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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.