Yes / BACKGROUND: Diffuse alopecia areata (DAA) often leads to a complete hair shedding within a few months. OBJECTIVE: To explore features and mechanisms underlying DAA. MATERIALS AND METHODS: Scalp and hair root dermoscopy were conducted on 23 DAA patients throughout the disease process, 20 patchy Alopecia areata patients, 23 acute telogen effluvium (ATE) patients and 10 normal controls. Histopathology was also evaluated. RESULTS: We found almost all hair roots were anagen in early stage DAA in 18 patients (18/23, 78.3%) within the first 4-8 weeks after hair loss onset. Anagen effluvium (~4 weeks) was followed by catagen (~4 weeks) and then telogen/exogen (~8 weeks) effluvium with overlap. Hair root and proximal hair shaft depigmentation was more prominent in later DAA disease stages. Black dots, exclamation mark hairs and inconsistent thickness of hair shafts were found more often in early than later DAA (Ps < 0.01). Early DAA histopathology revealed more prominent inflammation and hair follicle regression than that observed in the later stages. Patchy alopecia areata patients showed mixed anagen, catagen and telogen hair roots while ATE patients showed increased exogen and mildly decreased hair root pigmentation. CONCLUSION: Sequential cyclic staging of shed hairs in DAA indicates the insult may be hair-cycle specific. We suggest that DAA is initially an anagen effluvium disease involving an intense inflammatory insult, later progressing to a brief catagen effluvium, and then to telogen effluvium with premature exogen, in later stages of DAA. / This study was supported by the following grants to Xingqi Zhang: National Natural Science Foundation of China (81573066); Natural Science Foundation of Guangdong Province (2014A030313098).

No description available.

Für das Verständnis der Pathogenese entzündlicher Hauterkrankungen ist die Zusammensetzung des zellulären Entzündungsinfiltrates und die Verteilung der Entzündungszellen von wesentlicher Bedeutung. In Anbetracht der chemotaktischen Funktion der Chemokine liegt die Annahme nahe, dass das zelluläre Infiltrationsmuster in entzündlichen Hauterkrankungen das Expressionsmuster von Chemokinen und umgekehrt widerspiegelt. Die Infiltrationsroute der Leukozyten in die Haut erfolgt immer vom Lumen dermaler Gefäße in das dermale Milieu und ggf. weiter in das epidermale Kompartiment (sog. Epidermotropismus). Die Migration inflammatorischer Zellen über die Grenzen unterschiedlicher Hautkompartimente hinweg ist einzigartig und präsentiert ein ideales Modell, um die chemotaktischen Cytokin- bzw. Chemokinfunktionen zu evaluieren. Anhand verschiedener ausgewählter Hautdermatosen (Wundheilung, Psoriasis, Alopecia areata) wurden die unterschiedlichen Expressionsmuster einer Auswahl von Chemokinen untersucht. Dabei nehmen Chemokine, die von Endothelzellen exprimiert bzw. sezerniert werden, eine zentrale Rolle ein, da sie eine „Pförtnerfunktion“ ausführen. Diese Funktion ist entscheidend bei der Rekrutierung und Akkumulation der für das Erkrankungsbild und bei reparativen Vorgängen der Wundheilung spezifischen Leukozytensubpopulation ins dermale bzw. epidermale Gewebe / The composition of the cellular inflammatory infiltrates and the distribution of inflammatory cells is essential for the understanding of the pathogenesis of inflammatory skin diseases. In view of the chemotactic function of chemokines we assume that the cellular infiltration pattern in inflammatory skin diseases reflects the expression patterns of chemokines and vice versa. The route of leukocyte infiltration into the skin is always directed from the lumen of dermal vessels in the dermal milieu and in some cases further into the epidermal compartment (so-called epidermotropism). The migration of inflammatory cells across the borders of different skin compartments is unique and represents an ideal model to evaluate the chemotactic function of cytokines or chemokines. In various representative dermatoses (wound healing, psoriasis, alopecia areata) we investigated the different expression patterns of selected chemokines. Chemokines, expressed or secreted by endothelial cells, play an important role because they exert a "gatekeeper function". This is crucial in the recruitment and accumulation pattern of the disease and repair processes of wound-specific leukocyte subpopulation, which invade the dermal and epidermal compartment.

Estudo qualitativo, cujo objetivo foi compreender o significado da alopecia, decorrente de quimioterapia, para mulheres submetidas a esse tipo de tratamento para o câncer ginecológico ou mamário, e teve como referencial teórico o Interacionismo Simbólico. Os dados foram obtidos por meio de entrevistas e prontuários de 15 mulheres que apresentaram alopecia como evento adverso ao tratamento quimioterápico, e frequentavam um serviço especializado em reabilitação pós-mastectomia ou um ambulatório ou enfermaria de oncologia de um hospital universitário do interior de São Paulo. Foram identificadas duas unidades temáticas pela Análise de Conteúdo: 1) o significado da alopecia para as mulheres que a apresentam, na relação consigo próprias; e 2) na relação com os outros e com o mundo. Na relação consigo próprias, a alopecia significou necessidade de lidar com alterações emocionais e da autoestima, necessidade de disfarce, dificuldade de lidar com a alopecia, de se olhar no espelho e de falar sobre o assunto, sendo que a mulher descobriu formas de lidar com os problemas ocasionados pela queda de cabelo, embora este tenha sido um problema que muitas vezes trouxe sofrimento maior do que o câncer em si. Já na relação com os outros e com o mundo, a alopecia foi tida como um estigma relacionado ao câncer e seus tratamentos, trouxe mudanças nos hábitos e rotinas, além de interferir na sexualidade. Assim, puderam ser identificadas instituições que ofereceram apoio às mulheres. Compreender o significado pleno da experiência de alopecia na vida cotidiana dessas mulheres é fundamental para poder proporcionar-lhes apoio durante o curso da doença, e para auxiliá-las no desenvolvimento de estratégias para lidar com as mudanças que ocorrem durante o tratamento do câncer. / Qualitative study aimed to understand the meaning of hair loss because chemotherapy for women undergoing this type of treatment for breast or gynecological cancer, and had the theoretical Symbolic Interaction. Data were collected through interviews and medical records of15 women who had hair loss as an adverse event to chemotherapy, and attended a specialized rehabilitation postmastectomy or a clinic or oncology ward of a university hospital in São Paulo. Two thematic units were identified by Content Analysis: 1) the meaning of hair loss for women, in relation to themselves, and 2) the relationship with others and with the world. In relation to themselves, hair loss meant the necessity to deal with emotional and self-esteem, the necessity to disguise, difficulty to deal with alopecia, to look in the mirror and talk about it, although the woman discovered ways of dealing with the problems caused by hair loss, this has been a problem that often caused more suffering than the cancer. In the relation with others and with the world, the hair loss was seen as a stigma related to cancer and its treatments, caused changes in habits and routines, as well as interfere with sexuality. Therefore could be identified institutions which offered support for women. Understand the full meaning of the experience of hair loss in women\'s daily life is crucial to be able to provide them support during the course of the disease, and to assist them in developing strategies to deal with the changes that occur during cancer treatment

Orientador : Profª. Drª. Betina Werner / Coorientador : Profª. Fabiane Mulinari-Brenner / Dissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em Medicina Interna. Defesa : Curitiba, 06/12/2016 / Inclui referências : f. 69-73 / Resumo: Alopecia permanente após transplante de medula óssea é rara, porém cada vez mais casos têm sido descritos, tipicamente envolvendo altas doses de quimioterápicos usados em regimes de condicionamento para o transplante. O bussulfano, classicamente associado a casos de alopecia irreversível, permanece relacionado aos casos recentes. A patogênese envolvida