Fumaric acid esters suppress peripheral CD4- and CD8-positive lymphocytes in psoriasis.
BACKGROUND
For severe forms of psoriasis vulgaris, the antipsoriatic fumaric acid esters (FAE) therapy has recently gained increasing acceptance and importance. Until today, there is little knowledge about the mode of action of FAE. However, some evidence exists indicating immunosuppressive effects.


OBJECTIVE
The aim of this study was to examine the systemic, particularly the immunological changes in patients suffering from psoriasis treated with FAE over a long period of time, since we expect to see pharmacological effects of FAE at this point.


METHODS
This study is based on continuously recorded clinical data and laboratory parameters of 10 patients, who were treated over a period of 12 months with FAE. A quantitative analysis of lymphocytes and their subtypes was carried out by means of flowcytometric methods.


RESULTS
3 months after starting treatment with FAE, a clinical effect with a remission index > 95% was achieved in all 10 patients examined. This remained constant until the end of this study. Focusing on leukopenia, and particularly on lymphopenia as important parameters, these effects were found in all patients. The lymphocyte subpopulations data demonstrated extensive proportionate reductions. Within the T cell fraction a stronger suppression of CD8+ lymphocytes was observed.


CONCLUSIONS
Our investigations of systemic effects of fumaric acid esters demonstrate the suppressive character of this medication. Effects of cell count reduction in leukocyte and lymphocyte numbers over the entire period of 12 months could be observed. The lymphocytic cell count number is obviously linked to the clinical effect.
Höxtermann
S
S
Department of Dermatology, Ruhr-University, Bochum, Germany. stefan.m.hoextermann@rz.ruhr-uni-bochum.de
Nüchel
C
C
Altmeyer
P
P
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000187:drug effects / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000187:drug effects / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects; D001772:Blood Cell Count / Q000187:drug effects; D016516:CD4-CD8 Ratio / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects*; D003404:Creatinine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D005650:Fumarates / Q000008:administration & dosage / Q000627:therapeutic use*; D006684:HLA-DR Antigens / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D018655:Lymphocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D011565:Psoriasis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014508:Urea / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000187:drug effects / Q000378:metabolism
D005650:Fumarates; D006684:HLA-DR Antigens; D015375:Receptors, Interleukin-2; D014508:Urea; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase