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Liens entre troubles du spectre autistique et schizophrénies précoces ? / Links between autism spectrum disorders and early onset schizophrenia ?Coulon, Nathalie 30 September 2015 (has links)
Contexte : Autisme, trouble du spectre autistique, schizophrénies précoces voire même très précoces (SDTP)... autant de termes utilisés de nos jours! Même si les classifications restent aujourd'hui catégorielles, les travaux sont cependant croissants pour approfondir et comprendre un éventuel lien entre les troubles du spectre autistique et schizophrénique, et notamment un lien entre les troubles du spectre autistique (TSA) et les schizophrénies précoces. Objectif : Clarifier les liens cliniques et biologiques entre TSA et schizophrénies à début précoce (avant 18 ans) et même très précoce (avant 13 ans). Méthodologie: Population de 62 sujets, divisés en trois groupes selon l'âge de début de la pathologie schizophrénique : strictement avant 13 ans (Very Early Onset Schizophrenia, VEOS), entre 13 et 18 ans (Early Onset Schizophrenia, EOS) et supérieur ou égal à 18 ans (Adult Onset Schizophrenia, AOS). Pour chaque groupe, 2 évaluations cliniques sont effectuées : recherche d'antécédents prémorbides autistiques avec l'ADI-R (Autism Diagnostic Interview-Revised); l'autre phénotypique avec MINI (Mini International Neuropsychiatric Interview), BPRS (Brief Psychiatric Rating Scale), PANSS (Positive And Negative Symptoms Scale for schizophrenia), STAI (State Trait Anxiety Inventory), TAS (Toronto Alexithymia Scale) et NSS (Neurological Soft Signs). L'analyse biologique est basée sur des mesures du cycle du cortisol salivaire (jour 1: 8h00; 11h00; 16h00; 24h00 et jour 2 :8h00), afin d'évaluer la réponse au stress de l'axe hypothalamo-hypophyso-surrenalien. Résultats: un gradient des troubles VEOS > EOS > AOS apparaît. Plus la schizophrénie semble débuter tôt et plus sont retrouvés des antécédents prémorbides autistiques et une réactivité au stress, réponse également exacerbée chez les apparentés. Conclusion: Un lien clinico-biologique apparaît donc entre SDTP et TSA, avec notamment des troubles cliniques déjà présents avant trois ans et des anomalies de la réponse au stress. Les schizophrénies à début très précoce sont-elles ainsi à distinguer dans le grand ensemble des schizophrénies? En tout cas, un diagnostic à mieux connaître, afin de mieux le prendre en charge et de mieux accompagner patients et famille. / Context : Autism spectrum disorders (ASD) , early onset schizophrenia (EOS) or even very early onset schizophrenia (VEOS)... so many terms used these days! Although today, classifications are categorical, work is however increasing to deepen and understand a possible link between ASD and schizophrenia spectrum disorders, and especially a link between ASD and early onset schizophrenia. Objective : To clarify clinical and biological links between ASD and EOS (before age 18) and especially links between ASD and VEOS (before age 13). Méthod: 62 subjects, divided into three groups according to age at onset of schizophrenia : strictly before age 13 (VEOS ), between age 13 and 18 (EOS) and after 18 (Adult Onset Schizophrenia, AOS). For each group, two clinical evaluations are assessed: search early symptoms of autism with the ADI-R (Autism Diagnostic Interview-Revised) and phenotypic evaluation with MINI (Mini International Neuropsychiatric Interview), BPRS (Brief Psychiatric Rating Scale), PANSS (Positive And Negative Symptoms Scale for schizophrenia), STAI (State Trait Anxiety Inventory), TAS (Toronto Alexithymia Scale) et NSS (Neurological Soft Signs). Biological analysis is based on salivary cortisol measurements, collected during a 24-h period (0800h-day 1, 1100h, 1600h, 2400h, 0800h-day2), in order to evaluate the stress response of the hypothalamic-pituitary-adrenal axis. Résults: VEOS symptoms > EOS symptoms > AOS symtoms. The earlier the schizophrenia is and the more present premorbid history of autism is and the more abnormal stress response is (abnormal stress response also present in relatives). Conclusion: A clinico-biological link appears between VEOS and ASD, with early symtoms of autism before thirty six months and stress response abnormalities. Are VEOS different from schizophrenia? Anyway, a diagnosis to know better in order to improve patients and families cares.
