title: Dimethylfumarate for psoriasis: Pronounced effects on lesional T-cell subsets, epidermal proliferation and differentiation, but not on natural killer T cells in immunohistochemical study.
abstract: BACKGROUND
  T-cell infiltration, epidermal hyperproliferation, and disturbed keratinization are pathologic hallmarks of plaque psoriasis. Oral fumaric acid esters are an effective therapy for psoriasis and are believed to exert their effects mainly through their anti-inflammatory properties.
  
  
  OBJECTIVE
  To investigate the differential effects of dimethylfumarate (BG-12; FAG-201) for psoriasis on lesional T-cell subsets, natural killer (NK) T cells, and keratinocyte hyperproliferation and differentiation.
  
  
  METHODS
  A before-and-after clinical and immunohistochemical study as part of a larger clinical trial.
  
  
  METHODS
  Single outpatient clinic.
  
  
  METHODS
  Six patients with moderate-to-severe psoriasis.
  
  
  METHODS
  Dimethylfumarate 720 mg daily for 16 weeks.
  
  
  METHODS
  Biopsies were taken from the lesional skin of six psoriatic patients, at baseline and after 16 weeks of treatment with dimethylfumarate. Clinical severity scores were obtained (Psoriasis Area Severity Index [PASI] and psoriasis severity SUM scores). T-cell subsets (CD4+, CD8+, CD45RO+, CD45RA+, CD2+, CD25+), cells expressing NK receptors (CD94, CD161), an epidermal proliferation marker (Ki67), and a keratinization marker (K10) were immunohistochemically stained and, together with 'epidermal thickness,' quantified using image analysis.
  
  
  RESULTS
  At week 16, the mean PASI and SUM scores were reduced by 55% (p < 0.01) and 49% (p < 0.01), respectively. In line with these results, epidermal hyperproliferation, keratinocyte differentiation, and epidermal thickness significantly improved. In the dermis and the epidermis, the relevant T-cell subsets significantly declined. However, in both the lesional psoriatic dermis and epidermis, cells expressing NK receptors (CD94 and CD161) persisted after 16 weeks of treatment.
  
  
  CONCLUSIONS
  Dimethylfumarate is an effective therapy for moderate-to-severe plaque psoriasis. The drug may act by reducing lesional T-cell subsets and normalizing epidermal hyperproliferation and keratinization, but does not reduce NKT cells.
authors.affiliation: Department of Dermatology, Radboud University Nijmegen Medical Centre, the Netherlands. j.bovenschen@derma.umcn.nl
authors.forename: H Jorn
authors.initials: HJ
authors.lastname: Bovenschen
authors.forename: Annechien M G
authors.initials: AM
authors.lastname: Langewouters
authors.forename: Peter C M
authors.initials: PC
authors.lastname: van de Kerkhof
mesh_terms: D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003879:Dermatologic Agents / Q000627:therapeutic use*; D020405:Dermis / Q000276:immunology / Q000473:pathology; D000069462:Dimethyl Fumarate; D004817:Epidermis / Q000276:immunology / Q000473:pathology; D005260:Female; D005650:Fumarates / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000187:drug effects*; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000187:drug effects
chemical_list: D003879:Dermatologic Agents; D005650:Fumarates; D007166:Immunosuppressive Agents; D000069462:Dimethyl Fumarate