na queda dos fios ainda não está clara e há poucos estudos disponíveis. Além dos agentes quimioterápicos, outro fator que pode estar implicado como causa é a doença do enxerto contra hospedeiro crônica. No entanto, não há ainda critérios histopatológicos e dermatoscópicos definidos para diagnóstico. Os objetivos do trabalho foram avaliação clínica, histológica e dermatoscópica de casos de alopecia permanente após transplante de medula óssea, identificando características de alopecia permanente como manifestação de doença do enxerto contra hospedeiro crônica, e distinção de casos de alopecia permanente induzida por quimioterapia. Métodos: foram utilizados dados coletados de prontuários de doze pacientes, com descrição das características clínicas e revisão de lâminas e blocos de biópsias, e de dermatoscopias de couro cabeludo. Dois padrões histológicos distintos foram encontrados: o primeiro, semelhante à alopecia androgenética, não cicatricial, e outro semelhante ao líquen plano pilar, cicatricial. O primeiro padrão corrobora dados da literatura de casos de alopecia permanente induzida por agentes quimioterápicos, e o segundo é compatível com manifestação de doença do enxerto contra hospedeiro crônica em couro cabeludo, com achados ainda não descritos histologicamente. Foram observados dois padrões dermatoscópicos, com correlação histopatológica. Os resultados contribuem para elucidação dos fatores envolvidos nestes casos. Palavras-chave: Alopecia; Quimioterapia; Quimioterapia de indução; Transplante de medula óssea / Abstract: Permanent alopecia after bone marrow transplantation is rare, but a myriad of cases have been described, typically involving high doses of chemotherapeutic agents used in the conditioning regimen for the transplant. Busulfan, classically described in cases of irreversible alopecia, remains associated in recent cases. The pathogenesis involved in hair loss is not clear and there are few studies available. In addition to chemotherapeutic agents, another factor that has been implicated as a cause is chronic graft-versus-host disease. However, there are no histopathological and dermoscopic criteria for defining diagnosis yet. The aim of this study is to evaluate clinical, histological and dermoscopic aspects in cases of permanent alopecia after bone marrow transplantation, identifying features of permanent alopecia as a manifestation of chronic graft-versus-host disease, and distinguish from cases of permanent chemotherapy-induced alopecia. Data were collected from medical records of 12 patients, with description of the clinical features and review of glass slides and paraffin blocks of biopsies, and scalp dermoscopies. Two distinct histological patterns were found: the first one similar to androgenetic alopecia, nonscarring pattern, and another similar to lichen planopilaris, scarring alopecia. The first pattern corroborates the literature cases of permanent alopecia induced by chemotherapeutic agents, and the second is compatible with manifestation of chronic graft-versus-host disease on scalp, with findings that have not been described yet. Two dermoscopic patterns were observed, with histopathologic correlation. The results contribute to the elucidation of the factors involved in these cases. Keywords: Alopecia; Bone marrow transplantation; Drug therapy; Induction Chemotherapy

