MiRNAs control skin homeostasis through post-transcriptional gene repression by binding to their target mRNAs. However, their role in regulation of apoptosis and hair loss in alopecia areata (AA) is largely unknown, which became the aim of this study. In AA mouse model (C3H/HeJ), global miRNA profiling revealed 22 miRNAs with significant changes in their expression in AA affected skin. Amongst these miRNAs, miR-486-5p was dramatically decreased in alopecic skin in both humans and mice, in striking contrast to its prominent expression in the hair follicle (HF) epithelium of healthy anagen skin. Moreover, the expression of both pri-miR-486 and miR-486 is down-regulated in the human anagen HFs and keratinocytes treated with IFN-g, one of the key factors contributing to the immune privilege (IP) collapse in HFs. Intradermal delivery of miR-486-5p mimic into mouse skin affected by AA prevented premature entrance of HFs into catagen phase and reduced the numbers of CD4+ and CD8+ lymphocytes in the peri- and intra-follicular skin compartments. Consistently, subcutaneous administration of miR-486-5p inhibitor delayed anagen progression associated with a higher number of intrafollicular NKG2D+ cells in C3H/HeJ mice. Silencing of miR-486-5p in human anagen HFs ex vivo caused premature catagen development and led to suppression of IP by up-regulating HLA class 1, IRF1, ICAM1 and CADM1 expression of which CADM1 was confirmed to be a direct target of miR-486- 5p. Transcriptome profiling of primary human epidermal keratinocytes overexpressing miR-486-5p revealed damping the signalling pathways associated with inflammatory chemokines, cytokines and interleukins. Taken together, these data suggest that miR-486-5p plays a protective role in the pathogenesis of AA by maintaining anagen phase and preventing the IP collapse. / National Alopecia Areata Foundation

No description available.

Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2017-10-09T12:17:33Z No. of bitstreams: 1 Ademir Carvalho Leite Júnior.pdf: 1086030 bytes, checksum: a4a25c152f48c5f898a986313b25dbe0 (MD5) / Made available in DSpace on 2017-10-09T12:17:33Z (GMT). No. of bitstreams: 1 Ademir Carvalho Leite Júnior.pdf: 1086030 bytes, checksum: a4a25c152f48c5f898a986313b25dbe0 (MD5) Previous issue date: 2017-09-29 / Frontal fibrosing alopecia (AFF) is a primary cicatricial alopecia that was described in 1994. It predominantly affects women, most often in menopause. Studies have shown that alopecias, in general, may have stress as a trigger and maintenance factor. Regarding cicatricial alopecia, especially AFF, the relevance of these factors was little studied, however, studies suggest that stressful events may be associated with the onset of alopecia conditions. The objective of this study is to evaluate the relevance of suffering as a stressful event as a possible triggering factor for AFF patients. To perform this evaluation a socio-demographic form, a quality of life inventory in Dermatology (DQLI) and a semi-structured interview was held in a single meeting with the research volunteers. The 12 volunteers in the study present life stories with intense reports of frustration, impotence, insecurity, loss, shame and loneliness. DQLI, used to assess the impact of AFF on the life of the volunteers, was consistent with the observations made by them, that the disease accompanies a high degree of stress and suffering / A Alopecia Fibrosante Frontal (AFF) é uma alopecia cicatricial primária que foi descrita em 1994. Acomete predominantemente mulheres, na maior parte das vezes na menopausa. Estudos mostram que as alopecias, em geral, podem ter como fator causal e de manutenção o estresse. Sobre as alopecias cicatriciais, em especial a AFF, a relevância destes fatores foi pouco estudada, ainda assim, estudos sugerem que eventos estressantes podem estar associados ao surgimento de alopecias. O objetivo deste estudo é avaliar a relevância do sofrimento tendo o evento estressante como possível fator desencadeante de quadros de AFF. Para realizar esta avaliação um formulário sociodemográfico, um inventário de qualidade de vida em dermatologia (DQLI) e uma entrevista semiestruturada serão realizados em encontro único com os participantes da pesquisa. As doze voluntárias do estudo apresentam histórias de vida com intensos relatos de frustrações, impotência, insegurança, perdas, vergonha e solidão. O DQLI, utilizado para avaliação do impacto da AFF, na vida das voluntárias, foi coerente com as observações feitas pelas mesmas, de que a doença acompanha elevado grau de estresse e sofrimento

Yes / The development of androgenetic alopecia is associated with a risk of developing cardiovascular diseases, but the association of alopecia areata with cardiovascular diseases in humans is largely unexplored. We measured the plasma level of two common cardiovascular disease markers, cardiac troponin I and Creactive protein, in alopecia areata and androgenetic alopecia-affected subjects. Also, we investigated the possible presence of pro-apoptotic factors in the plasma of hair loss subjects. The mean plasma cardiac troponin I level was highest in alopecia areata subjects, moderately higher in androgenetic alopecia subjects, and lowest in subjects without hair loss (p < 0.05). Alopecia areata subjects not receiving treatments had highest levels of cardiac troponin I (p < 0.05). Alopecia areata plasma samples with high cardiac troponin I levels also induced significantly higher rates of cardiomyocyte apoptosis in cell culture assays. The results suggest the potential for increased heart remodelling. Close monitoring of cardiovascular health in alopecia areata subjects, as well as subsets of androgenetic alopecia patients, may be appropriate. / Canadian Institutes of Health Research (CIHR; MOP-82927). EW is the recipient of a Banting Postdoctoral Fellowship (SAC-92845).

