<p>Alopecia areata (AA) betyder fläckvis håravfall och uppstår vanligen på huvudet men även på kroppen. Det är en harmlös, reversibel, organ-specifik, autoimmun hudsjukdom som drabbar hårfolliklarna. Den autoimmuna reaktionen förmedlas av T-lymfocyter som angriper hårfolliklarna och hämmar hårväxt. Det årliga incidenstalet för både kvinnor och män är 20,2 per 100 000 personer och 1,7 % av befolkningen riskerar att drabbas någon gång under livet. Även om genetiskt anlag och miljöfaktorer, såsom emotionell stress, graviditet och tillfälliga infektioner kan utlösa sjukdomen så är den exakta orsaken fortfarande okänd. De behandlingar som finns mot AA påverkar inte den autoimmuna processen som orsakar alopecin utan syftet med dessa är att stimulera hårfolliklarna och dämpa sjukdomens aktivitet. Kortikosteroider används vid behandling mot AA, men kan ge svåra biverkningar vid långvarig behandling. De olika administrationsformer av kortikosteroider som används mot AA är främst lokala och systemiska, men även intralesionella.</p><p>Målet med denna litteraturstudie var att undersöka om kortikosteroider har någon effekt mot AA. Samtliga studier visade att kortikosteroider har effekt mot AA, men att risken för återfall är stor. Tre av de fem studierna visade att behandlingen gav bättre resultat hos de patienterna med mindre svår AA, kort duration och första episoden av sjukdomen. Dåliga prognostiska faktorer visade sig vara omfattande AA, lång duration, atopi, nagelinvolvering och flera episoder av sjukdomen.</p><p>En studie visade att patienter med plurifocal AA svarar bättre på behandlingen än patienter med ophiasic AA, AA totalis och AA universalis. I samtliga studier fick patienterna biverkningar av behandlingen med dessa var inte så allvarliga att patienterna fick avbryta behandlingen. Slutsatsen av detta arbete är att kortikosteroider har effekt mot AA, men att risken för återfall är stor.</p><p>2008:F3</p>

Tese de mestrado integrado. Bioengenharia. Faculdade de Engenharia. Universidade do Porto. 2012

Diese retrospektive Analyse untersucht die Behandlung von Patienten mit Alopecia areata in der Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie der Universitätsklinik Würzburg mit Diphenylcyclopropenon und beleuchtet Faktoren der durch die Behandlung beeinflussten Lebensqualität. / This study evaluates the efficacy of the treatment of alopecia areata in the dermatology department of the university clinic in Würzburg, Germany and shows prognostic factors that may be detrimental in regards to a positive outcome. Furthermore, the influence of the therapy's side-effects on everyday life are shown.

