published_or_final_version / Medicine / Master / Doctor of Medicine

Background: Birch pollen is an important outdoor allergen able to aggravate symptoms in atopic dermatitis (AD). Specific immunotherapy (SIT), an established procedure for allergic airway diseases, might also represent an attractive therapeutic option for the causal treatment of allergen-triggered cutaneous symptoms in these patients. Studies with house dust mite SIT have already shown beneficial effects in AD patients, whereas the safety and efficacy of SIT with birch pollen extract in AD patients have not been studied so far. The aim of this study was to evaluate for the first time the safety and efficacy of SIT with a depigmented polymerized birch pollen extract in AD patients. Methods: Fifty-five adult patients with moderate-to-severe AD and clinically relevant sensitization to birch pollen received SIT for 12 weeks. SIT was continued during birch pollen season. The assessment of safety, the total SCORAD value, and the Dermatology Life Quality Index (DLQI) were evaluated. Results: The median total SCORAD value was reduced by 34% (p < 0.001) during the course of treatment and the mean DLQI improved by 49% (p < 0.001) despite strong simultaneous birch pollen exposure. Eight patients (14.5%) developed systemic reactions and 19 patients (34.5%) developed local reactions which were of mild intensity in most cases. No patient discontinued the study prematurely due to adverse drug reactions. Coseasonal treatment was well tolerated. Conclusion: SIT with a depigmented polymerized birch pollen extract leads to significant improvement of the SCORAD value and the DLQI in patients suffering from moderate-to-severe AD sensitized to birch pollen. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Darbo tikslas – įvertinti dermatitu sergančių pacientų įsijautrinimą kontaktiniams alergenams ir su juo susijusius veiksnius. Darbo uždaviniai: 1. Nustatyti įsijautrinimo kontaktiniams alergenams dažnumą tarp dermatitu sergančių pacientų. 2. Įvertinti įsijautrinimo kontaktiniams alergenams dažnumo sąsajas su tiriamųjų amžiumi, lytimi ir profesija. 3. Nustatyti įsijautrinimo kontaktiniams alergenams klinikos ypatumus. 4. Įvertinti įsijautrinimo kontaktiniams alergenams sąsajas su atopiniu dermatitu, lėtine (-ėmis) kojos (-ų) opa (-omis) ir kitais veiksniais. Išvados: 1. Kontaktiniams alergenams įsijautrinę pusė dermatitu sergančių pacientų, dažniausiai – metalui nikeliui (17,1 proc.). Iš aromatinių medžiagų dažniausias yra įsijautrinimas Peru balzamui (8 proc.). Į pagrindinį alergenų rinkinį neįtrauktini retai (0,1 proc.) nustatyti alergenai: gumų medžiagos merkaptobenzotiazolas ir N-zopropil-N’-fenil-parafenilendiaminas. 2. Įsijautrinimas kontaktiniams alergenams jaunesniems nei 40 metų dermatitu sergantiems pacientams pasireiškia du kartus dažniau nei vyresniems, o moterims – du kartus dažniau nei vyrams. Žemės ūkio ir miškininkystės darbuotojai kontaktiniams alergenams įsijautrinę tris kartus dažniau nei kiti dirbantieji. Vertinant atskirus alergenus, jaunesni nei 40 metų pacientai dažniau nei vyresni yra įsijautrinę nikeliui, kobaltui ir kvaterniumui-15, o 40 metų ir vyresni – Peru balzamui, kanifolijai, aromatų mišiniui I, lanolinui, seskviterpenlaktonams ir... [toliau žr. visą tekstą] / The aim of the study: To evaluate contact sensitization and its associated factors in patients with dermatitis. The objectives of the study: 1. To determine the frequency of sensitization to contact allergens in patients with dermatitis. 2. To evaluate associations between the frequency of sensitization to contact allergens and age, sex and occupation in patients with dermatitis. 3. To determine clinical features of contact sensitization. 4. To evaluate associations between sensitization to contact allergens and atopic dermatitis, chronic leg ulcers and other factors. CONCLUSIONS 1.Half of the patients with dermatitis were sensitized to contact allergens, most frequently to metal nickel (17.1%). From the fragrances, bal¬sam of Peru was the most frequent contact allergen (8%). Rare allergens that should not be included in the baseline series are the substances present in the composition of rubber – mercaptobenzothiazole and N-isopropyl-N'-phenyl-p-phenylene diamine (IPPD). 