RESUMO
BACKGROUND: Psoriasis has an estimated prevalence of 0.5% to 2.0% in children. There is a paucity of data regarding the management and safety of treatments currently available for children with moderate to severe psoriasis. The aim of this study was to evaluate the treatment response and safety of systemic therapies used to manage moderate to severe pediatric psoriasis in a single referral center. Despite a small sample size, it was hypothesized that multiple therapeutics used for adult psoriasis would have a similar side-effect profile and positive disease response when used in a pediatric population. METHODS: A retrospective case series evaluated 51 children with moderate to severe psoriasis treated with systemic therapies for adverse event occurrence and for disease response using a 5-point Physician Global Assessment scale. RESULTS: Fifty-one patients, some of whom used multiple treatment options, produced 80 treatment data points. Adverse events were reported in 29 of these 80 treatments, with most being minor, subjective side effects. Overall, the most commonly reported side effect was fatigue, which was reported in 7.5% of treatments. Because of the small sample size, the data collected are limited and may not represent a comprehensive safety profile, nor do they allow comparison of efficacy between therapies. This case series found that biologic and immunomodulating therapies provide well-tolerated treatments with positive disease response for moderate to severe pediatric psoriasis. CONCLUSION: Although sample size and study design limit the data from this study, the study provides some guidance where little exists and helps to support the use of these treatments in this setting.
Assuntos
Psoríase/tratamento farmacológico , Acitretina/administração & dosagem , Adalimumab/administração & dosagem , Adalimumab/uso terapêutico , Adolescente , Artrite Psoriásica/tratamento farmacológico , Criança , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Etanercepte/administração & dosagem , Etanercepte/uso terapêutico , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Estudos Retrospectivos , Ustekinumab/administração & dosagemRESUMO
Palmoplantar psoriasis is a chronic debilitating type of psoriasis. Treatment options for this disease are poorly studied. This chart review evaluated the use of methotrexate alone and in combination with 7 other systemic therapies in 48 patients with palmoplantar psoriasis. The findings demonstrate that methotrexate is a relatively well-tolerated and effective treatment for palmoplantar psoriasis, amenable as either monotherapy or in combination with other systemic agents.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Psoríase/tratamento farmacológico , Adalimumab/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/efeitos adversos , Ciclosporina/uso terapêutico , Fármacos Dermatológicos/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Etanercepte/uso terapêutico , Feminino , Dermatoses do Pé/tratamento farmacológico , Dermatoses da Mão/tratamento farmacológico , Humanos , Imunossupressores/efeitos adversos , Infliximab/uso terapêutico , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Índice de Gravidade de Doença , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Ustekinumab/uso terapêutico , Adulto JovemRESUMO
Activation of G protein-coupled alpha(2) adrenergic receptors (ARs) inhibits epileptiform activity in the hippocampal CA3 region. The specific mechanism underlying this action is unclear. This study investigated which subtype(s) of alpha(2)ARs and G proteins (Galpha(o) or Galpha(i)) are involved in this response using recordings of mouse hippocampal CA3 epileptiform bursts. Application of epinephrine (EPI) or norepinephrine (NE) reduced the frequency of bursts in a concentration-dependent manner: (-)EPI > (-)NE >>> (+)NE. To identify the alpha(2)AR subtype involved, equilibrium dissociation constants (pK(b)) were determined for the selective alphaAR antagonists atipamezole (8.79), rauwolscine (7.75), 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane hydrochloride (WB-4101; 6.87), and prazosin (5.71). Calculated pK(b) values correlated best with affinities determined previously for the mouse alpha(2A)AR subtype (r = 0.98, slope = 1.07). Furthermore, the inhibitory effects of EPI were lost in hippocampal slices from alpha(2A)AR-but not alpha(2C)AR-knockout mice. Pretreatment with pertussis toxin also reduced the EPI-mediated inhibition of epileptiform bursts. Finally, using knock-in mice with point mutations that disrupt regulator of G protein signaling (RGS) binding to Galpha subunits to enhance signaling by that G protein, the EPI-mediated inhibition of bursts was significantly more potent in slices from RGS-insensitive Galpha(o)(G184S) heterozygous (Galpha(o)+/GS) mice compared with either Galpha(i2)(G184S) heterozygous (Galpha(i2)+/GS) or control mice (EC(50) = 2.5 versus 19 and 23 nM, respectively). Together, these findings indicate that the inhibitory effect of EPI on hippocampal CA3 epileptiform activity uses an alpha(2A)AR/Galpha(o) protein-mediated pathway under strong inhibitory control by RGS proteins. This suggests a possible role for RGS inhibitors or selective alpha(2A)AR agonists as a novel antiepileptic drug therapy.