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, 2011. / Submitted by Jadiana Paiva Dantas (jadi@bce.unb.br) on 2011-06-28T23:45:00Z No. of bitstreams: 1 2011_ Gabriela Andrade Santiago.pdf: 1160860 bytes, checksum: 4aeb312032a7ee2b57066ee85fdf8a42 (MD5) / Approved for entry into archive by Jaqueline Ferreira de Souza(jaquefs.braz@gmail.com) on 2011-07-13T21:23:43Z (GMT) No. of bitstreams: 1 2011_ Gabriela Andrade Santiago.pdf: 1160860 bytes, checksum: 4aeb312032a7ee2b57066ee85fdf8a42 (MD5) / Made available in DSpace on 2011-07-13T21:23:43Z (GMT). No. of bitstreams: 1 2011_ Gabriela Andrade Santiago.pdf: 1160860 bytes, checksum: 4aeb312032a7ee2b57066ee85fdf8a42 (MD5) / Alopecia areata é uma afecção crônica não cicatricial dos folículos pilosos, caracterizada por perda localizada ou difusa de cabelos ou pelos. Considerada doença autoimune mediada por células T, órgão-específica, onde uma infiltração linfocítica dos folículos pilosos resulta em ruptura de cabelos anágenos, ocasionando alopecia não inflamatória. Pode ocorrer em qualquer área corporal, sendo mais frequente em couro cabeludo e barba. Objetivos: O objetivo principal desta pesquisa foi investigar a presença de comorbidades e sua relação como fator agravante de alopecia areata. O objetivo secundário foi avaliar os aspectos epidemiológicos da alopecia areata, estudar a prevalência de alterações ungueais e a prevalência dos antecedentes pessoais e familiares de atopia nos pacientes participantes do estudo. Material e métodos: Desenvolveu-se o estudo com 30 pacientes portadores de Alopecia Areata, atendidas no Serviço de Dermatologia do Hospital Universitário de Brasília. Para elaboração dos testes foi utilizado o pacote estatístico SPSS, Statistical Package for the Social Sciences, versão 15.0, e para testar a associação entre as variáveis utilizou-se o teste exato de Fisher, agregado ao método computacional de Monte Carlo. Foi considerado significante valor inferior a 0,05. Resultados: A maior prevalência de AA encontra-se na faixa etária de crianças de 6 a 7 anos de idade (23,3%), sendo 18 pacientes do sexo feminino (60%) e 12 do sexo masculino (40%). Dos 30 pacientes avaliados, dez (33,3%) tinham antecedentes pessoais de atopia e 12 (40%) tinham alguma patologia concomitante. Destes, 7 (58%) pacientes tinham classificação S1 (<25% perda capilar); 2 (17%) tinham classificação S2 (25-49% perda capilar); 2 (17%) com classificação S4 (75-99% perda capilar) e 1 (8%) com classificação S5 (100% perda capilar). Conclusão: Associação com comorbidades não foi significativa para a gravidade da alopecia areata. _______________________________________________________________________________ ABSTRACT / Alopecia areata is a chronic non-scarring hair follicles, characterized by localized or diffuse hair loss disease. Considered an autoimmune disease mediated by T cells, organ-specific, where a lymphocytic infiltration of hair follicles results in disruption of anagen hair, causing non-inflammatory alopecia. It can occur in any body area, was more frequent in the scalp and beard. Objectives: The main objective of this research was to investigate the presence of comorbidities and their relationship as an aggravating factor for alopecia areata. The secondary objective was to evaluate the epidemiological aspects of alopecia areata, to study the prevalence of nail changes and the prevalence of personal and family history of atopy in the study participants. Methods: We developed the study with 30 patients with Alopecia Areata, served in the Department of Dermatology in the University Hospital of Brasilia. For preparation of tests, we used the SPSS statistical package, Statistical Package for the Social Sciences, version 15.0, and to test the association between the variables used the Fisher exact test, added to the computational method of Monte Carlo. Was considered significant below 0.05. Results: The higher prevalence of AA is in the age group of children 6-7 years old (23.3%), 18 female patients (60%) and 12 males (40%). Of the 30 patients evaluated, ten patients (33,3%) had as a personal history of atopy and 12 (40%) had some concomitant disease. Of these, 7 (58%) patients were rated S1 (<25% hair loss), 2 (17%) were rated S2 (25-49% hair loss), 2 (17%) were rated S4 (75-99% loss capillary) and 1 (8%) were rated S5 (100% hair loss). Conclusion: Association with comorbidities was not significant for the severity of alopecia areata.

