Yes / Background: This study investigated predictors of response to topical diphenylyclopropenone (DPCP) immunotherapy in patients with alopecia areata (AA). Objective: To identify predictors of response, or resistance, to treatment for AA through clinical observations and serum tests. Methods: Eighty four AA patients were treated with DPCP. Serum cytokine levels were measured in 33 AA patients pre- and post-treatment, and in 18 healthy controls, using ELISA assays. Results: Of patients, 56.1% responded to DPCP with satisfactory hair regrowth; the response rate was negatively correlated with hair loss extent. Before DPCP treatment, higher serum IFN-γ and IL-12 cytokine levels were observed in AA patients compared to healthy controls. Non-responders to DPCP had significantly elevated serum IL-4 pre-treatment (3.07 fold higher) and lower IL-12 levels compared with responders. After DPCP treatment, non-responders had persistently high IL-4, increased IL-12, negligible decrease in IFN-γ and decreased IL-10. Post-treatment DPCP responders exhibited significantly decreased IFN-γ and IL-12, and increased IL-4 and IL-10. Development of adverse side-effects was significantly associated with higher pre-treatment serum IgE levels. Limitations: A small number of subjects were evaluated. Conclusions: Potentially, elevated pre-treatment serum levels of IL-4 and IL-12 can be used as unfavorable and favorable predictors of DPCP therapeutic effect, respectively. In addition, pre-treatment elevated serum total IgE may predict increased risk for severe adverse side-effects to DPCP application. Whether serum cytokine expression levels can be used as predictors of response to other forms of treatment is unknown, but it may warrant investigation in the development of personalized treatments for AA. / This work is supported by the National Natural Science Foundation of China (81573066) and Natural Science Foundation of Guangdong Province (2014A030313098) to Xingqi Zhang.

Yes / Alopecia areata (AA) is thought to be an autoimmune process. In other autoimmune diseases, the innate immune system and Toll‐like receptors (TLRs) can play a significant role. Expression of TLR7, TLR9 and associated inducible genes was evaluated by quantitative PCR in peripheral blood mononuclear cells (PBMCs) from 10 healthy individuals and 19 AA patients, categorized according to disease duration, activity and hair loss extent. Microdissected scalp biopsies from five patients and four controls were also assessed by quantitative PCR and immunohistology. TLR9 was significantly upregulated 2.37 fold in AA PBMCs. Notably, TLR9 was most significantly upregulated in patients with active AA, as shown by a positive hair pull test, compared to stable AA patients. In hair follicle bulbs from AA patients, IFNG and TLR7 exhibited statistically significant 3.85 and 2.70 fold increases in mRNA, respectively. Immunohistology revealed TLR7 present in lesional follicles, while TLR9 positive cells were primarily observed peri‐bulbar to AA affected hair follicles. The increased expression of TLR7 and TLR9 suggest components of the innate immune system may be active in AA pathogenesis. / National Alopecia Areata Foundation; Canadian Dermatology Foundation; Michael Smith Foundation for Health Research, Grant/Award Number: CI‐SCH‐00480(06‐1); Canadian Institutes of Health Research, Grant/Award Number: MOP‐167368 and MSH‐192593‐140450

Yes / In this commentary, we focus on allergy as a facilitating factor in the pathogenesis of alopecia areata (AA). From previous studies on AA, it is well known that subsets of patients can have one or more of; seasonal relapse, comorbid atopic rhinitis, asthma and dermatitis, lesion infiltrating eosinophils and plasma cells, high levels of total IgE, specific IgE for house dust mites (HDMs), and/or disrupted skin barrier function by the evaluation of filaggrin. Allergy and AA share a similar genetic background; both contributing to an immune reaction imbalance. Furthermore, adjunctive treatment with antihistamines, or desensitization for HDM, can reduce the severity of alopecia in atopic AA patients. Therefore, allergies may contribute to the onset and relapse of AA. Identification of an allergic or atopic immune component in AA patient subsets may indicate adjunctive treatment intervention measures against allergies should be taken which may improve the success of conventional AA treatment.

Yes / Hair follicles (HFs) are immersed within dermal white adipose tissue (dWAT), yet human adipocyte-HF communication remains unexplored. Therefore, we investigated how perifollicular adipocytes affect the physiology of organ-cultured human anagen scalp HFs. Quantitative (immuno-)histomorphometry, microCT and transmission electron microscopy showed that the number and size of perifollicular adipocytes declined during anagen-catagen transition, whilst fluorescence lifetime imaging revealed increased lipid oxidation in adipocytes surrounding the bulge/sub-bulge region. Ex vivo, dWAT significantly stimulated hair matrix keratinocyte proliferation and HF pigmentation. Both dWAT pericytes and PREF1/DLK1+ adipocyte progenitors secreted hepatocyte growth factor (HGF) during human HF-dWAT co-culture, for which the c-Met receptor is expressed in the hair matrix and dermal papilla. These effects were abrogated by an HGF-neutralising antibody, and reproduced using recombinant HGF. Laser capture microdissection-based microarray analysis of the hair matrix showed that dWAT-derived HGF up-regulated KRT27, KRT73, KRT75, KRT84, KRT86 and TCHH. Mechanistically, HGF stimulated Wnt/β-catenin activity in the HM by inhibiting SFRP1 in the dermal papilla, up-regulating matrix AXIN2, LEF1, WNT6 and WNT10B expression. Our study demonstrates that dWAT regulates human hair growth and pigmentation via HGF secretion, and thus identifies important, molecular and cellular targets for therapeutic intervention in disorders of human hair growth and pigmentation.

Diante da hipótese de que micropartículas poliméricas podem atravessar a barreira epidérmica através da rota transfolicular, e baseado na evidência de que a iontoforese é um método que consegue direcionar a liberação de fármacos para os folículos pilosos, este trabalho teve como objetivo estudar in vitro a permeação cutânea do minoxidil sulfato (MXS), fármaco utilizado no tratamento da alopecia androgênica, tanto em sua forma microencapsulada como não encapsulada utilizando ou não a iontoforese, na tentativa de aumentar, controlar e direcionar a sua liberação tópica para o folículo piloso. O MXS foi primeiramente incorporado em um gel hidrofílico contendo 2,0% (m/m) do ativo e sua permeação e retenção cutânea in vitro verificada com e sem a presença de corrente elétrica durante 6 h, utilizando células de difusão e pele de orelha de porco. A quantidade de MXS retida no EC da pele foi determinada e diferenciada daquela retida nos folículos pilosos utilizando-se a técnica denominada tape stripping diferencial. Foi observado que o fluxo passivo de fármaco através da pele aumentou 150 vezes com aplicação de iontoforese anódica e que o aumento do pH da formulação de 3,5 para 5,5 restringiu 3 vezes essa permeação iontoforética e aumentou a retenção do MXS no EC e folículos pilosos. Estes resultados mostram que a iontoforese do MXS nestas condições é capaz de promover a liberação folicular do fármaco de maneira bastante significativa. Uma série de micropartículas de quitosana contendo MXS foi obtida por spray drying modificando quantidades e proporções de polímero e fármaco. O sistema selecionado para estudo foi obtido a partir de 1,50 g de polímero e 0,75 g de MXS, e apresentou alta eficiência de encapsulação (~82%), diâmetro médio igual a 3,05 µm, morfologia esférica e sem porosidades, e potencial zeta igual a + 5,87 mV. Quando incorporadas a uma formulação hidroalcoólica, essas micropartículas sofreram intumescimento, aumentando 1,5 vezes o seu diâmetro médio, mas não tiveram sua morfologia esférica alterada. Experimentos de liberação in vitro mostraram que as micropartículas obtidas foram capazes de sustentar 3,5 vezes a liberação do MXS. As micropartículas ainda restringiram a permeação passiva do fármaco, reduzindo 2 vezes seu fluxo de permeação e aumentando em 5 vezes a retenção de fármaco na região folicular, apesar das partículas em si não penetrarem