2.Patients under 40 years of age are two times more frequently sensitized than the older ones. In women contact allergy is twice as more frequent as in men. Agricultural and forestry workers are sensitized to contact allergens three times as more often as other employees. What regards individual allergens, among patients under 40 years of age sensitization to nickel, cobalt and quaternium-15 is more prevalent than in the older ones. Among patients who are 40 years of age and over contact sensitization to... [to full text]

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Orientador: Jose Inacio de Oliveira / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-15T19:21:40Z (GMT). No. of bitstreams: 1 Reis_FelipeRovereDiniz_M.pdf: 3469626 bytes, checksum: 9ef6c34f776f70e4620230f3b66bd0f4 (MD5) Previous issue date: 2010 / Resumo: Diversos estudos descrevem o perfil clínico-epidemiológico e os resultados dos testes de contato das populações atendidas com suspeitas de dermatite alérgica de contato. Alguns evidenciam a provável relação causal com o trabalho; outros alertam para a necessidade de repetição do teste quando ocorrem múltiplas reações, principalmente nas demandas trabalhistas. O objetivo foi analisar o perfil clínico-epidemiológico e os resultados dos testes de contato dos pacientes com suspeita de dermatite alérgica de contato ocupacional atendidos no Ambulatório de Medicina do Trabalho da Universidade Estadual de Campinas. Foi realizado um estudo descritivo transversal retrospectivo com pacientes atendidos entre 1 de janeiro de 1999 e 31 de dezembro de 2008, envolvendo as seguintes variáveis: idade, cor, sexo, ocupação, tempo na ocupação, agente referido como sensibilizante, local inicial do eczema, origem do encaminhamento, resultados dos testes de contato e nexo causal. Foram analisados 180 prontuários e os resultados mostraram que o perfil clínicoepidemiológico foi semelhante àqueles referidos na literatura, mas os índices desensibilização foram proporcionalmente maiores: 85% dos pacientes tiveram pelo menos uma reação positiva no primeiro teste de contato, a média de reações positivas por teste foi 3,38 e 68% dos testes positivos apresentaram mais de duas reações positivas. Os elevados índices de sensibilização e a existência simultânea de múltiplas reações na maioria dos pacientes podem ser explicados por condições predisponentes para polissensibilização - dermatite nas mãos cronificadas por repetidas exposições ocupacionais - e/ou pela interpretação de reações irritativas como reações positivas. Foi sugerida, então, uma Ficha de Coleta de Dados, a ser preenchida durante as avaliações clínicas e a repetição dos testes de contato quando ocorrerem mais de 2 reações positivas relevantes a substâncias não correlacionada / Abstract: Several studies describe the clinical and epidemiological profile and the results of patch tests of the targeted population with suspected allergic contact dermatitis. Some evidence the probable causal relationship to work; others warn of the need to repeat tests when multiple reactions occur, especially in the lawsuits. The objetive was to analyze the clinical and epidemiological profile and the results of patch tests of patients with suspected allergic contact dermatitis treated at the Campinas State University's Occupational Medicine Clinic. We conducted a retrospective cross-sectional study with patients treated between January 1, 1999 and December 31, 2008 involving the following variables: age, race, sex, occupation, time in occupation, sensitizing agent, eczema locus, referral source, results of patch tests and causal relationship. We analyzed 180 medical records and the results show that clinical and epidemiological profile was similar to those reported in the