<p>Contact allergy is one of the most common skin diseases with great social and economical impact. The origin and nature of contact allergens (haptens) capable of inducing T-cell mediated allergic reactions are diverse, ranging from organic molecules to metal ions. Most of the current knowledge on T-cell responses to haptens in humans with contact allergy have been established by studies on the metal ion nickel (Ni), the most common cause of contact allergy, whereas reactivity to the large group of organic haptens has been less studied.</p><p>Haptens are not immunogenic by themselves but must bind carrier molecules prior to their presentation on MHC class I or II molecules and subsequent recognition by T cells. Due to differences in their chemical nature, haptens interact with host molecules by different mechanisms and differences in their solubility can influence their access to different antigen-presenting pathways.</p><p>The aim of the present study was to define immune responses elicited by haptens of different chemical nature including Ni (hydrophilic metal ion), methylisothiazolinones (hydrophilic organic molecule) and parthenolide (lipophilic organic molecule). The immune response displayed by subjects with allergy to these substances, and non-allergic control subjects, was assessed by measuring hapten-induced cytokine production in peripheral blood mononuclear cells (PBMC) with a focus on ELISpot analysis of T-cell type 1 (e.g. IFN-g and IL-2) and type 2 (e.g. IL-4, IL-5 and IL-13) cytokines. For Ni and parthenolide, the phenotype of the hapten-reactive T cells was determined. The allergic status of subjects was defined by clinical history and patch testing. The latter is the established diagnostic method for contact allergy, based on applying various haptens to the subjects’ back and grading the skin reaction after 2-3 days.</p><p>All three haptens elicited a concomitant T-cell type 1 and 2 response in subjects with contact allergy to the corresponding hapten, suggesting the induction of a functionally related cytokine profile, irrespective of the chemical character of the hapten. The cytokine response was related to the degree of the subjects’ patch test reactivity; PBMC from a vast majority of subjects with strong and moderate patch test reactivity displayed detectable cytokine responses to the corresponding haptens, whereas subjects with weak or no (controls) patch test reactivity did not. Despite the similar cytokine profile induced, the phenotype of the reactive T cells was found to differ between haptens with Ni eliciting CD4+ T cells and parthenolide eliciting CD8+ T cells. This difference may be explained by a better ability of a lipophilic hapten to gain access to the MHC class I-restricted antigen-presentation pathway. Moreover, the data suggest that analysis of cytokine responses to haptens may facilitate future development of <i>in vitro</i>-based diagnostics assay for contact allergy.</p><p>Finally, the relationship between the variation over time in patch test reactivity and systemic reactivity to Ni, in terms of cytokine responses to Ni <i>in vitro</i>, was investigated. The degree of patch test reactivity is known to vary over time, in particular in subjects with weak reactivity. Ni-allergic subjects were patch tested three times with three month intervals and PBMC obtained at the same time points were assessed for<i> in vitro</i> reactivity to Ni. The overall reactivity in the patch test and the <i>in vitro</i> test was well correlated confirming that both methods provide a good and comparable estimate of the systemic reactivity to Ni. However, fluctuations in the patch test reactivity over time were not well correlated with variations in the cytokine response elicited <i>in vitro</i> suggesting that other parameters besides changes in the systemic reactivity could significantly contribute to the variation in patch test reaction over time.</p>

Contact allergy is one of the most common skin diseases with great social and economical impact. The origin and nature of contact allergens (haptens) capable of inducing T-cell mediated allergic reactions are diverse, ranging from organic molecules to metal ions. Most of the current knowledge on T-cell responses to haptens in humans with contact allergy have been established by studies on the metal ion nickel (Ni), the most common cause of contact allergy, whereas reactivity to the large group of organic haptens has been less studied. Haptens are not immunogenic by themselves but must bind carrier molecules prior to their presentation on MHC class I or II molecules and subsequent recognition by T cells. Due to differences in their chemical nature, haptens interact with host molecules by different mechanisms and differences in their solubility can influence their access to different antigen-presenting pathways. The aim of the present study was to define immune responses elicited by haptens of different chemical nature including Ni (hydrophilic metal ion), methylisothiazolinones (hydrophilic organic molecule) and parthenolide (lipophilic organic molecule). The immune response displayed by subjects with allergy to these substances, and non-allergic control subjects, was assessed by measuring hapten-induced cytokine production in peripheral blood mononuclear cells (PBMC) with a focus on ELISpot analysis of T-cell type 1 (e.g. IFN-g and IL-2) and type 2 (e.g. IL-4, IL-5 and IL-13) cytokines. For Ni and parthenolide, the phenotype of the hapten-reactive T cells was determined. The allergic status of subjects was defined by clinical history and patch testing. The latter is the established diagnostic method for contact allergy, based on applying various haptens to the subjects’ back and grading the skin reaction after 2-3 days. All three haptens elicited a concomitant T-cell type 1 and 2 response in subjects with contact allergy to the corresponding hapten, suggesting the induction of a functionally related cytokine profile, irrespective of the chemical character of the hapten. The cytokine response was related to the degree of the subjects’ patch test reactivity; PBMC from a vast majority of subjects with strong and moderate patch test reactivity displayed detectable cytokine responses to the corresponding haptens, whereas subjects with weak or no (controls) patch test reactivity did not. Despite the similar cytokine profile induced, the phenotype of the reactive T cells was found to differ between haptens with Ni eliciting CD4+ T cells and parthenolide eliciting CD8+ T cells. This difference may be explained by a better ability of a lipophilic hapten to gain access to the MHC class I-restricted antigen-presentation pathway. Moreover, the data suggest that analysis of cytokine responses to haptens may facilitate future development of in vitro-based diagnostics assay for contact allergy. Finally, the relationship between the variation over time in patch test reactivity and systemic reactivity to Ni, in terms of cytokine responses to Ni in vitro, was investigated. The degree of patch test reactivity is known to vary over time, in particular in subjects with weak reactivity. Ni-allergic subjects were patch tested three times with three month intervals and PBMC obtained at the same time points were assessed for in vitro reactivity to Ni. The overall reactivity in the patch test and the in vitro test was well correlated confirming that both methods provide a good and comparable estimate of the systemic reactivity to Ni. However, fluctuations in the patch test reactivity over time were not well correlated with variations in the cytokine response elicited in vitro suggesting that other parameters besides changes in the systemic reactivity could significantly contribute to the variation in patch test reaction over time.

The purpose of this study was to examine the hairdresser’s knowledge about the chemicals they handle in their business and how they were handling the chemicals and the risks that follows. 9 Salons were visited to gather information. The same questions were asked at the salons. A sample of hair color products was photographed to gather information about ingredients and labeling. The conclusions of the study were that hairdressers have good knowledge about the risks related to human health but they need to improve their knowledge when it comes to environmental risks. The deficiencies that were found were that they lack knowledge about the laws concerning the use and distribution of cosmetics products and that not all saloons are handling the hazardous waste and residues from treatments correctly. The risks that could follow are that not enough is done to protect human health and the environmental. To prevent that damage to human health and the environmental occurs they should use more sources that focus on health and environmental to gather information about the risks with the chemicals they are handling, they should also limit the treatments on children and always inform about the risks when they are using products that can cause an allergic reaction. Keywords: Risks hairdressing, cosmetics products, p-phenylenediamine, Toluene-2,5-diamine, ammonia.

The aim of this cross-sectional study was to evaluate the frequency of dental allergens and potential co-factors, especially hypothyroidism, for patients with an intraoral contact allergy. From 2015 to 2016, patients with confirmed symptoms of an intraoral contact allergy (study group SG n = 50) were recruited in the dental clinic of the University of Leipzig. The participants of the control group (CG n = 103) were patients without oral diseases or intraoral symptoms of a contact allergy. For the data collection, a new “Allergy questionnaire” was developed. Information on allergies and general diseases were collected. The statistical analysis was carried out with SPSS 23.0. Sensitizations/allergies to metals and composites were higher in SG compared to CG. Of all study participants (n = 148), 14.2% (n = 21) had a nickel allergy. In 18% (n = 8) of the SG a cobalt allergy based on all metal allergens could be seen. In addition, an association between a nickel and cobalt allergy was found. Hypothyroidism occurred significantly more frequently (p = 0.049) in SG than in CG. Sensitizations and allergies can occur to metals in dental alloys. Hypothyroidism increased the risk of having an allergy threefold.