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Les schizophrénies précoces : épidémiologie, exploration clinique et neurocognitive, phénotypage de familles d'enfants avec schizophrénie et autisme / Early-Onset Schizophrenia : epidemiology, clinical and neurocognitive exploration, phenotyping families of children with schizophrenia and autismDor-Nedonsel, Emmanuelle 13 November 2017 (has links)
La schizophrénie précoce (SP), trouble rare (~0,01%) du neurodéveloppement est décrite sous deux formes : la schizophrénie très précoce, avant 13 ans et celle de l’adolescence entre 13 et 18 ans. Le diagnostic complexe à poser et les méconnaissances de la SP font supposer qu’elle est sous diagnostiquée et que les propositions thérapeutiques et de prise en charge sont encore peu spécifiques. Nous avons mené une première étude épidémiologique de prévalence pour : (1) évaluer le taux de sujets répondant au diagnostic de SP dans un échantillon de 302 enfants issus des structures médico-sociales et sanitaires en région PACA ; (2) caractériser sur le plan clinique et neurocognitif les enfants avec SP ; (3) évaluer le taux d’enfants répondant à la fois aux diagnostics de SP et de Troubles du Spectre Autistique (TSA). Puis, une deuxième étude, du sous-groupe d’enfants ayant une comorbidité SP et TSA, a exploré la psychopathologie, la personnalité et les capacités cognitives des membres du 1er degré des familles de ces enfants. Les résultats sont : un taux de 8,9% de patients avec SP, dont 59,3% de garçons âgés de 12,4 ans en moyenne (ET=3,2), avec un Quotient Intellectuel moyen de 72,5 (ET=21,4), des hallucinations (82,8%), des symptômes négatifs (70%), une comorbidité avec un TSA (41.2%) et des traitements neuroleptiques (51,5%). L’étude des familles a montré que les mères ont plus de troubles de la personnalité, de traits autistiques, de pathologies psychiatriques et un QI moyen plus faible. La constitution et le phénotypage de cette cohorte a permis dans les suites de ce travail, de lancer une étude génétique familiale avec séquençage d’exome des parents et des enfants avec SP. / Early Onset Schizophrenia (EOS), a rare neurodevelopmental disorder (≈0.01%) is categorized into two types: Very Early Onset Schizophrenia, before age 13 and Adolescent Schizophrenia between ages 13 and 18. This diagnosis is a difficult one to make and considering the lack of knowledge on EOS, we can presume that it is in fact under-diagnosed and that our treatment and management options are still not very specific. We conducted a first epidemiological prevalence study consisted in evaluating: (1) the rate of subjects with EOS diagnostic criteria among 302 children who receive care in psychosocial and sanitary care facilities in the PACA region; (2) the clinical and neurocognitive characteristics of those children with EOS; (3) the rate of children with both EOS and ASD criteria within the same sample. In a second study, focusing on a subgroup of children with comorbid EOS and ASD, we analyzed first-degree relatives from a psychopathological, personality and cognitive viewpoint. The results are: a high rate of patients (8.9%) with an EOS diagnosis, a male gender majority (59.3%), an average age of 12.4 (SD=3.2), an average intelligence quotient of 72.5 (SD=21.4), a rate of 82.8% of subjects with hallucinations, 70% with EOS negative symptoms, 41.2% with comorbid autism, and 51.5% with antipsychotic medications. The study of family members shows that mothers have a higher rate of personality disorders, autistic traits and psychiatric disorders, as well as a lower average IQ. The creation and the characterization of a phenotype of this cohort have led to a family-genetic analysis based on exome sequencing in the parents and children with EOS following this study.
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Striving to be able and included : Expressions of sense of self in people with Alzheimer's diseaseHedman, Ragnhild January 2014 (has links)
According to research applying a social constructionist perspective, the sense of self is not lost in people with Alzheimer’s disease (AD). It is, however, greatly influenced by the symptoms and by how they are treated by other people. Without support, it is difficult to preserve a positive sense of self, when living with progressing cognitive impairments. The stigma associated with cognitive impairment also threatens their sense of self. Harré’s social constructionist theories of self and positioning have been used to study how people with AD express their sense of self. As there is a need to expand the previous research by involving additional participants and research contexts, the aim of the present thesis was to describe, in accordance with Harré’s theories of self and positioning, how people with AD expressed their sense of self in personal interviews and in support groups with other people with AD. The research consists of four substudies (I–IV), and has a qualitative, descriptive, and theory-testing approach. Thirteen people with mild and moderate AD were included, 11 of whom had the early onset form of the disease. Two support groups were formed, led by facilitators who supported the communication and the participants’ expressions of self. Each group met 10 times during an eight-month period. Topics were not predetermined, and introduced by both facilitators and participants. Semistructured interviews were conducted before the groups started and after they ended. The interviews and support group conversations were audio-recoded and analysed with qualitative content analysis, guided by Harré’s theories. In substudy I, the initial interviews were deductively analysed. The findings showed that Self 1 (the sense of being a singular, embodied person) was expressed by the participants without difficulties. Self 2 (the perception of one’s personal attributes and life history) was expressed as feeling mainly the same person. While some abilities had been lost, other had been developed. Self 3 (the socially constructed self) was described as mostly supported, but sometimes threatened in interactions with other people (I). In substudy II, support group conversations were analysed abductively with respect to expressions of Self 2. It was found that participants expressed Self 2 in terms of agency and communion, and a lack of agency and communion (II).In substudy III, a secondary analysis of the data from substudy II was performed inductively with the aim of describing how Self 3 was constructed in the interaction of the support group. Five first-order positions, generating lively interaction, were described: the project manager, the storyteller, the moral agent, the person burdened with AD, and the coping person (III). In substudy IV, all the collected data were reanalysed inductively, focusing on how participants expressed the experience of being research participants. Three themes were constructed: contributing to an important cause, gaining from participating, and experiencing risks and drawbacks (IV). In conclusion, it was found that participants constructed positive social selves through the support from each other, the facilitator, and researchers in the support group (III), and as research participants (IV). Agency and communion were central to Self 2, and decreased with the progression of AD (II). In spite of change, participants perceived themselves as basically the same people, with a potential to learn and develop as persons (I).
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Ulcerative colitis : colorectal cancer risk and surveillance in an unselected populationLindberg, Jan January 2007 (has links)
Ulcerative colitis is a chronic inflammatory disease that mainly affects the colon and rectum. Onset of disease is most common between the ages of 15-35 years. There is an observed increased risk of colorectal cancer associated with the disease. The risk is often described to be 2% after 10 years, 8% after 20 years and 18% after 30 years disease. Since 1977, all known patients with ulcerative colitis in the catchment area of Örnsköldsvik Hospital have been invited to attend a colonoscopic surveillance programme. At endpoint of the studies included in this thesis there were 214 patients that had attended the surveillance programme. The aims of these studies have been to evaluate the efficiency of the surveillance programme, analyse the impact of findings of DNA aneuploidy, and determine the outcome for patients that underwent limited resections instead of complete proctocolectomy. Further, we have studied the long-term outcome for patients who had an early onset of disease and analysed the expression of cytokeratin 7 and 20 in respect to findings of dysplasia, DNA aneuploidy and colorectal cancer. At the end of the studies the prevalence for ulcerative colitis was 261/100 000 and the incidence rate was 7.6/100 000/year. During the period 1977-2005, four patients died of ulcerative colitis. Nine colorectal cancers were diagnosed in eight patients, one of whom died of the cancer. Fifty-two patients had findings of dysplasia and five of these patients developed colorectal cancer. In the subgroup of patients studied (N= 147) for DNA aneuploidy, 20 were found to have specimens with DNA aneuploidy on at least one occasion. The sensitivity of aneuploidy for development of dysplasia (LGD or higher) was found to be 0.50 and the specificity 0.94. The investigation of the outcome for the patients that underwent limited resections of the colon or rectum showed that none of the patients under surveillance died of colorectal cancer or metachronous cancer in their remaining colon or rectum. A separate study concerning early onset of ulcerative colitis revealed no particular increased risk of colorectal cancer in this cohort but a fairly high incidence of primary sclerosing cholangitis was seen. In the analyses of cytokeratins it was found that 7 out of 10 patients with low-grade dysplasia and 3 of 6 with high-grade dysplasia were positive for CK7. Our results indicate a possible relationship between the expression of CK7 and CK20 and neoplastic development of colorectal mucosa in patients with ulcerative colitis. The studies on which this thesis is based, were performed on a relatively small number of patients, however the time of observation was long and, most importantly, the patients were from a well defined catchment area. We conclude that the surveillance programme has been efficient in minimising the risk of lethal colorectal cancer. Analysing DNA ploidy helps to target the patients that need more attention but the method cannot stand alone. Our study on cytokeratins points to a relationship between dysplasia and CK7 but the results are preliminary and further studies needs to be done. We have shown that it is safe to do a limited colorectal resection in respect to lethal colorectal cancer. Early onset of ulcerative colitis as a risk factor for colorectal cancer was not found in the group we have studied, which could be due to effective surveillance and/or medication. A fairly high operation rate in this group may also have contributed. The most important variable in the beneficial outcome regarding lethal colorectal cancer in these studies is, in our opinion, the outstanding compliance of the patients to the colonoscopic surveillance programme.
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Autobiographical Accounts of Early-Onset Alzheimer's Disease: Obituaries of the Living Dead?Stanley, Daina 14 November 2013 (has links)
The thesis was designed to gain insight into how Alzheimer’s disease influences selfhood from first-personal accounts of illness. The focus of the study was narrowed further by concentrating on the autobiographies of individuals diagnosed with Early-Onset Alzheimer’s disease (EOAD). The purpose of this thesis was to analyze the autobiographies of individuals with EOAD with the aim of understanding their selfhood. In this thesis I argue that, Alzheimer’s disease may influence a change in self, however, the self is not lost entirely. This thesis draws on the philosophical conception of narrated self as it allows for one perpetually constructed self, whereby a change in self does not necessarily mean the self is lost entirely. Through an interpretive analysis of six autobiographical accounts of Alzheimer’s, this thesis demonstrates that Alzheimer’s disease influences a loss of sense of self but that autobiography enables individuals with Alzheimer’s to (re)construct self.
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NEUROPROFILES : NEUROdevelopment in PReschool children Of FIfe and Lothian Epilepsy StudyHunter, Matthew January 2017 (has links)
Neurobehavioural problems (i.e. cognitive impairment/behaviour problems) are common in childhood epilepsy. There are very limited data in children with early-onset epilepsy (CWEOE; onset ≤4 years). This study: (1) estimated the incidence of early-onset epilepsy, (2) described the spectrum and prevalence of neurobehavioural problems in CWEOE, and their risk factors, and (3) explored eye-gaze behaviour as a marker of neurobehavioural problems. This two year, prospective, population-based, case-controlled study identified newly diagnosed CWEOE in South East Scotland using active multi-source capture-recapture surveillance. CWEOE and controls completed detailed age-appropriate neuropsychological assessment - including Bayley III/WPPSI III, NEPSY II and social-emotional behaviour questionnaires. Children completed five eye-tracking tasks which assessed memory, attention, and social cognition. 59 CWEOE were identified (36M:23F); ascertainment-adjusted incidence 62/100,000 ≤4yrs/yr (95%CI 40-88). Asian and White-European children were at increased risk of epilepsy. 46 CWEOE (95%CI 62-84, 27M:19F) and 37 sex-age matched controls (18M:19F) underwent neuropsychological assessment. CWEOE had poorer general cognitive ability (p < .001, η²=.24), and increased parent reports of abnormal behaviour – significantly so in adaptive behaviour, ASD behaviours, hyperactivity/inattention, and atypical social behaviour. Overall 63% of CWEOE met criteria for neurobehavioural problems across multiple domains, vs 27% of controls (p < .001). Risk factors varied by domain. Prematurity and symptomatic/cryptogenic aetiology were common risk factors but other seizure-related variables were not. CWEOE with social problems exhibited abnormal eye-gaze behaviour toward social stimuli. Subtle atypicalities in sustained attention were noted in CWEOE, and an unexpected absence of antisaccade production was seen in all children. This is the first population-based study to describe the neurobehavioural profile, and explore eye-gaze behaviour, in CWEOE. Neurobehavioural problems are present, detectable, and highly prevalent in CWEOE, with implications for medical, psychosocial and educational resource provision, and provides an argument for early intervention. Eye-tracking may be a viable marker of neurobehavioural problems, and this study provides impetus for future eye-tracking investigations in CWEOE. Lastly, certain ethnic groups may be at increased risk of early-onset epilepsy in Scotland, providing opportunity for targeted intervention.
