RESUMEN
Immunomodulation with anti-TNF-α is highly effective in the treatment of various immune-mediated inflammatory diseases, including hidradenitis suppurativa (HS). However, this may be responsible for unexpected paradoxical psoriasiform reactions. The pathogenic mechanisms underlying the induction of these events are not clear, even though the involvement of innate immune responses driven by plasmacytoid dendritic cells (pDC) has been described. In addition, the genetic predisposition to psoriasis of patients could be determinant. In this study, we investigated the immunological and genetic profiles of three HS patients without psoriasis who developed paradoxical psoriasiform reactions following anti-TNF-α therapy with adalimumab. We found that paradoxical psoriasiform skin reactions show immunological features common to the early phases of psoriasis development, characterized by cellular players of innate immunity, such as pDC, neutrophils, mast cells, macrophages, and monocytes. In addition, IFN-ß and IFN-α2a, two type I IFNs typical of early psoriasis, were highly expressed in paradoxical skin reactions. Concomitantly, other innate immunity molecules, such as the catheledicin LL37 and lymphotoxin (LT)-α and LT-ß were overproduced. Interestingly, these innate immunity molecules were abundantly expressed by keratinocytes, in addition to the inflammatory infiltrate. In contrast to classical psoriasis, psoriasiform lesions of HS patients showed a reduced number of IFN-γ and TNF-α-releasing T lymphocytes. On the contrary, IL-22 immunoreactivity was significantly augmented together with the IL-36γ staining in leukocytes infiltrating the dermis. Finally, we found that all HS patients with paradoxical reactions carried allelic variants in genes predisposing to psoriasis. Among them, SNPs in ERAP1, NFKBIZ, and TNFAIP genes and in the HLA-C genomic region were found.
Asunto(s)
Adalimumab/efectos adversos , Antiinflamatorios/efectos adversos , Erupciones por Medicamentos/inmunología , Hidradenitis Supurativa/tratamiento farmacológico , Psoriasis/inducido químicamente , Adulto , Erupciones por Medicamentos/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psoriasis/genética , Psoriasis/inmunología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresAsunto(s)
Dermatomiositis/inducido químicamente , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Simvastatina/efectos adversos , Anciano , Dermatomiositis/patología , Dislipidemias/tratamiento farmacológico , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Simvastatina/administración & dosificaciónRESUMEN
Toxic epidermal necrolysis (TEN) is a rare and acute severe adverse reaction to drugs, characterised by massive apoptosis and widespread epidermal and mucosal detachment. Although no gold standard therapy exists, human i.v. immunoglobulins have recently been described as an effective treatment for this disease. We report a case of phenobarbital-induced TEN in a 59-year-old white woman where the epidermal detachment stopped 48 h after beginning the etanercept treatment with complete healing after 20 days. To the best of our knowledge, this is only the second reported case of TEN successfully treated with etanercept.