literature, but the rates of awareness were proportionally larger: 85% of patients had at least one positive reaction in the first patch test, the average of positive reactions per test was 3.38 and 68% dos positive tests had more than two positive reactions. High levels of sensitization and the simultaneous existence of multiple reactions in most patients can be explained by predisposing factors to polysensization - cronic dermatitis on the hands caused by repeated occupational exposure - and/or by the interpretation of irritant reactions as positive reactions. It has been suggested then a sheet data collection to use in the clinic evaluation that includes the repetition of tests when more than 2 relevant positive reactions occurred to substances not correlated / Mestrado / Epidemiologia / Mestre em Saude Coletiva

M.Tech. / Diaper dermatitis (Nappy Rash) is an acute inflammation of the skin in the diaper area and is the most common cutaneous disease among infants and children (Concannon et al., 2001). It is estimated that 7% - 35% of diaper wearing infants are affected by Diaper dermatitis during the period of wearing diapers (Barkin and Rosen, 2003). The exact prevalence is not known as many cases are selfmedicated by parents or guardians (Wolf et al., 2000). Diaper dermatitis causes severe discomfort to the infants as well as anxiety and worry for the parents. Diaper dermatitis is characterised by redness, inflammation, dryness, scaling, itching, irritability, pain, satellite lesions, papulovesicular or pustular eruptions, and in severe cases ulceration of the skin (Visscher and Hoath, 2006). This study aimed to assess the efficacy of a Homoeopathic complex cream as a topical treatment for Diaper dermatitis. The complex consisted of Atropa belladonna 6cH, Calendula officinalis D1 and Sulphuricum acidum 6cH. Madaji milking cream was used as a base which contained: chlorhexidene; vitamin E; and lanolin. The treatment group received the medicated Madaji milking cream whereas the control group received the unmedicated Madaji milking cream. The Diaper dermatitis was evaluated using a 4-Point Grading Scale (Appendix D) and The Modified Lund and Browder Chart (Appendix E). Forty participants who met the inclusion and exclusion criteria were recruited to participate in this double blind control study by means of advertisements (Appendix A) that were placed on notice boards at the various campuses of the University of Johannesburg, nursery schools and hospitals, with relevant permission given. Participants were also recruited via word of mouth. Once participants were accepted into the study they were allocated to either Group A or Group B using matched pairs according to severity in order to ensure equal v distribution in both groups. There were 20 participants in each group. Group A was the treatment group which received the medicated Madaji milking cream. Group B was the control group which received the unmedicated Madaji cream. The study was completed over a seven day period. The ten areas most commonly affected by Diaper dermatitis were evaluated on the initial visit, day two, day four and day seven.

This investigation deals with the study of a possible hypersensitivity to the oleoresins of fifty common plants indigenous to Hunt County, Texas.

<p>Pojava alergijskog kontatnog dermatitisa koji nastaje kao komplikacija tokom lečenja hronične venske insuficijencije je dobro poznata. Cilj istraživanja je bio da se kod obolelih od hronične venske insuficijencije utvrdi učestalost kontaktne senzibilizacije ekcemskog tipa, potom da li postoji rizik za nastanak kontaktne senzibilizacije kao i postojanje korelacije između dužine trajanja bolesti i kontaktne senzibilizacije. Hipoteza rada je da osobe sa hroničnom venskom insuficijencijom značajno če&scaron;će razvijaju kontaktnu senzibilizaciju nego osobe bez hronične venske insuficijencije, da imaju veći rizik za nastanak kontaktne senzibilizacije kao i da je učestalost kontaktne senzibilizacije u pozitivnoj korelaciji sa