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Optimisation et évaluation de la perfusion cérébrale par technique de marquage de spin dans la Maladie d'Alzheimer à début précoce / Optimization and assessment of arterial spin labeled perfusion MRI in early-onset Alzheimer's diseaseVerclytte, Sébastien 23 September 2015 (has links)
Le diagnostic de maladie d'Alzheimer (MA) chez les patients de moins de 65 ans ou early-onset Alzheimer's disease (EOAD) est souvent difficile car la présentation clinique est fréquemment atypique, dominée par des signes non amnésiques. Les études antérieures sur les marqueurs de diagnostic précoce en imagerie se sont intéressées à l'imagerie structurelle et fonctionnelle dans l'EOAD mais aucune à la perfusion en IRM par la technique de marquage de spin ou arterial spin labeling (ASL). En effet, l'analyse de l'ASL demeure complexe, en particulier à l'échelle individuelle, du fait du faible rapport signal sur bruit des cartographies de perfusion et de l'hétérogénéité des zones atteintes à la phase initiale de la maladie. Notre premier objectif était technique et a consisté à optimiser l'interprétation des cartographies d'ASL grâce à la projection des anomalies de perfusion sur la surface du cortex extraite de l'acquisition morphologique T1 réalisée au cours du même examen, permettant d'accéder à une représentation tridimensionnelle interactive des données perfusionnelles. Le traitement des cartographies intégrait plusieurs étapes successives dont une correction des effets de volume partiel, une normalisation d'intensité spécifique et un lissage surfacique. Ce procédé a été appliqué sur les cartographies de 18 patients atteints d'EOAD avec une qualité de segmentation et de représentation des cartographies surfaciques obtenues jugées respectivement optimale et bonne dans 72 % des cas par deux lecteurs. Notre deuxième objectif était clinique et avait pour but de caractériser les altérations perfusionnelles et métaboliques par ASL et 18fluorodésoxuglucose-TEP (18F-FDG-TEP) sur un groupe de 37 patients atteints d'EOAD. Cette étude préliminaire à montré : (i) un pattern anatomique pathologique commun au niveau des lobules pariétaux inférieurs et des lobes temporaux ; (ii) des discordances entre les 2 techniques avec des lésions plus étendues en 18F-FDG-TEP et la détection en ASL de zones hypoperfusées additionnelles au niveau des lobes frontaux non visibles en 18F-FDGTEP. Ces deux travaux suggèrent que l'ASL pourrait donc devenir une séquence complémentaire clef dans l'arsenal des techniques d'imagerie utiles à un diagnostic précoce de l'EOAD et de la MA. Son utilisation en pratique clinique nécessite cependant une optimisation de sa représentation visuelle, et l'application corticale surfacique utilisée dans ce travail en représente une des voies potentielles. / The diagnosis of Alzheimer's disease (AD) in patients under the age of 65 years, called early-onset Alzheimer's disease (EOAD), remains a challenging issue due to the high incidence of atypical clinical presentations with non-memory symptoms. Although EAOD has been widely explored by structural and functional imaging, no previous study has examined the contribution of ASL in the assessment of cortical perfusion in this disease. Indeed, the analysis of ASL remains complex, especially at the individual level, due to the weak signal-to-noise ratio of the perfusion maps and the heterogeneity of pathological areas in the initial phase of the disease. Our first objective was technical and has consisted in optimizing the visual interpretation of ASL maps by the cortical surface-based projection of the perfusion alterations on the structural T1 sequence acquired during the same imaging protocol, providing a 3D interactive display of the perfusion data. Data processing included several successive steps, such as a partial volume effect correction, a specific intensity normalization and a surface-based smoothing process. It was applied on the perfusion maps of eighteen EOAD patients and the quality of segmentation and of cortical surface-based perfusion maps were scored as optimal in 72% in both cases by two readers. Our second objective was clinical and aimed to characterize the cerebral hypoperfusion and hypometabolism by ASL and 18F-FDG-PET in a group of 37 EOAD patients. Our preliminary study showed: (i) a similar pathological pattern located in the inferior parietal lobules and in the temporal cortex, (ii) discrepancies between the two modalities with the presence of more widespread hypometabolic regions detected by 18F-FDGPET and additionnai areas of alterations in the frontal lobes detected by ASL without apparent hypometabolism. Our studies suggest that ASL may become a useful complementary tool which, in combination with the existing structural and functional techniques, could offer improved efficiency in the difficult early detection of EOAD and AD. Its use in clinical practice, however, requires an optimization of its visual representation, and the cortical surface-based projection applied in this work represents one of the potential ways to this image quality improvement.