Introdução: Alopecia frontal fibrosante (AFF) é um tipo de alopecia cicatricial classificada, atualmente, como uma variante clínica do líquen plano pilar (LPP), afetando o couro cabeludo em um padrão clínico característico e apresentando padrão histológico similar ao LPP. Objetivos: Analisar e comparar as alterações clínico-patológicas e imunopatológicas do LPP e da AFF. Métodos: Neste estudo foram selecionados dez pacientes com AFF e dez com LPP objetivando caracterizar achados clínicos, histológicos e imunológicos. A revisão dos preparados histológicos em cortes longitudinais foi realizada comparando-se infiltrado linfocitário perifolicular, fibrose perifolicular, apoptose nos folículos pilosos, dilatação infundibular, infiltrado linfocitário liquenoide na interface entre a epiderme interfolicular e a derme, e reação granulomatosa tipo corpo estranho. Foram realizados estudos de imunofluorescência direta e imuno-histoquímica para a demonstração da expressão de CD1a, CD3, CD4, CD8, CD68 e IDO (indoleamine 2,3-dioxygenase) em biópsias de pele. Resultados: As principais manifestações clínicas verificadas nos pacientes com AFF incluíram: recesso frontotemporal simétrico e progressivo, ceratose e eritema folicular, pele atrófica desprovida de orifícios foliculares, rarefação dos supercílios e ausência de pelos velus na linha de implantação capilar. Já nos casos de LPP os principais achados clínicos incluíram: envolvimento multifocal e predominantemente difuso do couro cabeludo com presença de eritema, ceratose e descamação perifolicular. A descamação peripilar (80% no LPP e 50% na AFF) e o prurido (60% na AFF e 30% no LPP) foram os sinais e sintomas predominantes em ambas afecções. A histopatologia mostrou achados sobreponíveis entre os casos de LPP e AFF, incluindo alterações vacuolares de interface, infiltrado linfocítico liquenoide perifolicular, fibrose perifolicular, tratos cicatriciais, degeneração de queratinócitos basais e destruição da camada basal. Os achados mais característicos de imunofluorescência direta incluíram a presença de imunofluorescência granulosa moderada e contínua na zona de membrana basal e corpos citoides fluorescentes na derme papilar, principalmente, anti IgM, IgA e IgG presentes no LPP e na AFF. A comparação histopatológica e imunopatológica não mostrou diferenças significativas entre as duas afecções. Conclusão: Embora clinicamente diferentes, nosso estudo não evidenciou diferenças histopatológicas e imunopatológicas entre o líquen plano pilar e a alopecia frontal fibrosante, favorecendo o conceito de tratar-se, em ambos os casos, de aspectos clínicos distintos da mesma doença / Background: Frontal fibrosing alopecia (FFA) is a type of scarring alopecia currently considered as a clinical variant of lichen planopilaris (LPP), affecting the scalp in a distinctive clinical pattern but also presenting both characteristic and similar histological patterns. Objective: Analysing and comparing the clinicalpathological and immunological alterations between LPP and FFA. Methods: For our study, we have selected ten patients, women, with FFA and ten with LPP, so that clinical, histological and immunological findings were better characterized. The analysis of histological preparations in longitudinal sections was performed by comparing the following aspects: perifollicular lymphocytic infiltrate, perifollicular fibrosis, apoptosis in hair follicles, infundibular dilatation, lichenoid lymphocytic infiltrate at the interface between the interfollicular epidermis and the dermis and granulomatous foreign body reaction. Studies of direct immunofluorescence and immunohistochemistry were executed for demonstrating the expression of CD1a, CD3, CD4, CD8, CD68 and IDO (2,3-dioxygenase indoleamine) in skin specimens. Results: The main clinical manifestations observed in the studied patients with AFF include: symmetrical and progressive frontotemporal recession, follicular keratosis and erythema, atrophic skin devoid of hair follicles, thinning eyebrows and absence of vellus hair in the hairline. Concerning LPP cases, the mais clinical manifestations include multifocal and predominantly diffuse scalp involvement with the presence of erythema, perifolicular keratosis and scales. The associated signs and symptoms, for patients with LPP the main findings were perifollicular scale (80% and 50% LPP AFF) and pruritus (60% and 30% AFF LPP). The histopathology of both diseases showed overlapping findings, including interface vacuolar changes, perifollicular lichenoid lymphocytic cell infiltrate, hypergranulosis, hyperkeratosis, hyperacanthosis, degeneration of basal keratinocytes and destruction of the basal layer. The most common immunofluorescence findings of the patients were the presence of continuous and moderate granulous immunofluorescence in the basement membrane zone and cytoid fluorescent bodies in the papillary dermis mainly anti IgG, IgM and IgG present in the LPP and AFF. The immunohistochemical studies showed no significant difference in the two entities. Conclusion: Although clinically distinct, our study has not demonstrated neither histological nor immunological differences between lichen planopilaris and frontal fibrosing alopecia, sustaining, therefore, the concept of both cases being different clinical aspects of the same disease

INTRODUÇÃO: A alopecia frontal fibrosante (AFF) é uma alopecia cicatricial primária linfocítica descrita em 1994, cuja prevalência vem aumentando rapidamente em todo mundo. A participação de um fator desencadeante ambiental na patogênese da doença é aventada e uma pesquisa recente encontrou uma associação da doença com o uso de cosméticos faciais. Alterações da pele e dos pelos da face e do corpo têm sido descritas em pacientes com AFF nos últimos anos e alguns estudos sugerem que essas alterações possam preceder a perda dos cabelos, indicando o início da doença fora do couro cabeludo. OBJETIVO: Estudar o acometimento da pele e dos pelos na face, pescoço e região anterossuperior do tórax em uma série de pacientes com AFF. MATERIAL E MÉTODOS: A pesquisa constou de três partes. Na primeira parte foram investigadas evidências clínicas e dermatoscópicas do acometimento da pele e dos pelos fora do couro cabeludo em 37 pacientes. A segunda parte do estudo constou da avaliação da espessura epidérmica em biópsias realizadas na face, pescoço e região anterossuperior do tórax de 20 pacientes com AFF e 20 controles. Na terceira parte do estudo foi utilizada microscopia confocal de reflectância a laser \"in vivo\" para comparar a espessura epidérmica e a densidade folicular da pele da linha de implantação frontal de 21 pacientes a de 21 controles. RESULTADOS: O acometimento dos pelos velos da face não se restringiu a linha de implantação fronto-temporal e variou de 30 a 97% dependendo da região estudada, sendo mais frequente quanto mais próximo da linha de implantação frontal do couro cabeludo. Pápulas da face foram encontradas em 60% dos pacientes estudados, localizadas principalmente na região temporal (11/37 casos), seguida pela região malar (10/37 casos) e mento (6/37 casos). Metade dos pacientes (51%) apresentaram lesões hipercrômicas compatíveis com o diagnóstico de líquen plano pigmentoso associado a AFF, acometendo face (18/19 casos), pescoço (7/19 casos) e região anterossuperior do tórax (4/19 casos). As lesões hipercrômicas mostraram-se mais raras em pacientes com fototipo baixo (p=0,022). A espessura da epiderme dos pacientes de AFF não apresentou diferença quando comparada com a dos controles independente da metodologia utilizada. Densidade folicular menor que 3,56 folículos/mm2 na linha de implantação frontal ao exame de microscopia confocal apresentou 90,5% de sensibilidade e 90,5% de especificidade para o diagnóstico de AFF e implicou num risco 90,24 (IC95% 9,5-1132; p < 0,001) vezes maior de ter a doença. CONCLUSÕES: O acometimento dos pelos velos da face é frequente e pode ser detectado de forma rápida e não invasiva pela dermatoscopia. As pápulas da face estão presentes em 60% dos pacientes. As lesões de liquen plano pigmentoso são menos frequentes em pacientes com fototipos baixos. A epiderme dos pacientes de AFF não apresenta uma menor espessura quando comparada com controles pareados por gênero, idade, fototipo e local examinado. A densidade folicular da linha de implantação frontal \"in vivo\" medida através do exame de MCRL apresenta ótima acurácia para o diagnóstico de AFF / INTRODUCTION: Frontal fibrosing alopecia (FFA) is a lymphocytic primary cicatricial alopecia first described in 1994. Its incidence has been rapidly rising worldwide, possibly related to an environmental trigger. The use of facial leave-on creams has been associated with the disease in a recent publication. Vellus