No description available.

In der heutigen Zeit sind ca. 4000 Verbindungen bekannt, denen die Fähigkeit nachgesagt wird, eine Kontaktallergie auslösen zu können. Die Entscheidung, ob ein Stoff hautsensibilisierende Eigenschaften besitzt, wird dabei meist auf der Grundlage von Beobachtungen am Menschen und/oder von tierexperimentellen Befunden getroffen. Bedingt durch den vermehrten Einsatz exotischer Pflanzen und neu entwickelter synthetischer Substanzen im Bereich der Kosmetikindustrie besteht der Bedarf an einer einfachen Methode zur Vorhersage des kontaktallergenen Potentials einer Verbindung. Als zentraler Schritt bei der Manifestierung einer Kontaktallergie wird die Bildung eines Hapten-Carrier-Komplexes aus dem niedermolekularen Kontaktallergen (Hapten) und Hautproteinen (Carrier) angesehen. Zur Abschätzung der Sensibilisierungsfähigkeit kann daher auch die Reaktivität der Substanz oder ihrer Metaboliten gegenüber Proteinen herangezogen werden. Im Rahmen dieser Arbeit werden neben dem bedeutenden Phytoekzematogen Tulipalin A die bisher wenig untersuchten kontaktallergenen Duftstoffe Geraniol, 7-Hydroxycitronellal, Benzaldehyd, Salicylaldehyd, Vanillin, Zimtaldehyd, a-Amyl-zimtaldehyd und Benzylcinnamat hinsichtlich ihrer Reaktivität gegenüber peptidgebundenen Aminosäuren untersucht. Verwendet werden für diese Modellversuche Hippuryl-Derivate und Acetyl-Derivate der Aminosäuren Lysin, Histidin, Arginin bzw. Cystein sowie zusätzlich Glutathion. Die dabei gewählten Bedingungen sollen eine Adaption an physiologische Gegebenheiten erlauben. Ziel ist es, zu klären, ob die mit diesen Modellversuchen zu gewinnenden Ergebnisse mit dem bekannten kontaktallergenen Potential der eingesetzten Haptene korrelieren und somit geeignet sind, die Sensibilisierungsfähigkeit einer Substanz vorherzusagen. Über Konjugationsprodukte von Kontaktallergenen mit Peptiden oder Proteinen ist in der Literatur sehr wenig bekannt. Daher ist es ein weiteres Ziel dieser Arbeit, individuelle Produkte der Reaktionen der kontaktallergenen Substanzen mit den nukleophilen Aminosäureseitenketten zu isolieren und zu charakterisieren, um so definierte Hapten-Carrier-Konjugate, die unter physiologisch relevanten Bedingungen entstehen können, zu beschreiben. Aufbauend auf den gefundenen Strukturen sollte es auch möglich sein, Hinweise auf eventuelle Reaktionsmechanismen zu erhalten.