Estudo qualitativo, cujo objetivo foi compreender o significado da alopecia, decorrente de quimioterapia, para mulheres submetidas a esse tipo de tratamento para o câncer ginecológico ou mamário, e teve como referencial teórico o Interacionismo Simbólico. Os dados foram obtidos por meio de entrevistas e prontuários de 15 mulheres que apresentaram alopecia como evento adverso ao tratamento quimioterápico, e frequentavam um serviço especializado em reabilitação pós-mastectomia ou um ambulatório ou enfermaria de oncologia de um hospital universitário do interior de São Paulo. Foram identificadas duas unidades temáticas pela Análise de Conteúdo: 1) o significado da alopecia para as mulheres que a apresentam, na relação consigo próprias; e 2) na relação com os outros e com o mundo. Na relação consigo próprias, a alopecia significou necessidade de lidar com alterações emocionais e da autoestima, necessidade de disfarce, dificuldade de lidar com a alopecia, de se olhar no espelho e de falar sobre o assunto, sendo que a mulher descobriu formas de lidar com os problemas ocasionados pela queda de cabelo, embora este tenha sido um problema que muitas vezes trouxe sofrimento maior do que o câncer em si. Já na relação com os outros e com o mundo, a alopecia foi tida como um estigma relacionado ao câncer e seus tratamentos, trouxe mudanças nos hábitos e rotinas, além de interferir na sexualidade. Assim, puderam ser identificadas instituições que ofereceram apoio às mulheres. Compreender o significado pleno da experiência de alopecia na vida cotidiana dessas mulheres é fundamental para poder proporcionar-lhes apoio durante o curso da doença, e para auxiliá-las no desenvolvimento de estratégias para lidar com as mudanças que ocorrem durante o tratamento do câncer. / Qualitative study aimed to understand the meaning of hair loss because chemotherapy for women undergoing this type of treatment for breast or gynecological cancer, and had the theoretical Symbolic Interaction. Data were collected through interviews and medical records of15 women who had hair loss as an adverse event to chemotherapy, and attended a specialized rehabilitation postmastectomy or a clinic or oncology ward of a university hospital in São Paulo. Two thematic units were identified by Content Analysis: 1) the meaning of hair loss for women, in relation to themselves, and 2) the relationship with others and with the world. In relation to themselves, hair loss meant the necessity to deal with emotional and self-esteem, the necessity to disguise, difficulty to deal with alopecia, to look in the mirror and talk about it, although the woman discovered ways of dealing with the problems caused by hair loss, this has been a problem that often caused more suffering than the cancer. In the relation with others and with the world, the hair loss was seen as a stigma related to cancer and its treatments, caused changes in habits and routines, as well as interfere with sexuality. Therefore could be identified institutions which offered support for women. Understand the full meaning of the experience of hair loss in women\'s daily life is crucial to be able to provide them support during the course of the disease, and to assist them in developing strategies to deal with the changes that occur during cancer treatment

The most common form of hair loss in young and old people is androgenic alopecia. Hereditary hair loss affects both men and women. Hereditary hair loss in some women begins at the age of 30, but as a rule hair loss begins in post-menopausal women. In women the hair thins out in an oval portion of the front part of the scalp. In men, hair loss can start as early as at the age of 20. The hairline then starts to slowly creep upward along the temples and gives characteristic flaps, and on the scalp a bald spot appears that over time becomes larger and larger. Hereditary androgenic alopecia is caused by androgenic effects on the hair follicles causing the anagen phase to shorten and the telogen phase to extend while the hair follicle size decreases. Polymorphism in the androgen receptor has been linked to androgenic alopecia. Finasteride is a fat-soluble synthetic steroid originally intended for the treatment of benign prostatic hyperplasia (BPH). In 1992 it was approved for BPH-treatment and in 1997 it was approved for male pattern baldness. Finasteride inhibits the function of type ІІ 5-α-reductase, and therefore inhibits the conversion of testosterone to dihydrotestosterone(DHT). The purpose of this study was to examine the effectiveness of finasteride treatment against hereditary male pattern baldness. Six studies on finasteride were selected from searching the database PubMed in february 2013. To get the most relevant results the search terms "finasteride alopecia" were used. Out of 42 hits, six articles were selected. Only articles with clinical testing on humans were selected. The articles included in this study demonstrate that finasteride treatment slows the development of hair loss and increases hair growth. Increased hair growth, however, requires long-term treatment. After one year of treatment, or longer, with finasteride 1 mg daily the increase in hair growth is of the order 7-10% more hairs than at the beginning of the treatment. A larger increase in hair weight suggests that the treatment also increases the thickness and/or the length of hairs. Men 18-19 have been treated with finasterid in the studies. The concentration of DHT was decreased by finasteride treatment in all studies. Adverse reactions include decreased libido, erectile difficulty, ejaculation problems and depression can occur in fewer than 1 in 100 people which was also mentioned in the studies.