follicles involvement and epidermal changes outside the scalp region have been described in FFA patients in the past few years and seem to be an early event in the disease course. OBJECTIVES: To evaluate vellus follicle and epidermal involvement over the facial, neck and upper chest skin in a series of FFA patients. METHODS: This study consisted of three parts. In the first part, prevalence of clinical and dermoscopic findings related to vellus follicle and epidermal involvement in 37 FFA patients was investigated. In part two, epidermal thickness in skin biopsies from 20 FFA patients was compared with 20 control biopsies from the same body site. In the last part, epidermal thickness and follicular density over the frontal hairline were investigated in a group of 21 FFA patients and 21 gender, age and phototype matched controls through \"in vivo\" reflectance confocal microscopy. RESULTS: Vellus follicle involvement in FFA is not restricted to frontal hairline and varies from 30 to 97% according to facial region, with greater frequencies observed on the upper face region. Facial papules were detected in 60% of our patients, most frequently over the temples (11/37 patients), malar (10/37 patients) or chin (6/37 patients) area. Half of our patients (51%) presented hyperchromic lesions compatible with FFA associated lichen planus pigmentosus. Hyperchromic lesions were observed over the face (18/19 patients), but also over the neck (7/19 patients) and upper chest (4/19 patients) skin. Hyperchromic lesions were less frequent in patients with lighter phototypes (p=0.022). Epidermal thickness of FFA patients did not differ from controls both in histology and \"in vivo\" evaluation. Frontal hairline follicular density lower than 3.56 follicles/mm2 on confocal microscopy examination presented 90.5% sensitivity, 90.5% specificity and OR = 90.24 (CI95% 9.5-1132; p < 0.001) for FFA diagnosis. CONCLUSIONS: Facial vellus follicle involvement is frequent and can be easily detected through dermoscopy in most patients. Facial papules are observed in 60% of our patients. Lichen planus pigmentosus lesions are less frequently observed in fair skin patients. Epidermal thinning is not observed in FFA patients when adequate control group is included. Frontal hairline follicular density measured by confocal microscopy has high accuracy for FFA diagnosis

INTRODUÇÃO: A alopecia frontal fibrosante (AFF) é uma alopecia cicatricial primária linfocítica descrita em 1994, cuja prevalência vem aumentando rapidamente em todo mundo. A participação de um fator desencadeante ambiental na patogênese da doença é aventada e uma pesquisa recente encontrou uma associação da doença com o uso de cosméticos faciais. Alterações da pele e dos pelos da face e do corpo têm sido descritas em pacientes com AFF nos últimos anos e alguns estudos sugerem que essas alterações possam preceder a perda dos cabelos, indicando o início da doença fora do couro cabeludo. OBJETIVO: Estudar o acometimento da pele e dos pelos na face, pescoço e região anterossuperior do tórax em uma série de pacientes com AFF. MATERIAL E MÉTODOS: A pesquisa constou de três partes. Na primeira parte foram investigadas evidências clínicas e dermatoscópicas do acometimento da pele e dos pelos fora do couro cabeludo em 37 pacientes. A segunda parte do estudo constou da avaliação da espessura epidérmica em biópsias realizadas na face, pescoço e região anterossuperior do tórax de 20 pacientes com AFF e 20 controles. Na terceira parte do estudo foi utilizada microscopia confocal de reflectância a laser \"in vivo\" para comparar a espessura epidérmica e a densidade folicular da pele da linha de implantação frontal de 21 pacientes a de 21 controles. RESULTADOS: O acometimento dos pelos velos da face não se restringiu a linha de implantação fronto-temporal e variou de 30 a 97% dependendo da região estudada, sendo mais frequente quanto mais próximo da linha de implantação frontal do couro cabeludo. Pápulas da face foram encontradas em 60% dos pacientes estudados, localizadas principalmente na região temporal (11/37 casos), seguida pela região malar (10/37 casos) e mento (6/37 casos). Metade dos pacientes (51%) apresentaram lesões hipercrômicas compatíveis com o diagnóstico de líquen plano pigmentoso associado a AFF, acometendo face (18/19 casos), pescoço (7/19 casos) e região anterossuperior do tórax (4/19 