Nickel allergy is the most prevalent contact allergy and has been discussed as a possible riskfactor for hand eczema. However, hand eczema is one of the most frequently occurring skindiseases and has multifactorial origin. The aim of this thesis was to study the association between nickel allergy and hand eczema in the general population. There are only a fewpopulation-based studies previously published, that include patch testing. In addition, this thesis aimed to evaluate methods to follow the prevalence of nickel allergy.The study cohort consisted of 908 women who had been patch tested for the occurrence of nickel allergy as schoolgirls. Twenty years later, they were invited to participate in a follow-up questionnaire study. The response rate was 81%. In total, 17.6% of respondents reported handeczema after the age of 15 years and there was no statistically significant difference in the occurrence of hand eczema between those who were nickel-positive and those who were nickel negativeas schoolgirls. To further investigate possible links, another study was performed,which included a second questionnaire, a clinical investigation and patch testing. All schoolgirls from the baseline study who were still living in the area as adults were invited to participate and the participation rate was 77%. Patch test showed 30.1% nickel-positive individuals.When all participants were included in the analysis, there was no statistically significant difference between nickel-positive and nickel-negative women regarding occurrence of hand eczema. The most important risk factor for hand eczema was childhood eczema. Adjusted prevalence proportion ratio (PPR) for hand eczema after age 15 in relation to nickel patch testresults was 1.03 (95% CI 0.71--1.50) and in relation to childhood eczema 3.68 (95% CI 2.45--5.54). When women with and without history of childhood eczema were analyzed separately, the hand eczema risk was doubled in nickel-positive women without history of childhood eczema. In conclusion, the risk of hand eczema in nickel-positive women may previously havebeen overestimated. Next, the validity of self-reported nickel allergy was investigated. In the established cohort; two questions regarding nickel allergy were compared with patch test results. The validity of self-reported nickel allergy was low, and the questions regarding nickel allergy overestimated the true prevalence of nickel allergy. The positive predictive values were 59% and 60%. Another method for estimating the prevalence of nickel allergy, namely self-patch testing, was validated in the last study. In total, 191 patients from three different dermatology departments participated. The validity of self-testing for nickel allergy was adequate, with sensitivity 72%and proportion of agreement 86%. / Nickelallergi är vanligt förekommande. Prevalensen i Skandinavien är 15--25% hos kvinnor och cirka 3% hos män. Sambandet mellan nickelallergi och uppkomst av handeksem har tidigare diskuterats och i vissa studier anges att 30--45% av alla individer med nickelallergi får handeksem. Det finns dock endast ett fåtal publicerade studier där personer ur normalbefolkningen har lapptestats för nickel. Handeksem ärvanligt och har ofta flera olika kombinerade orsaker. Det övergripande syftet med avhandlingen var att studera nickelallergins betydelse för uppkomst av handeksem. Detfinns ett intresse av att följa förekomsten av nickelallergi över tid, speciellt sedan det i början av 2000-talet infördes ett EU-direktiv som begränsar nickelinnehåll i klockor,smycken, metallknappar etc. Ytterligare ett syfte med avhandlingen var att utvärderaepidemiologiska metoder för att följa förekomsten av nickelallergi.Den första studien var en uppföljningsstudie av 908 flickor ur normalbefolkningen,vilka i skolåldern lapptestats med nickel. Tjugo år senare skickades en enkät till dessa kvinnor, svarsfrekvensen var hög (81%). Förekomsten av självrapporterat handeksemefter 15 års ålder var 17.6%. Det förelåg ingen signifikant skillnad i förekomst avhandeksem mellan de kvinnor som var nickelallergiska som barn jämfört med dem som inte var nickelallergiska. År 2006 utfördes ytterligare en studie, som inkluderade de kvinnor som fortfarande bodde i Örebro län. Studien omfattade en klinisk undersökning av händerna samt ett lapptest. 30% av kvinnorna var positiva för nickel.Det förelåg ingen signifikant skillnad i förekomst av handeksem mellan de som var positiva för nickel och de som var negativa. Vid separat analys av de kvinnor som angav tidigare barneksem jämfört med dem som aldrig hade haft barneksem visade det sig att risken för handeksem var dubbelt så stor hos nickelallergiker i den gruppen som aldrig hade haft barneksem. Båda studierna visade att barneksem var den största riskfaktorn för att få handeksem som vuxen, med en 3-4 gånger ökad risk. Den tredje studien var en validering av självrapporterad nickelallergi. Överensstämmelsen var låg mellan enkätfrågor gällande nickelallergi och lapptestverifierad nickelallergi. Av dem som själva bedömde sig vara nickelallergiska var endast 59% positiva enligt lapptest. För att följa förekomsten av nickelallergi i befolkningen behövs därför andra metoder. I den fjärde studien utvärderades ett självtest för nickelallergi. 191 patienter från tre olika hudkliniker i Sverige deltog i studien. Validiteten för metoden självtest var tillfredsställande, sensitiviteten var 72%och graden av överensstämmelse var 86%.

