Karin Uta Schallreuter

NoBackground\ud \ud Generation and accumulation of reactive oxygen/nitrogen species in the epidermis of patients with vitiligo has been widely documented. Moreover, semiquinone radical-mediated sensitivity has been shown in blood lymphocytes of these patients.\ud Objectives\ud \ud To determine the possible mechanism behind Q10-induced facial vitiligo.\ud Methods\ud \ud This was a clinical assessment supported by in vivo Fourier transform–Raman spectroscopy and repigmentation.\ud Results\ud \ud Topical Q10 application generated hydrogen peroxide (H2O2) leading in turn to facial vitiligo in susceptible individuals. Proof of the basic result stemmed from reduction of epidermal H2O2 by using narrowband ultraviolet B-activated propseudocatalase PC-KUS in association with cessation of depigmentation and repigmentation of the lost skin colour.\ud Conclusions\ud \ud Over-the-counter availability of Q10-containing topical formulations can be harmful to individuals susceptible to vitiligo

Vitiligo is an acquired, non-contagious depigmentation disorder involving a patchy loss of skin color. It often leads to stigmatization, embarrassment, and reduced quality of life (QoL) in adult patients. Little is known about children's reactions. This study aimed to explore disease-related QoL and experiences in a multinational group of children and adolescents. Quality of life, disease-related experiences and behavior, and sociodemographic data were examined in 24 boys and 50 girls (age range: 7-17 years) using the Children's Dermatology Life Quality Index (CDLQI) and additional questions. Eighteen children without skin disorders served as age-, sex- and skin color-matched controls. The mean disease duration was 3.5 years. The most common sites of onset were the trunk, legs, and head and neck. Overall, 35.1% of the 74 subjects reported a positive family history, 91.9% had visited a doctor, and 75.7% had received treatment. Two-thirds (66.2%) were distressed by their vitiligo, and 93.2% had experienced low-key stigmatization, 44.6% nasty comments, and 21.7% bullying. A total of 24.4% had concealed their disease, and 29.7% had avoided situations because of vitiligo. Frequency of stigmatization influenced avoidant behavior. Parents, particularly mothers, and friends were important sources of support. Patients and controls had similar numbers of friends and leisure time activities. The mean CDLQI score of the group was low (2.8). Higher CDLQI scores were related to stigmatization, hiding of white spots, facial depigmentation, avoidance of situations, and a vitiligo-negative family history. Disease-related stigmatization, negative experiences, and avoidant behavior affect QoL. Therefore, the CDLQI should be combined with other instruments to screen for disease burden. These results call for the careful evaluation of young patients with vitiligo.

Nonsegmental vitiligo (NSV) is characterized by loss of inherited skin color. The cause of the disease is still unknown despite accumulating in vivo and in vitro evidence of massive epidermal oxidative stress via H ₂ O ₂ and peroxynitrite (ONOO ^– ) in affected individuals. The most favored hypothesis is based on autoimmune mechanisms. Strictly segmental vitiligo (SSV) with dermatomal distribution is a rare entity, often associated with stable outcome. Recently, it was documented that this form can be associated with NSV (mixed vitiligo). We here asked the question whether ROS and possibly ONOO ^– could be players in the pathogenesis of SSV. Our in situ results demonstrate for the first time epidermal biopterin accumulation together with significantly decreased epidermal catalase, thioredoxin/thioreoxin reductase, and MSRA/MSRB expression. Moreover, we show epidermal ONOO ^– accumulation. In vivo FT‐Raman spectroscopy reveals the presence of H ₂ O ₂ , methionine sulfoxide, and tryptophan metabolites; i.e., N ‐formylkynurenine and kynurenine, implying Fenton chemistry in the cascade ( n = 10). Validation of the basic data stems from successful repigmentation of skin and eyelashes in affected individuals, regardless of SSV or segmental vitiligo in association with NSV after reduction of epidermal H ₂ O ₂ ( n =5). Taken together, our contribution strongly supports H ₂ O ₂ /ONOO‐mediated stress in the pathogenesis of SSV. Our findings offer new treatment intervention for lost skin and hair color.—Schallreuter, K. U., Salem, M. A. E. L., Holtz, S., Panske, A., Basic evidence for epidermal H2O2/ONOO–‐mediated oxidation/nitration in segmental vitiligo is supported by repigmentation of skin and eyelashes after reduction of epidermal H2O2 with topical NB‐UVB‐activated pseudocatalase PC‐KUS. FASEB J. 27, 3113–3122 (2013). www.fasebj.org

Background  Vitiligo is an acquired, idiopathic, and worldwide common depigmentation disorder with an estimated prevalence from 0.1 to 8%. These numbers are based on clinical population studies and field research examining inhabitants of geographically enclosed areas. Our aim was to collect all available data on the prevalence of vitiligo in the general population, paying particular attention to children/adolescent groups and adults.Materials and methods  Screening of available literature and online databases using several key words.Results  We found more than 50 studies that used several methods and subgroups of the general population. The prevalence of vitiligo ranges from 0.06 to 2.28%, whereas this was 0.0–2.16% in children/adolescents populations.Conclusions  The often cited prevalence of 8% could not be confirmed after excluding clinical patient populations. Accordingly, the worldwide prevalence of vitiligo ranges between 0.5 and 2%.

