RESUMEN
BACKGROUND: Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially life-threatening autoimmune blistering diseases. Treatment is based on long-term immunosuppression with high doses of glucocorticosteroids in combination with potentially corticosteroid-sparing agents and/or rituximab. Immunoadsorption (IA) has emerged as a fast-acting adjuvant treatment option. OBJECTIVES: To assess the clinical efficacy of IA in addition to best medical treatment (BMT). METHODS: We conducted a multicentre (26 centres from Germany and Austria) randomized controlled trial in 72 patients with newly diagnosed, relapsed or chronic active PV or PF (34 female patients and 38 male patients, aged 42-72â years) comparing BMT (prednisolone 1.0â mg kg-1 per day plus azathioprine or mycophenolate) with adjuvant IA (BMT + IA). Central 1 : 1 randomization was done at the coordinating centre for clinical trials (KKS Marburg). The primary endpoint was analysed using Kaplan-Meier and Cox regression methods. RESULTS: The study was ended prematurely owing to safety concerns after random allocation of 72 patients to BMT + IA (n = 34) or BMT (n = 38). The primary endpoint, time to complete remission on therapy, was not significantly different for the two groups [hazard ratio (HR) 1.35, 95% confidence interval (CI) 0.68-2.69; P = 0.39]. The cumulative dose of prednisolone was significantly lower in the BMT + IA group compared with BMT alone (difference -1214, 95% CI -2225 to -70; P = 0.03). In a post hoc analysis, patients with more extensive PV/PF showed a tendency towards a shorter time to remission in the BMT + IA group compared with the BMT group (HR 1.87, P = 0.17 in patients with baseline Pemphigus Disease Area Index ≥ 15). While more adverse events were observed in patients in the BMT group (29 vs. 25), severe adverse events were more frequent in patients in the BMT + IA group (17 events in 10 patients vs. 11 events in 8 patients). CONCLUSIONS: In this study, adjuvant IA did not demonstrate a shorter time to clinical remission, but a corticosteroid-sparing effect was observed. In patients with extensive PV/PF, post hoc analysis suggests that adjuvant IA may lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits.
Pemphigus vulgaris and pemphigus foliaceus are potentially life-threatening autoantibody-driven blistering diseases, which present with erosions or blisters on skin and/or mucous membranes. Treatment is based on long-term immunosuppressive agents. Immunoadsorption (IA) is a procedure that removes autoantibodies from the blood and has emerged as a fast-acting treatment option for pemphigus.We conducted a trial comparing best medical treatment (BMT) (prednisolone 1.0 mg kg per day plus azathioprine or mycophenolate) with best medical treatment plus IA (BMT + IA). A total of 26 centres from Germany and Austria recruited 72 patients with active pemphigus (34 women and 38 men, aged 4272 years) who were randomly allocated in a ratio of 1 : 1 to the treatment groups.Following inclusion of 72 patients in the BMT + IA (n = 34) or BMT (n = 38) groups, the study ended prematurely owing to safety concerns. The main outcome, time to complete remission (relief of all symptoms) while still receiving therapy, was not significantly different for the two groups. In contrast, the cumulative dose of prednisolone was significantly lower in the BMT + IA compared with BMT alone. In an additional analysis, patients with more extensive pemphigus showed a tendency towards a shorter time to remission in the BMT + IA group compared with the BMT group. While more adverse events were observed in the BMT group (29 vs. 25), severe adverse events were more frequent in the BMT + IA group (17 vs. 11). In this study, IA did not show a shorter time to clinical remission, but a prednisolone-sparing effect was observed. In patients with extensive pemphigus, adjuvant IA may possibly lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits.
Asunto(s)
Pénfigo , Humanos , Masculino , Femenino , Inmunosupresores/uso terapéutico , Prednisolona/uso terapéutico , Rituximab/uso terapéutico , Adyuvantes Inmunológicos/uso terapéutico , Corticoesteroides/uso terapéuticoRESUMEN
Moderada a severa caída del cabello en psoriasis del cuero cabelludo se ha reportado. Sin embargo, la etiología de la alopecia en esta enfermedad aún no se conoce. El objetivo de nuestro estudio fue investigar, mediante inmunohistoquímica (técnica de APAAP), si el folículo piloso anágeno de cuero cabelludo afectado de psoriasis presenta cambios en la distribución de citoqueratinas y filagrina comparado con el folículo piloso de sujetos normales. La porción infraseboglandular del folículo piloso anágeno psoriático no presenta diferencias en la expresión de citoqueratina y filagrina en relación a los controles. En la porción supraseboglandular, el acrofundíbulo psoríatico muestra marcadas diferencias, similares a aquellas de la epidermis interfolicular. Los anticuerpos monoclonales anticitoqueratinas CK 8.12 Y PKK 2 marcan las capas suprabasales en la epidermis interfolicular como también en el acroinfundículo, mientras que normalmente se expresan sólo en la capa basal. Los anticuerpos monoclonales KL-1 U y CK 8.60 que marcan la capa basal y las citoqueratinas 1 y 2 (RPN 1161) no presentaron cambios en su patrón normal de marcaje de las capas suprabasales. Filagrina se mostró parcial totalmente ausente en las áreas paraqueratósicas de la epidermis interfoliar como también en la porción distal del acroinfundículo psoriático, mientras que la porción proximal se mostró prácticamente normal. De nuestros resultados concluimos que: 1) la porción no-permanente del folículo piloso anágeno psoriático no presenta cambios en la expresión de citoqueratinas y filagrina en comparación con los controles; 2) la caída del cabello en psoriasis debe atribuirse, por ejemplo, a efectos traumáticos de procedimientos terapéuticos y/o por la inflamación crónica que afecta a la porción permanente del folículo piloso