation consisted of measurements of serum peroxide levels, serum total antioxidative potential levels, and immunohistochemical analyses of ferritin in skin tissue samples. Results: Serum peroxide levels were significantly higher and serum total antioxidative potential levels were significantly lower in patients with rosacea than in healthy control subjects (P \.05). Compared with control subjects, the number of ferritin-positive cells was significantly higher (P \ .001) in skin samples from patients with rosacea, especially those with severe disease. Limitations: Patients with rosacea in the study were aged 30 to 70 years (average age was 56 years). Younger patients with flushing only were not included according to the request of the ethics committee, limiting the use of diagnostic biopsies only to the necessary cases. Conclusion: The statistically significant differences in the expression of ferritin, higher peroxide levels, and lower antioxidative potential support the onset of systemic oxidative stress in patients with rosacea. ( J Am Acad Dermatol 2009;60:270-6.) R osacea is a common chronic inflammatory dermatosis, characterized by various combi- nations of cutaneous signs such as flushing, erythema, telangiectasia, edema, papules, papulo- pustules, ocular lesions, and phymas. Women are affected at a younger age and more often than men, although more extreme cases with rhinophyma are mainly seen in men. 1,2 Although the pathogenesis of rosacea remains unknown, inflammation is a central process in this disorder. Recent evidence suggests that in rosacea inflammation is associated with production of reac- tive oxygen species (ROS) by inflammatory cells such as neutrophils. 3 ROS themselves do not necessarily have to lead to development of pathological processes; however, in the presence of transition metals, such as copper and iron, they easily generate harmful hydroxyl radicals. Iron has the capacity to accept and donate electrons readily, which makes it physiologically essential as a useful component of cytochromes and oxygen-bind- ing molecules. However, iron is also biochemically dangerous; it can damage tissues by catalyzing the conversion of hydrogen peroxide to free radicals that attack cellular membranes, proteins, and DNA. Iron overload may amplify the damaging effects of su- peroxide and peroxide overproduction in a broad spectrum of acute and chronic inflammatory condi- tions. 4 In cells, most of the iron that is not metabo- lized is sequestered in ferritin as a crystalline core of ferric (Fe 31 ) ions. To catalyze oxidative reactions, the iron must first be released from the core. Thus, ferritin is able to restrict the availability of iron to From the Polyclinic Department of Dermatology and Venereology, Dubrava University Hospital, Zagreb a ; Department of Derma- tology and Venereology, Zagreb University Hospital Center b ; Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb c ; Institute of Pathology, Medical School University of Zagreb d ; and KEG Co. Vienna. e Supported by Croatian Ministry of Science, Education, and Sports and by COST Action B35. Conflicts of interest: None declared. Accepted for publication June 26, 2008. Reprint requests: Neven Zarkovic, MD, PhD, Laboratory for Oxidative Stress, Division of Molecular Medicine, Rudjer Boskovic Institute, Bijenicka 54, HR-10002 Zagreb, Croatia. E-mail: zarkovic@irb.hr. Published online November 25, 2008. 0190-9622/$36.00 ª 2008 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2008.10.014 270