a pele após administração passiva. Assim, este sistema foi capaz de promover uma liberação mais sustentada do fármaco, o que deve reduzir o número de aplicações do produto pelo paciente ao longo do dia, e garantiu a entrada de grandes quantidades do fármaco nos folículos pilosos, seu alvo de ação. A iontoforese dessas micropartículas, apesar de também não fazê-las penetrar a pele, conseguiu direcioná-las mais rapidamente para as aberturas foliculares, como mostrou os estudos de microscopia confocal de varredura a laser das micropartículas marcadas. Adicionalmente, a iontoforese aumentou 6 vezes a quantidade de MXS retida nos folículos já nas primeiras 3 h de aplicação, garantindo assim que grandes quantidades do fármaco atingissem seu local de ação mais rapidamente que quando as partículas foram aplicadas passivamente sobre a pele. / Given the hypothesis that polymeric microparticles can penetrate the skin barrier along the transfollicular route, and based on the evidence that iontophoresis is a method that can direct the delivery of drugs to the hair follicles, this work aimed to study the in vitro skin permeation of minoxidil sulfate (MXS), a drug used to treat androgenic alopecia, both in its micro-encapsulated and non-encapsulated form, using or not iontophoresis, in an attempt to increase, control and direct its topical delivery to the hair follicle. The MXS was first incorporated in a hydrophilic gel containing 2.0% (w/w) MXS and its skin permeation and retention was in vitro observed with and without the presence of electric current for 6 h, using diffusion cells and skin of porcine\'s ears. The amount of MXS retained in EC was determined and differentiated from that retained in the hair follicles using the technique called differential tape stripping. It was observed that the passive flux of drug through the skin was increased 150-fold with the application of anodal iontophoresis and, by increasing the pH of the formulation from 3.5 to 5.5, iontophoretic permeation of MXS was 3-fold restricted, whereas it increased its retention in stratum corneum and hair follicles. These results show that iontophoresis of MXS in these conditions can promote the follicular delivery of the drug quite significantly. A series of chitosan microparticles containing MXS was obtained by spray drying, modifying quantities and proportions of polymer and drug. The system selected for study was obtained from 1.50 g of polymer and 0.75 g of MXS, and showed high encapsulation efficiency (~ 82%), mean diameter of 3.05 µm, spherical morphology without porosities, and zeta potential equal to + 5.87 mV. When incorporated into a hydro ethanolic formulation, these microparticles suffered swelling, increasing 1.5 times its diameter, but their spherical morphology was not modified. Permeation experiments showed in vitro that the microparticles obtained were able to sustain 3.5 times the release of MXS. The microparticles also restricted the passive permeation of the drug, reducing 2-fold its permeation flux and increasing by 5-fold the retention of drug in the follicular region, although the microparticles themselves did not penetrate the skin after passive administration. Thus, this system was able to promote a more sustained release of the drug, which must reduce the number of product applications by the patient throughout the day, and ensured the entry of large amounts of drug in hair follicles, their target. Iontophoresis of microparticles, although not making them penetrate the skin either, was able to direct them quickly to the follicular openings, as shown by laser confocal scanning microscopy studies of the labeled microparticles. In addition, iontophoresis increased 6-fold the amount of MXS retained in the follicles within the first 3 h of application, thereby ensuring that large quantities of the drug achieved its site of action more quickly than when the particles were applied passively to the skin.

