Skatrisyel alopesi olgularında pilosebase folikül kök hüçrelerinin durumu ve T lenfosit infiltrasyonu alt tiplerinin değerlendirilmesi
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Tarih
2016
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Yayıncı
Ege Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Sikatrisyel alopesiler etiyolojisi ve patogenezi henüz net aydınlatılamamış kronik, inflamatuvar bir hastalık grubudur. Kıl folikülü primer sikatrisyel alopesilerde (PSA) otoagresif immunitenin primer hedefi olarak bilinmektedir. Kıl folikülü kök hücrelerinin (KFKH) geri dönüşümsüz harabiyetinin genellikle inflamatuvar mekanizmalar sonucunda gerçekleştiği düşünülmektedir. Patogenezde birçok mekanizma suçlanmıştır. Bunlardan en çok göze çarpanı inflamasyon ve kök hücre harabiyetidir.
Çalışmamızda PSA’larda pilosebase foliküldeki kök hücrelerin varlığı, hastalık ilişkili inflamatuvar infiltratın tipinin belirlenmesi, varsa aralarındaki ilişkinin araştırılması amaçlanmıştır.
2007-2015 yılları arasında Ege Üniversitesi Tıp Fakültesi Deri ve Zührevi Hastalıkları ve Patoloji Anabilim Dalı’nda tanı alan 26 liken pilanopilaris (LPP), 15 diskoid lupus eritematozus (DLE), 7 (Brocq’un psödopeladı) BP olmak üzere toplam 48 PSA olgusu ve 9 normal saçlı deri örneği kontrol grubu olarak çalışmaya alındı. Hastalar dermatolojik ve histopatolojik olarak değerlendirildi. Dermatolojik muayenede olguların alopesik alanları, lokalizasyonu, skar varlığı, PSA alt tipi tanısına yönelik atrofi, eritem, skuam, püstül, perifoliküler hiperkeratoz, perifoliküler papüllerin varlığı değerlendirildi. Patolojik değerlendirmede ise tüm hastaların hematoksilen&eozin (H&E) boyali preparatları fibrozis, inflamasyon, folikültropizm açısından incelenirken ayrıca her olguya sitokeratin-15 (CK-15), CD34, nestin, CD4 ve CD8 immun boyama yapılarak immunhistokimyasal (İHK) olarak da değerlendirildi.
PSA’larda klinik olarak gözlenen ana bulgu skatris, alopesik odaklar iken, LPP’de perifoliküler likenoid papüller ve hiperkeratoz; DLE’de eritem, skuam, atrofi; BP’de ise değişik paternlerde gözlenen atrofik yamalar izlendi. PSA’larda histopatolojik olarak gözlenen ana bulgu sebase atrofi, perifoliküler yangısal infiltrasyon ve kıl folikülü harabiyeti idi. Dermoepidermal hasar bulgularından bazal membran kalınlaşması DLE’li olgularda, foliküler dilatasyon ve multinükleer dev hücre varlığı da LPP’li olgularda daha sık gözlendi. Perifoliküler inflamasyon DLE tanılı olgularda, LPP ve BP tanılı gruplara göre belirgin olarak daha yoğun izlendi. Perifoliküler yerleşimli infiltrasyon PSA alt tiplerinde en yoğundan en hafife sırasıyla DLE, LPP, BP şeklinde sıralandı.
Kök hücre belirteçleri olan CK-15, CD34 ve nestin pozitif hücreler folikülün farklı bölgelerinde gözlendi. Hastaların %89,6’sında CK-15 kaybı izlendi, CK-15 tam kaybı gözlenen hastalarda belirgin inflamasyon ve minimal fibrozis izlendi. CK-15’in DLE’de diğer PSA alt tipleri ve kontrol gruba göre hem epidermal hem foliküler bölgede kayıp olması anlamlı bulundu.
Sikatrisyel alopesilerin patogenezi ve kök hücre kaybı ile ilişkisi karmaşık bir süreçtir. Kök hücre harabiyetinin belirgin olduğu olgularda inflamatuvar infiltratın yoğun olması bu düşünceyi desteklemektedir. Yine de bu hastalık grubunun patofizyolojisinin daha net anlaşılabilmesi, patogenezde kök hücrelerin rolünü tanımlanabilmesi ve tedavide yeni, etkili terapötik ajanların geliştirilebilmesi için daha geniş kapsamlı çalışmalara ihtiyaç vardır.