dužinom trajanja bolesti. Istraživanje je sprovedeno nad 266 ispitanika. Formirane su dve grupe. Eksperimentalnu grupu su činili oboleli od hronične venske insuficijencije upućeni na alergolo&scaron;ko testiranje pod sumnjom na postojanje kontaktnog dermatitisa, a kontrolnu grupu su činili bolesnici bez hronične venske insuficijencije epikutano testirani pod sumnjom na postojanje kontaktnog dermatitisa. Obolelima od hronične venske insuficijencije je procenjena težina bolesti na osnovu CEAP klasifikacije. Potom je svaki ispitanik podvrgnut alergolo&scaron;kom epikutanom testiranju pač testom. Istraživanje je pokazalo da je učestalost kontaktne senzibilizacije među obolelima od hronične venske insuficijencije iznosila 49,3%. Učestalost kontaktne senzibilizacije kod osoba sa hroničnom venskom insuficijencijom na alergene: iz sastava Evropske standardne baterije je iznosila 31,55%; baterije specifične za hroničnu vensku insuficijenciju je iznosila 28,45%; komercijalno dostupne baterije alergena ubikvitarnih korovskih biljaka iz porodice Compositae je iznosila 6,69%; originalno spravljene ekstrakte ubikvitarnih korovskih biljaka Vojvodine je iznosila 6,11%. Ne postoji statistički značajna razlika u odnosu na pol. Prevalencija kontaktne senzibilizacije kod osoba sa hroničnom venskom insuficijencijom se nije statistički značajno razlikovala od osoba koje nisu imale hroničnu vensku insuficijenciju. Pozitivnost epikutanog alergolo&scaron;kog testa kojim se potvrđuje postojanje kontaktne senzibilizacije je bila statistički značajno vi&scaron;a kod osoba sa hroničnom venskom insuficijencijom. Osobe sa hroničnom venskom insuficijencijom su imale 2,45 puta vi&scaron;i rizik za nastajanje kontaktne senzibilizacije na dva i vi&scaron;e alergena, a 3,69 puta vi&scaron;i rizik za nastajanje kontaktne senzibilizacije na pet i vi&scaron;e alergena u odnosu na one bez hronične venske insuficijencije. Učestalost kontaktne senzibilizacije je u pozitivnoj korelaciji sa dužinom trajanja bolesti.</p> / <p>Development of allergic contact dermatitis as a complication of treatment of chronic venous insufficiency is well known. The aim of this study was to determine the incidence of eczematous contact sensitization in patients with chronic venous insufficiency, possible risks for the development of contact sensitization, and the correlation between disease duration and contact sensitization. The working hypothesis was that the incidence of contact sensitivity is significantly higher in individuals with chronic venous insufficiency than in those without chronic venous insufficiency, that they are at greater risk of developing contact sensitization, and that there is a positive correlation between the incidence of contact sensitization and the disease duration. The study included 266 patients. They were divided into two groups: the study group included patients with chronic venous insufficiency referred for allergy testing due to suspected contact dermatitis, and the control group included patients without chronic venous insufficiency patch tested for suspected contact dermatitis. The severity of chronic venous insufficiency was assessed by CEAP classification. Thereafter, each patient underwent patch testing. The research has shown that the incidence of contact sensitization among patients with chronic venous insufficiency was 49.3%. In these patients, the incidence of contact sensitization to the European standard battery of allergens was 31.55%; to the battery specific for chronic venous insufficiency it was 28.45%; to commercially available batteries of allergens of ubiquitous plants from the Compositae family it was 6.69%; and to originally prepared extracts of ubiquitous plants found in Vojvodina it was 6.11%. There was no statistically significant difference in relation to sex. The prevalence of contact sensitization in patients with chronic venous insufficiency was not significantly different from those without chronic venous insufficiency. Positive patch test reaction rates, confirming the existence of contact sensitization, were significantly higher in patients with chronic venous insufficiency. Patients with chronic venous insufficiency had a 2.45-fold higher risk for developing contact sensitization to two or more allergens, and a 3.69-fold higher risk for developing contact sensitization to five or more allergens compared to those without chronic venous insufficiency. There was a positive correlation between the incidence of contact sensitization and the duration of the disease.</p>

