Histologie de la peau et des follicules pileux

La peau est complexe, morphologiquement et biochimiquement. Le défi de ces dernières années a été de localiser précisément ses molécules de structure. Dans cet article, l’histologie normale de la peau et des follicules pilo-sébacés est brièvement décrite avec une iconographie en microscopies optique et électronique, afin de mieux comprendre où sont situées les molécules jouant un rôle clé dans la cohésion et la différenciation de l’épiderme, la mélanogenèse, la présentation des antigènes aux lymphocytes T, l’adhérence dermo-épidermique, la résistance et l’élasticité du derme et de l’hypoderme et, enfin, le renouvellement des follicules pileux. Les données présentées ont été établies par la confrontation d’études en peau normale, sur des souris invalidées et chez des patients souffrant de pathologies auto-immunes ou de génodermatoses. L’histologie moléculaire de la peau éclaire sous un autre jour la physiologie de la peau ; elle doit être connue pour valider les essais de thérapie génique ou cellulaire.The skin consists of an outer epidermis, the dermis, and the hypodermis. It includes nerves, blood vessels, glands and hair follicles. Epidermis is a continually renewing, stratified squamous epithelium. It is populated by keratinocytes (80 %) and dendritic cells (20 %) : melanocytes, Langerhans and Merkel cells. In standard histology, keratinocytes are arranged in layers that represent different stages of their differentiation while melanocytes and Langerhans cells appear as clear cells respectively between the basal and the supra-basal cells of epidermis. The Merkel cells cannot be clearly identified. Dendritic processes of the dendritic cells can only be recognized by immunocytochemistry. At the dermal-epidermal junction, a PAS reactive basement membrane follows the contour of the basal cells. Dermis consists of collagenous and elastic fibers embedded into an amorphous ground substance. Fibroblasts, macrophages, mast cells and lymphocytes are its resident cells. Hypodermis is composed of adipocyte lobules defined by fibrous connective tissue septa. Hair follicle consists of 3 parts : the lower portion, from the base of the follicle including hair bulb to the insertion of the arrector pili muscle or buldge ; the isthmus, from the insertion of the arrector pili to the entrance of the sebaceous duct, and the infundibulum, from the entrance of the sebaceous duct to the follicular orifice. The lower portion is composed of the dermal hair papilla, the hair matrix, the hair, and the inner and the outer root sheaths. The hair matrix cells within hair bulb give rise to the hair and to the inner root sheath. With the electron microscope, one can obtain a more detailed view of the characteristic skin structures. Much of them can now be explained in terms of function and in many instances, in correlation with its biochemical composition. An attempt has been made in this paper to precisely give the location of molecules that are relevant in basic skin functions and understanding of auto-immune and genetic diseases

Epidermolysis Bullosa Acquisita: The 2019 Update

Epidermolysis bullosa acquisita (EBA) is an orphan autoimmune disease. Patients with EBA suffer from chronic inflammation as well as blistering and scarring of the skin and mucous membranes. Current treatment options rely on non-specific immunosuppression, which in many cases, does not lead to a remission of treatment. Hence, novel treatment options are urgently needed for the care of EBA patients. During the past decade, decisive clinical observations, and frequent use of pre-clinical model systems have tremendously increased our understanding of EBA pathogenesis. Herein, we review all of the aspects of EBA, starting with a detailed description of epidemiology, clinical presentation, diagnosis, and current treatment options. Of note, pattern analysis via direct immunofluorescence microscopy of a perilesional skin lesion and novel serological test systems have significantly facilitated diagnosis of the disease. Next, a state-of the art review of the current understanding of EBA pathogenesis, emerging treatments and future perspectives is provided. Based on pre-clinical model systems, cytokines and kinases are among the most promising therapeutic targets, whereas high doses of IgG (IVIG) and the anti-CD20 antibody rituximab are among the most promising “established” EBA therapeutics. We also aim to raise awareness of EBA, as well as initiate basic and clinical research in this field, to further improve the already improved but still unsatisfactory conditions for those diagnosed with this condition

Surreprésentation des épidermolyses bulleuses acquises chez les patients de peau noire porteurs de l' allele HLA-DRB1*15:03

L épidermolyse bulleuse acquise (EBA) est une maladie bulleuse auto-immune (MBAI) se présentant sous diverses formes cliniques. Son incidence est faible et peu de séries ont été rapportées. Néanmoins, l existence d une incidence élevée d EBA et une prédisposition génétique impliquant un haplotype HLA (human leukocytes antigen) ont été suspectées dans certaines populations. Cette étude rétrospective évalue la surreprésentation des patients noirs atteints d EBA, leur caractéristiques cliniques, immunologiques et l existence d un lien avec le HLA-DRB1*15:03. Entre 2005 et 2009, 54% de patients avec EBA et 3% de patients atteints d une autre MBAI, vus successivement dans notre centre, étaient noirs (p=10-6). De même, entre 1983 et 2005, 12 patients de peau noire avaient un diagnostic d EBA. Parmi les 19 patients noirs atteints d EBA, la majorité présentait une forme clinique atypique. Ils se distinguaient également des descriptions classiques par leur jeune âge, la faible association à une maladie de Crohn, la gravité de leur pronostic et l importance du préjudice esthétique secondaire aux lésions. Neuf étaient originaires d Afrique sub-saharienne, 1 de la Réunion, 7 des Antilles et 2 avaient une origine mixte. La fréquence de l allèle HLA-DRB1*15:03, était de 50% pour les patients africains, significativement plus élevée que la population contrôle (p<10-3), et de 21% pour les antillais (non significatif). Une fréquence élevée d EBA avait déjà été rapportée chez des patients afro-américains, significativement associé au HLA-DR2. En conclusion, les patients noirs développant une EBA semblent avoir une prédisposition génétique, et l EBA devrait systématiquement être évoquée devant le diagnostic de MBAI dans cette population.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Erythème polymorphe récidivant à prédominance buccale

PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Mucous Membrane Pemphigoid, Bullous Pemphigoid, and Anti-programmed Death-1/ Programmed Death-Ligand 1: A Case Report of an Elderly Woman With Mucous Membrane Pemphigoid Developing After Pembrolizumab Therapy for Metastatic Melanoma and Review of the Literature

An 83-year-old patient developed erosions and a blister of the gingival mucous membrane, 6 months after discontinuation of the anti-programmed death-1 (anti PD-1) pembrolizumab therapy administered for 10 months for a metastatic melanoma. A diagnosis of mild mucous membrane pemphigoid (MMP) was made. Complete remission of MMP was rapidly obtained with minimal therapy (doxycycline). MMP remained in complete remission after a 3-month follow-up since discontinuation of the doxycycline therapy and no evidence of relapse of the melanoma was observed after a 14-month follow-up since discontinuation of the pembrolizumab therapy. The widespread use of anti PD-1 and anti-programmed death-ligand-1 (PD-L1) in several malignancies reveals new adverse events. MMP describes a group of chronic, inflammatory, mucous membrane-predominant, subepithelial auto-immune blistering diseases. It is clinically distinct from bullous pemphigoid another autoimmune blistering disease but shares some immunological similarities with it. Twenty-nine cases of bullous pemphigoid associated with anti PD-1/PD-L1 have been reported in the literature and one of MMP. Here, we described the case of a MMP developed after pembrolizumab and discussed the accountability of anti PD-1/PD-L1 in our case and the previous reported bullous pemphigoid and MMP cases using the Begaud system scoring

Gliptin Accountability in Mucous Membrane Pemphigoid Induction in 24 Out of 313 Patients

Mucous membrane pemphigoids (MMPs) and bullous pemphigoid (BP) are autoimmune bullous diseases that share physiopathological features: both can result from autoantibodies directed against BP180 or BP230 antigens. An association has been reported between BP and intake of gliptins, which are dipeptidyl peptidase-IV inhibitors used to treat type 2 diabetes mellitus. Clinical and immunological differences have been reported between gliptin-induced BPs and classical BPs: mucosal involvement, non-inflammatory lesions, and target BP180 epitopes other than the NC16A domain. Those findings accorded gliptins extrinsic accountability in triggering MMP onset. Therefore, we examined gliptin intrinsic accountability in a cohort of 313 MMP patients. To do so, we (1) identified MMP patients with gliptin-treated (challenge) diabetes; (2) selected those whose interval between starting gliptin and MMP onset was suggestive or compatible with gliptin-induced MMP; (3) compared the follow-ups of patients who did not stop (no dechallenge), stopped (dechallenge) or repeated gliptin intake (rechallenge); (4) compared the clinical and immunological characteristics of suggestive-or-compatible-challenge patients to 121 never-gliptin-treated MMP patients serving as controls; and (5) individually scored gliptin accountability as the trigger of each patient’s MMP using the World Health Organization-Uppsala Monitoring Center, Naranjo- and Begaud-scoring systems. 17 out of 24 gliptin-treated diabetic MMP patients had suggestive (≤12 weeks) or compatible challenges. Complete remission at 1 year of follow-up was more frequent in the 11 dechallenged patients. One rechallenged patient’s MMP relapsed. These 17 gliptin-treated diabetic MMP patients differed significantly from the MMP controls by more cutaneous, less buccal, and less severe involvements and no direct immunofluorescence IgA labeling of the basement membrane zone. Multiple autoantibody-target antigens/epitopes (BP180–NC16A, BP180 mid- and C-terminal parts, integrin α6β4) could be detected, but not laminin 332. Last, among the 24 gliptin-treated diabetic MMP patients, five had high (I4–I3), 12 had low (I2-I1) and 7 had I0 Begaud intrinsic accountability scores. These results strongly suggest that gliptins are probably responsible for some MMPs. Consequently, gliptins should immediately be discontinued for patients with a positive accountability score. Moreover, pharmacovigilance centers should be notified of these events

Calcinosis cutis: A rare reaction to subcutaneous injections of calcium-containing heparin in patients with renal failure

Calcinosis of the cutis and the subcutis is a rare complication of calcium-containing heparin cutaneous injections, mostly occurring in a context of severe renal failure. We report 2 cases. The first patient developed firm erythematous nodules on his thighs and right arm, in a context of disseminated tuberculosis and acute severe renal failure related to human immunodeficiency virus nephropathy. Cutaneous location of tuberculosis was suspected. Histological features allowed to establish the diagnosis of calcinosis of the cutis and the subcutis, showing violaceous and crackled von Kossa-positive calcium deposits in the whole reticular dermis and in thin collagenous septa of subcutaneous tissue. A retrospective inquiry confirmed that subcutaneous injections of calcium-containing heparin had been performed on the sites where lesions occurred. The second patient developed similar lesions at injection sites of calcium-containing heparin, in a context of non-Hodgkin lymphoma and end-stage renal failure. Similar histological features were observed. Calcinosis of the cutis and the subcutis after subcutaneous injections of calcium-containing heparin is rare. It always occurs in a context of elevated calcium-phosphate product, a situation mostly encountered in severe renal failure. Early cutaneous lesions do not bear specific clinical features