Scarring alopecias are a group of chronic, inflammatory diseases and their etiology and pathogenesis are not clearly identified. The hair follicle is the primary target of the auto-agressive immunity in primary scarring alopecias (PSA). The irreversible injury of the hair follicle stem cells is thought to have occurred usually as a result of inflammatory mechanisms. Several mechanisms have been implicated in the pathogenesis. The most prominent of those are inflammation and stem cell injury. In our study, we aimed to investigate the presence of stem cells in the pilosebaceous follicle in PSAs, to determine the type of disease associated inflammatory infiltrate and if any, the relationship between them. A total of 48 PSA cases consisting of 26 LPPs, 15 DLEs and 7 BPs that were diagnosed in Ege University Medical School Departments of Dermatology and Pathology between the years 2007 and 2015 and 9 normal scalp samples as the control group were included in the study. The patients were evaluated both dermatologically and histopathologically. In dermatologic examination, the alopecic areas, their localization, presence of scarring, and the presence of atrophy, erythema, scale, pustula, perifollicular hyperkeratosis and perifollicular papules for the PSA diagnostic subtype were evaluated. In the pathological examination, the hematoxylin-eosin stained slides of all the patients were examined in terms of fibrosis, inflammation and follicle tropism and every case was also evaluated immunohistochemically with the immun stains of CK-15, CD34, Nestin, CD4 and CD8. The main clinical findings observed in PSAs were scarring and alopecic areas, whereas they were perifollicular lichenoid papules and hyperkeratosis in lichen planopilaris (LPP); erythema, scaling, atrophy in discoid lupus erythematosus (DLE) and atrophic patches seen in different patterns in pseudopelade of Brocq (BP). The main histopathologic findings observed in PSAs were sebaceous atrophy, perifollicular inflammatory infiltration and hair follicle injury. The basement membrane thickening which is one of the findings of dermoepidermal injury was observed more in cases with DLE and folicular dilatation and the presence of multinucleated giant cells were observed more in cases with LPP. Perifolicular inflammation was observed more intensely in cases with DLE rather than in cases with LPP and BP. The perifollicular localized infiltration from the most intense to the mildest in PSA subtypes was listed as DLE, LPP, BP, respectively. The cells that are positive with the stem cell markers which are CK-15, CD34 and nestin were observed in different regions of the follicle. CK-15 loss was observed in 89,6% of the patients. Prominent inflammation and minimal fibrosis were observed in patients who had total loss of CK-15. The loss of CK-15 in both epidermal and follicular areas in DLE rather than in other PSA subtypes and the control group was found to be significant. The pathogenesis of scarring alopecias and the relationship with the loss of stem cells are complicated processes. The intense inflammatory infiltrate in cases with prominent stem cell injury supports this idea. However, more extensive studies are needed in order to understand the pathophysiology of this disease group more clearly, to identify the role of the stem cells in the pathogenesis and to develop new and effective therapeutic agents in treatment.
Scarring alopecias are a group of chronic, inflammatory diseases and their etiology and pathogenesis are not clearly identified. The hair follicle is the primary target of the auto-agressive immunity in primary scarring alopecias (PSA). The irreversible injury of the hair follicle stem cells is thought to have occurred usually as a result of inflammatory mechanisms. Several mechanisms have been implicated in the pathogenesis. The most prominent of those are inflammation and stem cell injury. In our study, we aimed to investigate the presence of stem cells in the pilosebaceous follicle in PSAs, to determine the type of disease associated inflammatory infiltrate and if any, the relationship between them. A total of 48 PSA cases consisting of 26 LPPs, 15 DLEs and 7 BPs that were diagnosed in Ege University Medical School Departments of Dermatology and Pathology between the years 2007 and 2015 and 9 normal scalp samples as the control group were included in the study. The patients were evaluated both dermatologically and histopathologically. In dermatologic examination, the alopecic areas, their localization, presence of scarring, and the presence of atrophy, erythema, scale, pustula, perifollicular hyperkeratosis and perifollicular papules for the PSA diagnostic subtype were evaluated. In the pathological examination, the hematoxylin-eosin stained slides of all the patients were examined in terms of fibrosis, inflammation and follicle tropism and every case was also evaluated immunohistochemically with the immun stains of CK-15, CD34, Nestin, CD4 and CD8. The main clinical findings observed in PSAs were scarring and alopecic areas, whereas they were perifollicular lichenoid papules and hyperkeratosis in lichen planopilaris (LPP); erythema, scaling, atrophy in discoid lupus erythematosus (DLE) and atrophic patches seen in different patterns in pseudopelade of Brocq (BP). The main histopathologic findings observed in PSAs were sebaceous atrophy, perifollicular inflammatory infiltration and hair follicle injury. The basement membrane thickening which is one of the findings of dermoepidermal injury was observed more in cases with DLE and folicular dilatation and the presence of multinucleated giant cells were observed more in cases with LPP. Perifolicular inflammation was observed more intensely in cases with DLE rather than in cases with LPP and BP. The perifollicular localized infiltration from the most intense to the mildest in PSA subtypes was listed as DLE, LPP, BP, respectively. The cells that are positive with the stem cell markers which are CK-15, CD34 and nestin were observed in different regions of the follicle. CK-15 loss was observed in 89,6% of the patients. Prominent inflammation and minimal fibrosis were observed in patients who had total loss of CK-15. The loss of CK-15 in both epidermal and follicular areas in DLE rather than in other PSA subtypes and the control group was found to be significant. The pathogenesis of scarring alopecias and the relationship with the loss of stem cells are complicated processes. The intense inflammatory infiltrate in cases with prominent stem cell injury supports this idea. However, more extensive studies are needed in order to understand the pathophysiology of this disease group more clearly, to identify the role of the stem cells in the pathogenesis and to develop new and effective therapeutic agents in treatment.
Açıklama
Anahtar Kelimeler
Sikatisyel Alopesi, Kök Hücre, Inflamasyon, Cicatricial Alopecia, Stem Cell, Inflamation