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The Origins of Life-Course Persistent Offending Revisited: Does Self-Control Mediate the Effect of Neuropsychological Deficits on Early-Onset Offending?January 2014 (has links)
abstract: The link between childhood neuropsychological deficits and early-onset offending--the assumed precursor to life-course persistent offending--has been well established, yet the underlying mechanisms facilitating this relationship are less understood. Support is growing for the claim that self-control is a key mechanism that links neuropsychological deficits to early-onset offending. Despite this, findings are mixed with regard to the mediating effect of self-control in the relationship between neuropsychological deficits and antisocial behavior. These studies largely support the notion that self-control exerts a mediating effect on neuropsychological deficits when the offending being studied is less serious. Using data from the National Longitudinal Survey of Youth (NLSY), the present study seeks to build upon the existing literature by examining whether self-control mediates the relationship between neuropsychological deficits and two types of early-onset offending--low and high risk--as a means of testing core tenets of Gottfredson and Hirschi's (1990) and Moffitt's (1993) criminological theories. Findings show that while self-control and neuropsychological deficits independently predict general early-onset offending, these effects vary as a consequence of early-onset offender type. The results point to the need for future research to explore the possibility that the early-onset offender group that leads to persistent offending could be more precisely defined. Examining early-onset offending as a single construct limits our ability to make inferences about those offenders that are the most persistent in their offending patterns and, arguably, more likely to continue offending over the life-course. / Dissertation/Thesis / M.S. Criminology and Criminal Justice 2014
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Autobiographical Accounts of Early-Onset Alzheimer's Disease: Obituaries of the Living Dead?Stanley, Daina January 2013 (has links)
The thesis was designed to gain insight into how Alzheimer’s disease influences selfhood from first-personal accounts of illness. The focus of the study was narrowed further by concentrating on the autobiographies of individuals diagnosed with Early-Onset Alzheimer’s disease (EOAD). The purpose of this thesis was to analyze the autobiographies of individuals with EOAD with the aim of understanding their selfhood. In this thesis I argue that, Alzheimer’s disease may influence a change in self, however, the self is not lost entirely. This thesis draws on the philosophical conception of narrated self as it allows for one perpetually constructed self, whereby a change in self does not necessarily mean the self is lost entirely. Through an interpretive analysis of six autobiographical accounts of Alzheimer’s, this thesis demonstrates that Alzheimer’s disease influences a loss of sense of self but that autobiography enables individuals with Alzheimer’s to (re)construct self.