Hintergrund: Bei der Entscheidung für eine intravenöse Kortikosteroid-Pulstherapie bei schweren Formen der AA ist die Abwägung von Therapieaufwand, Nebenwirkungen und Risiken einerseits und der Erfolgsaussicht andererseits von zentraler Bedeutung. Ziel: Ziel dieser retrospektiven Analyse war es daher, die Wirksamkeit und Sicherheit der intravenösen Kortikosteroid-Pulstherapie bei Patient:innen mit ausgeprägter AA klinikintern als qualitätssichernde Maßnahme zu untersuchen, prognostisch bedeutsame Faktoren für den Therapieeffekt zu ermitteln und hierdurch die beste Indikation herauszuarbeiten. Methode: 126 Patient:innen (13 Kinder und Jugendliche) erhielten Dexamethason 100 mg (122 Patienten) oder Methylprednisolon 20-30 mg/kg/KG (max. 1000 mg, 4 Patienten) an drei aufeinanderfolgenden Tagen für ein bis drei Zyklen. Ergebnisse: Patienten mit einer AA partialis bzw. diffusa zeigten im Hinblick auf ein vollständiges oder kosmetisch akzeptables Wiederwachstum die besten Ansprechraten (44,3%, n=43). Unter den Ophiasis-Patienten und den Patienten mit AA totalis/universalis sprach nur etwa ein Viertel auf die Therapie an (Ophiasis 23,8%, n=5; AA totalis/universalis: 25%, n=2). Schwerwiegende unerwünschte Nebenwirkungen wurden nicht beobachtet. Schlussfolgerung: In der vorliegenden Untersuchung ließen sich eine längere Bestandsdauer der Erkrankung und Erkrankungsepisode (über 6 Monate), ein schwerer Ausprägungsgrad (Ophiasis, AA totalis/universalis) und krankheitstypische Nagelveränderungen als wichtige ungünstige prognostische Faktoren nachweisen. Dagegen wirkten sich die untersuchten Kriterien Alter, Geschlecht, atopisches Ekzem und andere Erkrankungen des atopischen Formenkreises, Schilddrüsen- und Autoimmunerkrankungen in der Eigenanamnese sowie AA in der Familienanamnese nicht negativ auf den Behandlungserfolg aus. Patienten mit AA partialis und einer Bestandsdauer der AA von maximal 6 Monaten haben die besten Erfolgsaussichten. / Background: When deciding in favour of intravenous corticosteroid pulse therapy for severe forms of AA, it is of central importance to weigh up the therapeutic effort, side effects and risks on the one hand and the prospects of success on the other. Aim: The aim of this retrospective analysis was therefore to investigate the efficacy and safety of intravenous corticosteroid pulse therapy in patients with pronounced AA within the clinic as a quality assurance measure, to determine prognostically significant factors for the therapeutic effect and thus to identify the best indication. Methods: 126 patients (13 children and adolescents) received dexamethasone 100 mg (122 patients) or methylprednisolone 20-30 mg/kg/KG (max. 1000 mg, 4 patients) on three consecutive days for one to three cycles. Results: Patients with AA partialis or diffusa showed the best response rates in terms of complete or cosmetically acceptable regrowth (44.3%, n=43). Among the ophiasis patients and the patients with AA totalis/universalis, only about a quarter responded to the therapy (ophiasis 23.8%, n=5; AA totalis/universalis: 25%, n=2). No serious adverse events were observed. Conclusion: In the present study, a longer duration of the disease and disease episode (more than 6 months), a severe degree of severity (ophiasis, AA totalis/universalis) and nail changes typical of the disease were found to be important unfavourable prognostic factors. In contrast, the investigated criteria of age, gender, atopic eczema and other atopic diseases, thyroid and autoimmune diseases in the patient's own medical history and AA in the family history did not have a negative effect on the success of treatment. Patients with AA partialis and a maximum duration of AA of 6 months have the best chances of success.

No / Hair loss can be a psychologically devastating adverse effect of chemotherapy, but satisfactory management strategies for chemotherapy-induced alopecia remain elusive. In this Review we focus on the complex pathobiology of this side-effect. We discuss the clinical features and current management approaches, then draw upon evidence from mouse models and human hair-follicle organ-culture studies to explore the main pathobiology principles and explain why chemotherapy-induced alopecia is so challenging to manage. P53-dependent apoptosis of hair-matrix keratinocytes and chemotherapy-induced hair-cycle abnormalities, driven by the dystrophic anagen or dystrophic catagen pathway, play important parts in the degree of hair-follicle damage, alopecia phenotype, and hair-regrowth pattern. Additionally, the degree of hair-follicle stem-cell damage determines whether chemotherapy-induced alopecia is reversible. We highlight the need for carefully designed preclinical research models to generate novel, clinically relevant pointers to how this condition may be overcome.

