Journal Information
Vol. 98. Issue 8.
Pages 539-544 (October 2007)
Vol. 98. Issue 8.
Pages 539-544 (October 2007)
Original articles
Full text access
Analysis of Lymphocyte Populations in Psoriatic Plaques Following Inhibition of Tumor Necrosis Factor-α With Etanercept
Estudio de las Poblaciones Linfocitarias en las Lesiones de Psoriasis Tras el Bloqueo del Factor de Necrosis Tumoral Alfa con Etanercept
Visits
6103
L. Mahiquesa,
Corresponding author
laura_mahiques@aedv.es

Correspondence: Servicio de Dermatología. Hospital General Universitario de Valencia. Avda. Tres Cruces, s/n. 46014 Valencia. Spain.
, G. Pitarcha, J.L. Sánchez-Carazoa, A. Pérez-Ferriolsa, C.J. Sorianob, V. Alegrea
a Servicio de Dermatología, Hospital General Universitario de Valencia, Valencia, Spain
b Servicio de Cardiología, Hospital General Universitario de Valencia, Valencia, Spain
This item has received
Article information
Abstract
Introduction

Psoriasis is a disease with a strong immunological component in which there is a predominant T helper 1 cell-mediated immune response. Etanercept, a receptor for tumor necrosis factor a that blocks its action, is a new drug with proven efficacy in the treatment of psoriasis.

Objectives

The primary objective of this study was to assess the histological response to etanercept by analyzing the lymphocyte populations in psoriatic plaques. The secondary objectives were to assess the clinical response to the drug using the Psoriasis Area and Severity Index (PASI) and to analyze the effect of etanercept on peripheral blood lymphocyte populations.

Methods

Ten patients with plaque psoriasis and a PASI score greater than 10 were included in the study. A clinical assessment was performed in all patients along with a 4-mm skin punch biopsy of a plaque and analysis of peripheral blood lymphocyte populations at baseline and after 12 weeks of etanercept therapy at a dose of 50 mg per week.

Results

There was a significant reduction in different lymphocyte populations in the plaques following treatment with etanercept. The mean (SD) number of CD4+ T lymphocytes per microscopic field decreased from 16.93 (8.13) at baseline to 6.51 (3.46) after treatment with etanercept (P<007). CD8+ T lymphocytes also decreased from 17.73 (9.77) before treatment to 10.50 (9.4) after treatment (P<005). An overall improvement in PASI score was also observed: 33.30 (10.71) at baseline versus 15.20 (13.28) following treatment (P<008). Nine out of 10 patients showed improvement. No significant differences were observed in peripheral blood lymphocyte populations before and after treatment.

Conclusions

Etanercept leads to clinical improvement of psoriasis and reduces inflammatory infiltration of the lesions without affecting peripheral blood lymphocyte populations.

Key words:
psoriasis
lymphocytes
treatment
Resumen
Introducción

La psoriasis es una enfermedad de fuerte base inmune, con un predominio de respuesta inmune celular o Th1. Entre los nuevos fármacos que han demostrado eficacia está el etanercept, un receptor para el factor de necrosis tumoral alfa que bloquea su acción.

Objetivos

Como objetivos nos planteamos en primer lugar determinar la respuesta histológica a etanercept mediante la determinación de las poblaciones linfocitarias en las lesiones psoriásicas; y en segundo lugar, determinar la respuesta clínica al fármaco mediante el Psoriasis Area and Severity Index (PASI) y valorar el efecto de etanercept sobre las poblaciones linfocitarias en sangre.

Métodos

Tratamos 10 pacientes con psoriasis en placas con PASI > 10. Se les realizó una evaluación clínica, un punch de 4 mm en la placa y una determinación de poblaciones linfocitarias en sangre antes del comienzo y tras 12 semanas de tratamiento con etanercept 50 mg/semana.

Resultados

Hubo un descenso significativo en las distintas poblaciones linfocitarias de las lesiones tras el tratamiento con etanercept. Así, los linfocitos T CD4+ antes y después del tratamiento con etanercept registraron los siguientes valores: 16,93±8,13 y 6,51±3,46 (p<0,007), respectivamente. Y los linfocitos T CD8+ antes y después del tratamiento con etanercept registraron: 17,73±9,77 y 10,50±9,4 (p<0,005), respectivamente. El PASI mejoró globalmente tras 12 semanas de tratamiento. En un principio el PASI basal mostraba 33,30±10,71, y tras el tratamiento se registró 15,20±13,28, p<0,008. Nueve de los diez pacientes mejoraron y una paciente se mantuvo sin mejoría. No hubo diferencias significativas en las poblaciones linfocitarias sanguíneas antes y después del tratamiento.

Conclusiones

Etanercept es un fármaco que mejora clínicamente la psoriasis y disminuye la infiltración inflamatoria de las lesiones sin afectar a las poblaciones linfocitarias sanguíneas.

Palabras clave:
psoriasis
linfocitos
tratamiento
Full text is only aviable in PDF
References
[1]
B.J. Nickoloff, F.O. Nestle.
Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities.
J Clin Invest, 113 (2004), pp. 1664-1675
[2]
M.A. Lowes, W. Lew, J.G. Krueger.
Current concepts in the immunopathogenesis of psoriasis.
Dermatol Clin, 22 (2004), pp. 349-369
[3]
A.B. Gottlieb.
Psoriasis. Immunopathology and immunomodulation.
Dermatol Clin, 19 (2001), pp. 649-657
[4]
O. Boyman, H.P. Hefti, C. Conrad, B.J. Nickoloff, M. Suter, F.O. Nestle.
Spontaneous development of psoriasis in a new animal model shows an essential role for resident T cells and Tumor necrosis Factor-a.
J Exp Med, 199 (2004), pp. 731-736
[5]
L.M. Austin, T.R. Coven, N. Bhardwaj, R. Steinmann, J.G. Krueger.
Intraepidermal lymphocytes in psoriatic lesions are activated GMP-17(TIA-1) + CD8 + CD3 + CTLs as determined by phenotypic analysis.
J Cutan Pathol, 25 (1998), pp. 79-88
[6]
K. Ferenczi, L. Burack, M. Pope, J.G. Krueger, L.M. Austin.
CD69, HLA-DR and the IL-2R identify persistently activated T cells in psoriasis vulgaris lesional skin: blood and skin comparisons by flow cytometry.
J Autoimmun, 14 (2000), pp. 63-78
[7]
U. Chaudhari, P. Romano, L.D. Mulcahy, L.T. Dooley, D.G. Baker, A.B. Gottlieb.
Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomised trial.
Lancet, 357 (2001), pp. 1842-1847
[8]
P. Mease, B. Goffe, J. Metz, A. Van der Stoep, B. Finck, D.J. Burge.
Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial.
[9]
M.A. Magliocco, A.B. Gottlieb.
Etanercept therapy for patients with psoriatic arthritis and concurrent hepatitis C virus infection: Report of 3 cases.
J Am Acad Dermatol, 51 (2004), pp. 580-584
[10]
J.L. Estebaranz.
Etanercept. Estructura química, farmacocinética y mecanismo de acción.
Actas Dermosifiliogr, 96 (2005), pp. 2-9
[11]
A.M. Toby, B. Kirby.
TNF-a inhibitors in the treatment of psoriasis and psoriatic arthritis.
Biodrugs, 19 (2005), pp. 47-57
[12]
F. Capon, R.C. Trembath, J.N. Barker.
An update on the genetics of psoriasis.
Dermatol Clin, 22 (2004), pp. 339-347
[13]
S. Mehlis, K.B. Gordon.
From laboratory to clinic: rationale for biologic therapy.
Dermatol Clin, 22 (2004), pp. 371-377
[14]
B.J. Nickoloff, S.L. Kunkel, M. Burdick, R.M. Strieter.
Severe combined immunodeficiency mouse and human psoriatic skin chimeras: validation of a new animal model.
Am J Pathol, 146 (1995), pp. 580-588
[15]
A.B. Gottlieb, R.T. Matheson, N. Lowe, G.G. Krueger, S. Kang, B.S. Goffe, et al.
A randomized trial of etanercept as monotherapy for psoriasis.
Arch Dermatol, 139 (2003), pp. 1627-1632
[16]
A.B. Gottlieb, F. Chamian, S. Masud, I. Cardinale, M.V. Abello, M.A. Lowes, et al.
TNF inhibition rapidly down-regulates multiple proinflammatory pathways in psoriasis plaques.
J Immunol, 175 (2005), pp. 2721-2729
[17]
B.J. Nickoloff, T. Wrone-Smith.
Injection of pre-psoriatic skin with CD4+ T cells induces psoriasis.
Am J Pathol, 155 (1999), pp. 145-158
[18]
C.L. Leonardi, J.L. Powers, R.T. Matheson, B.S. Goffe, R. Zitnik, A. Wang, et al.
Etanercept as monotherapy in patients with psoriasis.
N Engl J Med, 349 (2003), pp. 2014-2022
[19]
M. Debandt, O. Vittecoq, V. Descamps, X. Le Loet, O. Meyer.
Anti-TNF-alpha-induced systemic lupus syndrome.
Clin Rheumatol, 22 (2003), pp. 56-61
[20]
G.G. Krueger, B. Elewski, K. Papp, A. Wang, R. Zitnik, A. Jahreis.
Patients with psoriasis respond to continuous open-label etanercept treatment after initial incomplete response in a randomized, placebo-controlled trial.
J Am Acad Dermatol, 543 (2006), pp. S112-S119
[21]
A. Mastroianni, E. Minutilli, A. Mussi, V. Bordignon, E. Trento, G. D’Agosto, et al.
Cytokine profiles during infliximab monotherapy in psoriatic arthritis.
Br J Dermatol, 153 (2005), pp. 531-536
[22]
M. Tigalonova, J.R. Bjerke, H. Gallati, M. Degré, S. Jablonska, S. Majewski, et al.
Serum levels of interferons and TNF-alpha are not correlated to psoriasis activity and therapy.
Acta Derm Venereol Suppl (Stochk), 186 (1994), pp. 25-27
Copyright © 2007. Academia Española de Dermatología y Venereología and Elsevier España, S.L.
Download PDF
Idiomas
Actas Dermo-Sifiliográficas
Article options
Tools
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?