Atopische Dermatitis (Atopisches Ekzem) ist die häufigste Erkrankung der Haut, und sie ist mit der Entwicklung anderer schwerwiegenden atopischen Erkrankungen wie Lebensmittelallergien, allergischer Rhinitis, Heuschnupfen und Asthma vergesellschaftet. Inaktivierende Mutationen im Filaggrin (FLG) Gen zeigten die stärkste Assoziation mit dem Krankheitsbild der atopischen Dermatitis. FLG wird fast ausschließlich in der Epidermis der Haut ausgeprägt und trägt maßgeblich zur normalen Differenzierung von Keratinozyten und zur Integrität der Hautbarriere bei. Bi-allelische inaktivierende Mutationen in dem Gen verursachen die Hauterkrankung Ichthyosis vulgaris, bei es zu Ausbildung einer übermäßig trockenen und schuppigen Hautoberfläche kommt. Etwa die Hälfte aller Ichthyosis vulgaris Patienten entwickeln ebenfalls atopische Dermatitis im Laufe Ihres Lebens. Zusätzlich treten in Ichthyosis vulgaris Patienten häufiger atopische Krankheitsbilder auf als in Gesunden. Als Modell zur Erforschung molekularer Grundlagen der Pahtologie des atopischen Ekzemes und von Pathomechanismen der Atopie eignet sich die „flaky tail“ Mauslinie. Diese Mäuse entwickeln typische Merkmale einer systemischen Atopie wie z.B. einen Barriere Defekt der Haut, ein Hautekzem, eine Entzündung der Lunge, sowie erhöhte Mengen an Immunglobulin E im Serum. In diesem Modell wird die Krankheitsentwicklung durch zwei natürlich entstandene Mutationen in den Genen Flg und Tmem79 verursacht. Die das Gen Flg betreffende Mutation bewirkt eine reduzierte Expression, welche einen Ichthyosis vulgairs ähnlichen Phänotyp auslöst, der durch Schuppenartige („flaky“) Haut am Schwanz („tail“) gekennzeichnet ist (Flgft). Die Mutation im Tmem79 Gen bewirkt eine matte Fellfarbe und wird daher als „matted“ Mutation (Tmem79ma) bezeichnet. Obwohl die Mutationen in benachbarten Regionen des Maus Chromosoms 3 zu finden sind, konnten diese genetisch getrennt werden. Dadurch gelang es zu zeigen, dass allein die Tmem79ma Mutation ausreicht, um Ekzeme und systemische Atopie in Mäusen auszulösen. Nach Rückkreuzung der Flgft Mutation auf den pro-allergischen BALB/c genetischen Hintergrund entwickelten die Flgft/ft BALB/c Mäuse eine - Erkrankung ähnlich der atopischen Dermatitis, die ebenfalls von spontanem Asthma und hohen IgE Konzentrationen im Serum gekennzeichnet war. Beides sind Hauptmerkmale des sogenannten atopischen Marsches. Diese Versuche implizierten, dass Filaggrin eine wichtige Funktion im Schutz vor der Entwicklung von Atopie in Mäusen ausübt. Im Gegensatz zu diesen Ergebnissen wurden nach dem Rückkreuzen von Flg knockout (Flg-/-) Mäusen auf den BALB/c Hintergrund nur ein transienter neonataler Ichthyose Phänotyp, aber keine Hautentzündung oder Atopie beobachtet. Um diese Diskrepanz besser zu verstehen, generierten wir Flg knockout Mäuse direkt im BALB/c Hintergrund. Diese genetisch reinen Flg-/-/BALB/c Mäuse rekapitulierten den neonatalen Ichthyose Phänotyp, und sie zeigten einen Barriere Defekt, der die perkutane Sensibilisierung förderte. Spontane Entzündungen der Haut oder systemische Atopie wurden allerdings nicht beobachtet. Um die genetische Ursache der Atopie in Flgft/ft BALB/c Mäusen zu verstehen, sequenzierten wir das Genom mittels PacBio long read sequencing und verglichen es mit dem BALB/c Referenzgenom. Überraschenderweise zeigte die Analyse, dass die kongenen Flgft/ft BALB/c Mäuse ebenfalls die Atopie-verursachende Tmem79ma Mutation im homozygoten Zustand trugen. Zuvor wurde berichtet, dass die Flgft