Individual and environmental risk factors in hand eczema have been investigated in a prospective cohort study of 2452 newly employed hospital workers with a follow-up time of 20 months. Current hand eczema was analyzed in 142 wet hospital workers from this cohort with respect to the etiologic importance of irritants, allergens and contact urticants. The density of the microflora and the effect on the microflora of topical treatment with a potent corticosteroid were studied in 20 patients with hand eczema. ’Wet’ hospital work was found to increase the odds of developing hand eczema only twice compared to 'dry' office work. Nursing children under four years old and the lack of a dish-washing machine significantly increased the risk of contracting hand eczema. Unfavourable combinations of these domestic factors increased the risk as much as wet work. A history of atopic dermatitis approximately tripled the odds both in wet as well as in dry work. Histories of earlier hand eczema (HHE), metal dermatitis (HMD) and of atopy were analyzed as risk factors for hand eczema in 1857 women in wet work. HHE increased the odds by a factor of 12.9 and created a subdivision of the population into high risk individuals and normal risk individuals. HHE was found in half of the subjects with atopic dermatitis, in one quarter of the subjects with atopic mucosal symptoms and in one fifth of the non-atopics. A HMD increased the odds by a factor of 1.8. This increase was seen as a high risk level in subjects with HHE and as a normal risk level in subjects with no HHE. A history of atopic disease as a complement to information about HHE and HMD increased the odds by another 1.3 times. The predicted probability of developing hand eczema ranged from 91 % in subjects with a combination of HHE, HMD and atopy to 24% in subjects with none of these risk factors. Subjects with AD were found to suffer a more severe form of hand eczema with significantly higher figures for medical consultation, sick- leave, termination due to hand eczema, early debut, permanent symtoms and vesicular lesions. Amongst the patients investigated for current hand eczema high risk individuals were overrepresented. It was claimed in 92.3% of the cases that trivial irritant factors had elicited the current episodes of hand eczema. In 35% of the cases the exposure to the irritant took place largely at home. Although contact sensitivity and contact urticaria were fairly common, they mostly seemed to be of minor importance in the etiology of the current hand eczema. Staphylococcus aureus colonized eczematous lesions of the hands in 18/20 patients. The density exceeded 105 colony forming units/cm2 in 15/20 patients. Only three of these patients showed signs of clinical infection. Successful topical treatment with a potent corticosteroid significantly reduced the colonization of S. aureus. / <p>Härtill 4 uppsatser</p> / digitalisering@umu

Chaque cadre doit contenir un résumé de 1700 caractères maximum, espaces compris. En cas de dépassement, lacoupure sera automatique.Le doctorant adresse son texte sous forme électronique selon les recommandations de la bibliothèqueLes dermocorticoïdes (DC) sont des anti-inflammatoires topiques largement prescrits pour traiter de nombreuses dermatoses. Actuellement, leur puissance, classée en quatre groupes, est déterminée par leur effet vasoconstricteur basé sur un test empirique obsolète, subjectif et réducteur vis-à-vis des nombreux autres effets des DC. L'objectif de ce travail était de comparer la puissance des DC dans trois de leurs indications et de la confronter à la classification actuelle:• Anti-inflammatoire. Une étude clinique randomisée contrôlée en double aveugle a été réalisée sur 21 patients allergiques aunickel traités par quatre DC. Les différents paramètres de l'inflammation ont été mesurés objectivement par des outils debiométrologie. La hiérarchisation de la puissance des DC variait en fonction du temps et des paramètres de l'inflammationétudiés. Sur ce modèle, la classification peut être simplifiée en trois groupes.• Antiprolifératif. L'efficacité de six DC sur la prolifération, le cycle cellulaire et l'apoptose de kératinocytes hyperproliféranten culture a été comparée. La classification de la puissance antiproliférative divergeait de la classification actuelle.