casos). As lesões hipercrômicas mostraram-se mais raras em pacientes com fototipo baixo (p=0,022). A espessura da epiderme dos pacientes de AFF não apresentou diferença quando comparada com a dos controles independente da metodologia utilizada. Densidade folicular menor que 3,56 folículos/mm2 na linha de implantação frontal ao exame de microscopia confocal apresentou 90,5% de sensibilidade e 90,5% de especificidade para o diagnóstico de AFF e implicou num risco 90,24 (IC95% 9,5-1132; p < 0,001) vezes maior de ter a doença. CONCLUSÕES: O acometimento dos pelos velos da face é frequente e pode ser detectado de forma rápida e não invasiva pela dermatoscopia. As pápulas da face estão presentes em 60% dos pacientes. As lesões de liquen plano pigmentoso são menos frequentes em pacientes com fototipos baixos. A epiderme dos pacientes de AFF não apresenta uma menor espessura quando comparada com controles pareados por gênero, idade, fototipo e local examinado. A densidade folicular da linha de implantação frontal \"in vivo\" medida através do exame de MCRL apresenta ótima acurácia para o diagnóstico de AFF / INTRODUCTION: Frontal fibrosing alopecia (FFA) is a lymphocytic primary cicatricial alopecia first described in 1994. Its incidence has been rapidly rising worldwide, possibly related to an environmental trigger. The use of facial leave-on creams has been associated with the disease in a recent publication. Vellus follicles involvement and epidermal changes outside the scalp region have been described in FFA patients in the past few years and seem to be an early event in the disease course. OBJECTIVES: To evaluate vellus follicle and epidermal involvement over the facial, neck and upper chest skin in a series of FFA patients. METHODS: This study consisted of three parts. In the first part, prevalence of clinical and dermoscopic findings related to vellus follicle and epidermal involvement in 37 FFA patients was investigated. In part two, epidermal thickness in skin biopsies from 20 FFA patients was compared with 20 control biopsies from the same body site. In the last part, epidermal thickness and follicular density over the frontal hairline were investigated in a group of 21 FFA patients and 21 gender, age and phototype matched controls through \"in vivo\" reflectance confocal microscopy. RESULTS: Vellus follicle involvement in FFA is not restricted to frontal hairline and varies from 30 to 97% according to facial region, with greater frequencies observed on the upper face region. Facial papules were detected in 60% of our patients, most frequently over the temples (11/37 patients), malar (10/37 patients) or chin (6/37 patients) area. Half of our patients (51%) presented hyperchromic lesions compatible with FFA associated lichen planus pigmentosus. Hyperchromic lesions were observed over the face (18/19 patients), but also over the neck (7/19 patients) and upper chest (4/19 patients) skin. Hyperchromic lesions were less frequent in patients with lighter phototypes (p=0.022). Epidermal thickness of FFA patients did not differ from controls both in histology and \"in vivo\" evaluation. Frontal hairline follicular density lower than 3.56 follicles/mm2 on confocal microscopy examination presented 90.5% sensitivity, 90.5% specificity and OR = 90.24 (CI95% 9.5-1132; p < 0.001) for FFA diagnosis. CONCLUSIONS: Facial vellus follicle involvement is frequent and can be easily detected through dermoscopy in most patients. Facial papules are observed in 60% of our patients. Lichen planus pigmentosus lesions are less frequently observed in fair skin patients. Epidermal thinning is not observed in FFA patients when adequate control group is included. Frontal hairline follicular density measured by confocal microscopy has high accuracy for FFA diagnosis