Vitiligo is characterized by a mostly progressive loss of the inherited skin color. The cause of the disease is still unknown, despite accumulating in vivo and in vitro evidence of massive oxidative stress via hydrogen peroxide (H ₂ O ₂ ) and peroxynitrite (ONOO ^– ) in the skin of affected individuals. The most favored hypothesis is based on autoimmune mechanisms. Since depletion of the essential amino acid L‐tryptophan (Trp) severely affects various immune responses, we here looked at Trp metabolism and signaling in these patients. Our in vivo and in vitro data revealed total absence of epidermal Trp hydroxylase activities and the presence of H ₂ O ₂ /ONOO ^– deactivated indoleamine 2,3‐dioxygenase. Aryl hydrocarbon receptor signaling is severely impaired despite the ligand (Trp dimer) being formed, as shown by mass spectrometry. Loss of this signal is supported by the absence of downstream signals (COX‐2 and CYP1A1) as well as regulatory T‐lymphocytes and by computer modeling. In vivo Fourier transform Raman spectroscopy confirmed the presence of Trp metabolites together with H ₂ O ₂ supporting deprivation of the epidermal Trp pool by Fenton chemistry. Taken together, our data support a long‐expressed role for in loco redox balance and a distinct immune response. These insights could open novel treatment strategies for this disease.—Schallreuter, K. U., Salem, M. A. E. L., Gibbons, N. C. J., Maitland, D. J., Marsch, E., Elwary, S., Healey, A. R. Blunted epidermal L‐tryptophan metabolism in vitiligo affects immune response and ROS scavenging by Fenton chemistry, part 2: epidermal H ₂ O ₂ /ONOO ^– ‐mediated stress in vitiligo hampers indoleamine 2,3‐dioxygenase and aryl hydrocarbon receptor‐mediated immune response signaling. FASEB J. 26, 2471‐2485 (2012). www.fasebj.org

Vitiligo is characterized by a progressive loss of inherited skin color. The cause of the disease is still unknown. To date, there is accumulating in vivo and in vitro evidence for massive oxidative stress via hydrogen peroxide (H₂O₂) and peroxynitrite (ONOO^–) in the skin of affected individuals. Autoimmune etiology is the favored theory. Since depletion of the essential amino acid L‐tryptophan (Trp) affects immune response mechanisms, we here looked at epidermal Trp metabolism via tryptophan hydroxylase (TPH) with its downstream cascade, including serotonin and melatonin. Our in situ immunofluorescence and Western blot data reveal significantly lower TPH1 expression in patients with vitiligo. Expression is also low in melanocytes and keratinocytes under in vitro conditions. Although in vivo Fourier transform‐Raman spectroscopy proves the presence of 5‐hydroxytryptophan, epidermal TPH activity is completely absent. Regulation of TPH via microphthalmia‐associated transcription factor and L‐type calcium channels is severely affected. Moreover, dopa decarboxylase (DDC) expression is significantly lower, in association with decreased serotonin and melatonin levels. Computer simulation supports H₂O₂/ONOO^–‐mediated oxidation/nitration of TPH1 and DDC, affecting, in turn, enzyme functionality. Taken together, our data point to depletion of epidermal Trp by Fenton chemistry and exclude melatonin as a relevant contributor to epidermal redox balance and immune response in vitiligo.—Schallreuter, K. U., Salem, M. A. E. L., Gibbons, N. C. J., Martinez, A., Slominski, R., Lüdemann, J., Rokos, H. Blunted epidermal L‐tryptophan metabolism in vitiligo affects immune response and ROS scavenging by Fenton chemistry, part 1: epidermal H₂O₂/ONOO^–‐mediated stress abrogates tryptophan hydroxylase and dopa decarboxylase activities, leading to low serotonin and melatonin levels. FASEB J. 26, 2457‐2470 (2012). www.fasebj.org

Vitiligo betrifft 1 von 200 Menschen in Nordeuropa. Die Krankheit erzeugt großen Leidensdruck bei Betroffenen. Die Patienten leiden unter massiver H₂O₂- und Peroxinitrit-induzierter Redoximbalance mit nachgewiesener DNS-Schädigung in der Haut und im Blut, die in der Folge viele verschiedene körpereigene Signale betrifft. Der Nachweis von konstant hochreguliertem funktionierendem p53 wird als Reparaturmöglichkeit vorgestellt. Es wird versucht, mögliche Autoimmunreaktionen im Zusammenhang mit diesem Geschehen und genetischer Prädisposition/Spontanmutation zu erklären. Weiterhin werden verschiedene Therapieansätze inklusive Reduktion des oxidativen Stresses mit Pseudokatalase PC-KUS und kombinierte Klimatherapie sowie Verhaltensempfehlungen für den Patienten unter besonderer Berücksichtigung der neuen Erkenntnisse diskutiert. Vitiligo occurs in Northern Europe in one of 200 people. The disease can cause significant psychological stress for the affected individual. These patients generate and accumulate massive amounts of H₂O₂- and peroxynitrite in the epidermal compartment. Consequently many proteins are oxidized or nitrated, leading in turn to partial or complete loss of functionality. Moreover, presence of DNA damage in the skin as well as in plasma has been shown, while apoptosis is not enhanced. Induction of DNA repair is associated with up-regulated functioning p53 protein. Considering possible genetic predisposition and /or spontaneous mutations, autoimmune reactions in the disease are put forward in the context of oxidative stress. In addition a review of recent and novel treatment modalities including the role of oxidative stress reduction and combined climatotherapy at the Dead Sea in a group are discussed.