Primary scalp alopecia is classically divided into cicatricial (scarring) and non-cicatricial (non-scarring). Challenging cases are assessed with a scalp biopsy. The use of both horizontal and vertical sections (HoVert sections) has dramatically improved the accuracy of histopathological diagnosis. In this work, we have used immunostaining to address diagnostic difficulties, which persist despite all currently available tools. We performed an immunostain panel (CD3, CD4, CD8 and CD20) in order to distinguish pattern hair loss from alopecia aerate in cases which do not have the usual peribulbar lymphocytic infiltrate and showed that CD3+ T-lymphocytes within the empty fibrous follicular tracts favor a diagnosis of alopecia areata. We performed CD123 in order to distinguish lichen planopilaris from alopecia lupus erythematosus in cases with only a superficial lymphocytic infiltrate and an uninvolved interfollicular epidermis and showed that clusters of CD123+ plasmacytoid dendritic cells favor a diagnosis of lupus erythematosus. We performed cytokeratin 15 in order to assess whether the loss of the follicular bulge stem cells has diagnostic value in cicatricial alopecia and demonstrated that the loss of cytokeratin 15+ bulge stem cells is identified in lichen planopilaris, frontal fibrosing alopecia, and lupus erythematous, so cytokeratin 15 has no diagnostic value. We have attempted to integrate the new concepts and our findings into the traditional classifications of alopecia and proposed a new diagnostic algorithm. In conclusion, immunostaining combined with HoVert grossing advances the accuracy of histopathological diagnosis of primary scalp alopecia. / L’alopécie primitive du cuir chevelu est habituellement classée en cicatricielle et non-cicatricielle. Dans les cas difficiles, la biopsie du cuir chevelu peut aider au diagnostic. L’utilisation de coupes, à la fois verticales et horizontales sur le même spécimen (technique HoVert), a radicalement amélioré le diagnostic histopathologique. Dans ce travail, nous avons utilisé l’immunohistochimie pour évaluer les difficultés diagnostiques qui persistent malgré tous les outils actuels. Nous avons utilisé les CD3, CD4, CD8 et CD20 pour différencier l’alopécie androgénique de la pelade dépourvue de l’infiltrat lymphocytaire péribulbaire habituel et nous avons démontré que la présence de lymphocytes CD3+ dans les travées folliculaires fibreuses est en faveur de la pelade. Nous avons utilisé le CD123 pour différencier le lichen plan pilaire du lupus érythémateux alopécie avec infiltrat lymphocytaire superficiel et sans atteinte de l’épiderme interfolliculaire et nous avons démontré que la présence d’amas de cellules dendritiques plasmacytoïdes CD123+ est en faveur du lupus érythémateux. Nous avons utilisé la cytokératine 15 pour évaluer si la perte des cellules souches du bulge a une valeur diagnostique dans l’alopécie cicatricielle et nous avons démontré que cette perte s’observait de manière identique dans le lichen plan pilaire, l’alopécie frontale fibrosante comme dans le lupus érythémateux et n’avait donc aucune valeur diagnostique. Nous avons tenté d’intégrer les nouveaux concepts et nos données dans les classifications traditionnelles des alopécies et nous avons élaboré un nouvel algorithme diagnostique. L’association des immunomarquages avec la technique HoVert ouvre de nouvelles perspectives dans le diagnostic histopathologique des alopécies primaires du cuir chevelu. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished

Alopecia areata (AA) betyder fläckvis håravfall och uppstår vanligen på huvudet men även på kroppen. Det är en harmlös, reversibel, organ-specifik, autoimmun hudsjukdom som drabbar hårfolliklarna. Den autoimmuna reaktionen förmedlas av T-lymfocyter som angriper hårfolliklarna och hämmar hårväxt. Det årliga incidenstalet för både kvinnor och män är 20,2 per 100 000 personer och 1,7 % av befolkningen riskerar att drabbas någon gång under livet. Även om genetiskt anlag och miljöfaktorer, såsom emotionell stress, graviditet och tillfälliga infektioner kan utlösa sjukdomen så är den exakta orsaken fortfarande okänd. De behandlingar som finns mot AA påverkar inte den autoimmuna processen som orsakar alopecin utan syftet med dessa är att stimulera hårfolliklarna och dämpa sjukdomens aktivitet. Kortikosteroider används vid behandling mot AA, men kan ge svåra biverkningar vid långvarig behandling. De olika administrationsformer av kortikosteroider som används mot AA är främst lokala och systemiska, men även intralesionella. Målet med denna litteraturstudie var att undersöka om kortikosteroider har någon effekt mot AA. Samtliga studier visade att kortikosteroider har effekt mot AA, men att risken för återfall är stor. Tre av de fem studierna visade att behandlingen gav bättre resultat hos de patienterna med mindre svår AA, kort duration och första episoden av sjukdomen. Dåliga prognostiska faktorer visade sig vara omfattande AA, lång duration, atopi, nagelinvolvering och flera episoder av sjukdomen. En studie visade att patienter med plurifocal AA svarar bättre på behandlingen än patienter med ophiasic AA, AA totalis och AA universalis. I samtliga studier fick patienterna biverkningar av behandlingen med dessa var inte så allvarliga att patienterna fick avbryta behandlingen. Slutsatsen av detta arbete är att kortikosteroider har effekt mot AA, men att risken för återfall är stor. 2008:F3