Introdução: Alopecia frontal fibrosante (AFF) é um tipo de alopecia cicatricial classificada, atualmente, como uma variante clínica do líquen plano pilar (LPP), afetando o couro cabeludo em um padrão clínico característico e apresentando padrão histológico similar ao LPP. Objetivos: Analisar e comparar as alterações clínico-patológicas e imunopatológicas do LPP e da AFF. Métodos: Neste estudo foram selecionados dez pacientes com AFF e dez com LPP objetivando caracterizar achados clínicos, histológicos e imunológicos. A revisão dos preparados histológicos em cortes longitudinais foi realizada comparando-se infiltrado linfocitário perifolicular, fibrose perifolicular, apoptose nos folículos pilosos, dilatação infundibular, infiltrado linfocitário liquenoide na interface entre a epiderme interfolicular e a derme, e reação granulomatosa tipo corpo estranho. Foram realizados estudos de imunofluorescência direta e imuno-histoquímica para a demonstração da expressão de CD1a, CD3, CD4, CD8, CD68 e IDO (indoleamine 2,3-dioxygenase) em biópsias de pele. Resultados: As principais manifestações clínicas verificadas nos pacientes com AFF incluíram: recesso frontotemporal simétrico e progressivo, ceratose e eritema folicular, pele atrófica desprovida de orifícios foliculares, rarefação dos supercílios e ausência de pelos velus na linha de implantação capilar. Já nos casos de LPP os principais achados clínicos incluíram: envolvimento multifocal e predominantemente difuso do couro cabeludo com presença de eritema, ceratose e descamação perifolicular. A descamação peripilar (80% no LPP e 50% na AFF) e o prurido (60% na AFF e 30% no LPP) foram os sinais e sintomas predominantes em ambas afecções. A histopatologia mostrou achados sobreponíveis entre os casos de LPP e AFF, incluindo alterações vacuolares de interface, infiltrado linfocítico liquenoide perifolicular, fibrose perifolicular, tratos cicatriciais, degeneração de queratinócitos basais e destruição da camada basal. Os achados mais característicos de imunofluorescência direta incluíram a presença de imunofluorescência granulosa moderada e contínua na zona de membrana basal e corpos citoides fluorescentes na derme papilar, principalmente, anti IgM, IgA e IgG presentes no LPP e na AFF. A comparação histopatológica e imunopatológica não mostrou diferenças significativas entre as duas afecções. Conclusão: Embora clinicamente diferentes, nosso estudo não evidenciou diferenças histopatológicas e imunopatológicas entre o líquen plano pilar e a alopecia frontal fibrosante, favorecendo o conceito de tratar-se, em ambos os casos, de aspectos clínicos distintos da mesma doença / Background: Frontal fibrosing alopecia (FFA) is a type of scarring alopecia currently considered as a clinical variant of lichen planopilaris (LPP), affecting the scalp in a distinctive clinical pattern but also presenting both characteristic and similar histological patterns. Objective: Analysing and comparing the clinicalpathological and immunological alterations between LPP and FFA. Methods: For our study, we have selected ten patients, women, with FFA and ten with LPP, so that clinical, histological and immunological findings were better characterized. The analysis of histological preparations in longitudinal sections was performed by comparing the following aspects: perifollicular lymphocytic infiltrate, perifollicular fibrosis, apoptosis in hair follicles, infundibular dilatation, lichenoid lymphocytic infiltrate at the interface between the interfollicular epidermis and the dermis and granulomatous foreign body reaction. Studies of direct immunofluorescence and immunohistochemistry were executed for demonstrating the expression of CD1a, CD3, CD4, CD8, CD68 and IDO (2,3-dioxygenase indoleamine) in skin specimens. Results: The main clinical manifestations observed in the studied patients with AFF include: symmetrical and progressive frontotemporal recession, follicular keratosis and erythema, atrophic skin devoid of hair follicles, thinning eyebrows and absence of vellus hair in the hairline. Concerning LPP cases, the mais clinical manifestations include multifocal and predominantly diffuse scalp involvement with the presence of erythema, perifolicular keratosis and scales. The associated signs and symptoms, for patients with LPP the main findings were perifollicular scale (80% and 50% LPP AFF) and pruritus (60% and 30% AFF LPP). The histopathology of both diseases showed overlapping findings, including interface vacuolar changes, perifollicular lichenoid lymphocytic cell infiltrate, hypergranulosis, hyperkeratosis, hyperacanthosis, degeneration of basal keratinocytes and destruction of the basal layer. The most common immunofluorescence findings of the patients were the presence of continuous and moderate granulous immunofluorescence in the basement membrane zone and cytoid fluorescent bodies in the papillary dermis mainly anti IgG, IgM and IgG present in the LPP and AFF. The immunohistochemical studies showed no significant difference in the two entities. Conclusion: Although clinically distinct, our study has not demonstrated neither histological nor immunological differences between lichen planopilaris and frontal fibrosing alopecia, sustaining, therefore, the concept of both cases being different clinical aspects of the same disease