Introdução: As alopecias cicatriciais são subdivididas em primárias e secundárias. Nas alopecias cicatriciais primárias o folículo piloso é o alvo principal da destruição; diferentemente das secundárias onde a destruição folicular não é o evento patológico primário. Objetivo: Revisar os achados histológicos de pacientes com diagnóstico de alopecia cicatricial primária, em uma fase tardia e reclassificá-los em seus respectivos subtipos. Casuística e Métodos: Os espécimes de biópsia de pacientes com diagnóstico histológico prévio de alopecia cicatricial foram revisados e submetidos a colorações por hematoxilina e eosina (HE), ácido periódico-Schiff (PAS) e Weigert, a fim de reclassificá-los de acordo com os diferentes subtipos de alopecia. Foram utilizados para a revisão histológica critérios de infiltrado inflamatório acrescidos de coloração para fibra elástica. Resultados: Os 37 casos de alopecia cicatricial primária foram reclassificados em: lupus eritematoso discóide (16), líquen plano pilar (4), pseudopelada de Brocq (12), foliculite decalvante (3), foliculite abscedante/dessecante (1), e alopecia não-específica (1). Conclusão: Mesmo em uma fase tardia, pauci ou não inflamatória, o exame histológico, utilizando colorações de rotina, PAS e coloração para fibra elástica, permitiu o diagnóstico mais acurado das alopecias cicatriciais primárias / BACKGROUND: Scarring alopecias are classified into primary and secondary according to the initial site of inflammation. In primary scarring alopecias, the hair follicle is the main target of destruction. The term secondary cicatricial alopecia implies that follicular destruction is not the primary pathologic event. AIMS: To review the histopathologic diagnoses of cases of cicatricial alopecia in order to classify them according to the North American Hair Research Society. PATIENTS AND METHODS: Patients with biopsy specimens diagnosed as cicatricial alopecia seen from 2000 to 2005 at the Dermatologic Department of Hospital das Clínicas, São Paulo University Medical School had hematoxylin and eosin, Periodic Acid-Schiff (PAS) and Weigert stained slides reevaluated and sub-typed into different primary cicatricial alopecias. RESULTS: Thirty-seven cases of primary cicatricial alopecias were reclassified as: discoid lupus erythematosus (16), lichen planus pilaris (4), pseudopelade of Brocq (12), folliculitis decalvans (3), dissecting folliculitis (1), and non-specific scarring alopecia (1). CONCLUSIONS: Even in late, pauci or noninflammatory phases, an approach with systematic evaluation of a constellation of criteria in routine hematoxylin and eosin stain, PAS and Weigert stain permitted an accurate diagnosis of cicatricial alopecias

Made available in DSpace on 2016-04-04T18:28:03Z (GMT). No. of bitstreams: 1 Andreia Cristina dos Santos Kleinhans.pdf: 1304307 bytes, checksum: b48ee8803ae01d7e3e971161a1351010 (MD5) Previous issue date: 2012-02-24 / Pontif?cia Universidade Cat?lica de Campinas / A Androgenic Alopecia (AA) is characterized by progressive hair loss and thinning and it may start at any age. It is identified as a genetically determine case, in which androgenic steroid hormones play a role. The objective of this study was to verify the existence of its possible association between stress and feelings of anger, in a sample of 20 diagnosed with AA, patients at a dermatology clinic in Curitiba. The instruments utilized for data collections were: identification sheet; Visual Analogue Scale (VAS), which had the function of verifying the level of discomfort to the problem; Lipp s Stress Symptoms Inventory for Adults (LSSI); and State-Trait Anger Expression Inventory (STAXI). Data analysis was both quantitative and qualitative. For responses obtained from LSSI and STAXI, the tables and norms from their respective manuals were utilized. The analysis of the answers obtained from the question was performed according to Bardin. The results show that 85% of individuals in the sample, (n=17), presented stress. Most women with stress were in the resistance phase 55% (n=11) whereas, 15% (n= 3) were at the almost exhaustion stage, 