und Tmem79ma Mutationen vor dem Rückkreuzen des Flgft Allels auf den BALB/c Hintergrund voneinander getrennt werden konnten. Unsere Beobachtungen erklären nun die phänotypische Diskrepanz zwischen den Flgft/ft BALB/c und den Flg-/-/BALB/c Mäusen. Die Daten implizieren, dass der alleinige Funktionsverlust von FLG keine Atopie auslöst und werden durch Beobachtungen in einem Teil der FLG-defizienten Ichthyosis vulgaris Patienten gestützt, die ebenfalls keine Atopie zeigen. Es ist trotzdem wahrscheinlich, dass der Verlust von Filaggrin im Zusammenspiel mit weiteren genetischen Barriere Defekten, wie z.B. Mutationen im Tmem79 Gen das Krankheitsbild der Atopie qualitativ beeinflusst.:Abbreviations 6 Summary 9 Zusammenfassung 11 Introduction 13 Skin 13 Epidermis 13 The immune system 15 Adaptive immune response effector mechanisms 17 Allergic diseases 19 Atopic march 19 Atopic dermatitis 19 Metabolics of AD skin 23 Filaggrin and AD 25 Current mouse models of barrier defect and AD 29 Induced AD mouse models 29 Transgenic and knock out (KO) AD mouse models 30 Inbred mouse strains spontaneously developing AD-like disease 31 Mouse models of FLG-deficiency 32 AD and microbiome 34 Aim 37 Material and methods 38 Generation of Flg-/- mice 38 Crispr targeting strategy 38 α-FLG Western Blot 39 Protein extract preparation 39 SDS Electrophoresis 39 α-FLG Immunofluorescence staining 40 PCR Typing 40 Isolation of genomic DNA from mouse tail tips 40 PCR typing strategy 41 H&E staining of neonatal mouse ear skin 42 Ear thickness measurement 44 Quantification of transepidermal water loss (TEWL) 44 Quantification of total and antigen-specific IgE 44 Whole back skin RNA Sequencing (RNA-Seq) 44 Sorting of basal ear skin keratinocytes for RNA extraction, by fluorescence-activated cell sorting (FACS) 45 Quantitative real time PCR (qRT-PCR) 47 Flow cytometric analysis of ear skin 48 Analysis of DO11.10+/4get transgenic T cell response to epicutaneous OVA immunization 49 Skin microbiome analysis 50 S.aureus colonization of Flg mutant mice 51 Long-term epicutaneous OVA treatment 52 Mapping of reads, assembly, annotation and variant calling 53 Statistical analysis 55 Results 56 Generation and validation of Flg-/-/ BALB/c mice 56 Large sequence deletions detected in Flg-mutant mice by PCR 56 Complete loss of FLG protein expression in Flg-/- mice 57 Flg-/-/BALB/c mice show a barrier-defective skin 59 FLG-deficient skin is devoid of inflammation 61 FLG-deficient skin shows age-related inside-out barrier defect 62 Mild T cell expansion and no other changes in the epidermal compartment of the Flg-/-/BALB/c mice 62 γδ T cell expansion in the whole ear skin suspensions of FLG-deficient mice 64 Lack of systemic atopy in FLG-deficient mice, as indicated by IgE quantification 67 S. aureus colonization does not trigger eczema or atopy in FLG-deficient mice 68 Sensitization with a protein Ag does not trigger inflammation in FLG-deficient mice 69 FLG-deficient skin shows age-related outside-in barrier defect 69 Mild inflammatory signature detected in Flg-/-/BALB/c back skin by RNA sequencing 71 Type 2 immune response signalling detected in Flg-/-/BALB/c ear skin keratinocytes by RNA sequencing 72 FLG-deficient ear skin shows elevated IL-1b expression 74 Reduced cutaneous commensal microbial diversity in FLG-deficient mice 75 Presence of atopy-causing Tmem79ma mutation in Flgft/ft BALB/c mouse genome account for phenotypic differences with our Flg-/-/BALB/c mice 76 Discussion 81 FLG-deficiency in mice does not trigger spontaneous atopic disease 81 FLG-deficiency in mice causes mild immunological perturbation 82 Atopic march, observed in Flgft/ft BALB/c congenic strain, can be explained by the presence of the matted mutation 88 Relevance of filaggrin deficiency for the pathogenesis of atopy in mouse and man 89 References 92 Acknowledgments 136 Erklärung zur Eröffnung des Promotionsverfahrens 137 Erklärung über die Einhaltung der gesetzlichen Vorgaben 138

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