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An investigation of late onset psoriasisTheodorakopoulou, Eleni January 2014 (has links)
Psoriasis is a chronic, clinically heterogeneous, skin condition that affects approximately 2% of the general population. In 1985, Henseler and Christophers, classified psoriasis into early onset (EOP; age at onset ≤40 years-y) and late onset disease (LOP; age at onset >40 y). Previous research suggests that there are genetic and immunological differences between EOP and LOP. In particular, the major genetic determinant for psoriasis, the human leukocyte antigen (HLA)-Cw6 allele, occurs more frequently in EOP (55-80%) compared to LOP (15-20%) patients. Epidermal Langerhans’ cells (LC) migration is also different in these 2 subtypes of psoriasis. The primary aim of this thesis was to further explore the clinical, histological and immunohistochemical (IHC) differences between EOP and LOP. We compared clinical characteristics in a total of 497 subjects, including 340 psoriasis patients (108 recruited prospectively; 76 EOP and 32 LOP, mean age of onset 20.3±9.9 and 55.6±7y respectively, and 232 retrospectively; 202 EOP and 30 LOP, mean age of onset 20.7±9.9 and 55.2±7.2y respectively) and 157 controls (mean age 66±11.2y). Information on demographics, family history of psoriasis, clinical features, treatment and co-morbidities were recorded. Patients were also assessed for health-related quality of life and psychological distress. A total of 31 psoriasis patients, ≥ 50y of age, participated in the histological and IHC evaluation; 17 EOP and 14 LOP, mean age of onset 21.1±8.5 and 55.4±7.7y respectively. Skin biopsies were taken from involved (PP) and uninvolved (PN) skin and stained with haematoxylin and eosin (H&E) and IHC antibodies against various T-cell (CD3, CD4, and CD8) and LC (CD1α) markers. The H&E parameters (morphological and inflammatory) were graded with the use of a study specific histological score, whilst IHC positive epidermal cells were counted per microscopic field at 200X magnification. The dermal IHC infiltrate was assessed with a semi-quantitative (0-3) scale. Gender, body mass index, disease duration and severity, diagnosed hypertension and dyslipidemia were treated as covariates. The clinical data showed that LOP patients had a lower likelihood of having a positive family history of psoriasis (62% of EOP versus 35.6% of LOP patients; chi square-x2, P=0.001). In addition, patients with EOP parent(s) were 91% less likely to develop LOP than EOP (odds ratio-OR=0.093, P=0.025, 95% confidence interval-CI 0.012-0.74). Moreover, compared to LOP, EOP patients had a more severe disease (x2, P=0.021), usually requiring 3rd line treatments (x2; P=0.010). They also experienced frequent flares, following upper respiratory tract infections (x2, P=0.049). When data were segregated by age (≥50years) and after accounting for covariates, we observed that, compared to the non-psoriasis population, LOP patients were approximately 3 times more likely to develop type 2 Diabetes Mellitus (OR=2.56, P=0.05, 95% CI 1.01-6.54), whilst, EOP subjects were 98% less likely to develop autoimmune thyroiditis (OR=0.025, P=0.02, 95% CI 0.001-0.55). Psychologically, LOP patients were found to be a clinically more anxious group compared to EOP (t-test, P=0.006). Microscopically, the results from the H&E study showed an increased total inflammatory infiltrate in LOP, PP sections compared to EOP, PP ones (t-test, P=0.028). With IHC stains, we observed that in the epidermis of LOP PP, there was a significantly higher count of CD4+ cells; mean CD4+ in LOP of 15.1 ± 6.2 versus 6.7±4.6 in EOP (Analysis of variance-ANOVA, P<0.001). This subsequently led to a higher epidermal CD4+/CD8+ ratio of 1.3 in the LOP versus 0.5 for the EOP sections (ANOVA, P=0.002). In the PP dermis, CD4+ were also more abundant in the LOP tissue (x2, P=0.049). To assess whether these CD4+ cells were either T-lymphocytes or LC, we examined for differences in the CD3+ and CD1α+ cells. The mean epidermal CD3+ tended to be higher in LOP PP sections; mean epidermal CD3+ in the LOP 42.8 ± 13.3 versus 31.7 ± 17.5 in the EOP group (ANOVA, P= 0.061), while the dermal infiltrate showed a similar pattern (x2,P=0.067). Finally, there was no difference in epidermal and dermal CD1α+ and CD8+ cells in PP between EOP and LOP sections. These data indicate differences in clinical phenotype, heritability, comorbidities and immunopathomechanism between EOP and LOP. Taken together they provide further evidence that EOP and LOP may be different diseases.
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