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INVESTIGATIVE REPORT ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
Inflammasome Activation Characterizes Lesional Skin of Folliculitis Decalvans
Alexia EYRAUD , Brigitte MILPIED , Denis THIOLAT , Anne-Sophie DARRIGADE , Katia BONIFACE , Alain TAIEB and Julien SENESCHAL Department of Dermatology and Pediatric Dermatology , National Centre for Rare Skin Disorders , Hôpital Saint-André , Bordeaux , France
Folliculitis decalvans ( FD ) is a chronic inflammatory disease leading to scarring alopecia with poorly defined pathogenesis . The aim of this study was to investigate the expression of markers associated with the activation of innate immune signals , such as inflammasome ( NALP1 and NALP3 ), interleukin ( IL ) -1β and IL-8 and type I interferon ( MxA ). A retrospective monocentric study was conducted and included 17 patients with FD with available biopsies . Disease activity ( stable vs . active ) was defined clinically and histologically . Immunostaining was performed using antibodies directed against NALP1 , NALP3 , IL-1β , IL-8 , and MxA on FD skin biopsies . Results were compared with normal controls and lichen planopilaris . Eleven patients had active disease and 6 had stable disease . NALP1 , NALP3 , and IL-1β expression were significantly increased in hair follicles in FD compared with controls and lichen planopilaris . This study highlights the predominant immune signal associated with inflammasome activation in FD , suggesting the use of IL-1β blockade in FD .
Key words : folliculitis decalvans ; cicatricial alopecia ; inflammasome activation ; treatment ; immunomodulating therapy .
Accepted Mar 15 , 2018 ; Epub ahead of print Mar 15 , 2018 Acta Derm Venereol 2018 ; 98 : 570 – 575 .
Corr : Julien Seneschal , Department of Dermatology and Pediatric Dermatology , National Centre for Rare Skin Disorders , Hôpital Saint-André , 1 rue Jean Burguet , FR-33075 Bordeaux Cedex , France . E-mail : julien . seneschal @ chu-bordeaux . fr
SIGNIFICANCE
Folliculitis decalvans ( FD ) is a rare chronic inflammatory disease leading to scarring alopecia and major impact on patients ’ quality of life . To date , FD could be seen as a near orphan disease because of the lack of effective therapies . Our study highlights the role of innate immune response involving the inflammasome and the Il-1β signalling pathway in FD supporting the potential use of IL-1β blockade therapies in FD .
Folliculitis decalvans ( FD ) is a chronic inflammatory disease leading to primary cicatricial alopecia , with a long-standing course . FD is difficult to treat . It is the second cause of cicatricial alopecia after lichen planopilaris ( 1 ). This condition , occurring in middle-aged adults , is characterized by the development of alopecic patches with slowly centrifugal spread , predominantly in the vertex and occipital area of the scalp . FD is associated with recurrent perifollicular erythema , follicular pustules and haemorrhagic crusts , leading to discomfort , pain and pruritus ( 1 – 3 ). Understandably , the result is reduced self-esteem and psychological effects impacting patients ’ quality of life ( 4 ). Histological findings include a dense perifollicular neutrophilic infiltrate , affecting the upper and middle part of the follicle in the acute phase of the disease , evolving to a lympho-plasmocytic nature extending to the advential dermis , with psoriasiform epidermal hyperplasia , deep follicular microcysts , polytrichia , disappearance of the sebaceous glands and dermal fibrosis in the late-stage ( 1 , 5 ).
The pathogenesis of FD is unknown . Early studies evaluated the role of the microbiota in the pathogenesis of FD . In 1999 , Powell et al . ( 2 ) hypothesized that FD could be the result of an abnormal response to toxins released from a straightforward infection with Staphylococcus aureus , with no defect in the T- or B-cell responses . The crucial role of bacterial biofilms , which can be present in the anaerobic part of the hair follicle , was suspected ( 6 ). On the other hand , antibacterial treatments have only a suspensive efficiency and several observations described improvement under immunomodulating treat ments ( 7 – 9 ). Paradoxically , inflammatory pathways implicated in this condition remain unknown . The implication of inflammasome has already been demonstrated in keratinocytes and neutrophil-rich dermatitis ( 10 ). Thus , the presence of a neutrophilic infiltrate in FD skin , suggest a role of inflammasome in FD ( which could be a consequence of microbiota dysbiosis ), as has been demonstrated in other diseases , such as psoriasis or hidradenitis suppurativa ( HS ) ( 10 ).
Inflammasome is part of innate immunity and is activated under infectious trigger or stress , leading to the production of pro-inflammatory cytokines , such as IL-1β ( 11 ). Although previous studies have suggested a role of inflammation and microbiota in FD , no clear evaluation of the innate immune component has been performed . The aim of this study was to analyse , in skin lesions of stable and active FD , the presence and intensity of markers associated with the inflammasome : NALP1 , NALP3 , IL-1β , and the expression of IL-8 , a cytokine induced in response to IL-1β , leading to the recruitment of neutrophils . doi : 10.2340 / 00015555-2924 Acta Derm Venereol 2018 ; 98 : 570 – 575
This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2018 Acta Dermato-Venereologica .