Alopecia Areata (AA) is a highly prevalent autoimmune disease in the US with a lifetime risk of 2.1%. In AA, autoimmunity develops against the hair follicles, which leads to infiltration of immune cells around affected follicles. Among genetic risk factors in complex autoimmune diseases, variants cluster in genes regulating the immune response, as well as the target organ. AA is believed to result from both genetic and environmental factors. To identify underlying genetic drivers in AA, we analyzed AA risk genes using various sequencing techniques and analysis methods to identify causal variants and placed them in functionally relevant contexts using innovative mapping techniques. To address the role of variants in immune function, we studied the Interleukin-2 Receptor Alpha (IL2RA), which we identified as a significant locus to study genetic factors underlying immune function from our AA GWAS studies (p=1.74*10-12)11. IL2RA plays a crucial role in regulating immune tolerance and controlling activity of regulatory T cells (Treg)13. We identified significant causal variants in the IL2RA region associated with AA using GWAS, targeted resequencing, and custom capture exome sequencing approaches. We validated the expression of these variants in immune cell cluster tissue types in silico, and specifically in CD4+ T cells. The variant rs3118740 increases AA susceptibility for carriers of the C allele. Such allele specific effects could lead to a perturbation of Treg function, for example, one study in T1D where patients with the rs3118470 risk variant have Treg with IL-2 signaling defects14. These studies demonstrated that identifying causal variants may lead to an improved understating of Treg function and risk of autoimmunity in AA. Next, to study genetic susceptibility in the target organ in AA, the hair follicle (HF), the second candidate GWAS susceptibility gene we studied was peroxiredoxin 5 (PRDX5) (p= of 8.7*10-14), which is also a GWAS gene in Crohn’s disease, sarcoidosis, and psoriasis15,16. PRDX5 is a member of the family of antioxidant enzymes that are crucial for regulating oxidative stress. Our lab performed whole exome sequencing in 849 AA patients, together with selected custom capture regions of genomic sequencing. Using a test of variant enrichment, we identified variants in PRDX5 that were significant in both our GWAS and exome studies, and thus represented likely candidate causal variants. Using Bayesian fine mapping, we identified a GWAS and exome sequencing variant, rs574087, that was significantly enriched in both, and is predicted to be a causal variant in keratinocytes and melanocytes. To functionally validate PRDX5, we immunostained healthy human HF and AA affected HF, and found that PRDX5 is upregulated AA human HF. PRDX5 is expressed in cultured melanocytes by immunostaining, which is consistent with melanocytes exhibiting high levels of oxidative stress. We postulated that PRDX5 may be involved in protection from oxidative stress, and that its dysregulation may contribute to autoimmunity. Finally, along with genetic predisposition, environmental triggers such as the microbiome have emerged as potential factors contributing to pathologic immune responses in autoimmune diseases. To determine the role of the microbiome in AA pathobiology, we performed 16S rRNA sequencing of skin swabs, hair follicles, and stool samples from a cohort of 34 AA patients and 12 healthy controls (HCs). Unexpectedly, we found evidence of striking gut dysbiosis, consisting of over-representation of Firmicutes and under-representation of Bacteroides in the gut microbiome of AA patients compared with healthy subjects, but no significant differences in skin or hair follicle (HF) microbiome composition. To investigate the role of the gut microbiome in AA development in vivo, we depleted the gut microbiome in C3H/HeJ mice and found that the mice were largely protected from AA developing. These data revealed a requirement for gut microbiota in the onset of murine AA. Taken together with recent reports in the literature of reversal of AA in several patients following fecal microbiota transplant (FMT)17,18, our findings suggest that restoring homeostasis of the gut microbiome may represent an effective new treatment modality in the management of AA.

No / It has long been appreciated in science that correlation does not imply causation. However, with any logical fallacy, simply spotting that the reasoning behind an argument is faulty does not imply that the resulting conclusion is false. Thus, I begin the tricky business of exploring the basis upon which researchers and clinicians are often tempted to conclude that two medical conditions (here alopecia areata and vitiligo), with some striking resemblances, are in fact related. This is relevant, particularly if assumptions of shared aetiology (and to some extent shared pathomechanism) encourage a common strategy to finding a treatment or cure.