Yes / This article is an editorial for the special focus theme issue on “hair research” published by the Experimental Dermatology journal. Here we introduce the articles from the special issue and pose a few questions. The full list of publications for the hair research special issue is available on the Journal’s web site. Many of the articles can be viewed free of charge on the web site. This is for; Experimental Dermatology, Volume 29, Number 3, published March 2020.

No description available.

Introduction: The hair follicle bulge has recently been added to a growing list of human tissue compartments that exhibit a complex combination of immunosuppressive mechanisms, termed immune privilege (IP), which appear to restrict immune mediated injury in specific locations. As epithelial hair follicle stem cells (eHFSC) reside in the hair follicle bulge region it is conceivable that these IP mechanisms protect this vital compartment from immune-mediated damage, thereby ensuring the ongoing growth and cyclic regeneration of the hair follicle. Lichen planopilaris (and variants) are inflammatory hair disorders that result in hair follicle destruction and permanent alopecia. Growing evidence suggests that eHFSC destruction is a key factor in the permanent follicle loss seen in these conditions, and that IP collapse may predispose these cells to immune mediated injury. Aims: The overall aim of this project was to generate immunohistomorphometric, gene profiling, and limited functional evidence to probe the 'bulge immune privilege collapse' hypothesis in a carefully selected model disease for inflammation-induced epithelial stem cell death, lichen planopilaris (LPP). Methods: Adult patients with LPP (or variant frontal fibrosing alopecia) were recruited. Biopsies from lesional and non-lesional scalp skin were performed and either snap frozen in liquid nitrogen, fixed in formalin for paraffin embedding or transferred immediately for hair follicle organ culture. Both frozen and paraffin embedded tissue was processed for immunohistochemistry (IHC) analysis using various immune privilege, hair bulge (eHFSC) and immune cell markers. Cultured samples were supplemented with various chemicals know to influence hair follicle immune privilege with analysis performed using IHC. Further, additional paired lesional and non-lesional samples were sectioned horizontally for laser capture microdissection of bulge cells. Following extraction of RNA, reverse transcription and amplification of cDNA from these selected bulge cells; gene expression profiling was performed comparing lesional with non-lesional samples. Selected, differentially regulated genes were validated using IHC and quantitative real-time PCR. Results: Bulge IP collapse is present in active LPP, as suggested by increased expression of MHC class I, β2microglobulin and MHC class II, along with reduced expression of the locally produced immunosuppressant TGFβ2, at both the gene and protein level. Microarray pathway analysis supports these data with the antigen processing canonical pathway being prominently enriched. Cell mediated immune responses are prominent in active disease, suggested by significantly increased numbers of activated and cytotoxic T-cells infiltrating the bulge epithelium, along with greater numbers of mast cells and macrophages in the peri-follicular connective tissue sheath. Bulge cell eHFSC loss is suggested by loss of bulge cell markers (e.g. keratin 15) on IHC, microarray and qPCR, and supported by microarray analysis showing virtually global loss of recognised bulge eHFSC signatures. Hair follicle organ culture experiments confirm bulge IP collapse in a separate cohort of patients, and demonstrate that the pro-inflammatory cytokine, interferon-γ can further collapse IP in the bulge epithelium of cultured hair follicles. Conclusion: These data identify collapse of immune privilege in bulge cells in active LPP, and identify prominent cell-mediated immune responses and loss of eHFSC signatures in active disease. The pro-inflammatory cytokine, interferon-γ also appears to play a prominent role in IP collapse and contributes to immune cell trafficking into affected tissue. Future study is required to ascertain triggering factors of IP collapse and pursue other identified candidates from gene expression analysis.