Facilities housing non-human primates are required to make provisions for their psychological wellbeing, which may include monitoring animals for signs of decreased wellbeing such as the presence of abnormal behaviors or alopecia. By analyzing archival behavioral data collected by the Behavior Management Unit at the Yerkes National Primate Research Center (YNPRC), I aimed to identify behavioral predictors of self-wounding and alopecia and to evaluate the effectiveness of current treatments in reducing abnormal behavior and alopecia in rhesus macaques (Macaca mulatta). The behaviors of self-biting and hair plucking (conditional logistic regression, p < .05) as well as floating limb and self-oral behaviors (Mantel-Haenszel chi-square tests, p < .05) were identified as behavioral predictors of self-wounding. Fear behaviors were associated with an increased risk of developing alopecia (Mantel-Haenszel chi square, p < .05). An inverse relationship was found between alopecia and stereotypic locomotor behaviors such as pacing, with animals who displayed these behaviors being less likely to develop significant hair loss (conditional logistic regression, p < .05). Overall, the type of treatment provided (e.g., additional foraging opportunities, the provision of toys, or the provision of visual barriers) did not predict improvement in levels of abnormal behavior or alopecia (logistic regression, p > .05). The results of these analyses add to the literature on self-wounding and alopecia and will allow refinement of the quantitative behavioral monitoring system at YNPRC such that more at-risk animals can be identified and treated prior to the development of abnormal or harmful behaviors.

Bakgrund: Människans försvar mot omvärlden och patogena mikrober består av ett väl utvecklat immunsystem innehållande det medfödda immunsystemet, innate, som inte förändras nämnbart över tid samt det adaptiva immunsystemet som skapar minnesceller efter immunrespons på peptidantigen. Det medfödda immunsystemets receptorer binder främmande strukturer och agerar snabbt genom att skapa inflammatorisk respons. Människans adaptiva immunsystem har celler som tar upp, bryter ned och via major histocompatibility complex (MHC) presenterar peptidantigen för T-celler. T-celler behöver flera stimuleringsvägar för att starta immunrespons. Immunsystemets celler kontrolleras så immunologisk tolerans upprätthålls. Autoimmunitet orsakas troligen av genetisk känslighet där den genetiska dispostitionen inte kan upprätthålla immunologisk tolerans vid trauma. Alopecia areata och vitiligo är de enda kända autoimmuna hudsjukdomarna som inte är antikroppsmedierade. Sjukdomarna drabbar 1 – 2 % av befolkningen. Hårfolliklar attackeras av autoreaktiva T-celler vid alopecia areata vilket ger håravfall. Vitiligo ger depigmenterade hudområden orsakat av autoreaktiva T-celler som förstört melanocyter. Sjukdomarna behandlas med immunsuppressiva läkemedel lokalt på huden eller systemiskt. Syfte: Examensarbetet syftade till att erhålla en djupare kunskap rörande likheter och skillnader i mekanism mellan de autoimmuna hudsjukdomarna alopecia areata och vitiligo samt undersöka och besvara frågeställningen vilken effekt olika typer av immunsuppressiv behandling har vid dessa sjukdomar.  Metod: Examensarbetet är en litteraturstudie som baseras på sex stycken vetenskapliga artiklar framsökta ur databasen PubMed genom flera sökningar. Sökningarna avgränsades genom användande av bl.a. sökorden alopecia areata, vitiligo, treatment, tacrolimus och janus kinase. Resultat: Studie 1 och 2 utvärderar systemisk puls-behandling med glukokortikoider. Patienterna i studie 1 hade alopecia areata med omfattande håravfall och behandlingsrespons sågs hos många patienter. Vitiligo-patienterna i studie 2 uppvisade minskad sjukdomsaktivitet vilket ses i färre nya lesioner samt repigmenterade lesioner, dock ses ingen repigmentering hos en del patienter. Studie 3 och 4 utvärderar lokal behandling med takrolimus-salva. Patienter med vitiligo i studie 3 fick viss