• Antiprurigineux à médiation histaminique. L'effet anti-histaminolibérateur de huit DC a été comparé sur des explants depeau à l'aide d'un dosage par microdialyse sous-cutanée. La classification de la puissance anti-histaminolibératrice divergeaitde la classification actuelle.Nous avons démontré que la classification actuelle des DC n'est pas exactement corrélée à leur effet anti-inflammatoire dansl'allergie de contact, à leur effet antiprolifératif ainsi qu'à leur effet sur la libération d'histamine. Notre nouvelle approche est deparler des puissances DC au pluriel. Une classification multimodale adaptée à la situation clinique permettrait une prescriptionplus efficiente et limiterait les échecs et effets indésirables. / Topical corticosteroids (TCS) are topical anti-inflammatory widely prescribed to treat many skin diseases. Currently, their potency, ranged into four groups, is determined by their vasoconstrictor effect based on an empirical, outdated, subjective and too restrictive test. The aim of this work was to compare specifically the potency of TCS in three situations and to compare it to the current classification:• Anti-inflammatory. A randomized controlled double-blind clinical study was performed on 21 nickel-sensitive patientstreated by four TCS. Different inflammation parameters were objectively assessed with bioengineering tools. The ranking ofTCS potency varied according to time and parameters of the inflammation studied. According to this model, the classificationmay be simplified into three groups.• Antiproliferative. The efficacy of six TCS on immortal keratinocytes proliferation, cell cycle and apoptosis was compared. Theclassification of the antiproliferative potency differed from the current classification.• Antipruritic histamine-mediated. The histamine-release inhibition of eight TCS was compared on skin explants by asubcutaneous microdialysis dosage. The classification of the histamine-release inhibition potency differed from the currentclassification.We have demonstrated that the current classification of TCS potency is not strictly correlated to their anti-inflammatory effect in the context of allergie contact dermatitis, to their antiproliferative effect and to their histamine-release inhibitor effect. Our new approach is to talk about TCS potencies in the plural. A specifie classification adapted to the therapeutic target is needed to be more efficient and reduce side effects.

In der heutigen Zeit sind ca. 4000 Verbindungen bekannt, denen die Fähigkeit nachgesagt wird, eine Kontaktallergie auslösen zu können. Die Entscheidung, ob ein Stoff hautsensibilisierende Eigenschaften besitzt, wird dabei meist auf der Grundlage von Beobachtungen am Menschen und/oder von tierexperimentellen Befunden getroffen. Bedingt durch den vermehrten Einsatz exotischer Pflanzen und neu entwickelter synthetischer Substanzen im Bereich der Kosmetikindustrie besteht der Bedarf an einer einfachen Methode zur Vorhersage des kontaktallergenen Potentials einer Verbindung. Als zentraler Schritt bei der Manifestierung einer Kontaktallergie wird die Bildung eines Hapten-Carrier-Komplexes aus dem niedermolekularen Kontaktallergen (Hapten) und Hautproteinen (Carrier) angesehen. Zur Abschätzung der Sensibilisierungsfähigkeit kann daher auch die Reaktivität der Substanz oder ihrer Metaboliten gegenüber Proteinen herangezogen werden. Im Rahmen dieser Arbeit werden neben dem bedeutenden Phytoekzematogen Tulipalin A die bisher wenig untersuchten kontaktallergenen Duftstoffe Geraniol, 7-Hydroxycitronellal, Benzaldehyd, Salicylaldehyd, Vanillin, Zimtaldehyd, a-Amyl-zimtaldehyd und Benzylcinnamat hinsichtlich ihrer Reaktivität gegenüber peptidgebundenen Aminosäuren untersucht. Verwendet werden für diese Modellversuche Hippuryl-Derivate und Acetyl-Derivate der Aminosäuren Lysin, Histidin, Arginin bzw. Cystein sowie zusätzlich Glutathion. Die dabei gewählten Bedingungen sollen eine Adaption an physiologische Gegebenheiten erlauben. Ziel ist es, zu klären, ob die mit diesen Modellversuchen zu gewinnenden Ergebnisse mit dem bekannten kontaktallergenen Potential der eingesetzten Haptene korrelieren und somit geeignet sind, die Sensibilisierungsfähigkeit einer Substanz vorherzusagen. Über Konjugationsprodukte von Kontaktallergenen mit Peptiden oder Proteinen ist in der Literatur sehr wenig bekannt. Daher ist es ein weiteres Ziel dieser Arbeit, individuelle Produkte der Reaktionen der kontaktallergenen Substanzen mit den nukleophilen Aminosäureseitenketten zu isolieren und zu charakterisieren, um so definierte Hapten-Carrier-Konjugate, die unter physiologisch relevanten Bedingungen entstehen können, zu beschreiben. Aufbauend auf den gefundenen Strukturen sollte es auch möglich sein, Hinweise auf eventuelle Reaktionsmechanismen zu erhalten.