10% (n=2) where at the exhaustion phase and only 5% (n=1) was at the alert phase, in accordance with the LSSI. In agreement with STAXI, a higher score was observed for the internal anger factor, with an average percentage of 56 (standard deviation of 18), whereas for the external anger factor, such percentage was 18 (standard deviation of 21). An important association between anger expression and the presence of stress was found (p= 0.03). There was no association between the analogue visual scale and stress. Considering the number of participants with stress and the tendency of directing anger outwardly, in addition to a high percentage for internal anger in participants of this research, there is a necessity of further studies involving psychological treatment for stress and an adequate anger management. / A Alopecia Androgen?tica (AA) ? caracterizada pela perda e afinamento progressivo dos cabelos e, pode surgir em qualquer idade. ? identificada como um quadro geneticamente determinado com a participa??o dos horm?nios ester?ides andr?genos. O objetivo desse estudo foi verificar a exist?ncia de poss?veis associa??es entre o stress e o sentimento de raiva, de uma amostra de 20 mulheres com diagn?stico m?dico para (AA), pacientes de uma cl?nica de Dermatologia em Curitiba. Os instrumentos utilizados para a coleta de dados foram: ficha de identifica??o; Escala Anal?gica Visual (EVA), cuja fun??o, foi verificar o n?vel de desconforto frente ao problema; Invent?rio de Sintomas de Stress para Adultos de Lipp (ISSL); Invent?rio de Express?o de Raiva como Estado e Tra?o (STAXI). A an?lise dos dados foi quantitativa e qualitativa. Para respostas obtidas a partir do ISSL e do STAXI utilizaram-se as tabelas e normas dos respectivos manuais. A an?lise das respostas obtidas a partir da pergunta foi realizada de acordo com Bardin. Os resultados apontaram que 85% do total da amostra, (n=17), apresentaram stress. A maioria das mulheres com stress estavam na fase de resist?ncia 55% (n=11) enquanto, 15% (n= 3) encontravam-se em quase exaust?o, 10% (n=2) na fase de exaust?o e apenas 5% (n=1) apresentou-se na fase de alerta segundo o ISSL. De acordo com o STAXI observou-se um escore superior para o fator de raiva para dentro com percentil m?dio de 56 para o fator (desvio-padr?o de 18), ao passo que para o fator raiva para fora, o percentil m?dio foi 18 (desvio-padr?o 21). Uma importante associa??o entre a express?o da raiva para fora e a presen?a de stress foi encontrada (p= 0.03). N?o houve associa??o entre a escala anal?gica visual e stress. Levando-se em considera??o o n?mero de participantes com stress e tend?ncia em direcionar a raiva para fora, al?m do alto percentil de raiva para dentro das participantes dessa pesquisa, atenta-se para a necessidade de outros estudos que envolvam o tratamento psicol?gico para o stress e o adequado manejo da raiva.

A alopecia difusa não-cicatricial (ADNC) acomete 7% dos pacientes HIV positivos. O objetivo deste trabalho foi comparar os achados histológicos e imunohistoquímicos (citoqueratina 19/TUNEL e caspase 3 clivada) em cortes transversais de couro cabeludo de 15 pacientes HIV-1 positivos com ADNC e de 12 controles sadios. A apoptose de células tronco-foliculares e amplificadoras transitórias na protuberância folicular foi demonstrada pela dupla marcação TUNEL/CK19 em 80% dos casos e em 25% dos controles e, pelo anticorpo anti-caspase 3 clivada em 61% dos casos e 16% dos controles. Não houve correlação entre a incidência de apoptose e o grau de imunodeficiência dentre os casos / Seven percent of HIV positive patients present diffuse non-cicatricial alopecia (DNCA). The aim of this study was to compare the histological and the immunohistochemical (cytokeratin 19/TUNEL and cleaved caspase 3) findings in transverse scalp sections of 15 HIV-1 positive patients with DNCA and 12 healthy controls. Follicular stem and transit amplifying cells apoptosis in the bulge was demonstrated by double labeling TUNEL/CK19 in 80% of cases and 25% of controls, and by the anti-cleaved caspase 3 antibody in 61% of cases and 16% of the controls. There was no relation between the incidence of apoptosis and the degree of immunodeficiency among cases