repigmentering av lesionerna och patienterna med alopecia areata i studie 4 fick delvis håråterväxt. Effekten av oralt administrerade januskinas-hämmare utvärderas i studie 5 och 6. Studie 5 visar att många patienter med alopecia areata fått mycket håråterväxt vid behandlingens slut och studie 6 påvisar behandlingsrespons hos hälften av vitiligo-patienterna där repigmentering främst ses på hudområden exponerade för solljus. Slutsats: Litteraturstudien visar att olika typer av immunsuppressiv behandling kan lindra sjukdoms-utbrott samt förkorta sjukdomstid vid de autoimmuna hudsjukdomarna alopecia areata och vitiligo. Immunologiskt sett har sjukdomarna liknande sjukdomsmekanismer genom inflammatorisk respons som ger aktivering av autoreaktiva T-celler. Behandlingsresistensförekommer och därför behövs fortsatt forskning kring sjukdomsmekanismer och nya läkemedel. / Humans are depending on a functional immune system that provides defense against microbes and other things in our environment that can harm us. The skin is the largest and the heaviest of our organs. It’s important to have a barrier between the inner functions of the body and the world outside. The innate immune system specificities are recognition of microbes and damage. The adaptive immune system includes B and T cells which develops from stem cells in the bone marrow. The mature B and T cells are tested for self-tolerance before they are released. Having a functional immune system needs immunologic cells with immunologic tolerance. Immunologic tolerance demand B and T cells to know the difference between self antigens and pathogens.  Autoimmunity is probably caused by genetic susceptibility under influence of trauma such as local tissue injury and infection. The trauma cause imbalance in the immune system and gives an autoimmune response with activated T cells reacting on self antigens. Autoimmune diseases can be systemic or organ specific and different mechanisms cause the damage of tissue. Diseases caused by autoimmunity tend to be chronic, self-perpetuating and progressive. Alopecia areata and vitiligo are autoimmune skin diseases which gives hair loss and depigmentation. Hair loss in alopecia areata is caused by autoimmune T cells attacking hair follicles and depigmentation in vitiligo is caused by destruction of melanocytes by autoimmune T cells. The diseases can’t be cured but immunosuppressive therapy can reduce disease activity and give faster recovery.  The aim of this literature study was to get a deeper knowledge about the autoimmune skin diseases alopecia areata and vitiligo, and evaluate the efficiency of different immunosuppressive therapies used against alopecia areata and vitiligo. Found six scientific articles from the database PubMed through several searches. The searches were delimited by use of the keywords alopecia areata, vitiligo, treatment, tacrolimus and janus kinase.  Studies 1 and 2 evaluate systemic pulse management with glucocorticoids. The patients in study 1 had alopecia areata with extensive hair loss and treatment reactions were seen in many patients. Vitiligo patients in study 2 show reduced disease activity as seen in fewer lesions as well as repigmented lesions, however, no repigmentation seen in some patients. Studies 3 and 4 evaluate local treatment with tacrolimus ointment. Patients with vitiligo in study 3 received some repigmentation of the lesions and the patients with alopecia areata in study 4 received partial hair regrowth. The effect of orally administered janus kinase inhibitors is evaluated in studies 5 and 6. Study 5 shows that many patients with alopecia have received a lot of hair regrowth at the end of treatment and study 6 shows treatment response in half of vitiligo patients where repigmentation is mainly seen in sunlight exposed areas.  The literature study shows that different types of immunosuppressive treatment can relieve disease outbreaks and shorten disease in autoimmune skin diseases alopecia areata and vitiligo. Immunologically the diseases have similar disease mechanisms through inflammatory responses that provide activation of autoreactive T cells. Conclusion of this smallscale literature study is the need for further research on mechanisms of the diseases and research on therapies because therapy resistance is seen in both diseases although many patients responded to the immunosuppressive therapies.