A alopecia difusa não-cicatricial (ADNC) acomete 7% dos pacientes HIV positivos. O objetivo deste trabalho foi comparar os achados histológicos e imunohistoquímicos (citoqueratina 19/TUNEL e caspase 3 clivada) em cortes transversais de couro cabeludo de 15 pacientes HIV-1 positivos com ADNC e de 12 controles sadios. A apoptose de células tronco-foliculares e amplificadoras transitórias na protuberância folicular foi demonstrada pela dupla marcação TUNEL/CK19 em 80% dos casos e em 25% dos controles e, pelo anticorpo anti-caspase 3 clivada em 61% dos casos e 16% dos controles. Não houve correlação entre a incidência de apoptose e o grau de imunodeficiência dentre os casos / Seven percent of HIV positive patients present diffuse non-cicatricial alopecia (DNCA). The aim of this study was to compare the histological and the immunohistochemical (cytokeratin 19/TUNEL and cleaved caspase 3) findings in transverse scalp sections of 15 HIV-1 positive patients with DNCA and 12 healthy controls. Follicular stem and transit amplifying cells apoptosis in the bulge was demonstrated by double labeling TUNEL/CK19 in 80% of cases and 25% of controls, and by the anti-cleaved caspase 3 antibody in 61% of cases and 16% of the controls. There was no relation between the incidence of apoptosis and the degree of immunodeficiency among cases

Introdução: As alopecias cicatriciais são subdivididas em primárias e secundárias. Nas alopecias cicatriciais primárias o folículo piloso é o alvo principal da destruição; diferentemente das secundárias onde a destruição folicular não é o evento patológico primário. Objetivo: Revisar os achados histológicos de pacientes com diagnóstico de alopecia cicatricial primária, em uma fase tardia e reclassificá-los em seus respectivos subtipos. Casuística e Métodos: Os espécimes de biópsia de pacientes com diagnóstico histológico prévio de alopecia cicatricial foram revisados e submetidos a colorações por hematoxilina e eosina (HE), ácido periódico-Schiff (PAS) e Weigert, a fim de reclassificá-los de acordo com os diferentes subtipos de alopecia. Foram utilizados para a revisão histológica critérios de infiltrado inflamatório acrescidos de coloração para fibra elástica. Resultados: Os 37 casos de alopecia cicatricial primária foram reclassificados em: lupus eritematoso discóide (16), líquen plano pilar (4), pseudopelada de Brocq (12), foliculite decalvante (3), foliculite abscedante/dessecante (1), e alopecia não-específica (1). Conclusão: Mesmo em uma fase tardia, pauci ou não inflamatória, o exame histológico, utilizando colorações de rotina, PAS e coloração para fibra elástica, permitiu o diagnóstico mais acurado das alopecias cicatriciais primárias / BACKGROUND: Scarring alopecias are classified into primary and secondary according to the initial site of inflammation. In primary scarring alopecias, the hair follicle is the main target of destruction. The term secondary cicatricial alopecia implies that follicular destruction is not the primary pathologic event. AIMS: To review the histopathologic diagnoses of cases of cicatricial alopecia in order to classify them according to the North American Hair Research Society. PATIENTS AND METHODS: Patients with biopsy specimens diagnosed as cicatricial alopecia seen from 2000 to 2005 at the Dermatologic Department of Hospital das Clínicas, São Paulo University Medical School had hematoxylin and eosin, Periodic Acid-Schiff (PAS) and Weigert stained slides reevaluated and sub-typed into different primary cicatricial alopecias. RESULTS: Thirty-seven cases of primary cicatricial alopecias were reclassified as: discoid lupus erythematosus (16), lichen planus pilaris (4), pseudopelade of Brocq (12), folliculitis decalvans (3), dissecting folliculitis (1), and non-specific scarring alopecia (1). CONCLUSIONS: Even in late, pauci or noninflammatory phases, an approach with systematic evaluation of a constellation of criteria in routine hematoxylin and eosin stain, PAS and Weigert stain permitted an accurate diagnosis of cicatricial alopecias